Culture

A 7- to 15-year longitudinal study of 358 diabetics has linked 3 proteins in blood with a slower progression of diabetic kidney disease and progressive kidney failure. The results from Zaipul Md Dom and colleagues suggest that the proteins could help researchers identify diabetics most at risk of kidney damage, potentially enabling earlier interventions and treatment. Despite advancements in blood sugar control and kidney therapies, patients with type 1 or type 2 diabetes still face a high risk of diabetic kidney disease. This condition can eventually progress to end-stage kidney disease, but some patients show slower kidney decline than others. In recent years, scientists have focused on understanding why some individuals progress at slower rates and whether they might harbor proteins that protect the kidneys from the effects of diabetes. As part of the Joslin Kidney study, Md Dom et al. followed two groups of patients with type 1 or type 2 diabetes and varying degrees of diabetic kidney disease (358 total) for between 7 to 15 years. While analyzing more than 1,000 proteins in the patients' plasma, the researchers discovered that patients who progressed slowly had higher amounts of the proteins ANGPT1, TNFSF12, and FGF20. The team confirmed this protective link in an independent group of 294 type 1 diabetics; they also found that FGF20 was elevated in healthy, non-diabetic parents of type 1 diabetics who remained free of kidney complications. If validated in larger studies, this finding "could have a profound implication in future research on determinants of progressive renal decline in [type 1 diabetes]," the authors say. However, they caution that more studies are necessary to confirm a causal link between the 3 proteins and protection from diabetic kidney disease.

Despite unprecedented advancements in technology and countless depictions of complex human-AI interactions in sci-fi movies, we have yet to fully achieve AI bots that can engage in conversation as naturally as humans can. Kushal Chawla, researcher at the USC Institute for Creative Technologies (ICT) and a doctoral student in computer science, along with collaborators at both the USC Information Sciences Institute (ISI) and ICT are taking us one step closer to this reality by teaching AI how to negotiate with humans.

The research, presented at the 2021 Annual Conference of the North American Chapter of the Association for Computational Linguistics (NAACL) this month, relied on a scenario-based dataset that was collected to teach negotiation skills to human users through role-play dialogue. With a campsite setting as the imaginary backdrop, participants in the data collection study were instructed to interact with each other as if they were campers negotiating for resources. The researchers discovered a total of nine strategies that the participants utilized throughout the exercise. The stand out lesson: cooperative strategies of negotiation were more effective than selfish strategies. This information can be used in the future to inform the creation of an automated system which takes various strategies of negotiation into account.

Training AI

CaSiNo, which stands for Camp Site Negotiations, is a scenario-based dataset that was collected to teach negotiation skills to human users through role-play dialogue.It consists of over a thousand negotiation dialogues which are carried out by two participants at a time. At the core of these dialogues, there are three essential camping items that the participants negotiated for -- food, water, and firewood. Each participant is assigned a preference order for these items and negotiates based on this model. As the participants negotiate with one another, they come to conclusions about how to allocate the items to best maximize each person's rewards.

Prior to these dialogues, participants underwent a training module which consisted of watching a video tutorial on negotiation. Doing so allowed participants to understand best practices of negotiation to be incorporated into the performance.

"We evaluate the negotiation performance of the participants in three ways: final points scored depending on what they were able to negotiate for, how satisfied they were with the outcome, and how much their opponents like them," explained Chawla. "All these metrics are crucial in the context of real-world negotiations."

Standing Out

Chawla has extensive prior research in AI, but CaSiNo is his most ambitious approach yet.

"One difference with these prior works is that in these cases, the negotiations don't involve language-based communication, but rather are based on button clicks and drop-down choices in a menu," explains Chawla. "However, our work on the CaSiNo dataset would promote the development of AI systems that can negotiate using language (such as in English) and have real, rich conversations with humans."

Similarly, most work in the field of automated negotiation systems has been focused on a menu-driven interface rather than language-based communication. Though these technologies have been easy to navigate, Chawla argued that "they fail to capture free-form emotion and persuasion, which are key components of real-world negotiations." Language, on the other hand, encapsulates human-like characteristics that help ground AI communication in the real world.

Achieving this new level of AI communication requires construction of complex negotiation datasets through which AI can be trained. It can be a challenge to construct the perfect dataset -- prior efforts at doing so have often been either too restrictive or too open-ended. In order to find the perfect balance between the two, Chawla and his team approached this challenge by "proposing a novel task that enables linguistically rich and personal conversations, but still in a constrained environment."

Applications in Pedagogy and Beyond

As an effective way of automating negotiation instead of relying on humans, it's no wonder CaSiNo has a variety of real-world applications. This technology can be applied to various industries, including business, education, entrepreneurship and tech. Specifically, CaSiNo can help with teaching negotiation skills in various pedagogical contexts, whether it be training business students to secure deals or helping lawyers to assess settlement rates more accurately.

CaSiNo is also highly valuable for improving negotiation skills of conversational AI assistants. Chawla mentions the Google Duplex prototype as an example, in which AI assistants express negotiation skills to automatically make appointments over the phone.

Future Directions

Going forward, Chawla and his team are broadly interested in looking deeper into other types of non-collaborative dialogue outside of negotiation, such as persuasion. Non-collaborative dialogue is generally defined as communication "where the goals of the involved parties may not perfectly align with each other."

More specifically, Chawla outlines two directions of future research based on the current work with CaSiNo. Firstly, the team is interested in looking at the predictive capabilities of AI through how emotional expression in CaSiNo dialogues correlates with the outcomes of negotiation. By doing so, these AI agents can be improved to become more emotion-aware. Secondly, the team is looking to improve the believability of negotiation skills by building upon realistic free-form language training. Ultimately, CaSiNo is a groundbreaking system that will serve as a solid foundation for improvements in human-computer interactions.

