Category Archives: Physiology

Physiology

UCLA-led team of scientists discovers why we need sleep | UCLA – UCLA Newsroom

Prolonged sleep deprivation can lead to severe health problems in humans and other animals. But why is sleep so vital to our health? A UCLA-led team of scientists has made a major advance in answeringthis question and has shown for the first time that a dramatic change in the purpose of sleep occurs at the age of about 2-and-a-half.

Before that age, the brain grows very rapidly. During REM sleep, when vivid dreams occur, the young brain is busy building and strengthening synapses the structures that connect neurons to one another and allow them to communicate.

Dont wake babies up during REM sleep important work is being done in their brains as they sleep, said senior study author Gina Poe, a UCLA professor of integrative biology and physiology who has conducted sleep research for more than 30 years.

After 2-and-a-half years, however, sleeps primary purpose switches from brain building to brain maintenance and repair, a role it maintains for the rest of our lives, the scientists report Sept. 18 in the journal Science Advances. This transition, the researchers say, corresponds to changes in brain development.

All animals naturally experience a certain amount of neurological damage during waking hours, and the resulting debris, including damaged genes and proteins within neurons, can build up and cause brain disease. Sleep helps repair this damage and clear the debris essentially decluttering the brain and taking out the trash that can lead to serious illness.

Nearly all of this brain repair occurs during sleep, according to senior author Van Savage, a UCLA professor of ecology and evolutionary biology and of computational medicine, and his colleagues.

I was shocked how huge a change this is over a short period of time, and that this switch occurs when were so young, Savage said. Its a transition that is analogous to when water freezes to ice.

The research team, which included scientists with expertise in neuroscience, biology, statisticsand physics, conductedthe most comprehensive statistical analysis of sleep to date, using data from more than 60 sleep studies involving humans and other mammals. They examined data on sleep throughout development including total sleep time, REM sleep time, brain size and body size and built and tested a mathematical model to explain how sleep changes with brain and body size.

The data were remarkably consistent: All species experienced a dramatic decline in REM sleep when they reached the human developmental equivalent of about 2-and-half years of age. The fraction of time spent in REM sleep before and after that point was roughly the same, whether the researchers studied rabbits, rats, pigs or humans.

REM sleep decreases with the growth in brain size throughout development, the scientists found. While newborns spend about 50% of their sleep time in REM sleep, that falls to about 25% by the age of 10 and continues to decrease with age. Adults older than 50 spend approximately 15% of their time asleep in REM. The significant dropoff in REM sleep at about 2-and-a-half happens just as the major change in the function of sleep occurs, Poe said.

Sleep is as important as food, Poe said. And its miraculous how well sleep matches the needs of our nervous system. From jellyfish to birds to whales, everyone sleeps. While we sleep, our brains are not resting.

A chronic lack of sleep likely contributes to long-term health problems such as dementia and other cognitive disorders, diabetes, and obesity, to name a few, Poe said. When you start to feel tired, she said, dont fight it go to bed.

I fought sleep and pulled all-nighters when I was in college, and now think that was a mistake, Savage said. I would have been better off with a good nights sleep. Now when I feel tired, I dont have any guilt about sleeping.

For most adults, a regular seven-and-a-half hours of sleep a night is normal and time lying awake doesnt count, Poe says. While children need more sleep, babies need much more, roughly twice as much as adults. The large percentage of REM sleep in babies is in stark contrast to the amount of REM sleep observed in adult mammals across an enormous range of brain sizes and body sizes. Adult humans have five REM cycles during a full night of sleep and can have a few dreams in each cycle.

A good nights sleep is excellent medicine, Poe says. And its free.

Co-authors of the study are Junyu Cao, who conducted research in Savages laboratory and is now an assistant professor at the University of Texas at Austin; Alexander Herman, an assistant professor of psychiatry at the University of Minnesota, Twin Cities; and Geoffrey West, a physicist who is the Shannan Distinguished Professor at the Santa Fe Institute.

Funding sources included the National Science Foundation and the Eugene and Clare Thaw Charitable Trust.

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UCLA-led team of scientists discovers why we need sleep | UCLA - UCLA Newsroom

Physiology

Linking physiology to ecological function: environmental conditions affect performance and size of the intertidal kelp hedophyllum sessile…

This article was originally published here

J Phycol. 2020 Sep 15. doi: 10.1111/jpy.13071. Online ahead of print.

ABSTRACT

For autogenic ecosystem engineers, body size is an aspect of individual performance that has direct connections to community structure; yet the complex morphology of these species can make it difficult to draw clear connections between the environment and performance. We combined laboratory experiments and field surveys to test the hypothesis that individual body size was determined by disparate localized physiological responses to environmental conditions across the complex thallus of the intertidal kelp Hedophyllum sessile, a canopy-forming physical ecosystem engineer. We documented substantial (> 40%) declines in whole-thallus photosynthetic potential (as Maximum Quantum Yield, MQY) as a consequence of emersion, which were related to greater than 10-fold increases in intra-thallus MQY variability (as Coefficient of Variation). In laboratory experiments, desiccation and high light levels during emersion led to lasting impairment of photosynthetic potential and an immediate > 25% reduction in area due to tissue contraction which was followed by complete loss of structural integrity after three days of submersion. Tissue exposed to desiccation and high light during emersion had higher nitrogen concentrations and lower phlorotannin concentrations than tissue in control treatments (on average 1.36 and 0.1x controls, respectively), suggesting that conditions during emersion have the potential to affect food quality for consumers. Our data indicate that the complex thallus morphology of H. sessile may be critical to this kelps ability to persist in the intertidal zone despite the physiological challenges of emersion, and encourage a more nuanced view of the concept of sub-lethal stress on the scale of the whole individual.

PMID:32931614 | DOI:10.1111/jpy.13071

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Linking physiology to ecological function: environmental conditions affect performance and size of the intertidal kelp hedophyllum sessile...

Physiology

Ig Nobel Prizes reward research on helium-huffing alligators and knives made of feces – Science Magazine

A study that placed Chinese alligators (Alligator sinensis) in helium chambers revealed mechanisms of their vocalizations and earned the authors a 2020 Ig Nobel Prize.

By Rasha AridiSep. 18, 2020 , 10:25 AM

The Ig Nobel Prizes, an annual event celebrating quirky, comical discoveries, carried on despite the pandemic in a virtual ceremony riddled with bugsand bug jokes. The Annals of Improbable Research, the science humor magazine that hosts the event, selected bugs as the theme for the 30th annual event, although the winning studies spanned an array of icky, wondrous, and unconventional research. The ceremony took place entirely online for the first time with a series of prerecorded speeches, musical numbers, and lightning-speed lectures.

This years prize in entomology went to an investigation of why so many insect researchers are themselves fearful of spiders. The survey of arachnophobic entomologists, published in 2013 in American Entomologist, explored why people who devoted their careers to critters such as cockroaches and maggots still found spiders unnerving. Among spidersmost disliked traits were their fast, unpredictable movements and their many legs.

