Earth

A genetic mutation that disrupts how DNA sends messages to the rest of a cell has been linked to a large number of blood cancers. Thanks to a collaboration between biologists at Cold Spring Harbor Laboratory (CSHL) and an oncologist at Memorial Sloan Kettering Cancer Center (MSKCC), we now know how the mutation triggers a chain of biological events that lead to most leukemias.

The deadly chain of events begins with RNA splicing, a process that converts messages from DNA into instructions for making proteins in a cell. Errors in RNA splicing can result in poorly formed proteins that are unable to do their job. The CSHL-MSKCC team found that in blood cancers, a process associated with splicing called Nonsense-mediated mRNA decay (NMD) is excessively active. After splicing converts DNA messages, the NMD process normally serves as "quality control," destroying messages that contain mistakes before a broken protein is made.

The Krainer lab at CSHL determined that when the gene called SRSF2 is mutated, NMD destroys many more messages, including some that have not been likely targets of NMD before. Messages that are important for healthy blood cell production are one of these new targets. The result of excessively active NMD is less healthy blood cells and more sickly or immature cells--a hallmark of blood cancer.

"RNA splicing factor mutations are seen in virtually all forms of leukemia, both chronic as well as acute myeloid leukemias and also even chronic lymphocytic leukemia," said Omar Abdel-Wahab, M.D. at MSKCC. "I'm a hematological oncologist--I think a lot about blood cancer--so this caught my attention right away."

Scientists have seen other cancers manipulate NMD into protecting solid tumors. However, the CSHL-MSKCC discovery, published in Genes and Development, is the first evidence of NMD contributing to blood cancer conditions.

Video: https://www.youtube.com/watch?v=7OoY0tbi8TU

To stop the mutated SRSF2 gene from affecting NMD, the researchers experimented with a technique called antisense oligonucleotide (ASO) therapy. As shown by CSHL Professor Adrian Krainer in past works, ASO therapy has been effective in combating other diseases resulting from defective RNA splicing. The next step will be to test many ASOs in animals, perfecting the team's approach until it is ready for the clinic.

"Before this collaboration, I knew very little about splicing factors or this process of NMD. Conversely, Adrian's lab didn't have much disease-specific experience with blood cancers, so it's been a synergistic experience," Abdel-Wahab added. "By combining forces, we've really been able to address what we've learned."

It's not an over-the-counter drug, but naloxone can now be dispensed by a pharmacist without a prescription in some states. Researchers have found it's made a huge impact on the number of prescriptions being dispensed in Ohio.

A new study by pharmacy researchers at the University of Cincinnati shows a 2,328% increase in the number of naloxone prescriptions dispensed in Ohio. The increase occurred since 2015 when the Ohio General Assembly approved a law that allows pharmacists to dispense naloxone -- the life-saving medicine given to those who overdose on drugs such as heroin -- without a prescription.

Researchers also found that low-employment counties had 18% more naloxone prescriptions dispensed per month compared to high employment counties.

The study, "Association between a Pharmacist Naloxone Dispensing Law and Naloxone Dispensing Rates in Ohio", now appears in the leading medical journal JAMA Network Open. It is the first of a two-part series by researchers from the UC James L. Winkle College of Pharmacy and funded by the U.S. Centers for Disease Control and Prevention.

This research aligns with UC's strategic direction, Next Lives Here, emphasizing discovery by investigating problems and innovating solutions.

"Our study shows that this change in the Ohio law allowed pharmacists to have more opportunity to participate in the management of patients addicted to opioids," says the study's lead faculty researcher Pam Heaton, a professor of pharmacy practice at UC's Winkle College.

Naloxone (commonly known as Narcan) is a medication called an opioid antagonist that is used to counter the effects of opioid overdose, such as with morphine and heroin. The majority of states allow pharmacists to dispense the medicine without a prescription under varying guidelines. As of May 2019, approximately 75% of community pharmacies in Ohio were registered to dispense naloxone without a prescription.

According to the Ohio state ruling, the law allows pharmacists and pharmacy interns to dispense naloxone using a specific physician approved protocol to: (1) An individual who there is reason to believe is experiencing or at risk of experiencing an opioid-related overdose; (2) A family member, friend or other person in a position to assist an individual who there is reason to believe is at risk of experiencing an opioid-related overdose; or (3) A peace officer as defined in section 2921.51 of the Revised Code.

In the study, the research team compared 18 months of post-policy data to pre-policy data from Ohio's Medicaid records and the database of the Kroger Co.'s Ohio pharmacies, which includes prescriptions for patients with all types of insurance, not just Medicaid. Ohio's Medicaid population is approximately 2.2 million, or 21% of the state's population of 11.42 million. Among Medicaid recipients, the total number of patients receiving naloxone increased from 183 patients in the pre-policy period to 3,847 patients in the post-policy period. The analysis using the Kroger data confirmed an increase in the number of naloxone prescriptions dispensed for all types of insurance including cash prescriptions.

The uptick in low employment areas, professor Heaton says, is most likely because the local pharmacy is often the sole health care contact for people living in these locations.

