Culture

Lizards have special superpowers. While birds can regrow feathers and mammals can regrow skin, lizards can regenerate entire structures such as their tails. Despite these differences, all have evolved from the same ancestor as lizards.

Spreading through the Americas, one lizard group, the anoles, evolved like Darwin's finches, adapting to different islands and different habitats on the mainland. Today there are more than 400 species.

Constructing a family tree for three lizard species collected in Panama at the Smithsonian Tropical Research Institute (STRI) and a fourth from the southeastern U.S., scientists at Arizona State University compared lizard genomes--their entire DNA code--to those of other animals.

The researchers discovered that changes in genes involved in the interbrain (the site of the pineal gland and other endocrine glands), for color vision, hormones and the colorful dewlap that males bob to attract females, may contribute to the formation of boundaries between species. Genes regulating limb development also evolved especially quickly.

"While some reptiles such as tortoises changed remarkably little over millions of years, anole lizards evolved quickly, generating a diversity of shapes and behaviors," said Kenro Kusumi, corresponding author and professor at ASU School of Life Sciences. "Now that sequencing entire genomes is cheaper and easier, we discovered molecular genetic evidence for rapid evolution that may account for striking differences between bodies of animals living in different environments."

Kusumi's lab, working with colleagues at the University of Arizona College of Medicine-Phoenix, is especially interested in how reptiles' genomes shape their ability to regenerate and to develop a diversity of body forms.

"This is the first time the complete genetic code--the genome--of any vertebrate species from Panama has been sequenced and analyzed," said Oris Sanjur, co-author and Associate Director for Science Administration at STRI. "Information from these three species is an important contribution to our understanding of biodiversity and the evolution of new species."

Scientists estimate that there are 40 species of anolid lizards living in Panama, compared to only one in the U.S. A team from ASU collected three species with permission from the Ministry of the Environment, MiAmbiente: the Central American giant anole, Anolis frenatus, lives high on tree trunks; the grass anole, A. auratus, perches on bushes or on grassy vegetation and the slender anole, A. apletophallus, found only in Panama, hangs out lower on tree trunks or on the ground.

Researchers at ASU's School of Life Sciences lined up the DNA sequences of the lizards with the DNA sequences of 31 other animals: the lobe-finned fish and the four-legged animal groups that evolved from them. They also took a careful look at genes that code for proteins: more than 22,000 genes in the green anole, A. carolinensis, versus approximately 20,000 identified each in A. auratus and A. frenatus and 13,000 in A. apletophallus.

One obvious explanation for a faster rate of evolution is the anole lizards' faster rate of reproduction. Anoles typically mate in their first year of life, while other reptiles take much longer to reach sexual maturity. They also breed with many other individuals so mutations that make it difficult for individuals to survive are eliminated fairly quickly.

The first and only other anole lizard to be sequenced previously was the green anole, A. carolinensis, the only anole species resident in the U.S. In that study from MIT, the A. carolinensis genome held evidence of more recent evolution and the loss of ancient repeated elements in the part of the DNA that does not code for proteins. In this sense, it was important to sequence the three Panamanian species, because the U.S. species may not be the most representative of the diverse anole group.

"For 15 years, an impressive amount of time and money poured into discovering the genomes of mammals, motivated by our drive to understand human evolution and to look for cures for disease. Even though the squamate reptiles include more than 10,000 species--almost double the number of mammal species--a single genome was not enough to understand the variability within this group," said the first author of the report, Marc Tollis, a post-doctoral fellow at ASU.

"By comparing these four anole lizard genomes, we're beginning to understand how one of the most diverse groups of vertebrates regenerate, develop and diversify," he added.

For previously healthy children, brain infections are rare. But about one out of every 10,000 people who are exposed to common viruses like herpes simplex or influenza will develop a potentially deadly disease, encephalitis.

Rockefeller's Jean-Laurent Casanova has identified mutations in a single gene that may explain what goes wrong in cases of encephalitis of the brain stem, the part of the brain that controls many basic functions including heart rate and breathing. Shen-Ying Zhang, assistant professor of clinical investigation in the Casanova lab, evaluated seven children from unrelated families who had been exposed to a common virus (herpes simplex virus 1, influenza virus, or norovirus) and developed a life-threatening or lethal infection of the brain stem. The scientists discovered mutations in a gene called DBR1, which is responsible for producing a protein that helps process the loops formed in RNA during a step called mRNA splicing. Without it, immunity to viruses is selectively impaired in the brain stem. Casanova's experiments, published in Cell, point to an almost complete loss of DBR1 as the culprit, enabling brain stem virus invasion in all seven patients. The findings also reveal an unexpected connection between an RNA processing mechanism and protective immunity in a specific region of the brain.

The study is a new example of the Casanova lab's ongoing work to identify mutations that underlie infectious diseases in otherwise healthy individuals. Previous work has found genetic factors that cause increased vulnerability to staph infections, the flu, and fungal infections, among others.

Chronic kidney disease causes irreversible deterioration in renal function, often requiring dialysis or transplant surgery.