The acoustics prize went to researchers who recreated in reptiles the party trick of inhaling helium from balloons. To study crocodilian vocalizations, the team placed alligators in an airtight, helium-filled chamber and found that the high-energy frequency bands of their bellows got even higher. The results, published in the Journal of Experimental Biology in 2015, are the first evidence that nonavian reptiles produce sound from vibrations in the vocal tract, known as formants.

A duo of researchers earned the prize in psychology for discovering thatdistinctive eyebrows are perceived as a cue of grandiose narcissism.By showing people photos of faces with different areas concealed, the researchers found eyebrows were an especially important nonverbal cue for gauging narcissistic personality traits, they reported in theJournal of Personalityin 2018. Study participants judged eyebrow distinctivenessthe eyebrows thickness and densityto be the most telling sign of narcissism.

Other winning research included a study revealingnew diagnostic criteria for a psychiatric disorder called misophonia, which makes people averse to certain breathing and eating sounds; evidence thatromantic partners in countries with higher levels of economic inequality kiss more often;and the finding thatknives cannot be crafted from frozen human feces, despite a previous account of an Inuit man doing so.

Winners received a $10 trillion Zimbabwean bill, equivalent to a few U.S. cents, and were emailed a six-page PDF to print and assemble into a cube-shaped trophy. The awards were presented by past Nobel laureatesEric Maskin (Economics, 2007),Frances Arnold (Chemistry, 2018),Richard Roberts (Physiology or Medicine, 1993),Martin Chalfie (Chemistry, 2008),Jerome Friedman (Physics, 1990), andAndre Geim (Physics, 2010).

The ceremony also featured the debut performance of Dream, Little Cockroach,a miniopera performed by the Nobel laureates alongside professional singers and other musically inclined scientists. In past years, the live audience has folded pages from the program into airplanes to toss onto the stage; this year, viewers were encouraged to make and toss their own planes at home. Host Marc Abrahams closed the ceremony with a classic Ig Nobel line: If you didnt win an Ig Nobel Prize tonightand especially if you didbetter luck next year.

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Ig Nobel Prizes reward research on helium-huffing alligators and knives made of feces - Science Magazine

Physiology

COVID-19 the tip of the iceberg of vulnerability for Hispanics – Abilene Reporter-News

Jacqueline Angel and Juan Fernando Torres-Gil Published 5:15 a.m. CT Sept. 20, 2020

When it rains, it pours.

This well-known phrase summarizes the experiences of the Hispanic population during our current coronavirus pandemic. There is nothing inherent about Hispanic physiology, but accumulated lifelong disadvantages increase exposure to the disease. In fact, it is well known that Hispanics are more likely than non-Hispanic whites to experience health conditions tied to poverty, low levels of educational attainmentand inadequate retirement income.

In other words, Hispanics in our country are getting a one-two punch. But it doesnt have to be this way.

Solutions are not simple though. COVID-19 is the tip of the iceberg of vulnerability for Hispanics.

A vaccination is a solution to one small part of the package of health vulnerabilities, but that will not address the underlying sources of vulnerability of a population that faces disadvantages at multiple levels. What it will take is a social movement to make this issue and many others facing Hispanic families a national priority.

Juan Fernando Torres-Gil, UCLA(Photo: Provided photo)

One of the consequences of COVID-19 and a key issue facing states nationwide are significant economic and educational disparities as the Hispanic population continues to grow and evolve.

Research clearly demonstrates that societal factors, not just clinical care, are key for Hispanics to achieve healthy aging. Those factors that place Hispanics at higher risk of diabetes, obesity and hypertension are linked to social factors and experiences that increase income and wealth inequality.

For older Hispanics and especially Mexican Americans, this leads to increased levels of dependency on their family members for care and support.

What we have also learned is that better education has a protective health effect by giving the brain more capacity, creating a cognitive reserve to postpone dementia. Understanding how the timing of exposure to early life risk factors, such as interrupted education, influences brain health may illuminate mechanisms driving adult Hispanic health inequalities and identify possible points for effective interventions.

Recognizing cognitive aging as developing across the life course also has implications for public health behavioral change programs.

COVID-19 has accentuated the disparities in access for Hispanics.

Although education levels have improved over the years, the pandemic has shifted this responsibility to families. A lack of access to technology and achievement gaps contribute to Hispanic students struggling to engage in online learning.

In fact, according to a Los Angeles Times survey, 33 percent of middle school students and 27 percent of high school lacked computers and internet access. Such homework gaps could be devastating to generations of students to come and for our labor force.

Ultimately, what can help Hispanics and their families are the very solutions that can benefit all Americans and their families: a robust social safety net that addresses the social determinants of health.

First, and foremost, what we need is a commitment from Congress to invest in the nations health. We need to create a universal system of health care coverage, closing the coverage gap for almost 28 million uninsured Americans, 10.6 million Hispanic working-age adults, and 4.1 million uninsured children, 1.6 million of whom are of Hispanic origin.

Jacqueline Angel, University of Texas at Austin(Photo: Provided photo)

We need legislation aimed to reduce disparities in housing, especially since home ownership is the major source of wealth for most low- and middle-income minority and immigrant families. Federal funding could expand down-payment assistance for mortgages, tax credits, and vouchers for rental assistance to foster homebuying and financial security.

Such housing policies also would strengthen low-opportunity neighborhoods and school districts. State and local governments can create new and innovative community assets like affordable adult day and child care services that are critical resources to improve intergenerational relations, health and well-being, as well as the academic success of generations to come.

Undeniably, once the pandemic passes, the economy will need the essential workers who were most disadvantaged low-income African Americans and Hispanics and with the nation slated to be a majority-minority society, we must assure all Americans that regardless of the vagaries of pandemics, unemployment, poverty and natural disasters, they will not face the dilemmas that we have seen with older Hispanics and their families.

Jacqueline L. Angel is a professor of sociology and public affairs at The University of Texas at Austin. Juan Fernando M. Torres-Gil is a professor and director of the Center for Policy Research on Aging at the University of California, Los Angeles.

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COVID-19 the tip of the iceberg of vulnerability for Hispanics - Abilene Reporter-News

Physiology

HEALTH AND FITNESS: Sports physiology in the Tour de France – Charleston Post Courier

The 2020 Tour de France, postponed from the traditional July start due to the COVID-19 pandemic, is underway. This year the race covers over 2,100 miles in 21 days of racing, comprised of team and individual time trials as well as stages through the cities, countryside and mountains of France. The Tour de France is especially interesting to me because it provides an excellent opportunity for a short lesson in sports physiology.

All the riders in the Tour are exceptionally fit since their bodies have adapted to years of dedicated, intense training. Endurance sports like cycling are dependent on the delivery of oxygenated blood to the muscle to produce ATP, the energy needed to sustain exercise.

The riders have large, strong hearts, allowing them to pump more blood to the muscle. Within the muscle there is an increase in the number of capillaries, the small blood vessels that deliver blood to the muscle, and mitochondria, the part of the cell that produces most of the ATP. Together, these adaptations allow the muscle to produce more ATP without fatigue, allowing the athlete to exercise at a higher intensity for a longer time.