"We do not know whether the naloxone was for personal use, a family member or a friend because the law was written to specifically allow access," Heaton says, adding that the study did not seek to quantify the impact of increased naloxone distribution on the rate of opioid abuse or mortality from overdose, but was designed to address access.

"Overdoses are not a planned event so during an emergency is not the time to try and access naloxone. The intent is for any adult to be able to go to a pharmacy and purchase naloxone for themselves or for anybody who might need it, so they are adequately prepared to administer a lifesaving medication," says Heaton.

Prior studies, however, estimate up to a 14% reduction in death by overdose in states where access is increased, says Neha Gangal, the study's first author. The reduction is pivotal, Gangal says, considering that drug overdose deaths doubled in the last decade; 70,200 deaths were reported in 2017 in the United States and between 2015 and 2017, among all states, Ohio had the second highest number of opioid-related deaths.

The bottom line, Gangal says, is that "legal barriers needed to be removed to address this important public health crisis. Pharmacists positively impact the health of patients every day and work tirelessly to address the opioid epidemic. By providing naloxone, pharmacists save lives."

London, UK: Migraine mechanisms are still far from being fully understood. Escalating data from animal models are "fact-checking" the neurophysiological and behavioral correlates of the migraine experience in humans. A series of studies published in the journal Cephalalgia, the official journal of the International Headache Society, have described the underlying mechanisms and molecules related to migraine, and how they may be affected by current anti-migraine drugs or might translate into new therapies.

Evidence suggests that migraine can originate from either central or peripheral mechanisms. Central mechanisms mean that changes in structures of the central nervous system, such as the cortex, hypothalamus, thalamus, among others, are altered, modifying brain excitability, leading to headache attacks. One mechanism believed to cause migraine is cortical spreading depression (CSD). CSD is a depolarization wave of the neurons that spreads from the occipital cortex (neck region) to parietal cortex and is also related to the migraine aura. The peripheral mechanism, on the other hand, involves the activation of nociceptors (neurons that process painful stimuli) in the meninges that surround the brain and cerebral vessels. However, CSD (with central origin) can activate the trigeminovascular system, where the nociceptors of the meninges and brain vessels come from. In a series of recent studies, these animal models are shedding more light on migraine therapies and etiological mechanisms.

Onabotulinum toxin A

Onabotulinum toxin type A (Botox) has been shown to be effective in the treatment of chronic migraine. Studies carried out with lab animals simulating neurophysiological mechanisms of the disease, are beginning to reveal how these medications work against migraine.

A research group from the Beth Israel Deaconess Medical Center and Harvard Medical School, led by Dr. Rami Burstein, showed that the induction of CSD in rats, simulating a migraine attack, activates the trigeminovascular system and increases the triggering of nociceptors from the meninges. More recently, these same group of researchers showed that in female rats the application of Botox applied peripherally to the lambdoid and sagittal sutures reduced the nociceptor shots induced by CSD by 72%, indicating that the activation of nociceptors by central migraine-inducing phenomena, such as CSD, can be blocked by Botox.

CGRP

The calcitonin gene-related peptide (CGRP)) is an inflammatory and vasodilator neuropeptide that is elevated in the circulation of people with migraine and induces migraine in these patients when injected intravenously.

A growing number of studies in preclinical migraine models have shown that females are more susceptible to the nociceptive effects of CGRP, possibly due to estrogen amplifying effects on CGRP receptors. A Brazilian study, led by Dr. Juliana Geremias Chichorro, from the Federal University of Paraná, showed in another animal model of migraine that the CGRP applied within the trigeminal ganglion was able to induce neurophysiological and behavioral responses in male and female rats similar to migraine in humans, such as cutaneous allodynia (when the scalp/skin becomes painful to non-painful stimuli), intolerance to light (photophobia) and anxiety behavior. Interestingly, drugs with neuroprotective actions such as minocycline and propentophylline were effective in inhibiting the effects of CGRP only in male rats. However, sumatriptan, which is currently prescribed to abort migraine attacks, was effective in inhibiting the action of CGRP in both sexes.

PACAP-38

Lastly, but not least, a research from Dr. Lars Edvinsson's lab at the University of Lund, Sweden, found that in rats, another migraine-related emerging neuropeptide, namely, the pituitary adenylate cyclase-activating polypeptide (PACAP-38), co-localized with CGRP in areas of the brain that are related to the origin of migraine attacks. PACAP-38 and CGRP matched well in the cerebral cortex, cerebellum, thalamus, hypothalamus, the pons and spinal trigeminal nucleus, which are well-known neuroanatomic sites related to migraine.

These are a few examples of how pre-clinical studies go further into migraine mechanisms of symptoms and behaviors in humans, as well as provide insightful data on migraine therapies' mechanisms of action.

New research techniques are being adopted by scientists tackling the most visible impact of climate change - the so-called greening of Arctic regions.

The latest drone and satellite technology is helping an international team of researchers to better understand how the vast, treeless regions called the tundra is becoming greener.

As Arctic summer temperatures warm, plants are responding. Snow is melting earlier and plants are coming into leaf sooner in spring. Tundra vegetation is spreading into new areas and where plants were already growing, they are now growing taller.