In children, genetic causes account for the greatest number of cases.

Published today in the Clinical Journal of the American Society of Nephrology the research shows children with CKD are at greater risk of deficits in academic skills, visual and verbal memory, and executive function.

The analysis included 34 studies of over 3000 children and adolescents under the age of 21 years.

Key findings

"The IQ of children with CKD is low to average," says the study's lead author, Dr Kerry Chen of the University of Sydney's Centre for Kidney Research.

Compared to healthy children, children with CKD were on average 10 IQ points lower regardless of their stage of kidney disease.

The IQs of children who received a kidney transplant were 11 points lower than their healthy counterparts and for those on dialysis, their IQs were 16 points lower.

What can be done?

"Educational support programs should specifically aim to minimise deficits in attention, memory, and executive function as a preventative measure," said Dr Chen.

"Families, educators and health teams also need to work together to ensure that CKD treatments for children do not disrupt their schooling too much or too often. Developing a comprehensive dialysis and post-transplant rehabilitation program would help these children."

How might chronic kidney disease and dialysis affect IQ and educational outcomes

While the evidence is not conclusive, experts have some hunches about how chronic kidney disease might affect IQ and educational outcomes in children and young adults.

"Firstly, increased plasma levels of uremic solutes arising from kidney disease may impair synaptic development," says Chen. "Dialysis may also lead to cognitive impairment through rapid changes in blood pressure. Also, the pathological effects associated with end-stage kidney disease, such as anaemia, hypertension and malnutrition, may reduce cognitive function among children on dialysis compared to other CKD stages.

"On top of that, treatments for CKD may compromise academic achievement. Firstly, the frequency of sleep disturbances in children with CKD may result in poor concentration, excessive daytime sleepiness and lower academic performance.

"Secondly, the interactions of complex medication routines and strict dialysis cycles may decrease attentional control, working memory, and executive function-cognitive domains that are important to children's ability to acquire, understand, and retain information in social and educational environments.

"Finally, ongoing dialysis sessions and recovery from transplant surgeries may reduce the amount and regularity of time spent in the classroom, with chronic absenteeism potentially preceding loss of interest, withdrawal, and poor school progression."

Dr Kerry Chen holds appointments at the University of Sydney's School of Public Health, The Kids Research Institute and Westmead Hospital.

Creating the perfect wearable device to monitor muscle movement, heart rate and other tiny bio-signals without breaking the bank has inspired scientists to look for a simpler and more affordable tool.

Now, a team of researchers at UBC's Okanagan campus have developed a practical way to monitor and interpret human motion, in what may be the missing piece of the puzzle when it comes to wearable technology.

What started as research to create an ultra-stretchable sensor transformed into a sophisticated inter-disciplinary project resulting in a smart wearable device that is capable of sensing and understanding complex human motion, explains School of Engineering Professor Homayoun Najjaran.

The sensor is made by infusing graphene nano-flakes (GNF) into a rubber-like adhesive pad. Najjaran says they then tested the durability of the tiny sensor by stretching it to see if it can maintain accuracy under strains of up to 350 per cent of its original state. The device went through more than 10,000 cycles of stretching and relaxing while maintaining its electrical stability.

"We tested this sensor vigorously," says Najjaran. "Not only did it maintain its form but more importantly it retained its sensory functionality. We have further demonstrated the efficacy of GNF-Pad as a haptic technology in real-time applications by precisely replicating the human finger gestures using a three-joint robotic finger."

The goal was to make something that could stretch, be flexible and a reasonable size, and have the required sensitivity, performance, production cost, and robustness. Unlike an inertial measurement unit--an electronic unit that measures force and movement and is used in most step-based wearable technologies--Najjaran says the sensors need to be sensitive enough to respond to different and complex body motions. That includes infinitesimal movements like a heartbeat or a twitch of a finger, to large muscle movements from walking and running.

School of Engineering Professor and study co-author Mina Hoorfar says their results may help manufacturers create the next level of health monitoring and biomedical devices.

"We have introduced an easy and highly repeatable fabrication method to create a highly sensitive sensor with outstanding mechanical and electrical properties at a very low cost," says Hoorfar.

To demonstrate its practicality, researchers built three wearable devices including a knee band, a wristband and a glove. The wristband monitored heartbeats by sensing the pulse of the artery. In an entirely different range of motion, the finger and knee bands monitored finger gestures and larger scale muscle movements during walking, running, sitting down and standing up. The results, says Hoorfar, indicate an inexpensive device that has a high-level of sensitivity, selectivity and durability.

New CHILD Study research has found that overweight and obese women are more like to have children who are overweight or obese by three years of age--and that bacteria in the gut may be partially to blame.

"We know that maternal overweight is linked to overweight in children," said Dr. Anita Kozyrskyj, the University of Alberta investigator who led the study. "What our study showed is that both the type of infant delivery--vaginal birth versus cesarean section birth--and changes in gut bacteria are also involved."

The study, published in JAMA Pediatrics, found that when an overweight woman delivered vaginally, the risk of overweight in her child was three times higher than normal. But the risk was five times higher than normal when the woman delivered via cesarean-section (C-section). This association persisted even after adjustment for multiple other factors.

