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Generic and Brand Name Review
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What is the generic name of Lunesta®?
donepezil
eszopiclone
zolpidem
atomoxetine
What is the generic name of Relpax®?
eletriptan
donepezil
aripiprazole
none of the answers are correct
What is the generic name of Lunesta®?
What is the generic name of Relpax®?
What is the brand name of mupirocin?
What is the generic name for Ciprodex® Otic?
What is the generic name of Norvasc®?
What is the brand name of divalproex sodium?
What is the brand name of adapalene?
What is the brand name for azithromycin?
What is the generic name of Zyprexa®?
What is the brand name of Alprazolam?
What is the generic name of Uroxatral®?
What is the generic name of Fosamax®?
What is the generic name of Dilantin®?
What is the generic name of Topamax®?
What is the brand name of estradiol?
What is the brand name of sumatriptan?
What is the brand name of triamterene/hydrochlorothiazide?
What is the brand name of benzonatate?
What is the generic name of Avodart®?
What is the brand name for clindamycin?
What is the generic name of Concerta®?
What is the brand name of budesonide?
What is the brand name of enalapril?
What is the generic name of Combivent®?
What is the generic name of Boniva®?
What is the generic name of Avalide®?
What is the brand name of Tiotropium?
What is the generic name of Keppra®?
What is the generic name for Tricor®?
What is the brand name of insulin aspart?
What is the generic name of Flovent® HFA?
What is the generic name of Lipitor®?
What is the brand name for desiccated thyroid extract?
What is the generic name for Zocor®?
What is the brand name of naproxen?
What is the brand name of ibuprofen?
What is the brand name of rosuvastatin?
What is the brand name of triamcinolone?
What is the generic name of Cheratussin® AC®?
What is the generic name for Augmentin®?
What is the generic name of Geodon®?
What is the brand name of citalopram?
What is the generic name of Restasis®?
What is the generic name for Ativan®?
What is the generic name of Singulair®?
What is the generic name of Diovan HCT®?
What is the brand name of Ropinirole?
What is the generic of Loestrin® Fe24?
What is the brand name of modafinil?
What is the brand name of tolterodine?
Plant cells have three kinds of structures that are not found in animal cells and that are extremely important to plant survival: plastids, central vacuoles, and cell walls. PLANT CELLS Most of the organelles and other parts of the cell just described are common to all eukaryotic cells. However, plant cells have three additional kinds of structures that are extremely important to plant function: cell walls, large central vacuoles, and plastids. To understand why plant cells have structures not found in ani- mal cells, consider how a plant’s lifestyle differs from an animal’s. Plants make their own carbon-containing molecules directly from carbon taken in from the environment. Plant cells take carbon diox- ide gas from the air, and in a process called photosynthesis, they convert carbon dioxide and water into sugars. The organelles and structures in plant cells are shown in Figure 4-21. SECTION 4 OBJECTIVES ● List three structures that are present in plant cells but not in animal cells. ● Compare the plasma membrane, the primary cell wall, and the secondary cell wall. ● Explain the role of the central vacuole. ● Describe the roles of plastids in the life of a plant. ● Identify features that distinguish prokaryotes, eukaryotes, plant cells, and animal cells. VOCABULARY cell wall central vacuole plastid chloroplast thylakoid chlorophyll Chloroplast Golgi apparatus Mitochondrion Cell membrane Nucleolus Nucleus Cytoskeleton Rough endoplasmic reticulum Pore Smooth endoplasmic reticulum Central vacuole Ribosome Cell wall In addition to containing almost all of the types of organelles that animal cells contain, plant cells contain three unique features. Those features are the cell wall, the central vacuole, and plastids, such as chloroplasts. FIGURE 4-21 Copyright © by Holt, Rinehart and Winston. All rights reserved. 88 CHAPTER 4 CELL WALL The cell wall is a rigid layer that lies outside the cell’s plasma membrane. Plant cell walls contain a carbohydrate called cellulose. Cellulose is embedded in a matrix of proteins and other carbohy- drates that form a stiff box around each cell. Pores in the cell wall allow water, ions, and some molecules to enter and exit the cell. Primary and Secondary Cell Walls The main component of the cell wall, cellulose, is made directly on the surface of the plasma membrane by enzymes that travel along the membrane. These enzymes are guided by microtubules inside the plasma membrane. Growth of the primary cell wall occurs in one direction, based on the orientation of the microtubules. Other components of the cell wall are made in the ER. These materials move in vesicles to the Golgi and then to the cell surface. Some plants also produce a secondary cell wall. When the cell stops growing, it secretes the secondary cell wall between the plasma membrane and the primary cell wall. The secondary cell wall is very strong but can no longer expand. The wood in desks and tabletops is made of billions of secondary cell walls. The cells inside the walls have died and disintegrated. CENTRAL VACUOLE Plant cells may contain a reservoir that stores large amounts of water. The central