Understanding how data captured from the air compare with observations made on the ground will help to build the clearest picture yet of how the northern regions of Europe, Asia and North America are changing as the temperature rises.

Now a team of 40 scientists from 36 institutions, led by two National Geographic Explorers, have revealed that the causes of this greening process are more complex - and variable - than was previously thought.

Researchers from Europe and North America are finding that the Arctic greening observed from space is caused by more than just the responses of tundra plants to warming on the ground. Satellites are also capturing other changes including differences in the timing of snowmelt and the wetness of landscapes.

Lead author Dr Isla Myers-Smith, of the University of Edinburgh's School of GeoSciences, said: "New technologies including sensors on drones, planes and satellites, are enabling scientists to track emerging patterns of greening found within satellite pixels that cover the size of football fields."

Professor Scott Goetz of the School of Informatics, Computing and Cyber Systems at Northern Arizona University, says this research is vital for our understanding of global climate change. Tundra plants act as a barrier between the warming atmosphere and huge stocks of carbon stored in frozen ground.

Changes in vegetation alter the balance between the amount of carbon captured and its release into the atmosphere. Small variations could significantly impact efforts to keep warming below 1.5 degrees centigrade - a key target of the Paris Agreement. The study will help scientists to figure out which factors will speed up or slow down warming.

Co-lead author Dr Jeffrey Kerby, who was a Neukom Fellow at Dartmouth College while conducting the research, said: "Besides collecting new imagery, advances in how we process and analyse these data - even imagery that is decades old - are revolutionising how we understand the past, present, and future of the Arctic."

Alex Moen, Vice President of Explorer Programs at the National Geographic Society, said: "We look forward to the impact that this work will have on our collective understanding of the Arctic for generations to come."

Monash University researchers are developing a revolutionary, portable blood pressure monitoring device that provides data continuously to patients.

A world-first trial took place with 43 participants. Blood pressure was measured in patients while sitting, standing, laying down, and exercising. Recordings were taken with 93 per cent accuracy.

The cuffed sphygmomanometer is the current industry gold standard. The device cannot provide continuous blood pressure results, nor can it be used while patients sleep, or if they're active.

Researchers at Monash University are on the verge of creating a revolutionary, portable blood pressure monitoring device that can provide data continuously to patients from the comfort of their home.

In a world-first study, led by Associate Professor Mehmet Yuce from Monash University's Department of Electrical and Computer Systems Engineering, 43 Australian participants trialed a wireless blood pressure monitoring device, developed by the research team, which provided continual readings across a 24-hour period.

Data was recorded during a range of sedentary and physical activities during the participants' regular day. Results were published in the prestigious international journal Nature Scientific Reports.

Blood pressure abnormalities, such as hypertension and hypotension, are important risk factors for many critical short- and long-term illnesses, with a global disease burden of 1.25 billion people. The current gold standard for blood pressure measurement is the cuffed sphygmomanometer, commonly seen at GP clinics and hospitals.

"For close to a century, the health sector has used the cuff device to measure blood pressure. More invasive measures are used to monitor the continuous blood pressure of critically ill patients, which are uncomfortable and could potentially cause infection due to ischemia," Associate Professor Yuce said.

Researchers used continuous wave radar (CWR) and photoplethysmogram (PPG) sensors to calculate continuous blood pressure measurements. The CWR and PPG sensors were placed on the sternum and left earlobe respectively.

By using radar technology, researchers were able to calculate the pre-ejection period (PEP) - the mechanical delay associated with heart movements ejecting the blood - and the pulse transit time to estimate blood pressure in patients while sitting, laying down or exercising.

Results on subjects participating in posture tasks were 93 per cent accurate, while those performing exercises achieved an 83 per cent success rate.

Associate Professor Yuce and his research team have developed several prototypes of the blood pressure device, and will conduct further tests to make it more accurate and suitable for clinical use.

"Clinicians still cannot continuously measure blood pressure during sleep, nor during times of activity such as walking or running. This means people with high, low or irregular blood pressure can't get the critical information they need about the state of their health around the clock," Associate Professor Yuce said.

"A wearable device that can provide comfort and portability while people are going about their daily lives will be a significant development for the health sector in Australia and internationally."

A trial was conducted on 43 participants, between the ages of 40 and 65, with no previous cardiovascular problems. Participants wore both the cuff device and the chest-based prototype to monitor the difference between blood pressure readings.

Blood pressure data was recorded on all participants while sitting, standing and laying in the supine position (facing upwards). Subsequent tests were also conducted with patients holding a handgrip for two minutes; cycling at a fixed speed across three different resistance levels; and at the recovery stage after the cycling tasks.

The technology has the capability of providing real-time access to data, and give doctors an overview of how their patients' blood pressure changes over the course of a day, rather than at the time of testing.

"The CWR sensors present a low-power, continuous and potentially wearable system with minimal body contact to monitor aortic valve activities directly. Doctors would be interested to see such information for long-term better diagnosis of their patients," Associate Professor Yuce said.

