Tech

Quantum chemistry on quantum computers

Quantum computing and quantum information processing technology have attracted attention in recently emerging fields. Among many important and fundamental issues in nowadays science, solving Schroedinger Equation (SE) of atoms and molecules is one of the ultimate goals in chemistry, physics and their related fields. SE is "First Principle" of non-relativistic quantum mechanics, whose solutions termed wave-functions can afford any information of electrons within atoms and molecules, predicting their physicochemical properties and chemical reactions. Researchers from Osaka City University (OCU) in Japan, Dr. K. Sugisaki, Profs. K. Sato and T. Takui and coworkers have found a novel quantum algorithm enabling us to perform full configuration interaction (Full-CI) calculations suitable for "chemical reactions" without exponential/combinatorial explosion. Full-CI gives the exact numerical solutions of SE, which are intractable problems with any supercomputers. Such a quantum algorithm contributes to the acceleration of implementing practical quantum computers. Nowadays chemistry and physics have sought to predict complex chemical reactions by invoking Full-CI approaches since 1929, but never been successful until now. Now Full-CI calculations are potentially capable of predicting chemical reactions, and a new Full-CI approach suitable for the prediction is implemented on quantum computers, for the first time.

The paper will be published at 8:00 AM on Jan. 2, 2019 (US Eastern Time Zone) in ACS (American Chemical Society) Central Science.

They said, "As Dirac claimed in 1929 when quantum mechanics was established, the exact application of mathematical theories to solve SE leads to equations too complicated to be soluble [1]. In fact, the number of variables to be determined in the Full-CI method grows exponentially against the system size, and it easily runs into astronomical figures such as exponential explosion. For example, the dimension of the Full-CI calculation for benzene molecule C6H6, in which only 42 electrons are involved, amounts to 1044, which are impossible to be dealt with by any supercomputers. What is worse, molecular systems during the dissociation process are characterized by extremely complex electronic structures (multiconfigurational nature), and relevant numerical calculations are impossible on any supercomputers."

According to the OCU research group, quantum computers can date back to a Feynman's suggestion in 1982 that the quantum mechanics can be simulated by a computer itself built of quantum mechanical elements which obey quantum mechanical laws. After more than 20 years later, Prof. Aspuru-Guzik, Harvard Univ. (Toronto Univ. since 2018) and coworkers proposed a quantum algorithm capable of calculating the energies of atoms and molecules not exponentially but polynomially against the number of the variables of the systems, making a breakthrough in the field of quantum chemistry on quantum computers [2].

When Aspuru's quantum algorithm is applied to the Full-CI calculations on quantum computers, good approximate wave functions close to the exact wave functions of SE under study are required, otherwise bad wave functions need an extreme number of steps of repeated calculations to reach the exact ones, hampering the advantages of quantum computing. This problem becomes extremely serious for the analyses of chemical reactions, which have many multiconfigurational nature due to electrons not participating in chemical bonding during the bond dissociation. The OCU researchers have tackled this problem, one of the most intractable issues in quantum science and chemistry, and made a breakthrough in implementing a new quantum algorithm generating particular wave functions termed configuration state functions (CSFs) in polynomial computing time in 2016 [3] and 2018 [4].

The previously proposed algorithms for quantum computing, however, are still demanding to efficiently solve SE for whole chemical reaction pathways, which inevitably involve the dissociation and formation of many chemical bonds and, as a result, generate so many electrons not participating in chemical bonds, making the quantum algorithms difficult to apply, termed "Quantum Dilemma". The OCU researchers have introduced a "diradical character, yi(0 ~ 1)" to measure and characterize the nature of open shell electronic structures, and exploited the diradical characters to construct multiconfigurational wave functions required for chemical reactions, executing the Full-CI calculations along the whole reaction pathways on quantum computers. This new procedure requires no time-consuming sophisticated post-Hartree-Fock calculations, avoiding the exponential explosion of the calculation and solving "Quantum Dilemma", for the first time. The OCU group said, "This is the first example of a practical quantum algorithm, which makes quantum chemical calculations for predicting chemical reaction pathways realizable on quantum computers equipped with a sizable number of qubits. The implementation empowers practical applications of quantum chemical calculations on quantum computers in many important fields of chemistry and materials science."

