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During development and associated processes, the programmed death of certain cells plays an essential role in shaping organs and allowing proper growth. This cell death is in some cases an effect of autophagy, a key cellular process responsible for the degradation and recycling of damaged or unwanted cellular components and which, taken to the extreme, may end up eliminating the cell itself.utophagy.During development and associated processes, the programmed death of certain cells plays an essential role in shaping organs and allowing proper growth. This cell death is in some cases an effect of autophagy, a key cellular process responsible for the degradation and recycling of damaged or unwanted cellular components and which, taken to the extreme, may end up eliminating the cell itself.
Led by Dr. Jordi Casanova and Dr. Panagiotis Giannios, a team of researchers at IRB Barcelona and IBMB(CSIC) has revealed the relationship between autophagy and polyploidy, the latter a phenomenon in which cells contain multiple copies of genetic material. In this regard, they have discovered a scenario where the level of autophagy is much higher in cells with several copies of DNA and that it can even trigger this programmed cell death.
Published in the journal Autophagy, this finding sheds light on the biological processes that shape organisms during the early stages of life, and it paves the way to a better understanding of developmental diseases and also cancer.
“Polyploidy is a common phenomenon in many species, including humans, and understanding its implications for embryonic development could have a significant impact medicine,” explains Dr. Casanova, head of the Development and Morphogenesis in Drosophila lab at IRB Barcelona.
Progenitor cells and polyploidy
Progenitor cells can give rise to different cell types. In the case of the Drosophila melanogaster fly, the animal model used in this study, the progenitor cells are larval cells that conserve the capacity to give rise to the adult organism. These cells do not present polyploidy (they have a single copy of the set of chromosomes) and this allows them to survive metamorphosis and form part of the adult.

Innovative treatment paves the way for reducing antimicrobial resistance in the treatment of a deadly infection in chickens, according to an international team of researchers led by the University of Surrey.
The ground-breaking study investigated the effectiveness of a novel metal-derived complex in treating Avian Pathogenic Escherichia coli (APEC), a serious respiratory infection of chickens which has become increasingly more resistant to antibiotics. A growing body of evidence indicates that the APEC could potentially spread to humans.
The international research team also included the University of Surrey, the Animal and Plant Health Agency, the University of Connecticut, the University of Sheffield and Institut für Anorganische Chemie, Julius-Maximilians-Universität Würzburg.
Professor Roberto La Ragione, Professor of Veterinary Microbiology and Pathology at the University of Surrey, said:
“Antimicrobial resistance is one of the biggest threats to human and animal health. Not being able to use antibiotics to treat an infection not only prolongs an illness and associated welfare issues, but also increases the likelihood of it spreading.
“Coronavirus demonstrated how easily a pandemic can happen, and the threat of another is looking more likely as antibiotics to treat simple bacterial infections are no longer working.”
To test the effectiveness of the metal complex, manganese carbonyl, researchers worked with the Greater Wax Moth larvae and APEC. Split into two groups, the first received manganese carbonyl, whilst the second, the controls, received either a phosphate-buffered saline (PBS) or dimethyl sulfoxide (DMSO). After four days, the survival rate for the larvae which received manganese carbonyl was between 56 – 75 per cent, whereas in the control group, the survival rate was between 25-45 per cent (PBS) and 19-45 per cent (DMSO), demonstrating the protective effect of the complex.

For millions of Americans who have heart surgery or experience cardiovascular complications, like heart attack or heart failure, they may be encouraged to participate in cardiac rehabilitation. The medically supervised program combines lifestyle changes, education and physical activity to help patients recover and reduce their risk of future problems.
A Michigan Medicine study now finds that people who participate in cardiac rehabilitation have a decreased risk of death years after surgery, with a trend towards better outcomes in patients who attend more sessions.
“Time and time again, cardiac rehabilitation has been shown to improve outcomes and quality of life for patients undergoing heart surgery, yet we often fall short in getting patients to attend,” senior author Michael P. Thompson, Ph.D., assistant professor of cardiac surgery at University of Michigan Medical School.
Researchers explored over 6,400 Medicare fee-for-service claims linked to clinical registry data to assess cardiac rehabilitation use by Michigan residents after coronary artery bypass grafting, a procedure commonly called heart bypass, between 2015 and late 2019. The surgery improves blood flow to the heart by connecting a healthy artery or vein from another part of the body to a portion of the coronary artery that is blocked.
The multicenter study concluded that patients who underwent cardiac rehabilitation after heart bypass surgery had a 3-5% absolute reduced mortality rate in the two years following the procedure. The greatest reduction in mortality was found in patients who completed 36 or more sessions, which is the recommended number for coronary artery bypass grafting patients.
“While attending any cardiac rehabilitation session was better than none at all, our data highlight that patients received a greater benefit when they attended more sessions,” Thompson said. “Focusing on both attendance and adherence to cardiac rehabilitation will benefit patients.”
The patients who tended to participate in cardiac rehab after coronary artery bypass grafting were older on average, discharged to their home more often than an extended care facility and spent less time in the hospital.

