Culture

A new study of more than 150 COVID-19 patients shows that IgA antibodies dominate the early response to the SARS-CoV-2 virus, coming on more quickly and strongly than IgG and IgM antibodies. This is a somewhat unexpected result, as IgM antibodies are usually the immune system's first responders. The finding may also inform the development of vaccines that encourage the IgA response, as well as IgA-based tests to detect infection at early stages, Delphine Sterlin and colleagues say. The researchers measured antibody responses in blood, saliva, and fluid from a broncho-alveolar wash in the patients, whose disease symptoms ranged in severity. They found that IgA concentrations were higher than IgG and IgM concentrations in these fluids for the first 3 to 4 weeks after the first appearance of symptoms and then waned, but IgA persisted in saliva for several more weeks. The surge in IgA was associated with an increase in IgA-secreting cells called plasmablasts, which can preferentially target the mucosal surfaces in the respiratory tract that the virus attacks. Sterlin et al. also found that IgA was more potent than IgG at neutralizing SARS-CoV-2.
     

In a separate, unrelated study, Zijun Wang and colleagues took a closer look at IgA responses to SARS-CoV-2 in 149 individuals recovering from COVID-19. After cloning antibodies taken from the patients, Wang et al. discovered that the dimeric form of IgA - consisting of two IgA molecules linked together - was roughly fifteen times better at neutralizing the SARS-CoV-2 virus than the monomeric form. Dimeric IgA is typically considered the most prevalent antibody isotype in mucosal tissues of the upper respiratory tract, a major point of entry for the virus. Given the potency of the dimeric IgA antibodies, Wang et al. suggest that a vaccine designed to induce dimeric IgA, perhaps delivered orally or nasally to target mucosal tissues, could offer protection against the virus.

HOUSTON - (Dec. 7, 2020) - Indian women past childbearing age are dying at a higher rate than those in other countries because of poverty and limited access to resources such as food and health care, according to a study from Rice University.

"Why Are Older Women Missing in India? The Age Profile of Bargaining Power and Poverty" was published in a recent edition of the Journal of Political Economy. The research examines the impact of India's substantial gender inequality on the health, poverty and mortality of Indian women 45 and older.

Rossella Calvi, an assistant professor of economics at Rice and the study's author, developed a theoretical model of household resource allocation and analyzed consumer spending in India. She used the model to examine how women's access to family resources, such as food and health care, varies over their lifetimes.

"In India, only 1 in 3 women work outside the home, and traditional norms dictate that their primary role is childbearing and child-rearing," Calvi said. "When women enter their post-childbearing years, one of their main productive activities disappears. Meanwhile, men of the same age remain productive by continuing to work. This fact has critical consequences for women's bargaining power within their families.

"The estimates from my model indicate that the decline in women's intrahousehold bargaining power during post-reproductive ages could help explain the excessively high mortality rates of older women in India," she continued. "The decrease in women's bargaining power is reflected in their diminished ability to access household resources. As a result, at older ages poverty rates are significantly higher among women than men, which negatively affects women's health and increases their mortality risk. The excessive poverty rates of women are even more pronounced in households where women beyond childbearing ages have no children to care for."

Calvi said India's inheritance laws may have exacerbated inequality between women and men. Until the 1970s, an Indian woman's ability to inherit family land was limited, and some restrictions remained in place until 2005, when a national amendment improved women's rights.

"Moving forward, we should expect women to have a slightly higher share of resources because of their improved ability to inherit property, which may boost their bargaining power," Calvi said.

Calvi said she hopes her research will lead to policies that support older women and improve their mortality rates in countries such as India.

A drug currently prescribed to treat a rare enzyme deficiency can help cells clear the herpes simplex 1 and herpes simplex 2 viruses, according to a new study published in the journal Science Advances.

The new data shows that the antiviral activity of the drug -- called phenylbutyrate, or PBA -- was even better when used along with acyclovir, a common HSV-1 treatment. When used in combination, less acyclovir is needed to effectively suppress the virus compared to acyclovir alone -- this is important because acyclovir is also known to have toxic side effects in the kidneys.

"There are very few drugs available to treat herpes simplex viruses, so when new drugs become available, especially drugs that enable fewer side effects, it is a welcome discovery," said Dr. Deepak Shukla, the Marion Schenk Professor of Ophthalmology and UIC professor of microbiology and immunology at the College of Medicine and corresponding author on the paper. "Acyclovir can have very toxic effects on the kidneys, especially when it is given in higher doses for HSV-induced encephalitis, which is rare but can be deadly. By combining acyclovir with PBA, we need less acyclovir to effectively treat HSV-1."

There are two types of herpes simplex virus: herpes simplex 1, which infects the eyes and mouth and is a leading cause of blindness, and herpes simplex 2, a genital infection that may cause painful sores and can seriously impair quality of life.

