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Which animal is the SMARTEST creature on the planet?
Which animal is the SMARTEST creature on the planet?
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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 DesirĂŠe 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. Š 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-Îą 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- Îą 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-Îą 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-Îą, 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-Îą 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. 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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. 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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. 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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 gover [t comes from the GREEK name "Epilepsia" which means "taking hold of or seizing". - It is a disorder characterized by: recurrent seizures. SEIZURES R ectment transient attacks of: R epresent: R esult from: ASSOCIATED WITH: somatic, psychic, or, autonomic clinical featmes. clinical features of abnormally hyperexcitable cortical neurons. paroxvsmal and excessive electrical neuronal discharges. EEG changes & may be disturbance of consciousness. same causes of convulsions 1. Idiopathic epile~ ⢠It is the commonest cause. no cause can be detected ( 65 % ) ⢠It may be associated with positive family history in some cases. ⢠It starts in the l st & 2nd decades in the form of: -- Grand ma! epilepsy. Petit mal epilepsy. Myoclonic epilepsy. Atonic seizures. 2. Secondary epilepsy A. Local causes in the brain: l. Congenital: 2. Traumatic: cerebral palsy. a cause can be detected cerebral contusion or laceration. 3. Inflammatory: 4. Neoplastic: 5. Degenerative: 6. Vascular: encephalitis, brain tumours. mening1t1s, presenile dementia. brain abscess. stroke (especially hemon-hagic), hypertensive encephalopathy. B. General causes with secondary effects on the brain: I. Toxic: 2. Iatrogenic: 3. Metabolic: 4. Endocrinal: 5. Organ failure: 6. Heart disease: 7. Nutritional: - Alcohol, cocaine, lead. - Lidocaine, INH. - j glucose & ! glucose. - Hypoparathyroidism. - Hepatic failme. - Adam's Stoke's attacks. - Pellagra. - Botulism, tetanus. - Ambilhar, Amphetamine, Aminophylline. - j Ca & ! Ca. - Hype1thyroid crisis. - Renal failure. - Fallot's tetralogy. - j Na & ! Na. - Vitamin B6 deficiency. 8. Physical: 9. HYSTERICAL. - High fevers. - Heat stroke. 136 137 CLINICAL PICTURE 1. GENERALISED SEIZURES " Excessive electrical discharges from cortical neurons in BOTH hemispheres simultaneously " I. II. 1. Grand Mal Epile~: 1. Pre-ictal stage "attacks of tonic-clonic convulsions " (aura) It is a warning sign of a coming attack. It may be: ⢠Somatic: ⢠Psychic: ⢠Autonomic: 2. Ictal stage Myoclonus, Hallucinations. Tachycardia, (seizure) Sudden loss of consciousness: Parasthesias. Sweating. for seconds to minutes. -- Tonic phase (few seconds) o The UL & LL: o o o o The HEAD: The JAWS: CYANOSIS: are extended. is retracted to one side & the eye balls rolled up. are firmly clenched, with biting of the TONGUE. due to impaired respiration. There may be incontinence of urine. Clonic phase (few minutes) o The UL & LL: o The HEAD: 3. Post-ictal stage - It may be: ⢠Somatic: ⢠Psychic: ⢠Autonomic: Drug of choice: contract & relax repeatedly & rapidly. jerks forcibly. (sequelae) Todd's paralysis(< 24 hours, due to neuronal exhaustion). Confusion. Vomiting. Carbamazepine (Tegretol) or Phenytoin (Epanutin) Petit Mal Epilepsy: "attacks of loss of consciousness " " Absence " It starts in childhood & improves at puberty & usually disappears at the age of 20. 2. It is NOT PRECEEDED by aura & NOT FOLLOWED by sequelae. 3. It is usually PRECIPITATED by: hyperventilation 4. It is characterized by: or photic stimulation. sudden loss of consciousness of short duration (few seconds). 5. It may be associated with: ⢠High frequency ( 50 attacks / day). ⢠Falling to the ground without warning. ⢠Jerky movements of the head & UL Drug of choice: (myoclonic petit mal). Valproate (Depakine) or Succinimide (Zarontin) 137 138 Ill. M oclonic Seizures: "attacks of involuntary clonic movements " - It is characterized by: sudden, jerky, shock-like INVOLUNTARY muscle contraction. ⢠The jerks are bilateral contractions, mainly of the shoulders and arms. ⢠However, some patients repmtjerking in the lower limbs, trunk, or head. - It may be of 2 types: - Occurs singly ⢠Simple: ⢠As a pait of: I Drug of choice: IV. Atonic seizures: (no loss of consciousness). - Grand mal epilepsy (aura). - Petit mal epilepsy. Valproate (Depakine) or Clonazepam (Rivotril) I - Transient attacks of brief loss of postural tone, often resulting in falls and injuries. 