As life expectancy increases worldwide, age-associated diseases such as osteoporosis are having an increasing impact. Although early detection could help physicians intervene as soon as possible — when treatment might offer the greatest benefit — this type of detection is not yet possible with current osteoporosis diagnostic tests. Now, researchers reporting in ACS Central Science have developed a biosensor that could someday help identify those most at risk for osteoporosis using less than a drop of blood.
Early intervention is critical to reducing the morbidity and mortality associated with osteoporosis, a condition characterized by an elevated risk of bone fractures and which affects about 54 million people in the U.S., according to the International Osteoporosis Foundation. The most common technique used to measure changes in bone mineral density (BMD) — dual-energy X-ray absorptiometry — is not sufficiently sensitive to detect BMD loss until a significant amount of damage has already occurred. Several genomic studies, however, have reported genetic variations known as single nucleotide polymorphisms (SNPs) that are associated with increased risk for osteoporosis. Using this information, Ciara K. O’Sullivan and colleagues wanted to develop a portable electrochemical device that would allow them to quickly detect five of these SNPs in finger-prick blood samples in a step toward early diagnosis.
The device involves an electrode array to which DNA fragments for each SNP are attached. When lysed whole blood is applied to the array, any DNA matching the SNPs binds the sequences and is amplified with recombinase polymerase that incorporates ferrocene, a label that facilitates electrochemical detection. Using this platform, the researchers detected osteoporosis-associated SNPs in 15 human blood samples, confirming their results with other methods.
As the DNA does not have to be purified from the blood, the analysis can be performed quickly (about 15 minutes) and inexpensively (< $0.5 per SNP). Furthermore, because the equipment and reagents are readily accessible and portable, the researchers say that the device offers great potential for use at point-of-care settings, rather than being limited to a centralized laboratory. The technology is also versatile and can be readily adapted to detect other SNPs, as the researchers showed previously when identifying drug resistance in Tuberculosis mycobacterium from sputum and cardiomyopathy risk from blood. Although the device does not diagnose osteoporosis itself, it might help physicians identify people whom they should monitor more closely.

Whether enjoyed on its own or mixed into a latte, Americano or even a martini, espresso provides an ultra-concentrated jolt of caffeine to coffee lovers. But it might do more than just wake you up. Research now published in ACS’ Journal of Agricultural and Food Chemistry shows that, in preliminary in vitro laboratory tests, espresso compounds can inhibit tau protein aggregation — a process that is believed to be involved in the onset of Alzheimer’s disease.
Roughly half of all Americans drink coffee every day, and espresso is a popular way to consume it. To “pull” an espresso shot, hot water is forced through finely ground coffee beans, creating a concentrated extract. This is often used as a base for other drinks, including the trendy espresso martini. Recent research has suggested that coffee could also have beneficial effects against certain neurodegenerative diseases, including Alzheimer’s disease. Although the exact mechanisms that cause these conditions are still unclear, it’s thought that a protein called tau plays a significant role. In healthy people, tau proteins help stabilize structures in the brain, but when certain diseases develop, the proteins can clump together into fibrils. Some researchers propose that preventing this aggregation could alleviate symptoms. So, Mariapina D’Onofrio and colleagues wanted to see if compounds in espresso could prevent tau aggregation in vitro.
The researchers pulled espresso shots from store-bought beans, then characterized their chemical makeup using nuclear magnetic resonance spectroscopy. They chose caffeine and trigonelline, both alkaloids, the flavonoid genistein and theobromine, a compound also found in chocolate, to focus on in further experiments. These molecules, along with the complete espresso extract, were incubated alongside a shortened form of the tau protein for up to 40 hours. As the concentration of espresso extract, caffeine or genistein increased, fibrils were shorter and didn’t form larger sheets, with the complete extract showing the most dramatic results. Shortened fibrils were found to be non-toxic to cells, and they did not act as “seeds” for further aggregation. In other experiments, the researchers observed that caffeine and the espresso extract could both bind pre-formed tau fibrils. Although much more research is needed, the team says that their preliminary in vitro findings could pave the way toward finding or designing other bioactive compounds against neurodegenerative diseases, including Alzheimer’s.

