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Medical Insurance Billing Quiz
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âHow many digits are there in a basic CPT code?
Six
Five
Four
Seven
âHow many Category Codes are found in the CPT manual?
Three
None of the above
Two
One
How many digits are there in a basic CPT code?
How many Category Codes are found in the CPT manual?
Which CPT manual appendix contains a complete list of all modifier -51 exempt codes?
These contain information that you will need to know in order to correctly code in the section
 When a patient has health insurance, the percentage of covered services that is the responsibility of the patient to pay is known as_______________.
Insurance that is meant to offset medical expenses resulting from a catastrophic illness is called____________.
An unexpected event which may cause injury is called_______________.
A doctor who agrees to accept an insurance company pre-established fee as the maximum amount to be collected is called______________.
A person who represents either party of an insurance claim is the_________________.
A request for payment under an insurance contractor bond is called a(n)_______________.
 Payment made periodically to keep an insurance policy in force is called_____________.
A person or institution that gives medical care is a(n)_______________.
An amount the insured must pay before policy benefits begin is called____________.
An organization that offers health insurance at a fixed monthly premium with little or no deductible and works through a primary care provider is called a(n)_______________.
A patient receiving ambulatory care at a hospital or other health facility without being admitted as a bed patient is called a(n)______________.
An injury that prevents a worker from performing one or more of the regular functions of his job would be known as a_______________.
One who belongs to a group insurance plan is called________________.
A sum of money provided in an insurance policy payable for covered services is called___________.
To prevent the insured from receiving a duplicate payment for losses under more than one insurance policy is called_____________.
When a patient has health insurance, the percentage of covered services that is the responsibility of the patient to pay is known as_______________.
Medical InsuranceMEDICAL & HEALTH INSURANCEMedical And Health Insurance Received: 26 November 2019 Revised: 10 January 2020 Accepted: 19 January 2020 DOI: 10.1111/obr.13005 PEDIATRICS/PHYSIOLOGY Adipokines: A gear shift in puberty DesirĂ©e Nieuwenhuis | NatĂ lia Pujol-Gualdo Amanda J. Kiliaan Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition and Behaviour, Preclinical Imaging Center PRIME, Nijmegen, The Netherlands Correspondence Amanda J. Kiliaan, PhD, Associate Professor, Department of Anatomy, Donders Institute for Brain, Cognition, and Behaviour, Preclinical Imaging Center PRIME, Radboud university medical center, 6500 HB Nijmegen, Geert Grooteplein 21N 6525 EZ Nijmegen, The Netherlands. Email: amanda.kiliaan@radboudumc.nl Funding information Europees Fonds voor Regionale Ontwikkeling (EFRO), Grant/Award Number: BriteN 2016 1 | INTRODUCTION The prevalence of obesity in adolescents and children is increasing in | Ilse A.C. Arnoldussen | Summary In this review, we discuss the role of adipokines in the onset of puberty in children with obesity during adrenarche and gonadarche and provide a clear and detailed overview of the biological processes of two major players, leptin and adiponectin. Adipokines, especially leptin and adiponectin, seem to induce an early onset of puberty in girls and boys with obesity by affecting the hypothalamic-pituitary- gonadal (HPG) axis. Moreover, adipokines and their receptors are expressed in the gonads, suggesting a role in sexual maturation and reproduction. All in all, adipokines may be a clue in understanding mechanisms underlying the onset of puberty in child- hood obesity and puberty onset variability. KEYWORDS adipokines, obesity, puberty 1,2 the age of 5 years were overweight or were with obesity in 2016, and 3 Obesity is defined by an excessive accumulation of white adipose tissue (WAT), and it is often indicated by a body mass index (BMI) 4 above 30. Two main types of adipose tissue were described: WAT and brown adipose tissue (BAT), which differ in morphology and func- 5-7 Ilse A.C. Arnoldussen and Amanda J. Kiliaan contributed equally to this work. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation Obesity Reviews. 2020;21:e13005. wileyonlinelibrary.com/journal/obr 1 of 10 https://doi.org/10.1111/obr.13005 alarming rates. Specifically, worldwide, 41 million children below this number is expected to increase to 70 million in 2025. obesity is associated with various severe health complications, includ- ing increased risk of diabetes mellitus type 2, hypertension, heart dis- eases, and disturbances in sex hormone levels. 5,6 and mitochondria and plays a role in thermogenesis. Adipocytes in tion. BAT consists of adipocytes containing multiple lipid droplets WAT contain only a few mitochondria and a single lipid droplet. Adipose tissue has several functions including the storage of energy, thermogenesis, and the production and secretion of adipokines Generally, two physiological processes, adrenarche and gonadarche, 11,24 Childhood 5,7,8 a key role in puberty onset. Puberty is known as a period through which the body changes physically, being a physiological process resulting in the maturation of children, i.e. they develop sexual characteristics and obtain reproduc- 9,11 Adipokines are involved in a number of physiological processes including blood pressure, metabo- lism, glucose, and vascular homeostasis and may play amongst others 8-10 (hormones, cytokines, and peptides). tive functions. between obesity and puberty,2,12-23 the biological mechanisms under- lying obesity and puberty onset remain unclear. Hereafter, we review in detail the role of adipokines in the onset of puberty in childhood obesity. Although many studies have shown associations 2 | INITIATION OF PUBERTY PHYSIOLOGICAL PROCESSES IN THE interact to regulate the onset of puberty. During adrenarche, the adrenal cortex secretes steroid hormones (including 2 of 10 NIEUWENHUIS ET AL. androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate (DHEAS), androstenedione, and cortisol), insulin-like growth factor, and growth hormone, which contribute to the pubertal insights on new genetic loci (e.g. melanocortin-4 receptor, mitochon- drial carrier 2, and mitogen-activated protein kinase 13) and on sev- eral pathways that regulate the timing of puberty; however, it partly 34 9,24,25 Both adrenarche and gonadarche are involved in the development growth spurt, body odor, skin oiliness, and skeletal maturation. explains puberty timing variation. Thereby, defining the role of 25 adipokines is of importance in elucidating the variability in puberty as the expression of adipokines is sex-specific and is altered with body composition, adiposity, and during growth spurts. Moreover, adipokines and their receptors are expressed in gonads and several brain regions suggesting involvement in the onset of puberty and sex- ual maturation. Lastly, adipokines interfere in processes regulating timing and duration of puberty, for instance in the HPA and HPG axes which are both key players during adrenarche and gonadarche. Involvement of adipokines in the onset of puberty and specifically in individuals with obesity will be further reviewed in the next 2,24 3 | Puberty onset in girls is assessed using different markers, such as thelarche (breast development), menarche (the start of of pubic hair. pituitary-gonadal (HPG) axis is activated,2,26 and several hormones have been identified to participate in the activation of the HPG axis During gonadarche (Figure 1), the hypothalamic- 2,27 Kisspeptin, neurokinin B, and dynorphin are released by specialized including kisspeptin, neurokinin B, dynorphin, leptin, and ghrelin. 28 key regulator of the pulsatile secretion of gonadotropin releasing neurons, the KNDy neurons in the hypothalamus. Kisspeptin is a 29,30 B stimulates, and dynorphin inhibits the release of kisspeptin, which hormone (GnRH) from the hypothalamus. In addition, neurokinin implies that both coordinate a pulsatile release of kisspeptin. 31 Sub- sections. sequently, the activated HPG axis induces the pituitary gland to secrete luteinising hormone (LH) and follicle stimulating hormone (FSH). As a result, gametogenesis occurs, and the gonads will release sex hormones. Consequently, secondary sex characteristics develop including breast development in girls and an increased testicular vol- 2,26,32 is possibly due to differences in levels of body fat, hypothalamic-pitui- THE ONSET OF PUBERTY IN GIRLS ume in boys. The age at puberty onset varies greatly among individuals, which 19 35 menstruation), and pubic hair development. 33 genome-wide association studies have provided important new tary-adrenal (HPA) axis activity, and genetic background. Recent The average age of However, this age differs between cultures and ethnicities, and since 1980, age at menarche is girls at start of menarche is 12.4 years. 36 significantly decreasing. 36-39 F I G U R E 1 Hormonal regulation in the initiation of puberty in boys and girls. The secretion of kisspeptin, neurokinin B, and dynorphin from KNDy neurons initiate the release of gonadotropin releasing hormone (GnRH) from the hypothalamus. This activates the pituitary gland to produce and secrete luteinising hormone (LH) and follicle stimulating hormone (FSH), which in turn stimulate the gonads to produce estrogen and testosterone in girls and boys, respectively 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 3 of 10 T A B L E 1 Summary of included studies Authors Year Country Study Design Primary Outcome Sex Sample Size (n) Age (y) Data Collection Lian et al21 2019 China Cross-sectional Puberty starts earlier in Chinese Han girls with obesity compared with Chinese Han girls with normal weight. Girls 2996 9-19 2012 and 2013 Biro et al12 Lazzeri et al20 2018 USA 2018 Italy Longitudinal Cross-sectional Body mass index had a greater effect on age at menarche than did race and ethnicity. Girls 946 6-16 2004-2014 Li et al23 2018 China Longitudinal For both, boys and girls, a higher BMI (ie, overweight and obese) is associated with earlier onset of puberty Girls Girls Boys Girls 542 Deng et al22 Flom et al15 2017 China Cross-sectional Increased BMI is associated with early timing spermarche and menarche. Boys Girls Girls 1278258 9-15 2005-2012 He et al24 Holmgren et al17 2017 China 2017 Sweden Cross-sectional Longitudinal Onset of puberty is not related to obesity in boys. Boys Boys Girls Girls 782 7-17 972 929 5839 Kelly et al19 2017 UK 2016 Brazil 2016 USA Longitudinal prospective cohort Higher BMI in girls is associated with the onset of menstruation at an earlier age. 11 10-18 11-17 Barcellos Gemelli et al25 Cross-sectional Longitudinal Excess weight is associated with early age of menarche. Girls 727 2014 2003-2009 Glass et al16 Lee et al26 In girls, but not in boys, greater adiposity is associated with the earlier onset of puberty. Boys Girls 135 Cabrera et al27 Leonibus et al14 2014 USA 2013 Italy Cross-sectional Longitudinal Thelarche occurred earlier than recently reported, while age of menarche remained unchanged. Girls 610 3-17.9 2007 2005-2012 Currie et al13 2012 Europe, USA, Canada Cross-sectional Overweight/obesity during childhood predicts the early onset of puberty in girls. Girls 20410 11, 13, 15 2005-2006 2017 USA Prospective birth cohort Overweight/obese status at the age of 7 ye was associated with increased risk of early menarche 788 From birth to menarche occurred Pregnancies 1959-1966 2016 USA Cross-sectional Boys with overweight enter puberty earlier compared with boys with normal weight or obesity, while puberty starts later in boys with obesity compared with boys with normal weight and overweight. Boys 3872 6-16 2005-2010 Overweight during childhood shows a relation with the early onset of puberty in girls. 6535 4259 695 11 15 5.8-12.2 2009/2010 2013/2014 2014-2017 Higher BMI during childhood is associated with early puberty. 