Although cardiovascular disease is the main cause of illness among women in the U.S., certain conditions such as coronary microvascular disease (CMD) cannot be easily diagnosed. In a new study, researchers at the University of Illinois Urbana-Champaign have identified specific biomarkers for CMD, which might reduce future hospitalizations.

CMD damages the inner walls of blood vessels causing spasms and decreased blood flow to the heart muscle. "Clinicians look for plaque formation in the blood vessels, which does not occur in CMD," said Zeynep Madak-Erdogan (CGD/EIRH/GSP), an associate professor of nutrition. "Usually, women leave without having the root causes of the chest pain addressed and they come back with further complications within a year. Since this condition is more common in postmenopausal women, we want to identify the biomarkers that are associated with CMD."

The researchers collected blood samples from three different groups containing 20-25 women each: postmenopausal women who were healthy, those with coronary artery disease, which is characterized by plaque formation, and those with CMD. The blood serum samples were then analyzed to see if there were any molecules that were different in the CMD group.

Out of 175 molecules scanned, the researchers identified stearic acid, which is found in animal and plant fats, and ornithine, an amino acid commonly found in meat, fish, diary, and eggs, as indicators of CMD.

Ornithine is formed from the amino acid arginine which is broken down by two separate pathways. One forms ornithine and the other forms nitric oxide, which helps in maintaining the normal functioning of the blood vessels.

"Our observations imply that the increase in ornithine means that the second branch is not working, which is why we can use this molecule as a biomarker for the disease," Madak-Erdogan said.

Interestingly, other researchers have found that estrogen may have a role in the development of CMD, as evidenced by hormone-replacement therapies which decrease CMD risk up to 30%. "Our observations further indicate that estrogen is involved because we know that it improves the function of nitric oxide," Madak-Erdogan said. "Since postmenopausal women have lower levels of estrogen, it would explain why this condition is more prevalent in these populations."

The researchers are trying to identify more biomarkers, such as proteins, that can be used to detect CMD. Additionally, they are testing more women to validate their findings. "This study was done with patients in Turkey, so we don't know if the same biomarkers will be present in the U.S. We want to look at bigger populations to see if we can combine the data to find efficient signatures for CMD," Madak-Erdogan said.

The study "Identification of circulating diagnostic biomarkers for coronary microvascular disease in postmenopausal women using machine-learning techniques" was published in Metabolites and can be found at https://doi.org/10.3390/metabo11060339.

The virus that gives rise to COVID-19 is the third coronavirus to threaten humanity in the past two decades. It also happens to move more efficiently from person to person than either SARS or MERS did. The first African case of COVID-19 was diagnosed in Egypt in mid-February of 2020. Four weeks later, the first lockdowns began across Africa. Steven Schiff, Brush Chair Professor of Engineering at Penn State, who already had established research partnerships in Uganda, saw an opportunity for his team to apply what they were learning from their ongoing efforts to track and control infectious disease and provide countries such as Uganda with more information to help guide policy to mitigate the viral pandemic.

The result was a multi-country collaboration to develop a surveillance modeling tool that provides a weekly projection of expected COVID-19 cases in all African countries, based on current case data, population, economic status, current mitigation efforts and meteorological sensing from satellites. Developed in collaboration with Uganda's National Planning Authority (NPA), the country's senior organization for development and economic planning, the tool's COVID-19 projections use openly available data to provide a projection of cases, as well as lower and upper ranges to help the country decide if mitigation policies need to be implemented or modified.

The researchers published their approach today (June 29) in the Proceedings of the National Academy of Sciences of the United States of America. The project was funded in part by the National Institutes of Health Director's Transformative Research Award, a grant awarded to Schiff in 2018 for his "high-risk, high-reward" approach to predictive, personalized public health (P3H).

Prediction guiding prevention in the face of a pandemic

"When the COVID-19 pandemic began, we had this unusual team of scientists hard at work on implementing P3H in Africa, and we thought that we had much we could contribute toward the fight against this new virus," said Schiff, who founded the Penn State Center for Neural Engineering and serves as a professor of engineering science and mechanics in the College of Engineering and of neurosurgery in the College of Medicine.

The team includes Paddy Ssentongo, assistant research professor of engineering science and mechanics. Ssentongo is originally from Uganda, where he earned a medical degree before moving to Penn State to complete a master of public health and a doctorate in epidemiology. He graduated this year.

"This pandemic has shown us that we need to put more emphasis on global public health -- especially in places with fragile health care systems, including many countries in Africa," Ssentongo said. "If we wait for people to get sick, we're already losing. The best thing we can do is prevention."

The researchers reached across disciplines to bring in experts -- from epidemiologists to meteorologists to economists -- on every factor influencing viral spread.

"We pulled together a large team to tackle what was necessary," said Schiff, who is also a researcher in the Penn State Neuroscience Institute. "The team consists of 19 people across four countries, plus many more individuals who contributed through discussions and support."

The complexity of mitigation

Equally important as understanding the number and location of people with active cases, according to Schiff, is understanding the importance of weather, geography and other factors, especially in developing countries where many people live and work in more exposed conditions than do people in industrialized countries.

"If a coastal country closes its borders, landlocked Uganda is likely going to see cases go up because they depend on the coastal countries for imports -- without the imports, people will move around and interact more to find work and food," Schiff said, noting that such changes in movement may create shifts in projections of new cases from neighboring countries versus internal cases. "You need information gathered in real-time on the virus, such as testing and lockdowns, as well as the other influencing factors such as the varied economic security of different countries and their health systems. Our strategy synthesizes all of these data across Africa to make surprisingly good projections of the expected number of cases based on how these factors interact and influence COVID transmission in the population."

Abraham J. B. Muwanguzi, paper co-author and manager of the science and technology department at the NPA, also serves as the principal investigator in Uganda on Schiff's NIH grant.

"We're working closely with the Ministry of Health to use the model in analyzing how the COVID trends are moving," Muwanguzi said. "In September and October of 2020, at the peak of COVID cases, the model projected an increase in cross-border cases, prompting the government to close our border. We had fewer cases than projected because we were able to mitigate a predicted source that was captured well in the model."

