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Sons do R
Quiz by Yvan Henrique
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SOCORRO
R FORTE ENTRE VOGAIS
URUBU
R FRACO
SOCORRO
URUBU
FURO
MORENA
CORAL
AREIA
RIMA
ROMA
REI
RUA
ARROZ
CORRER
BURRO
CARRO
A paisagem sonora é o resultado da soma de todos os sons de determinado espaço. (...) Como os espaços diferem entre si, cada paisagem sonora é singular e soa de modo peculiar. Ela é dinâmica e está em constante mutação, devido a uma série de fatores: estações do ano, hora do dia ou da noite, clima, presença ou ausência de máquinas, eletrodomésticos, pessoas, animais, vento, chuva..., exemplos que podem se suceder ao infinito. Então, cabe perguntar: Será que se conhece a paisagem sonora do espaço em que se habita? Ou do local de trabalho? Como se pode caracterizar a paisagem sonora de uma rua? De um bairro? De uma casa? Só se terá uma resposta a essas questões, se se ouvir intensamente, com cuidado, procurando perceber os sons e de onde provêm: De cima? De baixo? De dentro ou de fora de um determinado espaço? Que tipos de som são predominantes? De máquinas? De pessoas? De animais?
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.
You are an elementary school teacher. Create a 20 item multiple choice quiz using the story below. Include the key answers below the questions. "Many years after God made everything, the people of the earth became plenty in number. These people forgot about God and they became very bad. God became very sad. So God said, “I will wipe out all the people on the earth. | will destroy all the animals, birds and fish, and all the trees and plants. | am so hurt by what they do that | feel sorry that | made them.’ Yet, there was a man named Noah. He was a very good man among the people of that time. He obeyed God with all his heart and did not sin against God. Noah found favor in the eyes of the Lord. Noah had a wife and three sons named Ham, Shem, and Japheth. Unlike the people around them, Noah's family lived doing what was right in God's eyes, They loved each other as one family and they never forgot to pray to God. One day, the Lord God called Noah and told him about His plan to punish all His creation and put an end to all the people of the earth. God said, “Noah, make a giant ark with many, many rooms. Put a door on the side of the ark. Make a roof on it and a small window on one side. | am going to bring floodwaters on earth to destroy all living things. Gather all kinds of animals—two of every kind: one male and one female. When the floodwaters would come, you have to bring into the ark all kinds of animals. You are to take every kind of food that is to be eaten for you and for the animals.’ The bad people made fun of Noah’s family who were making a giant ark when in fact the weather was very good. There were no dark clouds and not even a drop of rain was falling down. They continued to do bad things while Noah did everything just as God commanded him. ™ Soon after the ark was finished, the floodgates of heaven were gPened and heavy rain fell on the earth. On that day, Noah and his family entered the ark together with all the different kinds of animals, both big and small. While Noah's family and all the animals were inside the ark, the heavy rain fell non-stop for forty days and forty nights. All the living things outside the ark were destroyed. When the rain stopped, there was a great flood all over the earth. The whole land was covered with water. The waters flooded the earth for 150 days. After 150 days, dry land started to appear so God told Noah to open the door and come out of the ark for the land was already dry. Then Noah sent out all the animals from the ark, too. Then God said to Noah, “I will make a promise to you. Never again will | bring great flood on the earth to destroy all creation. | will set a rainbow in the clouds as a sign of My promise to you and to all the people of the earth.’ So, every time the rainbow appears on the sky, just remember God's promise that He will never again destroy the earth by a flood."