vacuole is a large, fluid-filled organelle that stores not only water but also enzymes, metabolic wastes, and other materials. The central vacuole, shown in Figure 4-22, forms as other smaller vacuoles fuse together. Central vacuoles can make up 90 percent of the plant cell’s volume and can push all of the other organelles into a thin layer against the plasma membrane. When water is plentiful, it fills a plant’s vacuoles. The cells expand and the plant stands upright. In a dry period, the vacuoles lose water, the cells shrink, and the plant wilts. Other Vacuoles Some vacuoles store toxic materials. The vacuoles of acacia trees, for example, store poisons that provide a defense against plant-eating ani- mals. Tobacco plant cells store the toxin nicotine in a storage vacuole. Other vacuoles store plant pigments, such as the colorful pigments found in rose petals. The central vacuole occupies up to 90 percent of the volume of some plant cells. The central vacuole stores water and helps keep plant tissue firm. FIGURE 4-22 Central vacuole Nucleus Chloroplast Copyright © by Holt, Rinehart and Winston. All rights reserved. CELL STRUCTURE AND FUNCTION 89 PLASTIDS Plastids are another unique feature of plant cells. Plastids are organelles that, like mitochondria, are surrounded by a double mem- brane and contain their own DNA. There are several types of plastids, including chloroplasts, chromoplasts, and leucoplasts. Chloroplasts Chloroplasts use light energy to make carbohydrates from carbon dioxide and water. As Figure 4-23 shows, each chloroplast contains a system of flattened, membranous sacs called thylakoids. Thylakoids contain the green pigment chlorophyll, the main mole- cule that absorbs light and captures light energy for the cell. Chloroplasts can be found not only in plant cells but also in a wide variety of eukaryotic algae, such as seaweed. Chloroplast DNA is very similar to the DNA of certain photosyn- thetic bacteria. Plant cell chloroplasts can arise only by the divi- sion of preexisting chloroplasts. These facts may suggest that chloroplasts are descendants of ancient prokaryotic cells. Like mitochondria, chloroplasts are also thought to be the descendants of ancient prokaryotic cells that were incorporated into plant cells through a process called endosymbiosis. Chromoplasts Chromoplasts are plastids that contain colorful pigments and that may or may not take part in photosynthesis. Carrot root cells, for example, contain chromoplasts filled with the orange pigment carotene. Chromoplasts in flower petal cells contain red, purple, yellow, or white pigments. Other Plastids Several other types of plastids share the general features of chloro- plasts but differ in content. For example, amyloplasts store starch. Chloroplasts, chromoplasts, and amyloplasts arise from a common precursor, called a proplastid. Thylakoid Inner membrane Outer membrane chloroplast from the Greek chloros, meaning “pale green,” and plastos, meaning “formed” Word Roots and Origins A chloroplast captures energy from sunlight and uses that energy to convert carbon dioxide and water into sugar and other carbohydrates. FIGURE 4-23 Copyright © by Holt, Rinehart and Winston. All rights reserved. 90 CHAPTER 4 COMPARING CELLS All cells share common features, such as a cell membrane, cyto- plasm, ribosomes, and genetic material. But there is a high level of diversity among cells, as shown in Figure 4-24. There are signifi- cant differences between prokaryotes and eukaryotes. In addition, plant cells have features that are not found in animal cells. Prokaryotes Versus Eukaryotes Prokaryotes differ from eukaryotes in that prokaryotes lack a nucleus and membrane-bound organelles. Prokaryotes have a region, called a nucleoid, in which their genetic material is concen- trated. However, prokaryotes lack an internal membrane system. Plant Cells Versus Animal Cells Three unique features distinguish plant cells from animal cells. One is the production of a cell wall by plant cells. Plant cells contain a large central vacuole. Third, plant cells contain a variety of plastids, which are not found in animal cells. Cell walls, central vacuoles, and plastids are unique features that are important to plant function. 1. Identify three unique features of plant cells. 2. List the differences between the plasma mem- brane, the primary cell wall, and the secondary cell wall. 3. Identify three functions of plastids. 4. Name three things that may be stored in vacuoles. 5. Describe the features that distinguish prokary- otes from eukaryotes and plant cells from animal cells. CRITICAL THINKINGPharmacy Tech Brand and Generic Test Review 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 Desirée Nieuwenhuis | Natàlia 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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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 ‘onset of puberty and adiposity/obesity’, ‘onset of puberty’, ‘children with obesity’, ‘adipose tissue’, ‘childhood obesity’, ‘adiposity’, ‘obesity’, ‘adipokine(s)’, ‘HPG axis’, ‘adipokines ovary/ova- ries’, or ‘adipokines testes’, either alone or in combination. 