2008 and 2009 2000-2002 Obesity during childhood is related to the earlier onset of puberty. Boys Girls 84 123 71 (Continues) 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 10 NIEUWENHUIS ET AL. 3.1 | Fat storage For the initiation of puberty, the timing of stimulation and/or inhibi- tion of different hormones is important, and additionally, a certain amount and distribution of body fat is needed in order to start menar- che, which emphasizes the importance of body fat. From an evolution- ary point of view, body fat increases in mammalian females during puberty onset, and it highlights the need to guarantee a healthy preg- 40 women with anorexia nervosa. particularly body fat localized predominantly on the gluteofemoral fat depots, is profoundly associated with start of menarche, more than nancy, offspring, and maternal survival. fat, sex-hormones, and neuroendocrine alterations can evolve in men- strual dysfunction, for instance, in women with severe obesity or in 41-43 44-46 to gluteofemoral fat depots suggesting that leptin may convey infor- amount of total body fat. mation on body fat distribution to the hypothalamus during puberty. An improper level of body Importantly, body fat distribution, Blood leptin levels are strongly related 45 3.2 | HPG axis The HPG axis is activated by the release of kisspeptin resulting in the release of GnRH from the hypothalamus, and LH and FSH from the pituitary gland. In girls, FSH is involved in the development of the folli- cles in the ovaries, and it promotes the secretion of estrogen. LH stim- ulates the production of androgen hormones and induces ovulation 48 9,47 the release of kisspeptin and neurokinin B, and kisspeptin thereby (Figure 1). The secretion of estrogen has an inhibitory effect on inhibits the GnRH release from the hypothalamus. pattern of GnRH is important for the regulation of the menstrual cycle. This roughly 28-day-cycle comprises several phases, including the follicular phase and luteal phase. During the follicular phase, increasing levels of FSH stimulate the maturation of follicles and the production of estrogen from the ovaries. This in turn inhibits the release of FSH from the pituitary gland. A high level of estrogen will induce the production of LH by the pituitary gland, resulting in ovula- tion. The matured follicle secretes progesterone thereby inhibiting the release of GnRH. When the corpus luteum is demolished, there is less 48 3.3 | Adipokines According to results from studies reported in Table 1, girls with obe- sity enter puberty earlier compared with girls with normal higher leptin concentrations inhibit the intake of food and increases inhibition of GnRH. As a consequence, the cycle will start again. whole process, starting from the activated HPG axis, results in the development of the secondary sex characteristics in girls including 9,47 thelarche and menarche. 13,14,16-23,49-51 weight. these girls might be found in the secretion of adipokines. For instance, leptin is positively associated with the amount of body fat. Generally, energy expenditure. 9,52-54 An explanation for the early onset of puberty in The expression This TABLE 1 (Continued) Authors Year Country Study Design Primary Outcome Sample Sex Size (n) Age (y) Data Collection Herman-Giddens et al28 2012 USA Cross-sectional Observed mean ages of beginning genital and pubic hair growth and early testicular volumes were earlier than in past studies, depending on the characteristic and race/ethnicity. Boys 4131 6-16 2005-2010 Sorensen et al29 Aksglaede et al30 2010 2009 Denmark Denmark Cross-sectional/longitudinal Longitudinal Puberty onset at earlier ages was associated with an increased BMI in boys. Boys 1528 5.8-19.9 1991-1993/2006-2008 1930-1969 Juul et al31 Ribeiro et al32 2007 2006 Denmark Portugal Retrospective cohort Cross-sectional Higher BMI is associated with early voice break. 11-15 10-15 1990-1999 Kaplowitz et al18 Abbreviation: BMI, body mass USA Cross-sectional The early onset of puberty in Caucasian girls is likely related to an increased BMI. 5-12 1992-1993 2001 index. The higher BMI in boys and girls at 7 y of age, the earlier they enter puberty. Boys 21 612 Girls 135 223 Boys 463 Boys 382 Girls 437 Girls 10 750 Early sexual maturation in boys and girls is associated with overweight. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 5 of 10 Leptin may possibly play a role in adrenarche as its plasma level increases with higher levels of body fat and as it can modulate both girls. 33 ing adrenarche. In coherence, in children with obesity, the androgen These findings suggested that lower reproductive status was associated with higher total adiponectin concentrations and that a higher reproductive status was related to higher HMW adiponectin the HPA and HPG axes. These axes are functionally integrated dur- DHEAS was positively associated with leptin levels. Nevertheless, concentrations in girls. In addition, individuals with obesity often another study showed that enhanced adrenal androgen secretion in girls with premature adrenarche was not explained by leptin or BMI 55 ated with androgen levels in girls ; however, it was not related to levels. and IL-6. TNF-α alters, and IL-6 inhibits the expression of 56 8 In addition, the adipokine adiponectin was negatively associ- 57 differences of adiponectin seem to develop during the progression of 56 adiponectin (Figure 2). Thereby, a low level of total adiponectin and/or high levels of inflammatory cytokines in individuals with obe- sity can promote the onset of puberty. Many more adipokines are secreted by WAT including omentin, 52,65-67 9,36,62,68 adrenarche in girls with Prader-Willi syndrome. Interestingly, sex puberty. adrenarche; however, both are not required factors. Thus, leptin and adiponectin might be able to influence In gonadarche, leptin can stimulate the secretion of kisspeptin, and subsequently activation of the HPG axis, which eventually increases the expression of estrogen and androstenedione in the ova- 58 2,60 65-67 The expression of these ries (Figure 2). Ob gene in WAT, resulting in the synthesis and secretion of leptin. Thus, high levels of leptin promote onset of puberty in girls via secre- tion of kisspeptin, and estrogen stimulates leptin secretion addition- ally. Moreover, adiponectin can affect the HPG axis due to the expression of adiponectin receptors in the hypothalamus, pituitary In return, estrogen stimulates the expression of the 59 gland, and gonads. onset as it inhibits the secretion of kisspeptin and GnRH in the hypo- thalamus and the release of GH and LH in the pituitary gland, and 2,60-62 52,60 63 girls with central precocious puberty (CPP). Moreover, total adiponectin had negative correlations with progression of puberty in girls (defined by Tanner stages), whereas HMW adiponectin had FIGURE 2 Adipokinesaffectingthe initiation of puberty in girls. Leptin stimulates the release of kisspeptin in KNDy neurons, which activates the hypothalamus to produce gonadotropin releasing hormone (GnRH). In response to the release of GnRH, the pituitary gland secretes follicle stimulating hormone (FSH) and luteinising hormone (LH), which stimulates the ovaries to release estrogen resulting in the formation of secondary sex characteristics in girls. Estrogen stimulates the production of leptin. Adiponectin inhibits GnRH release resulting in reduced levels of GnRH and thereby a delayed onset of puberty. TNF- α and IL-6 inhibit the production of adiponectin and therefore stimulate the onset of puberty In detail, adiponectin is a regulator of puberty thereby inhibiting the onset of puberty (Figure 2). with obesity often have low levels of adiponectin. et al. showed that total adiponectin was significantly lower, whereas high molecular weight (HMW) adiponectin was significantly higher in ment. 55 63 develop a chronic low-grade inflammatory state, which can be indi- cated by a high level of circulating inflammatory cytokines like TNF-α 64 Individuals Sitticharoon positive associations with LH levels and the progression of puberty in 63 visfatin, resistin, and chemerin. and visfatin are expressed in the ovaries. adipokines in the ovaries suggests a role within the reproductive sys- tem; however, the exact biological processes have to be examined. Thus, specifically leptin, adiponectin, and inflammatory cytokines pro- duced by WAT could be permissive key players during an early onset of puberty in girls with obesity. As an exception, HMW adiponectin seems to have a stimulatory effect on peripheral repro- ductive function as HMW is not able to cross the blood brain 63 barrier. 4 | Markers that are used to assess puberty onset in boys are THE ONSET OF PUBERTY IN BOYS spermarche, voice break, testicular volume, and pubic hair develop- 35 spermarche develop in the early stages of puberty onset, voice In women, omentin, chemerin, While pubic hair development, larger testicular volume, and 69 testicular volume increases, which occurs at an average age of break usually appears in later stages of puberty. Generally, first 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 10 NIEUWENHUIS ET AL. 11.9 years, followed by the development of pubic hair at 12.2 years of average, and lastly, boys experience spermarche around an aver- 55 related with leptin levels. Thereby, leptin plausibly has a minor impact in adrenarche in boys. Since leptin receptors are found in the hypothalamus, pituitary gland, and testes, they might be involved in the onset of puberty by affecting the HPG axis during gonadarche. Leptin stimulates the release of kisspeptin and GnRH, and as a consequence, it accelerates the onset of puberty (Table 1, Figure 3). In contrast, adiponectin inhibits the secretion of GnRH, GH, LH, and FSH therewith delaying the onset of puberty. However, adiponectin levels are generally lower in men compared with women and even lower in men with obe- age age of 13.4 years. 70 4.1 | Fat storage Many aspects of the reproductive physiology are energetically demanding,71 and therefore, an adequate energy level is necessary. In boys, a dynamic change in body composition occurs around the age of 10 to 13 years, in which they gain approximately 40% of sity. culating inflammatory cytokines. levels can stimulate the HPG axis and therewith an early onset of puberty in boys. Nevertheless, leptin can inhibit the production of tes- 72 mostly consisting of lean mass, which causes exhaustion of most of fat. Subsequently, a growth spurt follows in which they gain tissue 72 in boys, an adequate amount of body fat is important in the onset of their body fat. These alterations in amount of body fat indicate that 4.2 | Puberty in boys is initiated by the release of kisspeptin. As mentioned before, this activates the HPG axis, resulting in the release of GnRH from the hypothalamus, and consequently the release of LH and FSH 9,74 puberty. tosterone from the testes, to estrogen (Figure 3). of the development of secondary sex characteristics in boys. Additionally, leptin can affect fertility in men as it can modulate the nutritional support of spermatogenesis, and moreover, dysfunction of spermatogenesis is associated with an increased leptin level and 73 58 2,60-62 HPG axis from the pituitary gland (Figure 1). and LH stimulates the secretion of testosterone from the testes, which inhibits the release of kisspeptin from the KNDy neurons and 9,48 in men, the release of kisspeptin is more consistent, causing a con- 29,48 subsequently GnRH from the hypothalamus. receptors expressed on KNDy neurons. In humans, KNDy neurons Contrarily to women, LH-induced testosterone levels lead to the stant release of LH. development of secondary sex characteristics in boys. differences between sexes in kisspeptin release are related to a sex- specific and sex steroid-dependent kisspeptin system as estrogen and progesterone modulate kisspeptin activity through the sex-steroid 48 in the infundibular nucleus are involved in negative and positive sex- 48 tal exposure to sex steroids and result in sex-specific differences in steroid feedbacks. kisspeptin release. These sexual dimorphisms are induced by perina- 75,76 4.3 | Adipokines The association between obesity and puberty onset in boys is rather controversial compared with findings in girls. Most studies reported an early onset of puberty in boys associated with increased ate adipose tissue from actual breast tissue. stages are more difficult to assess than female stages as boys lack a more determined marker such as menarche. Thirdly, puberty onset can be indicated by the activation of the HPG axis, and the presence of these secondary sex characteristics is the result of hormonal 2 14,17,22,23,50,51,77,78 BMI, 20,49 all while others reported no associations at Current markers used 79 16,80 or a delayed onset of puberty (Table 1). The presence of excessive adipose tissue can be involved in puberty onset in boys as the secretion of adipokines can modulate both adrenarche and gonadarche. Leptin can affect adrenarche by modulating both the HPG and HPA axes,33 and moreover, androgen levels were positively 55 nal androgen secretion in boys with premature adrenarche was not associated with plasma leptin levels. Nevertheless, enhanced adre- 9 In more detail, 61,62 adiponectin, and individuals with obesity often have high levels of cir- Moreover, inflammatory cytokines, TNF-α, and IL-6, inhibit expression of the leptin receptor in the testis. FSH induces spermatogenesis, too. function and role still have to be examined. 64 High leptin and low adiponectin and fat tissue can convert testosterone Both processes might result in the delay 29,61,79 81,82 In men, other adipokines like chemerin are found in the gonads 65 Thus, particularly high leptin and low adiponectin levels stimulate the HPG axis and thereby accelerate the onset of puberty in boys. Additionally, leptin can dysregulate the development of secondary sex characteristics and spermatogenesis by affecting testosterone levels and nutritional sup- port of spermatogenesis. 