Translator: Joseph Geni Reviewer: Morton Bast Before March, 2011, I was a photographic retoucher based in New York City. We're pale, gray creatures. We hide in dark, windowless rooms, and generally avoid sunlight. We make skinny models skinnier, perfect skin more perfect, and the impossible possible, and we get criticized in the press all the time, but some of us are actually talented artists with years of experience and a real appreciation for images and photography. On March 11, 2011, I watched from home, as the rest of the world did, as the tragic events unfolded in Japan. Soon after, an organization I volunteer with, All Hands Volunteers, were on the ground, within days, working as part of the response efforts. I, along with hundreds of other volunteers, knew we couldn't just sit at home, so I decided to join them for three weeks. On May the 13th, I made my way to the town of Ōfunato. It's a small fishing town in Iwate Prefecture, about 50,000 people, one of the first that was hit by the wave. The waters here have been recorded at reaching over 24 meters in height, and traveled over two miles inland. As you can imagine, the town had been devastated. We pulled debris from canals and ditches. We cleaned schools. We de-mudded and gutted homes ready for renovation and rehabilitation. We cleared tons and tons of stinking, rotting fish carcasses from the local fish processing plant. We got dirty, and we loved it. For weeks, all the volunteers and locals alike had been finding similar things. They'd been finding photos and photo albums and cameras and SD cards. And everyone was doing the same. They were collecting them up, and handing them in to various places around the different towns for safekeeping. Now, it wasn't until this point that I realized that these photos were such a huge part of the personal loss these people had felt. As they had run from the wave, and for their lives, absolutely everything they had, everything had to be left behind. At the end of my first week there, I found myself helping out in an evacuation center in the town. I was helping clean the onsen, the communal onsen, the huge giant bathtubs. This happened to also be a place in the town where the evacuation center was collecting the photos. This is where people were handing them in, and I was honored that day that they actually trusted me to help them start hand-cleaning them. Now, it was emotional and it was inspiring, and I've always heard about thinking outside the box, but it wasn't until I had actually gotten outside of my box that something happened. As I looked through the photos, there were some were over a hundred years old, some still in the envelope from the processing lab, I couldn't help but think as a retoucher that I could fix that tear and mend that scratch, and I knew hundreds of people who could do the same. So that evening, I just reached out on Facebook and asked a few of them, and by morning the response had been so overwhelming and so positive, I knew we had to give it a go. So we started retouching photos. This was the very first. Not terribly damaged, but where the water had caused that discoloration on the girl's face had to be repaired with such accuracy and delicacy. Otherwise, that little girl isn't going to look like that little girl anymore, and surely that's as tragic as having the photo damaged. (Applause) Over time, more photos came in, thankfully, and more retouchers were needed, and so I reached out again on Facebook and LinkedIn, and within five days, 80 people wanted to help from 12 different countries. Within two weeks, I had 150 people wanting to join in. Within Japan, by July, we'd branched out to the neighboring town of Rikuzentakata, further north to a town called Yamada. Once a week, we would set up our scanning equipment in the temporary photo libraries that had been set up, where people were reclaiming their photos. The older ladies sometimes hadn't seen a scanner before, but within 10 minutes of them finding their lost photo, they could give it to us, have it scanned, uploaded to a cloud server, it would be downloaded by a gaijin, a stranger, somewhere on the other side of the globe, and it'd start being fixed. The time it took, however, to get it back is a completely different story, and it depended obviously on the damage involved. It could take an hour. It could take weeks. It could take months. The kimono in this shot pretty much had to be hand-drawn, or pieced together, picking out the remaining parts of color and detail that the water hadn't damaged. It was very time-consuming. Now, all these photos had been damaged by water, submerged in salt water, covered in bacteria, in sewage, sometimes even in oil, all of which over time is going to continue to damage them, so hand-cleaning them was a huge part of the project. We couldn't retouch the photo unless it was cleaned, dry and reclaimed. Now, we were lucky with our hand-cleaning. We had an amazing local woman who guided us. It's very