"There seemed to be something about a C-section that increased the risk of childhood obesity," observed Kozyrskyj, senior author of the study and one of the world's leading researchers on the gut microbiome--the community of microorganisms or bacteria that live in the digestive tracts of humans. "We have shown in our previous research that an infant's gut microbiome is influenced by the type of delivery, so we wondered if this effect could be associated with obesity risk in early childhood."

To investigate further, Kozyrskyj and her research team studied over 930 mothers and their infants participating in AllerGen's CHILD Study, a national population-based birth cohort. DNA sequencing techniques performed in the laboratories of Drs James Scott and David Guttman at the University of Toronto provided information on the types and quantity of bacteria present in the infants' stool. An older analysis method not used in microbiome analyses--sequential mediation--was employed. The children's weights were assessed at one and three years of age.

"We found that an abundance of a family of bacteria called Lachnospiracae does in fact influence the relationship between maternal weight and child weight following vaginal and cesarean birth," said Dr. Hein Min Tun, who is the study's first author, a Canadian Institutes of Health Research (CIHR) postdoctoral fellow at the University of Alberta and an AllerGen Highly Qualified Personnel.

"Given that infant overweight and obesity are a major public health problem, our results reinforce increasing concerns over rising cesarean deliveries and affirm the role of the gut microbiota as a 'super organ' with diverse roles in health and disease," added Kozyrskyj.

Legalizing medical marijuana has not increased recreational use of the substance among U.S. adolescents, according to a new study conducted at Columbia University's Mailman School of Public Health. The findings are published online in the journal Addiction.

"For now, there appears to be no basis for the argument that legalizing medical marijuana has increased teens' use of the drug," said Deborah Hasin, PhD, professor of Epidemiology at Columbia's Mailman School and senior author of the study. "However, we may find that the situation changes as commercialized markets for medical marijuana develop and expand, and as states legalize recreational marijuana use."

The researchers analyzed the results of eleven separate studies dating back to 1991 using data from four large-scale U.S. surveys: Monitoring the Future; National Longitudinal Survey of Youth; National Survey on Drug Use and Health; and the Youth Risk Behavior Survey. No significant changes, increases or decreases, occurred in adolescent recreational use following enactment of medical marijuana laws.

In 1996, California became the first U.S. state to legalize marijuana use for medical purposes. Medical marijuana is now legal in 29 states. Opponents of medical marijuana have argued that such laws increase recreational marijuana use among adolescents.

Far fewer studies have examined the effects of medical marijuana laws among adults, according to Hasin, who is also a professor in the Department of Psychiatry at Columbia University Medical Center. "Although we found no significant effect on adolescent marijuana use, existing evidence suggests that adult recreational use may increase after medical marijuana laws are passed." She continues, "The $8 billion cannabis industry anticipates tripling by 2025. Obtaining a solid evidence base about harmful as well as beneficial effects of medical and recreational marijuana laws on adults is crucial given the intense economic pressures to expand cannabis markets".

Hasin also points out that the intensity of marijuana use in teens has not been explored thoroughly. "This warrants additional consideration, especially with the decreasing national trend of risk perception among adolescents and as the current perception gives rise to more medical marijuana stores and commercial opportunities."

ROCHESTER, Minn. - Patients who suffer from a type of heart attack that affects mainly younger women, called spontaneous coronary artery dissection or SCAD, may benefit most from conservative treatment, letting the body heal on its own. This is according to a new scientific statement by a Mayo Clinic led team, published by the American Heart Association in its journal, Circulation.

MULTIMEDIA ALERT: Video and audio are available for download on the Mayo Clinic News Network.

Most heart attacks occur when plaque builds up in arteries over a lifetime. The plaque ruptures, causing a blockage and a heart attack. In SCAD, a tear occurs inside an artery, and that can cause a blockage, leading to a heart attack.

"It may seem counterintuitive, but we discovered that treating SCAD the same way we treat heart attacks due to atherosclerosis can cause further tearing and damage to the vessel," says Sharonne Hayes, M.D., chair of the writing group for the new scientific statement and a Mayo Clinic cardiologist who founded its Women's Heart Clinic. "But the initial proper diagnosis is critical in guiding the care."

The statement is an overview of what an international group of experts know about SCAD, including:

Risk factors

Its high rate of post SCAD chest pain and recurrence

Its association with women, pregnancy, and physical and emotional stress triggers

Its connection to other diseases of the arteries, such as fibromuscular dysplasia

The best diagnosis and treatment recommendations based on new evidence and experts' care of SCAD patients

Until 2010, little was understood about SCAD, which had been described as a rare and universally fatal cause of acute coronary syndrome, heart attack and sudden cardiac arrest in women during and shortly after pregnancy.

Over the past several years research has refuted these misunderstandings. Increased understanding of SCAD, availability of intravascular imaging techniques, development of SCAD specific angiographic classification, increased awareness among providers, and efforts by SCAD patients using social media suggest that SCAD is much more common than previously thought, especially in young women.