"Results of this study demonstrate the potential superiority of CWR-based PEP extraction for various medical monitoring applications, including blood pressure monitoring."

Australian scientists have developed a nonflammable electrolyte for potassium and potassium-ion batteries, for applications in next-generation energy-storage systems beyond lithium technology. In the journal Angewandte Chemie, scientists write that the novel electrolyte based on an organic phosphate makes the batteries safer and also allows for operation at reduced concentrations, which is a necessary condition for large-scale applications.

Lithium-ion technology still dominates energy-storage applications, but it has intrinsic disadvantages, among which are the price, environmental issues, and the flammability of the electrolyte. Therefore, in next-generation technologies, scientists are replacing the lithium ion with more abundant and much cheaper ions, such as the potassium ion. However, potassium and potassium-ion batteries also face safety issues, and nonflammable electrolytes are not yet available for them.

Materials scientist Zaiping Guo, and her team from the University of Wollongong, Australia have found a solution. The researchers developed an electrolyte based on a flame-retardant material and adapted it for use in potassium batteries. Besides providing nonflammability, it could be operated in batteries at concentrations that are suitable for large-scale applications, write the scientists.

This novel electrolyte contained triethyl phosphate as the sole component of the solvent. This substance is known as a flame retardant. It has been tested in lithium-ion batteries, but only very high concentrations provided enough stability for long-term operation, too high for industrial applications. The battery industry demands dilute electrolytes, which are cheaper and ensure better performances. By using potassium ions, however, the concentrations could be reduced, the authors reported. They combined the phosphate solvent with a commonly available potassium salt and obtained an electrolyte that did not burn and allowed stable cycling of the assembled battery concentrations of 0.9 to 2 moles per liter, which are concentrations that are suitable for larger scales; for example, in smart-grid applications.

Key to that performance was the formation of a uniform and stable solid-electrolyte interphase layer, according to the authors. They observed this layer, which ensures operability of the electrodes, only with the phosphate electrolyte. Conventional carbonate-based electrolytes were unable to build up this layer. The authors also reported high cycling stability; whereas, under the same conditions, the conventional carbonate-based electrolyte decomposed.

Guo and her team have demonstrated that next-generation potassium-ion batteries can be made safe by using a novel inorganic, phosphate-based electrolyte. They suggest that electrolytes based on flame retardants can be developed further and could be used for the design of other nonflammable battery systems.

RESEARCH TRIANGLE PARK, N.C. -- New Army research provides a better understanding of the swelling that occurs in the brain during a stroke, which could contribute to new treatment strategies for stroke patients and have potential implications for traumatic brain injuries.

Cerebral edema, swelling that occurs in the brain, is a severe and potentially fatal complication for stroke victims. Research, funded in part by the Army Research Office and conducted at The University of Rochester Medical Center, shows for the first time that the glymphatic system -- normally associated with the beneficial task of waste removal -- goes awry during a stroke and floods the brain, promoting edema and drowning brain cells.

The research, conducted with mice, appears in the journal Science.

"These findings show that the glymphatic system plays a central role in driving the acute tissue swelling in the brain after a stroke", said Maiken Nedergaard, M.D., D.M.Sc., co-director of the University of Rochester Medical Center Center for Translational Neuromedicine and senior author of the article. "Understanding this dynamic -- which is propelled by storms of electrical activity in the brain -- point the way to potential new strategies that could improve stroke outcomes."

The glymphatic system, first discovered by the Nedergaard lab in 2012, consists of a network that piggybacks on the brain's blood circulation system and is comprised of layers of plumbing, with the inner blood vessel encased by a 'tube' that transports cerebrospinal fluid. The system pumps the fluid through brain tissue primarily during sleep, washing away toxic proteins and other waste.

Before the findings of the new study, scientists assumed that the source of brain swelling was exclusively the result of fluid from blood.

"Our hope is that this new finding will lead to novel interventions to reduce the severity of ischemic events, as well as other brain injuries to which Soldiers may be exposed," said Matthew Munson, Ph.D., program manager, fluid dynamics, ARO, an element of the U.S. Army Combat Capabilities Development Command's Army Research Laboratory. "What's equally exciting is that this new finding was not part of the original research proposal. That is the power of basic science research and working across disciplines. Scientists 'follow their nose' where the data and their hypotheses lead them -- often to important unanticipated applications."

AN ELECTRICAL WAVE, THEN THE FLOOD

Ischemic stroke, the most common form of stroke, occurs when a vessel in the brain is blocked. This blockage denies the nutrients and oxygen cells need to function, which results in their rapid depolarization. As the cells release energy and fire, they trigger neighboring cells, creating a domino effect that results in an electrical wave that expands outward from the site of the stroke, called spreading depolarization.

During the spreading depolarization, vast amounts of potassium and neurotransmitters released by neurons into the brain cause the smooth muscle cells that line the walls of blood vessels to seize up and contract, cutting off blood flow in a process known as spreading ischemia. Cerebrospinal Fluid then flows into the ensuing vacuum, inundating brain tissue and causing edema. The already vulnerable brain cells in the path of the flood essentially drown in fluid and the brain begins to swell. These depolarization waves can continue in the brain for days and even weeks after the stroke, compounding the damage.

