Publisher Health

Researchers from Carnegie Mellon University’s Computational Biology Department in the School of Computer Science have developed a new process that could reinvigorate the search for natural product drugs to treat cancers, viral infections and other ailments.
The machine learning algorithms developed by the Metabolomics and Metagenomics Lab match the signals of a microbe’s metabolites with its genomic signals and identify which likely correspond to a natural product. Knowing that, researchers are better equipped to isolate the natural product to begin developing it for a possible drug.
“Natural products are still one of the most successful paths for drug discovery,” said Bahar Behsaz, a project scientist in the lab and lead author of a paper about the process. “And we think we’re able to take it further with an algorithm like ours. Our computational model is orders of magnitude faster and more sensitive.”
In a single study, the team was able to scan the metabolomics and genomic data for about 200 strains of microbes. The algorithm not only identified the hundreds of natural product drugs the researchers expected to find, but it also discovered four novel natural products that appear promising for future drug development. The team’s work was published recently in Nature Communications.
The paper, “Integrating Genomics and Metabolomics for Scalable Non-Ribosomal Peptide Discovery,” outlines the team’s development of NRPminer, an artificial intelligence tool to aid in discovering non-ribosomal peptides (NRPs). NRPs are an important type of natural product and are used to make many antibiotics, anticancer drugs and other clinically used medications. They are, however, difficult to detect and even more difficult to identify as potentially useful.
“What is unique about our approach is that our technology is very sensitive. It can detect molecules with nanograms of abundance,” said Hosein Mohimani, an assistant professor and head of the lab. “We can discover things that are hidden under the grass.”
Most of the antibiotic, antifungal and many antitumor medications discovered and widely used have come from natural products.
Penicillin is among the most used and well-known drugs derived from natural products. It was, in part, discovered by luck, as are many of the drugs made from natural products. But replicating that luck is difficult in the laboratory and at scale. Trying to uncover natural products is also time and labor intensive, often taking years and millions of dollars. Major pharmaceutical companies have mostly abandoned the search for new natural products in the past decades.
By applying machine learning algorithms to the study of genomics, however, researchers have created new opportunities to identify and isolate natural products that could be beneficial.
“Our hope is that we can push this forward and discover other natural drug candidates and then develop those into a phase that would be attractive to pharmaceutical companies,” Mohimani said. “Bahar Behsaz and I are expanding our discovery methods to different classes of natural products at a scale suitable for commercialization.”
The team is already investigating the four new natural products discovered during their study. The products are being analyzed by a team led by Helga Bode, head of the Institute for Molecular Bioscience at Goethe University in Germany, and two have been found to have potential antimalarial properties.
This study was conducted in collaboration with researchers from the University of California San Diego; Saint Petersburg University; the Max-Planck Institute; Goethe University; the University of Wisconsin, Madison; and the Jackson Laboratory.
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Materials provided by Carnegie Mellon University. Original written by Aaron Aupperlee. Note: Content may be edited for style and length.

Many salamanders can readily regenerate a lost limb, but adult mammals, including humans, cannot. Why this is the case is a scientific mystery that has fascinated observers of the natural world for thousands of years.
Now, a team of scientists led by James Godwin, Ph.D., of the MDI Biological Laboratory in Bar Harbor, Maine, has come a step closer to unraveling that mystery with the discovery of differences in molecular signaling that promote regeneration in the axolotl, a highly regenerative salamander, while blocking it in the adult mouse, which is a mammal with limited regenerative ability.
“Scientists at the MDI Biological Laboratory have been relying on comparative biology to gain insights into human health since its founding in 1898,” said Hermann Haller, M.D., the institution’s president. “The discoveries enabled by James Godwin’s comparative studies in the axolotl and mouse are proof that the idea of learning from nature is as valid today as it was more than one hundred and twenty years ago.”
Instead of regenerating lost or injured body parts, mammals typically form a scar at the site of an injury. Because the scar creates a physical barrier to regeneration, research in regenerative medicine at the MDI Biological Laboratory has focused on understanding why the axolotl doesn’t form a scar — or, why it doesn’t respond to injury in the same way that the mouse and other mammals do.
“Our research shows that humans have untapped potential for regeneration,” Godwin said. “If we can solve the problem of scar formation, we may be able to unlock our latent regenerative potential. Axolotls don’t scar, which is what allows regeneration to take place. But once a scar has formed, it’s game over in terms of regeneration. If we could prevent scarring in humans, we could enhance quality of life for so many people.”