The average age of women with SCAD ranges from 45 to 53 years. SCAD occurs overwhelmingly in women, and among individuals who have few conventional cardiovascular risk factors, such as high blood pressure, unhealthy cholesterol levels or smoking, the statement says.

"Even with what we have learned over the past several years, SCAD continues to be misdiagnosed and underdiagnosed," Dr. Hayes says. "And we know it is not rare. It is the No. 1 cause of heart attack during pregnancy and in the period right after giving birth, and the No. 1 cause of heart attack in women under age 50."

Misdiagnoses often happen because of a low suspicion of heart attack in younger women who do not have typical heart disease risk factors but arrive at an emergency room with classical heart attack symptoms, such as discomfort in the chest and the upper body, shortness of breath, nausea and light-headedness, Dr. Hayes says. Misdiagnoses also can happen if the patient is sent to the catheterization lab, where stents are often used to open blocked arteries. The statement provides expert consensus to help health care providers know how to best treat SCAD patients.

The statement shows that, in most patients who did not receive stents, the dissections healed on their own within weeks and months. For some, the healing began within days, Dr. Hayes says.

The statement also emphasizes the importance of tailored cardiac rehabilitation programs for SCAD patients. In addition, addressing mental health is critical, the authors say. "Anxiety and depression are common in SCAD survivors, and they often are being treated by health care providers who have little familiarity of the disease or in providing psychosocial support," Dr. Hayes says. "We've found that online support groups can be immensely helpful in addition to finding a care team that is responsive to patients' concerns," she says.

The cause of SCAD is believed to be a combination of factors, including diseases of the arteries, genetic factors, hormonal influences and, less commonly, connective tissue diseases. These factors can be compounded by environmental stressors.

The statement points to persistent gaps in knowledge of SCAD. Only recently have there been limited prospective studies, and most available data are retrospective and observational. Larger-scale prospective and epidemiological studies are needed to understand the disease and improve treatment, Dr. Hayes says.

A study of the unusual digestive system of an ancient group of insects has provided new insights into future biofuel production.

Published in Nature Communications, the research reveals that the ability of some insects to efficiently digest cellulose could be exploited for industrial processes, such as the production of sustainable low carbon fuels to cut greenhouse gas emissions associated with fossil fuel use.

The surprising find occurred when the team at the University of York were investigating the digestive system of firebrats, which had been previously shown to thrive on crystalline cellulose, the natural fibre, abundant in straw, paper and cardboard.

Professor Simon McQueen Mason, from the University of York's Department of Biology, said: "Firebrats belong to one of the most primitive groups of insects; they appeared on land during the Devonian Period, some 420 million years ago. Despite this long evolutionary history, however, these insects have been generally overlooked by scientists. "Cellulose forms the fibres that give the cell walls of plants their strength and has a high degree of structural order, making it solid and tough."

Until now it was a mystery how firebrats had found a way to digest cellulose so effectively. In looking at their digestive system, the scientists discovered something they weren't expecting.

Dr Federico Sabbadin, from the University of York's Department of Biology, said: "Inside their gut the firebrats had a group of uncharacterised proteins that make up 20% of their carbohydrate digestive enzymes.

"On further inspection, these proteins proved to be a new class of enzyme, called lytic polysaccharide monooxygenases (LPMOs), which attack crystalline polysaccharides. Our study revealed that these enzymes are used by firebrats to greatly increase the rate of cellulose digestion."

Previously, LPMOs were only known to occur in fungi, bacteria and viruses, but analysis of this new family showed it was widespread among invertebrates. Scientists suggest that it is possible that these enzymes could be adopted in industrial processes to break down cellulose into fermentable sugars for biofuel production.

Professor McQueen Mason said: "These digestive LPMOs appear to have evolved from enzymes that digest a substance called chitin, which protects the respiratory system of insects.

"We found that these ancestral genes are essential for metamorphosis and that interfering with their function is lethal to insects. This could have important implications for the development of new methods to control disease-carrying mosquitoes and agricultural pests such as locusts."

More than half of gun owners do not safely store all their guns, according to a new survey of 1,444 U.S. gun owners conducted by researchers at the Johns Hopkins Bloomberg School of Public Health.

The survey, believed to be the first nationally representative sample in 15 years to examine gun storage practices in U.S. households, found that 54 percent of gun owners reported not storing all their guns safely. The internet-based survey was fielded by the survey research firm GfK Knowledge Networks between March 15 and April 13, 2016.

The survey defined safe storage as all guns stored in a locked gun safe, cabinet or case, locked into a gun rack or stored with a trigger lock or other lock. This definition is based on research showing these practices reduce the risk of unauthorized access or use.

The findings will be published Feb. 22 in the American Journal of Public Health.

"Household gun ownership can increase the risk of homicides, suicides, and unintentional shootings in the home, but practicing safe storage for all guns reduces these risks," says lead study author Cassandra Crifasi, PhD, MPH, an assistant professor with the Johns Hopkins Center for Gun Policy and Research. "The survey findings indicate a real public health emergency. More than half of gun owners in the U.S. are not storing all of their guns safely--in a locked gun safe, cabinet or case, locked into a gun rack, or secured with a trigger lock."