"When you force every single cell, which is essentially a battery, to release its charge it represents the single largest disruption of brain function you can achieve -- you basically discharge the entire brain surface in one fell swoop," said Humberto Mestre, M.D., a Ph.D. student in the Nedergaard lab and lead author of the study. "The double hit of the spreading depolarization and the ischemia makes the blood vessels cramp, resulting in a level of constriction that is completely abnormal and creating conditions for CSF to rapidly flow into the brain."

The study correlated the brain regions in mice vulnerable to the fluid propelled by the glymphatic system with edema found in the brains of humans who had sustained an ischemic stroke.

POINTING THE WAY TO NEW STROKE THERAPIES

The findings suggest potential new treatment strategies that, used in combination with existing therapies, focus on restoring blood flow to the brain quickly after a stroke. The study could also have implications for brain swelling observed in other conditions such as subarachnoid hemorrhage and traumatic brain injury.

Approaches that block specific receptors on nerve cells could inhibit or slow the cycle of spreading depolarization. Additionally, a water channel called aquaporin-4 on astrocytes -- an important support cell in the brain -- regulates the flow of the fluid. When the research team conducted the stroke experiments in mice genetically modified to lack aquaporin-4, the fluid flow into the brain slowed significantly.

Aquaporin-4 inhibitors currently under development as a potential treatment for cardiac arrest and other diseases could eventually be candidates to treat stroke.

Oncotarget Volume 11, Issue 4: Pathogenic or likely pathogenic alterations in these 14 DNA repair genes were less likely to be detected in African Americans as compared to Caucasians.

Upon a more in-depth analysis, the risk of germline pathogenic/likely pathogenic BRCA mutations was similar between the two populations whereas there was a lower risk among African Americans for the non-BRCA mutations.

Dr. Oliver Sartor from the Tulane Cancer Center at the Tulane University of School of Medicine in New Orleans Louisiana, United States said in an Oncotarget article, "African American (AA) men are incompletely characterized with regard to germline DNA repair mutations in the prostate cancer datasets published to date."

Herein the authors used a large commercial DNA germline assessment data set to compare frequencies of pathogenic/likely pathogenic alterations in 14 well characterized DNA repair genes assessed in both AA men and Caucasian American men with prostate cancer.

The Sartor Research Team concluded in their Oncotarget paper that they recognize not all of these mutations, such as the CHEK2 mutation, may be actionable at this time but these data may have implications as precision therapeutics evolve.

Cervical cancer could be eliminated worldwide as a public health issue within the next century. This is the conclusion of two studies published today in The Lancet by an international consortium of researchers codirected by Professor Marc Brisson from Université Laval's Faculty of Medicine and the CHU de Québec-Université Laval Research Centre. The researchers are even more optimistic about North America, stating that the disease could be almost completely eliminated by 2040.

The study used the human papillomavirus (HPV) vaccination and cervical screening targets defined in the WHO draft strategy of cervical cancer elimination. The plan calls for 90% of girls to be vaccinated against HPV by 2030. The plan also calls for 70% of women to be screened for cervical cancer once or twice in their lifetime, and for 90% of women with precancerous lesions or cervical cancer to receive appropriate treatment.

The researchers' analyses show that with vaccination alone, the cervical cancer cases will drop by 89% within a century in the 78 countries worst affected by the disease, with 60 million cases of cancer averted as a result. By adding the two screening tests and the treatment of precancerous cervical lesions, cervical cancer cases will drop by 97% and 72 million cervical cancer cases will be averted over the next century. Furthermore, with scale-up of appropriate cancer treatment, 62 million cervical cancer deaths will be averted.

"For the first time, we've estimated how many cases of cervical cancer could be averted if WHO's strategy is rolled out and when elimination might occur, says Marc Brisson. Our results suggest that to eliminate cervical cancer it will be necessary to achieve both high vaccination coverage and a high uptake of screening and treatment, especially in countries with the highest burden of the disease."

The results were used to develop WHO's cervical cancer elimination strategy which will be presented for adoption at the World Health Assembly in May 2020. "If the strategy is adopted and applied by member states, cervical cancer could be eliminated in high income countries by 2040 and across the globe within the next century, which would be a phenomenal victory for women's health," says Professor Brisson. "However, this can only be achieved with considerable international financial and political commitment, in order to scale up prevention and treatment"."

During an unprecedented scientific campaign on an Antarctic glacier notorious for contributions to sea-level, researchers took first-ever images at the glacier's foundations on the ocean floor. The area is key to Thwaites Glacier's potential to become more dangerous, and in the coming months, the research team hopes to give the world a clearer picture of its condition.

The images, taken by a robotic underwater vehicle, were part of a broad set of data collected in a variety of experiments by an international team. The International Thwaites Glacier Collaboration (ITGC) announced the completion of this first-ever major research venture on the glacier coincident with the 200-year anniversary of the discovery of Antarctica in 1820.

