Culture

A new study (the ATOMIC2 trial), presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) and published simultaneously in The Lancet Respiratory Medicine, shows the antimicrobial drug azithromycin - already approved for use in multiple infections - does not prevent mild COVID-19 cases progressing to hospitalisation or death.

The study, by Dr Timothy Hinks, John Radcliffe Hospital and University of Oxford, UK, and colleagues, shows that azithromycin should not be used as a treatment for COVID-19 and all countries must stop using it for this purpose, to prevent resistance developing to azithromycin in other infections.

The SARS-CoV-2 pandemic has not only started a rush to develop new treatments, but also investigations of already approved drugs to determine if they too can be used to treat COVID-19. Azithromycin is an antibiotic used to treat serious chest infections including pneumonias and drug-resistant tuberculosis, trachoma - a common preventable cause of blindness - sinus infections, Lyme disease, skin infections and some sexually transmitted infections such as chlamydia.

The antibacterial, anti-inflammatory and antiviral properties of azithromycin suggested it could have therapeutic potential against COVID-19. However, there is a lack of data from randomised controlled trials of azithromycin to treat mild-to-moderate COVID-19 disease. In this study, the authors assessed whether azithromycin is effective in reducing hospitalisation in patients with mild-to-moderate COVID-19. These were people with COVID-19 symptoms sufficiently severe to prompt them to seek hospital assessment, but not severe enough, initially, to require admission for oxygen therapy.

This randomised clinical trial at 19 centres in the UK enrolled adults aged 18 years and older, presenting to hospitals with clinically-diagnosed highly-probable or confirmed COVID-19 infection, with less than 14 days of symptoms, considered suitable for initial hospital assessment then treatment and/or observation at home. Patients were randomised (1:1) to azithromycin (500 mg daily orally for 14 days) or to observation at home only. The primary outcome was the difference in proportion of participants with death or hospital admission from any cause over the following 28 days.

A total of 298 participants were enrolled from June 2020 to January 2021 and 292 were included in the final analysis. The authors found no difference between the azithromycin and control groups in the risk of COVID-19 progressing to hospitalisation or death.

They explain that, in contrast to other studies the high dose of azithromycin in this new study (500 mg daily) and long duration (14 days) was selected to ensure that the trial adequately assessed potential antiviral, antibacterial and anti-inflammatory benefits. COVID-19 is considered to have a distinct early "viraemic" phase with a high viral load and a late inflammatory phase in some individuals, and therefore assessment of antiviral activity needed to be early in the disease course prior to onset of severe disease.

At the same time, it was not known what doses might be required to produce an adequate anti-inflammatory effect and so it was necessary to give a high dose of long duration to ensure the anti-inflammatory effect was tested throughout the late stage of innate/ acute phase of inflammatory cytokine dysregulation (known as the cytokine storm, which overwhelms the immune system of affected individuals and is often fatal).

The authors say: "In this trial of people with clinically-diagnosed mild-moderate COVID-19 managed without hospital admission, adding azithromycin to standard care treatment did not reduce the risk of subsequent hospitalisation or death, or of time to hospitalisation... this finding, taken together with clear negative results from other studies across the disease course from early, low risk patients, to severe hospitalised disease, provides strong confirmation that azithromycin is not effective in treating COVID-19. It is essential that clinicians worldwide stop using this medication as a treatment for COVID-19. We now know it is not effective against COVID-19 and we need urgently to protect against the very real threat of driving drug resistance to this precious class of antibiotics."

For interviews with the report authors, please contact Dr Waasila Jassat, National Institute for Communicable Diseases of the National Health Laboratory Service, South Africa E) waasilaj@nicd.ac.za T) +27(0)82 927 4138

Alternative contact in the ECCMID Press Room: Tony Kirby T) + 44(0)7834 385827 E) tony@tonykirby.com or Rachael Davies T) +44(0)797 456 0784 E) rachaelvdavies@hotmail.co.uk

Notes to editors:

[1] Wave 1: (14721 deaths/59617625 SA population)*100,000 = 24.7 deaths per 100,000 people
Wave 2: (28682 deaths/59617625 SA population)*100,000 = 48.1 deaths per 100,000 people

[2] Coronavirus deaths by country in Africa 2021 | Statista / South Africa | UNAIDS
https://www.statista.com/statistics/1170530/coronavirus-deaths-in-africa/

[3] See table 1; weeks with very high admissions; 27,949 deaths among 104,058 patients with outcomes (case fatality risk 26.9%). Weeks with low admissions; 8,985 deaths among 50,840 patients with outcomes (case fatality risk 17.7%).

The surveillance was funded by the National Institute for Communicable Diseases and the South African Government. The study did not receive any additional funding.

The authors declare no conflicts of interest.

The Lancet Global Health: Difference in mortality among individuals admitted to hospital with COVID-19 during the first and second waves in South Africa: a cohort study

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The Lancet Global Health

Although Covid-19 affects men and women differently, the large majority of current clinical studies of SARS-CoV-2 and COVID-19 makes no mention of sex/gender. Indeed, only a fraction, 4 percent, explicitly plan to address sex and gender in their analysis, concludes a new analysis of nearly 4,500 studies. 21 percent only take this variable into account when selecting participants while 5.4 % go as far as planning to have sex-matched or representative subgroups and samples. The article is published in Nature Communications.