2. PARTIAL SEIZURES "Excessive electrical discharges from cmtical neurons in a ce1tain area in ONE hemisphere" A. Simple seizures: " No disturbance in consciousness " - The CP depends on the site of the hyperexcitable neurones in the cerebral cortex, whether in: "Motor area or Senso,y areas". 1. Motor fits: ⢠Focal fits: ⢠Motor jacksonian fits: 2. General Sensory fits: ⢠Focal fits: ⢠Sensory jacksonian fits: 3. Special Senso1y fits: ⢠Visual hallucinations: ⢠Auditory hallucinations: ⢠Olfactory hallucinations: B. Complex seizures: - SITE: movement of part of a limb or the whole limb. movement of one side of the body (see before). parasthesia of part of a limb or the whole limb. parasthesia of one side of the body (see before). irritation of the visual sensory area. irritation of the auditory sensory area. initation of the uncus. " disturbance in consciousness " The hyperexcitable neurons are in the Temporal lobe "Temporal lobe epilepsy". - DURATION: The seizure lasts few seconds to few minutes. - The seizure starts with A ura, followed by A bsence, Automatism, Amnesia: 1. 2. 3. 4. A ura: A bsence: Automatism: A mnesia: Olfactory hallucinations, Deja-vu phenomenon, Sensation of fear. Absent patient with staring eyes (with no response to conversation). Involuntary Purposeless acts: motor ( eg, lip smacking, chewing) or verbal. No recalling of the seizure. 138 139 3. PARTIAL SEIZURES ~ GENERALISED SEIZURES " Partial seizures may spread to involve the whole brain .- secondarily generalised seizures " . HY-sterical epilepsY ⢠Usually: ⢠The cause: ⢠Incidence: young neurotic Sj2 . psychological & there is no organic lesion. usually occurs in the presence of people. ⢠It is associated with: ⢠EEG: ⢠It is not associated with: normal. ⢠Missed ttt. ⢠Menses. ⢠Alkalosis. anxiety, palpitaion & hyperventilation. tongue biting or incontinence of urine. ⢠Alcohol use & Drug abuse ( e.g. cocaine ). ⢠S timulation by photons & Hyperventilation. ⢠S leep deprivation & Stress & sudden withdrawal of antiepileptic drngs. INVESTIGATIONS 1. EEG: ⢠It is the most specific test for epilepsy because it records the electrical activity of the brain. ⢠It shows specific pattern: 2. LOCAL INVESTIGATIONS: "Epilepsy waves". "CT & MRI of the brain" ⢠To identify or exclude a LOCAL CAUSE of seizures in the brain. 3. GENERAL INVESTIGATIONS: "Laboratory investigations" ⢠To search for a GENERAL CAUSE of seizures, e.g. blood glucose. 139 140 TREATMENT A. General Measures: 1. 2. Moderation of the patient's physical activity. A void the precipitating factors ( Alcohol, hyperventilation, photic stimulation ...... ). 3. A ketogenic diet is encouraged because it will induce acidosis: - Acidosis is beneficial as it raises the threshold of stimulation of the brain cells. B. Specific Treatment: 2. 1. Treatment of the cause in secondary epilepsy. Anti-epileptic drugs: a) Always sta1t with one drug, then add another drug if there is no response. b) Always stop the drugs ONLY if: ⢠The patient stays free of symptoms for at least 2 years. ⢠The patient has a normal EEG. 3. Side effects of Anti-epileptic drugs: I . Skin rash. 2. 3. Bone marrow depression. Ataxia. Drug 1. Barbiturates (Pbenonobarbitone) 2. Hydantoin (Epanutin) 3. Carbamazepine 4. Clonazepam 5. Valproate 6. Succinamide ANTI-EPILEPTIC DRUGS NEW ANTI-EPILEPTIC DRUGS - These drugs are new dtugs that may be used in resistant seizures. 1. Lamotrigine: 200 - 400 mg/ day. 2. Felbamate: 3. Gabapentin: 400- 800 mg/ day. 600 - 1200 mg/ day. \ " General rules for use ": Dose 100-600 mg I day 100-600 mg / day 200-600 mg I day 2-6 mg I day 500-1500 mg I day 500-1000 mg / day Best indicated - Broad spectrum. - Not for petit mal. - Grand mal. - Motor Jacksonian fits. - Grand mal. - Motor Jacksonian fits. - Complex seizures. - Not for petit ma!. - Myoclonic. - Grand mat. - Broad spectrum. - Petit mat. 140 141 STATUS EPILEPTICUS DEFINITION - A medical emergency: 1. Repeated attacks of generalized convulsions, with lack of recove,y of consciousness, 2. Persistent attack of seizure lasting for at least 30 minutes. OR, - If the convulsions are not stopped rapidly, coma deepens & death may occur due to: heart failure or respiratory failure or brain damage or hyperpyrexia. - The most common causes are: sudden withdrawal of anti-epileptic drugs & stroke. TREATMENT A. General Measures: l. Take care of: " ABC " ⢠Place the patient on the ground, to guard against falling from bed. ⢠Mouth gag & 02 inhalation ( endo-tracheal intubation may be needed). ⢠Record the vital signs regularly. 