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Although cats have lived alongside humans for millennia, it remains a dogs’ world. This bias has historically bled into science as well. It’s time for cats to get their day, argues veterinary medicine expert Leslie Lyons in a Forum published July 28 in the journal Trends in Genetics. Cats, she says, have the potential to be a valuable model organism for geneticists, as the feline genome is ordered similarly to humans.
“Using cats in research is really overlooked, since people don’t realize the advantages,” says Lyons, of the Department of Veterinary Medicine & Surgery at the University of Missouri. “The dog or mouse genome have rearranged chromosomes that are quite different than humans, but the domestic cat has genes that are about the same size as humans, as well as a genome that, like humans, is very organized and conserved.”
Lyons writes that cats could be an asset for helping researchers better understand our genetic “dark matter.” Although making up 95% of our DNA, it has long been considered filler information of little to no consequences, yet approximately 10% of the noncoding regions within the dark matter of the genome are conserved across mammals, suggesting that it has an important, misunderstood role. Cats have been found to have genetic diseases related to dysfunction of their genetic dark matter, making them a potential model organism for this type of research.
“As we discover that perhaps animals have more similar spacing between genes and the genes are in the same order, maybe that will help us to decipher what’s going on with humans,” Lyons says. “Working with a primate is on the expensive side, but a cat’s affordability and docile nature make them one of the most feasible animals to work with to understand the human genome.”
Another reason why cats could enlighten the human genome is that we have the technology to clone cats and make transgenic cats. The first cat clone, Cc, short for CopyCat, was generated in 2001. Her cell donor was a typical calico cat with black, orange, and white fur, but Cc didn’t turn out to have any orange on her coat, defying Mendel’s laws and other basic genetic principles. This was a clue that something was happening in Cc’s genes that researchers are just now beginning to understand.
Cats could also play a role in precision medicine for genetic diseases, in which instead of treating the symptoms, researchers fix the actual gene and what the gene does. For example, certain breeds of cats are prone to the genetic illness polycystic kidney disease, which also afflicts humans. Lyons writes that if we could treat this disease with precision medicine in cats, we could apply those learnings to us.
“So, if you and your cat walk in the vet’s door and there is not a trauma, there is not a feeding problem, there might be a genetic problem with the cat. Vets could sequence the genes and potentially more quickly find the cause of what’s going on and then develop a treatment that is more appropriate than just treating the symptoms,” Lyons says. “We can provide a more tailored healthcare program for our pets, and more funding would put all the different pieces into place.”
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In a major advancement in the field of gene therapy for rare and devastating diseases, researchers at Children’s Hospital of Philadelphia (CHOP) have developed a “dimmer switch” system that can control levels of proteins expressed from gene therapy vectors. The system is based on alternative RNA splicing using an orally available small molecule and works effectively in tissues throughout the body, including the brain. The first research regarding this innovation was published today in the journal Nature.
“We’re taking the field of gene therapy to an entirely new level where fine-tuned dosing is required for safety, utility and success,” said senior study author Beverly L. Davidson, PhD, Director of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics and Chief Scientific Strategy Officer at Children’s Hospital of Philadelphia. “This study shows that by using a splicing modulator in combination with gene therapy tools, the dose of protein expressed from gene therapy vectors can be controlled for maximum therapeutic benefit.”
Many advancements in gene therapy have involved its delivery system, in the form of engineered viral vectors or lipid nanoparticles, but while improvements in these vehicles have delivered treatments to tissues more effectively, the cargo being delivered and elements controlling the resulting gene expression have not received the same amount of attention. Once gene therapy has been successfully delivered into the tissue, it is difficult to regulate the levels of expression. Too much expression may have toxic effects on the patient, and too little expression may mean that the patient does not receive the intended benefits of the therapy.
To address this problem, CHOP researchers developed a delivery system called the Xon system, which can finely control protein translation by using a “dimmer switch” to adjust the levels of expression up or down as needed. This method employs alternative RNA splicing, a process that allows a single gene to code for multiple proteins, depending on how the RNA is spliced. Using the Xon system, a gene therapy vector’s cargo is inactive until the oral drug is used, which then drives the splicing of the desired corrective gene into its active form.