During the corona pandemic, differences can be observed between men and women. Men are more vulnerable to a severe course of COVID-19; more men are hospitalized, and more men die from the effects of the virus. Why that is, we do not know exactly yet, but the consequence of the difference may be that men and women might need different therapies. At the same time, gender is connected to the risk of infection, for example because women more commonly are employed in positions with client or customer contact, or as care-givers, increasing the risk of exposure. This calls for attention to both dimensions in the conduction of clinical trials and planning public health measures.

Still, only a minority of 4,420 registered clinical studies on COVID-19 mention sex/gender in the study registration, a new analysis published in Nature Communications shows. The study is conducted by researchers at Nijmegen's Radboud University Medical Center, Aarhus University, University of Copenhagen and University of Bielefeld.

According to the last author of the article, Sabine Oertelt-Prigione from Radboud University and at the Medical School of the University of Bielefeld, the lacking consideration of sex and gender is problematic: "We have seen from the beginning that the disease does not have an identical course for women and men. The differences in rates of hospitalization and death point to this. This means that our care, such as medicines or other interventions, could also have a different outcome depending on whether the patient is a woman or a man."

Only 4 percent of studies registered plan to explicitly include sex as a variable in their analysis

The researchers looked at 4,420 COVID-19 studies registered with ClinicalTrials.gov, a U.S. database of more than 300,000 studies from 200 countries. In the COVID-19 sample, 1,659 were observational studies, and 2,475 were intervention studies.

Of these 4,420 registered studies, 935 (21.2%) explicitly addressed sex/gender solely as a recruitment criterion and only 178 (4%) mentioned sex/gender as a planned analytical variable. A further 237 (5.4%) planned sex-matched or representative samples (65) or emphasized sex/gender reporting (172). 124 studies (2.8%) focused solely on one sex, with 100 recruiting only female participants and 24 only male ones. Female-only studies mostly focused on the relation between COVID-19 and pregnancy outcomes.

Research under time pressure

A reason for not including data on sex and gender may be that the studies are conducted under high time pressure. Sabine Oertelt-Prigione: "Researchers are sometimes worried that analyzing sex differences in a study might mean more participants and longer recruitment times to reach their targets. Especially in the early phases of the pandemic, they were working under lots of time pressure ".

Emer Brady, first author of the study and working at the Danish Center for Studies in Research and Research Policy at Aarhus University supplements with: "On the subject of time pressures, we did hope that as the pandemic wore on and more awareness was raised about the sex and gender disparities we would see more of a focus on sex and gender in the study protocols being registered on ClinicalTrials.gov, but that turned out not to be the case. We also looked at the published trials, where the attention to sex and gender was higher, but still only one in four trials accounted for or reported sex or gender in their analyses."

Oertelt-Prigione emphasizes the importance of sex and genders role in clinical research: "We increasingly see that men and women respond differently to pharmacological interventions. Ignoring this in trials might lead to serious unwanted side effects later. Looking at sex differences has helped us understand the infection better and it will help us understand our treatment options better. Taking into consideration sex differences is an essential step toward more personalized healthcare."

Tokyo, Japan - Scientists from The University of Tokyo Institute of Industrial Science have designed a machine learning algorithm to predict the size of an individual cell as it grows and divides. By using an artificial neural network that does not impose the assumptions commonly employed in biology, the computer was able to make more complex and accurate forecasts than previously possible. This work may help advance the field of quantitative biology as well as improve the industrial production of medications or fermented products.

As in all of the natural sciences, biology has developed mathematical models to help fit data and make predictions about the future. However, because of the inherent complexities of living systems, many of these equations rely on simplifying assumptions that do not always reflect the actual underlying biological processes. Now, researchers at The University of Tokyo Institute of Industrial Science have implemented a machine learning algorithm that can use the measured size of single cells over time to predict their future size. Because the computer automatically recognizes patterns in the data, it is not constrained like conventional methods.

"In biology, simple models are often used based on their capacity to reproduce the measured data," first author Atsushi Kamimura says. "However, the models may fail to capture what is really going on because of human preconceptions,".

The data for this latest study were collected from either an Escherichia coli bacterium or a Schizosaccharomyces pombe yeast cell held in a microfluidic channel at various temperatures. The plot of size over time looked like a "sawtooth" as exponential growth was interrupted by division events. Human biologists usually use a "sizer" model, based on the absolute size of the cell, or "adder" model, based on the increase in size since birth, to predict when divisions will occur. The computer algorithm found support for the "adder" principle, but as part of a complex web of biochemical reactions and signaling.

"Our deep-learning neural network can effectively separate the history-dependent deterministic factors from the noise in given data," senior author Tetsuya Kobayashi says.

This method can be extended to many other aspects of biology besides predicting cell size. In the future, life science may be driven more by objective artificial intelligence than human models. This may lead to more efficient control of microorganisms we use to ferment products and produce drugs.

Split liver transplantation (SLT) provides an opportunity to divide a donor liver and offer transplants to two small patients, one or both of whom could be a child. SLT, which is underused in the United States, could be used more widely to decrease the number of deaths of people on transplant waiting lists. In a new article, researchers address some of the ethical decisions that go into decisions to split a liver and provide a model to help hospitals make SLT decisions.

