This deeper understanding of the ovary means researchers could potentially create artificial ovaries in the lab using tissues that were stored and frozen before exposure to toxic medical treatments such as chemotherapy and radiation. Currently, surgeons can implant previously frozen ovarian tissue to temporarily restore hormone and egg production. However, this does not work for long because so few follicles — the structures that produce hormones and carry eggs — survive through reimplantation, the researchers say.

The new atlas reveals the factors that enable a follicle to mature, as most follicles wither away without releasing hormones or an egg. Using new tools that can identify what genes are being expressed at a single-cell level within a tissue, the team was able to home in on ovarian follicles that carry the immature precursors of eggs, known as oocytes.

“Now that we know which genes are expressed in the oocytes, we can test whether affecting these genes could result in creating a functional follicle. This can be used to create an artificial ovary that could eventually be transplanted back into the body,” said Ariella Shikanov, U-M associate professor of biomedical engineering and corresponding author of the new study in Science Advances.

The majority of the follicles, called primordial follicles, remain dormant and are located in the outer layer of the ovary, called the cortex. A small portion of these follicles activate periodically and migrate into the ovary, to a region known as the growing pool. Only a few of those growing follicles go on to produce mature eggs that get released into the fallopian tube.

With the ability to guide follicle development and tune ovarian environment, the team believes that engineered ovarian tissue could function for much longer than unmodified implanted tissue. This means that patients would have a longer fertility window as well as a longer period in which their bodies produce hormones that help regulate the menstrual cycle and support muscular, skeletal, sexual and cardiovascular health.

“We’re not talking about utilizing a surrogate mother, or artificial insemination,” said Jun Z. Li, associate chair of U-M’s Department of Computational Medicine and Bioinformatics and co-corresponding author of the study. “The magic we’re working toward is being able to trigger an immature cell into maturity, but without knowing which molecules drive that process, we’re blind.”

U-M’s team utilized a relatively new technology, called spatial transcriptomics, to track all of the gene activity — and where it occurs — in tissue samples. They do this by reading strands of RNA, which are like notes taken from the DNA strand, revealing which genes are being read. Working with an organ procurement organization, U-M researchers performed RNA sequencing of ovaries from five human donors.

“This was the first time where we could target ovarian follicles and oocytes and perform a transcription analysis, which enables us to see which genes are active,” Shikanov said.

“The majority of ovarian follicles, already present at birth, never enter the growing pool and eventually self-destruct. This new data allows us to start building our understanding of what makes a good egg — what determines which follicle is going to grow, ovulate, be fertilized and become a baby.”

U-M’s work is part of the Human Cell Atlas project, which seeks to create “maps of all the different cells, their molecular characteristics and where they are located, to understand how the human body works and what goes wrong in disease.”

Shikanov, Li and U-M collaborators such as Sue Hammoud, U-M associate professor of human genetics and urology, are mapping other parts of the female reproductive system, including the uterus, fallopian tubes and ovaries. Other contributors include Andrea Suzanne Kuliahsa Jones, formerly of U-M and now at Duke University, and D. Ford Hannum, a U-M graduate student research assistant in bioinformatics.

The research was partially funded by the Chan Zuckerberg Initiative. Additional financial support was provided by the National Institutes of Health.

In the new findings, which were published in Science on April 5, 2024, Scripps Research chemists show that it’s possible to convert feedstock chemicals into quaternary carbons using a single, inexpensive iron catalyst. This method could benefit drug developers by making molecules cheaper and easier to produce at small and large scales.

“Quaternary carbons are ubiquitous across various areas of research — from drug discovery to material science,” says co-first author Nathan Dao, a PhD candidate at Scripps Research. “The synthesis of quaternary carbons, however, is a long-standing challenge in the field of organic chemistry, typically requiring numerous steps and relying on harsh conditions or less accessible starting materials.”