Treatment for both infections often includes acyclovir -- a systemic medication taken orally. However, long-term use often results in resistance to the drug as well as kidney damage.

Shukla and colleagues investigated the antiviral effects of PBA and found that in cells the drug disrupts the ability of the virus to hijack the cellular machinery used to produce proteins. Normally, viruses infect cells and force them to produce viral proteins so the virus can replicate itself. But the cell also continues to produce proteins for its own use, leading to a lot of stress in the structure -- called the endoplasmic reticulum, or ER for short -- that makes protein.

"We found that PBA reduces stress on the ER, which allows the cell to focus on clearing the virus on its own," said Tejabhiram Yadavalli, a UIC ophthalmology and visual sciences postdoctoral fellow and first author of the paper.

The researchers found that in cells, PBA alone was able to clear HSV-1 from cells of donated human corneas or from donated human skin tissue just as well as acyclovir. In a mouse model of ocular HSV-1 infection, PBA administered intraperitoneally was able to clear the virus from the eyes.

In an animal model of HSV-2 vaginal infection, mice that received PBA had no signs of the HSV-2 virus in tissues, similar to mice treated with acyclovir.

When they tested a combination of PBA with acyclovir cells infected with HSV-1, the drug combo was able to completely clear the virus from the cells faster and better than either drug alone. Additionally, in a mouse model of HSV-induced encephalitis, mice treated with PBA or acyclovir alone had significantly reduced death rates, but a combination of PBA and acyclovir was able to prevent death in all mice given this combination.

"PBA is an exciting new therapeutic for treating herpes infections that can help reduce side effects associated with long term or high dose use of acyclovir, a commonly prescribed medication to treat herpes viruses," Shukla said. "The added bonus of this drug already being approved by the FDA to treat a rare enzyme disorder means that we may be able to quickly develop a marketable new combination therapy in the near future."

UCLA researchers are the first to create a version of COVID-19 in mice that shows how the disease damages organs other than the lungs. Using their model, the scientists discovered that the SARS-CoV-2 virus can shut down energy production in cells of the heart, kidneys, spleen and other organs.

"This mouse model is a really powerful tool for studying SARS-CoV-2 in a living system," said Dr. Arjun Deb, a co-senior author of a paper about the study and a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA. "Understanding how this virus can hijack our cells might eventually lead to new ways to prevent or treat the organ failure that can accompany COVID-19 in humans."

Deb said the same model could also help researchers learn more about other similar viruses that might emerge in the future, and it could be useful for testing eventual treatments.

The paper, published in the journal JCI Insight, was co-led by Vaithilingaraja Arumugaswami, an associate professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA and a member of the Broad Stem Cell Research Center.

Researchers often study mice to understand the fundamentals of human disease, but translating human health conditions to animal models can be tricky. SARS-CoV-2, for instance, relies on the ACE2 protein to infect humans. But the virus doesn't recognize the mouse version of ACE2, so healthy mice exposed to the SARS-CoV-2 virus don't get sick.

In previous experiments by other research teams around the world, mice have been genetically engineered to have the human version of ACE2 in their lungs and then been infected -- through their noses -- with the SARS-CoV-2 virus. Although that enables the virus to infect the mice and cause pneumonia, animals in those experiments don't get as broad a range of other symptoms as humans do.

"Among COVID-19 patients, those who have organs involved other than the lungs are most at risk of a bad outcome," said Deb, who is also a cardiologist and professor of molecular cell and developmental biology. "So we felt it was really important to understand how the virus affects those other organs."

Research in humans has suggested that SARS-CoV-2 can circulate through the bloodstream to reach multiple organs. So in the UCLA experiment, the researchers first engineered mice to have the human version of ACE2 in the heart and other vital organs. Then, they infected half of the animals by injecting SARS-CoV-2 into their bloodstreams. Over the following days, the researchers tracked the animals' overall health and analyzed how levels of certain genes and proteins in their bodies changed.

Within seven days, all of the mice with COVID-19 had stopped eating and were completely inactive, and had lost, on average, about 20% of their body weight. Animals that had been engineered to carry the human ACE2 protein but had not been infected with the virus, on the other hand, did not lose a significant amount of weight.

Moreover, the COVID-19 infected animals had altered levels of immune cells, swelling of the heart tissue and wasting away of the spleen -- all symptoms that have been observed in people who are critically ill with COVID-19.

Deb's team also looked at which genes were turned on and off in the mice infected with SARS-CoV-2, and they discovered other signs of disease. Common molecular processes that help cells generate energy -- through mechanisms known as the tricarboxylic acid cycle, or TCA cycle, and electron transport chain -- were shut off in the heart, kidney, spleen and lungs.

"If a virus snuffs out the energy-generating pathways in multiple organs of the body, that's going to really wreak havoc," Deb said.