The axolotl as a model for regeneration
The axolotl, a Mexican salamander that is now all but extinct in the wild, is a favorite model in regenerative medicine research because of its one-of-a-kind status as nature’s champion of regeneration. While most salamanders have some regenerative capacity, the axolotl can regenerate almost any body part, including brain, heart, jaws, limbs, lungs, ovaries, spinal cord, skin, tail and more.

The organization of the human genome relies on physics of different states of matter — such as liquid and solid — a team of scientists has discovered. The findings, which reveal how the physical nature of the genome changes as cells transform to serve specific functions, point to new ways to potentially better understand disease and to create improved therapies for cancer and genetic disorders.
The genome is the library of genetic information essential for life. Each cell contains the entire library, yet it uses only part of this information. Special types of cells, such as a white blood cell or a neuron, have only certain “books” open — those containing information relevant for their function. Researchers have long sought to determine how the genome manages these enormous libraries and allows access to the “books” that are needed, while storing away the ones not in use.
In the newly published study, which appears in the journal Physical Review Letters, the researchers revealed how this happens within a cell.
“We found that the parts of the genome that are being used are liquid, while the unused parts form solid-like islands,” explains Alexandra Zidovska, an assistant professor in New York University’s Department of Physics and the senior author of the study. “These solid-like islands serve as library bookshelves storing the books with genes not currently in use, while the liquid genome part acts like an ‘open book,’ which is readily accessible and used for a cell’s life and function.”
The genome’s genetic information is encoded in the DNA molecule. Proper reading and processing of this information is critical for human health and aging. In a human cell, the genome, which contains the genetic code, is housed in the cell nucleus. Barely 10 micrometers in size — or about 10 times smaller than the width of a strand of human hair — it stores about two meters of DNA.
Storing this vast amount of genetic information in such a small space requires packing in such a way so that each piece of DNA, and thus of genetic code, is easily accessible when needed.

A new study published in the journal Stem Cell Reports by University of Alberta researchers is shedding light on why many COVID-19 patients, even those not in hospital, are suffering from hypoxia — a potentially dangerous condition in which there is decreased oxygenation in the body’s tissues. The study also shows why the anti-inflammatory drug dexamethasone has been an effective treatment for those with the virus.
“Low blood-oxygen levels have been a significant problem in COVID-19 patients,” said study lead Shokrollah Elahi, associate professor in the Faculty of Medicine & Dentistry. “Because of that, we thought one potential mechanism might be that COVID-19 impacts red blood cell production.”
In the study, Elahi and his team examined the blood of 128 patients with COVID-19. The patients included those who were critically ill and admitted to the ICU, those who had moderate symptoms and were admitted to hospital, and those who had a mild version of the disease and only spent a few hours in hospital. The researchers found that, as the disease became more severe, more immature red blood cells flooded into blood circulation, sometimes making up as much as 60 per cent of the total cells in the blood. By comparison, immature red blood cells make up less than one per cent, or none at all, in a healthy individual’s blood.
“Immature red blood cells reside in the bone marrow and we do not normally see them in blood circulation,” Elahi explained. “This indicates that the virus is impacting the source of these cells. As a result, and to compensate for the depletion of healthy immature red blood cells, the body is producing significantly more of them in order to provide enough oxygen for the body.”
The problem is that immature red blood cells do not transport oxygen — only mature red blood cells do. The second issue is that immature red blood cells are highly susceptible to COVID-19 infection. As immature red blood cells are attacked and destroyed by the virus, the body is unable to replace mature red blood cells — which only live for about 120 days — and the ability to transport oxygen in the bloodstream is diminished.
The question was how the virus infects the immature red blood cells. Elahi, known for his prior work demonstrating that immature red blood cells made certain cells more susceptible to HIV, began by investigating whether the immature red blood cells have receptors for SARS-CoV-2. After a series of studies, Elahi’s team was the first in the world to demonstrate that immature red blood cells expressed the receptor ACE2 and a co-receptor, TMPRSS2, which allowed SARS-CoV-2 to infect them.

It’s long been known that people living with HIV experience a loss of white matter in their brains. As opposed to “gray matter,” which is composed of the cell bodies of neurons, white matter is made up of a fatty substance called myelin that coats neurons, offering protection and helping them transmit signals quickly and efficiently. A reduction in white matter is associated with motor and cognitive impairment.
Earlier work by a team from the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP) found that antiretroviral therapy (ART) — the lifesaving suite of drugs that many people with HIV use daily — can reduce white matter, but it wasn’t clear how the virus itself contributed to this loss.