Already, Thwaites accounts for about four percent of global sea-level rise. Researchers have had concerns that a tipping point in the stability at its foundations could result in a run-away collapse of the glacier and boost sea levels by as much as 25 inches. By studying multiple aspects of Thwaites, the ITGC wants to understand more about the likelihood that the glacier the size of Florida may reach such instability in the coming decades.

Line of concern

The area of concern that the underwater vehicle visited is called the grounding line, and it is important to the stability of Thwaites Glacier's footing. It is the line between where the glacier rests on the ocean bed and where it floats over water. The farther back the grounding line recedes, the faster the ice can flow into the sea, pushing up sea-level.

"Visiting the grounding line is one of the reasons work like this is important because we can drive right up to it and actually measure where it is," said Britney Schmidt, an ITGC co-investigator from the Georgia Institute of Technology. "It's the first time anyone has done that or has ever even seen the grounding zone of a major glacier under the water, and that's the place where the greatest degree of melting and destabilization can occur."

The underwater robot, Icefin, was engineered by Schmidt's Georgia Tech lab. The Georgia Tech team was part of a greater collaboration between researchers from the U.S. and the British Antarctic Survey (BAS), who lived and worked on Thwaites in December and January. A BAS hot water drill melted a hole 590 meters deep (1,935 feet) to access the ocean cavity for Icefin.

"Icefin swam over 15 km (9.3 miles) round trip during five missions. This included two passes up to the grounding zone, including one where we got as close as we physically could to the place where the seafloor meets the ice," said Schmidt, who is an associate professor in Georgia Tech's School of Earth and Atmospheric Sciences. "We saw amazing ice interactions driven by sediments at the line and from the rapid melting from warm ocean water."

Historic research venture

In the coming months and years, the ITGC team, made up of researchers from multiple universities and research institutions in the U.S. and the UK will publish studies with thorough findings based on the unprecedented data collected during the field campaign.

The array of research the scientists carried out research included seismic and radar measurements and using hot water drills make holes between 300 and 700 meters (985 and 2,300 feet) deep down to the ocean and glacier bed below Thwaites' ice. Researchers also took cores of sediment from the seafloor and under parts of the glacier grounded on the bed to examine the quality of the foothold that it offers Thwaites.

"We know that warmer ocean waters are eroding many of West Antarctica's glaciers, but we're particularly concerned about Thwaites. This new data will provide a new perspective of the processes taking place, so we can predict future change with more certainty," said Keith Nicholls, an oceanographer from the British Antarctic Survey.

Nicholls is a co-principal investigator on the project that involved Schmidt along with David Holland of New York University. The research is funded by the National Science Foundation, the UK Natural Environment Research Council, the U.S. Antarctic Program, and British Antarctic Survey.

Antarctica sea-level background

Over the past 30 years, the amount of ice flowing to the sea from Thwaites and its neighboring glaciers has nearly doubled.

"While Greenland's contribution to sea level has already reached an alarming rate, Antarctica is just now picking up its contributions to sea level," Schmidt said. "It has the largest body of ice on Earth and will contribute more and more of sea level rise over the next 100 years and beyond. It's a massive source of uncertainty in the climate system."

In the first genetic analysis of schizophrenia in an ancestral African population, the South African Xhosa, researchers report that individuals with schizophrenia are more likely to carry rare damaging genetic mutations than those who are well. The work informs the understanding of schizophrenia for all human populations. Critically, this study was not undertaken because the Xhosa have an unusually high prevalence of schizophrenia, but rather, because ancestral African populations - which rarely have been the focus of genetics research - harbor the most human genetic diversity. The lack of genetics studies in Africa, where nearly 99% of human evolution took place, leaves a major gap in understanding the human genome and the genetic causes of complex diseases like schizophrenia. Without studies in Africa, many generations of human genetic history are missing from scientists' understanding of human adaptation and disease. Schizophrenia, a debilitating long-term mental disorder that can significantly impact how a person thinks, feels, and behaves, is estimated to affect between 0.3-0.7% of the world's population. The illness varies genetically among patients, and in many patients involves mutations that damage genes essential to brain development. Because fewer children are born to persons with schizophrenia, very recent and de novo mutations are a major factor in its development. Suleyman Gulsuner and colleagues from the U.S. and South Africa examined the DNA sequences of all genes from more than 1,800 Xhosa individuals from South Africa, roughly half of whom had been diagnosed with schizophrenia. Individuals with schizophrenia were more likely to carry one or more rare damaging mutations, particularly in genes that function in brain synapses. Human biology is universal. The greater genetic variation in Africans provides a unique opportunity to discover and evaluate disease-associated genes that are relevant to all human populations. These discoveries can help inform new treatments.

LA JOLLA--(January 30, 2020) Researchers at the Salk Institute have discovered a unique pattern of DNA damage that arises in brain cells derived from individuals with a macrocephalic form of autism spectrum disorder (ASD). The observation, published in the journal Cell Stem Cell, helps explain what might go awry in the brain during cell division and development to cause the disorder.

"Division, or replication, is one of the most dangerous things that a cell can do," says Salk Professor Rusty Gage, the study's senior author and president of the Institute. "Most DNA damage is repaired through a remarkably efficient repair process, but errors occur when the rate of division is altered genetically or environmentally, which can lead to long term functional defects."