Finally, the study also revealed that some changes were long-lasting throughout the organs in mice with COVID-19. In addition to temporarily altering which genes were turned on and off in some cells, the virus made epigenetic changes -- chemical alterations to the structure of DNA that cause more lasting effects. Deb said that could explain why, in some people with COVID-19, symptoms persist for weeks or months after their bodies are rid of the virus.

Although the findings don't have immediate implications for treating COVID-19, Deb said the mouse model will be useful for ongoing studies on how the virus infects vital organs other than the lungs, and for trials of new drugs to treat the disease.

(December 7, 2020) - A team of UTSA researchers has discovered that economic implications because of COVID-19 can have a devastating ripple effect on children. Monica Lawson, assistant professor of psychology, Megan Piel, assistant professor of social work and Michaela Simon, psychology graduate student in the UTSA College for Health, Community and Policy, have recently published a research article on the effects of parental job loss during the COVID-19 pandemic and risk of psychological and physical abuse toward children.

Using a community sample of 342 parents of 4- to 10-year-olds living in the United States, the researchers investigated factors associated with child maltreatment during the pandemic.

"We know that risk for child abuse increases during economic crises. We saw this during the Great Depression and the Great Recession and our study expanded this research to the COVID-19 pandemic," said Lawson. "We found that job loss due to the pandemic was associated with abuse towards children. Our study is unique by showing that positive coping strategies, however, can mitigate the risk for physical abuse against children, even among families where a parent lost their job."

The study included parental job loss and whether cognitive reframing moderated associations between job loss and child maltreatment. The researchers asked study participants to complete online questionnaires regarding their experiences with COVID-19, parental behaviors towards children, including psychologically and physically abusive behaviors, and coping strategies.

The research findings demonstrate that parental job loss due to the pandemic can have negative consequences on young children, including increased risk for psychological and physical abuse at the hands of their parents.

Another research finding demonstrates, however, that among parents who lost their jobs, physical abuse toward children decreased as parents engaged in more positive coping strategies. That is, parents who view hardships as something they can overcome without becoming too discouraged were less likely to physically abuse their children during the pandemic, even if they lost their jobs.

Importantly, these findings emerged when statistically controlling for whether families had a history of psychological and physical abuse before the pandemic, child and parent age and gender, parental depression, and family financial stability.

The researchers also found that the findings have consequences for economic policies and employment practices, but also indicate that focusing on parental mental health and, in particular, fostering healthy coping strategies among families is important during times of economic crises and may help to reduce family violence, including child abuse.

Lawson explains "We're just starting to understand the impact of the pandemic on family functioning and well-being." She adds, "Understanding factors that contribute to child abuse during the pandemic is critical for identifying at-risk families and providing services to protect children. This is especially important within the unique context of the pandemic when many children are at home and out of sight of mandated reporters."

A disease common during the First World War, trench fever, has been found in some urban populations experiencing homelessness in Canada, and physicians should be aware of this potentially fatal disease, highlights a practice article in CMAJ (Canadian Medical Association Journal).

The article describes a 48-year-old man who visited an emergency department in Manitoba with chest pain and shortness of breath. In the previous 18 months, the patient had sought care for episodes of chest pain and body lice infestation.

Bartonella quintana is a bacterium that is transmitted by body lice and causes a disease called trench fever, which killed millions of people during the First World War. It can lead to an infection of the heart, known as endocarditis, that can be fatal if untreated.

"Our public health message is that this disease is present in Canada and that people and physicians aren't always aware," says Dr. Carl Boodman, an infectious disease physician at the University of Manitoba, Winnipeg, Manitoba. "It's associated with homelessness and homeless shelters, and physicians should consider B. quintana infection in people who are unwell and have a history of body lice infestation."

The authors are aware of only 4 other cases in Canada over the last 20 years.

Symptoms of trench fever include fever, headache and malaise. It can be difficult to detect, requiring molecular testing and consultation with infectious disease experts.

"Clinicians should consider Bartonella serology, echocardiography and infectious disease consultation when caring for individuals who present unwell with a history of body lice infestation. B. quintana infection likely remains underdiagnosed," the authors conclude.

A novel form of an Alzheimer's protein found in the fluid that surrounds the brain and spinal cord indicates what stage of the disease a person is in, and tracks with tangles of tau protein in the brain, according to a study from researchers at Washington University School of Medicine in St. Louis. Tau tangles are thought to be toxic to neurons, and their spread through the brain foretells the death of brain tissue and cognitive decline. Tangles appear as the early, asymptomatic stage of Alzheimer's develops into the symptomatic stage.

The discovery of so-called microtubule binding region tau (MTBR tau) in the cerebrospinal fluid could lead to a way to diagnose people in the earliest stages of Alzheimer's disease, before they have symptoms or when their symptoms are still mild and easily misdiagnosed. It also could accelerate efforts to find treatments for the devastating disease, by providing a relatively simple way to gauge whether an experimental treatment slows or stops the spread of toxic tangles.