The article, by researchers at Carnegie Mellon University (CMU), appears in The BMJ, which is published by the Institute of Medical Ethics.

"Should a large liver always be split if it is medically safe to do so?" asks Sridhar Tayur, Professor of Operations Management at CMU's Tepper School of Business, who coauthored the article. "We say not always, and clarify under what circumstances SLT is ethically desirable."

Both the Organ Procurement and Transplant Network and the United Network for Organ Sharing have identified SLT as an important ethical issue. To flesh out the issues at play, the authors - including UCSF Transplant Surgeon, John Roberts who previously served as UNOS President - present several case studies regarding what to do with a large liver available for transplantation when recipients are different sizes and ages and have different levels of need.

Using philosophical theory, the authors - that include Alan Strudler, an ethicist from University of Pennsylvania -- address considerations that limit transplantation of portions of the liver. SLT requires that the relative size of the donor and the recipient match because if the portion of the liver is too small for the recipient, it will fail. The most common split results in one part of the liver that is about 75 percent of the original mass (typically transplanted to an adult) and one part that is 25 percent (typically transplanted to a child). However, the larger part may be inadequate for a large adult, and splitting raises logistical issues, such as preparing two recipients in the same operating room, the time and expertise needed to split the liver, and the transportation of the parts of the liver.

The authors suggest that hospitals use a flexible decision support model to allow for analyses that ask "what if" questions about the patients who need transplants and how their needs are changing. The model should consider various metrics of fairness and efficiency. For example, the medical community should reach reasonable consensus about what items constitute fairness, including patients' scores on measures of the severity of liver cirrhosis, which prioritize decisions about transplantation; waiting time until transplant; and likelihood of death.

"Much of the ethics involved in SLT suggest a dynamic problem whose answer requires a dynamic solution," explains Tae Wan Kim, Associate Professor of Business Ethics at CMU's Tepper School of Business, who coauthored the study. "The problem of liver transplantation is dynamic, so the solution must be dynamic and oscillate qualitatively between different demographics."

As an example of a dynamic allocation policy, decisions about SLT would oscillate between splitting a large liver if the health of the small patients involved were worse than that of the large patient and not splitting the liver if the opposite were true.

Research has shown that listening to music daily improves language recovery in patients who have experienced a stroke. However, the neural mechanisms underlying the phenomenon have so far remained unknown.

A study conducted at the University of Helsinki and the Turku University Hospital Neurocenter compared the effect of listening to vocal music, instrumental music and audiobooks on the structural and functional recovery of the language network of patients who had suffered an acute stroke. In addition, the study investigated the links between such changes and language recovery during a three-month follow-up period. The study was published in the eNeuro journal.

Based on the findings, listening to vocal music improved the recovery of the structural connectivity of the language network in the left frontal lobe compared to listening to audiobooks. These structural changes correlated with the recovery of language skills.

"For the first time, we were able to demonstrate that the positive effects of vocal music are related to the structural and functional plasticity of the language network. This expands our understanding of the mechanisms of action of music-based neurological rehabilitation methods," says Postdoctoral Researcher Aleksi Sihvonen.

Listening to music supports other rehabilitation

Aphasia, a language impairment resulting from a stroke, causes considerable suffering to patients and their families. Current therapies help in the rehabilitation of language impairments, but the results vary and the necessary rehabilitation is often not available to a sufficient degree and early enough.

"Listening to vocal music can be considered a measure that enhances conventional forms of rehabilitation in healthcare. Such activity can be easily, safely and efficiently arranged even in the early stages of rehabilitation," Sihvonen says.

According to Sihvonen, listening to music could be used as a cost-efficient boost to normal rehabilitation, or for rehabilitating patients with mild speech disorders when other rehabilitation options are scarce.

After a disturbance of the cerebral circulation, the brain needs stimulation to recover as well as possible. This is the goal of conventional rehabilitation methods as well.

"Unfortunately, a lot of the time spent in hospital is not stimulating. At these times, listening to music could serve as an additional and sensible rehabilitation measure that can have a positive effect on recovery, improving the prognosis," Sihvonen adds.

Mitochondria, the powerhouse of the cell, convert sustenance into energy, fueling the cell's activities. In addition to power, mitochondria also produce reactive oxygen species, byproduct molecules primed to help facilitate communication among the other units in the cells. But when produced too abundantly, they damage DNA and render some cellular components dysfunctional. Now, an international research team has revealed how mitochondria keep their reactive oxygen species production in check.

They published their results on June 30 in Frontiers in Cell and Developmental Biology.

"Excessive generation of reactive oxygen species in mitochondria damages mitochondria and reduces cell function, so the mechanism by which mitochondria maintain production of reactive oxygen species is crucial for cells," said lead paper author Yoshihiro Ohta, associate professor in the Department of Biotechnology and Life Science at Tokyo University of Agriculture and Technology in Japan. "In this study, we found that mitochondria have a mechanism to spontaneously avoid the production of excess reactive oxygen species."

Mitochondria are double membraned, with genetic information and functional units contained within its internal matrix. Mitochondria convert chemical energy into power for the cell by moving protons from outside to inside the matrix with the help of an enzyme responsible for energy conversion. But mitochondria also appear to impulsively and temporarily take up protons through another protein through a process called spontaneous transient depolarization.