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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 goverCell Size Cells differ not only in their shape but also in their size. A few types of cells are large enough to be seen by the unaided human eye. For example, the nerve cells that extend from a giraffe’s spinal cord to its foot can be 2 m (about 6 1/2 ft) long. A human egg cell is about the size of the period at the end of this sentence. Most cells, how- ever, are only 10 to 50 μm in diameter, or about 1/500 the size of the period at the end of this sentence. The size of a cell is limited by the relationship of the cell’s outer surface area to its volume, or its surface area–to-volume ratio. As a cell grows, its volume increases much faster than its surface area does, as shown in Figure 4-5. This trend is important because the materials needed by a cell (such as nutrients and oxygen) and the wastes produced by a cell (such as carbon dioxide) must pass into and out of the cell through its surface. If a cell were to become very large, the volume would increase much more than the surface area. Therefore, the surface area would not allow materials to enter or leave the cell quickly enough to meet the cell’s needs. As a result, most cells are microscopic in size. Comparing Surface Cells Materials microscope, prepared slides of plant (dicot) stem and ani- mal (human) skin, pencil, paper Procedure Examine slides by using medium magnification (100). Observe and draw the sur- face cells of the plant stem and the animal skin. Analysis How do the surface cells of each organism differ from the cells beneath the surface cells? What is the function of the surface cells? Explain how surface cells are suited to their function based on their shape. Quick Lab Small cells can exchange substances more readily than large cells because small objects have a higher surface area–to-volume ratio. FIGURE 4-5 mb06se_csfs02.qxd 5/18/07 10:54 AM Page 73 74 CHAPTER 4 BASIC PARTS OF A CELL Despite the diversity among cells, three basic features are common to all cell types. All cells have an outer boundary, an interior sub- stance, and a control region. Plasma Membrane The cell’s outer boundary, called the plasma membrane (or the cell membrane), covers a cell’s surface and acts as a barrier between the inside and the outside of a cell. All materials enter or exit through the plasma membrane. The surface of a plasma mem- brane is shown in Figure 4-6a. Cytoplasm The region of the cell that is within the plasma membrane and that includes the fluid, the cytoskeleton, and all of the organelles except the nucleus is called the cytoplasm. The part of the cytoplasm that includes molecules and small particles, such as ribosomes, but not membrane-bound organelles is the cytosol. About 20 percent of the cytosol is made up of protein. Control Center Cells carry coded information in the form of DNA for regulating their functions and reproducing themselves. The DNA in some types of cells floats freely inside the cell. Other cells have a mem- brane-bound organelle that contains a cell’s DNA. This membrane- bound structure is called the nucleus. Most of the functions of a eukaryotic cell are controlled by the cell’s nucleus. The nucleus is often the most prominent structure within a eukaryotic cell. It maintains its shape with the help of a protein skeleton called the nuclear matrix. The nucleus of a typical animal cell is shown in Figure 4-6b. Most animal cells have a cell membrane, a nucleus, and a variety of other organelles embedded in a watery substance. The surface of the cell membrane can be seen in (a). The organelles inside the cell are labeled in the diagram (b). FIGURE 4-6 (a) (b) Mitochondrion Microfilaments Lysosome Golgi apparatus Smooth ER Ribosomes Cell membrane Microtubules Rough ER Nuclear pore Nuclear envelope Nucleolus Nucleus Copyright © by Holt, Rinehart and Winston. All rights reserved. Cell wall Ribosome Cell membrane Peptidoglycan Pili Flagellum DNA CELL STRUCTURE AND FUNCTION 75 A prokaryotic cell lacks a membrane- bound nucleus and membrane-bound organelles. Most prokaryotic cells are much smaller than eukaryotic cells are. FIGURE 4-7 A white blood cell (eukaryotic) changes shape as it attacks purple- stained bacterial cells that are much smaller (prokaryotic). FIGURE 4-8 TWO BASIC TYPES OF CELLS Fossil evidence suggests that the earliest cells on Earth were simple cells similar to some present-day bacteria. As cells evolved, they differentiated into two major types: prokaryotes and eukaryotes. Prokaryotes Prokaryotes (proh-KAR-ee-OHTS) are organisms that lack a membrane- bound nucleus and membrane-bound organelles. Although prokaryotic cells lack a nucleus, their genetic information—in the form of DNA—is often concentrated in a part of the cell called the nucleoid. Figure 4-7 shows a typical prokaryotic cell. Prokaryotes are divided into two domains: Bacteria and Archaea (ahr-KEE-uh). The domain Bacteria includes organisms that are similar to the first cellular life-forms. The domain Archaea includes organisms that are thought to be more closely related to eukaryotic cells found in all other kingdoms of life. Eukaryotes Organisms made up of one or more cells that have a nucleus and membrane-bound organelles are called eukaryotes (yoo-KAR-ee-OHTS). Eukaryotic cells also have a variety of subcellular structures called organelles, well-defined, intracellular bodies that perform specific functions for the cell. Many organelles are surrounded by a mem- brane. The organelles carry out cellular processes just as a person’s pancreas, heart, and other organs carry out a person’s life processes. Eukaryotic cells are generally much