Culture

Within multicellular organisms, cells build connections with each other forming cell layers that cover the surfaces of tissues and organs and separate structures in the body. For example, the skin forms a mantle around the entire organism, and the layer of cells lining the blood vessels creates a boundary between the bloodstream and tissues. Special connections between neighbouring cells ensure that these cellular barriers are, on the one hand, stable and tight - thus protecting the body and organs against pathogens - while, on the other hand, they remain permeable to specific substances or migrating cells. This is how the cells allow dissolved nutrients to be transported into organs, and how cells of the immune system are able to migrate from the blood across the blood vessel wall into inflamed tissue.

Scientists at the University of Münster have now investigated a comparable process in the ovary of the fruit fly (Drosophila melanogaster). Here, the maturing egg cells are enclosed by a layer of epithelial cells through which the egg absorbs yolk-forming proteins. The researchers found that, at the points where three cells meet, the epithelial cells loosen their connections in a controlled manner and the yolk proteins are transported to the egg cell through the resulting gaps. At places where only two cells connect, the connections are maintained, thus keeping the tissue integrity intact. "Our findings contribute to a better understanding of how cellular barriers function and are restructured during development, which provides a basis for deciphering the mechanisms of certain pathological processes," explains Prof Dr Stefan Luschnig, a developmental biologist and leader of the research project. The study has now been published in the scientific journal "Developmental Cell".

Investigations during egg development in the fruit fly

Whenever substances are transported through a cell layer, the cells either take them up through the membrane on one side of the cell layer and then release them on the other side - which requires a lot of energy - or the substances diffuse through gaps between the cells. From studies of other insects, it was already known that yolk proteins are usually transported into egg cells via spaces between the epithelial cells that enclose the eggs. The new investigation confirmed that this is also the case for the fruit fly. However, it was not previously clear how the cells manage to transiently open up intercellular spaces while at the same time keeping the tissue intact.

To visualize these cellular processes live and analyze the molecular mechanisms behind them, the scientists genetically labelled certain proteins of the fruit fly with fluorescent molecules, kept the ovaries in tissue cultures, and examined the living tissue using confocal laser scanning microscopy. They focused their attention on the proteins on the surface of the epithelial cells. These so-called adhesion proteins mechanically hold the cellular network together and seal the spaces between cells.

Cell barrier opens at junctions of three cells

The scientists found that the epithelial cells sequentially removed four different adhesion proteins from their membranes. "This process takes several hours, and only when the last protein is gone do the cell junctions open," explains biologist Jone Isasti-Sanchez, who is the first author of the study and a doctoral candidate in the Integrated Research Training Group within the Collaborative Research Center 1348 "Dynamic Cellular Interfaces" at the University of Münster. After the junctions have opened, the uptake of yolk proteins into the egg proceeds over about 16 hours and, subsequently, the process reverses - the intercellular spaces close again. The researchers demonstrated that the cells open their contact sites by taking up adhesion proteins from the surface into the cell interior, using a basic cellular process called endocytosis. An important new finding is that endocytosis seems to take place to a greater extent at those points where three cells meet, and, as a result, the cell junctions only open up at these points. Where only two cells meet, the contact is maintained. "The fact that this process occurs selectively at the three-cell contact-points and, moreover, in such an orderly fashion, is probably important for preventing the tissue from falling apart," says Stefan Luschnig. In addition, he adds that the process presumably has to take place in a very controlled manner because the opening of gates in a tissue comes with the risk that pathogens will enter.

In their experiments, the scientists also genetically increased or reduced the amount of the adhesion protein E-cadherin and were able to show that the amount of this protein determines how wide the intercellular spaces open. In addition, they found that the mechanical tension in the cytoskeleton plays a key role in the process. This tension is generated by a structure consisting of the proteins actin and myosin, which encircles the cell periphery and is able to contract, similar to a rubber band. When the researchers increased the activity of myosin in the cell, the cytoskeleton contracted more, which prevented the cell junctions from opening.

Paleontologists have discovered two new species of mammal-like, burrowing animals that lived about 120 million years ago in what is now northeastern China. The new species, described today in the journal Nature, are distantly related but independently evolved traits to support their digging lifestyle. They represent the first "scratch-diggers" discovered in this ecosystem.

"There are many hypotheses about why animals dig into the soil and live underground," said lead author Jin Meng, a curator in the American Museum of Natural History's Division of Paleontology. "For protection against predators, to maintain a temperature that's relatively constant--not too hot in the summer and not too cold in the winter--or to find food sources like insects and plant roots. These two fossils are a very unusual, deep-time example of animals that are not closely related and yet both evolved the highly specialized characteristics of a digger."

The fossil mammaliamorph species--predecessors to mammals--were discovered in the Jehol Biota, which represents the Early Cretaceous epoch, about 145 to 100 million years ago. One is a mammal-like reptile called a tritylodontid and is the first of its kind to be identified in this biota. About a foot in length, it was given the name Fossiomanus sinensis (Fossio, "digging" and manus "hand;" sinensis, "from China"). The other is named Jueconodon cheni (Jue, "digging"--Chinese pinyin--and conodon "cuspate tooth"; cheni for Y. Chen, who collected the fossil). It is a eutriconodontan, a distant cousin of modern placental mammals and marsupials, which were common in the habitat. It is about 7 inches long.

Mammals that are adapted to burrowing have specialized traits for digging. The researchers found some of these hallmark features--including shorter limbs, strong forelimbs with robust hands, and a short tail--in both Fossiomanus and Jueconodon. In particular, these characteristics point to a type of digging behavior known as "scratch digging," accomplished mainly by the claws of the forelimbs.

"This is the first convincing evidence for fossorial life in those two groups," Meng said. "It also is the first case of scratch diggers we know about in the Jehol Biota, which was home to a great diversity of life, from dinosaurs to insects to plants."

The animals also share another unusual feature: an elongated vertebral column. Typically, mammals have 26 vertebrae from the neck to the hip. However, Fossiomanus had 38 vertebrae--a staggering 12 more than the common state--while Jueconodon had 28. To try to determine how these animals got their elongated trunks, the paleontologists turned to recent studies in developmental biology, finding that the variation could be attributed to gene mutations that determine the number and shape of the vertebrae in the beginning of the animals' embryotic development. Variation in vertebrae number can be found in modern mammals as well, including in elephants, manatees, and hyraxes.

Imagine the process of distributing electricity to homes from the power grid is like travelers boarding a train.

There are multiple steps to take before they can reach their final destination. First, they have to buy a ticket at the ticketing booth - this is where the power is generated. Then, they board a train that departs from the station - the power is transmitted over distances using transmission lines. Finally, the train takes the travelers (electricity) to their final destination. This final step of sending power to homes and businesses is called the distribution system - and it is critical that it remain reliable.

Chanan Singh and doctoral student Arun Karngala from the Department of Electrical and Computer Engineering at Texas A&M University, are working to develop a reliability framework for the distribution system so that utility companies can be better prepared for uncertainties that may arise. Singh is a Regents Professor, the Irma Runyon Chair Professor and University Distinguished Professor.

By developing these models and methods to perform the analysis of the distribution level of the power grid, adverse effects of localized weather events or equipment failure can potentially be prevented.

The researchers' framework can be also used to test the systemwide impact of installing rooftop solar and energy storage by the customers in the distribution system.

"We found that with 40% of customers installing solar capacity, that amounts to 1.5 times the peak demand of the respective households," Karngala said. "With sufficient energy storage systems, the reliability indices measured significant improvements. For example, the system average interruption frequency index was improved by 50%, the system average interruption duration index was improved by 70% and the customer average interruption duration index was improved by 45%."