The discovery of antibiotics in 1928 was a major turning point in the history of medicine. For the first time since the dawn of human civilization, doctors had gained access to an extremely powerful and effective tool to fight against a wide variety of bacterial infections. Today, bacterial diseases that were previously a death sentence can be cured, and infections following surgery or chemotherapy can be prevented or treated more effectively.
Unfortunately, the worldwide use (and abuse) of antibiotics led to the emergence of drug-resistant bacterial strains. Over time, bacteria that could normally be killed by a given antibiotic produced mutant offspring immune to it. These mutant strains are a major threat to public health, and the only safe course of action is to develop new antibiotic compounds.
Against this backdrop, a research team including Professor Isamu Shiina, Assistant Professor Takatsugu Murata and Mr. Hisazumi Tsutsui from the Tokyo University of Science (TUS) in Japan has now achieved a major breakthrough in the synthesis of new antibiotics. As reported in their paper published in ACS Omega in July 2023, the team achieved the first-ever gram-scale synthesis of tanzawaic acid B, which can serve as a candidate for the discovery of new drugs.
But what is tanzawaic acid B? In 1997, Professor Daisuke Uemura and colleagues working in the Tanzawa area of Japan isolated a series of organic polyketide compounds from the fungus Penicillium citrinum. These compounds were grouped together into what we now call the “tanzawaic” acid family, containing dozens of members ranging from A to Z1. In particular, tanzawaic acid B has attracted the most attention as it shares a common core structure with many tanzawaic acids, meaning that an artificial synthesis method for tanzawaic acid B could readily lead to synthesis methods for the rest.
However, synthesizing tanzawaic acid B from scratch is a challenging endeavor. The tanzawaic acids share a polysubstituted octalin skeleton — a structure composed of 10 carbon atoms in a tight pattern with multiple chemical groups at specific locations. The researchers synthesized this skeleton by utilizing a chain-like molecule that they had synthesized in a previous study. Then, by leveraging a carefully controlled intramolecular Diels-Alder reaction, they made these chains preferentially “fold” into the desired octalin skeleton.
The next challenge was to precisely modify the octalin skeleton in multiple steps to produce tanzawaic acid B. As octalin has eight carbon atoms that can participate in stereochemical reactions, any desired substitution effectively competes with 255 other possible arrangements. To tackle this issue, the researchers employed asymmetric alkylation and asymmetric Mukaiyama aldol reaction, which enabled them to produce the desired polysubstituted octalin compound tanzawaic acid B on gram scale.
Overall, this new synthesis technique could play a key role in the development of antibiotic drugs based on tanzawaic acids. Excited about the outcome of the study, Prof. Shiina comments: “For more than 25 years since its discovery, the total synthesis of tanzawaic acid B had not been realized, until now. The present synthesis method will hopefully lead to the creation of various compounds for pharmaceuticals in the future, including new antibiotic candidates for multidrug-resistant bacteria.”
With a continuous, large-scale supply of tanzawaic acids, researchers will soon be able to test their interesting biological activities, including antibacterial, antimalarial, and antifungal properties. “Further improvements to the synthesis of tanzawaic acid B are currently underway, along with the investigations of its biological activity and synthetic analogs,” concludes Prof. Shiina.