2. Take a sample of: - Venous blood: for the level of: - A.tierial blood: for the level of: 3. a nti-epileptic drugs, a lcohol. pH, p0 2, pC02, HC0 3. Give cerebral dehydrating measures: e.g. Frusemide, cone. Mannitol, Dexamethazone. B. Specific Treatment: - Phenytoin with diazepam (or clonazepam) immediately: 1. Phenytoin: 2. Diazepam: Clonazepam: seizures recur: 15 mg I Kg slow infusion. 5 mg slowly IV, to be repeated after 5 minutes if seizures recur: maximum dose: 20 mg. OR: 2 mg slowly IV, to be repeated after 5 minutes if maximum dose: 6 mg. - If seizures persist after 20 min. of Phenytoin & diazepam: 3. PHENOBARBITONE: - In resistant cases: 200 mg infusion. 4. GENERAL ANAESTHESIA: may be used.LESSON 3 Characteristics of Living Things Learning Objectives ⢠Describe each characteristic of life ⢠Relate each characteristic of life with how first forms of life evolved What sets living things apart from nonliving things? Organisms are equipped with different characteristics that allow them to grow, adapt, survive, and perpetuate. These include the ability to metabolize, respond to stimuli, interact, and reproduce, among others What are the characteristics of life? Try to look at your surroundings and identify the living things that you see. You have probably identified a lot. Many scientists believe that there are more than 10 million kinds of living things that exist on Earth today. But the question is, how can something be considered living? There are certain characteristics that all living things exhibit: the characteristics of life. Living things are made up of cells. They metabolize, grow and develop, respond to stimulus, adapt to their environment, and reproduce. Living Things Are Made up of Cells All living things are made up of cells. Cells are the basic building blocks of all living things. Each cell contains materials that carry out basic life processes such as respiration. In the 1600s, an argument against the theory of spontaneous generation was made. Italian physician and biologist Francesco Redi disproved the theory that all living things come from nonliving things. Cells have different properties and characteristics. The cell theory describes the properties of all cells. There are three tenets of the cell theory: 1. The cell is the basic unit of life. 2. All living things are composed of one or more cells. 3. All cells arise from preexisting cells. The discovery of the cell is largely attributed to Robert Hooke. Upon examining a piece of cork using a microscope that he built, Hooke observed tiny compartments that he called "cells" (from the Latin word cella, meaning "little room"). Matthias Schleiden suggested that all structural parts of plants are made up of cells. In 1839, Theodore Schwann stated that along with plants, all animals were composed of cells. From these conclusions about plants and animals, advancement on the study of animal parts and functions began. In 1855, Rudolf Virchow included the idea that all cells came from preexisting cells. Some living things are made up of only single cells. Single-celled or unicellular organisms include bacteria, some protists, and some fungi. Even though composed of single cells, these organisms carry out all the functions necessary for life. Most living things such as animals and plants, are multicellular organisms. They are composed of many cells, which are grouped together and perform specific tasks in the body. In different organisms, cells also vary in sizes, shapes, parts, and functions. There are two kinds of organisms according to their cell structure, the prokaryotes and eukaryotes (figure 5-3). Prokaryotes are single-celled organisms that lack a membrane-bound nucleus, mitochondria, and all other organelles. Its name comes from the Greek words pro, which means "before," and karyon, which means "nut or kernel." Eukaryotes are organisms with cells that contain membrane-bound nucleus and other membrane-bound organelles. The nucleus of a eukaryotic cell contains the genetic material (DNA), enclosed by a nuclear envelope. Other membrane-bound organelles are mitochondria, Golgi apparatus, and chloroplast found in photosynthetic organisms such as algae and plants. There are also unicellular eukaryotes known as protozoa. All other eukaryotes are multicellular organisms, such as