Muwanguzi also noted that the tool not only helps provide data for mitigation policies, but it also helps the country plan how to use its resources.

"For example, in March and April of this year, the model projected a tremendous drop in cases," Muwanguzi said. "Our hospital centers started emptying out -- there really were fewer cases. We could then scale down operations and reappropriate resources to other areas of need."

Yet, on June 18, Uganda entered a 42-day lockdown after the daily number of new cases increased from fewer than a hundred at the end of May to nearly 2,000. The week after the lockdown started, the model projected 11,222 new cases would be reported if no mitigation efforts were put in place.

"Unlike the previous wave where factors influencing the spread were mostly from outside the country, the current wave is influenced by internal factors," said Joseph Muvawala, executive director of NPA, in a column published by New Vision, a national newspaper in Uganda. "With these statistics, a total lockdown was inevitable, irrespective of the known economic consequences; human life is far too precious to lose."

According to Muvawala's column, the projected increases have helped Uganda better prepare their hospital centers by procuring enough supplies and planning to avoid overwhelming hospitals and health care workers.

However, Ssentongo warned, the model is only as good as the data provided to it.

"We hope other countries in Africa will not only use this tool, but also collaborate to make sure they are integrating data in terms of testing and reporting cases," Ssentongo said. "The tool is a roadmap to tell a country how the pandemic is evolving and where the country is going. It's successful if the country sees the projections, implements mitigation efforts and sees a lower number of actual cases."

Global benefit of global collaboration

According to Schiff, their findings clearly demonstrate the advantages of inter-country cooperation in pandemic control.

"This is a crisis that no single country can fully manage on its own," Schiff said.

The researchers plan to continue updating the tool with more information as it becomes available, as well as implement data regarding vaccinations as they become more available in Africa. It is available freely online.

"One of the limitations of doing science is that you can do clever work, publish in a good journal that is reviewed by your peers, but it is still difficult to translate the work into effective policy," Schiff said. "We wanted to implement this tool to do good and help save lives. We could never have accomplished this without the close collaboration with our African colleagues in Uganda. It was critical to make sure this was a framework that people who make policy can use and apply in their work -- that's what makes this valuable."

Even the mundane act of swallowing requires a well-coordinated dance of more than 30 muscles of the mouth. The loss of function of even one of these, due to disease or injury, can be extremely debilitating. For these people, nerve stimulation offers a ray of hope to regain some of their lost oral function.

In a new study, researchers at Texas A&M University have delineated the minimum size of electrical currents needed to provide sensation in different parts of the mouth. The researchers said their study is a first but vital step toward building electrical stimulation implants that can restore essential intraoral functions that are lost due to nerve or brain damage.

The results of the study are published in the journal Institute of Electric and Electronics Engineers' (IEEE) Transactions on Biomedical Engineering.

Many essential bodily functions are coordinated by the nervous system via sensorimotor feedback loops. As the name suggests, these neural circuits involve the brain interpreting incoming signals from sensory nerves and then commanding the motor nerves to execute a certain movement. So, for example, sensorimotor loops play a vital role in voluntary functions, like walking or holding an object, and involuntary movements, like sneezing or blinking.

Within the mouth, also referred to as the intraoral cavity, there is a rich supply of both sensory and motor nerves. In particular, sensorimotor nerves in the soft palate and tongue coordinate several intraoral movements related to swallowing, speech and respiration. And so, damage to either the sensory or motor nerve fibers due to neurotrauma or disease can compromise these essential functions, reducing the quality of life of those afflicted.

Electrical nerve stimulation might help jumpstart the nerves into action, much like how a pacemaker can electrically stimulate nerves in the heart, causing the heart muscle to contract. But unlike a pacemaker, the details on the frequency and amplitude of the electrical currents needed for proper stimulation of different parts of the mouth have not been investigated.

"Electrical stimulation can modulate nerve currents or action potentials, which are the mode of communication to and from the brain," said Dr. Hangue Park, assistant professor in the Department of Electrical and Computer Engineering. "And so, electrical stimulation should be carefully applied, because if not, then it might cause undesirable effects, or it might not stimulate anything at all."

To investigate the minimum stimulation currents needed, Park and his team inserted tiny metal electrodes into a standard dental retainer. These electrodes were positioned in subjects to stimulate either their soft palate or the side and tip of the tongue, which receive a rich supply of sensory nerves. For each of these locations, the researchers slowly changed the amplitude of the stimulation current, keeping the frequency fixed. Then, subjects were asked to report when they just began feeling a sensation and when the sensation was uncomfortable. Next, they repeated the same experiment for a higher frequency of current.

After compiling their data, the team determined the average perception and discomfort thresholds for the tongue and soft palate. In addition, they produced an equivalent circuit of the intraoral cavity to duplicate the electrical properties of that area. This circuit, the researchers said, can help to further study the effects of electrical stimulation offline without requiring human subjects.

The researchers noted that their next steps would be to electrically stimulate the intraoral region and investigate how these simulations change chewing, swallowing and other behaviors.

"Sensorimotor systems can be extremely vulnerable to damage due to neural defects, aging and neurodegenerative diseases," said Park. "In this study, we have begun to lay the groundwork for electrically stimulating parts of the mouth that control involuntary and voluntary movements. Our work is a seminal study and it is important so that we can, in the near future, help people that face enormous challenges doing everyday tasks that we take for granted."

A recent University of Arizona College of Pharmacy study suggests that Objective Structured Clinical Examinations (OSCEs) may be a valuable means of assesing clinical skills while providing learning experiences for pharmacy students in community pharmacy settings. While the OSCEs were designed to assess health care professionals in a clinical setting, there was limited data on its use in testing skills required in community pharmacies, until now.