“The newly developed switch not only controls protein levels, but if needed, those proteins can be induced again and again by the simple ingestion of an orally bioavailable drug,” said Alex Mas Monteys, PhD, a research assistant professor in Davidson’s lab at CHOP and co-lead author of the study.
In one example reported in this paper, the researchers used the Xon system in mice to adjust levels of erythropoietin (Epo), which is used to treat anemia associated with kidney disease. The researchers found that their delivery system induced hematocrit levels to 60 to 70% above baseline levels depending on the dose, and once levels slowly dropped to base levels, the system could be used again to safely re-induce the levels as would be needed for patients with chronic kidney disease.
The research was conducted as part of a multi-year collaboration with scientists at the Novartis Institutes for BioMedical Research (NIBR). CHOP and NIBR are collaborating to develop next-generation small molecule splicing modulators and the Xon system to achieve fine-tuned gene regulation across multiple clinical applications. The team has also shown that the Xon system can be used to control expression of gene products that are toxic to the brain when expressed at high levels.
“The dose of a drug can determine how high you want expression to be, and then the system can automatically ‘dim down’ at a rate related to the half-life of the protein,” Davidson said. “We can envision scenarios where a drug would be given only once, such as for controlling the expression of foreign proteins needed for gene editing, or with limited frequency. Since the splicing modulators we have tested are given orally, compliance to control protein expression from viral vectors employing Xon-based cassettes should be high.”
Although the paper focuses on using Xon with gene therapy delivered via viral vectors, the researchers note it could also be engineered for use in cell engineering for CAR-T cell therapy. Here, the Xon system could be used to pause therapy if needed to give T-cells a rest.
The work was supported by NIBR, the Hereditary Disease Foundation and National Institutes of Health grant 5T32HG009495-04, the Children’s Hospital of Philadelphia Research Institute.
Dr. Davidson is an inventor of the Xon system. CHOP has licensed this technology to Novartis. CHOP, and by extension Dr. Davidson, have received compensation from Novartis in exchange for the licensing of the Xon technology. CHOP’s and Dr. Davidson’s participation in this research was reviewed and approved by CHOP’s Conflict of Interest Committee.

The Biomedical Genomics laboratory at IRB Barcelona has developed a computational tool that identifies cancer driver mutations for each tumour type. This and other developments produced by the same lab seek to accelerate cancer research and provide tools to help oncologists choose the best treatment for each patient. The study has been published in the journal Nature.
Each tumour — each patient — accumulates many mutations, but not all of them are relevant for the development of cancer. Researchers led by ICREA researcher Dr. Núria López-Bigas at IRB Barcelona have developed a tool, based on machine learning methods, that evaluates the potential contribution of all possible mutations in a gene in a given type of tumour to the development and progression of cancer.
In previous work that is already available to the scientific and medical community, the laboratory developed a method to identify those genes responsible for the onset, progression, and spread of cancer. “BoostDM goes further: it simulates each possible mutation within each gene for a specific type of cancer and indicates which ones are key in the cancer process. This information helps us to understand how a tumour is caused at the molecular level and it can facilitate medical decisions regarding the most appropriate therapy for a patient,” explains Dr. López-Bigas, head of the Biomedical Genomics lab. In addition, the tool will contribute to a better understanding of the initial processes of tumour development in different tissues.
The new tool has been integrated into the IntOGen platform, developed by the same group and designed to be used by the scientific and medical community in research projects, and into the Cancer Genome Interpreter, also developed by this group and which is more focused on clinical decision-making by medical oncologists.
BoostDM currently works with the mutational profiles of 28,000 genomes analysed from 66 types of cancer. The scope of BoostDM will grow as a result of the foreseeable increase in publicly accessible cancer genomes.
An advance founded on evolutionary biology
To identify the mutations involved in cancer, the scientists based themselves on a key concept in evolution, namely positive selection. Mutations that drive the growth and development of cancer are found in higher numbers in distinct samples, compared to those that would occur randomly.

