Every 12 minutes, someone in the United States dies of pancreatic cancer, which is often diagnosed late, spreads rapidly and has a five-year survival rate at approximately 10 percent. Treatment may involve radiation, surgery and chemotherapy, though often the cancer becomes resistant to drugs.
Researchers at University of California San Diego School of Medicine and Moores Cancer Center, in collaboration with Sanford-Burnham-Prebys Medical Discovery Institute and Columbia University, demonstrated that a new tumor-penetrating therapy, tested in animal models, may enhance the effects of chemotherapy, reduce metastasis and increase survival.
The study, published online March 9, 2021 in Nature Communications, showed how a tumor-targeting peptide, called iRGD, can sneak inside the armor that the tumor built to protect itself and use the fibrous tissue as a highway to reach deeper inside, destroying the tumor from within.
The pancreas is a large gland located behind the stomach. It makes enzymes that aid digestion and hormones that regulate blood-sugar levels. Pancreatic ductal adenocarcinoma (PDAC) is a subtype of pancreatic cancer that is highly drug-resistant due, in part, by the hard shell-like outer layer surrounding the tumor.
“This type of tumor is made up of a dense fibrous tissue that acts as a barrier to drugs trying to get through. Many drugs can reach the vessels of the tumor, but they are not able to get deep into the tissue, making treatment less effective, and that is one reason why this type of cancer is so challenging to treat,” said Tatiana Hurtado de Mendoza, PhD, first author of the study and assistant project scientist at UC San Diego School of Medicine and Moores Cancer Center.
“Our study found that the tumor-penetrating peptide iRGD is able to use this fibrous network to deliver chemotherapy drugs deep into the tumor and be more effective.”
The research team examined the microenvironment of PDAC tumors in a mouse model. They found that after targeting the tumor blood vessels, iRGD binds to high levels of β5 integrin, a protein produced by cells known as carcinoma-associated fibroblasts (CAFs) that produce much of the tumor’s protective fibrous cover.
“We were able to closely replicate human disease in our mouse model and found that when iRGD was injected with chemotherapy in mice with high levels of β5 integrin, there was a significant increase in survival and a reduction in the cancer spreading to other organs in the body compared to chemotherapy alone. This could be a powerful treatment strategy to target aggressive pancreatic cancer,” said Andrew Lowy, MD, co-corresponding author of the study, professor of surgery at UC San Diego School of Medicine and chief of the Division of Surgical Oncology at Moores Cancer Center at UC San Diego Health.
“What is also exciting about this finding is the iRGD therapy did not produce any additional side effects. This is critically important when considering treatments for patients.”
The researchers said next steps include a national human clinical trial. They estimate the trial could begin in one year.
“The knowledge gained from our study has the potential to be directly applied to patient care. We also believe that the levels of β5 integrin within a pancreatic cancer could tell us which patients would benefit the most from iRGD-combination therapy,” said Lowy.

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Schizophrenia is a neurodevelopmental disorder that disrupts brain activity producing hallucinations, delusions, and other cognitive disturbances. Researchers have long searched for genetic influences in the disease, but genetic mutations have been identified in only a small fraction — fewer than a quarter — of sequenced patients. A new study now shows that “somatic” gene mutations in brain cells could account for some of the disease neuropathology.
The study, led by senior author Jeong Ho Lee, MD, PhD, at Korea Advanced Institute of Science and Technology and the team of Stanley Medical Research Institute, appears in Biological Psychiatry, published by Elsevier.
Traditional genetic mutations, called germline mutations, occur in sperm or egg cells and are passed on to offspring by their parents. Somatic mutations, in contrast, occur in an embryo after fertilization, and they can appear throughout the body or in isolated pockets of tissues, making them much harder to detect from blood or saliva samples, which are typically used for such sequencing studies.
Recently, more-advanced genetic sequencing techniques have allowed researchers to detect somatic mutations, and studies have shown that even mutations present at very low levels can have functional consequences. A previous study hinted that brain somatic mutations were associated with schizophrenia (SCZ), but it was not powerful enough to cement such an association.