plants, animals, and fungi. Living Things Metabolize Essential chemical reactions in life can be best described as building up (anabolism) and breaking down (catabolism) processes. In anabolism, the substances needed by organisms to grow, store energy, and repair tissues are synthesized. In contrast in catabolism, some complex substances are broken down, releasing the energy stored in their molecules. This happens in food digestion. This chemical building up and breaking down processes are collectively called metabolism. Metabolism, from the Greek word metabole meaning "change," is the sum total of all the life-sustaining chemical reactions in living things. It allows living things to grow, maintain their structures and functions, and respond to stimuli. Living Things Grow and Develop Growth and development are not new concepts to many. In all living things, growth involves the increase in one's size or height. However, growth is not just an increase in physical structure. It also involves complex changes in an organism. Growth and development occur rapidly from younger stages of life to maturity. In humans, animals, and plants, distinct changes brought by growth and development can be dearly identified. Microorganisms such as bacteria also undergo growth and development until they reach their maximum size and maturity. A life span is the average length of time a aving thing can live. Living things have different life spans. Humans have average life spectancy of 60 to 70 years, while some plants, such as the narra trees, can live for more than 100. Living Things Respond to Stimuli All living things respond to stimuli the environment. This responsiveness Increases survivability. Stimulus (plural: uli) is any signal or change in he environment of an organism that produces a response or reaction from that organism. Responses to stimuli depend on an organism's need. Responding to stimuli also maintains homeostasis in living things. Homeostasis is the internal balance of a body system. This balance is needed for the proper function and regulation of the living thing's body. For example, when a person is in a warmer environment, the body sweats, keeping the body maintain a temperature suited for the normal function of the body. Living Things Interact No living thing can live alone. Interaction among organisms is simultaneously happening on Earth. From the smallest microorganisms to the biggest organism, and from the North Pole to the South Pole of Earth, all are connected in one living system. An ecosystem is formed when a community of organisms interacts with another community and with their environment. Many processes and interactions, such as in a feeding relationship, life cycle, and the exchange of gases between plants and animals, occur in the ecosystem. These are some of the important processes needed to maintain life on Earth. Living Things Reproduce The ability of living things to produce offspring of their kind is called reproduction. Reproduction is not an individual organism's need, rather, it is for the species' perpetuation. In some cases, animals become extinct because of their inability to reproduce their kind. Higher forms of plants and animals reproduce through sexual reproduction. Sexual reproduction involves the union of sex cells or gametes-the egg cell from a female organism and the sperm cell from a male organism. This union gives rise to a new individual with characteristics or traits from both parents. Other simple organisms, such as bacteria and plants, can reproduce asexually. These organisms give rise to a new individual from their body. A bacterial cell divided in two through asexual reproduction gives rise to new bacteria, as shown in figure 5-5. A yeast can form buds that later on become separate individual. Plants grow new plants using their stem, leaf, and roots. Both sexual and asexual reproductions have important functions. In both cases, the genetic material (DNA) is passed on from one generation to the next, ensuring the survival of the species on Earth. 1. Bacteria copy their DNA by starting at any point on the circular chromosomes. 