Women diagnosed and treated for breast cancer have increased biological aging compared to women who remain free of breast cancer, according to a new study by researchers at the National Institutes of Health and their collaborators. Among women diagnosed with breast cancer, the association with faster biological aging was most pronounced for those who received radiation therapy, while surgery showed no association with biological aging. This finding suggests that developing cancer is not what increases the aging effect.
“Of the three treatment classes we looked at, radiation therapy had the strongest associations with the biologic age measures assessed in the study,” noted Jack Taylor, M.D., Ph.D., the senior author on the paper who is an Emeritus Scientist at NIEHS. “The increases can be detected years after treatment.”
Biological age reflects a person’s cell and tissue health, and it differs from chronological age. To measure biological age, the researchers studied 417 women who had blood samples collected at two time points about eight years apart. About half of the women studied were selected because they had developed breast cancer during that time span. The participants are enrolled in the Sister Study, a research effort that seeks to identify environmental risk factors for breast cancer risk and other health conditions, led by the National Institute of Environmental Health Sciences (NIEHS), part of NIH.
The researchers used three different established “methylation clocks” to determine if there were changes in a women’s biological age between the two time points. The clocks measure naturally occurring, chemical modifications to a person’s DNA, known as methylation changes. Small variations in methylation patterns can help determine a person’s risk of developing an age-related disease.
Women diagnosed with breast cancer had faster aging rates by all three clocks, with no significant racial differences, when compared to women who did not develop breast cancer.
Next the scientists examined whether biological age was associated with specific treatment regimens, such as surgery, chemotherapy, radiation therapy, and endocrine therapy. Among women with breast cancer, aging rates varied by treatment type.
“Radiation is a valuable treatment option for breast cancer, and we don’t yet know why it was most strongly associated with biological age,” noted Dale Sandler, Ph.D., chief of the NIEHS Epidemiology Branch and a co-author on the paper. “This finding supports efforts to minimize radiation exposures when possible and to find ways to mitigate adverse health effects among the approximately 4 million breast cancer survivors living in the United States.”
The scientists emphasized that women should not abandon radiation therapy as an option based on this research. Current breast cancer treatments that include radiation are very effective in preventing breast cancer from spreading.
“Women faced with a breast cancer diagnosis, should discuss all possible treatment options with their doctors to determine the best course of treatment for them,” said Katie O’Brien, Ph.D., a scientist in the NIEHS Epidemiology Branch and a co-author on the paper.
The lead author, Jacob Kresovich, Ph.D., is currently a researcher in the Cancer Epidemiology Program at the Moffit Cancer Center. He began this work while a post-doctoral researcher in Taylor’s research group in the intramural research program at NIEHS. The study was published in the Journal of the National Cancer Institute.

The same message can be interpreted differently by different individuals — also among cells. This is shown in a study by researchers at Linköping University who studied cell communication through Wnt signalling, which plays a decisive role in embryo development and cancer. Their findings, published in Cell Systems, are surprising in light of the prevailing conception of how Wnt signalling works.
The cells in our body are in constant communication. Although cell communication plays a decisive role in everything that happens in our bodies, cells have few ways to communicate with one another. Wnt signalling is one of them. It was discovered in the 1980s, through its role in the development of certain forms of cancer.
It soon turned out that Wnt signalling also has a basic function in embryo development in a variety of organisms, from fruit flies to humans.
“At the outset of life, Wnt signalling is vital for the body to form properly, while dysregulated communication between cells may lead to cancer. A key question we are trying to answer is whether this communication mode works in a similar way in these two distinct phases,” says Pierfrancesco Pagella, postdoc in the Department of Biomedical and Clinical Sciences at Linköping University.
It has long been known that when a cell sends a Wnt message to another cell, the receiving cell undergoes behavioural changes. This is achieved by activating certain genes in the genome and repressing others. Wnt signalling has long been regarded to always activate the same groups of genes, leading to the term “Wnt target genes.” But the current study upends this assumption, as the research group, led by Claudio Cantù, has shown that a signal may have radically different effects depending on its duration. In their experiments, the researchers saw that the same signal given to a specific cell type, such as embryonic stem cells, had significantly varying effects depending on the duration of the signal.
“The cell responds differently depending on whether the signal is delivered for 90 minutes, four hours or three days. It’s not simply a matter of prolonging the same message,” says Pierfrancesco Pagella.
A long-standing key issue in developmental biology is: as all cells contain the same genome, how does a cell know which of all the genome’s instructions to use to get its correct identity?