In a new study using both human and rodent cells, the team has hammered out a detailed mechanism, revealing how HIV prevents the myelin-making brain cells called oligodendrocytes from maturing, thus putting a wrench in white matter production. When the researchers applied a compound blocking this process, the cells were once again able to mature.
The work is published in the journal Glia.
“Even when people with HIV have their disease well-controlled by antiretrovirals, they still have the virus present in their bodies, so this study came out of our interest in understanding how HIV infection itself affects white matter,” says Kelly Jordan-Sciutto, a professor in Penn’s School of Dental Medicine and co-senior author on the study. “By understanding those mechanisms, we can take the next step to protect people with HIV infection from these impacts.”
“When people think about the brain, they think of neurons, but they often don’t think about white matter, as important as it is,” says Judith Grinspan, a research scientist at CHOP and the study’s other co-senior author. “But it’s clear that myelination is playing key roles in various stages of life: in infancy, in adolescence, and likely during learning in adulthood too. The more we find out about this biology, the more we can do to prevent white matter loss and the harms that can cause.”
Jordan-Sciutto and Grinspan have been collaborating for several years to elucidate how ART and HIV affect the brain, and specifically oligodendrocytes, a focus of Grinspan’s research. Their previous work on antiretrovirals had shown that commonly used drugs disrupted the function of oligodendrocytes, reducing myelin formation.

There is a long-held belief that having your pet sleep on the bed is a bad idea. Aside from taking up space, noisy scratching, or triggering allergies, the most common assertion averred that your furry companion would disrupt your sleep.
A new study published in the journal Sleep Health tells a different story. Researchers at Concordia’s Pediatric Public Health Psychology Lab (PPHP) found that the sleep quality of the surprisingly high number of children who share a bed with their pets is indistinguishable from those who sleep alone.
“Sleeping with your pet does not appear to be disruptive,” says the paper’s lead author, PhD student Hillary Rowe. “In fact, children who frequently slept with their pet endorsed having higher sleep quality.”
Rowe co-wrote the paper with fellow PPHP researchers Denise Jarrin, Neressa Noel, Joanne Ramil and Jennifer McGrath, professor of psychology and the laboratory’s director.
Serendipitous findings
The data the researchers used was found amid the findings of the larger Healthy Heart Project, a longitudinal study funded by the Canadian Institutes of Health Research, which explores the links between childhood stress, sleep and circadian timing.

Nano-sized particles have been engineered in a new way to improve detection of tumors within the body and in biopsy tissue, a research team in Sweden reports. The advance could enable identifying early stage tumors with lower doses of radiation.
In order to enhance visual contrast of living tissues, state-of-the-art imaging relies on agents such as fluorescent dyes and biomolecules. Advances in nanoparticle research have expanded the array of promising contrast agents for more targeted diagnostics, and now a research team from KTH Royal Institute of Technology has raised the bar further yet. They are combining optical and X-ray fluorescence contrast agents into a single enhancer for both modes.
Muhammet Toprak, Professor of Materials Chemistry at KTH, says the synthesis of contrast agents introduces a new dimension in the field of X-ray bio-imaging. The research was reported in the American Chemical Society journal, ACS Nano.
“This unique design of nanoparticles paves the way for in vivo tumor diagnostics, using X-ray fluorescence computed tomography (XFCT),” Toprak says.
He says the new “core-shell nanoparticles” may have a role to play in the development of theranostics, a portmanteau for therapy and diagnostics, in which for example single drug-loaded particles could both detect and treat malignant tissues.
The core-shell contrast agent gets its name from its architecture: it consists of a core combination of nanoparticles with previously-established potential in X-ray fluorescence imaging, such as ruthenium and molybdenum (IV) oxide. This core is encased in a shell comprised of silica and Cy5.5, a near-infrared fluorescence-emitting dye for optical imaging techniques such as optical microscopy and spectroscopy.
Toprak says that encapsulating the Cy5.5 dye within the silica shell improves the agent’s brightness and extends its photo-stability — enabling the dual optical/X-Ray imaging approach. In addition, silica provides the benefit of tempering the toxic effects of the core nanoparticles.
Tests with laboratory mice have shown that the XFCT contrast agents enable location of early stage tumors of only a few millimetres in size.
Toprak says the technology opens the possibility to identify early stage tumors in living tissue. That’s because the presence of multiple contrast agents increases the odds that diseased areas will show up in scans, even as the distribution of the nanoparticles becomes obscured by their interaction with proteins or other biological molecules.
“Nanoparticles of different size, originating from the same material, don’t appear to be distributed in the blood in the same concentrations,” Toprak says. “That’s because when they come into contact with your body, they’re quickly wrapped in various biological molecules — which gives them a new identity.”