2. The two copies of DNA attach to the inside wall of the bacterial cell. 3. The cell starts to divide, forming a new membrane and cell wall. 4. The bacterial cell splits into two separate cells, each with their own DNA. Living Things Adapt and Evolve All living things can adapt to their environment. This adaptation is necessary for rvival. Adaptation depends on the need of an individual. A polar bear, for example, would not be able to survive in an extremely cold environment without its capacity adapt. Adaptation is any response or reaction toward a stimulus that helps in the survival of an organism. A seed-eating bird will eventually eat a worm when there are seeds to be found. This change in food choice is therefore its adapting mechanism. Prolonged adaptation to certain environments may lead to the gradual evolution of the succeeding generations. Evolution is the gradual change in organisms over a long period in response to changing environment. Living Things Are Organized Life on Earth exhibits organization. The atom is the smallest unit of matter, lowed by molecules, which are combinations of atoms. When these molecules are grouped together, they form a cell. The cell is the basic unit of life. In multicellular organisms, such as plants and animals, cells are grouped as tissues to perform specific Functions. Different tissues can be grouped further and form organs. Organs in animals include the heart, brain, and lungs, among others. The organs form organ systems that makes the function of the body more complex and efficient. Organ systems form the whole organism. All living things exhibit organization, whether they are unicellular or multicellular organisms.. Title: The Adventures of Max and the Magical Computer (Shortened Version) Once upon a time, in a small town called Techville, there lived a curious fourth-grader named Max. One day, while exploring his grandmaâs attic, he found an old, dusty computer. As he cleaned it, the screen lit up, and a cheerful voice said, âHello, Max! Iâm Compy, your magical computer. Letâs learn about operating systems, files, and folders!â Max was thrilled. âA talking computer? Letâs go!â Chapter 1: The World of Windows Compy explained, âI run on Windows, the brain of the computer. It uses a Graphical User Interface (GUI), so you can interact with me using icons, menus, and buttons. Letâs start by changing my desktop backgroundâthe image on the screen.â Max chose a spaceship picture. âCool! Can I add a screen saver too?â âOf course!â said Compy. âItâs an image that appears when Iâm inactive. Try this swirling galaxy!â Max set the screen saver and giggled as it appeared. âThis is fun!â Chapter 2: Organizing with Folders and Files Compyâs screen filled with random icons. âOh no! My files are a mess. Can you help?â âSure! What are files and folders?â asked Max. âA file is information, like a picture or document. Files have names, like âHomework.docx.â The part after the dot, like .docx, is the file extension. It tells you the file type,â Compy explained. Max pointed to âGame.exe.â âSo, this is a program file?â âYes!â said Compy. âTo organize, we use foldersâlike drawers for files. You can even put folders inside folders!â Max created a âSchoolâ folder, added his homework files, and made a âProjectsâ folder inside it. âNow everythingâs neat!â Chapter 3: The File Explorer Adventure Compyâs screen flickered. âSome files are missing. Letâs use Windows Explorer to find them. Itâs like a map for files and folders.â Max opened Windows Explorer and saw a tree-like list of folders. âThis is like a tree with branches!â âExactly!â said Compy. âSearch for the missing files and move them to the right folders.â Max found the files in âDownloadsâ and moved them. âI feel like a computer detective!â Chapter 4: The Final Challenge Compyâs screen turned into a game board. âTime for a quiz! Whatâs the purpose of an operating system? How do you change the desktop background? Whatâs the difference between a file and a folder?â Max answered all the questions correctly, and fireworks lit up the screen. âCongratulations, Max! Youâre a computer whiz!â The End Max smiled. âThanks, Compy! I canât wait to teach my friends!â Compy replied, âRemember, Max, learning is an adventure. Keep exploring!â As Max turned off the computer, he knew his journey into technology had just begun.Brainy Starts 8.21Brainy Starts, 11.18Put on your brainy caps , My StarsTo understand melody in music, think about some music youâre familiar with. If you were asked to hum it, what would that sound like? The part of the music that youâd hum is the melody. Itâs the main thread of sound that your brain tracks and holds onto when youâre listening to music. In vocal music, the melody is sung by the lead singer. Other vocalists can provide harmony and instruments can add accompaniment, but the melody is the star of the show.What are the characteristics of melody in music? How do you describe a melody in music? A melody needs to have two things. The first is a sequence of notes, or pitches, which range from high to low. The second is rhythm, which is the timing and duration of each note. These two simple elements can create an incredible variety of combinations. Even though a melody only consists of one note at a time, it can convey so much energy and emotion. Melodies can be fast and sparkly, like âThe Flight of the Bumblebee.