Karngala said that this framework can also be used to decide the capacity of solar rooftop installation: "If the installed solar capacity is increased from one time the peak demand to two times the peak demand, the reliability indices show steady improvement. The improvement in indices tapers off after the installed solar capacity is increased more than 2.5 times the peak demand."

Performing reliability studies can help create business cases for purchasing such storage, and ongoing research on storage technologies is helping to provide more affordable and reliable alternatives.

The research team is focused on the analysis and reliability at the distribution level as it is the most vulnerable of all stages of power allocation and therefore can cause the most trouble for customers. Further, unlike high-level sectors of the power grid - such as power generation and transmission - that have existing methods of analysis and procedures to ensure that the reliability will be maintained in the presence of uncertainties at specified levels, the distribution level generally does not have such standards.

Most independent system operators (ISOs) ensure they have enough power generation reserve so that if an unexpected issue arises (e.g., transmission line failure, generator failure, the load being higher than forecasted, etc.) resulting in the total load not being supplied, the load can be adjusted so that it is not lost completely for all customers. Many ISOs use criteria that ensure that, on average, this load curtailment would not occur more than one day in 10 years. Such standards are not typically used at the distribution level.

This work was published in IEEE Transactions on Sustainable Energy in January.

"The winter storm event that happened recently in Texas was of a different nature that spanned the entire state," Singh said. "But extreme weather can be in a variety of forms. For example, you can have tornadoes or hurricanes where the effect is not statewide but instead more limited areas are affected. We believe that in those situations these models and the tools that they will provide to us to manage the system will enhance the reliability of the distribution system because you don't have to rely only on the power that is coming from the grid, but also from other local sources such as solar and perhaps wind."

One challenge that the team is facing is the many different kinds of generating systems being integrated into distribution systems that must be accounted for. Karngala said distribution systems previously were considered the only consumers of energy, but today there are newer technologies and many more distributed energy resources coming into the distribution system such as solar panels, wind generation and storage.

"The exciting part about working on distribution systems is that these are in a phase of change now," Karngala said. "These are changing from traditional systems to much more advanced systems, and we are in that transition phase where we need to develop models and methodologies."

Ultimately, the team is looking to build a comprehensive framework of reliability analysis where approaches such as demand response, price strategies and operational strategies can be included and be expanded upon as the power grid evolves.

"There is no shortage of projects that can be developed around this framework as many models, methods and operational strategies can be included in the reliability evaluation," Karngala said.

STUDY SHOWS PANDEMIC LIMITATIONS ON SURGERIES CAN IMPACT PATIENT CARE

https://www.hopkinsmedicine.org/news/newsroom/news-releases/covid-19-story-tip-study-shows-pandemic-limitations-on-surgeries-can-impact-patient-care

Media Contact: Waun'Shae Blount, wblount1@jhmi.edu

One of the most serious consequences of the current COVID-19 pandemic has been the postponement of non-essential surgeries -- defined by the federal government's Center for Medicare and Medicaid Services (CMS) as "medical procedures that are not necessary to address an emergency or to preserve the health and safety of a patient."

When the CMS issued guidelines in April 2020 for medical centers nationwide to limit non-essential operations until facilities could be declared free of COVID-19, the American Academy of Otolaryngology -- Head and Neck Surgery followed suit, telling its physician members to delay performing non-essential ear, nose and throat surgeries.

What was the impact? That's the question Johns Hopkins Medicine researchers attempted to answer in a recently published study comparing inpatient and outpatient surgical volumes from March 2020 through September 2020 with data from the same timeframe in 2019. A surgical volume is defined as the number of times a hospital has done a specific surgical procedure during a defined time.

A report on the findings appeared February 2020 in JAMA Otolaryngology-Head & Neck Surgery.

To conduct their study, the researchers used the healthcare performance improvement tool called Vizient. Researchers used data from 609 hospitals across the United States. Data were collected for the period March 1, 2019, through Sept. 30, 2020. Hospitals were included if they had a minimum of 20 otolaryngology cases per month pre-COVID and had reported volumes for all months in the study period.

Data came from 174 inpatient and 295 outpatient community facilities. The researchers found that in April 2020, outpatient surgical case volumes dropped to 18% compared to April 2019. Inpatient volumes dropped as well, especially in the Middle Atlantic and parts of the southern US, where volumes fell to 40% of the level in the previous year. Areas most affected corresponded with regions where the pandemic initially hit hardest. These data, the researchers say, might be used to determine how quickly institutions can resume surgeries following a future crisis.

By September 2020, the data showed that outpatient volumes climbed back to 97% and inpatient volumes improved to 99% of pre-pandemic levels. These recoveries over such a short period of time, the researchers say, indicate that providers were diligent about meeting patient care needs even when the country was still at the height of the pandemic.

"As the pandemic continues, we've noted that otolaryngology surgeries are still backlogged and this impacts the health and wellbeing of patients," says C. Matthew Stewart, M.D., Ph.D., associate professor of otolaryngology-head and neck surgery at the Johns Hopkins University School of Medicine and senior author of the study. "To address this, we plan to keep monitoring trends in surgical volumes to develop helpful strategies for reducing or eliminating such backlogs during future pandemics or other crises."

Stewart is available for interviews.

PROFILES OF IMMUNE CELLS SHOW DEFENSE AGAINST COVID-19 MUTANTS SIMILAR TO ORIGINAL VIRUS

https://www.hopkinsmedicine.org/news/newsroom/news-releases/covid-19-story-tip-profiles-of-immune-cells-show-defense-against-covid-19-mutants-similar-to-original-virus

Media Contact: Michael E. Newman, mnewma25@jhmi.edu

In January, an international research team -- led by Johns Hopkins Medicine and in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and ImmunoScape, a U.S.-Singapore biotechnology company -- published one of the most comprehensive profiles to date of T lymphocytes (more commonly known as T cells), the immune system cells that help protect us against SARS-CoV-2, the virus that causes COVID-19. The researchers felt that better defining which T cells interact with which specific portions of the virus could help accelerate the development of next-generation, more effective vaccines.

New variants of SARS-CoV-2 continue to spring up around the world, raising concerns that current vaccines -- designed to induce an immune response by recognizing spike proteins of the pandemic's original virus -- might not provide sufficient defense against a mutated strain. This could potentially make COVID-19 re-infection more likely or vaccination less effective.

To address these concerns, the same researchers who profiled the T cells responding to the original SARS-CoV-2 have done a second study, this time characterizing whether the immune cells also respond to three variant virus strains.

The team's findings, reported March 30 in the journal Open Forum Infectious Diseases, show that the T cells can get the job done.

The latest research used data generated from samples collected for the first study -- blood cells taken from 30 convalescent patients who had recovered from mild to moderate cases of COVID-19. The researchers used the data to assess how likely a specific type of T cell -- known as a CD8+ T cell (commonly called a "killer T cell" for its ability to eliminate cells that are infected with viruses) would recognize the three main SARS-CoV-2 variants that emerged in the past year in the United Kingdom (B.1.1.7), South Africa (B.1.351) and Brazil (B.1.1.248).

CD8+ T cells are covered in protein complexes called T cell receptors (TCRs) that bind to a specific protein fragment, known as an antigen, derived from a foreign body such as a virus. When this binding occurs, the T cell becomes activated and triggers an immune response against the invader. The ability of a specific TCR to recognize its target antigen defines that response.

In the earlier study assessing T cell response to the original SARS-CoV-2 in convalescent patients, the researchers tagged and identified the various types of CD8+ T cells specific for different parts of SARS-CoV-2. This enabled them to determine which of the viral antigens were targeted by the T cells.