The survey also found that children under the age of 18 were present in approximately one-third, or 34 percent, of the homes. Gun owners were 44 percent more likely to report safely storing all their firearms if they have a child under the age of 18 in the home: Slightly more than half, or 55 percent, of gun owners with children under 18 reported storing all of their guns safely.

Respondents were also asked about factors that influenced their gun storage practices. Concerns about home defense was selected by 43 percent, a gun safety training course by 35 percent, and family discussions by 30 percent.

In 2016, the most recent year of complete data, there were 1,637 firearm deaths among children under the age of 18; 39 percent of these deaths were the result of suicide. States with child access prevention laws that require gun owners to ensure children do not gain unauthorized access to their firearms report fewer firearm suicides among adolescents. Studies have also shown a decreased risk for self-inflicted injury among adolescents when guns are stored safely.

This new research finds that gun owners who reported a gun safety training course influenced their gun storage practices were twice as likely to practice safe storage for all their guns, and gun owners who cited discussions with family members as influencing their decisions were 39 percent more likely to practice safe storage.

"It's encouraging to see the positive associations between safety training and reporting safe storage practices," said study co-author Daniel Webster, ScD, MPH, director of the Johns Hopkins Center for Gun Policy and Research. "Requiring gun purchasers to take safety training classes, as a handful of states already do, might lead to more gun owners storing their guns safely."

The survey also found that gun owners who reported that their storage decisions were influenced by concerns about home defense were 30 percent less likely to practice safe storage for all their firearms.

"Many bring guns into their homes for self-defense, but unsecured guns can lead to unintentional shootings, suicides, and tragic cases of troubled teens using guns to commit acts of violence," said Crifasi. "Communicating with gun owners about the importance of safe storage is a challenging opportunity. If we are successful at improving storage practices among gun owners, particularly those with children in the home, we could reduce risks for gun violence and injury."

The survey also asked gun owners which groups could best communicate information about safe storage practices: 77 percent of respondents selected law enforcement as good messengers to teach gun owners about safe storage, followed by hunting/outdoor organizations (73 percent), active duty military (73 percent), military veterans (72 percent), and the NRA (71 percent). Physicians and celebrities scored lowest (19 percent and 11 percent, respectively).

Using an innovative crystallization technique for studying three-dimensional structures of gene transcription machinery, an international team of researchers, led by scientists at Penn State, has revealed new insights into the long debated action of the "magic spot"--a molecule that controls gene expression in Eschericahia coli and many other bacteria when the bacteria are stressed. The study contributes to our fundamental understanding of how bacteria adapt and survive under adverse conditions and provides clues about key processes that could be targeted in the search for new antibiotics. A paper describing the research appears on February 22, 2018 in the journal Molecular Cell.

"When bacteria experience stress, such as starvation, they remodel their gene expression," said Katsuhiko Murakami, professor of biochemistry and molecular biology at Penn State and an author of the paper. "In 1969, our coauthor, Michael Cashel, discovered that a new molecule appeared in E. coli when the bacteria were starved of key nutrients. Cashel called this molecule, which showed up as a new spot on a chromatogram, the 'magic spot,' because of its appearance from seemingly nowhere when bacteria were starved."

The magic spot subsequently was shown to be guanosine tetraphosphate, or ppGpp, a chemically modified analog of the G nucleotide in the ATCG alphabet of the genome. Its appearance following starvation and other stresses is associated with changes in the expression of over 500 genes, most prominently genes for the structural RNAs that are components of the ribosome-- the enzyme responsible for protein synthesis.

The ppGpp molecule interacts with E. coli's RNA polymerase--the cellular machine that produces RNA from genomic DNA--but precisely how this interaction controls gene expression remains a mystery. The new X-ray crystal structures, however, provide clues to this process by showing for the first time three-dimensional images of E. coli RNA polymerase in complex with ppGpp and another important factor that works with ppGpp, DksA.

The three-dimensional structure of RNA polymerase is well established, but seeing the structure of RNA polymerase while it is interacting with other molecules has proved to be technically difficult. The interacting molecules often disassociate during the crystallization process necessary to see their structure. The researchers overcame this difficulty by adding molecules of DksA and ppGpp to RNA polymerase that had been crystalized independently.

"We first created crystals of RNA polymerase, then soaked in DksA and ppGpp," said Vadim Molodtsov, assistant research professor in biochemistry and molecular biology at Penn State and another author of the paper. "When we did this, we saw that ppGpp bound to the complex of RNA polymerase and DksA in a way that changed the interaction between RNA polymerase and DksA. We think this change could be key to explain how ppGpp alters transcription so that the bacteria can respond to stress."

RNA polymerase in bacteria controls the expression of all genes, but in response to the presence of ppGpp, the expression levels of some genes are turned down, while many are unaffected and some are turned up. These changes in expression levels allow the bacteria to alter their composition to better survive stress. The researchers speculate that the different responses may be due to individual differences in the promotors--DNA sequences near the beginnings of genes that initiate expression--of individual genes.