larger than prokary- otic cells, as seen in Figure 4-8, which shows a white blood cell (eukaryote) destroying tiny bacterial cells (prokaryotes).L'attentato alle Torri Gemelle dell'11 settembre 2001 è stato orchestrato dall'organizzazione terroristica al-Qaida, guidata da Osama bin Laden. Al-Qaida, un gruppo estremista islamico, aveva l'obiettivo di colpire gli Stati Uniti per una serie di motivi, tra cui la loro presenza militare in Medio Oriente, il sostegno a Israele e le politiche economiche e geopolitiche percepite come oppressive nei confronti dei Paesi musulmani. L'attacco ha coinvolto 19 terroristi, che hanno dirottato quattro aerei commerciali: due hanno colpito le Torri Gemelle a New York, un altro il Pentagono vicino a Washington, D.C., mentre il quarto, United Airlines Flight 93, è precipitato in un campo in Pennsylvania dopo che i passeggeri hanno tentato di riprendere il controllo dell'aereo. Osama bin Laden ha rivendicato la responsabilità dell'attentato, che ha provocato circa 3.000 morti e ha avuto un impatto duraturo sulla politica internazionale, portando alle guerre in Afghanistan e Iraq e a significativi cambiamenti nella sicurezza globale Il fatto che quattro aerei dirottati siano riusciti a deviare dalla loro rotta senza un immediato intervento da parte delle autorità aeree è legato a una serie di fattori: 1. **Dirottamenti inattesi**: Prima dell'11 settembre 2001, il protocollo per gestire i dirottamenti aerei era molto diverso. I dirottamenti aerei, quando accadevano, di solito erano gestiti attraverso negoziazioni e si presumeva che i dirottatori cercassero principalmente attenzione o denaro, non attacchi suicidi. Non c'era una preparazione specifica per l'eventualità che gli aerei venissero usati come armi. 2. **Interruzione delle comunicazioni**: I dirottatori hanno spento i transponder sugli aerei (dispositivi che inviano segnali radar con informazioni su altitudine e posizione), rendendo difficile per i controllori del traffico aereo tracciare con precisione gli aerei. Gli aerei risultavano ancora visibili sui radar primari, ma senza i dati specifici del transponder era difficile capire immediatamente che c'era una deviazione fuori rotta. 3. **Tempo di reazione**: Gli eventi si sono svolti in un breve arco di tempo. I primi segni di problemi sui voli sono emersi intorno alle 8:14 (con l'American Airlines Flight 11), e il primo schianto contro la Torre Nord è avvenuto alle 8:46. Tra l'inizio dei dirottamenti e gli impatti, il tempo per reagire è stato limitato. La portata dell'attacco era senza precedenti, e nessuno si aspettava che i dirottatori avrebbero usato gli aerei come armi contro obiettivi civili. 4. **Coordination failures**: Anche se ci sono stati segnali di problemi, la comunicazione tra le varie agenzie coinvolte (Federal Aviation Administration, NORAD, ecc.) non era ottimale. La procedura per attivare la difesa aerea in caso di dirottamento era complessa, e la possibilità che aerei civili venissero utilizzati come armi suicide non era contemplata nei protocolli. 5. **NORAD e tempi di risposta**: Il NORAD (North American Aerospace Defense Command), incaricato della difesa aerea, aveva una capacità limitata di intercettare rapidamente aerei dirottati nello spazio aereo interno. Prima dell'11 settembre, le operazioni di difesa erano concentrate su possibili minacce esterne, e non su attacchi interni. Anche quando i caccia furono inviati, era troppo tardi per impedire gli impatti. Questi fattori, combinati con l'incredulità che un tale attacco potesse realmente accadere, hanno reso possibile che quattro aerei fossero dirottati e usati come armi senza un intervento preventivo efficace. Dopo l'11 settembre, furono apportati significativi cambiamenti ai protocolli di sicurezza aerea per prevenire simili attacchi in futuro. L'idea che l'11 settembre abbia fornito un "pretesto" per attaccare l'Afghanistan è stata ipotizzata da diverse teorie del complotto e punti di vista critici sulla politica estera degli Stati Uniti. Tuttavia, è importante distinguere tra i fatti documentati e le ipotesi non verificate. ### Fatti documentati: 1. **Al-Qaida e Osama bin Laden**: Gli attacchi dell'11 settembre sono stati rivendicati da al-Qaida, che aveva il suo quartier generale in Afghanistan sotto la protezione del regime talebano. Gli Stati Uniti hanno chiesto ai talebani di consegnare Osama bin Laden, ma il governo talebano ha rifiutato. Questo ha portato all'intervento militare in Afghanistan con l'obiettivo dichiarato di smantellare al-Qaida e rimuovere i talebani dal potere. 2. **Legittimazione internazionale**: L'invasione dell'Afghanistan è stata ampiamente appoggiata a livello internazionale, con il sostegno delle Nazioni Unite e della NATO. Il Consiglio di Sicurezza delle Nazioni Unite ha approvato risoluzioni che condannavano gli attacchi e riconoscevano il diritto di difesa degli Stati Uniti. ### Teorie del complotto: Alcuni teorici sostengono che l'11 settembre potrebbe essere stato usato come pretesto per giustificare una guerra che rientrava in più ampi interessi geopolitici. Secondo questa visione, l'invasione dell'Afghanistan non riguardava solo la lotta contro il terrorismo, ma anche: - **Influenza geopolitica**: Gli Stati Uniti avrebbero cercato di stabilire una maggiore presenza militare e influenza in una regione strategica, vicina a Paesi come l'Iran, la Cina e la Russia. - **Risorse naturali**: L'Afghanistan