Identifying those targeted antigens told the researchers which of the three SARS-CoV-2 variants to examine in the latest study. This time, they wanted to assess whether the genetic mutations associated with the variant strains might affect T cell recognition of the targets.
What they discovered was that the specific CD8+ T cells targets from the original SARS-CoV-2 remained virtually unchanged for all three mutant strains.

This finding is good news, the researchers say, because it suggests that T cell response to these viral targets in the convalescent patients studied -- and most likely, in people who have been fully vaccinated -- will not be greatly affected by the mutations found in the variants.
"Therefore, the vaccines currently being distributed worldwide should offer a reasonable measure of protection from either infection or serious disease caused by the three variant viruses and hopefully, any others that may emerge," says study lead author Andrew Redd, Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine and staff scientist at NIAID.

Redd is available for interviews.

Today, the Muon g-2 Collaboration finally published the highly anticipated first result from its measurement of the anomalous magnetic moment of the muon, a precision quantity that offers physicists one of the most promising means to test predictions of the actual Standard Model of particle physics. The measured value, which is more precise than all values before, strengthens evidence for the emergence of new physics beyond the Standard Model, and thus for the existence of previously unknown particles or forces. The result was presented at an online seminar at Fermilab (FNAL) and published in four scientific articles.

"In 2014, I started working on the Muon g-2 experiment as a postdoctoral researcher at the University of Washington, Seattle," says Prof. Martin Fertl, who has been performing research in the field of low-energy particle physics at the PRISMA+ Cluster of Excellence since 2019. "That's why today's a truly special day. We can now announce a first result, while also stating that this result has opened the door even wider to a previously unknown physics."

The new experimental value published today of the anomalous magnetic moment of the muon is a(FNAL) = 116 592 040(54) x 10^(-11), with a relative uncertainty of 460 parts in a billion. Combined with the result of the experiment at Brookhaven National Laboratory completed more than 20 years ago, the new experimental mean value is a(Exp.,avg) = 116 592 061(41) x 10^(-11). This contrasts with the theoretical predicted value obtained from the Standard Model of
a(Theor.) = 116 591 810(43) x 10^(-11). Physicists classify the difference between these two values as 4.2 standard deviations. In other words, the probability that this discrepancy between experiment and theory is due to chance is 0.0025 percent (1 in 40,000). Physicists consider a discovery - in this case, the refutation of the Standard Model - has been made when the probability is less than 0.00005 percent corresponding to 5 standard deviations.

Numerous contributions from Mainz - both experimental and theoretical

Martin Fertl's PRISMA+ work group is the only one in Germany that is involved in the Muon g-2 Collaboration in an experimental capacity. The collaborations "count
erpart" is the "Muon g-2 Theory Initiative", a worldwide association of more than 130 physicists working on the theoretical prediction within the framework of the Standard Model. The initiative was established in 2017 as a means of joining forces to significantly reduce the uncertainty of the predicted value of the anomalous magnetic moment of the muon. "Just last year, we established a common standard for the first time and agreed on a new theoretical value worldwide," says Prof. Hartmut Wittig, theoretical physicist as well as spokesperson for the PRISMA+ Cluster of Excellence. "Our goal is, in parallel with the experiment, to keep refining the theoretical prediction as well." Physicists at PRISMA+ are making crucial contributions here, from the measurement of experimental input quantities to the high-precision calculation of the contributions of the strong interaction using lattice quantum chromodynamics methods on the MOGON-II supercomputer located in Mainz.

Is the experiment seeing something not predicted by the theory?

The first time a discrepancy - of 3.7 standard deviations - emerged was when the theoretical prediction was compared with the findings of the experiment at the Brookhaven National Laboratory, mentioned above. In the 20 years since then, the aim of research worldwide has been to establish whether this deviation is "real" or "merely" the result of systematic uncertainties in theory and experiment. The current Muon g-2 experiment was developed to measure the magnetic properties of the muon more accurately than ever before. The Muon g-2 Collaboration involves more than 200 scientists from 35 institutions in seven countries.

The muon is the heavy brother of the electron and survives for only a millionth of a fraction of a second. It possesses a magnetic moment, a kind of miniature internal bar magnet. It also possesses a quantum mechanical angular momentum, termed spin, similar to a spinning top. The g-factor is the ratio of the observed strength of the magnet to a simple estimate based on the electric charge, mass, and spin of the muon. The name of the Muon g-2 experiment is based on the fact that the "g" of the muon always deviates slightly - by about 0.1 percent - from the simple prediction that g=2. This anomaly is commonly referred to as the anomalous magnetic moment of the muon (a = (g-2)/2). The Muon g-2 experiment measures the rate of gyration of the "internal compass needle" of muons in a magnetic field, as well as the magnetic field itself, and from this it can determine the anomalous magnetic moment. The muon beam is generated at FNAL`s Muon Campus specifically for the experiment - it has a purity that has never been achieved before.

More than eight billion muons already measured

"Our first analysis, which we are presenting today, already achieves an accuracy that is somewhat better than that of the previous experiment - and we've managed this by evaluating only less than 6 percent of the planned data set," explains Martin Fertl. "As a result, we think our goal of using the Muon g-2 experiment to ultimately improve the accuracy of the value by a factor of four to reach 140 parts per billion seems very realistic."

The data currently being analyzed are from the first round of measurements in 2018 - whereby the Fermilab experiment already collected more data than all prior muon g-factor experiments combined. The second and third rounds are also already "in the can." The third round had to be abruptly cancelled due to the global COVID-19 pandemic, so the fourth round is currently being conducted under tight safety restrictions and, to a large extent, remotely. A fifth round is scheduled to start in autumn 2021.

To ensure the objectivity of the analyses, several analysis teams are working in parallel and independently of one another. The experiment is also using blinding techniques similar to those employed in clinical trials. First, the analysis teams relate the frequencies they measure to a clock whose pace has been slightly altered - and is now running too fast or too slow. A clock on the wall of this kind, for instance, would tick 60 times, but the time elapsed would be slightly more or less than one minute. Only two people beyond the experiment know the factor by which the clock has been adjusted - in the experiment, this corresponds to a particular signal on the frequency measuring devices. Only when the relative results of the individual teams are consistent with each other (known as "relative unblinding") is this factor announced and can then be factored into the calculation. This "absolute unblinding" occurred for the evaluation now being presented at the end of February 2021.

The specialty of Martin Fertl and his working group is extreme precision measurement of the magnetic field in the muon storage ring over the entire measurement period of several years. In his former laboratory, he had already led the development of an array of highly sensitive magnetometers based on the principle of pulsed nuclear magnetic resonance. Several hundred of these measuring heads are installed in the walls of the vacuum chambers surrounding the muons. Another 17 measuring heads remotely circle the storage ring, which has a diameter of 14 meters, to measure the applied magnetic field even more comprehensively. "With the help of further calibration systems, we aim to determine the magnetic field in the muon storage ring with unprecedented accuracy. Only once we understand the magnetic field extremely precisely, and can also measure it, will we be able to determine the anomalous magnetic moment of the muon to the highest degree of precision," says Martin Fertl. "To determine the value to an accuracy of 140 parts per billion - which would be four times more accurate than the previous experiment - we need to be able to measure the magnetic field in which the muons are moving to an accuracy of 70 parts per billion."

As they progressed towards this goal, the researchers encountered some highly interesting and hitherto unknown effects. "We recorded, for instance, small but significant temporal changes in the magnetic field for the first time - and developed special measuring heads to accurately measure this effect. These findings can help us to improve our understanding of the magnetic field and thus to continuously refine our Muon g-2 experiment. This "work in progress" approach will bring us ever closer over the next few years to our ultimate goal of definitively answering the question of whether the anomalous magnetic moment of the muon is the key to a new physics."