The study is published Dec. 7 in the journal Brain.

"This MTBR tau fluid biomarker measures tau that makes up tangles and can confirm the stage of Alzheimer's disease by indicating how much tau pathology is in the brains of Alzheimer's disease patients," said senior author Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology. Bateman treats patients with Alzheimer's disease on the Washington University Medical Campus. "If we can translate this into the clinic, we'd have a way of knowing whether a person's symptoms are due to tau pathology in Alzheimer's disease and where they are in the disease course, without needing to do a brain scan. As a physician, this information is invaluable in informing patient care, and in the future, to guide treatment decisions."

Alzheimer's begins when a brain protein called amyloid starts forming plaques in the brain. During this amyloid stage, which can last two decades or more, people show no signs of cognitive decline. However, soon after tangles of tau begin to spread in the neurons, people start exhibiting confusion and memory loss, and brain scans show increasing atrophy of brain tissue.

Tau tangles can be detected by positron emission tomography (PET) brain scans, but brain scans are time-consuming, expensive and not available everywhere. Bateman and colleagues are developing diagnostic blood tests for Alzheimer's disease based on amyloid or a different form of tau, but neither test can pin down the amount of tau tangles across the stages of disease.

MTBR tau is an insoluble piece of the tau protein, and the primary component of tau tangles. Bateman and first author Kanta Horie, PhD, a visiting scientist in Bateman's lab, realized that specific MTBR tau species were enriched in the brains of people with Alzheimer's disease, and that measuring levels of the species in the cerebrospinal fluid that bathes the brain might be a way to gauge how broadly the toxic tangles have spread through the brain. Previous researchers using antibodies against tau had failed to detect MTBR tau in the cerebrospinal fluid. But Horie and colleagues developed a new method based on using chemicals to purify tau out of a solution, followed by mass spectrometry.

Using this technique, Horie, Bateman and colleagues analyzed cerebrospinal fluid from 100 people in their 70s. Thirty had no cognitive impairment and no signs of Alzheimer's; 58 had amyloid plaques with no cognitive symptoms, or with mild or moderate Alzheimer's dementia; and 12 had cognitive impairment caused by other conditions. The researchers found that levels of a specific form -- MTBR tau 243 -- in the cerebrospinal fluid were elevated in the people with Alzheimer's and that it increased the more advanced a person's cognitive impairment and dementia were.

The researchers verified their results by following 28 members of the original group over two to nine years. Half of the participants had some degree of Alzheimer's at the start of the study. Over time, levels of MTBR tau 243 significantly increased in the Alzheimer's disease group, in step with a worsening of scores on tests of cognitive function.

The gold standard for measuring tau in the living brain is a tau-PET brain scan. The amount of tau visible in a brain scan correlates with cognitive impairment. To see how their technique matched up to the gold standard, the researchers compared the amount of tau visible in brain scans of 35 people -- 20 with Alzheimer's and 15 without -- with levels of MTBR tau 243 in the cerebrospinal fluid. MTBR tau 243 levels were highly correlated with the amount of tau identified in the brain scan, suggesting that their technique accurately measured how much tau -- and therefore damage -- had accumulated in the brain.

"Right now there is no biomarker that directly reflects brain tau pathology in cerebrospinal fluid or the blood," Horie said. "What we've found here is that a novel form of tau, MTBR tau 243, increases continuously as tau pathology progresses. This could be a way for us to not only diagnose Alzheimer's disease but tell where people are in the disease. We also found some specific MTBR tau species in the space between neurons in the brain, which suggests that they may be involved in spreading tau tangles from one neuron to another. That finding opens up new windows for novel therapeutics for Alzheimer's disease based on targeting MTBR tau to stop the spread of tangles."

Cold Spring Harbor Laboratory (CSHL) scientists developed the world's first mobile genome sequence analyzer, a new iPhone app called iGenomics. By pairing an iPhone with a handheld DNA sequencer, users can create a mobile genetics laboratory, reminiscent of the "tricorder" featured in Star Trek. The iGenomics app runs entirely on the iOS device, reducing the need for laptops or large equipment in the field, which is useful for pandemic and ecology workers. Aspyn Palatnick programmed iGenomics in CSHL Adjunct Associate Professor Michael Schatz's laboratory, over a period of eight years, starting when he was a 14-year-old high school intern.

The iPhone app was developed to complement the tiny DNA sequencing devices being made by Oxford Nanopore. Palatnick, now a software engineer at Facebook, was already experienced at building iPhone apps when joining the Schatz laboratory. He and Schatz realized that:

"As the sequencers continued to get even smaller, there were no technologies available to let you study that DNA on a mobile device. Most of the studying of DNA: aligning, analyzing, is done on large server clusters or high-end laptops."