"Spontaneous fluctuations in mitochondrial membrane potential are physiological phenomena observed in a wide range of cells from plants to mammals," said Ohta. "In this study, we investigated how this spontaneous fluctuation occurs and what it is useful for."

The researchers found that increasing the pH of the matrix from neutral to basic significantly increased reactive oxygen species production. They also found that inhibition of the spontaneous fluctuation, or depolarization, increased both the matrix pH and presence of reactive oxygen species.

"Spontaneous transient depolarization may decrease reactive oxygen species production in the mitochondria by inhibiting sustained matrix pH elevation," Ohta said. "This is the first study suggesting the relationship between spontaneous transient depolarization and reactive oxygen species production."

While the researchers have not fully elucidated the mechanism by which mitochondria control their reactive oxygen species production, they did propose a model suggesting that spontaneous transient depolarization occurs when increased matrix pH facilitates moving more protons from outside the matrix into the matrix.

The researchers plan to further investigate the mechanism to understand not only how mitochondria can prevent overproduction of reactive oxygen species, but also if detecting the spontaneous fluctuation in mitochondria could indicate the oxidative stress state -- and damage -- of cells.

Anyone who likes to sing in the shower probably knows that they sometimes sing out of tune. But what about professional singers? How well do they evaluate their own abilities? And what role does this self-assessment play in becoming a better musician? A research team from the Max Planck Institute for Empirical Aesthetics in Frankfurt, New York University, and the University of Hamburg has now investigated these questions scientifically in a study of professional singers.

The study participants, all female sopranos, were each recorded singing "Happy Birthday" in a studio. They were then asked to listen to all of the recordings and rate the pitch accuracy of both their own vocal performances and those of their colleagues. In Western culture, pitch accuracy--i.e., singing in tune--is associated with acoustic characteristics that can be quantified and thus serves as an objective measure of proficiency.

The research team derived a statistical model from the participants' evaluations of others. Using this, they were able to determine how well a singer rated others as well as her own performance.

"The results show that the singers were surprisingly inaccurate in their self-assessment. Most overestimated their own performance," says lead author Pauline Larrouy-Maestri of the Max Planck Institute for Empirical Aesthetics.

In addition, the researchers observed a correlation between singing competence and self-assessment ability: the better the singer (in terms of pitch-accuracy) the better they evaluated themselves. This outcome is surprising since experts in a certain domain usually tend to underestimate their abilities in this domain.

The study, the findings of which have just appeared in the Journal of Voice, thus not only underscores the fact that even professional singers do not necessarily evaluate their own vocal performance correctly. But it also suggests that self-evaluation itself may be a key factor in the development of exceptional musical skills.

Coral reefs are a favorite spot for scuba divers and are among the world's most diverse ecosystems. For example, the Hawaiian coral reefs, known as the "rainforests of the sea," host over 7,000 species of marine animals, fishes, birds and plants. But coral reefs are facing serious threats, including a number of diseases that have been linked to human activity.

To understand the connection between human activity and a type of tumorlike disease called growth anomalies (GAs), researchers at the National Institute of Standards and Technology (NIST) have collaborated with the U.S Geological Survey (USGS) and the National Oceanic and Atmospheric Administration (NOAA) to use an emerging molecular profiling method to identify 18 small molecules that promise to help them better understand the series of molecular reactions that lead to the disease.

GAs affect both the coral skeleton and its soft tissues. Scientists don't know the cause of the disease or how it spreads but have hypothesized that there is a strong correlation between GA prevalence in coral colonies and human population density nearby.

Almost all types of corals are made of hundreds to millions of individual soft-bodied animals called polyps. The polyps secrete calcium carbonate to form a hard skeleton that lays the foundation for the coral colony. GAs affect corals through irregular and accelerated growth of their skeleton, causing it to be less dense and filled with holes. This results in a tumorlike mass in the skeleton of a coral colony with fewer polyps and a diminished ability to reproduce.

Shallow water corals receive food like carbohydrates and oxygen as a byproduct of photosynthesis from the symbiotic relationship they have with zooxanthellae, photosynthetic algae that live inside coral tissues. GAs can lead to fewer symbiotic zooxanthellae and therefore less energy being absorbed from photosynthesis.

Even though GAs do not typically directly lead to coral death, they do affect the overall health of coral colonies and can pose an ecological threat to coral populations. To analyze the disease, NIST researchers chose the coral species Porites compressa as their target sample.

This coral species is known as the "finger" or "hump" coral and is part of the stony coral family, which is "one of the important reef-building species in Hawaii," said NIST chemist Tracey Schock. "They lay the foundation for the coral reef."

P. compressa is found in shallow lagoons off the Hawaiian Islands, and the researchers obtained their coral samples from Kaneohe Bay, Oahu. The bay has been studied widely as a site affected by human activity such as sewage discharge and metal pollution. GAs have previously been observed in the coral species there.

In order to analyze and study GAs in P. compressa, researchers turned to the field of metabolomics, which is the study of small molecules, such as those making up living organisms found in tissues, blood or urine. These small molecules, known as metabolites, are the intermediate and end products in a linked series of biochemical reactions known as molecular pathways in an organism.