easy to do more damage to those damaged photos. As my team leader Wynne once said, it's like doing a tattoo on someone. You don't get a chance to mess it up. The lady who brought us these photos was lucky, as far as the photos go. She had started hand-cleaning them herself and stopped when she realized she was doing more damage. She also had duplicates. Areas like her husband and her face, which otherwise would have been completely impossible to fix, we could just put them together in one good photo, and remake the whole photo. When she collected the photos from us, she shared a bit of her story with us. Her photos were found by her husband's colleagues at a local fire department in the debris a long way from where the home had once stood, and they'd recognized him. The day of the tsunami, he'd actually been in charge of making sure the tsunami gates were closed. He had to go towards the water as the sirens sounded. Her two little boys, not so little anymore, but her two boys were both at school, separate schools. One of them got caught up in the water. It took her a week to find them all again and find out that they had all survived. The day I gave her the photos also happened to be her youngest son's 14th birthday. For her, despite all of this, those photos were the perfect gift back to him, something he could look at again, something he remembered from before that wasn't still scarred from that day in March when absolutely everything else in his life had changed or been destroyed. After six months in Japan, 1,100 volunteers had passed through All Hands, hundreds of whom had helped us hand-clean over 135,000 photographs, the large majority — (Applause) — a large majority of which did actually find their home again, importantly. Over five hundred volunteers around the globe helped us get 90 families hundreds of photographs back, fully restored and retouched. During this time, we hadn't really spent more than about a thousand dollars in equipment and materials, most of which was printer inks. We take photos constantly. A photo is a reminder of someone or something, a place, a relationship, a loved one. They're our memory-keepers and our histories, the last thing we would grab and the first thing you'd go back to look for. That's all this project was about, about restoring those little bits of humanity, giving someone that connection back. When a photo like this can be returned to someone like this, it makes a huge difference in the lives of the person receiving it. The project's also made a big difference in the lives of the retouchers. For some of them, it's given them a connection to something bigger, giving something back, using their talents on something other than skinny models and perfect skin. I would like to conclude by reading an email I got from one of them, Cindy, the day I finally got back from Japan after six months. "As I worked, I couldn't help but think about the individuals and the stories represented in the images. One in particular, a photo of women of all ages, from grandmother to little girl, gathered around a baby, struck a chord, because a similar photo from my family, my grandmother and mother, myself, and newborn daughter, hangs on our wall. Across the globe, throughout the ages, our basic needs are just the same, aren't they?" Thank you. (Applause) (Applause)
Create multiple choice questions using the following information: In November, Mrs. Baker has Holling read The Tempest. Despite his preconceptions, Holling is captivated by all the "good stuff" in the play, especially the cussing, which he decides to learn by heart. He figures that Mrs. Baker could not have read the play herself; if she had, she certainly would not have let him have it. Holling is amazed when he discovers that his teacher not only has read the play, but she knows the bad parts as well. Mrs. Baker gives Holling a one-hundred-and-fifty question test on The Tempest, and assigns him to read the play again, telling him "there is a lot more to (it) than a list of colorful curses." The deadline set by Holling's classmates for him to bring them cream puffs arrives, but although Holling's father's company has won the Baker's Sporting Emporium contract, he refuses to extend an advance on his son's allowance. Desperate, Holling goes to Goldman's Best Bakery, offering to work for the money he lacks to buy the cream puffs. Coincidentally, Mr. Goldman, who is active in Long Island's Shakespeare Company, needs a boy to perform in their upcoming Extravaganza, and because of his work with Mrs. Baker, Holling fits the bill. Mr. Goldman gives Holling the required number of cream puffs in exchange, but sadly, while the students are at recess, Caliban and Sycorax, the escaped rats who inhabit the classroom walls and ceiling, come out and decimate the treats. Somehow, the disaster is blamed on Holling; he must clean up the mess, and his classmates decree that he still owes them cream puffs. The next Wednesday, Holling brings five