In addition to Dao, the study’s co-first authors included Xu-Cheng Gan and Benxiang Zhang.

Catalysts are substances used to speed up the rate of a chemical reaction. Sometimes, several different catalysts are necessary to promote a certain reaction and obtain the desired result: a veritable ‘reaction soup’. But catalysts can be very expensive, and they don’t always react as intended — and the more catalysts used, the more waste that’s produced. But the Scripps Research scientists determined that a single catalyst could perform multiple crucial rolls.

“A difficult chemical reaction often requires many interacting components,” according to co-senior author, Ryan Shenvi, PhD, a professor in the Department of Chemistry at Scripps Research. “A benefit of this work is it’s incredibly simple.”

The team identified simple conditions to convert carboxylic acids and olefins, two major classes of chemical feedstocks — or raw materials that fuel a machine or industrial process — into quaternary carbons by using an inexpensive iron-based catalyst. In addition, these chemical feedstocks aren’t only abundant, but they’re also low cost.

“Similar reactions have been gaining traction lately, so this discovery was inevitable,” Shenvi explains. “The pieces were already in the literature, but no one had put them together before.”

Overall, the study, which was done in collaboration with the lab of senior co-author Phil Baran, PhD, the Dr. Richard A. Lerner Endowed Chair in the Department of Chemistry at Scripps Research, highlights the ongoing role of chemistry in the development of modern technology and pharmaceuticals.

“This work is yet another striking demonstration of the power of the collaborative atmosphere at Scripps Research to unearth new transformations that can have a dramatic impact on simplifying the practice of organic synthesis,” Baran adds.

This work and the researchers involved were supported by funding from the National Institutes of Health (grants GM122606 and GM118176), the National Science Foundation (CHE1955922), Nanjing King-Pharm Co., Ltd), Pfizer and Biogen.

A paper describing the new reconstruction, which used microcomputed tomography (micro-CT) to scan the fossil and reveal vertebrae and ribs of the fish that were previously hidden beneath rock, appeared April 2 in the journal Proceedings of the National Academy of Sciences.

“Tiktaalik was discovered in 2004, but key parts of its skeleton were unknown,” said Tom Stewart, assistant professor of biology in the Eberly College of Science at Penn State and one of the leaders of the research team. “These new high-resolution micro-CT scans show us the vertebrae and ribs of Tiktaalik and allow us to make a full reconstruction of its skeleton, which is vital to understanding how it moved through the world.”

Unlike most fish, which have vertebrae and ribs that are the same along the length of the trunk, the axial skeletons of limbed vertebrates show dramatic differences in the vertebrae and ribs from the head region to the tail region. The evolution of this regionalization allowed the performance of specialized functions, one of which was a mechanical linkage between ribs in the sacral region to the pelvis that enabled support of the body by the hind limbs.

The pelvic fins of fish are evolutionarily related to hind limbs in tetrapods — four-limbed vertebrates, including humans. In fish, the pelvic fins and bones of the pelvic girdle are relatively small and float freely in the body. For the evolution of walking, the researchers explained, the hind limbs and pelvis became much larger and formed a connection to the vertebral column as a way of bracing the forces related to supporting the body.

“Tiktaalik is remarkable because it gives us glimpses into this major evolutionary transition,” Stewart said. “Across its whole skeleton, we see a combination of traits that are typical of fish and life in water as well as traits that are seen in land-dwelling animals.”

The original description of Tiktaalik focused on the front portion of the skeleton. Fossils were meticulously prepared to remove the surrounding matrix of rock and expose the skull, shoulder girdle and pectoral fins. The ribs in this area were large and expanded, suggesting that they may have supported the body in some way, but it was unclear exactly how they would have functioned. In 2014, the fish’s pelvis, discovered in the same location as the rest of the skeleton, was also cleaned of matrix and described.