Some examples of such small molecules include sugars like glucose, amino acids, lipids and fatty acids. Their production can be influenced by genetic and environmental factors and can help researchers better understand the biochemical activity of tissue or cells. In this case, chemical analysis of metabolites provides significant information that helps researchers understand the physiology of the disease.

For their study, researchers sampled a coral colony that had both healthy and diseased tissue. They split up their samples so they could assess the healthy coral and diseased coral separately. They also had a separate adjacent sample that was free of diseased tissue.

The samples were frozen in liquid nitrogen, and then freeze-dried for practical sample processing while maintaining metabolic integrity. The researchers then separated the diseased parts from the healthy colony using a hammer and stainless-steel chisel and collected the tissue from the skeleton with a brush. In one of the final stages of the sample preparation, they chemically extracted the metabolites from the coral tissue using a combination of methanol, water and chloroform.

"The method is novel for coral studies," said Schock. "With metabolomics, it is critical to preserve the state of all metabolites in a sample at the time of collection. This requires halting all biochemical activity using liquid nitrogen and maintaining this state until chemical extraction of the metabolome. The complexity of a coral structure necessitates stringent collection and processing protocols."

The researchers then produced a metabolomic analysis of the coral samples by using a reproducible profiling technique known as proton nuclear magnetic resonance (1H NMR).

The 1H NMR technique exposes the coral extract to electromagnetic fields and measures the radio frequency signals released by the hydrogens in the sample. The various kinds of metabolites are revealed by their unique signals which inform of their chemical environment. NMR detects all signals from the magnetic nuclei within a sample, making it an unbiased "all-in-one" technique. Two-dimensional NMR experiments that can identify both hydrogens (1H) and their directly bound carbon (13C) atoms provide more chemical information, giving confidence in the accuracy of the identities of the various metabolites within a sample.

The study identified 18 different metabolites and a new GA morphological form in P. compressa. The researchers found that GA tumors have distinct metabolite profiles compared with healthy areas of the same coral colony and detected specific metabolites and metabolic pathways that may be important for these profile differences. They also discovered that the loss of internal pH regulation is seemingly responsible for the hollow skeletons that are a characteristic of GAs.

"We have not only characterized new aspects of GA physiology, but have also discovered candidate pathways that provide a clear path forward for future research efforts aiming to further understand GA formation and coral metabolism, in general," said Schock.

As studies of this type accumulate, the researchers envision a database that could pull together coral metabolite information from multiple coral species into an accessible location for all scientists.

Collaborating with other researchers in different fields could increase understanding of the biological impacts of this disease on coral colonies. "We are going to learn which species are tolerant and which species are sensitive to stresses, and the physiological adaptations or mechanisms of both types will be important to conservation efforts," said Schock.

For now, the researchers hope these findings will be helpful for other scientists analyzing coral species and ultimately be beneficial for the coral reefs themselves, potentially aiding efforts to better preserve them.

Contrary to conventional thought, songbirds can taste sugar--even though songbirds are the descendants of meat-eating dinosaurs and are missing a key protein that allows humans and many other animals to taste sweetness. An international team investigated how many bird species can taste sweet and how far back that ability evolved. Their work was published today in the journal Science.

The researchers offered two species of songbirds a choice between sugar water and plain water--nectar-taking honeyeaters, as well as canaries, a grain-eating bird not known for consuming sweet foods. They also examined taste receptor responses sampled from a variety of other species. Regardless of whether their main diet consisted of seeds, grains, or insects, songbird taste receptors responded to sugars.

"This was a clear hint that we should concentrate on a range of songbirds, not only the nectar-specialized ones, when searching for the origins of avian sweet taste," explains senior author Maude Baldwin at the Max Planck Institute for Ornithology in Germany. Baldwin led this study with Yasuka Toda from Meiji University in Japan.

Sugar is a vital carbohydrate providing lots of energy and may have had far-reaching effects on songbird evolution. Though it is thought that most bird lineages can't taste sweetness at all, the scientists now believe that songbirds, which account for more than 40% of the world's bird species, can actually taste sweet, and that sugary food sources may have contributed to their success.

Baldwin and Toda dug down to the molecular level to understand the modifications to the "umami" taste receptor that enabled sweet perception among songbirds.

"Because sugar detection is complex, we needed to analyze more than one hundred receptor variants to reveal the molecular mechanisms underlying the sugar responses," says Toda. These exact changes coincide only slightly with those seen in the distantly-related hummingbirds, even though similar areas of the receptor are modified.

Though songbirds evolved similar workarounds to taste sweetness, they did so at different times, in different places, and in slightly different ways--an example of "convergent evolution." Some songbirds, such as honeyeaters, sunbirds, honeycreepers, and flowerpiercers are now just as dependent on nectar as the hummingbirds.

"This study fundamentally changes the way we think about the sensory perceptions of nearly half the world's birds," says study co-author Eliot Miller at the Cornell Lab of Ornithology. "It demonstrates that most songbirds definitely can taste sweet and got there by following nearly the same evolutionary path that hummingbirds did--it's a neat story about how convergence happens."

Exploring the songbird family tree, the researchers conclude that songbirds evolved to sense sweetness approximately 30 million years ago, before the early ancestors of songbirds left Australia, where all songbirds originated. Even after songbirds radiated across the world, they kept their ability to taste sugar.