Credit: 
Osaka City University

The role of PCSK9 in the pathogenesis of non-alcoholic fatty liver disease

Statin treatment exhibits a beneficial effect in patients of cardiovascular diseases (CVD) and non-alcoholic fatty liver disease (NAFLD). Statins are common treatments for such conditions.

The role of pro-protein convertase subtilisin kexin type-9 (PCSK9) in the pathogenesis of NAFLD is summarized in this review. The authors also review the effects of the new hypolipidaemic drugs - PCSK9 inhibitors - on NAFLD. Increments in high intrahepatic or circulating PCSK9 levels in muscle and liver lipid storage was indicated by research data. The increment was also observed in adipose energy storage and hepatic fatty acids, as well as triglycerides storage and secretion, thus contributing to the pathogenesis of NAFLD.

These findings were the basis of a number of animal and human studies, aimed at reducing PCSK9 with inhibitors (human IGG antibodies, antisense particles against PCSK9 mRNA, and small anti PCSK9 antibodies). The results of these experiments point towards liver protection from NAFLD through inhibition of PCSK9 expression in the induction of degradation of hepatic HNF1a protein, insulin resistance (IR), and other mechanisms. The use of PCSK9 inhibitors ameliorates NAFLD, aside from beneficial effects on CVD and independently of low density lipoprotein cholesterol level reduction.

This article is Open Access. To obtain the article please visit http://www.eurekaselect.com/166125

Credit: 
Bentham Science Publishers

Smelling in tiny houses: how ciliary electric currents keep olfaction reliable

image: Reisert, a cell physiologist at the Monell Center, likes to tackle big questions in olfactory physiology.

Image: 
Paola Nogueras/Monell Center

PHILADELPHIA (December 31, 2018) - Imagine trying to figure out how something works when that something takes place in a space smaller than a femtoliter: one quadrillionith of a liter. Now, two scientists with a nose for solving mysteries have used a combination of mathematical modeling, electrophysiology, and computer simulations to explain how cells communicate effectively in highly constricted spaces such as the olfactory cilia, where odor detection takes place. The findings will inform future studies of cellular signaling and communication in the olfactory system and also in other confined spaces of the nervous system.

Study author Johannes Reisert, PhD, a Monell Center cell physiologist, comments, "Ion channels and how their currents change ion concentrations inside cells are notoriously difficult to study. Our modeling-based approach enables us to better understand not only how olfaction works, but also the function of small nerve endings such as dendrites, where pathology is associated with many neurodegenerative diseases."

In the study, published online in advance of print in the Proceedings of the National Academy of Sciences, the scientists asked why olfactory receptor cells communicate with the brain using a fundamentally different series of electrical events than used by sensory cells in the visual or auditory systems.

Olfaction begins when, in a process similar to a key fitting into a lock, an airborne chemical molecule travels through the nasal mucus to bind with an olfactory receptor embedded on the wall of a nerve cell within the nose. The olfactory receptors are located on cilia, elongated super-thin threadlike structures less than 0.000004 inches in diameter, which extend from the nerve cell into the mucus.

The act of odorant-receptor binding initiates a complex molecular cascade inside the olfactory cell, known as transduction, which results in the nerve sending an electrical signal to inform the brain that an odor has been detected.

The transduction process culminates with the opening of pores called ion channels, located in the nerve cell's wall. The open pores enable positive or negative electrically charged molecules (ions) to flow in and out of the cell. This ultimately changes the cell's overall electrical charge to a less negative state, which is what initiates the cell's signal to the brain.

Most ion channels are selective for a specific ion, including positively charged sodium (Na+) ions or negatively charged chloride (Cl-). The flow of an ion through its channel in either direction generates an electric current.

Receptor cells in both the visual and auditory systems depend on inward-flowing positive ion currents to elicit an electrical signal. In contrast, the olfactory system also relies on outward-flowing negative ion currents.