For pharmacists working in retail, guiding patients on the use of over-the-counter (OTC) drugs is a common part of the job. According to a recent survey from the American Pharmacists Association (APhA), pharmacists make an average of 29 OTC recommendations each week, and approximately 81% of consumers purchase an OTC product their pharmacists recommended. As the profession evolves to providing more patient care services, there is a continued need for pharmacy curricula to maintain pace.

Self-Care Pharmacotherapeutics, a course required by the UArizona Doctor of Pharmacy program, teaches students the appropriate use of medications for self-care inquiries including selection of medications, appropriate dosing, and analysis of safety in a community pharmacy setting. But there was limited information on how best to assess the skills taught during this training. Seeking to fill this gap, a study by College of Pharmacy Assistant Professors Bernadette Cornelison, PharmD, MS, BCPS, and Beth Zerr, PharmD, BCACP, evaluated the use of a community pharmacy-based OSCE in assessing pharmacy students in their first year. The analysis found that students and facilitators believed the OSCE tested the skills needed to provide care in a community setting.

"We teach the self-care therapeutics course in the first semester of the first year in pharmacy school," explained Dr. Cornelison. "We felt it was important to innovate and evaluate new ways of teaching that would educate the students and, hopefully, help them retain information."

The study, published in the Journal of the American College of Clinical Pharmacy, also found that the design of the simulation reflected the accurate amount of time a student intern would have to complete the Pharmacist' Patient Care Process (PPCP). This finding further demonstrates that the PPCP can be applied to patients even when time may seem limited. The standardization of this process is an important step in advancing pharmacists as recognized patient care providers across the country.

Drs. Cornelison and Zerr say the results show a strong case for fully implementing OSCEs in program curricula and are hopeful other colleges of pharmacy will, too.

Directing a meeting, dialing up an old acquaintance, dictating the perfect tuna salad sandwich across a drive-through window. For business and for pleasure, human beings are in constant communication.

Our proclivity for socialization is lifelong, equally prominent in the lives of adolescents and adults. A recent study determined key differences in the ways that various age groups communicate, as well as one conversational component that stands the test of time: friendship. Specifically, bonds between individuals who identify as female.

Led by former Beckman Institute postdoctoral researchers Michelle Rodrigues and Si On Yoon, an interdisciplinary team evaluated how interlocutors’ age and familiarity with one another impacts a conversation, reviewing the interaction’s overall effectiveness and stress responses generated as a result.

The study, titled “What are friends for? The impact of friendship on communicative efficiency and cortisol response during collaborative problem solving among younger and older women,” was published in the Journal of Women and Aging in May 2021.

Two hypotheses form the foundation of this female-focused study. First, the tend-and-befriend hypothesis, which challenges the traditionally masculine “fight-or-flight” dichotomy.

“Women have evolved an alternative mechanism in response to stress,” said Rodrigues, who is currently an assistant professor in the Department of Social and Cultural Sciences at Marquette University. “In order to deal with stress, women can befriend female peers.”

The team also tested the socio-emotional selectivity hypothesis, which postulates a social “pruning” as humans advance in age and pursue more intimate, higher-quality circles of friends.

The introduction of age as a variable is novel in the field and stems from an interdisciplinary Beckman collaboration.

“I was working with several different groups in several different disciplines, coming from the perspective of studying friendship but having previously done research on adolescent girls, but not older women,” Rodrigues said.

She combined forces with then-Beckman-postdoc Si On Yoon, who was studying the cognitive mechanisms of natural conversation across the lifespan, including healthy younger and older adults.

“My research program was focused on language measures in social interactions, and I was glad to work with Dr. Rodrigues to develop an integrative approach including both language processing and physiological measures to study social interactions,” said Yoon, who is currently an assistant professor in the Department of Communication Sciences and Disorders at the University of Iowa.

The interdisciplinary team merged both theories into a single query: Across women’s lifespans, how are the tendencies to “tend and befriend” as well as socially select reflected in their communication?

They tested a pool of 32 women: 16 “older adults” aged 62-79, and 16 “younger adults” aged 18-25. Each participant was either paired with a friend (a “familiar” conversation partner) or a stranger (“unfamiliar”).

The partnerships underwent a series of conversational challenges, wherein the participant instructed her partner to arrange a set of tangrams in an order that only the former could see. The catch? Each shape was abstract, their appearances purposefully difficult to describe.

“You could look at one [tangram] and say, ‘This looks like a dog.’ Or, you could say, ‘This looks like a triangle, with a stop sign, and a bicycle wheel,’” Rodrigues said.

This exercise helped quantify each conversation’s efficiency: partners who achieved the desired tangram arrangement in fewer words were considered more efficient, and pairs who needed more words to complete the task were considered less efficient.

The researchers found that while the younger adult pairs communicated more efficiently with familiar partners than their older counterparts, they communicated less efficiently with unfamiliar partners; alternatively, the older adults demonstrated conversational dexterity, quickly articulating the abstract tangrams to friends and strangers alike.

“A referential communication task like this requires that you see where the other person is coming from. It seems like the younger adults are a little more hesitant in trying to do that, whereas the older adults have an easier time doing that with strangers,” Rodrigues said.

This was not predicted based on the socio-emotional selectivity hypothesis, which anticipated a correlation between age and social isolation.

“Even though older adults choose to spend more time with people who matter to them, it’s clear that they have the social skills to interact with unfamiliar people if and when they choose to,” Rodrigues said.

Rodrigues' team also measured salivary cortisol to quantify and compare participants’ stress levels throughout the testing process.

“When you experience something stressful, if you have a stress response system that’s working as it should, the result is an elevated amount of cortisol, our primary stress hormone, which then tells our bodies to release glucose into our bloodstreams," she said. "That’s reflected in our saliva about 15 to 20 minutes after we experience it. If we see a rise in salivary cortisol from an individual’s baseline levels, that indicates that they are more stressed than they were at the time of the earlier measurements."