5 | LIMITATIONS AND FUTURE RESEARCH DIRECTIONS Even though multiple epidemiological studies have shown the link between puberty onset and obesity, there are some important limita- tions. Firstly, determining both the onset and stage of puberty is rather difficult. For instance, assessing the stage of breast develop- ment in girls with obesity is complicated as clinicians should differenti- 2 changes in response to the activated HPG axis. to determine the onset of puberty refer to secondary sex characteris- tics, such as testicular volume in boys and breast development in girls. A more accurate measurement of puberty onset would be to combine secondary sex characteristics with plasma or serum hormone level measurements such as LH, FSH, adipokines, e.g. leptin. Thereby, differences in puberty measurements could explain variations in the age of puberty onset between boys and girls within different Thereby, resistin is expressed in the testes of rats, but its exact 83 Secondly, male pubertal 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 7 of 10 FIGURE 3 Adipokines affecting the initiation of puberty in boys. Leptin activates kisspeptin secretion in KNDy neurons, this activates the production of gonadotropin releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to secrete follicle stimulating hormone (FSH) and luteinising hormone (LH), activating the production of testosterone from the testes allowing the development of secondary sex characteristics. Leptin also inhibits the production of testosterone, which may cause a delayed onset of puberty. Adiponectin inhibits GnRH release. Low levels of adiponectin, as a result of TNF-α and IL-6 expression, lead to a reduced inhibition of GnRH. In response to GnRH release, the pituitary gland will secrete FSH and LH, and the testes will produce testosterone resulting in the development of secondary sex characteristics in boys countries, and In addition, the inclusion of a of puberty. ferent time points is complicated, as subjects examined several decades ago presented pronounced differences concerning lifestyle patterns such as nutrition and exercise habits. Lastly, obesity or over- weight is often determined by BMI, a classification based on weight and height measurements. Additionally, it is important that all studies studies or across continents, ethnicities proper age range (8-16 years) is important when assessing the onset (Figure 4). 12-15,17,20-23,49,77-79,84,85 30,47 Furthermore, comparison between studies from dif- 86 Specifically in children, BMI is often dependent on age and growth use the same anthropometric standards and sex-specific cut-offs. 13,14,16-23,49-51,77-80 fat and would represent a more accurate measurement in its regard. Based on this review, several suggestions can be made for further research. Firstly, the roles of adipokines like resistin, chemerin, visfatin, and omentin in puberty onset, fertility, and sexual maturation should be examined in detail. Secondly, future research examining the onset of puberty should combine indicators of puberty onset (e.g. breast development or testicular volume) with plasma or serum hor- mone measurements such as LH, FSH, sex-steroids, adipokines (e.g. spurts. ment in case of growth spurts. distribution of body fat should be taken into account in determining puberty and obesity in children. For instance, the body adiposity index (BAI), which was introduced in 2011 by Bergman et al.,87 uses hip cir- cumference and height in order to estimate the percentage of body 87 Thereby, BMI is a less accurate measure- F I G U R E 4 87,88 Therefore, both percentage and Average age of puberty onset in Europe, China, and the United States according to several studies from Table 1. Age of puberty onset ranges from 8.47 to 13.33 years in girls and from 8.63 leptin), and body fat distribution (e.g. BAI,87 waist-hip ratio's and/or dual-energy X-ray absorptiometry (DXA)2). Additionally, defining con- sistent and general measurements of puberty in both boys and girls, combined with a proper age range (8-16 years), would facilitate the comparisons between different studies and their results. 12-15, 17, 20-23, 25-29, 31 to 13.7 years in boys. included if average age of markers used to assess puberty was not reported. Pink: girls. Blue: boys Studies (Table 1) were not 39, 56 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 8 of 10 NIEUWENHUIS ET AL. 6 | CONCLUSION In conclusion, epidemiological data regarding obesity and puberty onset in girls show similar outcomes as adiposity results in the early onset of puberty in girls. The majority of the studies examining boys with obesity indicate an early onset of puberty, while not all reported an earlier onset of puberty. In detail, high leptin, TNF-α, and IL-6 levels combined with low adiponectin levels stimulate the activation of the HPG axis in girls and boys with obesity, and 5, 45, 50, 51 REFERENCES 1. Kumar S, Kelly AS. Review of childhood obesity: from epidemiology, etiology, and comorbidities to clinical assessment and treatment. May- o Clin Proc. 2017;92(2):251-265. 2. Reinehr T, Roth CL. Is there a causal relationship between obesity and puberty? The Lancet Child & adolescent health. 2019;3(1):44-54. 3. WorldHealthOrganization. Facts and figures on childhood obesity. 2017. 4. Guglielmi V, Sbraccia P. Obesity phenotypes: depot-differences in adipose tissue and their clinical implications. Eat Weight Disord. 2018; 23(1):3-14. 5. Gomez-Hernandez A, Beneit N, Diaz-Castroverde S. Escribano O. 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Ahmed ML, Ong KK, Dunger DB. Childhood obesity and the timing of puberty. Trends in endocrinology and metabolism: TEM. 2009;20(5): 237-242. 12. Biro FM, Pajak A, Wolff MS, et al. Age of menarche in a longitudinal US cohort. J Pediatr Adolesc Gynecol. 2018;31(4):339-345. 13. Currie C, Ahluwalia N, Godeau E, Nic Gabhainn S, Due P, Currie DB. Is obesity at individual and national level associated with lower age at menarche? Evidence from 34 countries in the Health Behaviour in School-aged Children Study. The Journal of adolescent health: official publication of the Society for Adolescent Medicine. 2012;50(6): 621-626. 14. De Leonibus C, Marcovecchio ML, Chiavaroli V, de Giorgis T, Chiarelli F, Mohn A. Timing of puberty and physical growth in obese children: a longitudinal study in boys and girls. Pediatr Obes. 2014; 9(4):292-299. 15. Flom JD, Cohn BA, Tehranifar P, et al. Earlier age at menarche in girls with rapid early life growth: cohort and within sibling analyses. Ann Epidemiol. 2017;27(3):187-93.e2. 16. Glass NA, Torner JC, Letuchy EM, et al. The relationship between greater prepubertal adiposity, subsequent age of maturation, and bone strength during adolescence. Journal of bone and mineral research: the official journal of the American Society for Bone and Min- eral Research. 2016;31(7):1455-1465. 17. Holmgren A, Niklasson A, Nierop AF, et al. Pubertal height gain is inversely related to peak BMI in childhood. Pediatr Res. 2017;81(3): 448-454. 18. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman- Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics. 2001;108(2):347-353. 19. Kelly Y, Zilanawala A, Sacker A, Hiatt R, Viner R. Early puberty in 11-year-old girls: Millennium Cohort Study findings. Arch Dis Child. 2017;102(3):232-237. 20. Lazzeri G, Tosti C, Pammolli A, et al. Overweight and lower age at menarche: evidence from the Italian HBSC cross-sectional survey. BMC Womens Health. 2018;18(1):168-174. thereby an early onset of obesity. leptin can inhibit the production of testosterone in boys and subse- quently inhibit the development of secondary sex characteristics affecting spermatogenesis. for other adipokines, like resistin and omentin, are present in the testes and ovaries suggesting a role in puberty or reproduction; 58, 71 however, their plausible function is still unknown. that adipokines may be key regulators in an early onset of puberty in both girls and boys with obesity, specifically by affecting the HPG axis during gonadarche. Future research should focus on assessing puberty onset by measuring consistent puberty markers and determine the percentage of body fat and its distribution and adipokines and hormone serum levels particularly involved in the HPG axis. CONFLICTS OF INTEREST The authors declare no conflict of interest. FUNDING INFORMATION This research was funded by Europees Fonds voor Regionale Ontwikkeling (EFRO), project BriteN 2016. ORCID Ilse A.C. Arnoldussen Amanda J. Kiliaan https://orcid.org/0000-0002-7395-5284 https://orcid.org/0000-0002-2158-6210 13, 14, 16-26, 29-32 Furthermore, several receptors Nevertheless, We conclude Search strategy We searched PubMed for articles published before Novem- ber 15th, 2019 using relevant keywords, including âonset of puberty and adiposity/obesityâ, âonset of pubertyâ, âchildren with obesityâ, âadipose tissueâ, âchildhood obesityâ, âadiposityâ, âobesityâ, âadipokine(s)â, âHPG axisâ, âadipokines ovary/ova- riesâ, or âadipokines testesâ, either alone or in combination. Selection criteria used were English language, longitudinal or cross-sectional studies assessing the onset of puberty, including menarche, thelarche, spermarche, or voice break, combined with high BMI or obesity/adiposity, and articles assessing or reviewing adipokines and its effects on the reproductive system. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License NIEUWENHUIS ET AL. 9 of 10 21. Lian Q, Mao Y, Luo S, et al. Puberty timing associated with obesity and central obesity in Chinese Han girls. BMC Pediatr. 2019; 19(1):1-7. 22. Deng Y, Liang J, Zong Y, et al. Timing of spermarche and menarche among urban students in Guangzhou, China: trends from 2005 to 2012 and association with Obesity. Sci Rep. 2018;8(1):263-270. 23. Li W, Liu Q. Association of prepubertal obesity with pubertal devel- opment in Chinese girls and boys: a longitudinal study. 2018;30: e23195. 24. Mendle J, Beltz AM, Carter R, Dorn LD. Understanding puberty and its measurement: ideas for research in a new generation. Journal of research on adolescence: the official journal of the Society for Research on Adolescence. 2019;29(1):82-95. 25. Pagani S, Meazza C, Gertosio C, Bozzola E, Bozzola M. Growth hor- mone receptor gene expression in puberty. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2015;47:581-584. 26. Abreu AP, Kaiser UB. Pubertal development and regulation. Lancet Diabetes Endocrinol. 2016;4(3):254-264. 27. Aguirre RS, Eugster EA. Central precocious puberty: from genetics to treatment. Best Pract Res Clin Endocrinol Metab. 2018;32(4): 343-354. 28. Sultan C, Gaspari L, Maimoun L, Kalfa N, Paris F. Disorders of puberty. Best Pract Res Clin Obstet Gynaecol. 2018;48:62-89. 29. Skorupskaite K, George JT, Anderson RA. The kisspeptin-GnRH path- way in human reproductive health and disease. Hum Reprod Update. 2014;20(4):485-500. 30. Dahl SK, Amstalden M, Coolen L, Fitzgerald M, Lehman M. Dynorphin immunoreactive fibers contact GnRH neurons in the human hypothal- amus. Reprod Sci. 2009;16(8):781-787. 31. Navarro VM, Gottsch ML, Chavkin C, Okamura H, Clifton DK, Steiner RA. Regulation of gonadotropin-releasing hormone secretion by kisspeptin/dynorphin/neurokinin B neurons in the arcuate nucleus of the mouse. J Neurosci. 2009;29(38):11859-11866. 32. Zhai L, Liu J, Zhao J, et al. Association of obesity with onset of puberty and sex hormones in chinese girls: a 4-year longitudinal study. PLoS ONE. 2015;10(8):1-12, e0134656. 33. Cizza G, Dorn LD, Lotsikas A, Sereika S, Rotenstein D, Chrousos GP. Circulating plasma leptin and IGF-1 levels in girls with premature adrenarche: potential implications of a preliminary study. Horm Metab Res. 2001;33(3):138-143. 34. Cousminer DL, WidĂ©n E, Palmert MR. The genetics of pubertal timing in the general population: recent advances and evidence for sex-spec- ificity. Curr Opin Endocrinol Diabetes Obes. 2016;23(1):57-65. 35. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44(235):291-303. 36. Lacroix AE, Whitten R. Physiology. Treasure Island (FL): Menarche. StatPearls. StatPearls Publishing; 2018. 37. McDowell MA, Brody DJ, Hughes JP. Has Age at Menarche Chan- ged? Results from the National Health and Nutrition Examination Sur- vey (NHANES) 1999â2004. J Adolesc Health. 2007;40(3):227-231. 38. de Muinich Keizer SM, Mul D. Trends in pubertal development in Europe. Hum Reprod Update. 2001;7(3):287-291. 39. Talma H, Schönbeck Y, van Dommelen P, Bakker B, van Buuren S, Hirasing RA. Trends in menarcheal age between 1955 and 2009 in the Netherlands. PLoS ONE. 2013;8:e60056-e60056. 40. Kaplan HS, Lancaster JB. An evolutionary and ecological analysis of human fertility, mating patterns, and parental investment. Off- spring: Human fertility behavior in biodemographic perspective. 2003;1: 170-223. 41. Mitan LA. Menstrual dysfunction in anorexia nervosa. J Pediatr Adolesc Gynecol. 2004;17(2):81-85. 42. Xu H, Li P-H, Barrow TM, et al. Obesity as an effect modifier of the association between menstrual abnormalities and hypertension in young adult women: Results from Project ELEFANT. PLoS ONE. 2018; 13(11):e0207929-e0207929. 43. Tauqeer Z, Gomez G, Stanford FC. Obesity in women: insights for the clinician. J Womens Health (Larchmt). 2018;27(4):444-457. 44. de Ridder CM, Thijssen JH, Bruning PF, Van den Brande JL, Zonderland ML, Erich WB. Body fat mass, body fat distribution, and pubertal development: a longitudinal study of physical and hormonal sexual maturation of girls. J Clin Endocrinol Metab. 1992;75(2): 442-446. 45. Lassek W, Gaulin S. Brief communication: menarche is related to fat distribution. Am J Phys Anthropol. 2007;133(4):1147-1151. 46. Loomba-Albrecht LA, Styne DM. Effect of puberty on body composi- tion. Curr Opin Endocrinol Diabetes Obes. 2009;16:10-15. 47. Simonneaux V, Bahougne T. A multi-oscillatory circadian system times female reproduction. Front Endocrinol. 2015;6:1-15. 48. Marques P, Skorupskaite K, George JT, Anderson RA. Physiology of GNRH and gonadotropin secretion. In: Feingold KR, Anawalt B, Boyce A, et al., eds. Endotext. Endotext.org: South Dartmouth (MA); 2000. 