While only one in five practicing surgeons in the U.S. is female, women are entering the surgical field in increasing numbers. Women comprised 38 percent of surgical residents in 2018, but they nonetheless continue to face well-known challenges related to childbearing, with national surveys documenting pregnancy-related stigma, unmodified work schedules, brief maternity leave options, and little support for childcare and lactation needs after delivery. With many female trainees choosing to delay pregnancy until after the age of 35 — a risk factor for pregnancy complications — researchers from Brigham and Women’s Hospital and elsewhere surveyed 1,175 surgeons and surgical trainees from across the U.S. to study their or their partner’s pregnancy experiences. They found that 48 percent of surveyed female surgeons experienced major pregnancy complications, with those who operated 12-or-more hours per week during the last trimester of pregnancy at a higher risk compared to those who did not.
Their findings are published in JAMA Surgery.
“The way female surgeons are having children today makes them inherently a high-risk pregnancy group,” said corresponding author Erika L. Rangel, MD, MS, of the Division of General and Gastrointestinal Surgery. “In addition to long working hours, giving birth after age 35 and multiple gestation — which is associated with increased use of assisted reproductive technologies — is a risk factor for having major pregnancy complications, including preterm birth and conditions related to placental dysfunction.”
The researchers found that over half (57 percent) of female surgeons worked more than 60 hours per week during pregnancy and over a third (37 percent) took more than six overnight calls. Of the 42 percent of women who experienced a miscarriage — a rate twice that of the general population — three-quarters took no days off of work afterwards.
“As a woman reaches her third trimester, she should not be in the operating room for more than 12 hours a week,” Rangel said. “That workload should be offset by colleagues in a fair way so that it does not add to the already-existing stigma that people face in asking for help, which is unfortunately not a part of our surgical culture.”
The authors developed their survey with the input of surgeons, obstetricians, and gynecologists, distributing it electronically to a variety of surgical societies and practices. Male and female surgeons were asked to respond, with nonchildbearing surgeons answering questions regarding their partners’ pregnancies. Overall, female surgeons had 1.7 greater odds than female nonsurgeon partners of experiencing major pregnancy complications, along with greater odds of musculoskeletal disorders, non-elective cesarean delivery, and postpartum depression, which was reported by 11 percent of female surgeons.
“The data we have accumulated is useful because it helps institutions understand the need to invest in a top-down campaign to support pregnant surgeons and change the culture surrounding childbearing,” Rangel said. “We need to start with policy changes at the level of residency programs, to make it easier and more acceptable for women to have children when it’s healthier, while also changing policies within surgical departments. It is a brief period of time that a woman is pregnant, but supporting them is an investment in a surgeon who will continue to practice for another 25 or 30 years.”
Funding for this work was provided by the Brigham and Women’s Hospital Department of Surgery Robert T. Osteen Junior Fellowship award.
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A mother’s mental health may play a larger role in a child’s toothbrushing habits than previously thought.
It is no secret that brushing your teeth twice a day is highly effective in promoting healthy teeth and gums. The International Association of Pediatric Dentistry advocates brushing with toothpaste containing fluoride to prevent decayed, missing, or filled teeth — known as childhood dental caries (ECC) — in children.
Parents are instrumental in instilling good dental habits in their children.
In Japan, there is a worryingly high prevalence of ECC among children aged 3 years old. Postpartum depression and/or lack of affection caused by bonding disorders hamper a mother’s ability to cultivate healthy dental practices in children, and researchers were keen to explore this link.
Dr Shinobu Tsuchiya from Tohoku University Hospital led a research group that analyzed approximately 80,000 mother-infant pairs from the Ministry of Environment’s Japan Environment and Children’s Study.
They found children with mothers suffering from postpartum depression or bonding disorders brushed their teeth less often. Likewise, the frequency with which children brushed their teeth increased when mothers showed strong affection towards their children.
The research group hopes their research will foster greater mental support and management for mothers and that doctors will incorporate these factors when assessing children’s oral health.