But training isnt the only reason these athletes can sustain such intense exercise for so long. Proper nutrition, especially what the athletes eat and drink before, during and after each stage, also plays an important role. Intense endurance exercise like cycling relies on carbohydrates in particular, muscle glycogen as a fuel. Muscle glycogen is a storage form of glucose, sugar that the muscle converts into energy. During prolonged exercise that lasts several hours, muscle glycogen levels can be severely depleted.

Eating carbohydrates before exercise can boost muscle glycogen levels, so cyclists eat carbohydrate-rich foods before each day of racing. They also consume carbohydrates in the form of sports drinks (think Gatorade) and energy bars prior to starting. In fact, they start replenishing their muscle glycogen immediately after finishing the previous days ride. This usually begins with a recovery beverage, which may contain some protein for more rapid muscle glycogen synthesis, and extends through carbohydrate-rich meals and snacks that afternoon and evening.

During exercise it is crucial to maintain adequate blood glucose levels, which tend to drop since the muscle is using so much as a fuel. Failure to replenish blood glucose results in what cyclists call hitting the wall or bonking, which is like your car running out of gas. To prevent this, glucose must be replenished, typically with sports drinks, energy bars or a sugary mixture called goo.

Prolonged, intense exercise, especially in the heat, results in a high sweat rate which can lead to dehydration. Sweat loss of several liters per hour is not uncommon during cycling, so fluid intake is essential. This means that cyclists spend a lot of time drinking water while they ride. Sports drinks are also commonly used since they contain carbohydrates and electrolytes in addition to water.

Endurance events like cycling, especially multi-stage events like the Tour de France, highlight important concepts of sports physiology. Even though you may never compete at that level, understanding how training can improve your endurance is relevant if you cycle or run, walk or swim for exercise. Knowing how proper nutrition before, during and after exercise can improve performance can help you make better decision about what to eat. Hopefully it also gives you a greater appreciation for the sports science that goes into a performance like the Tour de France.

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HEALTH AND FITNESS: Sports physiology in the Tour de France - Charleston Post Courier

Physiology

The anatomy and physiology of vapes: Mods – FlipScience

This degree of adaptability is evident in the staggering diversity of mod vape hardware. There are dozensif not much, much moreof choices for a rig body and atomizer. Different brands come out with different lines, each with many different models and builds.

There are, for example, atomizers that come with prebuilt heating coils that vapers just need to replace once burnt out. Others yield even more control to the user, allowing them to assemble their own coil-and-wick setup.

In turn, this opens up layers upon layers of customization possibilities. Some coils are more resistive, have more turns, and are longer than others; some look like typical coils, while other come in mesh form. Wicks come in different materials. Some atomizers come with a tank, while others dont. Mouthpiece barrels have different allowances for airflow.

The one indispensable thing that all box modsand all vapes in generalshare is the need for e-juice. What good is a decked-out rig for if theres nothing to aerosolize?

But juices themselves are very diverse. Fundamentally, e-juices will contain some ratio of organic solvents that liquefy nicotine and carry it in the aerosols. Many different solvents can fill this role, but the most popular ones are propylene glycol and vegetable glycerin.

To add yet another layer to this variety, juices also come in many different flavors: tobacco; menthol; fruity, like mango and strawberry; and dessert, like cheesecake and cinnamon. Already,over 15,000 flavors had been documented as early as 2014, and the playing field was expanding by some 200 new flavors per month.

In a lot of ways, the market of mod vapes resembles the landscape of smartphones. The sheer number of options is daunting and overwhelming, but can also become intoxicating.

People have different needs, Jess says. For people who are just after high nicotine content, the small pods would be their best bet. The big mods and atomizers, usually those are for cloud chasers.

The dizzying variety of mod vapes shouldnt distract from the often-underplayed risks they come with, though.

Theyve been associated with explosions and poisoning, says Dr Riz Gonzalez, MD, Chairwoman of the Tobacco Control Advocacy Group of the Philippine Pediatric Society, referring to mod vapes.

Mods need regular maintenance and cleaning, particularly in its internal workings, she continues. Neglecting to do so might cause a short circuit and lead to an explosion. This may also be the case when the vape, particularly the battery, is exposed to moisture or extreme temperatures, or when improperly charged. (It is worth noting, though, that explosions have become increasingly rare, especially with the newer mods that have built-in safety features).

The coils themselves are cause for concern. During heating, they leach metallic nanoparticles into the juice, Dr Gonzalez said, and these are irritants. Several studies, indeed, have found considerable levels of metals such as aluminum, nickel, lead, copper, iron, tin, and zinc in the e-juice. And they dont just stay there. When the juice evaporates, it carries these tiny nanoparticles in the aerosols.

The microparticles float in the aerosols, and when you inhale, they go into the lungs, and lungs are only meant to inhale clean air, Dr Gonzalez explains. Anything beyond what is needed by the body, the body reacts to through inflammatory processes.

In the same way that the body tries to clot up a wound, it floods the lungs with platelets, fibrin, thrombin, and other coagulants in response to these metallic invaders. This blocks the airways. Its the same thing that happens with EVALI, she adds, referring to the e-cigarette-related lung injury epidemic that took the US by storm late last year.

This goes for e-juices, too. In fact, more particularly so. There continues to be a lot of debate about the safety of the solvents, particularly around propylene glycol and vegetable glycerin. Both have been designated by the US FDA as GRAS, or substances that are generally recognized as safe.

But Dr Gonzalez points out that these are GRAS for ingestion, not for inhalation. The cells that line the airway, after all, are different from the cells that line the stomach. It follows, too, that they respond to chemicals in different ways.

Several studies have shown, for example, that the aerosols from e-cigarettes mess with our respiratory tract even on a very basic, cellular level. Lab studies have shown that in response to these aerosols the cells that line the airway show signs of stress. Ultimately, such an exposure led to lower cell viability and an excess in the rate of cell death.

E-cigarette aerosols also assault the lungs. When exposed, in culture, to the aerosols, cells that line the tiny air sacs likewise show signs of stress and release indicators of cellular destruction. Aerosols might also make the lungs more susceptible to infection.

A 2016 study found that e-cigarette aerosols weaken the immune cells of the lungs. Mice who had inhaled these vapors showed altered inflammatory activity in their airways. To make things worse, the same type of exposure empowered Staphylococcus aureus, a common respiratory pathogen in humans. The bacteria grew more resistant to immune defenses, and became more potentsticking to the hosts cells better and entering them with greater ease.

The outbreak of EVALI late last year in the US demonstrates that what happens in the lab isnt just a test-tube artefact. Short for e-cigarette or vaping product use-associated lung injury, EVALI describes lung injuries and infections that were inexplicable except when seen in connection to the use of these devices.

Patients would present with unspecific symptoms: coughs, shortness of breath, and fevers. But in the most unfortunate cases, the disease would escalate and kill an otherwise healthy person.

Majority of cases were linked to vitamin E acetate, a common additive in juices that contained tetrahydrocannabinol, but a sizeable minority had no such connection. According to Dr Gonzalez, the culprit chemical (or chemicals) is still at large.

Though still such a very young phenomenon, there is already a substantial body of literature suggesting harms associated with vaping. It is true, however, that theres a shortage of conclusive, unassailable, clinical evidence that vaping does more harm than good. All there is, still, is smoke, not a smoking gun.

