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F.2 The Passive
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Chapter 7 - Review Data and Decision Making *Glow bus due at midnight, name and student number: answer questions using content in class People have created wonderful things for centuries, and management Management can be traced as far back as 500 bc when the ancient Sumerians used written records to improve government and business activities Why is it important to lean from the past Not to repeat our mistakes Classical management approaches Scientific management Administrative Principles Bureaucratic organisation Behavioural Management Approaches Follett’s Organizations as communities The Hawthorne studies Maslow’s theory of human needs Mcgregor’s Theory x and Theory Y Argyris Personality and organisation Modern Management foundations Organises as systems Contingency thinking Quality management Quantitative and analysis and tools Evidence-based management Contributions Frederick Taylor - Father of Scientific management He noticed that workers often did their jobs with wasted motions and without a constant approach. His resulted in inefficiency and low performance He believed the problem could be fixed if workers were taught to do their jobs in the best ways and ten were helped and guided by supervisors Four guiding principles of scientific management Rules of motion, standardized work and proper working conditions Select workers with the right abilities Train workers and give them incentives Support workers by planning and smoothing the way as they do their work Frank and Lillian Gilbreth Pioneered use of motitono studies as a management tool In one famous case, the gilbreaths cut down the number of motions used by bricklayers adn tripled their productivity Contributions from scientific management Make results-based compensation a performance incentive Carefully design jobs with efficient work methods Carefully select workers with the ability to perform the job Trian workers to execute activities to the best of their abilities Train supervisors to support workers so they can perform jobs to the best of their abilities Classical Management Adiminstative principle (Henro Fayol) 1919, after a career in French industry, Henri F published “adminisration Industrielle et Generale” (General and industrial management) in which we out like his views on the management of organiztion and workers Rules and duties in management Foresight - to complete a plan of action for the future Organization - To provide and mobilize resources to implement the plan Common- to lead, select and evaluate workers to get the best work toward the plan Coordination- to fit diverse efforts together and ensure information is shared and problems solved Control- to make sure things happen according to plan and to take necessary corrective action Classical management Bureacratic organiztion (Max Weber) Max weber (Bureaucrativ organization) - late 19th century German political economist who had a major impact in the fields of management and sociology Bureaucratic Organization An ideal, intentionally rational adn very efficient form of organization Based on the principles of logic, order and legitimate authority Characteristics of BO Clear division of labour Clear hierarchy of authority Formal rules and procedure Impersonality Careers based on merit What are some disadvantages of bureaucracy Takes a long time for problems to become solved bec there are procedures and there is a chain of people in command Having the power Rules have to follow Excessive paperwork or “red tape” Slowness in handling problems Rigidity in the face of shifting needs Resistance to change Employee apathy Behavioural Management Approaches (focus on understanding the elements that affect human behaviour in organisations) Follett’s Organizations as communites Mary park follett contributed to the transition from classical thinking inot behavioural management Groups and human cooperation Groups allow individuales too combine their talents for a greater good Organizations are cooperating “communites” of managers adn workers Managers job is to help people copperate and achive an integration of goals and intrests Forward-looking managment insight: Making every emploee an owner creates a sense of collective responsibility Prescursor of employrr ownership, profit sharing and gain sharing Buniess problems invovle a varity of inter realted factors Prescursor of systems thinking Private profits realtive to public good Precursor of managerial ethics and social respinsibility Hawthorne studies Took place at western electric chicago plan, a tran led by Harvards Elton Mayo set out to learn how econmic incentives and workplace conditions affected workers output Maing objective Intial study examined how ecomoin incentives adn physical conditions affected worker output (productivity) No consistent relationship found During experientmetn they had 2 groups The expertiant groups (impoved wokring ocnditions ) The control group ( no changes to original working conidtions) No consitant relationship found, perfomance in both groups increased even after removing