cream puffs to school, which is all he can afford. In addition to facing his classmates' ire, he has to deal with the fact that, in the Shakespeare Company Holiday Extravaganza, he must play the part of Ariel, who is a fairy, and wear yellow tights with white feathers on an unmentionable part of his anatomy; "not a good thing for a boy from Camillo Junior High." To Holling's surprise, just when things are at their darkest, Mrs. Baker comes through for him, bringing cream puffs for the students on his behalf. That afternoon, Mrs. Baker and Holling discuss The Tempest, and whether or not Caliban, the "monster," deserves a happy ending. Holling argues that, as the antagonist, he does not, but Mrs. Baker muses whether Shakespeare might have shown, even in a monster, the capacity of humankind to use defeat to grow. Mrs. Bigio stumbles into the classroom at this point, emitting sounds of indescribable sadness; she has just learned that her husband has been killed in a futile reconnaissance mission in Vietnam. Two nights after his funeral, the Catholic Relief Agency, which houses Vietnamese refugees, including Holling's classmate Mai Thi, is the target of a hate crime. Holling reflects that Shakespeare, with his happy endings for nearly everyone in The Tempest, is wrong. He says, "sometimes, there isn't a Prospero to make everything fine...and...the quality of mercy is strained." In December, Camillo Junior High is awash in "signs of the season." Mrs. Baker, however, does not share the holiday spirit, but Holling is too absorbed with his problems with the Shakespeare Holiday Extravaganza to wonder why. As always, Holling seeks help from his family, but to no avail; his mother comments insipidly that his embarrassing costume is cute, his father tells him to wear it to please Mr. Goldman, who might one day need an architect, and his sister warns him that if news of his role gets to the high school, no one better find out they are related. The only thing that prevents December from being a total disaster is Mrs. Baker's announcement that Mickey Mantle will be signing autographs at the Baker Sporting Emporium. Unfortunately, Mrs. Baker also tells the class about Holling and the Shakespeare Extravaganza, and encourages the students to attend both events. Holling's classmates are intensely curious about his role as Ariel, whom he euphemistically describes as "a warrior." Mr. Goldman tells Mrs. Baker that Holling needs "some practice on interpretation", and she practices with him, playing the part of Prospero. Mrs. Baker is a terrific reader, and when she and Holling rehearse the part where Prospero releases Ariel from bondage, Holling is inspired, realizing what it means to be free "to create his own happy ending." On the night of the performance, Mrs. Baker, Mrs. Bigio, Danny Hupfer and his parents, Meryl Lee, and Mai Thi are in the audience to support Holling, unlike his own parents, who do not want to miss the Bing Crosby Christmas Special on television. Holling executes his part with such passion that his classmates are moved to tears, and do not even notice what he is wearing. When the show is over, Holling, finding the dressing room locked, rushes outside, still in costume, where his father is supposed to be waiting to take him to Baker's Sporting Emporium to see Mickey Mantle. Typically, his father is not there, and Holling, frantic, flags down a bus and begs the driver to take him to the Emporium. The driver takes pity on him and complies, getting him to the Emporium just in time, but when Holling approaches Mickey Mantle for an autograph, the famous player looks derisively at his costume and snaps rudely, "I don't sign baseballs for kids in yellow tights." Danny Hupfer witnesses this snub, and loyally returns his own autographed baseball to Mickey Mantle, saying, "I guess I don't need this after all." Holling and Danny leave together in silence, smarting because "when gods die, they die hard." During the days remaining until holiday break, Mrs. Bigio is especially cantankerous; her cafeteria cooking is unappetizing at best, and her comments to the students are impatient and unkind. Holling, remembering Mrs. Bigio's sadness when she received the news of her husband's death, does not complain, but he is bewildered at the sheer desolation he witnesses when Mrs. Bigio bitterly tells Mai Thi that she "shouldn't even be here...a queen in a refugee home while American boys are sitting in swamps on Christmas Day." After school on the last day before break, Mrs. Baker gives Holling, Danny Hupfer, and Doug Swieteck each a new baseball and mitt, and sends them to the gym, where, to their delight, they meet Joe Pepitone and Horace Clark in their Yankee uniforms, and receive tickets to Opening Day at the Stadium. Mrs. Baker's family knows what happened with Mickey Mantle, and wants to make it up to the boys. The next day, President Johnson declares a Christmas ceasefire in Vietnam, and the holiday season begins in earnest.