In the current study, the researchers used deep whole-exome sequencing to determine the genetic code of all exomes, the parts of genes that encode proteins. The scientists sequenced postmortem samples from 27 people with schizophrenia and 31 control participants both from brain and from liver, heart or spleen tissue, allowing them to compare the sequences in the two tissues. Using a powerful analytic technique, the team identified an average of 4.9 somatic single-nucleotide variants (SNV), or mutations, in brain samples from people with SCZ and 5.6 somatic SNVs in brain samples from control subjects.
Although there was no significant quantitative difference in somatic SNVs between SCZ and control tissues, the researchers found that the mutations in SCZ patients were found in genes already associated with SCZ. Of the germline mutations that had previously been associated with schizophrenia, the genes affected encoding proteins associated with synaptic neural communication, particularly in a brain region called the dorsolateral prefrontal cortex.
The researchers then determined which proteins might be affected by the newly identified somatic mutations. Remarkably, a protein called GRIN2B emerged as highly affected, and two patients with SCZ carried somatic mutations on the GRIN2B gene itself. GRIN2B is a protein component of NMDA-type glutamate receptors, which are critical for neural signaling. Faulty glutamate receptors have long been suspected to contribute to SCZ pathology; GRIN2B ranks among the most-studied genes in schizophrenia.
John Krystal, MD, Editor of Biological Psychiatry, said of the work, “The genetics of schizophrenia has received intensive study for several decades. Now a new possibility emerges, that in some cases, mutations in the DNA of brain cells contributes to the biology of schizophrenia. Remarkably this new biology points to an old schizophrenia story: NMDA glutamate receptor dysfunction. Perhaps the path through which somatic mutations contribute to schizophrenia converges with other sources of abnormalities in glutamate signaling in this disorder.”
Dr. Lee and the team next wanted to assess the functional consequences of the somatic mutations. Because of the location of the GRIN2B mutations found in SCZ patients, the researchers hypothesized that they might interfere with the receptors’ localization on neurons. Experiments in cortical neurons from mice showed that the mutations indeed disrupted the receptors’ usual localization to dendrites, the “listening” ends of neurons, which in turn prevented the formation of normal synapses in the neurons. The finding suggests that the somatic mutations could disrupt neural communication, contributing to SCZ pathology.
The somatic mutations identified in the study had a variant allele frequency of only about 1 percent, indicating that the mutations were rare among brain cells as a whole. Nevertheless, they have the potential to create widespread cortical dysfunction.
Dr. Lee said of the findings: “Besides the comprehensive genetic analysis of brain-only mutations in postmortem tissues from schizophrenia patients, this study experimentally showed the biological consequence of identified somatic mutations, which led to neuronal abnormalities associated with SCZ. Thus, this study suggests that brain somatic mutations can be a hidden major contributor to SCZ and provides new insights into the molecular genetic architecture of SCZ.”

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Deforestation may cause an initial increase in malaria infections across Southeast Asia before leading to later decreases, a study published today in eLife suggests.
The results may help malaria control programs in the region develop better strategies for eliminating malaria infections and educating residents on how to protect themselves from infection.
Mosquitos spread the malaria parasite to humans causing infections that can be severe and sometimes deadly. In the area along the Mekong river in Southeast Asia, many residents hunt or harvest wood in the surrounding forests, which can increase their risk of infection. Yet recent outbreaks of malaria in the region have also been linked to deforestation.
“As countries in the region focus their malaria control and elimination efforts on reducing forest-related transmission, understanding the impact of deforestation on malaria rates is essential,” says first author Francois Rerolle, Graduate Student Researcher at the University of California San Francisco (UCSF), US, who works within the UCSF Malaria Elimination Initiative.
To better understand the effects of deforestation on malaria transmission, Rerolle and colleagues examined both forest cover data and village-level malaria incidence data from 2013-2016 in two regions within the Greater Mekong Sub-region.
They found that in the first two years following deforestation activities, malaria infections increased in villages in the area, but then decreased in later years. This trend was mostly driven by infections with the malaria parasite Plasmodium falciparum. Deforestation in the immediate 1-10-kilometer radius surrounding villages did not affect malaria rates, but deforestation in a wider 30-kilometer radius around the villages did. The authors say this is likely due to the effect that wider deforestation can have on human behaviour. “We suspect that people making longer and deeper trips into the forest results in increased exposure to mosquitoes, putting forest-goers at risk,” Rerolle explains.