incentives Social setting and human relations Concluded New “social setting” led workers to do good job Good “Human relations” = higher productivity The contect - The Great Depression (1929-1940) Employee attitudes and groups processes Osme thinsf satisifed some workers but not others People resticited output to adhere to groups norms (Avoid layoffs) Lessons from he hawthrone stufirs Social and human concerns are keys to prductivity Hawthrone effect - People who are singled out for special attention perform as expected Maslow’s Theory of human needs Human needs The work of psychologist Abraham Maslow in the area if human “needs,” also has had a major impact in the behavioual apporach to management Maslow’s hierarchy of human needs Self actualization needs Higherst level: need foe self fulfillment to grow and use abilites to fullest and most creative extent Esteem needs Needs fro esteem in eyes of others need for respect, prestige, recognition; need for self esteem, personal sense of competence, mastery Social needs Need for love, affection, sense of belongingness in ones relationship either other people Safett needs Need for security, protection and stability in teh events of day to day life Physiological needs Most basic of all human needs: need for biological maintence; food, water and phydical well being Principles Defict principle: A satidifed need is not a motivator of behaviour Progress principles: A need becomes a motivator once the preceding lower-level need is satisfied Both principles cease to operate at self actulilzation level McGregor’s Theories Thepry x assumes that workers; Dislike work Lack ambition Are irresponsible Resist change Prefer to be led Theoyry y assumes that workers are Willing to work Willing to accept responsibility Capable of self control Capable of self direction Imaginative and creative According to McGregor, Managers create: Self fulfilling prophecies Implications of Theory x and y Theory x managers: Create situations where workers become dependent, passive and reluctant Theory y managers create situations where workers respond with initiative and high performance Central to notions of empowerment and self management Argyris’s theory of adult personality Classical management principles and practices inhibit worker maturation and are inconsistent with the mature adult personality Management practices should accommodate the mature personality: Increasing task responsibility Increasing task variety Using participative decision making Modern Management Foundation Quantitative analysis and Tools Analytics: the use of large data bases and mathematics to solve problems and make informed decision using systematic analysis Organization as systems System Collection of interrelated parts that function together to achieve a common purpose Subsystem A smaller component of a larger system Open systems Organisations that interact with their environment Contingency thinking Tires to maths managerial responses with problem (situation) No “one best way” to manage The “appropriate way to to manage depends on the situations Quality management Qality anc competitive advantafe are linked Total quality managment (TQM) Comprehensive approach to contiou impovment on teh entire organization ISO certification Gloval quality management standards Refine and upgrade quality to meet ISO requirments Evidednce Based Managment Making management decision on “hard facts” about what really works Multiple Choice Questions A6. You’ve hired a third-party to gather information about your company’s servers and data. The third-party will not have direct access to your internal network but can gather information from any other source. Which of the following would BEST describe this approach? ❍ A. Backdoor testing ❍ B. Passive footprinting ❍ C. OS fingerprinting ❍ D. Partially known environment A7. Which of these protocols use TLS to provide secure communication? (Select TWO) ❍ A. HTTPS ❍ B. SSH ❍ C. FTPS ❍ D. SNMPv2 ❍ E. DNSSEC ❍ F. SRTP A8. Which of these threat actors would be MOST likely to attack systems for direct financial gain? ❍ A. Organized crime ❍ B. Hacktivist ❍ C. Nation state ❍ D. Competitor A9. A security incident has occurred on a file server. Which of the following data sources should be gathered to address file storage volatility? (Select TWO) ❍ A. Partition data ❍ B. Kernel statistics ❍ C. ROM data ❍ D. Temporary file systems ❍ E. Process table Quick Answer: 33 The Details: 43 Quick Answer: 33 The Details: 44 Quick Answer: 33 The Details: 45 Quick Answer: 33 The Details: 46 6 Practice Exam A - Questions A10. An IPS at your company has found a sharp increase in traffic from all-in-one printers. After researching, your security team has found a vulnerability associated with these devices that allows the device to be remotely controlled by a third-party. Which category would BEST describe these devices? ❍ A. IoT ❍ B. RTOS ❍ C. MFD ❍ D. SoC A11. Which of the following standards provides information on privacy and managing PII? ❍ A. ISO 31000 ❍ B. ISO 27002 ❍ C. ISO 27701 ❍ D. ISO 27001 A12. Elizabeth, a security administrator, is concerned about the potential for data exfiltration