By using multiple approaches to develop a testable model of olfactory transduction and ion currents, Reisert and his collaborator, computational neuroscientist Jürgen Reingruber, PhD, from the Ecole Normale Supérieure in Paris, were able to explain why the olfactory system functions differently.

The researchers demonstrated that relying on Cl- rather than Na+ as part of the transduction cascade provides several advantages that enable olfactory cells to respond to odors more consistently.

One constraint faced by the olfactory system is that the concentrations of Na+ and other positive ions in the mucus outside the olfactory cells vary dramatically as a function of the nose's external environment. This makes it difficult for olfactory cells to depend on externally-originating Na+ currents as a reliable component of the transduction response.

The olfactory cells counteract this problem by using a Cl- current that originates inside the cell, where ion concentrations are more stable, making the Cl- current more dependable overall.

"Imagine that you've been swimming in the ocean and your nose is bathed in salt water. That means that there's much more sodium outside the olfactory cells, but they need to be able to function reliably whether you've just been swimming in the ocean or are sitting in your kitchen," said Reisert. "Replacing the externally-originating Na+ current with Cl- ions that move from inside the cell to outside solves that problem."

The models also showed that using the outward flowing Cl- ion currents enables the olfactory cells to protect the infinitesimal intracellular space of the cilia, which is where olfactory transduction occurs. This is because inward-flowing positive ions would encourage extra water to enter the space, potentially resulting in osmotic swelling and related structural damage to the cilia.

The findings explain how the olfactory system is able to function dependably despite the challenging physical conditions of an unstable external environment and the small ciliary volume. An example of the powerful value of basic science, this modeling approach can now be used to investigate similar questions in other parts of the nervous system.

Credit: 
Monell Chemical Senses Center

Canagliflozin not associated with increased risk for fracture

1. Canagliflozin not associated with increased risk for fracture
Abstract: http://annals.org/aim/article/doi/10.7326/M18-0567
Editorial: http://annals.org/aim/article/doi/10.7326/M18-3550
URLs go live when the embargo lifts

Compared with a glucagon-line peptide-1 (GLP-1) agonist, canagliflozin was not associated with an increased risk for fracture in patients with type 2 diabetes at relatively low risk for fracture. Findings from a multidatabase cohort study are published in Annals of Internal Medicine.

Sodium-glucose cotransporter-2 (SGLT2) inhibitors promote glycosuria, resulting in possible effects on calcium, phosphate, and vitamin D homeostasis. Some studies suggest that canagliflozin, an SGLT2 inhibitor, is associated with decreased bone mineral density and a potential increased risk for fracture, which is important because people with type 2 diabetes are already at higher risk. These conflicting study results raise challenges in counseling patients prescribed canagliflozin about the risk for fracture.

Researchers from Brigham and Women's Hospital reviewed two U.S. commercial health care databases providing data on more than 70 million patients from March 2013 to October 2015 to estimate risk for nonvertebral fracture among new users of canagliflozin. Dr Mike Fralick, the study's lead author, indicated that the overall rate of fracture was similarly low among patients with type 2 diabetes who were treated with canagliflozin or a GLP-1 agonist. Findings were robust across multiple sensitivity and subgroup analyses and the study population is representative of a meaningful proportion of commercially insured patients with diabetes in the U.S. population.

According to the researchers, these results should be reassuring to patients and physicians who are considering the potential risks and benefits of canagliflozin. An accompanying editorial from the University of Manitoba supports this conclusion and stresses the importance of these real-world findings. However, the editorialists write that caution may still be appropriate when using canagliflozin in older patients who have high fracture risk, with particular attention given to hydration status and fall risk.

Media contact: For an embargoed PDF, please contact Lauren Evans at laevans@acponline.org. To interview the lead author, Michael Fralick, MD, SM, please contact Mark Murphy at mmurphy90@bwh.harvard.edu.