Tobruk, a small town on the Libyan coast, was central to much of the fighting that took place in the Western Desert during the Second World War. It had originally been developed by the Italians during their colonisation of eastern Libya during the early decades of the 20th century. With a sheltered deep water harbour it became a key naval outpost. It was fortified during the 1930s with both coastal defence batteries and a 50 kilometre-long perimeter of reinforced concrete platoon posts, and other supporting infrastructure such as gun positions, headquarters bunkers, underground supply dumps, and observation towers. When British and Commonwealth forces advanced out of Egypt and into Libya in January 1941, Tobruk was their second objective. The Italian defence perimeter was attacked by the 6th Australian Division on the morning of 22 January and the town fell the next morning. The operation resulted in approximately 27,000 Italian prisoners and the capture of over 200 artillery pieces, but cost 49 Australian lives. The 6th Division's advance pressed on beyond Tobruk and eventually they were withdrawn from Libya to be deployed to Greece.The 9th Australian Division was moved in to Libya in February 1941 to garrison the territory captured by the 6th. By this time, however, German troops had arrived in Libya to reinforce their Italian allies and they launched an offensive that the British Commonwealth forces were ill-disposed to hold back. A retreat towards Egypt commenced. The 9th Division was ordered to fall back upon Tobruk, hold it in order deny its port facilities to the Germans, and delay their advance so as to provide time for defences on the Egyptian frontier to be prepared. Tobruk and the 9th Division were subsequently encircled, beginning what became known as "the siege of Tobruk". Reinforced by the 18th Brigade of the 7th Australian Division and other British and Commonwealth troops, and resupplied by the sea, the 9th Division held Tobruk from April to September 1941. During this period it repelled two major German attacks. In September and October the 9th Division, its condition steadily declining, was relieved by the British 70th Division, which continued to defend Tobruk until the siege was finally lifted by Operation Crusader in December. The defence of Tobruk resulted in 749 Australian deaths, and another 604 became prisoners of war. Tobruk was the scene of further heavy fighting in June 1942 when the fortunes of war again saw a British Commonwealth force seeking to deny the port to the enemy. The Axis forces, however, were in no mood for another siege and launched a massive attack to capture it on 20 June. It remained in their hands until their final retreat from Libya in November 1942.John Hurst Edmondson (1914-1941), soldier, was born on 8 October 1914 at Wagga Wagga, New South Wales, only child of native-born parents Joseph William Edmondson, farmer, and his wife Maude Elizabeth, née Hurst. The family moved to a farm near Liverpool when Jack was a child. Educated at Hurlstone Agricultural High School, he worked with his father and became a champion rifle-shooter. He was a council-member of the Liverpool Agricultural Society and acted as a steward at its shows. Having served (from March 1939) in the 4th Battalion, Militia, he enlisted in the Australian Imperial Force on 20 May 1940 and was posted to the 2nd/17th Battalion. Later that month he was promoted acting corporal (substantive in November). Well built and about 5 ft 9 ins (175 cm) tall, Edmondson settled easily into army life and was known as a quiet but efficient soldier. His battalion embarked for the Middle East in October and trained in Palestine. In March 1941 the 2nd/17th moved with other components of the 9th Division to Libya and reached Marsa Brega before an Axis counter-attack forced them to retreat to Tobruk. The siege of the fortress began on 11 April. Two days later the Germans probed the perimeter, targeting a section of the line west of the El Adem Road near Post R33. This strong-point was garrisoned by the 2nd/17th's No.16 Platoon in which Edmondson was a section leader. The enemy intended to clear the post as a bridgehead for an armoured assault on Tobruk.Under cover of darkness thirty Germans infiltrated the barbed wire defences, bringing machine-guns, mortars and two light field-guns. Lieutenant Austin Mackell, commanding No.16 Platoon, led Edmondson's five-man section in an attempt to repel the intruders. Armed with rifles, fixed bayonets and grenades, the party of seven tried to outflank the Germans, but were spotted by the enemy who turned their machine-guns on them. Unknown to his mates, Edmondson was severely wounded in the neck and stomach. Covering