People who contract COVID-19 but never develop symptoms — the so-called super dodgers — may have a genetic ace up their sleeve. They’re more than twice as likely as those who become symptomatic to carry a specific gene variation that helps them obliterate the virus, according to a new study led by UC San Francisco researchers. 
The paper, published July, 19, 2023 in Nature, offers the first evidence that there is a genetic basis for asymptomatic SARS-CoV-2. The research helps to solve the mystery of why some people can be infected without ever getting sick from COVID-19. 
The secret lies with the human leukocyte antigen (HLA), or protein markers that signal the immune system. A mutation in one of the genes coding for HLA appears to help virus-killing T cells identify SARS-CoV-2 and launch a lighting attack. The T cells of some people who carry this variant can identify the novel coronavirus, even if they have never encountered it before, thanks to its resemblance to the seasonal cold viruses they already know. The discovery points to new targets for drugs and vaccines.
“If you have an army that’s able to recognize the enemy early, that’s a huge advantage,” explained the study’s lead researcher, Jill Hollenbach, PhD, MPH, professor of neurology, as well as epidemiology and biostatistics, and a member of the Weill Institute for Neurosciences at UCSF. “It’s like having soldiers that are prepared for battle and already know what to look for, and that these are the bad guys.” 
The mutation — HLA-B*15:01 — is quite common, carried by about 10% of the study’s population. It doesn’t prevent the virus from infecting cells but, rather, prevents people from developing any symptoms. That includes a runny nose or even a barely noticeable sore throat. 
UCSF researchers found that 20% of people in the study who remained asymptomatic after infection carried at least one copy of the HLA-B*15:01 variant, compared to 9% of those who reported symptoms. Those who carried two copies of the variant were far more likely — more than eight times — to avoid feeling sick.
Leveraging a national marrow donor database
Researchers suspected early on that HLA was involved, and fortunately a national registry existed that contained the data they were looking for. The National Marrow Donor Program/Be The Match, the largest registry of HLA-typed volunteer donors in the U.S., matches donors with people who need bone marrow transplants.

You may be familiar with the art of origami, in which paper is intricately folded to create shapes. But did you know that proteins in the human body also undergo an intricate folding process that is essential to their structure and function? Recently, researchers in the U.S. and Japan have shed new light on protein folding stability, or the propensity of a protein to maintain its folded shape — a factor at the center of diseases such as cancer, Alzheimer’s disease, and cystic fibrosis.
In a new study published in Nature, a research team from Northwestern University and recently joining the Institute for Industrial Science, The University of Tokyo have developed a new high-throughput approach known as cDNA display proteolysis to evaluate the folding stability of nearly a million proteins in a single experiment.
A protein is initially generated as a single chain of amino acids that is then folded into a three-dimensional shape. Failure to fold properly or maintain this three-dimensional structure can disrupt protein function and lead to disease. Insight into how protein folding stability is maintained will therefore shed new light on diseases involving misfolded proteins. However, it has previously been difficult to evaluate protein folding stability in an efficient and large-scale manner. Therefore, the research team sought to develop a platform to assess protein folding stability in a reproducible, high-throughput way.
“We began with a technique in which proteins are attached to their own DNA,” says lead author of the study Kotaro Tsuboyama. “Using DNA libraries, we generated a large number of these protein-DNA complexes and treated them with enzymes that destroy unfolded proteins. The intact proteins, which were able to maintain their folded structures during enzyme treatment, were then identified using DNA sequencing.”
This method allowed the research team to evaluate the stability of up to 900,000 protein sequences in a single test tube. To examine how individual elements within a protein sequence affect folding stability, the researchers used this method to analyze a series of natural and designed protein domains.
“We were able to identify a number of factors that contribute to protein stability,” says senior author Gabriel J. Rocklin at Northwestern University. “We also used our approach to analyze the effects of specific mutations in protein sequences, and to identify determinants of stability in designed proteins, providing insight that can help advance protein design methods in the future.”
While previous methods for assessing protein stability have been limited to evaluating single-protein sequences, the cDNA display proteolysis method permits the evaluation of many proteins in a single experiment, supplying an unprecedented amount of information regarding protein stability. This approach may advance the development of new predictive models of protein folding, which may further our understanding of diseases involving protein misfolding.