“From past studies, we knew that the pelvis was large, and we had a sense that the hind fins were large too, but until now couldn’t say if or how the pelvis interacted with the axial skeleton,” Stewart said. “This reconstruction shows, for the first-time, how it all fit together and gives us clues about how walking might have first evolved.”

The researchers explained that, unlike our own hips where our bones fit tightly together, the connection between the pelvis and axial skeleton of Tiktaalik was likely a soft-tissue connection made of ligaments.

“Tiktaalik had specialized ribs that would have connected to the pelvis by a ligament,” Stewart said. “It’s astonishing really. This creature has so many traits — large pair of hind appendages, large pelvis, and connection between the pelvis and axial skeleton — that were key to the origin of walking. And while Tiktaalik probably wasn’t walking across land, it was definitely doing something new. This was a fish that could likely prop itself up and push with its hind fin.”

The new reconstruction of the skeleton also sheds light on specializations for head mobility in Tiktaalik and new details of the fish’s pelvic fin anatomy.

“It’s incredible to see the skeleton of Tiktaalik captured in such vivid detail,” said Neil Shubin, Robert R. Bensley Distinguished Service Professor of Organismal Biology and Anatomy at the University of Chicago and one of the authors of the paper. “This study sets the stage for ones that explore how the animal moved about and interacted with its environment 375 million years ago.”

In addition to Stewart and Shubin, the research team includes Justin B. Lemberg, Emily J. Hillan, and Isaac Magallanes at The University of Chicago, and Edward B. Daeschler at Academy of Natural Sciences of Drexel University.

Support from the Brinson Foundation, the Biological Sciences Division of The University of Chicago, an anonymous donor to the Academy of Natural Sciences of Drexel University, and the U.S. National Science Foundation funded this research. Fieldwork was made possible by the Polar Continental Shelf Project of Natural Resources, Canada; the Department of Heritage and Culture, Nunavut; the hamlets of Resolute Bay and Grise Fiord of Nunavut; and the Iviq Hunters and Trappers of Grise Fiord.

New research from Lan Yang, the Edwin H. & Florence G. Skinner Professor in the Preston M. Green Department of Electrical & Systems Engineering in the McKelvey School of Engineering at Washington University in St. Louis, unlocks the power of exceptional points (EPs) for advanced optical sensing. In a study published April 5 in Science Advances, Yang and first author Wenbo Mao, a doctoral student in Yang’s lab, showed that these unique EPs — specific conditions in systems where extraordinary optical phenomena can occur — can be deployed on conventional sensors to achieve a striking sensitivity to environmental perturbations.

Yang and Mao developed an EP-enhanced sensing platform that overcomes the limitations of previous approaches. Unlike traditional methods that require modifications to the sensor itself, their innovative system features an EP control unit that can plug into physically separated external sensors. This configuration allows EPs to be tuned solely through adjustments to the control unit, allowing for ultrahigh sensitivity without the need for complex modifications to the sensor.

“We’ve implemented a novel platform that can impart EP enhancement to conventional optical sensors,” Yang said. “This system represents a revolutionary extension of EP-enhanced sensing, significantly expanding its applicability and universality. Any phase-sensitive sensor can acquire improved sensitivity and reduced detection limit by connecting to this configuration. Simply by tuning the control unit, this EP configuration can adapt to various sensing scenarios, such as environmental detection, health monitoring and biomedical imaging.”

By decoupling the sensing and control functions, Yang and Mao have effectively skirted the stringent physical requirements for operating sensors at EPs that have so far hindered their widespread adoption. This clears the way for EP enhancement to be applied to a wide range of conventional sensors — including ring resonators, thermal and magnetic sensors, and sensors that pick up vibrations or detect perturbations in biomarkers — vastly improving the detection limit of sensors scientists are already using. With the control unit set to an EP, the sensor can operate differently — not at an EP — and still reap the benefits of EP enhancement.