fire from R33 ceased at the pre-arranged time of 11.45 p.m. and Mackell ordered his men to charge. Despite his wounds, Edmondson accounted for several enemy soldiers and saved Mackell's life. When the remaining Germans fled, the Australians returned to their lines. Although Edmondson was treated for his wounds, he died before dawn on 14 April 1941. The Germans' armoured attack that morning was thwarted, partly due to the earlier disruption of their plans. Edmondson was buried in Tobruk war cemetery. He had not married. His Victoria Cross, gazetted on 4 July, was the first awarded to a member of Australia's armed forces in World War II. In April 1960 Mrs Edmondson gave her son's medals to the Australian War Memorial, Canberra, where they are displayed alongside his portrait (1958) by Joshua Smith. At Liverpool a public clock commemorates Edmondson, as do the clubrooms used by the sub-branch of the Returned Services League of Australia.Perhaps my nerves will be more under control when I am by myself. There were no entries in the diary until Friday April 18 when she wrote: Fighting terrific in Greece and North Africa…. I dread the casualty list also the heaviest air raid over London to date. Account …. of heavy fighting and much use of bayonet at Tobruk. Also gives an account of a charge in which a Lieutenant and a Corporal took prominent parts on Easter Sunday night. Of course, no names. When I read it …. I was sure the Corporal was Jack…. It said no casualties but …. I know … that all is not well with Jack. ….. (and) Stuffy ….has not come home yet. On Wednesday April 23 she received a letter from Jack dated March 30 and for the first time he said the conditions were bad. The food short, water one bottle for 48 hours. It worried me terribly so I posted a parcel (of) milk tablets, chocolate milk, biscuits (and) cigarettes.Tuesday April 15 I was feeling afraid of something while I was working and packing the cake (and) had a couple of brandys to (keep going).April 26 Received the following telegram in the mail, the bus man brought it in. “It is with deep regret that I have to inform you that Corporal John Hurst Edmondson was killed in action on the 14th April and desire to convey the profound sympathy of the Ministry for the Army and the Military Board.”Her final entry
Dès le début de vos recherches, vous allez collecter, produire et exploiter des données. La gestion des données (Research Data Management - RDM) fait partie du processus de recherche. Elle concerne l'ensemble des opérations de collecte, description, stockage, traitement, analyse, archivage et mise en accès des données. (extrait de : Passeport pour la Science Ouverte. Guide pratique pour les doctorants ) "La science ouverte est la diffusion sans entrave des publications et des données de la recherche. Elle s’appuie sur l’opportunité que représente la mutation numérique pour développer l’accès ouvert aux publications et – autant que possible – aux données de la recherche. "Les données de la recherche sont la matière première de la connaissance. Les partager, c'est ouvrir de nouvelles perspectives scientifiques" Source : Plan national pour la Science ouverte - Ministère ESR - Juillet 2018 Source image : https://bibliotheques.univ-tlse3.fr/file/composantes-science-ouverte Cette page est une introduction à la gestion des données de recherche. Elle présente quelques concepts et étapes clés pour vous engager dans cette démarche. Consultez les liens pour approfondir vos connaissances. • What are data ? Définition des données de recherche de l’OCDE (2007) « Enregistrements factuels (chiffres, textes, images, sons) utilisés comme source principale pour la recherche scientifique et généralement reconnus par la communauté scientifique comme nécessaires pour valider les résultats de la recherche. Un ensemble de données de recherche constitue une représentation systématique et partielle du sujet faisant l’objet de la recherche ». Exemples • les images d’une ville préhistorique deviennent des données pour un chercheur qui étudie l’histoire de cette ville; • les « données » d’un linguiste peuvent être des écrits ou des discours, des enregistrements de locuteurs ; • les « données » d’un médiéviste sont des sources archivistiques, archéologiques, épigraphiques, iconographiques, littéraires ; • les « données » d’un géologue rassemblent des coupes et observations de terrain consignées sur un carnet, des résultats de carottage, des analyses d’échantillons, des données sismographiques… • • Pourquoi partager ses données ? "La science ouverte vise à construire un écosystème dans lequel la science est plus cumulative, plus fortement étayée par des données, plus transparente, plus rapide et d’accès plus