The same can be said, though, of safety. There likewise hasnt been irrefutable proof that these chemicals, and vaping in general, are completely devoid of serious health risks.

This is especially true in the face of all the flavorings. Many sweet flavors, like butter, caramel, and strawberry, owe their appeal to diacetyl, acetylpropionyl, and acetoin. Diacetyl is also GRAS for the stomach, but definitely not for the lungs. Used traditionally as the main butter flavoring in popcorn, diacetyl has since become notorious as the culprit behind bronchiolitis obliteransmore commonly known as popcorn lung.

Flavorings are also chiefly responsible for the aldehydes produced during vaping. Under heat, flavoring compounds break down into their aldehyde building blockslike formaldehyde, benzaldehyde, and acroleinin levels that exceed occupational safety thresholds.

Theres little doubt in her head that vapes will emerge more harmful than beneficial. But as of the moment, Dr Gonzalez concedes, theres no way for us know, with a comfortable degree of statistical certainty, how harmful it truly is. Its just still too early.

Maybe in a few years, she says, though even now, were starting to see some cases of COPD. Before, it [used to take] about 20 to 30 years. Vaping, in comparison, has been around 17 years, and only in the most recent handful years did it hit its stride. Its going to take time for all the chronic side effects to arise, and even more time to study and peer-review any future findings.

Unfortunately, this high bar of scientific rigor is more of a convenience than a requirement for marketing. In the face of these sparsely substantiated claims, all health advocates like Dr Gonzalez can do is call for caution and wait.

[Vapes] still do contain unidentified harmful chemicals and still-unidentified carcinogens because of the process of heating, she says. They say its for harm-reduction, but in the long run, its still really not safe.MF

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The anatomy and physiology of vapes: Mods - FlipScience

Physiology

The diagnosis of the infertile couple – Contemporary Obgyn

Introduction

Many couples choose to be childless; no one chooses to be infertile. In a classic 1956 study by Alan Guttmacher examining conception rates among 5,574 women attempting pregnancy, 85% conceived within 12 months.1

However, it has also become increasingly clear that time to conception is strongly influenced by age-related factors, including declining oocyte quantity and quality over time. Indeed, Guttmacher also reported a doubling of median conception time from age 24 to 44.1

Thus, while infertility is more the lack of a normal physiological outcome than a disease per se, a thorough workup for infertility is essential to identify underlying disease. In addition, lifestyle issues and environmental factors can adversely affect infertility.

Importantly, infertility may be a marker of non-reproductive disease and often portends serious health issues. This discussion will highlight how each of these factors affect normal physiology, their diagnosis, and the treatment designed to achieve the delivery of a healthy term baby.

The breathtaking physiology of reproduction may go astray in any facet and result in infertility. Evaluation for that aberration, followed by diagnosis-specific treatment, is perhaps the most cost-effective way to help a couple conceive. This is an opportune time to add antenatal screening to the basic diagnostic evaluation of the infertile couple (Table 1).

Tubal disease is a common cause of infertility, with reported rates between 25-35% of infertility diagnoses2 though these numbers can vary widely3 depending on the population being tested. Tubal obstruction is suspected in women with a history of sexually transmitted infection, cervical dysplasia, abdominal surgery or previous intra-abdominal infection (e.g., ruptured appendix).

While laparoscopy with chromotubation is often considered the gold standard for evaluation of tubal disease, hysterosalpingography (HSG), with a sensitivity and specificity of 65% and 83%, respectively4,5 is considered the first-line diagnostic tool. 6,7

Radiopaque dye is injected into the uterus and followed through the Fallopian tubes under fluoroscopy. A similar procedure utilizing ultrasound instead of fluoroscopy, sonohysterography (SHG), is less reliable in determining tubal patency although more accurate for uterine evaluation6 with a sensitivity and specificity of 76% and 67%.8

Treatment options for tubal infertility include tubal cannulation (for proximal tubal obstruction)9, surgery for tubal reanastomosis, or in vitro fertilization (IVF), which bypasses tubal blockage, with IVF being frequently employed due to success rates and comparable costs with surgery.

Endometriosis is a complex condition characterized by the presence of endometrial tissue in sites outside the uterine cavity. Endometriosis frequently presents with pain and affects 25-40% of women with infertility.10 Posited mechanisms for the relationship between endometriosis and infertility include distortion of pelvic anatomy, tubal obstruction, impaired oocyte quality, release and pickup, and altered endometrial receptivity, although a definite cause-effect relationship between any of these pathologies and endometriosis-related infertility is controversial.

While excisional surgery has been shown to improve spontaneous pregnancy rates in women with endometriosis11, surgery is not recommended for the routine evaluation of infertility in women without other symptoms of endometriosis.12

Endometrial polyps, intracavity leiomyomas, intrauterine synechiae and Mullerian anomalies with associated distortion of the endometrial cavity may be associated with infertility.

Superior to the HSG in detecting uterine anomalies, sonohysterography detects intrauterine polyps or leiomyomas with a sensitivity and specificity of 91% and 84%, respectively.13 Direct visualization via hysteroscopy may be used to confirm the diagnosis (Figure 1). Treatment to remove the distorting mass is surgical.

The cervix is the entry to the upper reproductive tract. Its alkaline mucus protects sperm from the acidity of the vagina and guides sperm into the upper reproductive tract.

Structural alterations of the cervix, either congenital or post-surgical (for example, after loop electrosurgical excision procedure (LEEP) or large cervical cone biopsy) can cause cervical stenosis and prevent sperm entry.14

Post-operative stenosis is diagnosed by the failure to pass a 1 mm probe into the uterine cavity. The post-coital test, performed after intercourse to assess the viability of sperm in mucus, has been used to evaluate cervical function; however, the limited predictive value of this test has relegated it to history (Table 2).

In the absence of mucus and in the presence of cervical stenosis, intrauterine insemination is a successful therapy, assuming all other factors are normal.

Failure to ovulate results from a variety of non-reproductive influences including thyroid disease, pituitary disease, elevated androgens from adrenal hyperplasia, obesity, and stress. Anovulation is diagnosed by a mid-luteal serum progesterone concentration <3 ng/ml, although mid-luteal serum progesterone levels are usually higher than 7 ng/mL,15 and should be suspected when cycles are irregular and occur more often than every 21 days and less often than every 36 days.

The most common cause of anovulation is a metabolic disease, polycystic ovarian syndrome (PCOS) in which multiple follicles exist in various stages of development and are simultaneously a result of and caused by an altered hormonal milieu including insulin resistance, elevated LH, and elevated androgens.16

Women who do not ovulate do not produce progesterone and thus are at risk for the consequences of unopposed estrogen:endometrial hyperplasia and cancer.

Similarly, women with PCOS may experience non-reproductive disorders, particularly, acne, hirsutism and hyperinsulinemia. The metabolic consequences of PCOS increase a womans risk of diabetes mellitus, hyperlipidemia, gestational hypertension and gestational diabetes.