“A mother’s psychological well-being provides valuable screening information for identifying children at a high risk of ECC,” said Tsuchiya
In future studies, Tsuchiya and her team hope to examine other environmental influences on poor oral health.
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Survival rates after a heart transplant are unaffected if the organ donor had used illicit drugs or died due to an overdose, a fact that is increasing the availability of hearts due to the rise in drug overdose deaths in the U.S., according to two new unrelated research studies published today in two of the American Heart Association’s scientific journals.
During a heart transplant, the patient’s failing heart is replaced with a healthy heart from a recently deceased donor. The most common reasons for a heart transplant are that one or both ventricles of the heart aren’t functioning properly or severe heart failure is present. In 2019, the United States recorded the highest number of heart transplants, with 3,552 transplantations performed. As of March 11, 2020, 3,661 people were on the waiting list for a heart transplant, and 52 people were on the waiting list for a heart and lung transplant, according to the American Heart Association’s 2021 Heart Disease and Stroke Statistical Update.
Data made available in 2019 found “no downside” to transplanting hearts from people who had used illicit drugs, and the practice has become routine, according to Howard Eisen, M.D., chair of the American Heart Association’s Heart Failure and Transplantation Committee of the Clinical Cardiology Council, who was not involved in either study.
“This research confirms previous data that these hearts — once considered high risk — are safe,” Eisen said. “These findings should encourage institutions who are not routinely using hearts from drug users to do so. It will reduce the waiting time and the number of deaths among people on the heart transplant waitlist.”
The first study, “Intoxicated Donors and Heart Transplant Outcomes: Long Term Safety,” reviewed data from 2007- 2017 and is published today in Circulation: Heart Failure, an American Heart Association journal.
Tragically, the opioid epidemic has led to an increase in potential heart donations, however, many of these hearts go unused due to the concern that the donor’s illicit drug use may decrease the chances of survival among heart-transplant recipients, explained lead study author David A. Baran, M.D., system director for advanced heart failure and transplantation at Sentara Heart Hospital in Norfolk, Virginia.

Women often struggle with managing their weight and other health risk factors, such as high cholesterol, once they transition through menopause. A new study suggests that dancing may effectively lower cholesterol levels, improve fitness and body composition and in the process, improve self-esteem. Study results are published online today in Menopause, the journal of The North American Menopause Society (NAMS).
After menopause, women are more likely to experience weight gain, overall/central body adiposity increases, and metabolic disturbances, such as increases in triglycerides and bad cholesterol. Together, these changes ultimately increase cardiovascular risk. Around this same time, women often are less physically active, which translates into reductions in lean mass and an increased risk of falls and fractures. As a result of all these changes, postmenopausal women often suffer from decreased self-image and self-esteem, which are directly related to overall mental health.
Physical activity has been shown to minimize some of the many health problems associated with menopause. The effect of dancing, specifically, has already been investigated with regard to how it improves body composition and functional fitness. Few studies, however, have investigated the effects of dance on body image, self-esteem, and physical fitness together in postmenopausal women.
This new study was designed to analyze the effects of dance practice on body composition, metabolic profile, functional fitness, and self-image/self-esteem in postmenopausal women. Although the sample size was small, the study suggested some credible benefits of a three-times-weekly dance regimen in improving not only the lipid profile and functional fitness of postmenopausal women but also self-image and self-esteem.
Dance therapy is seen as an attractive option because it is a pleasant activity with low associated costs and low risk of injury for its practitioners. Additional confirmed benefits of regular dancing include improvement in balance, postural control, gait, strength, and overall physical performance. All of these benefits may contribute to a woman’s ability to maintain an independent, high-quality lifestyle throughout her lifespan.
Study results are published in the article “Dance practice modifies functional fitness, lipid profile, and self-image in postmenopausal women.”
“This study highlights the feasibility of a simple intervention, such as a dance class three times weekly, for improving not only fitness and metabolic profile but also self-image and self-esteem in postmenopausal women. In addition to these benefits, women also probably enjoyed a sense of comradery from the shared experience of learning something new,” says Dr. Stephanie Faubion, NAMS medical director.