using external storage drives. Which of the following would be the BEST way to prevent this method of data exfiltration? ❍ A. Create an operating system security policy to prevent the use of removable media ❍ B. Monitor removable media usage in host-based firewall logs ❍ C. Only allow applications that do not use removable media ❍ D. Define a removable media block rule in the UTM Quick Answer: 33 The Details: 47 Quick Answer: 33 The Details: 48 Quick Answer: 33 The Details: 49 Practice Exam A - Questions 7 A13. A CISO (Chief Information Security Officer) would like to decrease the response time when addressing security incidents. Unfortunately, the company does not have the budget to hire additional security engineers. Which of the following would assist the CISO with this requirement? ❍ A. ISO 27701 ❍ B. PKI ❍ C. IaaS ❍ D. SOAR A14. An insurance company has created a set of policies to handle data breaches. The security team has been given this set of requirements based on these policies: • Access records from all devices must be saved and archived • Any data access outside of normal working hours must be immediately reported • Data access must only occur inside of the country • Access logs and audit reports must be created from a single database Which of the following should be implemented by the security team to meet these requirements? (Select THREE) ❍ A. Restrict login access by IP address and GPS location ❍ B. Require government-issued identification during the onboarding process ❍ C. Add additional password complexity for accounts that access data ❍ D. Conduct monthly permission auditing ❍ E. Consolidate all logs on a SIEM ❍ F. Archive the encryption keys of all disabled accounts ❍ G. Enable time-of-day restrictions on the authentication server Quick Answer: 33 The Details: 50 Quick Answer: 33 The Details: 51 8 Practice Exam A - Questions A15. Rodney, a security engineer, is viewing this record from the firewall logs: UTC 04/05/2018 03:09:15809 AV Gateway Alert 136.127.92.171 80 -> 10.16.10.14 60818 Gateway Anti-Virus Alert: XPACK.A_7854 (Trojan) blocked. Which of the following can be observed from this log information? ❍ A. The victim's IP address is 136.127.92.171 ❍ B. A download was blocked from a web server ❍ C. A botnet DDoS attack was blocked ❍ D. The Trojan was blocked, but the file was not A16. A user connects to a third-party website and receives this message: Your connection is not private. NET::ERR_CERT_INVALID Which of the following attacks would be the MOST likely reason for this message? ❍ A. Brute force ❍ B. DoS ❍ C. On-path ❍ D. Disassociation A17. Which of the following would be the BEST way to provide a website login using existing credentials from a third-party site? ❍ A. Federation ❍ B. 802.1X ❍ C. PEAP ❍ D. EAP-FAST Quick Answer: 33 The Details: 53 Quick Answer: 33 The Details: 54 Quick Answer: 33 The Details: 55 Practice Exam A - Questions 9 A18. A system administrator, Daniel, is working on a contract that will specify a minimum required uptime for a set of Internet-facing firewalls. Daniel needs to know how often the firewall hardware is expected to fail between repairs. Which of the following would BEST describe this information? ❍ A. MTBF ❍ B. RTO ❍ C. MTTR ❍ D. MTTF A19. An attacker calls into a company’s help desk and pretends to be the director of the company’s manufacturing department. The attacker states that they have forgotten their password and they need to have the password reset quickly for an important meeting. What kind of attack would BEST describe this phone call? ❍ A. Social engineering ❍ B. Tailgating ❍ C. Watering hole ❍ D. On-path A20. A security administrator has been using EAP-FAST wireless authentication since the migration from WEP to WPA2. The company’s network team now needs to support additional authentication protocols inside of an encrypted tunnel. Which of the following would meet the network team’s requirements? ❍ A. EAP-TLS ❍ B. PEAP ❍ C. EAP-TTLS ❍ D. EAP-MSCHAPv2 Quick Answer: 33 The Details: 56 Quick Answer: 33 The Details: 57 Quick Answer: 33 The Details: 58 10 Practice Exam A - Questions A21. Which of the following would be commonly provided by a CASB? (Select TWO) ❍ A. List of all internal Windows devices that have not installed the latest security patches ❍ B. List of applications in use ❍ C. Centralized log storage facility ❍ D. List of network outages for the previous month ❍ E. Verification of encrypted data transfers ❍ F. VPN connectivity for remote users A22. The embedded OS in a company’s time clock appliance is configured to reset the file system and reboot when a file system error occurs. On one of the time clocks, this file system error occurs during the startup process and causes the system to constantly reboot. Which of the following BEST describes this issue? ❍ A. DLL injection ❍ B. Resource exhaustion ❍ C. Race condition ❍ D. Weak configuration A23. A recent audit has found that existing password policies do not include any restrictions on password attempts, and users are not required to periodically change their passwords. Which of the following would correct these policy issues? (Select TWO) ❍ A. Password