Across both age groups, those working with familiar partners had consistently lower cortisol levels than those working with unfamiliar partners.

“A lot of the research on the tend-and-befriend hypothesis has only focused on young women, so it’s great to have these results that pull that out to the end of life. We can see that friendship has that same effect throughout the lifespan. Familiar partners and friendship buffer stress, and that’s preserved with age,” Rodrigues said.

Wine grapes are particularly finicky when it comes to their environment. For instance, heatwaves and droughts lead to earlier berry ripening and lackluster wine. And these types of episodes are expected to intensify as Earth's climate changes. Now, researchers reporting in ACS' Journal of Agricultural and Food Chemistry have tweaked growing conditions for Cabernet Sauvignon grapes to slow down their ripening, which increased the levels of compounds associated with wine's characteristic floral and fruity notes.

As grapes ripen and change color from light green to deep red, sugars and aroma compounds accumulate in the berries. But, when they ripen quickly because of heat or water stress, the resulting fruits produce a less desirable wine with more alcohol, a duller color and a lingering taste of cooked fruit. To counteract these negative effects of climate change on wine quality, scientists have been testing different ways to grow the plants. Previous researchers have shown that reducing the crop on the vines can speed-up grape ripening, while more intense irrigation later in the growing season can delay the process. Christopher Ford and colleagues wanted to examine the impacts of these techniques on the chemical components that contribute to the berries' quality.

The researchers grew Cabernet Sauvignon wine grapes at a commercial vineyard in the San Joaquin Valley in California. Then, they either removed a portion of the clusters on the vines, irrigated the plants more during the later growing season, did both or did neither, and collected grapes throughout the ripening period. The plants with the fewest berry clusters had the fastest increase in sugar content and were ripe the earliest for all of the tested conditions. However, the plants that were both thinned and watered more had the slowest rate of sugar accumulation. The researchers found that slowing down grape ripening decreased six-carbon aldehydes and alcohols and 2-isobutyl-3-methoxypyrazine -- associated with green and vegetal wine notes -- and increased norisoprenoids and terpenes -- associated with pleasant floral and fruity wine notes. The longer growing time improved the quality of grapes for winemaking, the researchers explained, but these adaptation strategies should be monitored over several years before changes are made to current practices.

Amyotrophic lateral sclerosis, or ALS, attacks nerve cells known as motor neurons in the brain and spinal cord, gradually leading to paralysis. The loss of function of an important gene, C9orf72, may affect communication between motor neurons and muscles in people with this disease. These findings were revealed by the team of Dr Kessen Patten of the Institut national de la recherche scientifique (INRS) in the prestigious journal Communications Biology.

A mutation in the C9orf72 gene is the primary genetic cause of ALS. The mutation in C9orf72 consists of an expansion of a sequence of six DNA bases (GGGGCC) that is very unusual, going from a few copies (less than 20 in a healthy person) to more than 1000 copies. The mutation, in part resulting in a loss of function, may be responsible for 40% to 50% of hereditary cases of ALS, and 5% to 10% of cases without family history.

Dr Patten's team investigated this gene's loss of function in genetically modified zebrafish models. In their work, led by PhD student Zoé Butti, the group noted symptoms similar to ALS, namely motor disorders, muscle atrophy, loss of motor neurons, and mortality of individuals.

Synaptic transmission

The study showed the effect of the loss of function induced by the mutation of the C9orf72 gene on communication between motor neurons and muscles. "This synaptic dysfunction is observed in all people with the disease and occurs before the death of motor neurons," noted the researcher and holder of the Anna Sforza Djoukhadjian Research Chair.

The research group also revealed the gene's role on the protein TDP-43 (transactive response DNA binding protein 43) which plays an important role in ALS. The C9orf72 gene may affect the protein TDP-43's location within the cell. "In approximately 97% of ALS patients, the TDP-43 protein is depleted from the nucleus and forms aggregates in the cytoplasm rather than being in the nucleus, as is the case in healthy people. We want to investigate this relationship between the two proteins further," explained Professor Patten.

Now that the team has developed a model, it will be able to test therapeutic molecules. The aim is to find a drug to restore the synaptic connection between neurons and muscles. It may also lead to a therapeutic target to rectify the abnormality of the TDP-43 protein.

Na3V2(PO4)2F3(NVPF), a cathode material used in sodium-ion batteries (SIB), features ultrafast Na+ migration and high structural stability because of its three-dimensional open framework. However, the poor intrinsic electronic conductivity of NVPF often leads to high polarization, low Coulombic efficiency, and unsatisfactory rate performance, which hinder its commercial application.

Recently, a group led by Prof. Shuangqiang Chen and Prof. Yong Wang from Shanghai University synthesized zirconium-doped NVPF nanoparticles coated with a nitrogen-doped carbon layer and demonstrated a synergistic effect on the overall electrochemical performance. Specifically, the optimized NVPF-Zr-0.02/NC electrode led to high reversible capacity (119.2 mA h g-1 at 0.5 C), superior rate capacity (98.1 mA h g-1 at 20 C), and excellent cycling performance (capacity retention of 90.2% in 1000 cycles at 20 C). In situ XRD characterization of the NVPF-Zr-0.02/NC electrode was performed to monitor the real-time structural evolution in different charge/discharge states. The results confirmed the presence of several intermediates with new phases, following a step-wise Na-extraction/intercalation mechanism with reversible multiphase changes. In addition, NVPF-Zr-0.02/NC//hard carbon full cells demonstrated a high reversible capacity of 99.8 mA h g-1 at 0.5C, with an average output voltage of 3.5 V, high energy density of ~194 Wh kg-1, and good cycling stability, thus indicating excellent potential for practical application.

"Such attempts provide meaningful guidance and reference for practical SIBs with high capacity, long cycle life, and good structural stability," said Prof. Chen.