Correcting thyroid deficiency, lowering elevated prolactin, blocking elevated adrenal androgen production often stimulates ovulation. Weight loss of 15% of body weight often prompts ovulation to resume.17

Infertility associated with anovulation is best treated with ovulation induction unless other factors such as diminished ovarian reserve and male factors are present.

Female fecundity (the ability to conceive and carry a pregnancy to term) declines with increasing age, decreasing more rapidly after age 35,18,19 reflecting, in part, the progressive loss of oocytes (the ovarian reserve) that occurs with age. Aging oocytes also accumulate meiotic defects and DNA damage, causing deterioration of gamete quality and increasing the risk of aneuploid embryos and miscarriage.20,21

Therefore, women over 35 who have failed to conceive for six months should be offered expedited evaluation and treatment; for women over 40, immediate evaluation is warranted.19

Ovarian reserve refers to the number of oocytes available for stimulation and ovulation. It can be evaluated using serum FSH and estradiol concentrations on days 3-5 of a menstrual cycle, serum anti-Mllerian hormone (AMH), and/or ultrasound imaging of the ovaries for antral follicle count and ovarian volume determination (Table 3).22-26

Notably, these tests may be predictive of response to exogenous ovarian stimulation and are not predictive of live birth or even natural fertility. Accelerated oocyte loss can result in loss of fertility and early menopause (prior to age 40).

While the majority of these cases are idiopathic,27 ovarian reserve should be monitored in women with a history of prior ovarian surgery, chemotherapy, radiation therapy, or with a family history of premature menopause. These women may be at risk for carrying the fragile X (FMR1) pre-mutation and also the consequences of estrogen deprivation.

Disorders of male physiology occur in 35% of infertile couples and are the sole factor in 17% of couples.28 Similar to the female, in the male, FSH and LH stimulate the testes to produce testosterone and develop the immature gametes. Unlike the oocytes, sperm mature for three months in the male reproductive tract before being ejaculated.

Hormonal dysfunction of the male may arise from all areas of male reproductive physiology. When testosterone is low but not absent, erectile dysfunction and decreased libido commonly accompany alter semen parameters29 resulting in infertility.

Testicular failure also results in azoospermia. In addition, the concomitant lack of testosterone results in decreased libido and erectile dysfunction. As testosterone concentrations drop in the male, risk for heart disease, hyperlipidemia, osteopenia, and muscular mass loss increases.

Testosterone failure is diagnosed by a low serum testosterone and elevated LH and FSH. Of course, correcting any hormonal abnormality and screening for related disorders should precede treatment.

Diagnosis of male factor infertility begins with a well collected, comprehensive semen analysis performed in a certified andrology laboratory (Table 4). The semen sample is best collected at the laboratory, but when it must be collected at home, it should be delivered to the laboratory at body temperature within 30 to 60 minutes after ejaculation.

A diagnosis of an abnormal semen analysis should only be made after a confirmatory semen analysis has been performed, and must be interpreted in the context of the couples overall fertility evaluation. Other tests of sperm function are available, but their practical diagnostic value is subject to interpretation and are clinically not as useful.

Azoospermia is the absence of sperm in the ejaculate, not necessarily indicating an absence of sperm in the upper reproductive tract or the testes.

When the vas is patent, retrograde ejaculation may be diagnosed by retrieving sperm from the urine after orgasm and may be washed and used for intrauterine insemination. If the vas is blocked, sperm may be aspirated from the epididymis (MESA) or surgically extracted from the testes (TESA) and used for intracytoplasmic sperm injection (ICSI) at IVF.

In cases of azoospermia in which the sperm must be retrieved from the testes, testing for a mutation in the DAZ (Deleted in Azoospermia) gene can be a useful predictor of testicular sperm presence, as presence of the DAZ-c mutation predicts an almost 0% likelihood of finding sperm in the testes.30These genes may also be passed on to offspring; affected male patients may opt to use a donor sperm to prevent this outcome.

Similarly, men with an absent vas deferens may have a mutated allele for cystic fibrosis or a 5-T variant and if sperm is aspirated from the epididymis or testes for use in IVF, the resultant child may inherit cystic fibrosis.31 Thus, screening for the mutations is recommended when an absent vas deferens is detected.

Oligozoopspermia, or less than 15 million sperm/ml, and may signal partial retrograde ejaculation, hormonal disturbance or genetic conditions. If the testosterone levels are normal or low and the LH and FSH are normal, an empirical treatment with clomiphene citrate for 6 to 12 months may increase the sperm count.32

Monitoring testosterone and the semen analysis after three months is recommended. Asthenozoospermia is diagnosed when motility is < 40%, while teratospermia refers to the presence of < 4% normally formed sperm.

Male factor infertility may be treated by intrauterine insemination, possibly combined with ovulation induction of the female (COH-IUI) as discussed below. However, success rates with ICSI at IVF far exceed those with COH-IUI, especially when the normal morphology is <4% or the count is < 2million sperm/cc.

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Dr.Kallen is an assistant professor of Obstetrics, Gynecology, and Reproductive Sciences in the Division of Reproductive Endocrinology and Infertility within the Department of Obstetrics, Gynecology, and Reproductive Sciences at Yale School of Medicine, Yale University.

Dr. Carson is a professor of Obstetrics, Gynecology, and Reproductive Sciences in the Division Chief, Division of Reproductive Endocrinology and Infertility within the Department of Obstetrics, Gynecology, and Reproductive Sciences at Yale School of Medicine, Yale University.

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1. Guttmacher AF. Factors affecting normal expectancy of conception. J Am Med Assoc [Internet]. 1956 Jun 30;161(9):855860. Available from: https://doi.org/10.1001/jama.1956.02970090081016

2. American Society for Reproductive Medicine: Diagnostic evaluation of the infertile female. Fertil Steril [Internet]. Elsevier Inc.; 2015;103(6):e44e50. Available from: http://dx.doi.org/10.1016/j.fertnstert.2015.03.019

3. Audu BM, Massa AA, Bukar M, El-Nafaty AU, SaAd ST. Prevalence of utero-tubal infertility. J Obstet Gynaecol (Lahore). 2009;29(4):326328. PMID: 19835502

4. Broeze KA, Opmeer BC, Van geloven N, Coppus SFPJ, Collins JA, Den hartog JE, Van der Linden PJQ, Marianowski P, Ng EHY, Van der Steeg JW, Steures P, Strandell A, Van der Veen F, Mol BWJ. Are patient characteristics associated with the accuracy of hysterosalpingography in diagnosing tubal pathology? An individual patient data meta-analysis. Hum Reprod Update. 2011;17(3):293300.

5. Swart P, Mol BWJ, Van der Veen F, Van Beurden M, Redekop WK, Bossuyt PMM. The accuracy of hysterosalpingography in the diagnosis of tubal pathology: A meta-analysis. Fertil Steril [Internet]. Elsevier Masson SAS; 1995;64(3):486491. Available from: http://dx.doi.org/10.1016/S0015-0282(16)57781-4 PMID: 7641899

6. Kodaman P, Arici A, Seli E. Diagnosis and Management of Tubal Factor Infertility. Curr Opin Obstet Gynecol. 2004;16(3):221229.