universel.La science ouverte favorise également les avancées scientifiques, particulièrement les avancées imprévues, ainsi que l’innovation, les progrès économiques et sociaux, en France, dans les pays développés et dans les pays en développement. Enfin, la science ouverte constitue un levier pour l’intégrité scientifique et favorise la confiance des citoyens dans la science. Elle constitue un progrès scientifique et un progrès de société." Source : Plan national pour la Science Ouverte (2018) Les enjeux de l'Open Data • enjeux patrimoniaux o preuve et mémoire (éviter les pertes de données) • enjeux économiques o valeur économique de la donnée o réutilisation gratuite ou payante des données, exploitation des résultats de recherches antérieures (éviter de refaire ce qui a déjà été validé), o accélération de l'innovation et le retour sur investissement dans la R&D • enjeux scientifiques o de "hypothesis-driven" à "data-driven" o plus de visibilité pour le scientifique • enjeux sociétaux o participation des citoyens et de la société civile : "Citizen science" o confiance en la recherche Pour aller plus loin • Site Doranum : https://doranum.fr/enjeux-benefices/fiche-synthetique/ • Adopter de bonnes pratiques tout au long du cycle de vie des données De bonnes pratiques de gestion à toutes les étapes du cycle de vie de la donnée sont un préalable indispensable à l’ouverture des données et à leur réutilisation. • Rechercher des données Pour identifier des jeux de données (datasets) pertinents pour votre thèse, des outils de recherche sont disponibles. Suivez ces liens pour les découvrir : • Site Doranum : https://doranum.fr/acces-visualisation/rechercher-donnees/ • Site DataCC - Vos besoins, trouver des données : https://www.datacc.org/vos-besoins/trouver-des-donnees/ • Fiche CoopIST : Trouver des jeux de données via des bases pluridisciplinaires et des moteurs de recherche Pensez-aussi à consulter l'entrepôt institutionnel Data INRAE Page de présentation du portail • Choisir les bons formats et bien organiser vos données Choisir des formats de fichier : https://www6.inrae.fr/datapartage/Gerer/Choisir-des-formats-de-fichier Nommer et organiser vos fichiers de données : https://www6.inrae.fr/datapartage/Gerer/Nommer-et-organiser-ses-fichiers-de-donnees Pour aller plus loin • Jaouen, G.- Gérer ses données. Pourquoi, Comment ? Séminaire - Guadeloupe, du 25 au 27 Novembre 2019 – CRAG INRA • Bien décrire et documenter ses données La description d’un jeu de données se fait à l’aide de métadonnées (*) qui doivent apporter suffisamment d'éléments (sur la collecte des données, les unités de mesure employées...) pour chercher et trouver le jeu de données, juger de sa qualité/fiabilité, et pouvoir le comprendre ou le réutiliser dans un autre contexte. (*) Définition des métadonnées : Ensemble d’informations structurées qui décrit, explicite, localise une ressource informationnelle, dans le but d’en faciliter la recherche, l’usage, et la gestion. Source : NISO. Understanding Metadata. 2004. Quelques liens utiles : • Site Doranum : https://doranum.fr/metadonnees-standards-formats/ • DataCC : https://www.datacc.org/vos-besoins/documenter-ses-donnees/metadonnees/ • Site DataPartage INRAE : https://www6.inrae.fr/datapartage/Gerer/Documenter-les-donnees En complément des métadonnées, la rédaction d'un fichier READ ME.txt est également recommandée. • Stocker, sécuriser, préserver ses données Bien différencier les notions de stockage et d'archivage. Anticiper pour déterminer les données à éliminer et celles qui doivent être préservées à long terme. • Dans l'environnement INRAE : https://www6.inrae.fr/datapartage/Gerer/Stocker-les-donnees • Site Doranum : https://doranum.fr/stockage-archivage/ • Site DataCC : https://www.datacc.org/vos-besoins/conserver-ses-donnees/ • Partager, ne pas partager ses données ? Dans le cadre de la Science Ouverte, il y a de plus en plus d'incitations voire d'exigences pour rendre accessibles les données, en particulier les données liées aux publications : • de l'édition scientifique : de plus en plus de revues adoptent une "data policy" (à consulter dans les instructions aux auteurs) et exigent des auteurs qu'ils fournissent les données associées aux publications, • des organismes de financement (ANR, Commission Européenne ...), • des politiques nationale (Plan national pour la Science ouverte - Ministère ESR - Juillet 2018) et institutionnelle. Mais attention, toutes les données ne sont pas partageables : assurez-vous que vos données sont bien diffusables au regard du droit et des conditions d'exercice de votre thèse et de son mode de financement (se reporter à votre contrat de thèse). Les données produites dans les organismes de recherche