As a proof-of-concept, Yang’s team tested a system’s detection limit, or ability to detect weak perturbations over system noise. They demonstrated a six-fold reduction in the detection limit of a sensor using their EP-enhanced configuration compared to the conventional sensor.

“With this work, we’ve shown that we can significantly enhance our ability to detect perturbations that have weak signals,” Mao said. “We’re now focused on bringing that theory to broad applications. I’m specifically focused on medical applications, especially working to enhance magnetic sensing, which could be used to improve MRI technology. Currently, MRIs require a whole room with careful temperature control. Our EP platform could be used to enhance magnetic sensing to enable portable, bedside MRI.”

A new study led by scientists at the University of Alaska Fairbanks and the University of Reading calls into question Bergmann’s rule, an 1800s-era scientific principle stating that animals in high-latitude, cooler climates tend to be larger than close relatives living in warmer climates.

The fossil record shows otherwise.

“Our study shows that the evolution of diverse body sizes in dinosaurs and mammals cannot be reduced to simply being a function of latitude or temperature,” said Lauren Wilson, a UAF graduate student and a lead author of a paper published today in the journal Nature Communications. “We found that Bergmann’s rule is only applicable to a subset of homeothermic animals (those that maintain stable body temperatures), and only when you consider temperature, ignoring all other climatic variables. This suggests that Bergmann’s ‘rule’ is really the exception rather than the rule.”

The study started as a simple question Wilson discussed with her undergraduate advisor: Does Bergmann’s rule apply to dinosaurs?

After evaluating hundreds of data points gleaned from the fossil record, the answer seemed a solid “no.”

The dataset included the northernmost dinosaurs known to scientists, those in Alaska’s Prince Creek Formation. They experienced freezing temperatures and snowfall. Despite this, the researchers found no notable increase in body size for any of the Arctic dinosaurs.

Next the researchers tried the same evaluation with modern mammals and birds, the descendants of prehistoric mammals and dinosaurs. The results were largely the same: Latitude was not a predictor of body size in modern bird and mammal species. There was a small relationship between the body size of modern birds and temperature, but the same was not the case for prehistoric birds.

The researchers say the study is a good example of how scientists can and should use the fossil record to test current-day scientific rules and hypotheses.

“The fossil record provides a window into completely different ecosystems and climate conditions, allowing us to assess the applicability of these ecological rules in a whole new way,” said Jacob Gardner, a postdoctoral researcher at the University of Reading and the other lead author of the paper.

Scientific rules should apply to fossil organisms in the same way they do modern organisms, said Pat Druckenmiller, director of the University of Alaska Museum of the North and one of the co-authors of the paper.

“You can’t understand modern ecosystems if you ignore their evolutionary roots,” he said. “You have to look to the past to understand how things became what they are today.”

The paper is the first clear evidence demonstrating an effect of climate change on this charismatic species. Specifically, the paper shows that July rainfall results in reduced July water clarity in loon territories. Reduced water clarity, in turn, makes it difficult for adult loons to find and capture their prey (mainly small fishes) under water, so they are not able to meet their chicks’ metabolic needs. The result is low chick weight and higher chick mortality. Since loons use the same foraging mode across their breeding range, the impact of water clarity on loon breeding success found in Wisconsin is likely to be echoed from Alaska to Iceland.

Piper, in collaboration with Max Gline and Kevin Rose from Rensselaer Polytechnic Institute, reports several important findings. Over the past 25 years, there has been a consistent decline in water clarity. During the same period, body weights of adult males, adult females, and chicks have also declined. By searching among a large number of environmental variables, the authors were able to pinpoint mean water clarity during the month of July — the month of most rapid growth in chicks — as the strongest predictor of body weight. In a separate analysis, the authors found that rainfall in July impacts water clarity negatively. That is, heavy rainfall in July results in reduced water clarity, whereas light rainfall leads to high clarity and good foraging conditions for loons. Consequently, the rise in rainfall observed in recent decades, attributed to climate change, poses challenges for adult loons in feeding their offspring and diminishes chick survival rates.