A multitude of contrast agents for XFCT would enable studying the biodistribution of nanoparticles in-vivo using low-dose X-rays, he says. That would allow identifying the best size and surface chemistry of the nanoparticles for the desired targeting and imaging of the diseased region.
In addition to Toprak, the study was co-authored by Giovanni M. Saladino, Carmen Vogt, Yuyang Li, Kian Shaker, Bertha Brodin, Martin Svenda and Hans M. Hertz.
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Autistic people’s ability to accurately identify facial expressions is affected by the speed at which the expression is produced and its intensity, according to new research at the University of Birmingham.
In particular, autistic people tend to be less able to accurately identify anger from facial expressions produced at a normal ‘real world’ speed. The researchers also found that for people with a related disorder, alexithymia, all expressions appeared more intensely emotional.
The question of how people with autism recognise and relate to emotional expression has been debated by scientists for more than three decades and it’s only in the past 10 years that the relationship between autism and alexithymia has been explored.
This new study, published in the Journal of Autism and Developmental Disorders, uses new techniques to explore the different impacts of autism and alexithymia on a person’s ability to accurately gauge the emotions suggested by different facial expressions.
Connor Keating, a PhD researcher in the University of Birmingham’s School of Psychology and Centre for Human Brain Health, is lead author of the study. He says: “We identified that autistic people had a specific difficulty recognising anger which we are starting to think may relate to differences in the way autistic and non-autistic people produce these expressions. If this is true, it may not be accurate to talk about autistic people as having an ‘impairment’ or ‘deficit’ in recognising emotion — it’s more that autistic and non-autistic faces may be speaking a different language when it comes to conveying emotion.”
In the study, 31 autistic and 29 non-autistic participants were asked to identify emotions from a series of moving images made up of dots representing the key dynamic points of a facial expression — a little bit like the dots used to translate human movement into CGI animation. The images were displayed at a range of emotional intensities by varying the amount of movement in each expression, and at a variety of speeds.
The team found that both autistic and non-autistic participants had similar recognition capabilities at different speeds and intensities across all the emotions shown, except for one particular aspect — the autistic group were less able to identify angry expressions produced at normal speed and intensity. These represented the sorts of angry expressions that might be encountered in everyday life.
“When we looked at how well participants could recognise angry expressions, we found that it was definitely autistic traits that contribute, but not alexithymic traits,” explained Connor. “That suggests recognising anger is a difficulty that’s specific to autism.”
A key trait that the team found was specific to participants with alexithymia was a tendency to perceive the expressions to be intensely emotional. Interestingly though, people with alexithymia were more likely to give higher correct and incorrect emotion ratings to the expressions. To give an example, those with alexithymia would rate a happy expression as more intensely happy and more intensely angry and sad than someone without alexithymia.
Connor explains: “One idea is that people with alexithymia are less able to gauge the intensity of emotional expressions and are more likely to get confused about which emotion is being presented.”
He adds: “Everyone will know or meet somebody with autism at some point in their lives. By better understanding how people with autism perceive and understand the world we can start to develop training and other interventions for both autistic and non-autistic people to overcome some of the barriers to interacting successfully.”
This project was supported by the Medical Research Council (MRC, United Kingdom) MR/R015813/1 and the European Union’s Horizon 2020 Research and Innovation Programme under ERC-2017-STG Grant Agreement No. 757583.
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The gut and the brain communicate with each other in order to adapt satiety and blood sugar levels during food consumption. The vagus nerve is an important communicator between these two organs. Researchers from the Max Planck Institute for Metabolism Research in Cologne, the Cluster of Excellence for Ageing Research CECAD at the University of Cologne and the University Hospital Cologne now took a closer look at the functions of the different nerve cells in the control centre of the vagus nerve, and discovered something very surprising: although the nerve cells are located in the same control center, they innervate different regions of the gut and also differentially control satiety and blood sugar levels. This discovery could play an important role in the development of future therapeutic strategies against obesity and diabetes.
When we consume food, information about the ingested food is transmitted from the gastrointestinal tract to the brain in order to adapt feelings of hunger and satiety. Based on this information, the brain decides, for example, whether we continue or stop eating. In addition, our blood sugar level are adapted by the brain. The vagus nerve, which extends from the brain all the way down to the gastrointestinal tract, plays an essential role in this communication. In the control center of the vagus nerve, the so-called nodose ganglion, various nerve cells are situated, some of which innervate the stomach while others innervate the intestine. Some of these nerve cells detect mechanical stimuli in the different organs, such as stomach stretch during feeding, while others detect chemical signals, such as nutrients from the food that we consume. But what roles these different nerve cells play in transmitting information from the gut to the brain, and how their activity contributes to adaptations of feeding behavior and blood sugar levels had remained largely unclear.