Previously, studies on the Amazon in South America have found increased malaria infections in the first 6-8 years after deforestation, after which malaria rates fall. The difference in timing may be due to regional differences. The previous studies in the Amazon looked at deforestation driven by non-indigenous people moving deeper into the forest, while communities in the current study have long lived at the forest edges and rely on subsistence agriculture.
“Our work provides a more complete picture of the nuanced effects of deforestation on malaria infections,” says senior author Adam Bennett, Program Lead at the UCSF Malaria Elimination Initiative. “It may encourage more in-depth studies on the environmental and behavioural drivers of malaria to help inform strategies for disease elimination.”

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Spinal cord injuries can be life-changing and alter many important neurological functions. Unfortunately, clinicians have relatively few tools to help patients regain lost functions.
In APL Bioengineering, by AIP Publishing, researchers from UCLA have developed materials that can interface with an injured spinal cord and provide a scaffolding to facilitate healing. To do this, scaffolding materials need to mimic the natural spinal cord tissue, so they can be readily populated by native cells in the spinal cord, essentially filling in gaps left by injury.
“In this study, we demonstrate that incorporating a regular network of pores throughout these materials, where pores are sized similarly to normal cells, increases infiltration of cells from spinal cord tissue into the material implant and improves regeneration of nerves throughout the injured area,” said author Stephanie Seidlits.
The researchers show how the pores improve efficiency of gene therapies administered locally to the injured tissues, which can further promote tissue regeneration.
Since many spinal cord injuries result from a contusion, the biomaterial implants need to be injected in or near the injured area without causing damage to any surrounding spared tissue. A major technical challenge has been fabricating scaffold materials with cell-scale pore sizes that are also injectable.
In the researchers’ method, they injected beads of material through a small needle into the spinal cord, where the beads stick together to form a scaffold, where cells can crawl in the pore spaces between the beads. The researchers found inclusion of these larger cell-scale pores within biomaterial scaffolds improved cell infiltration, gene delivery, and tissue repair after spinal cord injury, compared to more conventional materials with nanoscale pores.
The researchers made the highly porous scaffolds using two different methods. One was simpler but created a more irregularly sized pore network. The second was more complicated but created a highly regular pore structure.
Even though both materials had the same average pore size and chemical composition, more regenerating nerves were found to infiltrate scaffolds with regularly shaped pores.
“These results inform how to maximize interfacing with the nervous system,” said Seidlits. “This has potential applications not only for developing new therapies for brain and spinal cord repair but also for brain-machine interfaces, prosthetics, and treatment of neurodegenerative diseases.”

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Astronauts face many challenges to their health, due to the exceptional conditions of spaceflight. Among these are a variety of infectious microbes that can attack their suppressed immune systems.
Now, in the first study of its kind, Cheryl Nickerson, lead author Jennifer Barrila and their colleagues describe the infection of human cells by the intestinal pathogen Salmonella Typhimurium during spaceflight. They show how the microgravity environment of spaceflight changes the molecular profile of human intestinal cells and how these expression patterns are further changed in response to infection. In another first, the researchers were also able to detect molecular changes in the bacterial pathogen while inside the infected host cells.
The results offer fresh insights into the infection process and may lead to novel methods for combatting invasive pathogens during spaceflight and under less exotic conditions here on earth.
The results of their efforts appear in the current issue of the Nature Publishing Group journal npj Microgravity.
Mission control
In the study, human intestinal epithelial cells were cultured aboard Space Shuttle mission STS-131, where a subset of the cultures were either infected with Salmonella or remained as uninfected controls.

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The new research uncovered global alterations in RNA and protein expression in human cells and RNA expression in bacterial cells compared with ground-based control samples and reinforces the team’s previous findings that spaceflight can increase infectious disease potential.