complexity ❍ B. Password expiration ❍ C. Password history ❍ D. Password lockout ❍ E. Password recovery Quick Answer: 33 The Details: 59 Quick Answer: 33 The Details: 60 Quick Answer: 33 The Details: 61 Practice Exam A - Questions 11 A24. What kind of security control is associated with a login banner? ❍ A. Preventive ❍ B. Deterrent ❍ C. Corrective ❍ D. Detective ❍ E. Compensating ❍ F. Physical A25. A security team has been provided with a noncredentialed vulnerability scan report created by a thirdparty. Which of the following would they expect to see on this report? ❍ A. A summary of all files with invalid group assignments ❍ B. A list of all unpatched operating system files ❍ C. The version of web server software in use ❍ D. A list of local user accounts A26. A business manager is documenting a set of steps for processing orders if the primary Internet connection fails. Which of these would BEST describe these steps? ❍ A. Communication plan ❍ B. Continuity of operations ❍ C. Stakeholder management ❍ D. Tabletop exercise A27. A security administrator is concerned about data exfiltration resulting from the use of malicious phone charging stations. Which of the following would be the BEST way to protect against this threat? ❍ A. USB data blocker ❍ B. Personal firewall ❍ C. MFA ❍ D. FDE Quick Answer: 33 The Details: 62 Quick Answer: 33 The Details: 63 Quick Answer: 33 The Details: 64 Quick Answer: 33 The Details: 65 12 Practice Exam A - Questions A28. A company would like to protect the data stored on laptops used in the field. Which of the following would be the BEST choice for this requirement? ❍ A. MAC ❍ B. SED ❍ C. CASB ❍ D. SOAR A29. A file server has a full backup performed each Monday at 1 AM. Incremental backups are performed at 1 AM on Tuesday, Wednesday, Thursday, and Friday. The system administrator needs to perform a full recovery of the file server on Thursday afternoon. How many backup sets would be required to complete the recovery? ❍ A. 2 ❍ B. 3 ❍ C. 4 ❍ D. 1Sadlier Level F Unit 2 Choose the Right Word Part 1Please create English vocabulary fill-in-the-blank quiz questions for the following English words. . accept
各acceptance
acceptable
2. achieve lativ」完成；達到
【91學測】
名 achievement達成；成就
形 achievable可完成的；做得成的
3. adopt la'dapt」收養；採納【88、97學測】
相似 adapt 動（使）適應；改編
4. agree la'gril同意 （with / to)
{F施5-10）
名 agreement一致；協議
IF M5-10;
形 agreeable同意的
(F NE5-10;
片語 agree with +人/to +事情同意〜
5.allow [alau] 九許；給予(F2-2,F地1-5,L1-93
名 allowance津貼；零用錢
6. announce lanaunsl 宣布
F5-1？192學測〕
名 announcement宣告；通告
F5-1
7. appear [a prr] 出現；呈現；似乎
各 appearance顯露；出現；外表
8. apply laplar] 申請；應用【94學測】
冬 application申請（書）；用途；敷用
多 appliance 工具；用具；器具【97學測】
冬 applicant 申請人
片語 apply A to B 應用A於B
apply for 申請~
9. assume lasiuml 假定
留 assumption 假設；假裝；擔任
片語 assuming = if (that) +S+V...
10. assure [arur] 確保；保證（of)
（F #2-11,L4-4}【104學測，99指考】
名 assurance IU」自信； 保險[C］保證
11. attend la'tend」 出席：照料
2-5,S1-9}
客 attendance到場；出席人數
片語 attend to + 0 注意〜
12. bear [ber」 承受；忍耐：具有
{饰3-12}
相似 stand 動 忍受
13. cause ［koz］ 引起；起因（n.）；原則目
標（n.） = lead to = bring about
14. choose [tuz」 挑選；選擇
F1-2}
(chose • chosen)
15. claim [kleml 要求；奪走；聲稱 （n.)
{L4-10,S1-11;【99學測】
16. collapse ［kalleps」 倒塌；崩潰
【88、89、102學測】
形 collapsed 崩潰的
17. complete [kam plit」完成
{F5-1,F5-2}
各 completion LU完成；結束
SI 98B9 .08
形 complete完全的：澈底的
18. concern [kan'ssn］涉及；關心；憂慮；
關心的事 （n.)；擔心（n.)
【87學測】
concerning = regarding 關於
{L5-6}
片語 be concered about 擔心~
19. consider [kan'srdal考慮；認為
各 considerationIUI體貼；考慮
形 considerable相當多的；非常【90學測】
形 considerate體貼的；考慮周全的
【100學測，91指考】
1S5-1) 20. contain 「kan'tenl包含；容納：控制
{F4-4,F能1-7,L1-12,S2-6}【99學測！
各 container容
【100學測】
(L4-1,53-91 21. create [krret』創造；創作
{F1-9,F3-5,F4-9,F街1-12,S2-9}
名 creation 創造：產物；天地萬物
形 creative 有創造力的；獨創的
各 creativity 創造力 SYI-1.D: Describe the structure and/ or function of subcellular components and organelles. ★ SYI-1.E: Explain how subcellular components and organelles contribute to the function of the cell. ★ SYI-1.F: Describe the structural features of a cell that allow organisms to capture, store, and use energy. ★ ENE-1.B: Explain the effect of surface area-to-volume ratios on the exchange of materials between cells or organisms and the environment. ★ ENE-1.C: Explain how specialized structures and strategies are used for the efficient exchange of molecules to the environment. ★ ENE-2.A: Describe the roles of each of the components of the cell membrane in maintaining the internal environment of the cell. ★ ENE-2.B: Describe the Fluid Mosaic Model of cell membranes. ★ ENE-2.C: Explain how the structure of biological membranes influences selective permeability. ★ ENE-2.D: Describe the role of the cell wall in maintaining cell structure and function. ★ ENE-2.E: Describe the mechanisms that organisms use to maintain solute and water balance. ★ ENE-2.F: Describe the mechanisms that organisms use to transport large molecules across the plasma membrane. ★ ENE-2.G: Explain how the structure of a molecule affects its ability to pass through the plasma membrane. ★ ENE-2.H: Explain how concentration gradients affect the ★ movement of molecules across membranes. ★ ENE-2.I: Explain how osmoregulatory mechanisms contribute to the