ha un'importanza geopolitica anche per i suoi potenziali corridoi energetici e per le sue risorse minerarie, anche se non ha ricchezze petrolifere significative come altri Paesi del Medio Oriente. ### Critiche legittime: Al di là delle teorie del complotto, ci sono critiche legittime alla risposta degli Stati Uniti e all'espansione della guerra al terrorismo. Ad esempio: - **La guerra in Iraq**: Mentre l'invasione dell'Afghanistan fu largamente supportata, l'invasione dell'Iraq nel 2003 fu molto più controversa. Molti analisti ritengono che l'amministrazione Bush abbia sfruttato la paura generata dall'11 settembre per giustificare un attacco all'Iraq, anche se non c'erano prove concrete di un collegamento tra il regime di Saddam Hussein e al-Qaida. - **Durata della guerra**: La guerra in Afghanistan si è trasformata in un conflitto di lunga durata, che molti vedono come fallimentare, con risultati incerti nonostante il grande impegno militare ed economico. ### Conclusione: Sebbene sia possibile che alcune figure politiche o militari abbiano sfruttato l'attacco dell'11 settembre per portare avanti agende geopolitiche preesistenti, i fatti storici mostrano che l'invasione dell'Afghanistan fu una reazione diretta agli attacchi e alla minaccia di al-Qaida. Le decisioni successive, in particolare l'espansione della "guerra al terrorismo", sono state oggetto di forti critiche e controversie, ma non ci sono prove concrete che l'11 settembre sia stato pianificato o lasciato accadere per giustificare un'invasione. La **caduta delle Torri Gemelle** l'11 settembre 2001 è stata causata principalmente dai **danni strutturali provocati dall'impatto degli aerei e dal conseguente incendio**, secondo le indagini ufficiali. Le teorie che ipotizzano l'uso di esplosivi sono state ampiamente investigate ma smentite dalle analisi tecniche e dalle prove disponibili. ### Versione ufficiale: 1. **Impatto degli aerei**: Gli aerei di linea colpirono le Torri Gemelle a una velocità molto elevata, causando danni immediati e significativi alle colonne portanti esterne e interne degli edifici. Questi danni strutturali compromettevano già parte della stabilità delle torri. 2. **Incendi**: L'impatto degli aerei ha causato l'esplosione del carburante contenuto nei serbatoi, innescando vasti incendi. Il calore generato dagli incendi all'interno degli edifici raggiunse temperature estremamente elevate (fino a 1000°C o più), che indebolirono ulteriormente l'acciaio delle strutture portanti. 3. **Cedimento strutturale**: L'acciaio non deve necessariamente fondere per perdere la sua capacità portante; a temperature elevate, l'acciaio diventa più malleabile e perde resistenza. Questo, unito al danno meccanico già causato dall'impatto degli aerei, ha portato al cedimento progressivo delle strutture superiori, che sono collassate sui piani inferiori in una sorta di effetto domino. Questo spiega il "crollo verticale" delle torri. ### Investigazioni tecniche: 1. **Rapporto del NIST**: Il **National Institute of Standards and Technology (NIST)** ha condotto un'indagine approfondita sulla caduta delle torri. Secondo il rapporto del NIST, **non ci sono prove** che suggeriscano l'uso di esplosivi o ordigni nei crolli delle torri. I crolli sono stati attribuiti esclusivamente ai danni strutturali causati dagli impatti e agli incendi successivi. 2. **Simulazioni e analisi**: Gli ingegneri hanno simulato il comportamento degli edifici durante l'attacco e hanno concluso che l'indebolimento delle strutture portanti a causa del calore è stato sufficiente a spiegare il collasso. Il crollo avvenne in maniera progressiva e non con le caratteristiche di una demolizione controllata, come l'uso di esplosivi. ### Teorie del complotto: Nonostante le spiegazioni tecniche ufficiali, alcune persone sostengono che il crollo sia stato causato da esplosivi piazzati all'interno delle torri. Queste teorie si basano su: - **Testimonianze di esplosioni**: Alcune persone hanno riportato di aver sentito rumori di esplosioni prima o durante i crolli. Tuttavia, gli esperti hanno spiegato che questi rumori possono essere attribuiti a numerosi fattori, come i cedimenti strutturali e le esplosioni secondarie dovute al cedimento di infrastrutture interne (ad esempio, serbatoi di gas o trasformatori elettrici). - **Crollo simmetrico**: Alcuni teorici sostengono che il crollo delle torri sia stato troppo "ordinato" per essere casuale. Tuttavia, il collasso verticale è stato spiegato come il risultato del cedimento simultaneo di più colonne portanti indebolite dal calore. - **Teoria del crollo controllato**: Alcuni sostengono che le torri siano cadute con la rapidità e la precisione di una demolizione controllata. Tuttavia, studi dettagliati del NIST e altre organizzazioni non hanno trovato alcuna prova di esplosivi o segni di una demolizione pianificata. ### Conclusione: Le indagini ufficiali e i rapporti tecnici indicano chiaramente che il crollo delle Torri Gemelle è stato causato dagli impatti degli aerei e dai successivi incendi che hanno indebolito la struttura, portando al collasso progressivo. Le teorie che ipotizzano l'uso di esplosivi sono state esaminate ma non supportate da prove concrete. L'11 settembre 2001 ha avuto un impatto profondo anche sulla musica, influenzando artisti di diversi generi e portandoli a esprimere il dolore, la rabbia, la riflessione e la speranza che l'evento ha generato. La musica ha raccontato l'episodio da diverse prospettive, esplorando sia il trauma individuale che quello collettivo, e offrendo una forma di guarigione o commemorazione per chi l'ha vissuto. ### Canzoni che hanno affrontato l'11 settembre: 1. **Bruce Springsteen – "The Rising" (2002)** Questo album è uno dei più emblematici legati all'11 settembre. La title track, "The Rising", racconta la storia di un pompiere che sale verso le Torri Gemelle e riflette sul sacrificio e la speranza. L'intero album esplora i temi della perdita e della resilienza attraverso il prisma dell'America post-11 settembre, e rappresenta una sorta di catarsi per molte persone che hanno cercato conforto nella musica. 