Nickerson and Barrila, researchers in the Biodesign Center for Fundamental and Applied Microbiomics, along with their colleagues, have been using spaceflight as a unique experimental tool to study how changes in physical forces, like those associated with the microgravity environment, can alter the responses of both the host and pathogen during infection. Nickerson is also a professor in the School of Life Sciences at ASU.
In an earlier series of pioneering spaceflight and ground-based spaceflight analogue studies, Nickerson’s team demonstrated that the spaceflight environment can intensify the disease-causing properties or virulence of pathogenic organisms like Salmonella in ways that were not observed when the same organism was cultured under conventional conditions in the laboratory.
The studies provided clues as to the underlying mechanisms of the heightened virulence and how it might be tamed or outwitted. However, these studies were done when only the Salmonella were grown in spaceflight and the infections were done when the bacteria were returned to Earth.
“We appreciate the opportunity that NASA provided our team to study the entire infection process in spaceflight, which is providing new insight into the mechanobiology of infectious disease that can be used to protect astronaut health and mitigate infectious disease risks,” Nickerson says of the new study. “This becomes increasingly important as we transition to longer human exploration missions that are further away from our planet.”
Probing a familiar adversary

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Salmonella strains known to infect humans continue to ravage society, as they have since antiquity, causing around 1.35 million foodborne infections, 26,500 hospitalizations, and 420 deaths in the United States every year, according to the Centers for Disease Control. The pathogen enters the human body through the ingestion of contaminated food and water, where it attaches and invades into intestinal tissue. The infection process is a dynamic dance between host and microbe, its rhythm dictated by the biological and physical cues present in the tissue’s environment.
Despite decades of intensive research, scientists still have much to learn about the subtleties of pathogenic infection of human cells. Invasive bacteria like Salmonella have evolved sophisticated countermeasures to human defenses, allowing them to flourish under hostile conditions in the human stomach and intestine to stealthily evade the immune system, making them highly effective agents of disease.
The issue is of particular medical concern for astronauts during spaceflight missions. Their immune systems and gastrointestinal function are altered by the rigors of space travel, while the effects of low gravity and other variables of the spaceflight environment can intensify the disease-causing properties of hitchhiking microbes, like Salmonella. This combination of factors poses unique risks for space travelers working hundreds of miles above the earth — far removed from hospitals and appropriate medical care.
As technology advances, it is expected that space travel will become more frequent — for space exploration, life sciences research, and even as a leisure activity (for those who can afford it). Further, extended missions with human crews are on the horizon for NASA and perhaps space-voyaging companies like SpaceX, including trips to the Moon and Mars. A failure to keep bacterial infections at bay could have dire consequences.
Hide and Seq
In the current study, human intestinal epithelial cells, the prime target for invasive Salmonella bacteria, were infected with Salmonella during spaceflight. The researchers were keen to examine how the spaceflight setting affected the transcription of human and bacterial DNA into RNA, as well as the expression of the resulting suite of human proteins produced from the RNA code, products of a process known as translation.
The research involved the close examination of transcriptional profiles of both the pathogenic Salmonella and the human cells they attack, as well as the protein expression profiles of the human cells to gauge the effects of the spaceflight environment on the host-pathogen dynamic.
To accomplish this, researchers used a revolutionary method known as dual RNA-Seq, which applied deep sequencing technology to enable their evaluation of host and pathogen behavior under microgravity during the infection process and permitted a comparison with the team’s previous experiments conducted aboard the Space Shuttle.
The host and pathogen data recovered from spaceflight experiments were compared with those obtained when cells were grown on earth in identical hardware and culture conditions (e.g., media, temperature).
Earth and sky
Earlier studies by Nickerson and her colleagues demonstrated that ground-based spaceflight analogue cultures of Salmonella exhibited global changes in their transcriptional and proteomic (protein) expression, heightened virulence, and improved stress resistance — findings similar to those produced during their experiments on STS-115 and STS-123 Space Shuttle missions.
However, these previous spaceflight studies were done when only the Salmonella were grown in spaceflight and the infections were done when the bacteria were returned to Earth.