2. Alirocumab not cost-effective for lowering LDL cholesterol
Substantial price reductions occurred following the presentation of these cost-effectiveness results in March 2018, suggesting the importance of just-in-time analyses to inform payers, providers, patients, and policy makers about cost-effective prices of new therapeutics
Abstract: http://annals.org/aim/article/doi/10.7326/M18-1776
Editorial: http://annals.org/aim/article/doi/10.7326/M18-3632
URLs go live when the embargo lifts

Despite substantial cardiovascular benefits, the price of alirocumab would need to be reduced by 86 percent to be considered cost-effective for treating LDL cholesterol. Results from a just-in-time analysis initially presented in March 2018 to coincide with the release of the ODYSSEY Outcomes Trial results and are now published in Annals of Internal Medicine.

The ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial included participants with a recent acute coronary syndrome. Compared with participants receiving statins alone, those receiving a statin plus alirocumab had lower rates of myocardial infarction, stroke and death. While the medication is considered very expensive at a cost of $14,000 per year (about 100 times the cost of a generic statin), many hoped it would be cost-effective given the potential for savings on costs associated with coronary heart disease and stroke, such as hospitalizations, revascularization procedures, and other medical costs.

Researchers from the University of California, San Francisco used a computer model specifically designed to determine cost-effectiveness to assess alirocumab in these circumstances. They specifically compared the cost-effectiveness ratio of alirocumab or ezetimibe added to statin therapy. Their model showed that compared with a statin alone, the addition of ezetimibe cost $81,000 per quality-adjusted life year (QALY), while the addition of alirocumab cost $308,000 per QALY. Based on its current price, the cost of alirocumab would have to be reduced from $14,560 annually to $874, which would be unprecedented for biologic therapies in the U.S. market.

The results of this cost effectiveness analysis were announced in March 2018 and timed to coincide with the release of the ODYSSEY results. Immediately following this release, the maker of alirocumab announced a plan to effectively lower the price and several subsequent announcements have also resulted in substantial lowering of the price of this class of medications.

The authors suggest that early just-in-time cost effectiveness analyses are critical for payers, providers, patients, and policy-makers to have the tools to negotiate for cost-effective prices for new therapeutics.

Media contact: For an embargoed PDF, please contact Lauren Evans at laevans@acponline.org. To interview the lead author, Kirsten Bibbins-Domingo, PhD, MD, MAS, please contact her directly at Kirsten.bibbins-domingo@ucsf.edu.

3. Assessing CHA2DS2-VASc scores annually in patients with AF could improve risk predictions, inform anticoagulant prescribing
Abstract: http://annals.org/aim/article/doi/10.7326/M18-1177
URLs go live when the embargo lifts

Assessing CHA2DS2-VASc scores annually in patients with atrial fibrillation could improve stroke risk predictions and inform oral anticoagulant prescribing. Findings from a brief research report are published in Annals of Internal Medicine.

International guidelines suggest that oral anticoagulants can be omitted for patients with atrial fibrillation (AF) without a CHA2DS2-VASc score greater than 0 in men or 1 in women. While it is recommended that risk is periodically re-assessed, a reasonable interval for re-evaluation has not been studied. This is important because stroke risk is not static among patients with atrial fibrillation, and about 90 percent develop at least one new risk factor before presentation with ischemic stroke, which means they would no longer be accurately described as "low-risk."

Researchers from Taipei Veterans General Hospital and National Yang-Ming University used a national database to identify 14,606 patients with newly diagnosed atrial fibrillation who were not prescribed an anticoagulant based on their CHA2DS2-VASc score. The researchers found that about 16.1 percent of men and 16.2 percent of women who were initially at low risk had a high-risk CHA2DS2-VASc score 1 year after incident atrial fibrillation. This finding suggests that CHA2DS2-VASc scores should be reassessed at least annually in patients with atrial fibrillation so that oral anticoagulants can be prescribed in a timely manner for stroke prevention.

Media Contact: For an embargoed PDF or author contact information, please contact Lauren Evans at laevans@acponline.org. To reach the lead author, Shih-Ann Chen, MD, please contact him directly at epsachen@gmail.com.