2. **Paul McCartney – "Freedom" (2001)** Paul McCartney era a New York il giorno degli attacchi e ha scritto questa canzone in risposta, cercando di trasmettere un messaggio di forza e resistenza. "Freedom" è stata eseguita al concerto benefico **"The Concert for New York City"**, un evento organizzato per raccogliere fondi per le vittime dell'attacco e celebrare il coraggio dei soccorritori. 3. **Toby Keith – "Courtesy of the Red, White and Blue (The Angry American)" (2002)** Questa canzone country ha rappresentato il lato più patriottico e arrabbiato della reazione americana agli attentati. Toby Keith esprime il desiderio di giustizia (o vendetta), e la canzone è diventata molto popolare tra coloro che volevano una risposta forte agli attacchi. Sebbene controversa per i suoi toni duri, ha rappresentato una parte significativa del sentimento nazionale. 4. **Alan Jackson – "Where Were You (When the World Stopped Turning)" (2001)** Questa ballata country ha cercato di catturare lo shock, la confusione e il dolore collettivo che l'11 settembre ha causato. La canzone pone domande che molti si sono fatti: "Dov'eri quando il mondo si è fermato?" Il tono è riflessivo e malinconico, ed è diventata una delle canzoni più ricordate che trattano direttamente dell'evento. 5. **U2 – "Walk On" (2001)** Sebbene scritta prima dell'11 settembre, "Walk On" è diventata una sorta di inno di resilienza dopo l'attacco. U2 ha dedicato diverse performance della canzone alle vittime dell'11 settembre, e il testo, che parla di andare avanti di fronte alle avversità, è stato interpretato come un messaggio di forza per chi cercava di ricostruire la propria vita. 6. **Neil Young – "Let’s Roll" (2001)** Questa canzone è stata ispirata dagli atti eroici dei passeggeri del volo United 93, che si sono ribellati contro i dirottatori, impedendo che l'aereo colpisse un obiettivo a terra. La frase "Let's roll" era ciò che uno dei passeggeri, Todd Beamer, ha detto mentre guidava la ribellione. Neil Young ha scritto questo brano per onorare quei passeggeri coraggiosi. ### Concerti e eventi musicali commemorativi: - **The Concert for New York City (2001)** Subito dopo gli attacchi, questo grande concerto benefico si è tenuto al Madison Square Garden per raccogliere fondi a favore delle vittime e per rendere omaggio ai soccorritori. Vi hanno partecipato artisti come Paul McCartney, The Who, Mick Jagger, David Bowie e molti altri. L'evento è stato una celebrazione dell'unità e della solidarietà di fronte alla tragedia. - **America: A Tribute to Heroes (2001)** Questo telethon, trasmesso a livello nazionale, ha visto la partecipazione di artisti come Bruce Springsteen, U2, Celine Dion e molti altri. Lo scopo era quello di raccogliere fondi per le vittime e i loro familiari, e molte delle performance erano riflessive e piene di emozione, offrendo un momento di unità e commiserazione collettiva. ### Effetti sull’industria musicale: L'11 settembre ha avuto anche un impatto diretto sull'industria musicale: - **Censura e sensibilità**: Molte canzoni che potevano essere considerate inappropriate o troppo aggressive dopo l'11 settembre furono temporaneamente rimosse dalle playlist radiofoniche, come "Imagine" di John Lennon (per il suo messaggio pacifista) o "New York, New York" di Frank Sinatra, per il legame con la città colpita. - **Modifiche ai testi e alle copertine**: Alcuni artisti modificarono testi o copertine di album che potevano sembrare insensibili o inappropriate nel clima post-11 settembre. Ad esempio, i Dream Theater cambiarono la copertina del loro album "Live Scenes from New York" perché raffigurava il World Trade Center in fiamme, una coincidenza che uscì pochi giorni prima degli attacchi. ### Conclusione: La musica ha offerto un modo per elaborare il trauma dell'11 settembre, sia attraverso canzoni che commemorano i caduti, sia con inni che hanno ispirato resistenza e speranza. Artisti di ogni genere hanno interpretato l'evento in modi diversi, riflettendo la complessità delle emozioni che ha suscitato, dall'angoscia e la perdita alla forza e la solidarietà. Sì, le **Dixie Chicks** (oggi conosciute come **The Chicks**) hanno avuto notevoli problemi, ma non per aver trattato direttamente il tema dell'11 settembre. I problemi che hanno affrontato sono legati alle loro critiche alla guerra in Iraq e alla presidenza di **George W. Bush**, che erano strettamente connesse al clima politico post-11 settembre. ### Contesto: Nel marzo 2003, durante un concerto a Londra, la cantante **Natalie Maines**, frontwoman delle Dixie Chicks, fece una dichiarazione che scatenò una controversia a livello nazionale negli Stati Uniti. Mentre l'invasione dell'Iraq era imminente, Maines disse al pubblico: > **"Just so you know, we’re ashamed that the President of the United States is from Texas."