Researchers at Chalmers University of Technology, Sweden, have succeeded in developing a method to label mRNA molecules, and thereby follow, in real time, their path through cells, using a microscope - without affecting their properties or subsequent activity. The breakthrough could be of great importance in facilitating the development of new RNA-based medicines.

RNA-based therapeutics offer a range of new opportunities to prevent, treat and potentially cure diseases. But currently, the delivery of RNA therapeutics into the cell is inefficient. For new therapeutics to fulfil their potential, the delivery methods need to be optimised. Now, a new method, recently presented in the highly regarded Journal of the American Chemical Society, can provide an important piece of the puzzle of overcoming these challenges and take the development a major step forward.

"Since our method can help solve one of the biggest problems for drug discovery and development, we see that this research can facilitate a paradigm shift from traditional drugs to RNA-based therapeutics," says Marcus Wilhelmsson, Professor at the Department of Chemistry and Chemical Engineering at Chalmers University of Technology, and one of the main authors of the article.

Making mRNA fluorescent without affecting its natural activity

The research behind the method has been done in collaboration with chemists and biologists at Chalmers and the biopharmaceuticals company AstraZeneca, through their joint research centre, FoRmulaEx as well as a research group at the Pasteur Institute, Paris.

The method involves replacing one of the building blocks of RNA with a fluorescent variant, which, apart from that feature, maintains the natural properties of the original base. The fluorescent units have been developed with the help of a special chemistry, and the researchers have shown that it can then be used to produce messenger RNA (mRNA), without affecting the mRNA's ability to be translated into a protein at natural speed. This represents a breakthrough which has never before been done successfully. The fluorescence furthermore allows the researchers to follow functional mRNA molecules in real time, seeing how they are taken up into cells with the help of a microscope.

A challenge when working with mRNA is that the molecules are very large and charged, but at the same time fragile. They cannot get into cells directly and must therefore be packaged. The method that has proven most successful to date uses very small droplets known as lipid nanoparticles to encapsulate the mRNA. There is still a great need to develop new and more efficient lipid nanoparticles - something which the Chalmers researchers are also working on. To be able to do that, it is necessary to understand how mRNA is taken up into cells. The ability to monitor, in real time, how the lipid nanoparticles and mRNA are distributed through the cell is therefore an important tool.

"The great benefit of this method is that we can now easily see where in the cell the delivered mRNA goes, and in which cells the protein is formed, without losing RNA's natural protein-translating ability," says Elin Esbjörner, Associate Professor at the Department for Biology and Biotechnology and the second lead author of the article.

Crucial information for optimising drug discovery

Researchers in this area can use the method to gain greater knowledge of how the uptake process works, thus accelerating and streamlining the new medicines' discovery process. The new method provides more accurate and detailed knowledge than current methods for studying RNA under a microscope.

"Until now, it has not been possible to measure the natural rate and efficiency with which RNA acts in the cell. This means that you get the wrong answers to the questions you ask when trying to develop a new drug. For example, if you want an answer to what rate a process takes place at, and your method gives you an answer that is a fifth of the correct, drug discovery becomes difficult," explains Marcus Wilhelmsson.

On the way to utilisation - directly into IVA's top 100 list

When the researchers realised what a difference their method could make and how important the new knowledge is for the field, they made their results available as quickly as possible. Recently, the Royal Swedish Academy of Engineering Sciences (IVA) included the project in its annual 100 list and also highlighted it as particularly important for increasing societal resilience to crises. To ensure useful commercialisation of the method, the researchers have submitted a patent application and are planning for a spin-off company, with the support of the business incubator Chalmers Ventures and the Chalmers Innovation Office.

How common COVID-19 is among infants may depend on the degree of the pandemic virus circulating in a community, a new study finds.

Published online June 30 in the journal Pediatrics, the study found specifically that rates of the infection with the virus that causes COVID-19 were higher among infants hospitalized, not for COVID-19 - but instead because they were being evaluated for a potential serious bacterial infection (SBI) - during periods of high COVID-19 circulation in New York City. The study also found rates of COVID-19 positivity in this age group were lower when infection rates in the city were low.

Led by researchers from NYU Langone Health, the study also examined the clinical course of the infection in young infants and found that the most common presentation of COVID-19 was a fever without other symptoms.

"Enhancing our knowledge of how COVID-19 infection affects young infants is important for informing clinical practice, and for planning public health measures such as vaccination distribution," says Vanessa N. Raabe, MD, assistant professor in NYU Langone's Departments of Medicine and Pediatrics, in the Division of Pediatric Infectious Diseases, and one of the study's principal investigators.

New York City was the early epicenter of COVID-19 in the United States, with more than 190,000 reported infections during the peak of the NYC epidemic between March and May in 2020. Three percent of the reported cases were in children under 18 years of age, although these numbers may underestimate the true incidence given the lack of adequate testing. Most children infected with the disease were asymptomatic or had mild symptoms. However, cases of severe illness have been reported and some reports suggest young infants may be at higher risk for severe disease than older children.

Young babies are often treated with antibiotics in the hospital when they run a fever until doctors can make sure they don't have a serious bacterial infection, such as meningitis or a bloodstream infection, say the study authors.

"Because fever is a common symptom of COVID-19 in children, clinicians must consider COVID-19 as a potential cause of fever and not solely rely on laboratory or imaging results to guide decision-making on whether or not to test hospitalized infants for COVID-19," says Dr. Raabe.

The current study analyzed data from infants less than 90 days of age admitted for SBI evaluation at NYU Langone Health hospitals and NYC Health + Hospitals/Bellevue Hospital between March and December 2020. Among 148 infants, 15 percent tested positive for COVID-19, and two of the 22 infants with COVID-19 required ICU admission, but were discharged safely. Specifically, the team found that only 3 percent of infants tested positive during periods of low community circulation, compared to 31 percent in communities with high infection rates.