health and survival of organisms. ★ ENE-2.J: Describe the processes that allow ions and other molecules to move across membranes. ★ ENE-2.K: Describe the membrane-bound structures of the eukaryotic cell. ★ ENE-2.L: Explain how internal membranes and membrane- bound organelles contribute to compartmentalization of eukaryotic cell functions. ★ EVO-1.A: Describe similarities and/or differences in compartmentalization between prokaryotic and eukaryotic cells. ★ EVO-1.B: Describe the relationship between the functions of endosymbiotic organelles and their free-living ancestral counterparts 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 gover1.1945-1949: The immediate years after the Second World War ● At the end of 1945, Mao Zedong had come to see the USA as the greatest threat to his aspirations. a. He understood that East Asians were looking to the USA as the true liberator from Japanese imperialism. b. The USA’s support for the Kuomintang(KMT) and the restoration of U.S. authority in formerly Japanese Manchuria clashed with the CCP’s plans to use the region for its own needs in the impending civil war between the CCP and the GMD. ■ To compound matters, while the KMT was recognised internationally as the official government in China, Mao and the CCP saw the party as a puppet of U.S. imperialism. ● While Mao saw the USA as the greater threat to the CCP’s plans, Soviet actions also frustrated him. a. The USSR provided minimal and incoherent support for the Chinese Communists in Yan’an and Manchuria. b. Stalin also attempted to extract territorial and economic concessions from the Guomindang government in the Friendship and Alliance Treaty China signed in August 1945 under American and Soviet pressure in exchange for Soviet entry into the Second World War against Japan. ● The emerging superpower conflict over Europe and over American intervention in the impending civil war in China led to Mao’s ideological perception of the 8838/01 H1 History Paper 1 Theme II: The Cold War and East Asia (1945-1991) \ Page | 8 USA as an aggressive imperialist power that was hostile towards other countries, especially the USSR and China. ● In 1946, Mao promoted the theory of the intermediate zone, which envisioned a global united front against American imperialism. a. Mao saw the emerging superpower conflict as an American-Soviet contest for the intermediate zones, the capitalist, colonial and semi- colonial countries of West Europe, Africa, and Asia. b. Mao believed that the USSR was the defender of world peace. c. The intermediate zone, which included China, would not be part of the socialist camp. d. Despite the tremendous potential that U.S. aid held for China’s reconstruction, Mao’s ideological worldview and the impending civil war against the Guomindang prevented him from seeking normalised relations with the USA. In 1949, Mao decided to lean towards the side of the USSR despite two decades of unreliable support from them. e. Mao saw the anti-bourgeois campaigns in East Europe as evidence that China should isolate capitalist-bourgeois forces within it.2 f. Stalin had expelled Yugoslavia from the socialist camp as its leader, Tito was seen to have directly challenged Stalin’s authority. ■ Mao thus saw it as imperative to stress close unity to the USSR lest he was seen as a second Josip Broz Tito. At the same time, Mao sought a loose partnership with the USSR because Mao believed that China should preserve a high measure of self- reliance and zili gengsheng (自力更生) (regeneration through one’s own efforts). ● When the People’s Republic of China was formed on 1 October, 1949, relations between China’s and the USSR’s communists had improved substantially. a. However, the Chinese Communist Party (CCP) was also aware that the USSR never treated Chinese interests as a priority. What the CCP failed to fully understand was that Stalin ruled East Europe much like it was his empire and how this would have implications for China. b. In Mao’s first visit to the USSR in December 1949, Stalin was non- committal regarding the interests raised by the Chinese, and treated Mao as an underling as he feared that closer relations with the PRC would cause the USSR to lose privileges gained from the KMT. _________________________ 2 What Mao did not realise at that point was that the anti-bourgeois campaigns in East European countries were part of Stalin’s intentional design to consolidate the power of communists in them. 8838/01 H1 History Paper 1 Theme II: The Cold War and East Asia (1945-1991) \ Page | 9 A note on Sino-American relations 2. Early 1950: The USA’s hands-off policy towards Taiwan begins to change ● By early 1950, the Truman administration had written off Taiwan and believed it was only a matter of time before the island fell to the PLA. ● Two events in early 1950 changed the USA’s position on East Asia. ○ The formation of the USSR-PRC alliance in February 1950 ○ The North Korean invasion of South Korea in June 1950 3. 1950: The Sino-Soviet Friendship, Alliance and Mutual Assistance Treaty ● Signed on 14 February, 1950. 