â They can be slow and majestic, like âFinlandia.â They might be sweeping and graceful, like a Strauss waltz. Or they can be fun and exciting, like your favorite pop tunes that you love to sing along with. Melodies often tell you a lot about where a piece of music comes from. Itâs easy to recognize and identify melodies from different folk traditions such as the Japanese folk song âSakuraâ or the Irish tune âStar of the County Down.â Learn how to play your favorite melodies on piano, and more! Sign up now. What is melody in music? Here are some examples. Here is the famous melody for the song âLean on Meâ written out on a staff. Notice the way that the notes move up, down, and then repeat. What is melody in music? Example of Lean On Me notes on treble staff. A melody all by itself is great, but music can be even more fun when thereâs an accompaniment. Here are a few bars of âLean on Meâ with the accompaniment written out. As you listen to this song, notice how the accompaniment has a very similar rhythm and movement to the melody. Then thereâs that one note in the bass line that comes along every measure with its own rhythm, which adds some extra energy and movement to the song. What makes a good melody? When you create a melody, there are four types of movement you can use: Repeat (same note) Step (up or down) Skip (up or down) Leap (up or down) Stepping and repeating are the most common types of melodic motion, and this makes a melody easier to sing. Most âhummableâ tunes use steps and repeats almost exclusively. This kind of melody is called conjunct. Beethovenâs âOde to Joy,â one of the most famous melodies of all time.Skips and leaps are generally more sparing in melodies, but when thoughtfully placed they can have a powerful emotional impact. Tunes with a lot of leaps are called disjunct. Listen to Sarah Brightman sing All I Ask of You from The Phantom of the Opera starting at 0:39. This is a very disjunct melody, and challenging to sing. Great melodies also incorporate patterns that blend unity, repetition, and contrast. Our ears love patterns, but they also love novelty and growth. A good melody incorporates all of these elements. For example, listen to John Williamâs âPrincess Leia Theme.â Can you hear the repeated pattern in the melody that gradually moves higher as the theme progresses? Now listen to the way it changes and develops into something that fits with what came before but sounds new at the same time. This is some great melodic writing! Can melody exist without rhythm? There is no way for a melody to exist without rhythm. Even if your melody only has one note, that note has a duration, and thatâs the rhythm. If your melody has two notes, how long those notes last and how much time passes between hearing them is also a rhythm. A melody in music can often be recognized even when itâs performed with different rhythms. This frequently happens in live performances of pop, rock, and jazz, in which singers typically improvise slight rhythmic differences with each performance. No two renditions are exactly the same, and this constant reinterpretation keeps the music fresh. How to make a melody for a song on piano Creating your own melodies on the piano is easy and fun! There are so many ways you can discover a melody all your own. Here are a few ideas. Get some inspiration from the world around you. What can you hear right now? A clock ticking? A bird song? A car passing by your house? See if you can find some notes on the piano that imitate the sounds you hear. Think of a feeling youâd like to put into a melody. What are some ways you could make a string of notes sound happy, sad, angry, or maybe just thoughtful. Choose a line from a poem you like, or write your own. Read it out loud and put some feeling into it. Did your voice rise and fall in pitch as you were reading? Now go to the piano, start on any note you like, and try to imitate what happened when you read. Go up when your voice naturally went up, go down when your voice naturally went down. How did that sound? Now you have the perfect melody to go with those words. Too many keys on the piano? The truth is, most melodies use only a limited number of different notes. Try creating a melody using only the