** Questa dichiarazione era una critica diretta al presidente **George W. Bush**, nato in Texas come Maines e il resto della band. La critica arrivava in un momento in cui il patriottismo e il sostegno alla guerra erano fortemente presenti negli Stati Uniti, specialmente nel Sud, dove le Dixie Chicks avevano una vasta base di fan nella comunità country. ### Conseguenze: 1. **Boicottaggi e censure**: Dopo il commento di Maines, molte stazioni radio, soprattutto quelle country, **boicottarono le Dixie Chicks**, rimuovendo le loro canzoni dalle playlist. In alcune parti degli Stati Uniti, i fan organizzarono pubblici **roghi dei loro album**. 2. **Perdita di supporto nel mondo country**: La comunità della musica country, che spesso riflette valori patriottici e conservatori, si rivolse contro di loro. Molti artisti e fan country criticarono duramente le Dixie Chicks per aver espresso opinioni contro la guerra e contro il presidente in un momento in cui il sostegno alla leadership nazionale era considerato importante. 3. **Minacce e ostilità**: Le Dixie Chicks ricevettero **minacce di morte** e furono soggette a intense campagne di odio. Questo dimostrò quanto fossero polarizzate le opinioni politiche negli Stati Uniti all'epoca, specialmente nell'industria della musica country. 4. **Carriera messa in pausa**: Dopo la controversia, la loro carriera negli Stati Uniti subì un grave colpo. Le vendite dei loro album calarono, e per diversi anni furono considerate una "band alienata" dall'industria country. Tuttavia, il gruppo trovò maggiore supporto nel pubblico internazionale e in generi musicali non tradizionalmente legati al country. ### La risposta delle Dixie Chicks: Le Dixie Chicks risposero alla controversia con coraggio e determinazione. Nel 2006, pubblicarono l'album **"Taking the Long Way"**, che includeva la famosa canzone **"Not Ready to Make Nice"**. Questo brano affrontava direttamente le critiche ricevute e il loro rifiuto di scusarsi per aver espresso le proprie opinioni. > **"Not Ready to Make Nice"** fu un grande successo e vinse diversi Grammy Awards, incluso quello per il **Miglior Album dell'Anno** e la **Canzone dell'Anno**. L'album rappresentava un chiaro messaggio: non erano pronte a cedere alla pressione e non si scusavano per aver esercitato la loro libertà di espressione. ### Riflessione sulla controversia: La controversia rifletteva una tensione più ampia nella società americana post-11 settembre, dove il patriottismo era visto da molti come un valore sacro e la critica alle politiche governative, specialmente riguardo alla guerra, poteva essere percepita come un tradimento. Le Dixie Chicks divennero un simbolo di questa polarizzazione e del conflitto tra libertà di espressione e patriottismo. ### Conclusione: Sebbene le Dixie Chicks non abbiano trattato direttamente l'11 settembre, la loro critica alla guerra in Iraq e a George W. Bush, strettamente connessa agli eventi post-11 settembre, portò a una delle più grandi controversie nella storia della musica country. Tuttavia, con il tempo, il gruppo è riuscito a superare le difficoltà e ha ottenuto una sorta di redenzione artistica e pubblica, guadagnando il rispetto di molti per la loro integrità e il loro coraggio nel difendere le proprie opinioni. Sì, i **Green Day** hanno trattato indirettamente i temi legati all'11 settembre e le sue conseguenze, soprattutto attraverso il loro album più famoso, **"American Idiot"** (2004). L'album non affronta direttamente gli attacchi dell'11 settembre, ma esplora il clima politico e sociale che si è sviluppato negli Stati Uniti dopo gli attentati, in particolare la guerra in Iraq, il patriottismo estremo e la manipolazione dei media. ### Contesto di "American Idiot": "American Idiot" è un concept album che segue un personaggio chiamato **Jesus of Suburbia**, che rappresenta la frustrazione e l'alienazione della generazione cresciuta nell'America post-11 settembre. L'album racconta una storia di rabbia, disillusione e ribellione contro il governo, i media e la società americana dell'epoca. ### Temi principali legati all'11 settembre e alle sue conseguenze: 1. **Critica ai media e alla manipolazione dell'informazione**: - La title track, **"American Idiot"**, critica aspramente la manipolazione dei media e il modo in cui la società americana è stata spinta verso un patriottismo cieco e un clima di paura. La canzone si scaglia contro l'idea che gli americani vengano indotti a seguire passivamente le direttive dei media e del governo, un tema strettamente legato alla narrazione post-11 settembre e alla propaganda che ha accompagnato la guerra in Iraq. > "Don't wanna be an American idiot, Don't want a nation under the new media." Qui, la band esprime il loro disgusto per l'influenza della propaganda mediatica e la crescente polarizzazione politica. 2. **Disillusione verso il governo e la guerra**: - Il brano **"Holiday"** è una feroce critica alla guerra in Iraq e alla politica estera dell'amministrazione Bush, spesso vista come una conseguenza diretta degli attacchi dell'11 settembre. La canzone denuncia l'ipocrisia e l'avidità che, secondo i Green Day, hanno guidato la decisione di invadere l'Iraq. > "This is the dawning of the rest of our lives, On holiday." Il termine "holiday" viene usato sarcasticamente per indicare una pausa dalla realtà, mentre la guerra viene condotta senza una giustificazione morale valida. 