“To investigate the function of the nerve cells in the nodose ganglion, we developed a genetic approach that enables us to visualize the different nerve cells and manipulate their activity in mice. This allowed us to analyze which nerve cells innervate which organ, pointing to what kind of signals they detect in the gut,” says study leader Henning Fenselau. “It also allowed us to specifically switch on and off the different types of nerve cells to analyze their precise function.”
Different food activates different nerve cells
In their studies, the researchers focused primarily on two types of nerve cells of the nodose ganglion, which is just one millimeter in size. “One of these cell types detects stomach stretch, and activation of these nerve cells causes mice to eat significantly less,” Fenselau explains. “We identified that activity of these nerve cells is key for transmitting appetite-inhibiting signals to the brain and also decreasing blood sugar levels.” The second group of nerve cells primarily innervates the intestine. “This group of nerve cells senses chemical signals from our food. However, their activity is not necessary for feeding regulation. Instead, activation of these cells increases our blood sugar level,” says Fenselau. Thus, these two types of nerve cells in the control center of the vagus nerve fulfil very different functions.
“The reaction of our brain during food consumption is probably an interplay of these two nerve cell types,” Fenselau explains. “Food with a lot of volume stretches our stomach, and activates the nerve cell types innervating this organ. At a certain point, their activation promotes satiety and hence halts further food intake, and at the same time coordinates the adaptations of blood sugar levels. Food with a high nutrient density tends to activate the nerve cells in the intestine. Their activation increases blood glucose levels by coordinating the release of the body’s own glucose, but they do not halt further food intake.” The discovery of the different functions of these two types of nerve cells could play a crucial role in developing new therapeutic strategies against obesity and diabetes.
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Materials provided by Max-Planck-Gesellschaft. Note: Content may be edited for style and length.

A facial expression or the sound of a voice can say a lot about a person’s emotional state; and how much they reveal depends on the intensity of the feeling. But is it really true that the stronger an emotion, the more intelligible it is? An international research team comprised of scientists from the Max Planck Institute for Empirical Aesthetics, New York University, and the Max Planck NYU Center for Language, Music, and Emotion (CLaME) has now discovered a paradoxical relationship between the intensity of emotional expressions and how they are perceived.
Emotions vary in their intensity. A person being attacked by a house cat may well feel fear; but certainly their fear would be even greater if a lion or tiger were attacking them. So our emotions differ in terms of degrees of strength. But how does this affect our ability to infer meaning from how an emotion is expressed? Research on emotion has so far assumed that emotion expressions become more distinct as their intensity increases. But there is little empirical evidence to support this intuitive-sounding idea.
A team of researchers from Frankfurt am Main and New York have now systematically investigated the role of emotional intensity for the first time. They collected a multitude of nonverbal vocalizations, including screams, laughter, sighs, groans, etc. These sounds all expressed different positive and negative emotions ranging from minimal to maximal emotional intensity. They then examined how listeners perceived these sounds differently depending on the emotional intensity they expressed.
The team came to a surprising conclusion: at first, as the intensity of the emotions increased, participants’ ability to judge them also improved, attaining a kind of ‘sweet spot’ in perceiving moderate to strong emotions. When the emotions became maximally intense, however, their legibility decreased quite drastically. Lead author Natalie Holz of the Max Planck Institute for Empirical Aesthetics explains:
“Counterintuitively, we found that maximally intense emotions are not the easiest to infer meaning from. In fact, they are the most ambiguous of all.”
And the paradox? For extremely intense emotions, neither their individual categories, such as surprise and triumph, nor valence, such as pleasantness and unpleasantness, could be distinguished reliably; nor could they be classified as being more positive or negative. Nevertheless, both the intensity itself and the state of arousal were perceived consistently and clearly. Holz suggests a reason for this:
“At peak intensity, the most vital job might be to detect big events and to assess relevance. A more fine-grained evaluation of affective meaning may be secondary.”
The research team’s article, just published in the journal Scientific Reports, makes clear that emotional intensity is a dominant factor in the perception of emotion, but in a far more complex way than previously thought. This poses a challenge to prevailing theories of emotion. The study of emotional intensity, and of peak emotions in particular, can enrich our understanding of affective experience and how we communicate emotion.
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