49. Barcellos Gemelli IF, Farias EDS, Souza OF. Age at menarche and its association with excess weight and body fat percentage in girls in the Southwestern Region of the Brazilian Amazon. J Pediatr Adolesc Gynecol. 2016;29(5):482-488. 50. Aksglaede L, Juul A, Olsen LW, Sorensen TI. Age at puberty and the emerging obesity epidemic. PLoS ONE. 2009;4:1-6, e8450. 51. Ribeiro J, Santos P, Duarte J, Mota J. Association between over- weight and early sexual maturation in Portuguese boys and girls. Ann Hum Biol. 2006;33(1):55-63. 52. Budak E, Fernandez Sanchez M, Bellver J, Cervero A, Simon C, Pellicer A. Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system. Fertil Steril. 2006;85(6):1563-1581. 53. Castellano JM, Tena-Sempere M. Metabolic control of female puberty: potential therapeutic targets. Expert Opin Ther Targets. 2016; 20(10):1181-1193. 54. Venancio JC, Margatho LO, Rorato R, et al. Short-term high-fat diet increases leptin activation of CART neurons and advances puberty in female mice. Endocrinology. 2017;158(11):3929-3942. 55. l'Allemand D, Schmidt S, Rousson V, Brabant G, Gasser T, Gruters A. Associations between body mass, leptin, IGF-I and circulating adrenal androgens in children with obesity and premature adrenarche. Eur J Endocrinol. 2002;146(4):537-543. 56. Böttner A, Jr K, MĂŒller G, et al. Gender Differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metabol. 2004;89(8):4053- 4061. 57. Unanue N, Bazaes R, Iñiguez G, Cortes F, Avila A, Mericq V. Adre- narche in Prader-Willi syndrome appears not related to insulin sensi- tivity and serum adiponectin. Horm Res. 2007;67(3):152-158. 58. Michalakis K, Mintziori G, Kaprara A, Tarlatzis BC, Goulis DG. The complex interaction between obesity, metabolic syndrome and repro- ductive axis: a narrative review. Metabolism: clinical and experimental. 2013;62(4):457-478. 59. Machinal-Quelin F, Dieudonne MN, Pecquery R, Leneveu MC, Giudicelli Y. Direct in vitro effects of androgens and estrogens on ob gene expression and leptin secretion in human adipose tissue. Endo- crine. 2002;18(2):179-184. 60. Dobrzyn K, Smolinska N, Kiezun M. Adiponectin: A new regulator of female reproductive system. Int J Endocrinol. 2018;2018:1-12, 7965071. 61. Martin LJ. Implications of adiponectin in linking metabolism to testic- ular function. Endocrine. 2014;46(1):16-28. 62. Mathew H, Castracane VD, Mantzoros C. Adipose tissue and repro- ductive health. Metabolism: clinical and experimental. 2018;86:18-32. 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 10 of 10 NIEUWENHUIS ET AL. 63. Sitticharoon C, Sukharomana M, Likitmaskul S, Churintaraphan M, Maikaew P. 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The usefulness of circulating levels of leptin, kisspeptin, and neurokinin B in obese girls with precocious puberty. 2018;34:627-630. 69. Lee J, Song J, Hootman JM, et al. Obesity and other modifiable fac- tors for physical inactivity measured by accelerometer in adults with knee osteoarthritis: data from the osteoarthritis initiative (OAI). Arthritis Care Res (Hoboken). 2012;53-61. 70. Bramswig J, Dubbers A. Disorders of pubertal development. Deutsches Arzteblatt international. 2009;106:295-303. quiz 04 71. Elias CF, Purohit D. Leptin signaling and circuits in puberty and fertil- ity. Cell Mol Life Sci. 2013;70(5):841-862. 72. Riumallo J, Durnin JV. Changes in body composition in adolescent boys. Eur J Clin Nutr. 1988;42(2):107-112. 73. Siervogel RM, Demerath EW, Schubert C, et al. Puberty and body composition. Horm Res. 2003;60(Suppl 1):36-45. 74. Zhang J. Gong M. Andrologia: Review of the role of leptin in the regu- lation of male reproductive function; 2018. 75. Kauffman AS, Gottsch ML, Roa J, et al. Sexual differentiation of Kiss1 gene expression in the brain of the rat. Endocrinology. 2007;148(4): 1774-1783. 76. Zeydabadi Nejad S, Ramezani Tehrani F, Zadeh-Vakili A. The role of kisspeptin in female reproduction. Int J Endocrinol Metab. 2017;15:1- 11, e44337. 77. Sorensen K, Aksglaede L, Petersen JH, Juul A. Recent changes in pubertal timing in healthy Danish boys: associations with body mass index. J Clin Endocrinol Metab. 2010;95(1):263-270. 78. Juul A, Magnusdottir S, Scheike T, Prytz S, Skakkebaek NE. Age at voice break in Danish boys: effects of pre-pubertal body mass index and secular trend. Int J Androl. 2007;30(6):537-542. 79. Lee JM, Wasserman R, Kaciroti N, et al. Timing of puberty in overweight versus obese boys. Pediatrics. 2016;137(2):137-146, e20150164. 80. He F, Guan P, Liu Q, Crabtree D, Peng L, Wang H. The relationship between obesity and body compositions with respect to the timing of puberty in Chongqing adolescents: a cross-sectional study. BMC Pub- lic Health. 2017;17:664-673. 81. Ishikawa T, Fujioka H, Ishimura T, Takenaka A, Fujisawa M. Expres- sion of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia. 2007;39(1):22-27. 82. Martins AD, Moreira AC, Sa R, et al. Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility? Biochim Biophys Acta. 1852;2015: 1824-1832. 83. Morash BA, Willkinson D, Ur E, Wilkinson M. Resistin expression and regulation in mouse pituitary. FEBS Lett. 2002;526(1-3):26-30. 84. Cabrera SM, Bright GM, Frane JW, Blethen SL, Lee PA. Age of thelarche and menarche in contemporary US females: a cross- sectional analysis. Journal of pediatric endocrinology & metabolism: JPEM. 2014;27(1-2):47-51. 85. Herman-Giddens ME, Steffes J, Harris D, et al. Secondary sexual characteristics in boys: data from the Pediatric Research in Office Settings Network. Pediatrics. 2012;130(5):e1058-e1068. 86. WHO. Physical status: the use and interpretation of anthropometry. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1995;854:1-452. 87. Akin I, Tolg R, Hochadel M, et al. No evidence of âobesity paradoxâ after treatment with drug-eluting stents in a routine clinical practice: results from the prospective multicenter German DES.DE (German Drug-Eluting Stent) Registry. JACC Cardiovasc Interv. 2012;5(2): 162-169. 88. Marcovecchio ML, Chiarelli F. Obesity and growth during childhood and puberty. World Rev Nutr Diet. 2013;106:135-141. How to cite this article: Nieuwenhuis D, Pujol-Gualdo N, Arnoldussen IAC, Kiliaan AJ. Adipokines: A gear shift in puberty. Obesity Reviews. 2020;21:e13005. https://doi.org/ 10.1111/obr.13005 1467789x, 2020, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1111/obr.13005, Wiley Online Library on [10/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are goverâThereâs No Such Thing as Sound Scienceâ by By Christie Aschwanden was a lead science writer for FiveThirtyEight. FiveThirtyEight, Science, Dec. 6, 2017 Science is being turned against itself. For decades, its twin ideals of transparency and rigor have been weaponized by those who disagree with results produced by the scientific method. Under the Trump administration, that fight has ramped up again. In a move ostensibly meant to reduce conflicts of interest, Environmental Protection Agency Administrator Scott Pruitt has removed a number of scientists from advisory panels and replaced some of them with representatives from industries that the agency regulates. Like many in the Trump administration, Pruitt has also cast doubt on the reliability of climate science. For instance, in an interview with CNBC, Pruitt said that âmeasuring with precision human activity on the climate is something very challenging to do.â Similarly, Trumpâs pick to head NASA, an agency that oversees a large portion the nationâs climate research, has insisted that research into human influence on climate lacks certainty, and he falsely claimed that âglobal temperatures stopped rising 10 years ago.â Kathleen Hartnett White, Trumpâs nominee to head the White House Council on Environmental Quality, said in a Senate hearing last month that she thinks we âneed to have more precise explanations of the human role and the natural roleâ in climate change. The same entreaties crop up again and again: We need to root out conflicts. We need more precise evidence. What makes these arguments so powerful is that they sound quite similar to the points raised by proponents of a very different call for change thatâs coming from within science. This other movement strives to produce more robust, reproducible findings. Despite having dissimilar goals, the two forces espouse principles that look surprisingly alike: Science needs to be transparent. Results and methods should be openly shared so that outside researchers can independently reproduce and validate them. The methods used to collect and analyze data should be rigorous and clear, and conclusions must be supported by evidence. These are the arguments underlying an âopen scienceâ reform movement that was created, in part, as a response to a âreproducibility crisisâ that has struck some fields of science.1 But theyâre also used as talking points by politicians who are working to make it more difficult for the EPA and other federal agencies to use science in their regulatory decision-making, under the guise of basing policy on âsound science.â Scienceâs virtues are being wielded against it. What distinguishes the two calls for transparency is intent: Whereas the âopen scienceâ movement aims to make science more reliable, reproducible and robust, proponents of âsound scienceâ have historically worked to amplify uncertainty, create doubt and undermine scientific discoveries that threaten their interests. âOur criticisms are founded in a confidence in science,â said Steven Goodman, co-director of the Meta-Research Innovation Center at Stanford and a proponent of open science. âThatâs a fundamental difference â weâre critiquing science to make it better. Others are critiquing it to devalue the approach itself.â Calls to base public policy on âsound scienceâ seem unassailable if you donât know the termâs history. The phrase was adopted by the tobacco industry in the 1990s to counteract mounting evidence linking secondhand smoke to cancer. A 1992 Environmental Protection Agency report identified secondhand smoke as a human carcinogen, and Philip Morris responded by launching an initiative to promote what it called âsound science.â In an internal memo, Philip Morris vice president of corporate affairs Ellen Merlo wrote that the program was designed to âdiscredit the EPA report,â âprevent states and cities, as well as businesses from passing smoking bansâ and âproactivelyâ pass legislation to help their cause. The sound science tactic exploits a fundamental feature of the scientific process: Science does not produce absolute certainty. Contrary to how itâs sometimes represented to the public, science is not a magic wand that turns everything it touches to truth. Instead, itâs a process of uncertainty reduction, much like a game of 20 Questions. Any given study can rarely answer more than one question at a time, and each study usually raises a bunch of new questions in the process of answering old ones. âScience is a process rather than an answer,â said psychologist Alison Ledgerwood of the University of California, Davis. Every answer is provisional and subject to change in the face of new evidence. Itâs not entirely correct to say that âthis study proves this fact,â Ledgerwood said. âWe should be talking instead about how science increases or decreases our confidence in something.â The tobacco industryâs brilliant tactic was to turn this baked-in uncertainty against the scientific enterprise itself. While insisting that they merely wanted to ensure that public policy was based on sound science, tobacco companies defined the term in a way that ensured that no science could ever be sound enough. The only sound science was certain science, which is an impossible standard to achieve. âDoubt is our product,â wrote one employee of the Brown & Williamson tobacco company in a 1969 internal memo. The note went on to say that doubt âis the best means of competing with the âbody of factââ and âestablishing a controversy.â These strategies for undermining inconvenient science were so effective that theyâve served as a sort of playbook for industry interests ever since, said Stanford University science historian Robert Proctor. The sound science push is no longer just Philip Morris sowing doubt about the links between cigarettes and cancer. Itâs also a 1998 action plan by the American Petroleum Institute, Chevron and Exxon Mobil to âinstall uncertaintyâ about the link between greenhouse gas emissions and climate change. Itâs industry-funded groupsâ late-1990s effort to question the science the EPA was using to set fine-particle-pollution air-quality standards that the industry didnât want. And then there was the more recent effort by Dow Chemical to insist on more scientific certainty before banning a pesticide that the EPAâs scientists had deemed risky to children. Now comes a move by the Trump administrationâs EPA to repeal a 2015 rule on wetlands protection by disregarding particular studies. (To name just a few examples.) Doubt merchants arenât pushing for knowledge, theyâre practicing what Proctor has dubbed âagnogenesisâ â the intentional manufacture of ignorance. This ignorance isnât simply the absence of knowing something; itâs a lack of comprehension deliberately created by agents who donât want you to know, Proctor said.2 In the hands of doubt-makers, transparency becomes a rhetorical move. âItâs really difficult as a scientist or policy maker to make a stand against transparency and openness, because well, who would be against it?