"We are full of bacteria," said Sarah Ades, associate professor of biochemistry and molecular biology at Penn State and an author of the paper. "They affect our mood, they affect our weight, they affect our immune systems. The ppGpp system is important in lots of these bacteria, allowing them to sense their environment and adjust to stress. Understanding how ppGpp functions will allow us to better understand these bacteria and how they affect us. The system is also important in bacterial pathogens that cause infectious disease. Understanding how ppGpp works could allow us to find ways to disrupt its functions and develop new antibiotics."

Schizophrenia may be related to neurodevelopment changes, including brain’s inability to create the appropriate vascular system, according to new study resulted from a partnership between the D'Or Institute for Research and Education, the University of Chile and the Federal University of Rio de Janeiro (UFRJ). The results broaden the understanding about the causes of this severe and disabling disorder, which affects about 1% of the world's population.

"A partnership between Brazilian and Chilean groups allowed us to create this singular study, combining expertise on neurodevelopment and formation of blood vessels to investigate schizophrenia," says neuroscientist Stevens Rehen, a researcher at D’Or Institute and UFRJ and one of the study’s coordinators. Veronica Palma, from University of Chile, led the study with Rehen and highlights the combined approaches allowed the creation of an environment that mimics the one during embryonic brain development. The study was published on February 22nd in the journal Translational Psychiatry (Nature Publishing Group).

Characterized by episodes of hallucinations, confused thoughts and delusions, schizophrenia has no cure and the available treatment is only partially effective. Investigating causes of the disease can bring new therapeutic solutions and early diagnosis tools.

Previous studies on post-mortem brains and blood samples from patients with schizophrenia indicated that their brains show differences in terms of vascularization. It is also known that the interaction between blood vessels and neurons is essential for the correct development of the brain, as it allows the correct supply of oxygen and nutrients to neural cells and remove potentially harmful molecules.

The group investigated the ability of human neural cells to aid the formation of blood vessels during brain development. They used human induced pluripotent stem (iPS) cells created at D’Or Institute from the skin cells of three patients with schizophrenia and three people without the disorder. These cells were transformed into neural stem cells, which give rise to nerve cells. In addition, the scientists also used neurospheres - three-dimensional clusters of neural stem cells that begin to transform into neurons.

The cells were cultured in a suitable medium and the researchers checked the molecules they produced, in particular the pro-angiogenic ones, that is, molecules that nurture the production of new blood vessels. The experiment showed that neural cells originating from schizophrenic patients produced a smaller amount of these substances. Neurospheres from these patients also showed impairment of the ability to create new vessels, with low concentration of VEGFA, one of the most important angiogenesis regulatory molecules, and increased concentration of TIMP-1, an antiangiogenic protein.

“This is the first demonstration of the profile of angiogenic molecules expression using neural stem cells derived from patients with schizophrenia, which shows they have a less angiogenic profile when compared to controls”, says Palma. “Indeed, this model of cell culture may reproduce what happens under physiological conditions”.

To test the hypothesis that angiogenesis was compromised in the cells of patients with schizophrenia, a second experiment was performed. It consisted in exposing human umbilical cord endothelial cells to the substances produced by the nerve cells of the previous experiment. The same was done with chicken eggs, which served as in vivo model.

The umbilical cord endothelial cells have great capacity to form blood vessels. Chicken eggs have an extra-embryonic membrane that makes strong angiogenesis during development to nourish the embryo – a perfect in vivo assay to test for angiogenesis., as well as the membrane just beneath the eggshell. Therefore, those were chosen to test whether the molecules produced by the neural stem cells of patients alter the angiogenic capacity of the cells. The results confirmed the results – substances produced by schizophrenia patients’ nerve cells can hold back the angiogenic capacity of the endothelial cells.

"Advances on this subject bring new perspectives for the treatment and diagnosis of schizophrenia," Rehen says. Soon, he and his team plan to evaluate new biomarkers - that is, biological indicators, such as molecules that suggest the presence of the disease - that can identify the disorder regardless of symptoms. "This is a completely new approach on neuro-vascular mechanisms in mental disorders”, he concludes.

Researchers at New York University College of Dentistry (NYU Dentistry), in collaboration with Rheonix, Inc. (Ithaca, NY), are developing a novel test for Zika virus that uses saliva to identify diagnostic markers of the virus in a fraction of the time of current commercial tests.

The test, which was adapted from an existing model developed by NYU and Rheonix for rapid HIV testing, is described in two new publications appearing in PLOS ONE and the Journal of Visualized Experiments (JoVE).

How Zika is Tested

Outbreaks of infectious diseases are occurring with growing frequency thanks to factors such as population concentration and global air travel. A 2015 outbreak of Zika virus in Brazil spread to other countries in Central and South America, the Caribbean, and the Southern United States, leading the World Health Organization to declare Zika and its link to birth defects a public health emergency.