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New research has identified proteins in a common weed which could play havoc for Australian farmers growing gluten-free crops, such as millet, buckwheat and sorghum, and people suffering from gluten intolerance.
The gluten-like proteins found in ryegrass could be mixing with crops commonly used as gluten-free products or wheat replacements and causing a reaction among people with coeliac disease or gluten intolerance.
The work, led by Edith Cowan University (ECU) and Australia’s national science agency, CSIRO, identified the proteins in 10 cultivars of ryegrass (Lolium species), a costly and invasive family of weeds commonly found in Australian cereal crops.
Dr Sophia Escobar-Correas, a researcher based at ECU and CSIRO said the team identified 19 proteins found in ryegrass which had similar properties to gluten proteins.
“We have developed a method to detect these ryegrass proteins that allows us to distinguish them from other grains,” she said.
“While these proteins aren’t strictly defined as gluten, they have the potential to trigger reactions for people who are coeliac and those with a gluten intolerance.”
This fundamental research helps understand whether ryegrass might be a problem so science can start to determine the impact it might — or might not — be having and devise solutions that give the best outcomes if it is.

Healthy lifestyle factors such as abstinence from smoking and drinking, low body mass index, and exercise correlated with decreased cancer incidence, even in individuals with a high genetic risk.
As genetic research continues to uncover loci, or areas in DNA, with specific changes that influence cancer risk, researchers can define polygenic risk scores (PRS) — personalized estimates of an individual’s cancer risk — based on a patient’s unique combination of these changes. However, most PRS are generated for a specific cancer type, rather than for overall cancer risk.
“A PRS indicating risk of a certain cancer is important but not enough,” Jin said. “We tried to create an indicator — the cancer polygenic risk score (CPRS) — to measure the genetic risk of cancer as a whole.”
Jin and colleagues calculated individual PRS for 16 cancers in men and 18 cancers in women, using available data from genome-wide association studies. They then used statistical methods to combine these scores into a single measure of cancer risk, based on the relative proportion of each cancer type in the general population. Separate CPRS were generated for men and women.
To validate their CPRS, the researchers utilized genotype information from 202,842 men and 239,659 women from the UK Biobank, a cohort of general-population participants recruited from England, Scotland, and Wales between 2006 and 2009, and calculated a CPRS for each individual.
UK Biobank participants were surveyed upon enrollment for various lifestyle factors, including smoking and alcohol consumption, body mass index, exercise habits, and typical diet. Based on these factors, Jin and colleagues classified each patient as having an unfavorable (zero to one healthy factors), intermediate (two to three healthy factors), or favorable (four to five healthy factors) overall lifestyle.
Patients with the highest quintile CPRS were nearly twice as likely (for men) and 1.6 times as likely (for women) to have a cancer diagnosis by their most recent follow-up, in 2015 or 2016. Notably, 97 percent of patients in the study had a high genetic risk (top quintile) of at least one cancer type. “This suggests that almost everyone is susceptible to at least one type of cancer,” Jin said. “It further indicates the importance of adherence to a healthy lifestyle for everyone.”
Patients with an unfavorable lifestyle and the highest quintile genetic risk were 2.99 times (in men) and 2.38 times (in women) more likely to develop cancer than those with a favorable lifestyle and the lowest quintile of genetic risk.
Among patients with high genetic risk, the five-year cancer incidence was 7.23 percent in men and 5.77 percent in women with an unfavorable lifestyle, compared with 5.51 percent in men and 3.69 percent in women with a favorable lifestyle. The decreased percentages are comparable to the cancer risk in individuals with intermediate genetic risk, Jin said. Similar trends were observed in all genetic risk categories, suggesting that patients could benefit from a healthy lifestyle regardless of genetic risk.
Limitations of this study include the fact that only the strongest genetic risk loci were included in the individual PRS, which disregards the influence of loci with weaker effects. Researchers also noted an imbalance in the number of loci included between different cancer types, which can potentially skew their individual impact.