â said Karen Levy, researcher on information science at Cornell University. But at the same time, âyou can couch everything in the language of transparency and it becomes a powerful weapon.â For instance, when the EPA was preparing to set new limits on particulate pollution in the 1990s, industry groups pushed back against the research and demanded access to primary data (including records that researchers had promised participants would remain confidential) and a reanalysis of the evidence. Their calls succeeded and a new analysis was performed. The reanalysis essentially confirmed the original conclusions, but the process of conducting it delayed the implementation of regulations and cost researchers time and money. Delay is a time-tested strategy. âGridlock is the greatest friend a global warming skeptic has,â said Marc Morano, a prominent critic of global warming research and the executive director of ClimateDepot.com, in the documentary âMerchants of Doubtâ (based on the book by the same name). Moranoâs site is a project of the Committee for a Constructive Tomorrow, which has received funding from the oil and gas industry. âWeâre the negative force. Weâre just trying to stop stuff.â Some of these ploys are getting a fresh boost from Congress. The Data Quality Act (also known as the Information Quality Act) was reportedly written by an industry lobbyist and quietly passed as part of an appropriations bill in 2000. The rule mandates that federal agencies ensure the âquality, objectivity, utility, and integrity of informationâ that they disseminate, though it does little to define what these terms mean. The law also provides a mechanism for citizens and groups to challenge information that they deem inaccurate, including science that they disagree with. âIt was passed in this very quiet way with no explicit debate about it â that should tell you a lot about the real goals,â Levy said. But whatâs most telling about the Data Quality Act is how itâs been used, Levy said. A 2004 Washington Post analysis found that in the 20 months following its implementation, the act was repeatedly used by industry groups to push back against proposed regulations and bog down the decision-making process. Instead of deploying transparency as a fundamental principle that applies to all science, these interests have used transparency as a weapon to attack very particular findings that they would like to eradicate. Now Congress is considering another way to legislate how science is used. The Honest Act, a bill sponsored by Rep. Lamar Smith of Texas,3 is another example of what Levy calls a âTrojan horseâ law that uses the language of transparency as a cover to achieve other political goals. Smithâs legislation would severely limit the kind of evidence the EPA could use for decision-making. Only studies whose raw data and computer codes were publicly available would be allowed for consideration. That might sound perfectly reasonable, and in many cases it is, Goodman said. But sometimes there are good reasons why researchers canât conform to these rules, like when the data contains confidential or sensitive medical information.4 Critics, which include more than a dozen scientific organizations, argue that, in practice, the rules would prevent many studies from being considered in EPA reviews.5 It might seem like an easy task to sort good science from bad, but in reality itâs not so simple. âThereâs a misplaced idea that we can definitively distinguish the good from the not-good science, but itâs all a matter of degree,â said Brian Nosek, executive director of the Center for Open Science. âThere is no perfect study.â Requiring regulators to wait until they have (nonexistent) perfect evidence is essentially âa way of saying, âWe donât want to use evidence for our decision-making,ââ Nosek said. Most scientific controversies arenât about science at all, and once the sides are drawn, more data is unlikely to bring opponents into agreement. Michael Carolan, who researches the sociology of technology and scientific knowledge at Colorado State University, wrote in a 2008 paper about why objective knowledge is not enough to resolve environmental controversies. âWhile these controversies may appear on the surface to rest on disputed questions of fact, beneath often reside differing positions of value; values that can give shape to differing understandings of what âthe factsâ are.â Whatâs needed in these cases isnât more or better science, but mechanisms to bring those hidden values to the forefront of the discussion so that they can be debated transparently. âAs long as we continue down this unabashedly naive road about what science is, and what it is capable of doing, we will continue to fail to reach any sort of meaningful consensus on these matters,â Carolan writes. The dispute over tobacco was never about the science of cigarettesâ link to cancer. It was about whether companies have the right to sell dangerous products and, if so, what obligations they have to the consumers who purchased them. Similarly, the debate over climate change isnât about whether our planet is heating, but about how much responsibility each country and person bears for stopping it. While researching her book âMerchants of Doubt,â science historian Naomi Oreskes found that some of the same people who were defending the tobacco industry as scientific experts were also receiving industry money to deny the role of human activity in global warming. What these issues had in common, she realized, was that they all involved the need for government action. âNone of this is about the science. All of this is a political debate about the role of government,â she said in the documentary. These controversies are really about values, not scientific facts, and acknowledging that would allow us to have more truthful and productive debates. What would that look like in practice? Instead of cherry-picking evidence to support a particular view (and insisting that the science points to a desired action), the various sides could lay out the values they are using to assess the evidence. For instance, in Europe, many decisions are guided by the precautionary principle â a system that values caution in the face of uncertainty and says that when the risks are unclear, it should be up to industries to show that their products and processes are not harmful, rather than requiring the government to prove that they are harmful before they can be regulated. By contrast, U.S. agencies tend to wait for strong evidence of harm before issuing regulations. Both approaches have critics, but the difference between them comes down to priorities: Is it better to exercise caution at the risk of burdening companies and perhaps the economy, or is it more important to avoid potential economic downsides even if it means that sometimes a harmful product or industrial process goes unregulated? In other words, under what circumstances do we agree to act on a risk? How certain do we need to be that the risk is real, and how many people would need to be at risk, and how costly is it to reduce that risk? Those are moral questions, not scientific ones, and openly discussing and identifying these kinds of judgment calls would lead to a more honest debate. Science matters, and we need to do it as rigorously as possible. But science canât tell us how risky is too risky to allow products like cigarettes or potentially harmful pesticides to be sold â those are value judgements that only humans can make.Why should mankind explore space? Why should money, time and effort be spent exploring, investigating and researching something with so few apparent benefits? Why should resources be spent on space rather than on conditions and people on Earth? These are questions that, understandably, are very often asked. Perhaps the best answer lies in our genetic makeup as human beings. What drove our distant ancestors to move from the trees into the plains, and on into all possible areas and environments? It appears that we are driven to ensure the success and continuation of not just our own genes, but of the species as a whole. The wider the distribution of a species, the better its chance of survival. Perhaps the best reason for exploring space is this genetic predisposition to expand wherever possible. Nearly every successful civilisation has explored, because by doing so, any dangers in surrounding areas can be identified and prepared for. These might be enemies in neighbouring cultures, physical features of the area, a change in the area which might affect food supplies, or any number of other factors. They all pose a real danger, and all can be made less threatening if certain preparations are made. Without knowledge, we may be completely destroyed by the danger. With knowledge, we can lessen its effects. Exploration also allows minerals and other potential resources to be located. Additional resources are always beneficial when used wisely, and can increase our chances of survival. Even if we have no immediate need of them, they will perhaps be useful later. Resources may be more than physical assets. Knowledge or techniques acquired through exploration, or preparing to explore, filter from the developers into society at large. The techniques may have medical applications which can improve the length or quality of our lives. Techniques may be social, allowing members of society better to understand those within or outside the culture. Better understanding may lead to more efficient use of resources, or a reduction in competition for resources. We have already benefited from other spin-offs, including improvements in earthquake prediction â which has saved many lives â in satellites used for weather forecasting and in communications systems. Even non-stick saucepans and mirrored sunglasses are by-products of technological developments in the space industry! While many resources are spent on what seems a small return, the exploration of space allows creative, brave and intelligent members of our species to focus on what may serve to save us. While space may hold many wonders and explanations of how the universe was formed or how it works, it also holds dangers. The chances of a large comet or asteroid hitting the Earth are small, but it could happen in time. Such strikes in the past may account for the extinction of dinosaurs and other species. Human technology is reaching the point where it might be able to detect the possibility of this happening, and enable us to minimise the damage, or prevent it completely, allowing us as a species to avoid extinction. The danger exists, but knowledge can help human beings to survive. Without the ability to reach out across space, the chance to save ourselves might not exist. In certain circumstances, life on Earth may become impossible: over-population or epidemics, for instance, might eventually force us to find other places to live. While Earth is the only planet known to sustain life, surely the adaptive ability of humans would allow us to inhabit other planets and moons. It is true that the lifestyle would be different, but human life and cultures have adapted in the past and surely could in the future. The more a culture expands, the less chance there is that it will become extinct. Space allows us to expand and succeed: for the sake of everyone on the Earth, now and in the future, space exploration is essential.Owls, such as the young snowy owls on the previous page, have for centuries been symbols of both wisdom and mystery. To many cultures their piercing eyes have conveyed a look of intelligence. Their silent flight through darkened landscapes in search of prey has projected an air of power or wonder. For this chapter and this book, owls are an engaging example of a living organism from the world of biologyâthe study of life. BIOLOGY AND YOU Living in a small town, in the country, or at the edge of the suburbs, one may be lucky enough to hear an owl's hooting. This experience can lead to questions about where the bird lives, what it hunts, and how it finds its prey on dark, moonless nights. Biology, or the study of life, offers an organized and scientific framework for posing and answering such questions about the natural world. Biologists study questions about how living things work, how they interact with the environment, and how they change over time. Biologists study many different kinds of living things ranging from tiny organisms, such as bacteria, to very large organisms, such as elephants. Each day, biologists investigate subjects that affect you and the way you live. For example, biologists determine which foods are healthy. As shown in Figure 1-1, everyone is affected by this impor- tant topic. Biologists also study how much a person should exer- cise and how one can avoid getting sick. Biologists also study what CHARACTERISTICS OF LIFE The world is filled with familiar objects, such as tables, rocks, plants, pets, and automobiles. Which of these objects are living or were once living? What are the criteria for assigning something to the living world or the nonliving world? Biologists have established that living things share seven characteristics of life. These characteristics are organization and the presence of one or more cells, response to a stimulus (plural, stimuli), homeostasis, metabolism, growth and development, reproduction, and change through time. Organization and Cells Organization is the high degree of order within an organismâs internal and external parts and in its interactions with the living world. For example, compare an owl to a rock. The rock has a spe- cific shape, but that shape is usually irregular. Furthermore, differ- ent rocks, even rocks of the same type, are likely to have different shapes and sizes. In contrast, the owl is an amazingly organized individual, as shown in Figure 1-2. Owls of the same species have the same body parts arranged in nearly the same way and interact with the environment in the same way. Copyright © by Holt, Rinehart and Winston. All rights reserved. ORGANISM (Barn Owl) ORGAN (Owlâs Ear) TISSUE (Nervous Tissue Within the Ear) CELL (Nerve Cell) your air, land, and fAll living organisms, whether made up of one cell or many cells, have some degree of organization. A cell is the smallest unit that can perform all lifeâs processes. Some organisms, such as bacteria, are made up of one cell and are called unicellular (YOON-uh-SEL-yoo-luhr) organisms. Other organisms, such as humans or trees, are made up of multiple cells and are called multicellular (MUHL-ti-SEL-yoo-luhr) organisms. Complex multicellular organisms have the level of orga- nization shown in Figure 1-2. In the highest level, the organism is made up of organ systems, or groups of specialized parts that carry out a certain function in the organism. For example, an owlâs ner- vous system is made up of a brain, sense organs, nerve cells, and other parts that sense and respond to the owlâs surroundings. Organ systems are made up of organs. Organs are structures that carry out specialized jobs within an organ system. An owlâs ear is an organ that allows the owl to hear. All organs are made up of tissues. Tissues are groups of cells that have similar abilities and that allow the organ to function. For example, nervous tissue in the ear allows the ear to detect sound. Tissues are made up of cells. A cell must be covered by a membrane, contain all genetic information necessary for replication, and be able to carry out all cell functions. Within each cell are organelles. Organelles are tiny structures that carry out functions necessary for the cell to stay alive. Organelles contain biological molecules, the chemical compounds that provide physical structure and that bring about movement, energy use, and other cellular functions. All biological molecules are made up of atoms. Atoms are the simplest particle of an ele- ment that retains all the properties of a certain element. Response to Stimuli Another characteristic of life is that an organism can respond to a stimulusâa physical or chemical change in the internal or external environment. For example, an owl dilates its pupils to keep the level of light entering the eye constant. Organisms must be able to respond and react to changes in their environment to stay alive. ORGANELLE (Mitochondrion) BIOLOGICAL MOLECULE (Phospholipid) ATOM (Oxygen) cell from the Latin, cella meaning âsmall room,â or âhutâ Word Roots and Origins www.scilinks.org Topic: Characteristics of Life Keyword: HM60257 mb06se_bios01.qxd 5/18/07 10:37 AM Page 7 8 CHAPTER 1 Homeostasis All living things, from single cells to entire organisms, have mecha- nisms that allow them to maintain stable internal conditions. Without these mechanisms, organisms can die. For example, a cellâs water content is closely controlled by the taking in or releas- ing of water. A cell that takes in too much water will rupture and die. A cell that doesnât get enough water will also shrivel and die. Homeostasis (HOH-mee-OH-STAY-sis) is the maintenance of a stable level of internal conditions even though environmental conditions are constantly changing. Organisms have regulatory systems that maintain internal conditions, such as temperature, water content, and uptake of nutrients by the cell. In fact, multi- cellular organisms usually have more than one way of maintain- ing important aspects of their internal environment. For example, an owlâs temperature is maintained at about 40°C (104°F). To keep a constant temperature, an owlâs cells burn fuel to produce body heat. In addition, an owlâs feathers can fluff up in cold weather. In this way, they trap an insulating layer of air next to the birdâs body to maintain its body temperature. Metabolism Living organisms use energy to power all the life processes, such as repair, movement, and growth. This energy use depends on metabolism (muh-TAB-uh-LIZ-uhm). Metabolism is the sum of all the chemical reactions that take in and transform energy and materials from the environment. For example, plants, algae, and some bacteria use the sunâs energy to generate sugar molecules during a process called photosynthesis. Some organisms depend on obtaining food energy from other organisms. For instance, an owlâs metabolism allows the owl to extract and modify the chemi- cals trapped in its nightly prey and use them as energy to fuel activities and growth. Growth and Development All living things grow and increase in size. Some nonliving things, such as crystals or icicles, grow by accumulating more of the same material of which they are made. In contrast, the growth of living things results from the division and enlargement of cells. Cell division is the formation of two new cells from an existing cell, as shown in Figure 1-3. In unicellular organisms, the primary change that occurs following cell division is cell enlargement. In multi- cellular life, however, organisms mature through cell division, cell enlargement, and development. Development is the process by which an organism becomes a mature adult. Development involves cell division and cell differen- tiation, or specialization. As a result of development, an adult organism is composed of many cells specialized for different func- tions, such as carrying oxygen in the blood or hearing. In fact, the human body is composed of trillions of specialized cells, all of which originated from a single cell, the fertilized egg. This unicellular organism, Escherichia coli, inhabits the human intestines. E. coli reproduces by means of cell division, during which the original cell splits into two identical offspring cells. FIGURE 1-3 Observing Homeostasis Materials 500 mL beakers (3), wax pen, tap water, thermometer, ice, hot water, goldfish, small dip net, watch or clock with a second hand Procedure 1. Use a wax pen to label three 500 mL beakers as follows: 27°C (80°F), 20°C (68°F), 10°C (50°F). Put 250 mL of tap water in each beaker. Use hot water or ice to adjust the tem- perature of the water in each beaker to match the temperature on the label. 2. Put the goldfish in the beaker of 27°C water. Record the number of times the gills move in 1 minute. 3. Move the goldfish to the beaker of 20°C water. Repeat observations. Move the goldfish to the beaker of 10°C. Repeat observations. Analysis What happens to the rate at which gills move when the temp- erature changes? Why? How do gills help fish maintain homeostasis? Quick Lab mb06se_bios01.qxd 5/18/07 10:37 AM Page 8 THE SCIENCE OF LIFE 9 Reproduction All organisms produce new organisms like themselves in a process called reproduction. Reproduction, unlike other characteristics, is not essential to the survival of an individual organism. However, because no organism lives forever, reproduction is essential for the continuation of a species. Glass frogs, as shown in Figure 1-4, lay many eggs in their lifetime. However, only a few of the frogsâ off- spring reach adulthood and successfully reproduce. During reproduction, organisms transmit hereditary informa- tion to their offspring. Hereditary information is encoded in a large molecule called deoxyribonucleic acid, or DNA. A short segment of DNA that contains the instructions for a single trait of an organism is called a gene. DNA is like a large library. It contains all the booksâgenesâthat the cell will ever need for making all the struc- tures and chemicals necessary for life. Hereditary information is transferred to offspring during two kinds of reproduction. In sexual reproduction, hereditary information recombines from two organisms of the same species. The resulting offspring are similar but not identical to their parents. For example, a male frogâs sperm can fertilize a femaleâs egg and form a single fer- tilized egg cell. The fertilized egg then develops into a new frog. In asexual reproduction, hereditary information from different organisms is not combined; thus the original organism and the new organism are genetically the same. A bacterium, for example, reproduces asexually when it splits into two identical cells. Change Through Time Although individual organisms experience many changes during their lifetime, their basic genetic characteristics do not change. However, populations of living organisms evolve or change through time. The ability of populations of organisms to change over time is important for survival in a changing world. This factor is also impor- tant in explaining the diversity of life-forms we see on Earth today. 1. How does biology affect a personâs daily life? 2. How does biology affect society? 3. Name the characteristics shared by living things. 4. Summarize the hierarchy of organization found in complex multicellular organisms. 5. What are the different functions of homeostasis and metabolism in living organisms? 6. How does the growth among living and nonliv- ing things differ? 7. Why is reproduction an important characteristic of life? CRITICAL THINKING 8. Applying Information Crystals of salt grow and are highly organized. Why donât biologists con- sider them to be alive? 9. Analyzing Models When a scientist designs a space probe to detect life on a distant planet, what kinds of things should it measure? 10. Making Comparisons Both cells and organisms share the characteristics of life. How are cells and organismsood supply will be like in the near future.EVOLUTION OF LIFE Individual organisms change during their lifetime, but their basic genetic characteristics do not change. However, populations of liv- ing organisms do change through time, or evolve. Evolution, or descent with modification, is the process in which the inherited characteristics within populations change over generations, such that genetically distinct populations and new species can develop. Evolution as a theme in biology helps us understand how the various branches of the âtree of lifeâ came into existence and have changed over time. It also explains how organisms alive today are related to those that lived in the past. Finally, it helps us understand the mechanisms that underlie the way organisms look and behave. Natural Selection The ability of populations of organisms to change over time is important for survival in a changing world. According to the theory of evolution by natural selection, organisms that have certain favorable traits are better able to survive and reproduce success- fully than organisms that lack these traits. One product of natural selection is the adaptation of organisms to their environment. Adaptations are traits that improve an indi- vidualâs ability to survive and reproduce. For example, rabbits with white fur and short ears in a snowy place, such as the one in Figure 1-7a, may avoid predators and frostbitten ears more often than those with dark fur and long ears. Thus, the next generation of rabbits will have a greater percentage of animals carrying the genes for white fur and short ears. In contrast, the brown, long- eared rabbit, as shown in Figure 1-7b, would survive and reproduce more successfully in a hot desert environment. The survival and reproductive success of organisms with favor- able traits cause a change in populations of organisms over gener- ations. This descent with modification is an important factor in explaining the diversity of organisms we see on Earth today. 1. Name three unifying themes found in biology. 2. How is the unity and diversity in the living world represented? 3. Identify the three domains and the kingdoms found in each domain. 4. How are organisms interdependent? 5. Describe why evolution is important in explain- ing the diversity of life. 6. Distinguish between evolution and natural selection. CRITICAL THINKING 7. Applying Information Assign the various top- pings you put on pizza to the appropriate domains and kingdoms of life. 8. Analyzing Graphics According to the âtreeâ in Figure 1-5, which of these pairs are more closely related: Archaea:Bacteria or Archaea:Eukarya? 