"The recent Zika virus outbreak confirms that we need an effective surveillance and diagnostic program to reduce the impact of future emerging infectious diseases," said Maite Sabalza, PhD, a postdoctoral associate at the Department of Basic Science and Craniofacial Biology at NYU Dentistry and the lead author of the studies in PLOS ONE and JoVE.

Identifying pathogens early is critical for combatting the spread of infectious diseases. Testing often involves two separate steps: one to detect a pathogen's nucleic acids (RNA or DNA) and another to test for antibodies, the proteins the body produces in response to pathogens.

Blood samples are most often used to test for Zika virus and are typically processed using a common diagnostic technique called real-time polymerase chain reaction (RT-PCR). But blood may not be the best fluid: While the virus disappears in the blood a week or two after a person is infected, it can persist longer in saliva, semen, and urine. In addition, antibodies can remain for months or years in those bodily fluids, which is why it is essential for diagnosis to also detect antibodies after infection.

Backed by funding from the National Institutes of Health, NYU Dentistry researchers are developing a rapid Zika test that combines both nucleic acid and antibody assays using saliva, given that Zika virus and antibodies persist in saliva. A saliva test is also noninvasive, cost effective, and easier to collect than blood or urine.

Faster Results

The new test also has the potential to produce results in a matter of minutes instead of hours or days. Current RT-PCR tests take around three hours and specific antibody tests can take several weeks. NYU researchers are using a different method called isothermal amplification, which can detect a virus' nucleic acids in as little as 20 minutes, and antibody tests that can take less than an hour using Zika-specific antigens.

"The sooner you can identify a pathogen, the sooner steps can be taken to treat and isolate people. During an epidemic, you could test people before they get on a plane. The future of going through security at the airport may not be taking off your shoes, but instead spitting into a tube," said study author Daniel Malamud, PhD, professor of basic science at NYU Dentistry.

From HIV to Zika

The research team is building on its earlier collaborative work with Rheonix developing a rapid saliva test for HIV that can detect both viral RNA and antibodies.

"When we developed the HIV test, we knew we could use the same model for any infectious disease. All we need to know is the nucleic acid sequence and an antigen to identify specific antibodies," Malamud said.

In PLOS ONE, the researchers describe how they altered this model to use markers that detect Zika nucleic acid sequences instead of those for HIV. They then used a portable isothermal amplification device - which could be used for point-of-care testing - to identify Zika RNA.

After showing that the test could confirm the presence of the virus using both purified Zika RNA and Zika-infected saliva, they adapted the test to the Rheonix CARD® cartridge and workstation, enabling them to estimate the viral load in saliva samples. Knowing the amount of virus present is useful for understanding disease severity and immune responses, particularly among pregnant women and fetuses.

The researchers also identified Zika-specific antigens - which can be used to detect the Zika specific antibodies needed for testing - using a high density peptide microarray they describe in JoVE. Because Zika can be easily confused with other viruses such as Dengue and Chikungunya, identifying Zika-specific antigens paves the way for more precise diagnostic testing.

With evidence showing that both the nucleic acid and antibody tests work, the researchers can combine them in the Rheonix CARD® cartridge to process both diagnostic assays automatically and simultaneously. Researchers at NYU and around the world are continuing to validate their findings in further experiments using Zika-infected saliva.

"In working towards the goal of quickly making effective diagnostics available, we have developed a generic protocol that can not only be used to test for Zika virus but can be adapted for the next emerging or re-emerging infectious disease," said Sabalza. Study author Richard Montagna, PhD, FACB, Rheonix's Senior Vice President for Scientific & Clinical Affairs, added, "In addition to being able to react very quickly to any newly emerging or re-emerging infectious disease, our fully automated testing platform requires virtually no hands-on efforts and is well suited for use by individuals with minimal training."

MINNEAPOLIS - Tears may hold clues to whether someone has Parkinson's disease, according to a preliminary study released today that will be presented at the American Academy of Neurology's 70th Annual Meeting in Los Angeles, April 21 to 27, 2018.

"We believe our research is the first to show that tears may be a reliable, inexpensive and noninvasive biological marker of Parkinson's disease," said study author Mark Lew, MD, of the Keck School of Medicine of the University of Southern California in Los Angeles and a Fellow of the American Academy of Neurology.

Lew says the research team investigated tears because they contain various proteins produced by the secretory cells of the tear gland, which is stimulated by nerves to secrete these proteins into tears. Because Parkinson's can affect nerve function outside of the brain, the research team hypothesized that any change in nerve function may be seen in the protein levels in tears.

For the study, tear samples from 55 people with Parkinson's were compared to tear samples from 27 people who did not have Parkinson's but who were the same age and gender. Tears were analyzed for the levels of four proteins.

Researchers found differences in the levels of a particular protein, alpha-synuclein, in the tears of people with Parkinson's compared to controls. Additionally, levels of another form of alpha-synuclein, oligomeric alpha-synuclein, which is alpha-synuclein that has formed aggregates that are implicated in nerve damage in Parkinson's, were also significantly different compared to controls. It is also possible that the tear gland secretory cells themselves produce these different forms of alpha-synuclein that can be directly secreted into tears.