In contrast, the new study explores for the first time, a co-culture of human cells and pathogen during spaceflight, providing a unique window into the infection process. The experiment, called STL-IMMUNE, was part of the Space Tissue Loss payload carried aboard STS-131, one of the last four missions of the Space Shuttle prior to its retirement.
The human intestinal epithelial cells were launched into space (or maintained in a laboratory at the Kennedy Space Center for ground controls) in three-dimensional (3-D) tissue culture systems called hollow fiber bioreactors. The hollow fiber bioreactors each contained hundreds of tiny, porous straw-like fibers coated with collagen upon which the intestinal cells attached and grew. These bioreactors were maintained in the Cell Culture Module, an automated hardware system which pumped warm, oxygenated cell culture media through the tiny fibers to keep the cells healthy and growing until they were ready for infection with Salmonella.
Once in orbit, astronauts aboard STS-131 activated the hardware. Eleven days later, S. Typhimurium cells were automatically injected into a subset of the hollow fiber bioreactors, where they encountered their target — a layer of human epithelial cells.
The RNA-Seq and proteomic profiles showed significant differences between uninfected intestinal epithelial cultures in space vs those on earth. These changes involved major proteins important for cell structure as well as genes important for maintaining the intestinal epithelial barrier, cell differentiation, proliferation, wound healing and cancer. Based on their profiles, uninfected cells exposed to spaceflight may display a reduced capacity for proliferation, relative to ground control cultures.
Infections far from home
Human intestinal epithelial cells act as critical sentinels of innate immune function. The results of the experiment showed that spaceflight can cause global changes to the transcriptome and proteome of human epithelial cells, both infected and uninfected.
During spaceflight, 27 RNA transcripts were uniquely altered in intestinal cells in response to infection, once again establishing the unique influence of the spaceflight environment on the host-pathogen interaction. The researchers also observed 35 transcripts which were commonly altered in both space-based and ground-based cells, with 28 genes regulated in the same direction. These findings confirmed that at least a subset of the infection biosignatures that are known to occur on Earth also occur during spaceflight. Compared with uninfected controls, infected cells in both environments displayed gene regulation associated with inflammation, a signature effect of Salmonella infection.
Bacterial transcripts were also simultaneously detected within the infected host cells and indicated upregulation of genes associated with pathogenesis, including antibiotic resistance and stress responses.
The findings help pave the way for improved efforts to safeguard astronaut health, perhaps through the use of nutritional supplements or probiotic microbes. Ongoing studies of this kind, to be performed aboard the International Space Station and other space habitats, should further illuminate the many mysteries associated with pathogenic infection and the broad range of human illnesses for which they are responsible.
“Before we began this study, we had extensive data showing that spaceflight completely reprogrammed Salmonella at every level to become a better pathogen,” Barrila says. “Separately, we knew that spaceflight also impacted several important structural and functional features of human cells that Salmonella normally exploits during infections on earth. However, there was no data showing what would happen when both cell types met in the microgravity environment during infection. Our study indicates that there are some pretty big changes in the molecular landscape of the intestinal epithelium in response to spaceflight, and this global landscape appears to be further altered during infection with Salmonella.”

Researchers at Charité — Universitätsmedizin Berlin and TU Berlin as well as the University of Oslo have developed a new tissue-section analysis system for diagnosing breast cancer based on artificial intelligence (AI). Two further developments make this system unique: For the first time, morphological, molecular and histological data are integrated in a single analysis. Secondly, the system provides a clarification of the AI decision process in the form of heatmaps. Pixel by pixel, these heatmaps show which visual information influenced the AI decision process and to what extent, thus enabling doctors to understand and assess the plausibility of the results of the AI analysis. This represents a decisive and essential step forward for the future regular use of AI systems in hospitals. The results of this research have now been published in Nature Machine Intelligence.
Cancer treatment is increasingly concerned with the molecular characterization of tumor tissue samples. Studies are conducted to determine whether and/or how the DNA has changed in the tumor tissue as well as the gene and protein expression in the tissue sample. At the same time, researchers are becoming increasingly aware that cancer progression is closely related to intercellular cross-talk and the interaction of neoplastic cells with the surrounding tissue — including the immune system.