3.1Implications for Sino-Soviet relations ● Stalin saw it as a means to get concessions that he had failed to get from the Kuomintang (KMT) government in 1945. ● For Mao and the newly founded People’s Republic of China (PRC), the alliance would provide security against U.S. imperialism and allow the PRC to get economic aid for reconstruction from the USSR. ● The Chinese realised soon after the 1950 treaty had been signed that the Soviet Union was intent on exploiting the agreement in its own favour. 8838/01 H1 History Paper 1 Theme II: The Cold War and East Asia (1945-1991) \ Page | 10 ● The Sino-Soviet alliance was officially directed against Japanese militarism and its allies, especially the USA. ● The Sino-Soviet alliance comprised three elements: party, military and economic relations. ○ Party: The Chinese Communist Party (CCP) was included in the customs of communist party internationalism, such as regular exchange of party delegations to congresses of the fraternal parties in Stalin’s socialist camp. ■ This move was meant to bring the PRC’s ideological beliefs about communism into greater alignment with the USSR’s. ○ Military: The alliance was supposed to provide the newly formed and weak PRC with a strategic deterrent and military aid against the USA on three fronts: Guomindang-held Taiwan, divided Korea, and Vietnam where France attempted to reestablish its colonial control. ■ Convinced that the USA would aggressively seek ways to undermine the CCP-led PRC through Taiwan, Korea and Vietnam, Mao sought an active defence. ● While in Moscow, Mao unsuccessfully asked Stalin to provide military assistance for the liberation of Taiwan. ● At the beginning of 1950, the PRC delivered large-scale military aid to Hanoi. The PRC was the first country to grant the communist-led Democratic Republic of Vietnam diplomatic recognition on 18 January 1950; Mao persuaded Stalin to do so on 30 January 1950. ● The PRC committed itself to North Korea, where Mao saw the commitment to North Korea both as a defence against U.S. imperialism and as support for a fellow communist country. ○ Economic: During Mao’s first stay in Moscow, Stalin had personally promised the delivery of fifty projects for primary industrialisation. ■ The agreement also led to a series of supplementary ones, such as a US$ 300 million loan that the PRC would repay with a mixture of strategic materials, rubber, agricultural products, goods for daily use and hard currency. ■ Significantly, Stalin used Soviet military and economic aid to extract concessions similar to those he failed to get from the Guomindang government in 1945. ■ The USSR and PRC would disagree on the pace and extent of the PRC’s planned development. ● In the last five weeks of Stalin’s life in early 1953, he attempted to pressure the PRC to reduce the planned 8838/01 H1 History Paper 1 Theme II: The Cold War and East Asia (1945-1991) \ Page | 11 development speed to a mere annual growth of 13-14 percent, and to plan individual projects in detail beforehand. These moves would potentially result in the PRC’s economy growing at a slower rate than initially projected. ● However, after Stalin’s death on 5 March 1953, the PRC’s Zhou Enlai decided to use his visit of condolence to the USSR to press forward negotiations. ○ When talks resumed in 1 April 1953, Beijing pressed for 150 Soviet industrial projects, but Moscow reduced them to 91 on the basis of insufficient data provided by the Chinese. ■ The economic disarray after China’s civil war and the economic pressures that came with the Korean War influenced recovery and reconstruction in the early years of the PRC. ● Despite the PRC being unable to tap into Soviet economic assistance immediately, mutual trade between China and the USSR nevertheless increased 6.5 times from 1950 to 1956. ● Together with the 50 projects promised by Stalin in 1950, the final version of the First FYP for the PRC included 141 Soviet and 68 East European projects in a total of 649 planned. Three thousand Soviet advisers sent to China in subsequent years were directly linked to the First FYP. ● By 1955, over 60 percent of China’s goods exchange was with the USSR. ● Soviet economic assistance to China added up to the largest foreign development venture in the socialist camp ever. ○ The total number of planned projects amounted to between 300 and 360 projects. ○ However, the number of total finished projects ranged between 134 and 150. ● Transfers of knowledge and expertise were important to China’s economic development. ○ A study on Soviet experts counts 1,445 political advisers and 9,313 technical specialists sent to China until their sudden withdrawal in mid-1960. ■ For political reasons, the gradual withdrawal of advisers began after late 1956.LESSON 4. Cellular Respiration • Define cellular respiration • Identify the stages of clan respiration You have just learned how the energy from the sun is captured, processed, and stored in the form of glucose. Cellular respiration, another important life process, is the means by which cells release the stored energy in glucose to make adenosine triphosphate (ATP). The primary goal of this life process is to convert stored energy into usable form, such as ATP, for the cells to carry out their functions. Cellular respiration involves several chemical reactions. The reactions can be summed up in the following equation: C6 H12 O6 + 602 ----- 6 CO₂ +6H₂O + ATP Glucose oxygen carbon dioxide water energy Aerobic respiration reactions, or cellular respiration that takes place in the presence of oxygen, can be grouped into three stages glycolysis, Krebs cycle, and electron transport chain (ETC). Stage 1: Glycolysis Glycolysis is the process that breaks down one molecule of 6-C glucose into 3-C pyruvates or pyruvic acids. It also releases four molecules of ATP. This process occurs in the cytoplasm of the cell. The following is the step-by-step process of glycolysis. Take note that several enzymes are involved in this process. 