JUPITER, FL - People with Crohn's disease are typically treated with powerful anti-inflammatory medications that act throughout their body, not just in their digestive tract, creating the potential for unintended, and often serious, side effects. New research from the lab of Mark Sundrud, PhD, at Scripps Research, Florida suggests a more targeted treatment approach is possible.

Crohn's disease develops from chronic inflammation in the digestive tract, often the small intestine. More than half a million people in the United States live with the disease, which can be debilitating and require repetitive surgeries to remove irreversibly damaged intestinal tissue.

Writing in the journal Nature on April 7, Sundrud's team finds that certain immune cells in the small intestine have evolved a molecular sensing mechanism to protect themselves from the toxic effects of high bile acid concentrations there. This sensory mechanism can be manipulated with small drug-like molecules, they find, and the treatment reduced small bowel inflammation in mice.

"It seems that these immune cells, called T effector cells, have learned how to protect themselves from bile acids," Sundrud says. "These T cells utilize an entire network of genes to interact safely with bile acids in the small intestine. This pathway may malfunction in at least some individuals with Crohn's disease."

Bile acids are made in the liver and released during a meal to help with digestion and absorption of fats and fat-soluble vitamins. They are actively recaptured at the end of the small intestine, in an area called the ileum, where they pass through layers of tissue that contain the body's dense network of intestinal immune cells, and ultimately re-enter the blood stream for return to the liver.

Because they are detergents, bile acids can cause toxicity and inflammation if the system becomes unbalanced. The whole process is kept humming along thanks to an intricate signaling system. Receptors in the nucleus of both liver cells and intestinal barrier cells sense the presence of bile acid and tell the liver to back off on bile acid production if there's too much, or to produce more if there aren't enough to digest a big steak dinner, for example.

Given how damaging bile acids can potentially be to cells, scientists have wondered how immune cells that live in or visit the small intestine tolerate their presence at all. Sundrud's team previously reported that a gene called MDR1, also known as ABCB1, becomes activated when an important subset of immune cells that circulate in blood, called CD4+ T cells, make their way into the small intestine. There, MDR1 acts in transitory T cells to suppress bile acid toxicity and small bowel inflammation.

In the new study, Sundrud's team uses an advanced genetic screening approach to uncover how T cells sense and respond to bile acids in the small intestine to increase MDR1 activity.

"The basic discovery that T cells dedicate so much of their time and energy to preventing bile acid-driven stress and inflammation highlights completely new concepts in how we think about and treat Crohn's disease," Sundrud says. "It's like we've been digging in the wrong spot for treasure, and this work gives us a new map showing where X marks the spot."

The T cells contain a receptor molecule in their nucleus known as CAR, short for constitutive androstane receptor. Acting in the small intestine, CAR promotes expression of MDR1, and also plays a role in activating an essential anti-inflammatory gene, IL-10, the team found.

"When we treated mice with drug-like small molecules that activate CAR, the result was localized detoxification of bile acids and reduction of inflammation," Sundrud says.

Sundrud says exploring the therapeutic potential of CAR activation will require caution and creativity, because CAR is also critical for breaking down and eliminating other substances in the liver, including many medicines.

"Ultimately, the Crohn's disease therapy that emerges from this work could be something that activates CAR locally in small intestinal T cells, or something that targets another gene that is similarly responsible for promoting the safe communication between small intestinal T cells and bile acids," Sundrud says.

Also interesting, the team found that the bile acid-inflammation feedback system worked somewhat differently in the colon in concert with gut microbiome factors. While gut flora had more influence on T cell development and function in the colon, it was the nuclear receptor CAR that had more influence on inflammation in the small intestine.

Inflammation plays both positive and negative roles in the body. It can damage tissue, but it also suppresses cancer growth and fights infections. The current anti-inflammatory treatments shut it down systemically, throughout the entire body. That can have potentially serious consequences, such as lowering resistance to infections or easing off the brake on cancer. Directing treatment for inflammatory diseases only to the affected tissue would be preferable whenever feasible, he says.

"The roughly 50 million people living in the US with some sort of autoimmune or chronic inflammatory disease are all treated the same, medically," Sundrud says. "The holy grail would be to come up with druggable approaches to treat inflammation in only specific tissues and leave the rest of the immune cells in your body untouched, and able to fend of cancer and microbial infections."

Harmful algal blooms (HABs) occur in all 50 U.S. states and many produce toxins that cause illness or death in humans and commercially important species. However, attempts to place a more exact dollar value on the full range of these impacts often vary widely in their methods and level of detail, which hinders understanding of the scale of their socio-economic effects.

In order to improve and harmonize estimates of HABs impacts nationwide, the National Oceanic and Atmospheric Administration (NOAA) National Center for Coastal Ocean Science (NCCOS) and the U.S. National Office for Harmful Algal Blooms at the Woods Hole Oceanographic Institution (WHOI) convened a workshop led by WHOI Oceanographer Emeritus Porter Hoagland and NCCOS Monitoring and Event Response (MERHAB) Program Manager Marc Suddleson. Participants focused on approaches to better assess the socio-economic effects of harmful algal blooms in the marine and freshwater (primarily Great Lakes) ecosystems of the United States. The workshop proceedings report describes the group's objectives, and presents recommendations developed by 40 participants, mostly economists and social scientists from a range of universities, agencies, and U.S. regions. Their recommendations fall under two broad categories: those intended to help establish a socio-economic assessment framework, and those to help create a national agenda for HABs research.

"This has been a goal of the research and response communities for a long time, but coming up with a robust national estimate has been difficult, for a number of reasons, mainly related to the diversity of algal species and the wide variety of ways they can affect how humans use the oceans and freshwater bodies," said Hoagland. "This gives us a strong base on which to build the insight that will vastly improve our estimates."

Framework recommendations call for enhancing interagency coordination; improving research communications and coordination among research networks; integrating socioeconomic assessments into HAB forecasts and observing networks; using open-access databases to establish baselines and identify baseline departures; facilitating rapid response socio-economic studies; improving public health outcome reporting and visibility of HAB-related illnesses; fostering the use of local and traditional ecological knowledge to improve HAB responses; engaging affected communities in citizen science; and engaging graduate students in HAB socio-economic research.

Research agenda recommendations include elements necessary for addressing gaps in our understanding of the social and economic effects of HABs. They include a suggested approach for obtaining an improved national estimate of the economic effects of HABs; supporting rapid ethnographic assessments and in depth assessments of social impacts from HABs; defining socioeconomic impact thresholds for triggering more detailed studies of impacts (such as in the case of designated HAB events of significance); sponsoring research on the value of scientific research leading to improved understanding of bloom ecology; assessing the value of HAB mitigation efforts, such as forecasts, and control approaches and their respective implementation costs; and supporting research to improve HAB risk communication and tracking and to better understand the incidence, severity, and costs of HAB-related human illnesses.

"These recommendations give us a strong series of next steps to increase focus on HAB-related socio-economic research," said Don Anderson, director of the U.S. National Office for Harmful Algal Blooms. "The report is certain to spur increased collaborations that will provide a better understanding of the many complex socio-economic effects of HABs and provide the tools to increase the effectiveness of efforts to minimize impacts on society and the environment."

The detailed final proceedings report and more information about the workshop is available on the U.S. National HAB Office website.

Scientists are testing our fundamental understanding of the universe, and there’s much more to discover.

What do touch screens, radiation therapy and shrink wrap have in common? They were all made possible by particle physics research. Discoveries of how the universe works at the smallest scale often lead to huge advances in technology we use every day.