publics sont communicables à tous si elles n'entrent pas dans le cadre d'exceptions légales (sécurité défense, sécurité des populations, patrimoine scientifique et technique, données personnelles, données liées au secret, statistique, etc.) Liens utiles : • sur le site Data Partage, la page Partager-Publier ou la page : "Données de la recherche : qui a les droits, qui doit partager ?" • le site INRAE dédié à la protection des données personnelles et l'application du RGPD (Règlement général sur la protection des données) : https://intranet.inrae.fr/cil-dpo • Valoriser ses données Voici les principales voies de diffusion • Partager ses données en les déposant dans un entrepôt Choisir un entrepôt Déposer dans Data INRAE Partager ses données comme matériel supplémentaire d'un article (à la demande de l'éditeur) Publier un Data Paper (article de données) : la meilleure voie en terme de visibilité des données, et pour faciliter leur réutilisation. Pour aller plus loin • Site Doranum o Dépôts et entrepôts. Comment et où déposer mes données ? o Data papers et Data journals. Comment publier mes données comme un article scientifique ? • Site DataCC o Valoriser ses données • Site CoopIST o Déposer des données de recherche dans un entrepôt o Rédiger et publier un data paper dans une revue scientifique A télécharger : Synthèse du processus de rédaction d'un article avec des données associées • Pourquoi ne pas rédiger un plan de gestion de données (PGD) pour votre thèse ? La thèse peut être assimilée à un projet et certaines universités au Royaume Uni, aux Pays-Bas et plus récemment en France préconisent la rédaction d'un plan de gestion associé à la thèse. Le PGD (ou DMP = Data Management Plan) est un outil de planification qui peut vous aider à anticiper et bien gérer toutes les étapes du cycle de vie de vos données, à limiter les risques de perte ou corruption de données, à adopter de bonnes pratiques de gestion, pour in fine produire des données respectueuses des principes FAIR, adoptés aujourd'hui par l'ensemble des acteurs de la recherche. Il est désormais exigé par la plupart des financeurs de la recherche (Commission Européenne et ANR ...) dans le cadre de projets financés. Rédiger un PGD pour votre thèse, peut être un bon exercice pour vous préparer à la future rédaction de réponses à des appels d'offre. Comment faire en pratique ? • Site DataPartage : Pourquoi et comment rédiger un plan de gestion de données ? • Site Doranum : https://doranum.fr/plan-gestion-donnees-dmp/, La minute vidéo PGD • Site DataCC : https://www.datacc.org/bonnes-pratiques/adopter-un-plan-de-gestion-des-donnees/ • Suivre une classe virtuelle INRAE : Open Class "Rédaction d'un PGD" • Produire des données FAIR ! Favoriser la production de données FAIR (Findable - Accessible - Interoperable - Reusable) est aujourd'hui un objectif soutenu par l'ensemble des acteurs de la recherche. Source : https://open-science-training-handbook.gitbook.io/book/ Si vous suivez les conseils et recommandations de cette page, vous avez toutes les chances d'avoir produit des données de qualité. Si vous préférez une version illustrée : "Pensez FAIR" - https://datapartage.inrae.fr/Gerer/Cycle-de-la-donnee Affiche cycle de vie des données réalisée dans le cadre des Missions QualiNous & RGPD, INRAE-ACT Vous pouvez tester le niveau de "Fairification" de vos données grâce à ces outils : ARDC : https://ardc.edu.au/resources/working-with-data/fair-data/fair-self-assessment-tool • D'autres ressources pour se former ou s'autoformer En interne INRAE • Formation à la science ouverte OSCAR - Module "Gestion et partage des données" • Le site "Gestion et partage des données" • Des classes virtuelles d'environ 2h (Open Class) sont régulièrement proposées sur : o la rédaction des plans de gestion de données, o le dépôt et la description d'un jeu de données dans Data INRAE, o la rédaction et la publication de data papers, Sites externes • Le site DORANUM (Données de la Recherche : Apprentissage NUMérique à la gestion et au partage) propose un dispositif de formation à distance intégrant de nombreuses ressources d’auto-formation déclinées sur différents supports (textes, infographies, vidéos) et sur 9 thématiques. o Parcours interactif sur la gestion des données de la recherche (2020) o • Le site DataCC. Accompagnement à la gestion des données de recherche en physique et en chimie : https://www.datacc.org/ o Data Stories : https://www.datacc.org/reseau-datacc/data-stories/ o • Le dossier "Open Access & Open Data" réalisé par l'Ecole des Ponts - ParisTech • • The Open Science Training Handbook : https://www.ouvrirlascience.fr/the-open-science-training-handbook/
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 gover