7. Practice Committee of the American Society for Reproductive Medicine. Role of tubal surgery in the era of assisted reproductive technology: A committee opinion. Fertil Steril [Internet]. Elsevier Inc.; 2015;103(6):e37e43. Available from: http://dx.doi.org/10.1016/j.fertnstert.2015.03.032

8. Maheux-Lacroix S, Boutin A, Moore L, Bergeron ME, Bujold E, Laberge P, Lemyre M, Dodin S. Hysterosalpingosonography for diagnosing tubal occlusion in subfertile women: A systematic review with meta-analysis. Hum Reprod. 2014;29(5):953963.

9. De Silva PM, Chu JJ, Gallos ID, Vidyasagar AT, Robinson L, Coomarasamy A. Fallopian tube catheterization in the treatment of proximal tubal obstruction: A systematic review and meta-analysis. Hum Reprod. 2017;32(4):836852.

10. Ozkan S, Murk W, Arici A. Endometriosis and infertility: Epidemiology and evidence-based treatments. Ann N Y Acad Sci. 2008;1127:92100.

11. Brown J, Farquhar C. Endometriosis: An overview of Cochrane Reviews. Cochrane Database Syst Rev. 2014;2014(3). PMID: 24610050

12. American Society for Reproductive Medicine Practice Committee: Endometriosis and infertility. Fertil Steril [Internet]. American Society for Reproductive Medicine; 2012;98(3):591598. Available from: http://dx.doi.org/10.1016/j.fertnstert.2012.05.031

13. Bittencourt CA, dos Santos Simes R, Bernardo WM, Fuchs LFP, Soares Jnior JM, Pastore AR, Baracat EC. Accuracy of saline contrast sonohysterography in detection of endometrial polyps and submucosal leiomyomas in women of reproductive age with abnormal uterine bleeding: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2017;50(1):3239.

14. Boss EA, Van Golde RJT, Beerendonk CCM, Massuger LFAG. Pregnancy after radical trachelectomy: A real option? Gynecol Oncol. 2005.

15. Carmina E, Stanczyk F, Lobo R. Laboratory Assessment. In: Strauss J, Barbieri R, editors. Yen Jaffes Reprod Endocrinol Physiol Pathophysiol Clin Manag. Eighth. Elsevier; 2019. p. 887915.

16. Sirmans SM, Pate KA. Epidemiology, diagnosis, and management of polycystic ovary syndrome. Clin Epidemiol. 2013; PMID: 24379699

17. Clark AM, Ledger W, Galletly C, Tomlinson L, Blaney F, Wang X, Norman RJ. Weight loss results in significant improvement in pregnancy and ovulation rates in anovulatory obese women. Hum Reprod. 1995;10(10):27052712. PMID: 8567797

18. Laing LM. Declining Fertility in a Religious Isolate: The Hutterite Population of Alberta, Canada. Hum Biol. 1980;52(2):289310.

19. American Society for Reproductive Medicine: Female age-related fertility decline. Fertil Steril [Internet]. American Society for Reproductive Medicine; 2014;101(3):633634. Available from: http://dx.doi.org/10.1016/j.fertnstert.2013.12.032

20. Jones KT. Meiosis in oocytes: Predisposition to aneuploidy and its increased incidence with age. Hum Reprod Update. 2008;14(2):143158. PMID: 18084010

21. Oktay K, Turan V, Titus S, Stobezki R, Liu L. BRCA Mutations, DNA Repair Deficiency, and Ovarian Aging. Biol Reprod. 2015;93(3):110. PMID: 26224004

22. Tal R, Seifer DB. Ovarian reserve testing: a user s guide. Am J Obstet Gynecol [Internet]. Elsevier Inc.; 2017;217(2):129140. Available from: http://dx.doi.org/10.1016/j.ajog.2017.02.027

23. Steiner AZ, Pritchard D, Stanczyk FZ, Kesner JS, Meadows JW, Herring AH, Baird DD. Association Between Biomarkers of Ovarian Reserve and Infertility Among Older Women of Reproductive Age. Jama. 2017;318(14):13671376. PMID: 29049585

24. Hawkins Bressler L, Steiner A. Anti-Mllerian hormone as a predictor of reproductive potential. Curr Opin Endocrinol Diabetes Obes. 2018;25(6):385390.

25. Pfeifer S, Butts S, Dumesic D, Fossum G, Giudice L, Gracia C, La Barbera A, Odem R, Pisarska M, Rebar R, Richard R, Rosen M, Sandlow J, Vernon M, Widra E. Testing and interpreting measures of ovarian reserve: A committee opinion. Fertil Steril [Internet]. American Society for Reproductive Medicine; 2015;103(3):e9e17. Available from: http://dx.doi.org/10.1016/j.fertnstert.2014.12.093

26. ACOG Committee Opinion No. 773: The Use of Antimllerian Hormone in Women Not Seeking Fertility Care. Obstet Gynecol. 2019;133(4):e274e278.

27. Bachelot A, Rouxel A, Massin N, Dulon J, Courtillot C, Matuchansky C, Badachi Y, Fortin A, Paniel B, Lecuru F, Lefrere-Belda MA, Constancis E, Thibault E, Meduri G, Guiochon-Mantel A, Misrahi M, Kuttenn F, Touraine P. Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure. Eur J Endocrinol. 2009;161(1):179187.

28. Odisho AY, Nangia AK, Katz PP, Smith JF. Temporal and geospatial trends in male factor infertility with assisted reproductive technology in the United States from 1999-2010. Fertil Steril. 2014;

29. Nikoobakht MR, Aloosh M, Nikoobakht N, Mehrsay A, Biniaz F, Karjalian MA. The role of hypothyroidism in male infertility and erectile dysfunction. Urol J. 2012; PMID: 22395839

30. Ferlin A, Tessari A, Ganz F, Marchina E, Barlati S, Garolla A, Engl B, Foresta C. Association or partial AZFc region deletions with spermatogenic impairment and male infertility. J Med Genet. 2005;

31. Chilln M, Casals T, Mercier B, Bassas L, Lissens W, Silber S, Romey MC, Ruiz-Romero J, Verlingue C, Claustres M, Nunes V, Frec C, Estivill X, Estivill X. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med. 1995;

32. Willets AE, Corbo JM, Brown JN. Clomiphene for the treatment of male infertility. Reproductive Sciences. 2013.

33. La Marca A, Sighinolfi G, Radi D, Argento C, Baraldi E, Artenisio AC, Stabile G, Volpe A. Anti-Mllerian hormone (AMH) as a predictive marker in assisted reproductive technology (ART). Hum Reprod Update. 2009;16(2):113130.

34. Kruger TF, Acosta AA, Simmons KF, Swanson RJ, Matta JF, Oehninger S. Predictive value of abnormal sperm morphology in in vitro fertilization. Fertil Steril. 1988; PMID: 3335257

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The diagnosis of the infertile couple - Contemporary Obgyn

Physiology

Shoots and leaves: the shotgun scientist who hunts moving trees – The Guardian

Angelica Patterson is on the lookout, shotgun in hand, as she hikes through New York states Black Rock Forest. She focuses on her target high up in the canopy, then bang a branch falls to the ground. I cant climb trees, building scaffolding is expensive, and using a slingshot requires a lot of skill, she says. A shotgun is an efficient, cheap and effective way to collect the high-up leaves that have full exposure to the sun.