Scientists from the U.S. Department of Energy’s (DOE) Argonne National Laboratory and Fermi National Accelerator Laboratory, along with collaborators from 46 other institutions and seven countries, are conducting an experiment to put our current understanding of the universe to the test. The first result points to the existence of undiscovered particles or forces. This new physics could help explain long-standing scientific mysteries, and the new insight adds to a storehouse of information that scientists can tap into when modeling our universe and developing new technologies.

“These findings could have major implications for future particle physics experiments and could lead to a stronger grasp on how the universe works.” — Ran Hong, Argonne postdoctoral appointee

The experiment, Muon g-2 (pronounced Muon g minus 2), follows one that began in the ‘90s at DOE’s Brookhaven National Laboratory, in which scientists measured a magnetic property of a fundamental particle called the muon.

The Brookhaven experiment yielded a result that differed from the value predicted by the Standard Model, scientists’ best description of the makeup and behavior of the universe yet. The new experiment is a recreation of Brookhaven’s, built to challenge or affirm the discrepancy with higher precision.

The Standard Model very precisely predicts the muon’s g-factor — a value that tells scientists how this particle behaves in a magnetic field. This g-factor is known to be close to the value two, and the experiments measure their deviation from two, hence the name Muon g-2.

The experiment at Brookhaven indicated that g-2 differed from the theoretical prediction by a few parts per million. This miniscule difference hinted at the existence of unknown interactions between the muon and the magnetic field — interactions that could involve new particles or forces.

The first result from the new experiment strongly agrees with Brookhaven’s, strengthening the evidence that there is new physics to discover. The combined results from Fermilab and Brookhaven show a difference from the Standard Model at a significance of 4.2 sigma (or standard deviations), slightly less than the 5 sigma that scientists require to claim a discovery, but still compelling evidence of new physics. The chance that the results are a statistical fluctuation is about 1 in 40,000.

Particles beyond the Standard Model could help to explain puzzling phenomena in physics, such as the nature of dark matter, a mysterious and pervasive substance that physicists know exists but have yet to detect.

“This is an incredibly exciting result,” said Argonne’s Ran Hong, a postdoctoral appointee who worked on the Muon g-2 experiment for over four years. “These findings could have major implications for future particle physics experiments and could lead to a stronger grasp on how the universe works.”

The Argonne team of scientists contributed significantly to the success of the experiment. The original team, assembled and led by physicist Peter Winter, included Argonne’s Hong and Simon Corrodi, as well as Suvarna Ramachandran and Joe Grange, who have since left Argonne.

“This team has an impressive and unique skill set with high expertise regarding hardware, operational planning and data analysis,” said Winter, who leads the Muon g-2 contributions from Argonne. “They made vital contributions to the experiment, and we could not have obtained these results without their work.”

To derive the muon’s true g-2, the scientists at Fermilab produce beams of muons that travel in a circle through a large, hollow ring in the presence of a strong magnetic field. This field keeps the muons in the ring and causes the direction of a muon’s spin to rotate. The rotation, which scientists call precession, is similar to the rotation of earth’s axis, only much, much faster.

To calculate g-2 to the desired precision, the scientists need to measure two values with very high certainty. One is the rate of the muon’s spin precession as it traverses the ring. The other is the strength of the magnetic field surrounding the muon, which influences its precession. That’s where Argonne comes in.

Field trip

Although the muons travel through an impressively constant magnetic field, ambient temperature changes and effects from the experiment’s hardware cause slight variations throughout the ring. Even these small shifts in field strength, if not accounted for, can significantly impact the accuracy of the g-2 calculation.

In order to correct for the field variations, the scientists constantly measure the drifting field using hundreds of probes mounted to the walls of the ring. In addition, they send a trolley around the ring every three days to measure the field strength where the muon beam actually passes through. Mounted on the trolley are probes that map out the magnetic field with incredibly high precision throughout the ring’s 45-meter circumference.

To reach the ultimate uncertainty goal of less than 70 parts per billion (around 2.5 times better than the field measurement in the previous experiment), Argonne scientists refurbished the trolley system used in the Brookhaven experiment with advanced communication abilities and new, ultraprecise magnetic field probes developed by the University of Washington.

The trolley goes around the ring in both directions, taking around 9,000 measurements per probe and direction. The scientists use the measurements to reconstruct slices of the magnetic field and then derive a full, 3D map of the field in the ring. Field values at points on the map go into the g-2 calculation for muons passing through those locations. The better the field measurements, the more meaningful the final result.

The scientists also converted some of the analog signals used in the old experiment into digital signals to increase the amount of data they could obtain from the probes. This required complex engineering of the trolley’s communications system to minimize disturbances to the sensitive probing mechanisms.

“It was quite challenging to make the trolley operate smoothly and safely. It required the control system to handle routine operations but also identify emergencies and react appropriately,” said Hong, whose background in both scientific research and engineering was crucial for designing the trolley to operate with limited disruption to the experiment.

The team plans to upgrade the trolley system for the next data taking period to further improve the measurements by reducing the uncertainty bit by bit.

Fine tuning

In precision experiments like Muon g-2, the main objective is to reduce any systematic uncertainty or error that could affect the measurements.

“Measuring the raw numbers is relatively easy — figuring out how well we know the numbers is the real challenge,” said Corrodi, a postdoctoral appointee in Argonne’s High Energy Physics division (HEP).

To ensure the accuracy of the magnetic field measurements, the scientists calibrated the probes using Argonne’s 4-Tesla Solenoid Facility, which houses a magnet from a former magnetic resonance imaging (MRI) scanner. The magnet produces a uniform and stable magnetic field with over 400 times the strength of a refrigerator magnet.

Argonne scientists calibrated the probes in the trolley against readings from a probe that was designed and tested inside the solenoid magnet. This process ensures the probes each read the same measurement when in the same magnetic field and enables the scientists to make accurate corrections. The test facility allowed the scientists to achieve field measurements down to several parts per billion — like measuring the volume of water in a swimming pool down to the drop.

“In addition to calibrating the probes, we improved the field measurements by adjusting operation settings on the fly,” said Corrodi, “During data analysis, we found some effects we did not expect.”

When Corrodi and team saw glitches in the data, they investigated the system to pinpoint the cause. For example, certain devices in the ring focus the muon beam to keep it centered. These devices, however, slightly disrupt the magnetic field in the ring. The scientists designed a way to measure this effect in order to remove it from the analysis.

To view related video, click here.

Putting it all together

The journey of the magnetic field data from probe to computer is complex. Corrodi, Hong and others configured the hardware and software to read the data from the field probes with the correct time and location stamps. They also had to make sense of the data, which start out in binary code, in order to integrate them with the common analysis framework for the experiment.

“We had to convert the raw data into something we could work with,” said Hong, “and we were in charge of the data quality control, determining what flawed data to discard in the ultimate g-2 analysis.”

Corrodi will lead the analysis team for the magnetic field, resolving conflicts with equipment and making sure the various teams in the experiment converge on the next result, said Winter. “You really need to understand the entire field analysis in order to reach our scientific goals.”

The future of muon experiments

The first thing the scientists plan to do is to double-check the results.

“So far, the precision of the ultimate g-2 measurement is comparable to that of the Brookhaven experiment, but that is dominated by the fact that the data are limited so far,” said Corrodi. “We have only analyzed 6% of the data we plan to take over the entire experiment. Those added data will reduce the uncertainty significantly.”

The first result is also encouraging to scientists conducting other present and planned muon experiments, including a future g-2 experiment that will be conducted in Japan, and the next muon experiment at Fermilab — the Mu2e experiment. These projects are already using Argonne’s Solenoid Facility to cross-calibrate their magnetic field probes with the ones used at Fermilab.