Researchers in Japan, Germany, the United States, Hong Kong, and Australia participated in this study. Future studies will explore how sweet perception has coevolved with other physiological traits, such as changes in digestion and metabolism, across bird evolution.

A team of physicists from the Harvard-MIT Center for Ultracold Atoms and other universities has developed a special type of quantum computer known as a programmable quantum simulator capable of operating with 256 quantum bits, or "qubits."

The system marks a major step toward building large-scale quantum machines that could be used to shed light on a host of complex quantum processes and eventually help bring about real-world breakthroughs in material science, communication technologies, finance, and many other fields, overcoming research hurdles that are beyond the capabilities of even the fastest supercomputers today. Qubits are the fundamental building blocks on which quantum computers run and the source of their massive processing power.

"This moves the field into a new domain where no one has ever been to thus far," said Mikhail Lukin, the George Vasmer Leverett Professor of Physics, co-director of the Harvard Quantum Initiative, and one of the senior authors of the study published today in the journal Nature. "We are entering a completely new part of the quantum world."

According to Sepehr Ebadi, a physics student in the Graduate School of Arts and Sciences and the study's lead author, it is the combination of system's unprecedented size and programmability that puts it at the cutting edge of the race for a quantum computer, which harnesses the mysterious properties of matter at extremely small scales to greatly advance processing power. Under the right circumstances, the increase in qubits means the system can store and process exponentially more information than the classical bits on which standard computers run.

"The number of quantum states that are possible with only 256 qubits exceeds the number of atoms in the solar system," Ebadi said, explaining the system's vast size.

Already, the simulator has allowed researchers to observe several exotic quantum states of matter that had never before been realized experimentally, and to perform a quantum phase transition study so precise that it serves as the textbook example of how magnetism works at the quantum level.

These experiments provide powerful insights on the quantum physics underlying material properties and can help show scientists how to design new materials with exotic properties.

The project uses a significantly upgraded version of a platform the researchers developed in 2017, which was capable of reaching a size of 51 qubits. That older system allowed the researchers to capture ultra-cold rubidium atoms and arrange them in a specific order using a one-dimensional array of individually focused laser beams called optical tweezers.

This new system allows the atoms to be assembled in two-dimensional arrays of optical tweezers. This increases the achievable system size from 51 to 256 qubits. Using the tweezers, researchers can arrange the atoms in defect-free patterns and create programmable shapes like square, honeycomb, or triangular lattices to engineer different interactions between the qubits.

"The workhorse of this new platform is a device called the spatial light modulator, which is used to shape an optical wavefront to produce hundreds of individually focused optical tweezer beams," said Ebadi. "These devices are essentially the same as what is used inside a computer projector to display images on a screen, but we have adapted them to be a critical component of our quantum simulator."

The initial loading of the atoms into the optical tweezers is random, and the researchers must move the atoms around to arrange them into their target geometries. The researchers use a second set of moving optical tweezers to drag the atoms to their desired locations, eliminating the initial randomness. Lasers give the researchers complete control over the positioning of the atomic qubits and their coherent quantum manipulation.

Other senior authors of the study include Harvard Professors Subir Sachdev and Markus Greiner, who worked on the project along with Massachusetts Institute of Technology Professor Vladan Vuleti?, and scientists from Stanford, the University of California Berkeley, the University of Innsbruck in Austria, the Austrian Academy of Sciences, and QuEra Computing Inc. in Boston.

"Our work is part of a really intense, high-visibility global race to build bigger and better quantum computers," said Tout Wang, a research associate in physics at Harvard and one of the paper's authors. "The overall effort [beyond our own] has top academic research institutions involved and major private-sector investment from Google, IBM, Amazon, and many others."

The researchers are currently working to improve the system by improving laser control over qubits and making the system more programmable. They are also actively exploring how the system can be used for new applications, ranging from probing exotic forms of quantum matter to solving challenging real-world problems that can be naturally encoded on the qubits.

"This work enables a vast number of new scientific directions," Ebadi said. "We are nowhere near the limits of what can be done with these systems."

Although the giant panda is in practice a herbivore, its masticatory system functions differently from the other herbivores. Through the processes of natural selection, the giant panda's dietary preference has strongly impacted the evolution of its teeth and jaws. Researchers from the Institute of Dentistry at the University of Turku and the Biodiversity unit of the University of Turku together with researchers from the China Conservation and Research Center for Giant Panda (CCRCGP) have been the first in the world to solve the mystery of how the giant panda's special stomatognathic system functions.

The bamboo diet of the giant panda (Ailuropoda melanoleuca) has long been a mystery for researchers. The panda is in practice a herbivore, and its diet only consists of few dozen species of bamboo. Related to the consumption of bamboo, the giant panda has a special characteristic of peeling the green outer skin of all bamboo shoots, rich in abrasive and toxic compounds, by the highly adapted premolars.

Herbivores have usually evolved to have ridged molars that help them grind the plant material and jaws capable of moving sideways which is essential for grinding their food. Although the teeth of giant pandas have been studied extensively, until now, researchers have not paid attention to why the large canines of their upper jaw do not prevent the sideways movement of the lower jaw typical for herbivores - and also humans. The key to this has been the evolution of the temporomandibular joint and the premolar teeth.