The precise way in which rainfall leads to reduced water clarity is currently under investigation. The authors suggest that rain might carry dissolved organic matter (DOM) into lakes from adjacent streams and shoreline areas. But it is also possible that nutrients (such as fertilizers used on lawns by lake residents), pet waste, or even leaks from septic systems might be to blame.

This study represents a unique partnership between diverse fields. Piper’s three-decade-long study of loon behavioral ecology in northern Wisconsin intersects with Gline and Rose’s use of Landsat imagery to calculate freshwater lake clarity. Combining data from these sources has illuminated the cause behind the sharp decline in breeding success in northern Wisconsin. It is now evident that both the loss of water clarity — as well as increasing populations of black flies, which have increased due to greater rainfall — are to blame for the population downturn.

“Few animals on Earth are at once so beloved and so poorly understood as Common Loons,” Piper said. “This partnership between a loon behaviorist and lake ecologists who collect satellite data on water clarity has given us a unique and powerful window onto foraging efficiency and the loon population as a whole that might help us conserve the species.”

Piper is in the process of establishing a second marked study population of loons, equal in size to the first, in Minnesota. There he will determine whether the recent decline in loon breeding success recorded by the Minnesota Department of Natural Resources results from a loss of water clarity, as in Wisconsin.

“We found several proteins important for vision that were affected by thermal stress,” says Dr Qiaz Hua, a recent PhD graduate from the University of Adelaide’s School of Biological Sciences.

“One of them is a structural protein found in high abundance in animal eye lenses to preserve lens transparency and optical clarity, and another is responsible for the regeneration of visual pigments in the photoreceptors of the eyes.

“The levels of both of these proteins were significantly reduced under projected ocean warming conditions, which suggests that octopus vision is likely to be impaired under thermal stress.”

Octopuses are highly visual animals, with 70 per cent of the octopus brain dedicated to vision — which is 20 per cent more than in humans.

“The primary functions of vision include but are not limited to visual acuity, discrimination of brightness, depth perception, motion detection and polarisation, and it is crucial for detecting predator and prey as well as for communication,” says Dr Hua.

“Having impaired vision will affect an octopus’s chances of survival in the wild through increased predator risk as well as lower foraging success.”

To make this finding, the research team, including academics from the University of South Australia, University of California Davis, and the South Australian Research and Development Institute’s aquatic sciences division, exposed Octopus berrima embryos to different temperature treatments, a control 19°C exposure, 22°C to model current summer temperatures, and 25°C to model projected summer temperatures.

“The future-projected temperature was based on the Intergovernmental Panel on Climate Change’s projected increase of about 3°C of warming by 2100,” Dr Hua says.

In addition to impaired vision, Dr Hua found increased ocean water temperatures would have a negative effect on octopus broods.

“We found a high mortality rate under future warming conditions. Out of three replicate octopus broods, none of the eggs hatched for two of them and less than half of the eggs hatched for the remaining brood,” Dr Hua says.

“In the broods where none of the eggs hatched, the mothers died naturally while the eggs were still in early development stages.

“Because maternal care of embryos occurs in octopuses, global warming could have a simultaneous impact on multiple generations, with the low survival rate of the embryos caused by the direct effect of thermal stress as well as the indirect effect of thermal stress on the mothers.

“Our study shows that even for a highly adaptable taxon like octopuses, they may not be able to survive future ocean changes.”

Other effects of higher temperatures which have been observed in octopuses include a higher metabolic rate, reduced size at maturity, and even a range shift in the distribution of some species.

“We hope that future research would examine a combination of environmental stressors including ocean acidification, warming, and deoxygenation,” Dr Hua says.

“It would also be useful to do a transgenerational experiment to see if sensitivity or tolerance to the environmental stressors is passed down from one generation to the next, which help us understand the impacts on the continuation of the species.”