ASD, a developmental disorder of communication and behavior, affects about 1 in 59 children in the US, according to the Centers for Disease Control and Prevention. Research into the underlying causes of the disorder, as well as possible treatments, has been slow.

In 2016, Gage and his colleagues discovered that brain stem cells from people with the macrocephalic form of autism grew more quickly than cells from unaffected individuals. (Brain stem cells are precursors to more-specialized types of cells, such as neurons.) The finding explained, in part, why many people with ASD also have macrocephaly, or unusually large heads: more proliferation of brain stem cells during development can lead to larger brains.

In the new research, Gage and his colleagues again looked at these neural precursor cells (NPCs). As all cell types proliferate and mature during embryonic development, it's normal for their quickly-replicating strands of DNA to accumulate small errors, most of which are corrected and never do any harm. The researchers wondered whether this DNA damage that occurred during the stress of replication was more common in the quickly dividing neural precursors of people with autism.

The researchers collected skin cells from individuals with both ASD and macrocephaly, as well as from neurotypical individuals (without ASD), and used stem-cell reprogramming technology to coax each person's cells into NPCs.

Gage's team used a chemical compound to induce replication stress on the NPCs derived from people without autism and studied where DNA damage was most likely to accumulate. They compared this induced damage in cells from individuals without autism to where DNA damage naturally accumulated in the cells from people with autism. The NPCs from autistic individuals had heightened levels of DNA damage, clustered in 36 of the same genes that had also been damaged in healthy cells exposed to replication stress. And 20 of the genes had been previously linked to autism in separate genetic studies.

"What the new results are telling us is that cells from people with macrocephalic autism not only proliferate more but naturally experience more replication stress," says Meiyan Wang, a graduate student in the Gage lab and first author of the new paper.

Fast proliferation of NPCs may lead to both macrocephaly and cellular stress that spurs DNA damage, she says. That damage could be one source of mutations associated with ASD. While the technology used in the study told the researchers where DNA damage occurred, they don't know how much of that damage was repaired before cells matured into adult neurons and how much of it leads to lasting mutations.

"We'd like to look deeper at how replication stress and DNA damage affects neuronal function in the long term and whether adult neurons arising from these stem cells have more mutations than usual," says Wang.

LA JOLLA--(January 30, 2020) Salk scientists have discovered how a powerful class of HIV drugs binds to a key piece of HIV machinery. By solving, for the first time, three-dimensional structures of this complex while different drugs were attached, the researchers showed what makes the therapy so potent. The work, which appeared in Science on January 30, 2020, provides insights that could help design or improve new treatments for HIV.

"The drugs we studied are the latest compounds available in the clinic today, as well as several important pre-clinical molecules. Until now, no one knew exactly how they bound to this HIV complex," says the study's senior author Dmitry Lyumkis, an assistant professor in Salk's Laboratory of Genetics. "A better understanding of how the drugs work will help us improve them and design new therapeutic compounds."

The intasome is a crucial structure of the virus that enables infection, composed of the HIV protein integrase and strands of viral DNA that form when the virus enters human cells. The intasome moves into each human cell and then carries out the chemical reactions necessary to integrate the virus' genetic material into human DNA.

Some drugs, called integrase strand transfer inhibitors (INSTIs), have managed to block the intasome; HIV can't infect human cells when the complex can't integrate viral DNA into the human genome. There are currently four INSTIs approved by the US Food and Drug Administration, as well as others under development.

Despite the success of these molecules, researchers have struggled to study how they inhibit the HIV intasome, largely due to difficulty in isolating intasomes for structural studies. In the past, most research on the intasome and INSTIs was carried out on another retrovirus called prototype foamy virus, or PFV. In 2017, Lyumkis and his colleagues were the first to determine the structure of purified HIV intasomes.

In the new work, Lyumkis' team went a step further: they obtained the structure of HIV intasomes while they were being actively blocked by one of four INSTIs--the commercially available drug bictegravir or three experimental compounds known as 4f, 4d and 4c. The team used tilted single-particle cryo-electron microscopy (cryo-EM), an imaging technique they've helped optimize, to reveal the structure of each intasome-drug complex.

The first observation that Lyumkis made was just how differently the drugs attached to the HIV intasome than what had been seen with the PFV intasome. The compound known as 4f, for instance, loops backwards onto itself as it binds to the PFV intasome but remains relatively flat as it attaches to the HIV version of the complex, details which can help researchers improve the binding properties of potential future molecules.

"To this day, everyone is still using the PFV intasome structure to rationalize and understand the mechanism of action of these drugs," says Dario Passos, the study's co-first author and a staff scientist in Lyumkis' laboratory. "But we've shown that the field really needs to move and study the HIV structure if we want to make further progress."

"We and many others have been working towards this goal for several decades and it is exciting that at long last we can now understand how HIV inhibitors work in detail and aid the development of new drugs." says Min Li, co-first author and a staff scientist at the National Institute of Diabetes and Digestive and Kidney Diseases.