1. The first step of glycolysis requires energy. It can only proceed when the two ATP molecules donate energy to the glucose by transferring a phosphate group with the help of an enzyme, producing glucose 6-phosphate 2. Then, a specific enzyme promotes the rearrangement of the atoms, producing the fructose 6-phosphate. 3. The action of the enzyme in step 2 promotes the transfer of a phosphate group from another ATP molecule, forming fructose 1,6-bisphosphate. 4. The resulting fructose 1,6-bisphosphate molecules, with the help of another enzyme, splits into two molecules, each with three carbon backbones. These two sugars are dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. 5. Another important enzyme then rapidly interconverts the molecules of dihydro-xyacetone phosphate and glyceraldehyde 3-phosphate. This produces two molecules of glyceraldehyde 3-phosphate or 3-phosphoglyceraldehyde (PGAL) 6. The succeeding step involves another enzyme-mediated action. The hydrogen (H) from PGAL is transferred to the oxidizing agent, nicotinamide adenine dinucleotide (NAD), which forms NADH. A phosphate (P) is also added from the cytosol of the cell to oxidize the two molecules of PGAL, forming two 1.3-bisphosphoglycerate. 7. A phosphate (P) from 1,3-biphosphoglycerate is transferred to ADP to form ATP. This happens for each of the two 1,3-bisphosphoglycerate. resulting to a yield of two ATP and two 3-phosphoglycerate molecules. 8. A phosphate is transferred from 3-phosphoglycerate molecules from the third carbon to the second carbon, forming 2-phosphoglycerate molecules A hydrogen atom and a hydroxyl ((OH) group is released, which then combines to form water (H2O). The removal of H2O from 2-phosphoglycerate results in the formation of 2- phosphoglycerate molecules. 9. A hydrogen atom and a hydroxyl ((OH) group is released, which then combines to form water (H2O). The removal of H2O from 2-phosphoglycerate results in the formation of two phosphoenolpyruvic acid (PEP) 10. Phosphate (P) from PEP is transferred to ADP (and forms ATP) and the final product, pyruvic acid. This reaction yields two molecules of pyruvic acid and two ATP molecules In summary, a single glucose molecule that undergoes the process of glycolysis produces two molecules of pyruvic acid, four molecules of ATP, two molecules of NADEL and two molecules of H.O. However, only two molecules of ATP are counted as net products since two molecules of ATP are spent throughout the process. Stage II: Krebs Cycle The Krebs cycle, named after its proponent Sir Hans Adolf Krebs, is a cyclical series of enzyme-controlled reactions. This stage of cellular respiration occurs in the matrix of the mitochondria. It is sometimes. called the citric acid cycle (CAC) since it produces citric acid. Citric acid contains three carboxyl (COOH) groups; hence, it is also called the tricarboxylic acid cycle (TCA). This requires the pyruvic acids produced during glycolysis. The main function of this cycle is to produce high-energy-yielding molecules, namely, NADH and flavin adenine dinucleotide (FADH) that will later on be used in the electron transport chain reaction. Figure 6-7. Summary of glycolysis and corresponding products in each reaction presented (See Appendix F on page 285 for an enlarged and complete version of the image.) An initial process is needed for the Krebs cycle to begin. As a pyruvate molecule from glycolysis enters the mitochondrion, it undergoes an important preliminary ate to form acetyl-CoA reaction. Coenzyme-A (COA) combines with pyruvate help of an enzymatic complex. This conversion also produces CO, and NADH. The Krebs cycle is summarized as follows. Take note that several enzymes are involved in this process. 1. The Krebs cycle technically begins when the acetyl-CoA combines with oxaloacetic acid (OAA), a 4-C molecule, to produce citric acid, a 6-C molecule. 2. With the aid of an enzyme, the citric acid now goes through a series of reactions that releases energy. Water molecule is removed from the citric acid and is returned in a different location. The-OH group is repositioned, forming the molecule isocitrate. 