A protein that helps regulate calcium signaling within heart cells could play a key role in preventing chronic heart failure, according to an international study led by University of Utah Health scientists. The researchers say disruption in the signaling pathway for this protein, VDAC2, causes severe impairment of heart cell contraction, making it harder for the heart to deliver blood to the body. The finding suggests that drugs and other therapeutic treatments targeting VDAC2 could eventually help alleviate heart failure.
“Based on our human and labratory research, it appears that If VDAC2 is not working properly, then everything in the heart can cascade downward from there,” says Stavros Drakos, Professor of Medicine, Director of Cardiovascular Research for the Division of Cardiology at U of U Health, and senior author of the study. “If we can figure out ways to help this protein do its job again, then it’s possible that we might be able to address heart failure far earlier in the disease process.”
The study appears in Nature Communications.
Scientists have long known that calcium — the mineral that keeps your teeth and bones strong — plays a vital role in the heart. Between heart beats, calcium levels in heart muscle cells (called myocytes) diminish, allowing the cell to relax. During contraction, a large amount of calcium surges out of a small cellular structure called sarcoplasmic reticulum, causing the cell to contract. It’s this constant ebb and flow of calcium in and out of the inner fluid of heart muscle cells that is critical to keep the heart beating.
Researchers also know that an organelle called mitochondria, relies on calcium to help produce biochemical energy that keeps cells alive. Mitochondria communicates with the sarcoplasmic reticulum, but its specific role in calcium signaling and thus cardiovascular health isn’t well understood.
In their study, Drakos and colleagues sought to get a better understanding of mitochondria’s role in the calcium cycle within heart cells. In earlier research with human heart tissue from heart failure patients, they detected a positive correlation between improved heart function and VDAC2 activity, a protein on the outer membrane of the mitochondria that allows calcium to flow into the mitochondria. As a result, they suspected that VDAC2 could play an important role in this disease.
In laboratory mice, they disabled, or knocked out, VDAC2. Without it, calcium flow in the mitochondria was severely impaired, and heart cells couldn’t beat properly. The mice also developed enlargement of the heart’s left ventricle or pumping chamber. This condition, called dilated cardiomyopathy, made it harder for the heart to pump blood and eventually led to heart failure and death.
Specifically, the researchers found that VDAC2 interacts with a pair of proteins in the sarcoplasmic reticulum. Hindering this protein-to-protein communication leads to impaired cellular calcium signaling and heart failure. However, restoring VDAC2 in knock-out mice reversed many of the effects of heart failure, including reduced swelling of the left ventricle, and prevented death.
In other experiments with mice that are genetically prone to develop heart failure, the researchers found that an experimental drug called efsevin, which binds to VDAC2 and increases mitochondrial calcium uptake, improved cardiovascular health. The scientists say this suggests that efsevin and other drugs that target VDAC2 are good drug candidates for further testing as treatments for heart failure.
“Our study shows the importance of VDAC2 in normal cardiac function,” says Thirupura Sundari Shankar, lead author of the study and a graduate PhD student in the Drakos lab. “Through this unique role, VDAC2 emerges as a potential therapeutic target for heart failure patients.”
The study, “Cardiac-specific Deletion of Voltage Dependent Anion Channel 2 Leads to Dilated Cardiomyopathy by Altering Calcium Homeostasis,” appears in Nature Communications. It was supported by the American Heart Association, the National Heart, Lung and Blood Institute, and the Nora Eccles Treadwell Foundation.
In addition to Shankar and Dr. Drakos, U of U Health researchers D.K.A. Ramadurai, S. Sommakia, R. Badolia, A.T. Krokidi, D. Calder, S. Navankasattusas, A. Aravamudhan, J. Ling, K.J. Whitehead, F.B. Sachse, K.W. Spitzer, and D. Chaudhuri contributed to this research. Collaborating institutions included the VA Salt Lake City Medical Center, University of Connecticut, University of California, Los Angeles, and Ludwig Maximilian University of Munich.