The team also found a relatively low incidence (six percent) of infection of the hospitalized infants with other commonly occurring viruses, whether or not they had COVID-19. "This likely reflects community-wide decreases in other respiratory viruses reported in New York during the study period due to enhanced infection control practices, like social distancing and mask wearing, at the height of the pandemic," says Raabe.

The researchers recommend clinicians continue to assess young infants that present with fevers for bacterial infections, regardless of the COVID-19 status, and given the potential severe consequences if not treated.

"It may be intuitive that what is happening in children reflects conditions in the surrounding community, but we find it reassuring that the evidence confirms this relationship," says lead author Michal Paret, MD, a fellow in the Department of Pediatrics, Division of Pediatric Infectious Diseases at NYU Langone. "The epidemiology of COVID-19 continues to evolve with the emergence of variant viruses and vaccination implementation. In the face of these changes physicians need to continue studying this age group, with the goal of determining ultimately whether a selective or universal testing strategy best serves the health of infants long-term."

Our universe is expanding, but our two main ways to measure how fast this expansion is happening have resulted in different answers. For the past decade, astrophysicists have been gradually dividing into two camps: one that believes that the difference is significant, and another that thinks it could be due to errors in measurement.

If it turns out that errors are causing the mismatch, that would confirm our basic model of how the universe works. The other possibility presents a thread that, when pulled, would suggest some fundamental missing new physics is needed to stitch it back together. For several years, each new piece of evidence from telescopes has seesawed the argument back and forth, giving rise to what has been called the 'Hubble tension.'

Wendy Freedman, a renowned astronomer and the John and Marion Sullivan University Professor in Astronomy and Astrophysics at the University of Chicago, made some of the original measurements of the expansion rate of the universe that resulted in a higher value of the Hubble constant. But in a new review paper accepted to the Astrophysical Journal, Freedman gives an overview of the most recent observations. Her conclusion: the latest observations are beginning to close the gap.

That is, there may not be a conflict after all, and our standard model of the universe does not need to be significantly modified.

The rate at which the universe is expanding is called the Hubble constant, named for UChicago alum Edwin Hubble, SB 1910, PhD 1917, who is credited with discovering the expansion of the universe in 1929. Scientists want to pin down this rate precisely, because the Hubble constant is tied to the age of the universe and how it evolved over time.

A substantial wrinkle emerged in the past decade when results from the two main measurement methods began to diverge. But scientists are still debating the significance of the mismatch.

One way to measure the Hubble constant is by looking at very faint light left over from the Big Bang, called the cosmic microwave background. This has been done both in space and on the ground with facilities like the UChicago-led South Pole Telescope. Scientists can feed these observations into their 'standard model' of the early universe and run it forward in time to predict what the Hubble constant should be today; they get an answer of 67.4 kilometers per second per megaparsec.

The other method is to look at stars and galaxies in the nearby universe, and measure their distances and how fast they are moving away from us. Freedman has been a leading expert on this method for many decades; in 2001, her team made one of the landmark measurements using the Hubble Space Telescope to image stars called Cepheids. The value they found was 72. Freedman has continued to measure Cepheids in the years since, reviewing more telescope data each time; however, in 2019, she and her colleagues published an answer based on an entirely different method using stars called red giants. The idea was to cross-check the Cepheids with an independent method.

Red giants are very large and luminous stars that always reach the same peak brightness before rapidly fading. If scientists can accurately measure the actual, or intrinsic, peak brightness of the red giants, they can then measure the distances to their host galaxies, an essential but difficult part of the equation. The key question is how accurate those measurements are.

The first version of this calculation in 2019 used a single, very nearby galaxy to calibrate the red giant stars' luminosities. Over the past two years, Freedman and her collaborators have run the numbers for several different galaxies and star populations. "There are now four independent ways of calibrating the red giant luminosities, and they agree to within 1% of each other," said Freedman. "That indicates to us this is a really good way of measuring the distance."

"I really wanted to look carefully at both the Cepheids and red giants. I know their strengths and weaknesses well," said Freedman. "I have come to the conclusion that that we do not require fundamental new physics to explain the differences in the local and distant expansion rates. The new red giant data show that they are consistent."

University of Chicago graduate student Taylor Hoyt, who has been making measurements of the red giant stars in the anchor galaxies, added, "We keep measuring and testing the red giant branch stars in different ways, and they keep exceeding our expectations."

The value of the Hubble constant Freedman's team gets from the red giants is 69.8 km/s/Mpc--virtually the same as the value derived from the cosmic microwave background experiment. "No new physics is required," said Freedman.

The calculations using Cepheid stars still give higher numbers, but according to Freedman's analysis, the difference may not be troubling. "The Cepheid stars have always been a little noisier and a little more complicated to fully understand; they are young stars in the active star-forming regions of galaxies, and that means there's potential for things like dust or contamination from other stars to throw off your measurements," she explained.

To her mind, the conflict can be resolved with better data.

Next year, when the James Webb Space Telescope is expected to launch, scientists will begin to collect those new observations. Freedman and collaborators have already been awarded time on the telescope for a major program to make more measurements of both Cepheid and red giant stars. "The Webb will give us higher sensitivity and resolution, and the data will get better really, really soon," she said.

But in the meantime, she wanted to take a careful look at the existing data, and what she found was that much of it actually agrees.

"That's the way science proceeds," Freedman said. "You kick the tires to see if something deflates, and so far, no flat tires."

Some scientists who have been rooting for a fundamental mismatch might be disappointed. But for Freedman, either answer is exciting.

"There is still some room for new physics, but even if there isn't, it would show that the standard model we have is basically correct, which is also a profound conclusion to come to," she said. "That's the interesting thing about science: We don't know the answers in advance. We're learning as we go. It is a really exciting time to be in the field."

Almost twenty years ago, the process of RNA silencing was discovered in plants, whereby small fragments of RNA inactivate a portion of a gene during protein synthesis. These fragments--called microRNAs (abbreviated as miRNAs)--have since been shown to be essential at nearly every stage of growth and development in plants, from the production of flowers, stems, and roots to the ways plants interact with their environment and ward off infection.