Schatz recognized that scientists studying pandemics were "flying in suitcases full of Nanopores and laptops and other servers to do that analysis in the remote fields." iGenomics helps by making genome studies more portable, accessible, and affordable.

Users can AirDrop sequencing data to each other, enabling DNA analysis in the most remote locations--even those without internet access. iGenomics may soon even find its way into the hands of astronauts, Schatz describes:

"There's a lot of interest to do DNA sequencing in space. I'm trying to see if there's a way we can get iGenomics up there. There's a lot of people that are interested to do that. It's a real testament about how it would be impossible to do, you know, any sort of analysis on regular computers. It's just impossible to bring them with you."

In the journal Gigascience, Palatnick and Schatz report the iGenomics algorithm can quickly map DNA sequences of viral pathogens, such as a flu virus or Zika virus, and identify mutations important for diagnosis and treatment. They also provide an online tutorial for analyzing other viral genomes, such as from a SARS-CoV-2 patient.

Schatz dreams that this device will help field workers and citizen scientists alike:

"Today, we all carry professional cameras in our pockets, so it's not that hard to imagine in the next couple years, all of us carrying our own DNA sequencers on our smartphones, as well. There's just so many opportunities to do measurements of our environment and look for pathogens, maybe even do scans of yourself."

UCLA RESEARCH ALERT

FINDINGS

UCLA Jonsson Comprehensive Cancer Center researchers studying cancer evolution have created a framework to help determine which tool combinations are best for pinpointing the exact timing of DNA mutations in cancer genomes. There are currently many different algorithms that researchers have developed to help determine the timing of mutations, but until now, it has been unclear which algorithm will work best for which cancer, and what common biases influence their results.

BACKGROUND

Cancer is a disease of the genome. As a cancer develops, its DNA is constantly acquiring new mutations and the population of cancer cells is continuously evolving. Knowing the order of changes that have happened allows researchers to study the evolution of the cancer over time and see how the cancer cell population may have diversified, or became more uniform. The diversity or uniformity in the cancer cell population is related to patient response to therapy and reveals vulnerabilities that can be used to create highly targeted treatments.

METHOD

The study assessed 22 different pipelines for timing mutations in cancer genomes. Researchers tested the algorithms on a cohort of nearly 300 clinical prostate cancer samples to evaluate each pipeline and see how their results differed in various aspects. This allowed the team to see the variability across tools and have an unbiased view of how each performed.

IMPACT

Understanding when and why a tumor metastasizes, or spreads to other parts of the body, can influence how a person with cancer is treated. The framework developed in the study can help researchers decide which tool would be the most accurate for their case and generate a more personalized and targeted treatment plan for patients, minimizing the risk of cancer coming back in the future.

AUTHORS

The senior author is Paul Boutros, PhD, a professor of urology and human genetics at the David Geffen School of Medicine at UCLA who serves as associate director of cancer informatics at the UCLA Institute for Precision Health and director of cancer data science at the Jonsson Cancer Center. The first author is Lydia Liu, a PhD candidate at the University of Toronto and Visiting Graduate Researcher at UCLA, co-supervised by Dr. Thomas Kislinger at the University of Toronto and Dr. Boutros at UCLA.

JOURNAL

The study was published online in Nature Communications.

FUNDING

The work was supported in part by Prostate Cancer Canada, the Movember Foundation, the Canadian Cancer Society, the Canadian Institutes of Health Research and National Cancer Institute.

How well women with cervical cancer respond to treatment and survive correlates with the level of 10 proteins in their blood that also are associated with a "zombie" cell state called senescence, Medical College of Georgia scientists report.

They looked at pretreatment levels of these proteins in the blood of 565 Peruvian women with stage 2 and 3 cervical cancer, who received standard treatments of internal radiation, called brachytherapy, external radiation or both. They found that women with low levels of the proteins secreted by senescent cells had higher survival rates than those with high levels of these senescence-associated secreted phenotypes, or SASPs.

Additionally they found that brachytherapy, which implants a radiation source close to the cervix, greatly improved survival of patients who had high levels of these SASPs but had little impact on those with low levels.

"These results demonstrate that cellular senescence is a major determining factor for survival and therapeutic response in cervical cancer, and suggest that senescence reduction therapy may be an efficacious strategy to improve the therapeutic outcome of cervical cancer," they write in the journal Cancers.

"We want to figure out how we can treat cervical cancer better than we do. Beyond stage and treatment modality, what other factors are playing a big role in determining which patients survive and how they respond to radiation therapy," says Dr. Jin-Xiong She, director of the MCG Center for Biotechnology and Genomic Medicine, Georgia Research Alliance Eminent Scholar in Genomic Medicine and the study's corresponding author.