Credit: 
American College of Physicians

Thriving on teamwork: new research shows how brain cells filter information in groups

image: New work by Salk scientists (from left) Tom Albright, Ambarish Pawar and Sergei Gepshtein shows how brain cells filter information in groups.

Image: 
Salk Institute

LA JOLLA--(December 31, 2018) When we perceive the world around us, certain objects appear to be more noticeable than others, depending on what we do. For example, when we view a forest-covered mountain from a distance, the forest looks like a large green carpet. But as we get closer, we start noticing the individual trees, and the forest fades to the background. What happens in the brain as our experience changes so drastically?

For decades, scientists studying the visual system thought that individual brain cells, called neurons, operate as filters. Some neurons would prefer coarse details of the visual scene and ignore fine details, while others would do the opposite. Every neuron was thought to do its own filtering.

A new study led by Salk Institute researchers challenges this view. The study revealed that the same neurons that prefer coarse details could change to prefer finer details under different conditions. The work, which appeared in the journal Neuron on December 31, 2018, could help to better understand neural mechanisms that shape our perceptions of the world.

"We were trying to look beneath the hood and figure out how these filters work," says Professor Thomas Albright, director of Salk's Center for Neurobiology of Vision and a senior author of the study.

"The selectivity of neurons was thought to be stable, but our work has shown that the filtering properties of neurons are much more flexible than was previously thought," adds study first author Ambarish Pawar, a postdoctoral researcher at Salk.

The team focused on neurons in the visual cortex in an animal model. Animals were shown optical patterns in which the researchers varied the contrast between dark and light areas and measured neurons' preferences to coarse and fine details. The goal was to see how neurons process these patterns, specifically in the brain's middle temporal area within the visual cortex. Scientists expected to find that the neurons were strictly "tuned" to perceive either coarse or fine details, but not both. What they found instead that an individual neuron could filter both fine as well as coarse detail, depending on the contrast of the pattern.

By measuring the firing rates of multiple neurons activated by the optical stimuli, the researchers showed that such flexibility was more likely if entire networks of neurons acted as filters rather than individual neurons.

"Our results suggest that the previously common description of individual neurons as filters was incorrect," says Sergei Gepshtein, a scientist with the Center for Neurobiology of Vision at Salk and co-author of the new study.

"The preference of neurons may shift due to a change in the balance of positive (excitatory) signals and negative (inhibitory) signals by which neurons communicate in the network," adds Pawar.

The researchers showed that teaming up endows networks of neurons with a high amount of flexibility in their preferences could easily adapt and tune the brain to the changing conditions, just as you might tune a radio to get good reception as you drive.

"We've uncovered a new dimension of adaptability of cortical networks," says Gepshtein. "Our results made it clear that to understand that adaptability we have to rethink what the computing units of the brain are. It is the team of connected neurons--the malleable neural network--that is more suited as such a unit rather than an individual neuron."

"This unexpected finding could help us shed light on the neural mechanisms that underlie the brains' enormous adaptability to a continuously changing environment," says Pawar.

Albright adds that, "even though the study centered on the visual system, this same flexible quality of neural networks is likely to hold true for other parts of the brain."

Now that they've seen the adaptable neuronal networks in action, the researchers next plan to study how changes in these networks affect behavior.

Credit: 
Salk Institute

Patient preferences for collecting sexual, gender identity information

Bottom Line: Emergency department patients who are sexual or gender minorities reported greater satisfaction when information on sexual and gender identity was collected on forms during registration instead of by nurses who asked about it during the visit. Understanding patient preferences for collecting this information is important because health care disparities exist for sexual and gender minority patients (including lesbian, gay, bisexual or transgender identities) but the extent of those disparities is not known because of a lack of routine collection of information about sexual and gender identity from patients. This observational study analyzed survey data from 540 emergency department. It is unclear if these findings can be generalized to medical settings outside the emergency department.

Authors: Adil Haider, M.D., M.P.H., Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts, and coauthors

To Learn More: The full study is available on the For The Media website.

(doi:10.1001/jamanetworkopen.2018.6506)

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

Credit: 
JAMA Network

Speed up public health decisions on scabies by skipping full-body exams, study says

image: Scabies lesions on hand.