“There could be a renewed effort to look for muons at the Large Hadron Collider, searching for possible hints of the new physics behind the g-2 value,” said Carlos Wagner, a theoretical physicist in Argonne’s HEP, who works to try to explain these phenomena. “There could also be renewed interest in the construction of a muon collider, which could provide a direct way of checking this new physics.”

Once scientists get a handle on this new physics, it may be able to inform cosmological and quantum mechanical models, or even help scientists to invent new technologies down the road — the next shrink wrap, perhaps.

Published in the Proceedings of National Academy of Sciences, researchers in the Climate Intervention Biology Working Group -- including Jessica Hellmann from the University of Minnesota Institute on the Environment -- explored the effect of solar climate interventions on ecology.

Composed of climate scientists and ecologists from leading research universities internationally, the team found that more research is needed to understand the ecological impacts of solar radiation modification (SRM) technologies that reflect small amounts of sunlight back into space. The team focused on a specific proposed SRM strategy -- referred to as stratospheric aerosol intervention (SAI)) -- to create a sulfate aerosol cloud in the stratosphere to reduce a portion of incoming sunlight and radiation. In theory, this cloud could be controlled in size and location.

SAI is like placing tiny reflective particles in the atmosphere to bounce a portion of the solar radiation back to space, so that some of the radiation does not reach -- and warm -- Earth.

The team emphasizes that greenhouse gas emissions reduction and conservation of biodiversity and ecosystem functions must be the priority.

"We are just starting to consider the risks and benefits of geoengineering, and it's critical that we include ecosystems in cost-benefit studies", said Hellmann, director at the U of M Institute on the Environment. "We should only pursue geoengineering if its benefits strongly outweigh its downsides. Because our efforts to stem climate change are modest and slow, the case for considering geoengineering is growing, and this paper represents the ecologists chiming in to the geoengineering conversation."

The complexity of cascading relationships between ecosystems and climate under SAI -- in combination with the timing, amount, length and termination of SAI scenarios -- means that SAI is not a simple thermostat that turns down the heat a couple of degrees. Other potential effects of SAI include shifts in rainfall and increases in surface UV rays. While SAI might cool an overheated Earth, it would not be able to counter all of the effects of rising atmospheric CO2, such as halting ocean acidification.

"When we approach complex questions like these, there is a broad scale, theoretical understanding of the inherent patterns of biodiversity across the surface of Earth, but this understanding is often informed by finer-scale experiments that test the biological and physical mechanisms underlying those patterns," said Phoebe Zarnetske, study co-lead and an associate professor in Michigan State University's Department of Integrative Biology and the Ecology, Evolution, and Behavior program.

"I hope the paper can convince ecologists that research about nature's responses to solar geoengineering is not just important, but also interesting -- touching on core ecological questions about topics as varied as photosynthesis and animal migration," said U of M alum Shan Kothari, who contributed to the study during his time at the College of Biological Sciences before going to the University of Montreal.

Kothari said that an example of how other scientists can consider the study's findings is to contemplate the unique conditions resulting from solar geoengineering scenarios that may aid or impede the ability for ecosystems to store carbon. He added that such research could help the international community consider solar geoengineering with a stronger awareness of the potential risks and benefits involved.

BIRMINGHAM, Ala. - Race associates with the risk of death from end-stage heart failure. So, identifying the molecular determinants of that risk may help the pursuit of the novel diagnosis and prognosis of heart failure, and its therapy.

A University of Alabama at Birmingham study of end-stage heart-failure patients has found that cytosine-p-guanine, or CpG, methylation of the DNA in the heart has a bimodal distribution among the patients, and that race -- African American versus Caucasian -- was the sole variable in patient records that explained the difference. A subsequent look at the census tracts where the patients lived showed that the African American subjects lived in neighborhoods with more racial diversity and poverty, suggesting that the underlying variable may be a socioeconomic difference.

Methylation of DNA is a form of epigenetics, an indirect method of gene regulation that can change with gene-environment interaction. Previously the Wende laboratory has shown that these DNA modifications differentiate ischemic and non-ischemic heart failure.

The current UAB study included a pilot cohort of 11 heart-failure patients, followed by a testing cohort of 31 heart-failure patients, all of them male. The heart muscle tissue for the study was obtained when patients underwent surgery to install a left ventricular assist device, or LVAD -- a small mechanical pump carried outside the body that helps a weakened heart pump blood. During the surgery, a piece of the left ventricle is excised; it is otherwise discarded but could be used for this study.

Heretofore, epigenetics has been an underexplored source of heterogeneity among patients with end-stage heart failure. The UAB researchers found differential promoter hyper-methylation of genes involved in fatty acid metabolism among African American heart muscle samples, relative to Caucasian samples, and also higher expression of lipogenesis genes. Such metabolic perturbations are a pathological hallmark of end-stage heart failure, as the heart gets more of its energy from glycolysis -- that is from glucose sugar -- as it fails.

This finding generated two hypotheses, says Adam R. Wende, Ph.D., the associate professor in the UAB Department of Pathology who led the study: 1) that the epigenetic remodeling of cardiac gene regulation determines the therapeutic potential of LVADs, and 2) that epigenetic reprogramming of cardiac gene regulation constitutes a mechanism that may influence responsiveness to LVAD-induced cardiac unloading, meaning possible improvement of the heart as the pump takes over part of the work.

In contrast to the hyper-methylated promoters, the genes that had differentially hypo-methylated promoters, or lower levels of methylation, in African American hearts disproportionately represented inflammatory signaling cascades.

Additionally, the UAB researchers did a retrospective analysis of deaths from any cause in the 31 testing cohort patients two years after heart pump implantation. African Americans had a significantly higher rate of death, eight of 15 patients, versus Caucasians, two of 14.

The need for better treatment of heart failure is great. Only half of heart-failure patients respond to medical management, and African Americans experience worse clinical outcomes than any United States race or ethnicity.

"African Americans with heart failure are hospitalized at a rate 2.5-times higher than other races or ethnicities," Wende said. "Furthermore, despite a threefold higher mortality from heart-failure complications, the prevalence of heart failure among African Americans continues to increase."

"It is estimated that 3.6 percent of this community will live with heart failure by 2030, exceeding the predicted prevalence of any other race or ethnicity in America," Wende said. "Therefore, it is paramount to identify and address the issues that underly these disturbing racial differences in heart-failure morbidity and mortality."

The UAB researchers noted the limitation that this was a single-center study; but Wende said, "Nevertheless, we provide preliminary evidence that socioeconomic factors are likely associated with racial differences in cardiac DNA methylation among men with end-stage heart failure."

More than 20 years after the discovery of the parkin gene linked to young-onset Parkinson's disease, researchers at The Ottawa Hospital and the University of Ottawa may have finally figured out how this mysterious gene protects the brain.

Using human and mouse brain samples and engineered cells, they found that the parkin protein works in two ways. First, it acts like a powerful antioxidant that disarms potentially harmful oxidants in the brain, including dopamine radicals. Second, as the brain ages and dopamine radicals continue to build up, parkin sequesters these harmful molecules in a special storage site within vulnerable nerve cells, so they can continue to function normally throughout our lifespan.

In people with mutations in both copies of the parkin gene, these protective effects are missing, and as a result Parkinson's develops before the age of 40 years. If confirmed, the results could point the way towards the development of new treatments.

"If we could deliver antioxidants or a healthy copy of the parkin gene into the brains of people with these mutations, this could help slow down or even halt early-onset Parkinson's," said co-corresponding author and scientific project manager Dr. Julianna Tomlinson.