Although microscopic techniques enable biological processes to be studied with high spatial detail, they only permit a limited measurement of molecular markers. These are rather determined using proteins or DNA taken from tissue. As a result, spatial detail is not possible and the relationship between these markers and the microscopic structures is typically unclear. “We know that in the case of breast cancer, the number of immigrated immune cells, known as lymphocytes, in tumor tissue has an influence on the patient’s prognosis. There are also discussions as to whether this number has a predictive value — in other words if it enables us to say how effective a particular therapy is,” says Prof. Dr. Frederick Klauschen of Charité’s Institute of Pathology.
“The problem we have is the following: We have good and reliable molecular data and we have good histological data with high spatial detail. What we don’t have as yet is the decisive link between imaging data and high-dimensional molecular data,” adds Prof. Dr. Klaus-Robert Müller, professor of machine learning at TU Berlin. Both researchers have been working together for a number of years now at the national AI center of excellence the Berlin Institute for the Foundations of Learning and Data (BIFOLD) located at TU Berlin.
It is precisely this symbiosis which the newly published approach makes possible. “Our system facilitates the detection of pathological alterations in microscopic images. Parallel to this, we are able to provide precise heatmap visualizations showing which pixel in the microscopic image contributed to the diagnostic algorithm and to what extent,” explains Prof. Müller. The research team has also succeeded in significantly further developing this process: “Our analysis system has been trained using machine learning processes so that it can also predict various molecular characteristics, including the condition of the DNA, the gene expression as well as the protein expression in specific areas of the tissue, on the basis of the histological images.
Next on the agenda are certification and further clinical validations — including tests in tumor routine diagnostics. However, Prof. Klauschen is already convinced of the value of the research: “The methods we have developed will make it possible in the future to make histopathological tumor diagnostics more precise, more standardized and qualitatively better.”

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Preterm birth is a leading cause of infant deaths and illness in the U.S. — yet its underlying molecular causes remain largely unclear. About 40 to 50% of preterm births, defined as births before 37 weeks of pregnancy, are estimated to be “idiopathic,” meaning they arise from unexplained or spontaneous labor. And, maternal stress linked to depression and post-traumatic stress disorders as well as fetal stress have been strongly implicated in preterm births with no known cause.
Now, for the first time, a University of South Florida Health (USF Health) preclinical study has uncovered a mechanism to help explain how psychological and/or physiological stress in pregnant women triggers idiopathic preterm birth. A research team at the USF Health Morsani College of Medicine Department of Obstetrics and Gynecology shows how cortisol — the “fight-or-flight” hormone critical for regulating the body’s response to stress — acts through stress-responsive protein FKBP51 binding to progesterone receptors to inhibit progesterone receptor function in the uterus. This reduced progesterone receptor activity stimulates labor.
The findings were reported online first March 8 in Proceedings of the National Academy of Sciences (PNAS).
“This new study fills in some longstanding mechanistic gaps in our understanding of how normal labor begins and how stress causes preterm birth,” said the paper’s senior author Charles J. Lockwood, MD, senior vice president of USF Health, dean of the USF Health Morsani College of Medicine, and a professor of obstetrics and gynecology specializing in maternal-fetal medicine.
Dr. Lockwood was a co-principal investigator for the study along with the paper’s lead author Ozlem Guzeloglu-Kayisli, PhD, a USF Health associate professor of obstetrics and gynecology. Nihan Semerci, MSc, a senior biological scientist, shares the lead authorship with Dr. Guzeloglu-Kayisli.
Progesterone reduces contractions of the uterus and sustained levels are essential to prevent a baby from being born too early. Reduced uterine progesterone receptor expression and signaling stimulates labor. In the brain, elevated FKBP51 expression has been strongly associated with increased risk for stress-related disorders.

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Previous work by the USF Health team showed that normal human labor starting at term (between 37 and 42 weeks of pregnancy) was associated with reduced expression of progesterone receptors and increased expression of FKBP51, specifically in maternal decidual cells (specialized cells lining the uterus).