Patterson puts the northern red oak branch into a bucket of water, cutting the submerged stem to ensure that its leaves continue to function, before walking back to her laboratory in the forest.

Here she studies how trees adapt and move in response to increasing average air temperatures. When I first started learning about how plant communities change through time, Id never associated trees with migration because theyre sessile and dont move like four-legged creatures or fly like insects. So its eye-opening to realise that tree communities shift their ranges to migrate to places where they can thrive, says Patterson, 39, a PhD student at Columbia Universitys department of earth and environmental science.

Its as simple as seed dispersal. But just because a seed from a tree can move to a place doesnt mean it will successfully grow or reproduce. Other factors come into play in order to establish a thriving population.

Black Rock Forest is unusual because extensive data collected since the 1930s shows exactly how tree distribution has changed there. Over the past 90 years, theres been a shift in forest composition. Three species have left the region or become locally extinct and 11 have migrated in naturally from the south or been introduced anthropogenically, Patterson says. I wanted to find out what mechanism drives this shift and how that affects the ability of our forest to become a source rather than a sink of carbon dioxide, therefore perpetuating climate change.

The forests in the north-eastern US are one of the worlds fastest growing carbon stores on land as timber harvesting, large-scale agriculture and fire disturbance have declined. But a shifting forest composition could have a drastic impact on this regions carbon storage capacity if the forests carbon balance is disrupted, more carbon could be released into the atmosphere.

Northern red oaks are so important to this region, they influence soil health, water quality, nutrients. When you start to lose large populations of trees, that complex forest ecosystem can break down, says Patterson.

If an invasive tree comes into play, youll start to have a monoculture and lose that biodiversity; then the whole system just isnt healthy.

Patterson, who also works as an educator, admits she has never really been a city person. She grew up immersed in nature and trees in the rural town of Lackawaxen, Pennsylvania, and thrives in the multisensory experience of a forest. I love the calm, the peace, the intrigue; I can go for a walk and find a plant Ive never seen before or hear a new bird call, or discover a weird fungus. This forest is an amazing space to be, says Patterson, who lives just 20 minutes away. This place allows me to calm my mind but also stimulate it at the same time. Ive never found another environment that does that.

Over the past eight years she has studied how hundreds of leaves from 22 species function differently to investigate how environments that are extreme to certain species can influence the physiology of the tree. I liken it to working out which tree has the engine of a Toyota and which has the engine of a Ferrari the oaks are not Ferraris. However, they are extremely resilient and theres a reason theyve been dominant here for centuries, says Patterson, who explains the survival strategy of the northern red oak, which makes up 70% of this forest. These oaks can live up to 350 years so theyre long-lived, they produce dominant seeds [acorns] and tolerate high-stress conditions.

In the past, Black Rock Forest has been subject to fires but the oaks acorns can survive underground until conditions improve. However, now there are more settlements locally, fires are suppressed so these oaks must compete with fire-sensitive trees that would not have survived previously. More frequent tropical storms and heavy winds also threaten mature oak trees, a disease called oak blight is spreading into this region and deer browsing affects oak regeneration, potentially allowing other migrant trees to more easily fill this niche.

Kevin Griffin, professor in plant physiology at Columbia University, is Pattersons PhD supervisor. He explains why Black Rock Forest is such a significant place to study tree migration. Theres a huge mix of species here because tree species that typically have a southern or northern range all seem to crash together right in the Hudson valley, he says. At the end of the last ice age 14,000 years ago, glaciers receded from the Hudson valley and now after ecological succession were looking at this beautiful oak deciduous forest, but thats just a snapshot in time.

A plant or animals range the geographical area in which a species can be found is in constant flux. Ranges naturally shift, expand and contract over time, but it is the current speed of change that concerns scientists like Patterson and Griffin. If the rate of change [in ranges] is greatly accelerated from human activities, then how does the ecology keep up with that? asks Griffin.

For trees that grow and reproduce incredibly slowly, migration is a huge challenge. As Griffin puts it, trees dont have legs, seeds travel short distances and lots of things eat those seeds, plus trees need pollinators and the right soil for germination, so the ecology is fascinating but not obvious. Crucially, theres a mismatch between the speed at which ranges shift and the speed at which trees can respond and migrate.

Griffin and Patterson are investigating how shifting ranges affect the physiology or inner workings of these trees: Were trying to build a clearer picture of how the trees are currently surviving, how competitive they are and at what rate they may or may not be able to keep up with this shift in climatic conditions, says Griffin, who says that temperature is one of the key drivers for shifting ranges.

According to the US Forest Service Northern Research Station, more than 70% of saplings from northern tree species in the eastern US are showing a northwards migration. But temperature certainly isnt the only variable. In 2017, forest ecologist Songlin Fei at Indianas Purdue University found more species moving west than north in eastern areas, possibly due to changes in precipitation or rainfall rather than changes in temperature. Total annual rainfall in central US had increased by more than 150mm and declined significantly in the south-east.

In order to compare metabolic activity inside every leaf she collects, Patterson clamps each one into the chamber of a photosynthesis machine. I set the relative humidity, light, carbon dioxide levels and temperature to mimic the local conditions in the forest, or to recreate the southern range limit conditions, then allow each leaf to acclimatise and become happy. This encourages the stomas [pores] to open so that gas exchange can flow freely, she says. Patterson measures the rates of respiration and photosynthesis in mature trees.

Griffin likens this to a bank account: You have what you make and what you spend; tree growth is whats left over. So we study both photosynthesis how carbon gets into the tree and respiration how carbon leaves the tree to see if we can understand why some plants appear more or less successful.

In Black Rock Forest, the northern red oak is central to its range. But other broad-leaved and conifer trees found here might be living at the southern limit of their region (these northern-ranged trees include paper birch and red pine), or at the northern limit of their region (southern-ranged trees such as American sycamore and Atlantic white cedar). Pattersons initial results show that there are significant differences in the physiological capacities between northern-, central- and southern-ranged trees in Black Rock Forest.

The patterns we find suggest that resident or centrally ranged trees, such as northern red oak, are physiologically disadvantaged when compared [with] the northern- and southern-ranged trees, she says.

But the trees may have been able to adapt to current climate conditions. Within the next 50-100 years, high carbon emission scenarios predict that temperatures could feel as warm as Georgias. So the oaks ability to continue to physiologically acclimate to a warming climate and persist among disturbance regimes such as deer browsing or ice storms will [influence] the health and survival of the oak population and the carbon storage potential of this regions forests, Patterson says.

Theres also scope for this data to be incorporated into climate models so it might help predict future atmospheric carbon dioxide levels and evaluate which of the north-east US tree species may be better able to tolerate warmer climates over coming decades.

The best approach to surviving a warming climate, according to researchers, could be to maintain connective corridors to allow trees to naturally migrate to new areas in a changing future and not be stopped by artificial boundaries such as cities, lakes or farmland.