black keys. These form whatâs called a pentatonic scale. Itâs used in a lot of folk music traditions around the world and can be a great place to start if you want to create your own melodies. Remember, when you create your melody, keep it simple. Use repeated notes and steps, but add a few skips to keep things interesting. One tip about leaps: when you do put in a big leap, try doubling back and filling in the empty space you leaped over. This keeps the melody self-contained and easier to sing. Also, see if you can use the same patterns of notes and rhythms to give the melody unity, but also change those patterns to give it variety. There is no right or wrong way to create your own music. Keep trying combinations of notes and rhythms until you find something that you like. How many bars and notes are in a melody? Many types of music tend to have a prescribed number of bars, or measures. This will vary widely between different genres, and creates an overall sense of musical structure. If youâre writing a pop song, a verse will usually have between eight and sixteen bars. The prechorus that follows often has just four bars, and this âforeshorteningâ creates a sense of acceleration, driving the listener toward the chorus. The number of notes can also vary widely. A melody in music needs at least two notes, and a long and complex one can have hundreds or even thousands of notes. What is a countermelody in music? How many melodies should a song have? A counter melody is a melodic line that interacts with the primary melody as an independent but supportive voice. A great example of this is the song âWe Donât Talk about Bruno.â Each character sings their own melody during the piece, but these melodies all combine at the end as countermelodies. This produces a musical texture known as counterpoint. The same thing happens in âOne Day Moreâ from Les Miserables. The different melodies are first sung separately, but end up being combined in a splendid, complex texture that leads the music to its thrilling conclusion. The difference between a countermelody and regular harmony is that harmony usually supports the rhythms of the melody. A countermelody will move more independently, with different rhythms from those of the melody, and will often sound âmelodicâ when sung or played all by itself. A melodic song should have one main melody. This is the part that the lead voice sings. Itâs usually in the spotlight, and will be the most memorable part of the music. Anything else is either harmony, countermelody, or accompaniment. Does all music have to have a melody? A piece of music doesnât have to have a melody. There are many different kinds of music without melody. For example, a lot of music played on percussion instruments wonât have a melody. Listen to this example of Tahitian drumming. This is some great music, exciting and fun to listen to, but youâd have a hard time humming it. Itâs music, but it doesnât have a melody. Rap music is another style of music where there doesnât have to be a melody. In rap, words are chanted rather than sung. The performer will raise and lower the pitch of their voice for emphasis, but itâs the rhythm of the words that creates most of the music. Music can even lack any melody, at least in some sections. Listen to the opening chords of âDuel of the Fates.â This choral passage is all about harmony, with little rhythmic variance or sense of melody. But it makes an effective contrast with the next section, which is bustling with rapid instrumental melodies. In some pieces, there are multiple melodic lines but there is no one main melody. When music is made up of equally important countermelodies, it creates a contrapuntal texture. Baroque composer J.S. Bach was one of the greatest masters of this style, such as in his Little Fugue in G minor. It starts with a single melodic line, the subject, but then a countermelody is added, and then more and more until several melodic lines are playing together. Itâs fun to listen to, but once all the countermelodies are playing together it becomes hard to decide which part to hum along with! Youâll also hear a lot of counterpoint in jazz music, in which the different instruments are all playing together and improvising their own melodies that combine to create a rich, thick musical texture. Experience the wonder of melody in music! Whether youâre humming your favorite tune, or creating a new song all your own, melody is a memorable, shareable part of music. Enrich your music experience by being aware of, listening for, and enjoying the melodies all around you.