Evolution of the Temporomandibular Joint Allows Sideways Movement

Using modern 3D scanning methods, the research group studied the movement of the giant panda's jaw and the structure of its teeth and found the answer to the question that had puzzled researchers for over a century: how are giant pandas able to use bamboo as their diet. The solution was that the panda's temporomandibular joint has evolved to differ from that of e.g. brown bear and polar bear. In addition to the open-closed movement reminding that of a hinge, the joint also allows the jaw to be moved sideways, which is required to peel the bamboo. Interestingly, this movement isn't prevented by the large canines the male pandas need to fight.

- The necessity to ensure adequate nutrition has helped evolve the temporomandibular joint and the shape of the teeth to allow efficient peeling of the bamboo without without exposing the premolars to the attritive or other damaging effect of bamboo diet, explains Professor Pekka Vallittu from the Institute of Dentistry.

The evolution of the giant panda's masticatory system, as demonstrated in the study, allowed them to be the only large mammals to access an endless source of nutrition in the form of bamboo in the early Pleistocene.

- The premolars giant pandas use for peeling bamboo are unique among the family of bears and allow the removal of the poisonous green skin of the bamboo which also includes mineral crystals which would wear their teeth, says Professor Juha Varrela from the Institute of Dentistry.

The study of how the giant panda's masticatory system functions also helps to understand human's occlusion and its characteristics better.

- Whether giant pandas grind their teeth still remains to be seen, ruminates Vallittu.

- This newly published study is of great scientific significance because it solves the long-prevailing mystery of the ecological interrelationship between the pandas and the bamboo plants, says Professor Jukka Salo from the Biodiversity Unit of the University of Turku.

12,000 people in Denmark and 7 to 10 million people worldwide suffer from Parkinson's Disease (PD). It is the second most common neurogenerative disorder of aging and the most common movement disorder, but the cause of the disease is largely unknown.

In a new study, researchers from the University of Copenhagen show that the most common form of the disease, encompassing 90 to 95 percent of all Parkinson's Disease cases known as sporadic PD, is caused by a blockage of a pathway that regulates the nerve cell's powerhouse, the mitochondria.

'Just like when people eat, cells take what they need and get rid of the rest waste products. But if our brain cells have this specific kind of signaling blockage, it means that the powerhouse of the cell - mitochondria - cannot get cleaned up after being damaged', explains corresponding author and group leader Professor Shohreh Issazadeh-Navikas at the Biotech Research & Innovation Centre.

The blockage leads to an accumulation of high amounts of damaged mitochondria, while not being able to produce enough energy for the cells. It causes neurons to gradually die, which is the reason for the development of Parkinson's Disease symptoms, and why it leads to dementia.

The blockage is caused by a dysregulation of the immune genes, more specifically a pathway called type 1 interferon, which is normally important for fight against viruses, but now we show that it is also responsible for regulating the energy supply of the nerve cells.

'Every part of our body needs to be regulated. We get a signal to stop eating, when we are full, and the same thing happens everywhere else in our body. If we get an infection, parts of our body need to fight it and stop it from replicating. But when the infection is cleaned up, the signal should subside. This is the job of a protein called PIAS2. That causes the blockage of the type 1 interferon-pathway, and when the infection is over, the blockage should stop and go back to normal. But that does not seem to be the case in patients with Parkinson's Disease. We further demonstrate that this dysregulation leads to a defect in the mitochondrial energy supply, as mentioned before', says Shohreh Issazadeh-Navikas.

These pathways are very important for brain functions, but they are also associated with microbial and virus recognition. For example, they are very important for fighting COVID-19, and a mutation in the related gene has been shown to be linked to a deadly outcome after contracting COVID-19.

The researchers combined and analyzed four data sets, which studied neurons from brains with Parkinson's Disease and looked at what type of genes they express.

They then looked at which gene patterns were disturbed in patients with Parkinson's Disease and especially those who had also developed PD with dementia.

In order to test the results, the major findings of the combined data was tried in three different mouse models using a negative regulator of the type I interferon pathway, PIAS2, which had been identified from the patients study as one of the key proteins linked to the progression of Parkinson's Disease and dementia.

'We show that a high accumulation of the PIAS2-protein is what is causing the blockage in the pathway, which should have activated the processes responsible for removing damaged protein and mitochondrial garbage', says Shohreh Issazadeh-Navikas.

'The accumulation of damaged mitochondrial mass further leads to increase of other toxic proteins. So when we compare patients to same-aged healthy patients without Parkinson's Disease, we see that this PIAS2-protein is highly expressed in the neurons, which is why this pathway should be evaluated for potential roles in the other forms of familial Parkinson's Disease that we have not studied here.'

The researchers hope the study will encourage research to counteract the pathway blockage, which could have a beneficial impact on the disease and towards preventing dementia.

In the next stages, the Shohreh Group will study how the pathway contributes to neuronal homeostasis and survival, as well as how its dysregulation causes neuronal cell death.

A presentation at this year's European Congress on Clinical Microbiology & Infectious Diseases (ECCMID), held online this year, will discuss the growing evidence that the beta SARS-CoV-2 variant first identified in South Africa is leading to more severe disease in people living with HIV, and that failure to clear SARS-CoV-2 infection in a patient with advanced HIV creates conditions that can lead to evolution of dangerous mutations in SARS-CoV-2.