"What we don't know yet is whether such an approach could also benefit individuals with late-onset Parkinson's that is not linked to the parkin gene," added co-corresponding author Dr. Michael Schlossmacher, neurologist and Director of Neuroscience at The Ottawa Hospital. "We are eager to investigate this."

With a lethal, airborne virus spreading fast, hospitals had to change how they treated patients and policies for how caregivers provided that treatment. But for maternity patients and nurses some of those changes had negative outcomes, according to a new University of Washington study.

"We found that visitor restrictions and separation policies were harming families and nurses. The effects for patients included loneliness, isolation and mistrust, while nurses described mistrust and low morale," said Molly Altman, lead author of the study and assistant professor in the UW School of Nursing.

Importantly, Altman added, both nurses and patients described how COVID "amplified existing racially biased and disrespectful care experiences for Black women and birthing people, in part due to loss of protection and advocacy that support people provide."

The study, published March 31 in Global Qualitative Nursing Research, involved in-depth interviews with 15 patients from Washington state and 14 nurses from Washington, New York, Georgia and Michigan. Nearly half of participants in both groups self-identified as BIPOC and for slightly more than half this was their first birth.

Under COVID-19 restrictions, patients experienced a shift from in-person visits, a source of social and emotional support, to virtual conversations or telehealth and more perfunctory exchanges in offices with physical distancing. Pregnancy education and group classes all moved online, while family and friends were excluded from patient care when in the hospital or clinic. Meanwhile, nurses experienced shifting policies and procedures that led to a collective mistrust of management and administration.

In the interviews, researchers wrote, patient responses focused on how hospital adaptations "were inadequate to meet their needs" and, in addition to mistrust, nurse responses focused on how inconsistencies in policies and policy implementation affected their ability to "safely care for patients."

Here are a few verbatim transcriptions of statements patients gave researchers (with minor edits):

About telehealth ...

I want to be able to actually have a check-in and actually have a doctor be able to check everything's fine and make sure the baby's heartbeat is still okay or see how my uterus is measuring and things like that that are more concrete. ... I see the phone conversation just more being like, "Is everything okay," and me saying "Yes" and then that kind of being it.

Communication with providers ...

We don't talk about how this is affecting us or what it means for the future. It's just they leave you hanging like, "Okay, well I'm guessing everything's okay so I'm just going to walk on out of here." But if you could just say something nice, concise and brief but meaty it would be perfect.

Education and nursing support ...

I lost ... the classes that we were supposed to need. I was so excited to join those classes because I could get a chance to meet with other mothers that we may build connections, right? But because of COVID we just don't have the chance of doing that.

People were there [in labor] to support me and to make sure I was okay and then I felt like postpartum everyone disappeared.

Racial bias ...

Being [a person] of color, you already kind of deal with the standoffish approach from certain people and so like ... the virus kind of gives [them] that reason to, it's just like that. It's like even though I already feel this way, now I have a reason to act this way.

I'm an educated Black woman. I'm a nurse. I know what's going on with my body and I know how this stuff works and I still feel like so inferior, like to my [birth] team. That's crazy to me.

Following are a few verbatim transcriptions of statements nurses gave researchers (with minor edits):

Lack of planning ...

I was disappointed to see that in the, at least a month, more like six weeks since we'd had just the one COVID patient, that not a lot had been done to prepare in the meantime, both on a national scale and just at our hospital.

Policy changes ...

I felt like at times on my shift, policies would change literally every 15 to 30 minutes. You do something one way and you get an email within the hour that this now has changed and we're doing this procedure this way and it was just constant like nobody knows what they're doing so it was very stressful.

Morale problems ...

I'm just doing everything for this patient and then I'm not thinking about my own family. Even if I [say] let whatever happen to me ... I have responsibilities for my family too. I'm not just a nurse, right? I'm a mother. When I took the oath to be a nurse, before that maybe I took an oath to be a good mother.

[a patient complained and] that stung because I remember going to my manager's room that day and asking for more supplies so that I could go into the room more frequently without having to break the gowns and reuse the gowns and she said, "You use what you have and I'm not giving you anything else."

Racial bias ...

[obstetrical resident physician] went in to go talk to [a patient] about the need for induction and instead of including the father in the conversation or even introducing herself, she went in, completely turned her back on the dad ... I've been there 10 years and I have never seen that with any Caucasian couple.

"We need to really center the voices and experiences of marginalized people, especially BIPOC, in policy. We need to ensure that communication is transparent and that we are trustworthy to the groups we develop policies for -- patients, nurses, the public, everyone," said Meghan Eagen-Torkko, study co-author and assistant professor in UW Bothell School of Nursing and Health Studies. "We have to stop thinking of policy as a top-down process, because Covid has shown us quite clearly that this doesn't work."

How many species of birds are there in the world? It depends on whose count you go by. The number could be as low as 10,000 or as high as 18,000. It's tough to standardize lists of species because the concept of a "species" itself is a little bit fuzzy.

That matters because conserving biodiversity requires knowing what diversity exists in the first place. So biologists, led by University of Utah doctoral candidate Monte Neate-Clegg of the School of Biological Sciences, set out to compare four main lists of bird species worldwide to find out how the lists differ--and why. They found that although the lists agree on most birds, disagreements in some regions of the world could mean that some species are missed by conservation ecologists.

"Species are more than just a name," Neate-Clegg says. "They are functional units in complex ecosystems that need to be preserved. We need to recognize true diversity in order to conserve it."

The results are published in Global Ecology and Biogeography.

On the origin of species

The definition of a species isn't clear-cut. Some scientists define populations as different species if they're reproductively isolated from each other and unable to interbreed. Others use physical features to delineate species, while yet others use genetics. Using the genetic definition produces many more species, but regardless of the method, gray areas persist.

"Species are fuzzy because speciation as a process is fuzzy," Neate-Clegg says. "It's a gradual process so it's very difficult to draw a line and say 'this is two species' vs. 'this is one species.'"

Also, he says, physical features and genetic signatures don't always diverge on the same timescale. "For example," he says, "two bird populations may diverge in song and appearance before genetic divergence; conversely, identical populations on different islands may be separated genetically by millions of years."

Comparing the lists

At this point in the story, it's time to introduce four lists, each of which purports to include all the bird species in the world. They are:

The Howard and Moore Checklist of the Birds of the World
The eBird/Clements Checklist of Birds of the World
The BirdLife International Checklist of the Birds of the World
The International Ornithological Community (IOC) World Bird List

"Being active field ornithologists who are always trying to ID bird species means that one is always faced with the issue of some species being on one list but not the other," says Çağan Şekercioğlu, associate professor in the School of Biological Sciences. "So our field experience very much primed us to think about this question and inspired us to write this paper."

The lists have different strengths depending on their application. The BirdLife International list, for example, integrates with the IUCN Red List, which reports on species' conservation status. The IOC list is updated by experts twice a year, Şekercioğlu says. The list is open access with comparisons to other major lists, and changes are documented transparently.

"But as a birdwatcher, I use eBird all the time, which uses the Clements checklist, and that dataset is very powerful in its own right," Neate-Clegg says. "So there is no single best option."

One example of the disagreement between lists might be the common bird Colaptes auratus. The eBird list calls it the northern flicker, a woodpecker. But the BirdLife International list delineates the eastern population as the yellow-shafted flicker and the western population as the red-shafted flicker.

In 2020, Neate-Clegg and his colleagues read a study that compared the raptor species on each list, finding that only 68% of species were consistent among all four lists.

"We thought it would be interesting to investigate taxonomic agreement for all 11,000 bird species," Neate-Clegg says. "More importantly, we wanted to try and work out what species characteristics led to more or less taxonomic confusion."