For the current study focused on maternal stress-induced idiopathic preterm birth, the researchers combined experiments in human maternal decidual cells and a mouse model in which FKBP5, the gene that makes FKBP51, had been removed, or “knocked out.” Altogether, their results revealed a novel functional progesterone withdrawal mechanism, mediated by maternal stress-induced uterine FKBP51 overexpression and enhanced FKPB51-progesterone receptor binding, that decreased progestational effects and triggered preterm birth. The researchers found that Fkbp5 knockout mice (with depletion of the gene encoding for FKBP51) exhibit prolonged gestation and are completely resistant to maternal stress-induced preterm birth.
Among the USF Health team’s key findings:
– FKPB51 levels were greater and FKPB51 binding to progesterone receptors was significantly increased in the decidual cells of women with idiopathic preterm birth, compared to decidual cells of gestational age-matched controls.
– The study reports for the first time that Fkbp5-deficient (knockout) mice are completely resistant to maternal stress-induced preterm birth and exhibit prolonged pregnancies accompanied by slower decline in systemic progesterone levels. This indicates that FKBP51 plays a crucial role in the length of pregnancy and initiation of labor and delivery.
– In contrast, mice with the FKPB5 gene intact and normal levels of FKPB51 protein (wild type mice) delivered earlier when exposed to maternal stress than either non-stressed wild type mice or FKPB5 knockout mice under nonstressed or stressed conditions.

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“Collectively, these results suggest that FKBP51 plays a pivotal role both in term labor and stress-associated preterm parturition (birth) and that inhibition of FKBP51 may prove to be a novel therapy to prevent idiopathic preterm birth,” the study authors conclude.
Currently, injectable progesterone is the only drug approved to help prevent preterm birth in high-risk women who have had a previous preterm birth. However, its effectiveness was not confirmed by a recent large clinical trial, sparking debate in the health care community. The authors finding that progesterone receptor activity was reduced in idiopathic preterm birth may explain the apparent lack of effectiveness of supplemental progesterone.
Babies born before 37 weeks, particularly those born before 34 weeks, have more health problems and may face long-term health complications, including childhood lung or heart disease and neurodevelopmental delays, Dr. Guzeloglu-Kayisli said. The likelihood of poor outcomes decreases as gestational age (length of the pregnancy) increases.
“Prevention of idiopathic preterm birth by extending gestation even two or three weeks can benefit the newborn, because it provides critical time needed for the fetus’s lungs and brain to mature,” Dr. Guzeloglu-Kayisli said. “Our research indicates the importance of investigating the potential use of FKBP51 inhibitors as a targeted therapy to reduce the risk of stress-related preterm birth.”
The USF Health study was supported in part by The March of Dimes Prematurity Research Center Ohio Collaborative grant.

Scientists at the University of Virginia School of Medicine have developed a tool to monitor communications within the brain in a way never before possible, and it has already offered an explanation for why Alzheimer’s drugs have limited effectiveness and why patients get much worse after going off of them.
The researchers expect their new method will have tremendous impact on our understanding of depression, sleep disorders, autism, neurological diseases and major psychiatric conditions. It will speed scientific research into the workings of the brain, they say, and facilitate the development of new treatments.
“We can now ‘see’ how brain cells communicate in sharp detail in both the healthy and diseased brains,” said lead researcher J. Julius Zhu, PhD, of UVA’s Department of Pharmacology.
Unexpected Transmissions
The new method developed by Zhu and his collaborators lets scientists examine transmissions inside the brain at both the microscopic level and the far, far smaller nanoscopic level. It combines a biological “sensor” with two different forms of cutting-edge imaging.
The approach can quantify “neuromodulatory” transmissions, which are associated with major brain disorders, including addiction, Alzheimer’s, depressive disorders and schizophrenia. They’re also linked to autism, epilepsy, eating disorders and sleep disorders.
Neuromodulatory transmissions are the “slower” transmissions in the brain. They’re typically thought to involve lots of neurons in large regions. That’s in contrast to the much faster transmissions that happen neuron-to-neuron.
But Zhu’s new tool has already shown it’s not that simple.