3. Isocitrate is then oxidized, forming the a-ketoglutarate, a 5-C molecule. The byproducts of this reaction are NADH and CO, 4 The a-ketoglutarate loses its CO, and a coenzyme-A is added in its place. The decarboxylation occurs with the help of NAD, which then becomes NADH. The resulting molecule is called succinyl-CoA. 5. Succinyl-CoA is converted into succinate. Also in this reaction, a molecule of guanosine triphosphate (GTP) is synthesized. The GTP molecule has similar structure and energy properties to that of ATP and is used by cells the same way. The free phosphate group attacks the succinyl-CoA molecule, which detaches the COA. Then, phosphate is attached to GDP to come up with GTP, similar to the process that occur in ATP synthesis (from ADP to ATP). 6. Two hydrogens are removed from succinate, A molecule of flavin adenine dinucleotide (FAD), a coenzyme similar to NAD, is reduced to FADH, as it takes the hydrogens from the succinate. This reaction produces the fumarate. 7. Fumarate is then converted into malate as the addition of a water molecule is catalyzed. The final reaction is the regeneration of oxaloacetate. The resulting byproduct of this regeneration is NADH Recall that two pyruvate molecules were produced during glycolysis, causing the Krebs cycle to turn twice. Each tuts produces three molecules of NADH, single ATH one FADIH, and the by-product CO, which is exhaled. Stage III: Electron Transport Chain The electron transport chain (ETC) is a series of photon pumps on the inner membrane of the mitochondrion. Electron transport is the last stage of the cellular respiration. In this stage, the energy from NADH and FADH, from the Krebs cycle is transferred to ADP to produce ATP. This process is generally known as oxidative phosphorylation. This energy coupling mechanism in the cell was revealed by the work of Peter stored energy in the form of proton (1) gradient to phosphorylate (add phosphate) ADP and produce ATP. The pumping of hydrogen sons across the inner membrane creates higher concentration ions in the inner membrane than on the outside of the membrane. This chemiosmotic gradient causes the ions to flow back across the membrane where the concentration of ions is lower. ATP synthase lined in the matrix serve as a channel protein, helping the ions to move across the membrane. The chemiosmotic gradient powers the phosphorylation of ADP to ATP, which also occurs in the ATP synthase. After passing through the ETC, the oxygen, being the final hydrogen acceptor, combines with two electrons and two protons, forming a water molecule. Water is a by-product of cellular respiration and is excreted. MINI TEST 6-3 1. Which energy-releasing pathway yields the most ATF in each glucose molecule? 2. Briefly describe the two stages of aerobic respiration that follow glycolysis: (a) Krebs cycle (b) Electron transport chain Anaerobic Respiration Most cells carry out arrobic respiration when oxygen is present. Aerobic respiration is an efficient process that yields a lot of ATP. However, many organisms thrive in mud, marshes, animal gut, canned goods, sewage treatment pond, and deep oceans where oxygen is scarce. Organisms that can live without oxygen are called anaerobes. Cellular respiration that proceeds without the presence of oxygen is called anaerobic respiration. In the event that the oxygen supply becomes low, aerobic cells also perform fermentation and lactic acid fermentation anaerobic pathways. There are two common anaerobic pathways in these cells, alcoholic fermentation and lactic acid fermentation. In alcoholic fermentation, ethyl alcohol and carbon dioxide are produced by some cells using the pyruvate from glycolysis. Each pyruvate molecule is rearranged into acetaldehyde and carbon dioxide, which is eventually released. NADII gives up electrons to acetaldehyde to form ethanol Fermentation is widely used in the industry. Yeast, a fungus used in making bread. can undergo anaerobic respiration. Bakers aux sugar, flour, water, and yeast to form the bread dough. The dough rises due to the carbon dioxide and alcohol released by the yeast cells trapped in air bubbles. Beer and wine manufacturers, we yeast to ferment the sugars in wheat and grape juice, forming alcoholic beverages such as beer and wine. In some cells, glycolysis produces two pyruvates, two NADH molecules, and two ATP molecules. Pyruvate itself becomes the final acceptor of the electrons from the NADH that produces the final product: lactate. Oftentimes, this product is called lactic acid. Human skeletal muscles can carry out fermentation when the blood cannot supply the cells with adequate oxygen during strenuous activities. When lactic acid builds up in the muscles, fatigue, burning sensation, and cramps result. Lactic acid will continue to build up until there is adequate supply of oxygen. Lactic acid is then converted back into pyruvate in the liver. Muscles also restore normal functions. Have you ever wondered why milk or cream turns sour after some time? Bacterial cells that undergo fermentation are responsible in producing lactate that turns the milk sour. These bacteria are used in manufacturing yogurt and sour milk products. Fermentation pathways do not breakdown and utilize the glucose completely. ATP is no longer produced beyond the process of glycolysis. Thus, energy produced is just enough for some single-celled organisms, or the energy can only be used by multicellular organisms for a short period.