9. Making Hypotheses Fossil evidence shows that bats descended from shrewlike organisms that could not fly. Write a hypothesis for how natural selection might have led to flying bats. SECTION 2 REVIEW (a) This short-eared arctic hare, Lepus arcticus, is hidden from predators and protected from frostbite in a snowy environment. (b) The mottled brown coats of desert rabbits blend in with the dirt and dry grasses, and their long ears help them radiate excess heat and thus avoid overheating. FIGURE 1-7 (a) (b) Copyright © by Holt, Rinehart and Winston. All rights reserved. THE SCIENCE OF LIFE 13 TH E STUDY OF BIOLOGY Curiosity leads us to ask questions about life. Science provides a way of answering such questions about the natural world. Science is a systematic method that involves forming and testing hypotheses. More importantly, science relies on evidence, not beliefs, for drawing conclusions. SCIENCE AS A PROCESS Science is characterized by an organized approach, called the scientific method, to learn how the natural world works. The methods of science are based on two important principles. The first principle is that events in the natural world have natural causes. For example, the ancient Greeks believed that lightning and thunder occurred because a supernatural god Zeus hurled thunderbolts from the heavens. By contrast, a scientist considers lightning and thunder to result from electric charges in the atmos- phere. When trying to solve a puzzle from nature, all scientists, such as the one in Figure 1-8, accept that there is a natural cause to solve that puzzle. A second principle of science is uniformity. Uniformity is the idea that the fundamental laws of nature operate the same way at all places and at all times. For example, scientists assume that the law of gravity works the same way on Mars as it does on Earth. Steps of the Scientific Method Although there is no single method for doing science, scientific studies involve a series of common steps. 1. The process of science begins with an observation. An observation is the act of perceiving a natural occurrence that causes someone to pose a question. 2. One tries to answer the question by forming hypotheses (singular, hypothesis). A hypothesis is a proposed explanation for the way a particular aspect of the natural world functions. 3. A prediction is a statement that forecasts what would happen in a test situation if the hypothesis were true. A prediction is recorded for each hypothesis. 4. An experiment is used to test a hypothesis and its predictions. 5. Once the experiment has been concluded, the data are analyzed and used to draw conclusions. 6. After the data have been analyzed, the data and conclusions are communicated to scientific peers and to the public. This way oth- ers can verify, reject, or modify the researcherâs conclusions. SECTION 3 OBJECTIVES â Outline the main steps in the scientific method. â Summarize how observations are used to form hypotheses. â List the elements of a controlled experiment. â Describe how scientists use data to draw conclusions. â Compare a scientific hypothesis and a scientific theory. â State how communication in science helps prevent dishonesty and bias. VOCABULARY scientific method observation hypothesis prediction experiment control group experimental group independent variable dependent variable theory peer review All researchers, such as the one releasing an owl above, use the scientific method to answer the questions they have about nature. FIGURE 1-8 Copyright © by Holt, Rinehart and Winston. All rights reserved. 14 CHAPTER 1 OBSERVING AND ASKING QUESTIONS The scientific method generally begins with an unexplained observa- tion about nature. For example, people have noticed for thousands of years that owls can catch prey in near total darkness. As shown in steps and of Figure 1-9, an observation may then raise ques- tions. The owl observation raises the question: How does an owl detect prey in the dark? FORMING A HYPOTHESIS After stating a question, a biologist lists possible answers to a sci- entific questionâhypotheses. Good hypotheses answer a question and are testable in the natural world. For example, as shown in step Figure 1-9, there are several possible hypotheses for the question of how owls hunt at night: (a) owls hunt by keen vision in the dark; (b) owls hunt by superb hearing; or (c) owls hunt by detecting the preyâs body heat. Predicting To test a hypothesis, scientists make a prediction that logically fol- lows from the hypothesis. A prediction is what is expected to hap- pen if each hypothesis were true. For example, if hypothesis (a) is true, (owls hunt by keen night vision) then one can predict that the owl will pounce only on the mouse in either a light or a dark room. If hypothesis (b) is true (owls hunt by hearing), then one can pre- dict that in a lighted room, the owl will pounce closer to the mouseâs head. But, in a dark room, the owl should pounce closer to a rustling leaf attached to the mouse. Finally, if hypothesis (c) is true (owls hunt by sensing body heat), then an owl would strike only the prey no matter the room conditions, because owls hunt by detecting the preyâs body heat. 3 1 2 Copyright © by Holt, Rinehart and Winston. All rights reserved. A scientific study includes observations, questions, hypotheses, predictions, experiments, data analysis, and conclu- sions. A biologist can use the scientific method to set up an experiment to learn how an owl captures prey at night. FIGURE 1-9 1 OBSERVATION Owls capture prey on dark nights. 2 QUESTION How do owls detect prey on dark nights? 3 HYPOTHESES a) Owls hunt in the dark by vision. b) Owls hunt in the dark by hearing. c) Owls hunt in the dark by sensing body heat. THE SCIENCE OF LIFE 15 Notice that these predictions make it difficult to distinguish be- tween the vision and body heat hypotheses. The reason is that both hypotheses predict that the owl could grab the mouse in a dark room. Also, these three hypotheses do not eliminate all other factors that could influence how the owl finds its prey. However, testing predictions can allow one to begin rejecting hypotheses and thus to get closer to determining the answer(s) to a question. DESIGNING AN EXPERIMENT Biologists often test hypotheses by setting up an experiment. Step in Figure 1-9 outlines an experiment to test the hypotheses about how an owl hunts at night. First, experimenters set up a room with an owl perch high on one side and a small trap door on the other side for releasing mice. Then, they tied a leaf to each mouseâs tail with a string and released each mouse into the room. Next, each mouse ran silently across the room, but the leaf trailed behind, making a rustling noise. During half of the trials, the lights were on. During the other half, the room was dark. Technicians videotaped all the action in the chamber with an infrared light, which owls cannot see. The researchers then viewed the videos and measured the position of the owlâs strike relative to each mouseâs head. Performing the Experiment Many scientists use a controlled experiment to test their hypotheses. A controlled experiment compares an experimental group and a control group and only has one variable. The control group pro- vides a normal standard against which the biologist can compare results of the experimental group. The experimental group is iden- tical to the control group except for one factor, the independent variable. The experimenter manipulates the independent variable, sometimes called the manipulated variable. 4 4 EXPERIMENT 5 DATA COLLECTION AND ANALYSIS Measure and compare the distance from the owlâs strike to the mouse and to the leaf in light and dark. 6 CONCLUSION Data supported the hearing hypothesis: Owls hunt in the dark by hearing. prey Test predictions of the three hypotheses. Control: In the light Experimental: In the dark 1 2 3 4 5 6 7 8 9 10 11 Predicting Results Materials 2 Petri dishes with agar, cellophane tape, wax pen Procedure 1. Open one of the Petri dishes, and streak your finger across the surface of the agar. 2. Replace the lid, and seal it with the tape. Label this Petri dish with your name and a number 1. 3. Seal the second Petri dish with- out removing the lid. Label this Petri dish with your name and the number 2. 4. Write a prediction about what will happen in each dish. Store your dishes as your teacher directs. Record your observations. Follow your teacherâs directions for disposal of your dishes. Analysis Was your prediction accurate? What evidence can you cite to support your prediction? If you did not obtain the results you predicted, would you change your testing method or your prediction? Explain. Evaluate the importance of obtaining a result that does not support your prediction. Quick Lab mb06se_bios03.qxd 5/18/07 10:40 AM Page 15 16 CHAPTER 1 The independent variable in the owl experiment is the presence or absence of light. In the owl experiment, the control group hunts in the light, and the experimental group hunts in the dark. In addi- tion to varying the independent variable, a scientist observes or measures another factor called the dependent variable, or respond- ing variable, because it is affected by the independent variable. In the owl experiment, the dependent variable is distance from the owlâs strike to the mouseâs head. Testing the Experiment Some controlled experiments are conducted âblind.â In other words, the biologist who scores the results is unaware of whether a given subject is part of the experimental or control group. This factor helps eliminate experimenter bias. Experiments should also be repeated, because living systems are variable. Moreover, scien- tists must collect enough data to find meaningful results. COLLECTING AND ANALYZING DATA Most experiments measure a variableâthe dependent variable. This measurement provides quantitative data, data measured in numbers. For example, in the experiment above, scientists mea- sured the distance of an owlâs strike from the preyâs head in cen- timeters, as shown in step of Figure 1-9. An eventâs duration in milliseconds is also an example of quantitative data. Biologists usually score the results of an experiment by using one of their senses. They might see or hear the results of an experiment. Scientists also extend their senses with a micro- scope for tiny objects or a microphone for soft sounds. In the owl experiment, biologists extended their vision with infrared cameras. Analyzing and Comparing Data After collecting data from a field study or an experiment and then organizing it, biologists then analyze the data. In analyzing data, the goal is to determine whether the data are reliable, and whether they support or fail to support the predictions of the hypothesis. To do so, scientists may use statistics to help determine relation- ships between the variables involved. They can then compare their data with other data that were obtained in other similar studies. It is also important at this time to determine possible sources of error in the experiment just per- formed. Scientists usually display their data in tables or graphs when analyzing it. For the owl study, biologists could have made a bar graph such as the one in Figure 1-10, which shows the average distance from the owlâs strike relative to the mouseâs head or the leaf in the light and in the dark. 5 5 0 10 15 20 25 In the light In the dark Average distance from strike (cm) Distance Between Owl Strike and a Mouse or From a Leaf Attached to Mouse 30 Mouse Leaf Mouse Leaf The data below are hypothetical results that might occur from the described owl experiment.The independent variable is the darkness of the room, and the dependent variable is how far the owl struck from the mouseâs head.The data show that the owl strikes more accurately at the mouse in the light but strikes more accurately at the leaf in the dark. FIGURE 1-10 Copyright © by Holt, Rinehart and Winston. All rights reserved. THE SCIENCE OF LIFE 17 DRAWING CONCLUSIONS Biologists analyze their tables, graphs, and charts to draw conclu- sions about whether or not a hypothesis is supported, as shown in step of Figure 1-9. The hypothetical owl data show that in the light, owls struck with greater accuracy at the mouse than at the leaf, but in the dark, owls struck with greater accuracy at the leaf than the mouse. Thus, the findings support the hearing hypothe- sis, but not the vision hypothesis. An experiment can only disprove, not prove, a hypothesis. For example, one cannot conclude from the results that the hearing hypothesis is proven to be true. Perhaps the owl uses an unknown smell to strike at the mouse. One can only reject the vision hypothe- sis because it did not predict the results of the experiment correctly. Acceptance of a hypothesis is always tentative in science. The scientific community revises its understanding of phenomena, based on new data. Having ruled out one hypothesis, a biologist will devise more tests to try to rule out any remaining hypotheses. Making Inferences Scientists often draw inferences from data gathered during a field study or experiment. An inference (IN-fuhr-uhns) is a conclusion made on the basis of facts and previous knowledge rather than on direct observations. Unlike a hypothesis, an inference is not directly testable. In the owl study, it is inferred that the owl detects prey from a distance rather than by direct touch. Applying Results and Building Models As shown in Figure 1-11, scientists often apply their findings to solve practical problems. They also build models to represent or describe things. For example in 1953, James Watson and Francis Crick used cardboard balls and wire bars to build physical models of atoms in an attempt to understand the structure of DNA. Mathematical models are sets of equations that describe how dif- ferent measurable items interact in a system. The experimenter can adjust variables to better model the real-world data. CONSTRUCTING A THEORY When a set of related hypotheses is confirmed to be true many times, and it can explain a great amount of data, scientists often reclassify it as a theory. Some examples include the quantum the- ory, the cell theory, or the theory of evolution. People commonly use the word âtheoryâ in a different way