Further research by the University of Tennessee indicates that underground soil highways could also be important, with certain combinations of fungi and bacteria microbiomes encouraging heat-sensitive trees to migrate to higher elevations where they can thrive.

Ultimately, tree migration is incredibly complex. But Pattersons work represents a valuable benchmark. Having recorded GPS coordinates for every leaf studied, researchers could take further measurements to assess how tree function changes over time.

This is just a small snapshot of whats happening with certain trees, she says. But it gives insight into which species will tolerate particular environments and that could help forest management now and in the future.

Find more age of extinction coverage here, and follow biodiversity reporters Phoebe Weston and Patrick Greenfield on Twitter for all the latest news and features

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Shoots and leaves: the shotgun scientist who hunts moving trees - The Guardian

Physiology

Researchers identify the missing link in the production of nitric oxide – News-Medical.net

Reviewed by Emily Henderson, B.Sc.Sep 14 2020

Some microorganisms, the so-called methanotrophs, make a living by oxidizing methane (CH4) to carbon dioxide (CO2). Ammonia (NH3) is structurally very similar to methane, thus methanotrophs also co-metabolize ammonia and produce nitrite.

While this process was observed in cell cultures, the underlying biochemical mechanism was not understood. Boran Kartal, head of the Microbial Physiology Group at the Max Planck Institute for Marine Microbiology in Bremen, Germany, and a group of scientists from Radboud University in Nijmegen, The Netherlands, now shed light on an exciting missing link in the process: the production of nitric oxide (NO).

Nitric oxide is a highly reactive and toxic molecule with fascinating and versatile roles in biology and atmospheric chemistry. It is a signaling molecule, the precursor of the potent greenhouse gas nitrous oxide (N2O), depletes the ozone layer in our atmosphere, and a key intermediate in the global nitrogen cycle.

It now turns out that NO is also the key for the survival of methanotrophs that face ammonia in the environment - which they do more and more as fertilizer input into nature increases. When methanotrophs co-metabolize ammonia they initially produce hydroxylamine, which inhibits other important metabolic processes, resulting in cell death.

Thus, methanotrophs need to get rid of hydroxylamine as fast as possible. "Carrying a hydroxylamine-converting enzyme is a matter of life or death for methane-eating microbes", Kartal says.

For their study, Kartal and his colleagues used a methanotrophic bacterium named Methylacidiphilum fumariolicum, which originates from a volcanic mud pot, characterized by high temperatures and low pH, in the vicinity of Mount Vesuvius in Italy.

From this microbe, we purified a hydroxylamine oxidoreductase (mHAO) enzyme. Previously it was believed that mHAO enzyme would oxidize hydroxylamine to nitrite in methanotrophs. We now showed that it actually rapidly produces NO."

Boran Kartal, Head of the Microbial Physiology Group, Max Planck Institute for Marine Microbiology

The mHAO enzyme is very similar to the one used by "actual" ammonia oxidizers, which is quite astonishing, as Kartal explains: "It is now clear that enzymatically there is not much difference between aerobic ammonia- and methane-oxidizing bacteria. Using essentially the same set of enzymes, methanotrophs can act as de facto ammonia oxidizers in the environment. Still, how these microbes oxidize NO further to nitrite remains unknown."

The adaptation of the mHAO enzyme to the hot volcanic mud pots is also intriguing, Kartal believes: "At the amino acid level, the mHAO and its counterpart from ammonia oxidizers are very similar, but the protein we isolated from M. fumariolicum thrives at temperatures up to 80 C, almost 30 C above the temperature optimum of their "actual" ammonia-oxidizing relatives. Understanding how so similar enzymes have such different temperature optima and range will be very interesting to investigate."

According to Kartal, production of NO from ammonia has further implications for methane-eating microbes: "Currently there are no known methanotrophs that can make a living out of ammonia oxidation to nitrite via NO, but there could be methanotrophs out there that found a way to connect ammonia conversion to cell growth."

Source:

Journal reference:

Versantvoort, W., et al. (2020) Multiheme hydroxylamine oxidoreductases produce NO during ammonia oxidation in methanotrophs. Proceedings of National Academy of Sciences. doi.org/10.1073/pnas.2011299117.

Link:
Researchers identify the missing link in the production of nitric oxide - News-Medical.net

Physiology

Health Makers: How the App GlucoseZone Helps People With Diabetes Exercise Safely – Everyday Health

He recalls his training schedule during college, which began with breakfast at 7 a.m. They serve bacon, egg, cheese, and fruit, and practice is at 8, he says. How much insulin do you take at breakfast?

Another example: Its 11 a.m. and youve been at practice for three hours and your blood sugar is 280 milligrams per deciliter (mg/dl). According to the American Diabetes Association, the recommended range is between 80mg/dl and 130 mg/dl. What do you do? he asks.

It was a total disaster because nobody there had a clue how to help me. I was the only athlete there with type 1 diabetes, OConnell explains.

His coaches eventually set a refrigerator aside in the training room filled with everything from maple syrup to vials of insulin. I persevered through that situation, and I love U Penn, but at the time, it was a very frustrating experience, and I felt that diabetes had really hindered my athletic potential, he says.

RELATED: 7 Tips for Staying Motivated to Exercise When Managing Diabetes

After graduation he moved to New York City, began working in tech, and quit exercising. The fear and anxiety he experienced during college worrying about hypoglycemia, or low blood sugar was so overwhelming that he lost his motivation.

The problem was that I had come to fear my relationship with exercise, OConnell says. Then I realized that I cant have something that I really love being active be dominated by fear and anxiety.

He began a personal quest to figure it out: What type of exercise should he do? Or how should he prepare for different types of exercise? Why did his blood sugar drop when he did aerobic exercise that is, workouts of low to high intensity and elevate when he did anaerobic exercise, or short bursts of high intensity.

These are detailed and challenging physiological questions that type 1 diabetics have to manage every time they do physical activity, he says. And I realized, if this has taken me three years of studying intensely and I love exercise, what about the person who just wants to do a Spin class and not have a hypoglycemic incident?

RELATED: 6 Diabetes Exercise Mistakes and How to Avoid Them

During this time, he learned about physiology and type 1 and type 2 diabetes, and began developing the foundation of the GlucoseZone algorithm, which takes independent variables like blood sugar, heart rate levels, and medication and analyzes them to make exercise recommendations.

Depending on a persons blood sugar levels, it may not be safe to exercise, OConnell says. Depending on the medication profile theyre on, it may not be safe to exercise.

GlucoseZone has teamed up with the American Diabetes Association and is being used in 20 countries. When the COVID-19 pandemic hit, he decided to offer it free for a limited time. On October 1, the app will cost $4.95, down from $12.95 before the pandemic.

People with diabetes are more susceptible to COVID-19-related issues than the general population, and they have a requirement to be physically active on a daily basis, OConnell says. My ultimate goal is to be the global resource for people living with diabetes to reach their fitness goals.

RELATED: How Exercise Helps Prevent or Manage Type 2 Diabetes

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Health Makers: How the App GlucoseZone Helps People With Diabetes Exercise Safely - Everyday Health