The structures also revealed why the drugs are so potent and what makes them so good at avoiding drug resistance. The INSTIs, Lyumkis and his colleagues found, fill the entire space that's normally occupied by DNA. That means if the HIV intasome develops a mutation that blocks the INSTI drugs from binding, it also blocks the DNA from attaching, rendering the complex useless for invading human cells.

Finally, the extremely high resolution of the structure obtained by the Salk researchers lets them see details on how the drugs chemically interacted with this binding pocket, and how INSTIs displaced water molecules to do so, which gave the team even more information on what makes INSTIs so successful in the clinic.

"In previous structures, we learned about intasome biology," says Lyumkis. "But here, we've really started to gain insight into the therapeutic angle of how drugs can target these important viral assemblies."

The researchers are planning additional work on the experimental drugs--focusing on the compound known as 4d, which, based on both preclinical testing and the new structural insight, shows more promise against HIV than other compounds. They also want to better understand what happens to the structure of the intasome in cases where it develops resistance to INSTIs. This could help them design more efficient drugs in the future, says Lyumkis.

The climate change record could reveal future climate changes. Scientists gather information about the past environment from proxies such as deep-sea sediments and Antarctic ice cores. These samples are scarce in number because of the limited sampling locations and the high financial and temporal costs. Therefore, paleoenvironmental data have been obtained for a restricted number of places and periods. A collaborative research team from the National Institute of Polar Research (NIPR) and Ibaraki University focused on the usefulness of fossil foraminifers obtained from marine sediment uplifted on to land instead of sediment on the seafloor.

"Current global warming is considered to be anthropogenic, so we need to evaluate its effectiveness," said Dr. Yuki Haneda, NIPR scientist and the first author of a report in Earth and Planetary Science Letters published online on November 18.

"To assess anthropogenic effects, it is necessary to compare the current climate with that of the past, which has comparable parameters regarding the Earth's orbital path and axis tilt--the factors of climate change--but no anthropogenic effects. The current interglacial period, which began 10,000 years ago, is similar to the warm period "MIS19", which lasted from approximately 790,000 to 760,000 years ago. We suggested analyzing marine foraminifers to elucidate changes in the marine environment during this period''

The researchers collected four species of fossil foraminifers with different habitat depths from the Chiba composite section containing the MIS19 layer and conducted oxygen isotope analyses. Former studies have shown that low oxygen isotope values in fossil foraminifers correspond with higher water temperatures and vice versa. The analysis reveals that, in addition to the glacial-interglacial cycle that recurs on a tens of thousands of year time scale, extreme changes in water temperature--equivalent to approximately 7 ° C--are repeated every few thousand years.

A close comparison of the results of research on the North Atlantic deep-sea sediment reveals that this temperature change is likely to have occurred due to iceberg runoff and the resulting decline of deep-water circulation.

"Surprisingly, changes in the North Atlantic caused dramatic water temperature fluctuations in the remote Northwest Pacific" said Dr. Haneda. "We believe that the fossils collected from the ground outcrop are a tracer that complements the data reported from deep-sea sediments. The Chiba composite section is the Global Boundary Stratotype Section and Point (GSSP) of the Lower-Middle Pleistocene boundary, and offers considerable understanding of global environmental change during that period.

We want to improve our understanding of climate change during MIS19 to predict future climate change more precisely. "

Talk of deep-rooted division in society following the fall-out of the Brexit referendum in the UK may be overblown, according to a new study. Contrary to popular belief, 'Leavers' and 'Remainers' agree on much more than they disagree on, say researchers from the universities of Bath and Essex.

The study led by Dr Paul Hanel and Dr Lukas Wolf shows that 90% of the time the two groups agree on important topics including poverty, climate change, housing, life satisfaction and the importance of communities.

Even on subjects viewed as the most divisive, such as attitudes to immigration and national identity, the two groups showed more than 50% similarity. With responses from over 1,700 people who completed online questionnaires, their findings point to high similarities across fundamental values such as security, tradition, helpfulness, and freedom.

The team behind the study hopes that the results can help recast the long-standing debate that has played out between the two camps by offering a more nuanced and realistic picture for most people in society.

Lead researcher Dr Paul Hanel from the Department of Psychology at the University of Essex explained: "It has been claimed the EU referendum of June 2016 revealed a divided, rather than a United Kingdom, with growing tensions among those who voted 'leave' and those who voted 'remain'.

"Previous research has concentrated on the differences between the two sides, but our study shows that in fact there is more to unite them than divide them."

The research, carried out with Dr Lukas Wolf from the University of Bath, also assessed whether presenting a more balanced picture that highlights similarities instead could improve social cohesion. The team found support for the idea that accentuating such similarities can encourage Leavers and Remainers to get along better.

Co-author, Dr Lukas Wolf from the University of Bath's Department of Psychology added: "Many people seem to be worried about an increasingly fractious society and therefore it is encouraging to see that people are actually quite similar. Realising that fact seems to have a positive effect on bringing people together again."

The paper, Leavers and Remainers after the Brexit referendum: more united than divided after all? is published in The British Journal of Social Psychology.