They began by collecting the most recent version of each list (the IOC checklist is updated biannually, the researchers write, and the Clements and BirdLife lists annually, while Howard and Moore has not been updated since 2014) and trimming them down to exclude subspecies and any extinct species. Using a few other data processing rules, they assigned a single name to every possible species across all four lists. Then the comparisons began.

Where the lists agree and disagree

The researchers found that the four lists agreed on the vast majority of bird species--89.5%. For the remaining 10.5%, then, they started to look for patterns that might explain the disagreement. Some of it was likely geographical. Birds from the well-studied Northern Hemisphere were more likely to find agreement than birds from the relatively understudied Southeast Asia and the Southern Ocean.

Some of it was habitat-based. Agreement was higher for large, migratory species in relatively open habitats.

"I think the most surprising result was that agreement was not lower for highly forest-dependent species," Neate-Clegg says. "We expected these denizens of the rainforest floor to be the most cryptic and hard to study, with more uncertainty on their taxonomic relationships. Yet we found it was actually species of intermediate forest dependency that had lower taxonomic agreement. We believe that these species move about just enough to diverge, but not so much that their gene pools are constantly mixing."

And part of the issue with species classification on isolated islands, such as those in Southeast Asia and the Southern Ocean, was a phenomenon called "cryptic diversification." Although islands can foster species diversification because of their isolation, sometimes two populations on different islands can appear very similar, even though their genes suggest that they've been isolated from each other for millions of years. So, depending on the definition, two populations could count as two species or as only one.

"In addition," Neate-Clegg says, "it's very hard to test the traditional biological species concept on island fauna because we cannot know whether two populations can interbreed to produce fertile young if they are geographically isolated."

Why it matters

So what if some people disagree on species designations? Conservation actions are usually on the species level, Neate-Clegg says.

"If a population on one island goes extinct, people may care less if it's 'just a subspecies,'" he says. "And yet that island is potentially losing a functionally unique population. If it was recognized as a full species it might not have been lost."

Neate-Clegg hopes the study points ornithologists towards the groups of species that merit additional attention.

"We also want conservation biologists to recognize that cryptic diversity may be overlooked," he adds, "and that we should consider units of conservation above and below the species level."

A new analysis of lung epithelial cells from COVID-19 patients reveals how the protective complement branch of the immune system, which usually plays roles in both innate and adaptive immunity, can convert to a harmful system during COVID-19. Blocking excessive complement activity in lung epithelial cells with a combination of existing chemotherapy and antiviral medications - ruxolitinib and remdesivir, respectively - helped normalize the production of complement proteins by infected lung epithelial cells in human cell culture experiments, the researchers found. Thus, the drug duo could serve as a promising strategy to treat damaging inflammation during severe COVID-19, the authors say. Overactivation of complement proteins can contribute to diseases such as acute respiratory distress syndrome, and increasing evidence suggests that excessive complement responses also correlate with disease severity in patients with severe COVID-19. However, it remains unclear what rewires this normally protective system into a dangerous one during severe COVID-19. To dig into this question, Bingyu Yan and colleagues analyzed bulk and single cell RNA-sequencing data from blood and lung tissues of patients with COVID-19 and compared them with those from healthy controls. In COVID-19 patients, the complement system was one of the most highly induced pathways in lung epithelial cells infected by SARS-CoV-2, as indicated by the high expression of genes that control expression and activation of complement protein C3. Further analyses showed that the IFN-JAK1/2-STAT1 inflammatory pathway and NF-κB transcription factor were highly involved in the transcription of complement genes in infected lung epithelial cells. Blocking these pathways using the cancer chemotherapy drug ruxolitinib helped normalize expression of complement and IFN-controlling genes in human lung epithelial cell lines. Combining ruxolitinib with the antiviral drug remdesivir additionally blocked NF-κB activity, inhibiting overproduction of C3a by infected cells and further normalizing the transcription and production of complement protein fragments. This heightened understanding of the complement system's contribution to COVID-19 could drive the discovery of much-needed treatments, the authors say.

WYOMISSING, Pa. -- Teaching people to become entrepreneurs requires more than just passing on entrepreneurial skills, according to a team of Penn State Berks-led researchers. Would-be entrepreneurs also need to understand -- and negotiate -- the barriers that they might face.

In a study, researchers built a multidimensional model to measure the effectiveness of entrepreneurship education. The model not only includes teaching entrepreneurial skills, but also addresses the students' intentions to start a business and their perceptions of the barriers they might encounter when starting a business.

"There are a lot of studies in the literature that focus on, for example, how entrepreneurship education influences the students' competence in starting a business," said Abdullah Konak, professor of information sciences and technology. "But, our model does not look at it from one perspective. We look at it from three perspectives -- competencies, intentions and barriers. What we found was that entrepreneurship education helps to increase the students' skills. If those skills help to reduce the barriers, then it increases their intentions to start a business."

Traditionally, much of entrepreneurship education offers students lessons to develop skills, for example, offering them an understanding of finance, marketing, intellectual property and team management, Konak added. However, the acquisition of these skills may not directly lead people to start businesses.

"There are a lot of reasons why people don't want to become entrepreneurs, but one of those reasons is that they see barriers," said Konak, who is also an Institute for Computational and Data Sciences associate. "Maybe they're not sure on how to start a business, maybe they're worried it will take too much time, maybe they think they don't know the domain well enough -- there are a lot of issues."

According to the researchers, who report their findings in a recent issue of Studies in Educational Evaluation, lessons can be designed so that they not only teach entrepreneurial skills, but also show that barriers may not be as daunting as the students believe.

"For example, take a simple step, like registering a business," said Konak. "One lesson we use is to have the students go to a government website and search for company names and whether the business they are visualizing is registered. Then, the students learn the steps of what it takes to register a business in Pennsylvania. This is a very simple assignment, but I think it helps them remove a barrier."

Entrepreneurism helps the economy in several ways, said Konak, who worked with Haibin Liu, associate professor at the Institute of Employment and Entrepreneurship Education at Northeast Normal University, who was also the paper's first author, and Sadan Kulturel-Konak, professor of management information systems and the director of Flemming Creativity, Entrepreneurship and Economic Development (CEED) Center at Penn State Berks. Liu visited Penn State Berks between 2018 and 2020 to collaborate with Kulturel-Konak and Konak on entrepreneurship education.

First, entrepreneurism drives economic development and growth, he said.

"There is a real strong connection between well-being of people, economic growth and entrepreneurial activity," said Konak. "Entrepreneurial activity is how we grow the economy -- not just in the U.S., but globally. A lot of people might think of entrepreneurism as just a money-making activity, but it's actually about growing the entire pie for everyone."

He added that entrepreneurship education can also help established businesses by training employees to become more innovative workers.

"Our goal in entrepreneurship education is not just about starting up businesses, but it's actually about instilling an innovative mindset in our students," Konak said. "That's the broader goal of entrepreneurship education."

The researchers collected data from 416 college students at two different campuses of a major Chinese university located in China. The students were business, engineering and social sciences undergraduate students who participated in a four-month entrepreneurship education program. The participants were asked a series of questions about their participation in entrepreneurship education programs, their intentions to become an entrepreneur and their understanding of entrepreneurial barriers.

Penn State Berks has a long history of entrepreneurship studies, said Konak. The Flemming Creativity, Entrepreneurship, and Economic Development Center (CEED) Center, for example, was established in the fall of 2011 to inspire an entrepreneurial spirit and innovative thinking in the Penn State Berks local community.

In the future, the team plans to continue to develop and refine these models of entrepreneurship education.