3. **Riflessioni sulla paura e l'ansia della generazione post-11 settembre**: - **"Boulevard of Broken Dreams"** esplora temi più personali di alienazione e solitudine, ma riflette anche l'ansia e la disillusione che molti americani, specialmente giovani, hanno provato nell'era post-11 settembre. Il senso di isolamento e la perdita di speranza di Jesus of Suburbia rappresentano simbolicamente il malessere di una generazione confusa e incerta sul futuro. > "I walk a lonely road, The only one that I have ever known." 4. **Rabbia verso l'apatia sociale**: - In **"Wake Me Up When September Ends"**, molti hanno visto una connessione simbolica con gli attacchi dell'11 settembre. Sebbene la canzone sia stata scritta dal frontman **Billie Joe Armstrong** come una riflessione personale sulla morte di suo padre, è diventata una sorta di inno per chiunque cercasse di elaborare il dolore e il trauma degli eventi del 2001. L'uso di "September" nel titolo ha portato molti a collegare il brano agli eventi dell'11 settembre e al desiderio di superare quel periodo buio. > "Here comes the rain again, Falling from the stars, Drenched in my pain again, Becoming who we are." La canzone evoca sentimenti di perdita e desiderio di guarigione, temi che risuonano con l'atmosfera post-attentati. ### Impatto di "American Idiot": "American Idiot" è stato un successo enorme e ha avuto un impatto culturale significativo. L'album ha dato voce a una generazione di giovani disillusi dalla politica americana e dalla guerra, riflettendo il malcontento diffuso verso l'amministrazione Bush e il modo in cui il paese aveva reagito agli eventi dell'11 settembre. Il successo dell'album ha portato anche alla produzione di un musical omonimo, che ha continuato a esplorare questi temi. ### Conclusione: I Green Day non hanno trattato direttamente gli attacchi dell'11 settembre, ma il loro album "American Idiot" è una risposta critica alle conseguenze politiche e sociali di quell'evento, in particolare la guerra in Iraq, la manipolazione dei media e la disillusione dei giovani. L'album è stato un potente veicolo di protesta contro il clima politico dell'epoca e ha dato voce alla frustrazione di molti americani.Recognizing Generic and Specific Words Memory updated Here's a brief description of each category of gastrointestinal (GI) drugs along with their trade and generic names: Electrolyte Modifiers Description: These agents help maintain electrolyte balance in the body. Trade/Generic Names: Calcium Carbonate (Tums, Caltrate) Calcium Gluconate (Kalcinate) Potassium Chloride (Klor-Con, Micro-K) Sodium Bicarbonate (Baking Soda, Alka-Seltzer) Sodium Polystyrene Sulfonate (Kayexalate) Gastric Mucosa Protectors Description: These drugs protect the stomach lining and reduce acid production. Trade/Generic Names: Famotidine (Pepcid) Ranitidine (Zantac) Cimetidine (Tagamet) Nizatidine (Axid) Esomeprazole (Nexium) Omeprazole (Prilosec) Pantoprazole (Protonix) Lansoprazole (Prevacid) Misoprostol (Cytotec) Sucralfate (Carafate) Antidiarrheals Description: These medications help reduce diarrhea. Trade/Generic Names: Bismuth Subsalicylate (Pepto-Bismol) Atropine (Atropen) Hyoscyamine (Levsin) Diphenoxylate/Atropine (Lomotil) Loperamide (Imodium) Codeine (Various) Irritable Bowel Syndrome (IBS) Treatments Description: Medications specifically aimed at treating symptoms of IBS. Trade/Generic Names: Alosetron (Lotronex) Laxatives/Bowel Preps/Antiflatulents Description: These drugs aid in relieving constipation, preparing the bowel for procedures, or reducing gas. Trade/Generic Names: Psyllium (Metamucil) Methylcellulose (Citrucel) Polyethylene Glycol/Electrolyte (MiraLAX, GoLYTELY) Simethicone (Gas-X) Sennoside (Senokot) Bisacodyl (Dulcolax) Lactulose (Enulose) Docusate Calcium/Docusate Sodium (Surfak/Colace) Magnesium Oxide/Magnesium Sulfate/Magnesium Hydroxide (Mag-Ox/Epsom Salt/Milk of Magnesia) Antiemetics Description: Medications used to prevent or treat nausea and vomiting. Trade/Generic Names: Scopolamine (Transderm Scop) Meclizine (Antivert) Prochlorperazine (Compazine) Metoclopramide (Reglan) Ondansetron (Zofran) Appetite Stimulants Description: These drugs are used to stimulate appetite, often in conditions like cancer or AIDS. Trade/Generic Names: Dronabinol (Marinol) Nabilone (Cesamet)DESCRIPTIVE TEXT Definition of Descriptive Text Descriptive Text is a text which says what a person or a thing is like. Its purpose is to describe and reveal a particular person, place, or thing.” Generic Structure of Descriptive Text # Identification : Identifies phenomenon (person, place, or thing) that will be described. (berisi tentang identifikasi hal / seorang yang akan dideskripsikan.) # Description : Describes parts, qualities, characteristics, etc (berisi tentang penjelasan / penggambaran tentang hal / seseorang dengan menyebutkan beberapa sifatnya.) The Characteristics / Language Feature of Descriptive Text 1. The use of adjective to clarify the noun, for example: a beautiful beach, a handsome man, the famous place in jepara, etc. 2. Focus on specific participant, has a ertain object , is not common, for example Sadengan Beach, Borobudur Temple,Christiano Ronaldo, etc 3. The use of simple present tense: The sentence pattern used is simple present because it tells the fact of the object described. 4. Action verb : verbs that show an activity( for example ; run, walk, sleep, etc)