Control of HIV with antiretroviral therapy could be the key to preventing such evolution of SARS-CoV-2 in patients with advanced HIV, since clearance of the virus is compromised if HIV is allowed to replicate for a long time and results in major damage to the immune system.

"Evolved mutations lead to escape from neutralisation, which means antibodies made as a result of previous natural infection or vaccination would work less well to protect you from a new infection," explains session presenter Dr Alex Sigal, Africa Health Research Institute, KwaZulu-Natal, South Africa, and Max Planck Institute for Infection Biology, Berlin, Germany. "SARS-CoV-2 may mutate extensively within one person if infection persists."

In his talk, Dr Sigal will present a case study of a patient with advanced HIV who, despite having only mild COVID-19 illness, tested SARS-CoV-2 positive for 216 days. Genomic sequencing revealed shifts in the patient's SARS-CoV-2 viral population over time, involving multiple mutations at key sites including the spike protein domain which SARS-CoV-2 uses to enter human cells. The evolved virus was tested and shown to have variant-like properties in terms of its ability to escape antibodies.

"Such findings underline the need to make sure everyone living with HIV has appropriate treatment. If not, it is possible that potentially more potent variants than the ones circulating now could emerge from people whose immune systems are severely damaged," he explains.

It is believed to be involved in the development of chronic inflammatory intestinal diseases, to trigger diabetes, to be responsible for obesity, even neurological diseases such as multiple sclerosis and Parkinson's could have their causes here - not to mention depressions and autistic disorders. We are talking about the microbiome - the vast collection of bacteria in the human gut. It is estimated that each person carries around 100 trillion bacterial cells in their digestive tract, belonging to several thousand species.

The microbiome has been the focus of research for 20 years - ever since a new technique made it possible to analyse these bacteria quickly and precisely: high-throughput sequencing. Since then, there has been an increasing body of findings that the microbiome, which is sometimes also referred to as the second human genome, is not only of central importance for digestion, but also influences, if not controls, at least a large number of body functions. The immune system is mentioned particularly frequently.

The microbiome influences the immune system

Scientists at the Universities of Würzburg and Marburg have now succeeded for the first time in experimentally demonstrating that bacterial metabolites are able to increase the cytotoxic activity of certain immune cells and thus positively influence the efficiency of tumour therapies. Ideally, the composition of the bacterial species in the microbiome could be used to control its influence on the success of the therapy.

The research team published the results of its study in the journal Nature Communications. Dr. Maik Luu, postdoc in the laboratory of Professor Michael Hudecek at the Medical Clinic and Polyclinic II of the University Hospital of Würzburg, was responsible for the finding. Another participant was Professor Alexander Visekruna from the Institute of Medical Microbiology and Hygiene at the Philipps University in Marburg, where Luu did research before moving to Würzburg.

Fatty acids increase the activity of killer cells

"We were able to show that the short-chain fatty acids butyrate and, in particular, pentanoate are able to increase the cytotoxic activity of CD8 T cells," Maik Luu describes the central result of the now published study. CD8 T cells are sometimes also called killer cells. As part of the immune system, it is their task to specifically kill cells that are harmful to the organism.

Short-chain fatty acids, in turn, belong to the most dominant class of metabolites of the gut microbiome. On the one hand, they can boost the metabolism of T cells by inducing central regulators of energy metabolism. On the other hand, they can inhibit specific enzymes that regulate the accessibility to the genetic material and thus the gene expression in the T cells. In doing so, they induce epigenetic changes.

Solid tumor models are combated more effectively

"When short-chain fatty acids reprogram CD8 T cells, one of the results is increased production of pro-inflammatory and cytotoxic molecules," Luu explains. In the experiment, treatment with the fatty acid pentanoate increased the ability of tumor-specific T cells to fight solid tumor models. "We were able to observe the same effect when fighting tumor cells with so-called CAR-T cells," says the scientist.

CAR-T cells are written out as "chimeric antigen receptor T cells". While normal T cells are largely "blind" to tumor cells, CAR T cells are able to recognize specific target antigens on the tumor surface and destroy the cancer cells thanks to a genetic modification. Michael Hudecek is one of the leading experts in the field of CAR-T cell research.

Targeted control via the composition of the microbiome

"The results are an example of how metabolites of intestinal bacteria can change the metabolism and gene regulation of our cells and thus positively influence the efficiency of tumor therapies," says Maik Luu. In particular, the use of CAR-T cells against solid tumors could benefit from this.

In these cases, therapy with genetically modified cells has so far been much less effective than the treatment of haematological tumours such as leukaemia. This could change if the CAR-T cells were treated with pentanoate or other short-chain fatty acids before being used in patients, the scientists hope.

This effect might specifically be exploited via the composition of the bacterial intestinal colonisation - especially since Luu and the others involved in the study were also able to identify the essential pentanoate producer of the intestinal flora: the bacterium Megasphaera massiliensis.

A long way to clinical applications

However, there is still a long way to go before the new findings will lead to new therapies for cancer patients. In a next step, the research team will initially expand the spectrum of tumour diseases investigated and, in addition to other solid tumours, also look at haematological tumour diseases such as multiple myeloma. In addition, it wants to investigate the functioning of short-chain fatty acids more intensively in order to identify starting points for targeted genetic modifications.