In Alzheimer’s disease, Zhu and his colleagues discovered a surprising degree of “fine control and precision” in the supposedly shotgun neuromodulatory transmissions. Widely used Alzheimer’s drugs known as acetylcholinesterase inhibitors may inhibit this precise communication, the scientists report. That may explain the limited effectiveness of the drugs, they say.
The researchers went on to identify potential changes in the brain that could be brought about by long-term use of the drugs, which could explain why patients often get much worse when they stop taking them. “The new method points out Alzheimer’s defects in the unprecedented spatial and temporal resolution, defining the precise targets for medicine,” Zhu said.
Alzheimer’s, the researchers say, is just the tip of the iceberg. The new system has “broad applicability” across the spectrum of neurological and psychiatric diseases and disorders, they report. In the years to come, the scientists predict, it will help doctors understand neurological illnesses and psychiatric problems, screen drugs for potential treatments, identify disease-causing genes and develop better, more personalized medicine tailored for specific patient needs.
“If we see problems,” Zhu said, “we will be ready to treat them.”

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When airborne pollen levels are higher, increased SARS-CoV-2 infection rates can be observed. These results were determined by a large-scale study conducted by an international team headed by researchers at the Technical University of Munich (TUM) and the Helmholtz Zentrum München. Members of high-risk groups could protect themselves by watching pollen forecasts and wearing dust filter masks.
In the spring of 2020, the outbreak of the coronavirus pandemic appeared to coincide with the tree pollen season in the northern hemisphere. These observations prompted an international team of researchers to conduct an extensive investigation: The scientists wanted to know whether there is a demonstrable link between airborne pollen concentrations and SARS-CoV-2 infection rates.
Pollen is a significant environmental factor influencing infection rates
Under the leadership of first author Athanasios Damialis, the team at the Chair of Environmental Medicine at TUM collected data on airborne pollen concentrations, weather conditions and SARS-CoV-2 infections — taking into consideration the variation of infection rates from one day to another and the total number of positive tests. In their calculations, the team also included data on population density and the effects of lockdown measures. The 154 researchers analyzed pollen data from 130 stations in 31 countries on five continents.
The team showed that airborne pollen can account for, on average, 44 percent of the variation in infection rates, with humidity and air temperature also playing a role in some cases. During intervals without lockdown regulations, infection rates were on average 4 percent higher with every increase of 100 grains of airborne pollen per cubic meter. In some German cities, concentrations of up to 500 pollen grains per cubic meter per day were recorded during the study — which led to an overall increase in infection rates of more than 20 percent. In regions where lockdown rules were in effect, however, the infection numbers were on average only half as high at comparable pollen concentrations.
Airborne pollen weakens immune response
High pollen concentrations lead to a weaker immune response in airways to viruses that can cause coughs and colds. When a virus enters the body, infected cells usually send out messenger proteins. This is also the case with SARS-CoV-2. These proteins, known as antiviral interferons, signal nearby cells to escalate their antiviral defenses to keep the invaders at bay. Additionally, an appropriate inflammation response is activated to fight the viruses.
But if airborne pollen concentrations are high, and pollen grains are inhaled with the virus particles, fewer antiviral interferons are generated. The beneficial inflammatory response itself is also affected. Therefore, on days with a high concentration of pollen, it can lead to an increase in the number of respiratory illnesses. This also holds true for Covid-19. Whether individuals are allergic to the different pollen types is irrelevant.
“You cannot avoid exposure to airborne pollen,” says Stefanie Gilles who is also first author of the study. “People in high-risk groups should, therefore, be informed that high levels of airborne pollen concentrations lead to an increased susceptibility to viral respiratory tract infections.” Athanasios Damialis emphasizes: “When studying the spread of SARS-CoV-2, environmental factors such as pollen must be taken into account. Increased awareness of these effects are an important step in preventing and mitigating the impact of Covid-19.”
Particle filtering masks provide protection
What can vulnerable people do to protect themselves? Claudia Traidl-Hoffmann, last author and a professor of environmental medicine, advises people at high-risk to monitor pollen forecasts over the coming months. Claudia Traidl-Hoffmann states: “Wearing a particle filtering mask when pollen concentrations are high can keep both the virus and pollen out of the airways.”

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