than scientists use the word. People may say âItâs just a theoryâ suggesting that an idea is untested, but scientists view a theory as a highly tested, generally accepted principle that explains a vast number of observations and experimental data. 6 Copyright © by Holt, Rinehart and Winston. All rights reserved. Biologists often apply their knowledge of the natural world to practical problems. Studies on the owlâs keen ability to locate sounds in space despite background noise are helping biotechnologists and bioengineers develop better solutions for people with impaired hearing, such as the people shown in this picture. FIGURE 1-11 18 CHAPTER 1 COMMUNICATING IDEAS An essential aspect of scientific research is scientists working together. Scientists often work together in research teams or sim- ply share research results with other scientists. This is done by publishing findings in scientific journals or presenting them at sci- entific meetings, as shown in Figure 1-12. Sharing information allows others working independently to verify findings or to con- tinue work on established results. For example, Roger Payne pub- lished the results of his owl experiments in a journal in 1971. Then, other biologists could repeat it for verification or use it to study the mechanisms introduced by the paper. With the growing impor- tance of science in solving societal issues, it is becoming increas- ingly vital for scientists to be able to communicate with the public at large. Publishing a Paper Scientists submit research papers to scientific journals for publica- tion. A typical research paper has four sections. First, the Introduction poses the problem and hypotheses to be investigated. Next, the Materials and Methods describe how researchers proceeded with the experiment. Third, the Results state the findings the experiment presented, and finally, the Discussion gives the significance of the experiment and future directions the scientists will take. Job Description Forensic biolo- gists are scientists who study biological materials to investigate potential crimes and other legal issues against humans and animals. Forensic scientists have knowledge in areas of biology, such as DNA and blood pattern analysis, and work in private sector and public laboratories. Focus On a Forensic Biologist As a law enforcement forensic specialist for the Texas Parks and Wildlife Department, Beverly Villarreal assists the game warden in investigations of fish and wildlife violations, such as illegal hunting and fishing. Villarreal analyzes blood and tissue samples to identify species of animals such as fish, birds, and reptiles. Her work helps game wardens as they enforce state laws regarding hunting and fishing. Most people think of forensic scientists as the glamorous crime investigators on TV, but according to Villarreal real forensic scientists âspend a great deal of time at a lab bench running analysis after analysis.â Many of the methods used in animal forensics, such as DNA sequenc- ing, are also used in human forensics. Education and Skills âą High schoolâthree years of science courses and four years of math courses. âą Collegeâbachelor of science in biol- ogy, including course work in zoology and genetics, plus experience in per- forming DNA analyses. âą Skillsâpatience, attention to detail, and ability to use fine tools. Careers in BIOLOGY Forensic Biologist For more about careers, visit go.hrw.com and type in the keyword HM6 Careers. www.scilinks.org Topic: Scientific Investigations Keyword: HM61358 mb06se_bios03.qxd 5/18/07 10:40 AM Page 18 THE SCIENCE OF LIFE 19 1. What two principles make the scientific method a unique process? 2. Define the roles of observations and hypotheses in science. 3. Summarize the parts of a controlled experiment. 4. Summarize how we make conclusions about the results of an experiment. 5. Why is the phrase, âitâs just a theoryâ misleading? 6. Give another example of a conflict of interest. CRITICAL THINKING 7. Making Hypotheses On a nocturnal owlâs skull, one ear points up, and the other ear points down. Suggest a hypothesis for this observation. 8. Designing Experiments Design an experiment to establish if owls hunt by keen sight or hunt by heat seeking. 9. Calculating Information What was the average distance between the owlâs strike and the mouse if the recorded differences in this experiment were 25, 22, 19, 19, and 15? SECTION 3 REVIEW After scientists submit their papers to a scientific journal, the editors of that journal will send the paper out for peer review. In a peer review, scientists who are experts in the field anonymously read and critique that research paper. They determine if a paper pro- vides enough information so that the experiment can be duplicated and if the author used good experimental controls and reached an accurate conclusion. They also check if the paper is written clearly enough for broad understanding. Careful analysis of each otherâs research by fellow scientists is essential to making scientific progress and preventing scientific dishonesty. HONESTY AND BIAS The scientific community depends on both honesty and good sci- ence. While designing new studies, experimenters must be very careful to prevent previous ideas and biases from tainting both the experimental process and the conclusions. Scientists have to keep in mind that they are always trying to disprove their favorite ideas. Scientists repeat experiments to verify previous findings. This allows for science to have a method for self-correction and it also keeps researchers honest and credible to their peers in the field. Conflict of Interest For most scientists, maintaining a good reputation for collecting and presenting valid data is more important than temporary prestige or income. So, scientists try to avoid any potential conflicts of interest. For example, a scientist who owns a biotechnology company and manufactures a drug would not be the best researcher to critically test that drugâs safety and effectiveness. To avoid this potential con- flict of interest, the scientist allows an unaffected party, such as a research group, to test the drugâs effectiveness. The threat of a potential scandal based on misleading data or conclusions is a pow- erful force in science that helps keep scientists honest and fair. Scientists present their experiments in various forms. The scientists above are presenting their work in the form of a poster at a scientific meeting. FIGURE 1-12 Copyright © by Holt, Rinehart and Winston. All rights reserved. The Internet can provide a wealth of scientific information for a report, but the information may not always be credible or accurate. You can use the methods above to check the accuracy and credibility of your sources. SCIENCE TECHNOLOGY SOCIETY SCIENCE ON THE INTERNET: A New Information Age I n the past, students research- ing a science topic would typ- ically begin their research by visiting a library to use printed reference materials, such as encyclopedias. Today, most stu- dents research topics by using a computer and searching for information on the Internet. The Internet can provide students with a wealth of infor- mation. But which Web sites have accurate information, and which Web sites do not? Checking Web Addresses Students should use the Web address, or URL, to establish the Web siteâs credibility. Usually, the domain name can suggest who has published the Web site. Web sites can be pub- lished by governmental agen- cies (ends in âdot govâ or .gov), by educational institutions (ends in âdot eduâ or .edu), by organizations (ends in âdot orgâ or .org), or by commercial businesses (ends in âdot comâ or .com). Government Web sites are usually reliable. Examples of credible governmental Web sites are the National Institutes of Health (NIH) and the Food and Drug Administration (FDA). University and medical school sites are also reliable sources of information. Many organiza- tions that research and teach the public about specific diseases and conditions can also provide reliable information. Examples of such organizations are the American Cancer Society and the American Heart Association. Evaluating Web Sites The credibility of the author of the Web site should also be checked. Make sure the author is not trying to sell anything and is established in his or her field. For example, a health Web siteâs author should be a med- ical professional. It is also important to check the date that the information was posted on the Web to ensure that the information is current. Also, the Web site should provide ref- erences from valid sources, such as scientific journals or govern- ment publications. Finally, the student should always double-check informa- tion between several reliable Web sites. If two or three reliable sites provide the same informa- tion, the student can feel confi- dent in using that information. Web Sites for Students The Internet Connect boxes in this textbook have all been reviewed by professionals at the National Science Teachers Association (NSTA). Students can trust that these sites are reliable sources for science- or health-related topics. REVIEW 1. Which types of Web addresses are the most reliable? 2. List four important features to evaluate when using a Web site for research. 3. Supporting Reasoned Opinions Why do you think a Web site that is advertising a product may not offer accurate information? REVIEW 20 www.scilinks.org Topic: Using the Internet Keyword: HM61589 mb06se_biosts.qxd 5/18/07 10:42 AM Page 20 TOOLS AND TECHNIQUES With proper equipment and good methods, biologists can see, manipulate, and understand the natural world in new ways. Microscopes are one of many useful tools used to unlock natureâs biological secrets. MICROSCOPES AS TOOLS Tools are objects used to improve the performance of a task. Microscopes are tools that extend human vision by making enlarged images of objects. Biologists use microscopes to study organisms, cells, cell parts, and molecules. Microscopes reveal details that otherwise might be difficult or impossible to see. Light Microscopes To see small organisms and cells, biologists typically use a light microscope, such as the one shown in Figure 1-13. A compound light microscope is a microscope that shines light through a spec- imen and has two lenses to magnify an image. To use this micro- scope, one first mounts the specimen to be viewed on a glass slide. The specimen must be thin enough for light to pass through it. For tiny pond organisms, such as the single-celled paramecium, light passing through the organism is not a problem. For thick objects, such as plant stems, biologists must cut thin slices for viewing. There are four major parts of a compound light microscope. For further description of the parts of a micro- scope, see the Appendix. 1. Eyepiece The eyepiece (ocular (AHK-yoo-luhr) lens) magnifies the image, usually 10 times. 2. Objective Lens Light passes through the specimen and then through the objective lens, which is located directly above the specimen. The objective lens enlarges the image of the specimen. Scientists sometimes use stains to make the image easier to see. 3. Stage The stage is a platform that supports a slide holding the specimen. The slide is placed over the opening in the stage of the microscope. 4. Light Source The light source is a light bulb that provides light for viewing the image. It can be either light reflected with a mirror or an incandescent light from a small lamp. SECTION 4 OBJECTIVES â List the function of each of the major parts of a compound light microscope. â Compare two kinds of electron microscopes. â Describe the importance of having the SI system of measurement. â State some examples of good laboratory practice. VOCABULARY compound light microscope eyepiece (ocular lens) objective lens stage light source magnification nosepiece resolution scanning electron microscope transmission electron microscope metric system base unit Compound light microscopes open the human eye to an interesting world including tiny pond organisms, healthy and diseased cells, and the functioning of cell parts. FIGURE 1-13 Objective lens Eyepiece (ocular lens) Stage Light THE SCIENCE OF LIFE 21 Copyright © by Holt, Rinehart and Winston. All rights reserved. 22 CHAPTER 1 Magnification and Resolution Microscopes vary in powers of magnification and resolution. Magnification is the increase of an objectâs apparent size. Revolving the nosepiece, the structure that holds the set of objective lens, rotates these lenses into place above the specimen. In a typical com- pound light microscope, the most powerful objective lens produces an image up to 100 times (100) the specimenâs actual size. The degree of enlargement is called the power of magnification of the lens. The standard ocular lens magnifies a specimen 10 times (10). To compute the power of magnification of a microscope, the power of magnification of the strongest objective lens (in this case, 100) is multiplied by the power of magnification of the ocular lens (10). The result is a total power of magnification of 1000. Resolution (REZ-uh-LOO-shuhn) is the power to show details clearly in an image. The physical properties of light limit the ability of light microscopes to resolve images, as shown in Figure 1-14a. At pow- ers of magnification beyond about 2,000, the image of the speci- men becomes fuzzy. For this reason, scientists use other microscopes to view very small cellsMedical