The detection and characterization of miRNAs is an active field of research. In the decade following their discovery in plants, over 1,000 bioinformatic tools were used to identify miRNAs and map out potential places to look for them.

In a new study published in the journal Applications in Plant Sciences, researchers set out to simplify the process of miRNA discovery and characterization by testing eight of the most commonly used miRNA applications, evaluating each based on accuracy, sensitivity, speed, and the amount of computer memory used by the software.

The sheer number of applications available can make studying miRNAs a daunting task. The majority of these tools (77%) were also developed and tested with animal systems in mind, making it unclear whether their utility can be extended for the detection and analysis of miRNAs in plants.

"The biosynthetic pathways of miRNA in plants and animals are different," said Dr. Qi You, a lecturer at the Agricultural College of Yangzhou University and senior author of the study. "At the same time, the stem-loop structure of plant miRNA precursors is larger than that of animals. Plant miRNAs will be modified by methylation, but animal miRNAs will not."

Things get even trickier when considering that individuals of the same plant species can have varying genome sizes, making it difficult to develop a single standardized approach. Additionally, some programs only look for miRNAs that are already known to exist, while others comb through genomes to find new additions to the list.

Finally, while most tools use search criteria to directly identify miRNA sequences in a genome, others are designed to search for miRNAs in their early developmental stages (precursor miRNA), when more base pairs are attached at either end before a molecular cleaving process trims them down to size.

You and her colleagues took eight miRNA applications (one that was developed for use in animals, and two that are exclusively used to locate precursor miRNA) and vigorously tested them on four different plant species, each with varying genome sizes: thale cress (Arabidopsis thaliana), rice (Oryza sativa), maize (Zea mays), and wheat (Triticum aestivum).

While all eight programs had similar performance in terms of accuracy, there were some obvious winners and losers for all other metrics scored, analyzed both together and separately.

First, the software developed for miRNA detection in animals scored low on sensitivity and on average took longer to run than most of the other programs. It was particularly bad at identifying known miRNAs in maize and had a high rate of true to false positives in wheat, indicating it likely isn't reliably suitable for use in plants.

Two programs stood out from the rest for their high sensitivity and low run times. The first, miRExpress--a program developed in 2009 for the detection of putative novel miRNAs--had the highest sensitivity for three of the four species tested and used the least amount of memory. The runner-up was the program sRNAbench, which had the highest sensitivity for wheat and similar run times.

Of the two, sRNAbench has many of the same functions and utility as the program developed for animal systems tested in this study, making it a solid stand-in for use in plants.

Ultimately, however, there's no one-size-fits-all option when it comes to choosing the best program, and researchers should choose based on their needs and available resources, You said.

"Researchers should consider the size of the genome of the tested species, the size of the sample data, and the configuration of their own computer equipment."

For labs that might not have access to high-performance computing or that don't have ample computer memory space, the authors recommend miRExpress, which maintains high accuracy rates while being less resource-intensive.

For those with more RAM, sRNAbench is the next step up, with high accuracy and applicability to several species with varying genome sizes. Similarly, detecting precursor miRNA requires large amounts of RAM, for which the authors recommend the program miRkwood.

There might be fewer bonobos left in the wild than we thought. For the last 40 years, scientists have estimated the abundance of endangered bonobos by counting the numbers of sleeping nests left by the apes in forests of the Congo Basin. Now, researchers from the Max Planck Institute of Animal Behavior report that the rate of sleeping nest "decay" has lengthened by 17 days over the last 15 years as a result of declining rainfall in the Congo Basin. The study warns that longer nest decay times have serious implications for ape conservation: failure to account for these changes would lead to overestimating population density by up to 60 percent, subsequently jeopardizing conservation of these endangered great apes in the wild.

Bonobos (Pan paniscus) are a species of great ape similar to chimpanzees that are found only in the rainforests of the Congo Basin--the second largest forest area of the planet and known as one of Earth's "green lungs."

The study of the LuiKotale Bonobo Project, which is part of an ongoing collaboration with scientists at Liverpool John Moores University, the Centre for Research and Conservation, and the Max Planck Institute of Animal Behavior, aimed to assess the influence of weather on the decomposition of bonobo sleeping platforms, also called nests. In the LuiKotale research site in the Democratic Republic of the Congo, the scientists studied 15 years of climate data, including rainfall, and 1,511 bonobo nests observed from construction to disappearance. "While climate change is known to be impacting Central African rainforests, a lack of real data from the Congo Basin meant that we didn't know how this was affecting the region and bonobos," says Barbara Fruth, Group Leader at the Max Planck Institute of Animal Behavior in Konstanz, Germany, who is senior author on the study. "Our study provides evidence that the world's largest freshwater reservoir is suffering from climate change," she says.

How to convert nest counts into ape counts

This troubling trend has added importance for bonobos, and great apes in general, because their populations are estimated not by counting actual apes, but rather the nests left by the primates each night. Knowing how fast these nests disappear is essential for converting nest counts to ape counts. The study's results showed a steady decline of rainfall across years and the impact of this on bonobo nest decay times. Less rain meant that nests persisted for longer in the forest. Further, the scientists observed bonobos using more solid construction types in response to more unpredictable storms.

The connection between nest decay and climate change is relevant to conservation of all great apes because nest counts are used as the "gold standard for estimating their populations," says first author Mattia Bessone, a PhD student at Liverpool John Moores University who is working on validating cutting-edge methods for assessing threatened species. "As climate change continues to affect both the process of nest decay and ape nest building behaviour, great ape nest decomposition times are likely only to increase further in future years. "We stress the absolute necessity to take into account the specific impact of climate on nests in areas where these are being used to surveying great apes. Failure to do so will invalidate biomonitoring estimates of global significance and subsequently jeopardize the conservation of great apes in the wild."