"The most important conclusion of our paper is you want to manage senescence to improve therapy for cervical cancer," She says.

In women with moderate to high blood levels of SASPs, use of a class of drugs called senolytics -- which target these cells for elimination and are under study to improve age-related problems and disease -- as an adjunct therapy could help, says Dr. Sharad Purohit, biochemist in the MCG Center for Biotechnology and Genomic Medicine and the study's first author.

Cervical cancer is the most common gynecological cancer, caused almost exclusively by the human papillomavirus. While it is largely preventable by regular Pap smears that can detect early, precancerous changes, or by vaccines against HPV, survival rates for those who get it have been stagnant for decades, the scientists say. In fact, survival rates of the most common cancers have improved since the mid-1970s, except for cervical and endometrial cancer, according to the American Cancer Society.

Purohit, She and their colleagues would like to change that, and have some of the first evidence that targeting senescence is one way to do it.

They looked at blood levels of a total of 19 proteins they had found secreted by cells in a pathological site like a precancerous or cancerous cervix, although why the proteins are made is a question they can't yet answer, says Purohit. This type of "liquid biopsy" can enable regular monitoring without actually doing a tissue biopsy each time, She says of the approach gaining ground in the cancer field.

They found that levels of 10 of the proteins had an impact on cervical cancer survival in the women who were an average of 49-years-old. All 10 were associated with cellular senescence, either as the largely destructive and inflammatory SASPs themselves or involved in regulating SASPs.

While cancer cells more typically are associated with rapid reproduction that enables cancer's growth, senescent cells cannot divide and reproduce. But She categorizes the proteins these senescent cancer cells are secreting as "bad stuff," which helps create an inflammatory state in which cancer thrives and helps lay the groundwork for cancer spread. It also provides some protection from radiation therapy, which like chemotherapy, works in part by killing off typically rapidly dividing cancer cells.

"The senescent proteins really change how cancer cells may respond to therapy," She says.

They used machine learning, a form of artificial intelligence that enables computers to figure out what the data means, to make the association between high SASP level and low survival and vice versa.

In the patients included in the study, everyone with stage 2 and most with stage 3 cancer received both internal and external radiation; 86 patients with stage 3 only received external beam radiation.

Whether patients with low SASP levels could benefit from brachytherapy should be further explored, but they found no clear benefit to them, She and his colleagues write.

Organisms excrete DNA in their surroundings through metabolic waste, sloughed skin cells or gametes, and this genetic material is referred to as environmental DNA (eDNA).

As eDNA can be collected directly from water, soil or air, and analysed using molecular tools with no need to capture the organisms themselves, this genetic information can be used to report biodiversity in bulk. For instance, the presence of many fish species can be identified simultaneously by sampling and sequencing eDNA from water, while avoiding harmful capture methods, such as netting, trapping or electrofishing, currently used for fish monitoring.

While the eDNA approach has already been applied in a number of studies concerning fish diversity in different types of aquatic habitats: rivers, lakes and marine systems, its efficiency in quantifying species abundance (number of individuals per species) is yet to be determined. Even though previous studies, conducted in controlled aquatic systems, such as aquaria, experimental tanks and artificial ponds, have reported positive correlation between the DNA quantity found in the water and the species abundance, it remains unclear how the results would fare in natural environments.

However, a research team from the University of Hull together with the Environment Agency (United Kingdom), took the rare opportunity to use an invasive species eradication programme carried out in a UK fishery farm as the ultimate case study to evaluate the success rate of eDNA sampling in identifying species abundance in natural aquatic habitats. Their findings were published in the open-access, peer-reviewed journal Metabarcoding and Metagenomics.

"Investigating the quantitative power of eDNA in natural aquatic habitats is difficult, as there is no way to ascertain the real species abundance and biomass (weight) in aquatic systems, unless catching all target organisms out of water and counting/measuring them all," explains Cristina Di Muri, PhD student at the University of Hull.

During the eradication, the original fish ponds were drained and all fish, except the problematic invasive species: the topmouth gudgeon, were placed in a new pond, while the original ponds were treated with a piscicide to remove the invasive fish. After the eradication, the fish were returned to their original ponds. In the meantime, all individuals were counted, identified and weighed from experts, allowing for the precise estimation of fish abundance and biomass.

"We then carried out our water sampling and ran genetic analysis to assess the diversity and abundance of fish genetic sequences, and compared the results with the manually collected data. We found strong positive correlations between the amount of fish eDNA and the actual fish species biomass and abundance, demonstrating the existence of a strong association between the amount of fish DNA sequences in water and the actual fish abundance in natural aquatic environments", reports Di Muri.

The scientists successfully identified all fish species in the ponds: from the most abundant (i.e. 293 carps of 852 kg total weight) to the least abundant ones (i.e. one chub of 0.7 kg), indicating the high accuracy of the non-invasive approach.