Total levels of alpha-synuclein were decreased in people with Parkinson's, with an average of 423 picograms of that protein per milligram (pg/mg) compared to 704 pg/mg in people without Parkinson's. But levels of oligomeric alpha-synuclein were increased in people with Parkinson's, with an average of 1.45 nanograms per milligram of tear protein (ng/mg) compared to 0.27 ng/mg in people without the disease. A picogram is 1,000 times smaller than a nanogram.

"Knowing that something as simple as tears could help neurologists differentiate between people who have Parkinson's disease and those who don't in a noninvasive manner is exciting," said Lew. "And because the Parkinson's disease process can begin years or decades before symptoms appear, a biological marker like this could be useful in diagnosing, or even treating, the disease earlier."

More research now needs to be done in larger groups of people to investigate whether these protein changes can be detected in tears in the earliest stages of the disease, before symptoms start.

DURHAM, N.C. -- The fungus that causes athlete's foot and other skin and toenail infections may have lost its ability to sexually reproduce as it adapted to grow on its human hosts.

Scientists analyzed samples of this tenacious organism, called Trichophyton rubrum, and found that nearly all belonged to a single mating type. What's more, when they tried to set the fungi up with members of another mating type, they refused to do the deed, even after the scientists enlisted a variety of seduction schemes -- lowering the lights, cloaking the Petri dishes in plastic, flipping them upside down.

If this fungus can't sexually reproduce, it can't diversify, and if it can't diversify, that may mean its days on this planet are numbered, said Joseph Heitman, MD, PhD, senior study author and professor and chair of molecular genetics and microbiology at Duke University School of Medicine.

But don't expect toenail fungus to appear on the endangered species list anytime soon. "It is commonly thought that if an organism becomes asexual, it is doomed to extinction," Heitman said. "While that may be true, the time frame we are talking about here is probably hundreds of thousands to millions of years."

Though that timeline won't be much help to the nearly 2 billion people who currently suffer from fungal infections of the skin and nails, the discovery that this species may be asexual -- and therefore nearly identical at the genetic level -- does highlight potential vulnerabilities that researchers could exploit in designing more effective antifungal medications. The findings appear online in the journal Genetics.

Fungal infections affect approximately 25 percent of the world's population, and Trichophyton rubrum is usually the species to blame. People can pick up this infection by walking barefoot around swimming pools, showers or locker rooms, or by sharing personal items such as towels or nail clippers. Though there are plenty of over-the-counter powders and ointments along with prescription anti-fungal drugs on the market, most keep the infection at bay but don't clear it. The infection is notoriously difficult to cure, and recent evidence suggests it may often be drug-resistant.

In this study, an international team of researchers decided to take a close look at the genetic makeup and sexual predilections of this fungus. They collected 135 different Trichophyton rubrum samples from around the world and determined their mating type by searching the fungal genome for either the alpha or the HMG domain, which is essentially the molecular equivalent of looking between a dog's legs. The researchers were amazed to find that all but one of the samples were from a single mating type.

Though the findings suggested the fungi had become asexual, the scientists wondered if they would mate if given the opportunity. They placed the isolates in petri dishes along with a variety of potentially compatible mating types, under a variety of different conditions, and then waited to see if any magic would happen. After five months, the researchers looked at the petri dishes under a light microscope, scanning for the growth of coiled appendages that might contain spores. They didn't see any.

Curious, the researchers sequenced the genome of the organism. They found that the organism is very clonal, meaning that different isolates (populations) are nearly perfect clones of each other, with little variation from one genome to the next. Any two genomes of Trichophyton rubrum are 99.97 percent identical, which translates to three differences out of every 10,000 genetic letters. Other fungi such as Cryptococcus are only 99.36 percent identical, differing in 64 out of 10,000 letters, making them 21 times more diverse than the toenail fungus.

"Such incredibly high clonality across isolates from around the world is remarkable, and suggests that this organism is very well adapted to humans," said Christina Cuomo, PhD, senior study author and a group leader for the Fungal Genomics Group at the Broad Institute of MIT and Harvard.

But there is a silver lining. Because the fungus is so clonal and could also be asexual, its ability to adapt further may be more limited than some other fungi. Thus, any new strategies that researchers could develop against this species may have a higher chance of success than those targeting sexual species, which are more capable of mutating or amplifying drug-resistance genes.

Researchers who analyzed gene expression in synovial tissue samples from rheumatoid arthritis patients' joints identified different patterns that may be clinically meaningful. The findings, which are published in Arthritis & Rheumatology, indicate that the mechanisms of pain differ in patients with different synovial subtypes of rheumatoid arthritis, and they may help guide clinicians as they develop optimal treatment strategies for patients.

"We were surprised to find that some patients had high pain, tenderness, and even swollen joint counts while exhibiting minimal inflammation in their tissue or blood. This suggests that some patients can have high disease activity scores with little inflammation," said lead author Dr. Dana Orange, of The Rockefeller University. "It stands to reason that patients with minimal tissue inflammation may not respond to our usual immune-targeting drugs."