"Furthermore, we used different methods of eDNA capture and eDNA storage, and found that results of the genetic analysis were comparable across different eDNA approaches. This consistency allows for a certain flexibility of eDNA protocols, which is fundamental to maintain results comparable across studies and, at the same time, choose the most suitable strategy, based on location surveyed or resources available," elaborates Di Muri.

"The opportunity of using eDNA analysis to accurately assess species diversity and abundance in natural environments will drive a step change in future species monitoring programmes, as this non-invasive, flexible tool is adaptable to all aquatic environments and it allows quantitative biodiversity surveillance without hampering the organisms' welfare."

Scientists striving to understand how and when volcanoes might erupt face a challenge: many of the processes take place deep underground in lava tubes churning with dangerous molten Earth. Upon eruption, any subterranean markers that could have offered clues leading up to a blast are often destroyed.

But by leveraging observations of tiny crystals of the mineral olivine formed during a violent eruption that took place in Hawaii more than half a century ago, Stanford University researchers have found a way to test computer models of magma flow, which they say could reveal fresh insights about past eruptions and possibly help predict future ones.

"We can actually infer quantitative attributes of the flow prior to eruption from this crystal data and learn about the processes that led to the eruption without drilling into the volcano," said Jenny Suckale, an assistant professor of geophysics at Stanford's School of Earth, Energy & Environmental Sciences (Stanford Earth). "That to me is the Holy Grail in volcanology."

The millimeter-sized crystals were discovered entombed in lava after the 1959 eruption of Kilauea Volcano in Hawaii. An analysis of the crystals revealed they were oriented in an odd, but surprisingly consistent pattern, which the Stanford researchers hypothesized was formed by a wave within the subsurface magma that affected the direction of the crystals in the flow. They simulated this physical process for the first time in a study published in Science Advances Dec. 4.

"I always had the suspicion that these crystals are way more interesting and important than we give them credit for," said Suckale, who is senior author on the study.

Detective work

It was a chance encounter that prompted Suckale to act upon her suspicion. She had an insight while listening to a Stanford graduate student's presentation about microplastics in the ocean, where waves can cause non-spherical particles to assume a consistent misorientation pattern. Suckale recruited the speaker, then-PhD student Michelle DiBenedetto, to see if the theory could be applied to the odd crystal orientations from Kilauea.

"This is the result of the detective work of appreciating the detail as the most important piece of evidence," Suckale said.

Along with Zhipeng Qin, a research scientist in geophysics, the team analyzed crystals from scoria, a dark, porous rock that forms upon the cooling of magma containing dissolved gases. When a volcano erupts, the liquid magma - known as lava once it reaches the surface - is shocked by the cooler atmospheric temperature, quickly entrapping the naturally occurring olivine crystals and bubbles. The process happens so rapidly that the crystals cannot grow, effectively capturing what happened during eruption.

The new simulation is based on crystal orientations from Kilauea Iki, a pit crater next to the main summit caldera of Kilauea Volcano. It provides a baseline for understanding the flow of Kilauea's conduit, the tubular passage through which hot magma below ground rises to the Earth's surface. Because the scoria can be blown several hundred feet away from the volcano, these samples are relatively easy to collect. "It's exciting that we can use these really small-scale processes to understand this huge system," said DiBenedetto, the lead author of the study, now a postdoctoral scholar at the Woods Hole Oceanographic Institution.

Catching a wave

In order to remain liquid, the material within a volcano needs to be constantly moving. The team's analysis indicates the odd alignment of the crystals was caused by magma moving in two directions at once, with one flow directly atop the other, rather than pouring through the conduit in one steady stream. Researchers had previously speculated this could happen, but a lack of direct access to the molten conduit barred conclusive evidence, according to Suckale.

"This data is important for advancing our future research about these hazards because if I can measure the wave, I can constrain the magma flow - and these crystals allow me to get at that wave," Suckale said.

Monitoring Kilauea from a hazard perspective is an ongoing challenge because of the active volcano's unpredictable eruptions. Instead of leaking lava continuously, it has periodic bursts resulting in lava flows that endanger residents on the southeast side of the Big Island of Hawaii.

Tracking crystal misorientation throughout the different stages of future Kilauea eruptions could enable scientists to deduce conduit flow conditions over time, the researchers say.

"No one knows when the next episode is going to start or how bad it's going to be - and that all hinges on the details of the conduit dynamics," Suckale said.

CLEVELAND--Researchers at the Case Western Reserve University School of Medicine have identified a new target in development of Alzheimer's disease (AD) that could lead to therapies focused on treating the neurodegenerative condition early in its progression.

The discovery helps bolster a promising approach to AD research: finding and manipulating processes earlier in the disease's development with hopes of slowing its advance.

"This is a missing part of the puzzle," said Xin Qi, a professor in the Department of Physiology and Biophysics at the School of Medicine and lead researcher of the study, just published in the journal Science Advances. "We've discovered a pathway that is accessible to detection and potential treatment, prior to much of the disease's damage and well before clinical symptoms appear."

First identified more than 100 years ago, AD is an age-related neurodegenerative disorder that is associated with deposits of plaques of amyloid beta protein and tangles of tau protein in the brain, along with progressive nerve cell death. The cause of AD is not known, and the greatest risk factors for developing AD are age, genetics, and a previous traumatic brain injury.

Before the defining pathological characteristics of the disease are in place, the new pathway identified by Case Western Reserve researchers can be targeted by potential therapeutics that aim to mitigate the degeneration of white matter that impairs the normal functions of brain circuitry.

"There is a growing body of evidence in the field that AD develops much earlier than previously thought, most likely decades before our current ability to clinically diagnose the condition," said study co-author Andrew A. Pieper, the Morley-Mather Chair in Neuropsychiatry in the School of Medicine, Director of the Harrington Discovery Institute Neurotherapeutics Center at University Hospitals.

"Detecting the disease--and potentially treating it--at earlier stages will be critical to our battle against its devastating effects. The new pathway uncovered by Dr. Qi's laboratory could be targeted for therapy before the disease has progressed to the point of causing cognitive problems," said Pieper, also a psychiatrist at the Louis Stokes Cleveland VA Medical Center Geriatrics Research Education and Clinical Center (GRECC).

The Drp1 pathway

Researchers found that the pathway--known as Drp1-HK1-NLRP3--plays a key role in disrupting normal function of brain cells that produce the protective white matter sheathing for nerves, known as myelin.

The dysfunction and eventual death of these myelin-producing cells--called oligodendrocytes (OLs)--are well-established early events in AD that lead to cognitive deficits.

The new findings illuminate how OLs start to go awry: the overexpression of a certain protein (Drp1) within the recently discovered pathway.

It's the hyperactivation of Drp1 protein that triggers inflammation and injury to OLs, culminating in a reduction of myelin--slowing communication in the brain--which leads to the degeneration of white matter and significant cognitive impairment.

What's next--targeting with therapeutics

A near total degeneration of OLs occurs before common symptoms of AD become apparent in most patients.

As such, researchers hope to target and manipulate the pathway with therapeutics that regulate the expression of Drp1, thereby slowing or reducing damage to myelin-producing OLs.

In fact, Qi's lab has patented a small molecule, known as a peptide inhibitor, that regulates the expression of Drp1--putting the brakes on degeneration of brain cells.

In the study published by Science Advances, researchers found that eliminating Drp1 expression in mouse models corrected the energy-related defect in OLs associated with the hyperexpression of that protein; this approach also reduced the activation of inflammation OLs, lessened tissue damage at those brain sites and improved cognitive performance.

"Our results show promise that targeting the Drp1-HK1-NLRP3 pathway and reducing the expression of the Drp1 protein could help reduce the downstream cascade of abnormal brain functions associated with the progression of AD," said Qi, whose lab has studied Drp1 for a decade, mostly in Parkinson's and Huntington's diseases."

"If therapies targeting this pathway can slow, stop or even reverse early stage AD progression, then possibly there can be a reduction or delay to later stage damage and impairments," Qi said.

Most AD diagnoses are in patients 65 or older, so identifying the disease in younger patients can be difficult. Many patients experience a significant loss in their brain's white matter--central to cognition, emotion and consciousness--before receiving a diagnosis.

"Identifying how AD unfolds in its earliest processes will help scientists better understand how to focus research into potential solutions for patients," said Pieper. "The Qi lab's findings may help in targeting AD earlier, potentially leading to better management of its symptoms and progression.

"There have still been only a very small number of approved medications for AD since its discovery in 1907. While these medicines augment neurotransmission to provide temporary symptomatic benefit, they do nothing to slow disease progression," said Pieper. "Identification of earlier approaches to treating AD--such as this research--is critical for society as the magnitude of AD is growing explosively with our aging population."

Researchers validated the discovery of the pathway using mouse models and post-mortem brain samples of AD patients.

What The Study Did: COVID-19 outcomes based on race and ethnicity were compared in this observational study of patients in a large health system in New York City, and the association of any disparities with coexisting medical conditions and neighborhood characteristics also was assessed.

Authors: Gbenga Ogedegbe, M.D., M.P.H., of the NYU Grossman School of Medicine in New York, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.26881)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

What The Study Did: This observational study assessed the rate of appendix perforations during the COVID-19 pandemic at a children's hospital compared with 2019.

Authors: Rick Place, M.D., M.H.A., of Inova Fairfax Medical Campus in Falls Church, Virginia, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamanetworkopen.2020.27948)

Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.