Image: 
Lucia Romani, 2018, CC BY 4.0

For years, the diagnosis of scabies has relied on time-consuming and intrusive full-body examinations. Now, researchers reporting in PLOS Neglected Tropical Diseases have found that an exam of just a patient's hands, feet and lower legs may have the potential to catch more than 90 percent of all scabies cases, regardless of severity. These speedier exams may be useful in public health assessments on the prevalence of scabies.

Scabies, a skin condition caused by the microscopic mite Sarcoptes scabiei, is a major public health problem in low- and middle-income tropical settings. There is no laboratory test for infestation and diagnosis is almost always made with clinical examination. Scabies control relies traditionally on diagnosing individual patients, however there is increasing use of mass drug administration programs. For mass drug administration to be a viables approach surveys of communities to gauge scabies prevalence will be needed.

In the new work, Michael Marks of the London School of Hygiene & Tropical Medicine and colleagues analyzed data from three recent large population-based surveys of scabies in the Solomon Islands and Fiji. In all three surveys, examinations of covered the arms, legs, face and torso. If patients reported itching in the groin, buttocks or breasts, these areas were also examined. Exams in children under 1 year covered the whole body. Reports of scabies in examined patients included which of nine body regions lesions were found in.

Based on the information where lesions were found, the team concluded that exams of exposed body regions--the hands, feet and lower legs-- had close to 90 percent sensitivity for detecting scabies compared to a whole-body exam. Further restricting exams limited sensitivity, however, with a sensitivity of only 51.2 percent for exams of the hands alone.

"Our study adds valuable data to the development of a simplified diagnostic process for scabies that may be applied to guide decisions about future public health interventions," the authors say.

Credit: 
PLOS

Contact with monkeys and apes puts populations at risk

image: In southeastern Cameroon, human contact with monkeys are frequent, especially with abundant species like this greater spot-nosed monkey (Cercopithecus nictitans).

Image: 
S. Rupp, 2018 (CC BY 4.0)

Animal diseases that infect humans are a major threat to human health, and diseases often spillover to humans from nonhuman primates. Now, researchers reporting in PLOS Neglected Tropical Diseases have carried out an extensive social sciences evaluation of how populations in Cameroon interact with nonhuman primates, pointing toward behaviors that could put people at risk of infection with new diseases.

Zoonotic diseases-- those which originate in other animal species before spilling over to humans--now constitute more than 60 percent of emerging infectious diseases. Of these zoonotic diseases, 70 percent reportedly come from wild animals. Because of the similarity between humans and nonhuman primates, these monkeys and apes serve as frequent reservoirs or amplifiers for pathogens that pose a risk to human populations.

In the new work, Tamara Giles-Vernick of the Institut Pasteur, France, and Victor Narat of the French Center for National Scientific Research, with their colleagues carried out surveys, real-time data collection, oral history interviews, and wild meat surveys to paint a full picture of the physical exposure of people in southeastern Cameroon to nonhuman primate species. Data were collected in 2016 and 2017 and included information from multiple villages and hundreds of people.

The researchers found that Cameroonian adults have frequent physical contact with primates, and more with monkeys than apes. This contact is most often through hunting, butchering, preparing and consuming meat, but also includes injuries sustained from gorillas. Some 85% of questionnaire respondents had eaten primate meat in their lifetimes. In general, the exposure risk in any given village was directly related to the relative density of nonhuman primates and their proximity to human settlements.

"National and international authorities should support improved surveillance of humans and abundant monkey species, as well as popular messages to promote safe meat handling practices," the researchers say. "Multidisciplinary social science and ecological approaches should be used to improve surveillance and communications with forest populations about neglected tropical diseases."

Credit: 
PLOS

Yale experts treat severe, disfiguring sarcoidosis with novel therapy

New Haven, Conn. -- An all-Yale team of researchers successfully treated a patient with disfiguring sarcoidosis, a chronic disease that can affect multiple organs, with a drug approved for rheumatoid arthritis. Successful treatment of two other patients with similarly severe disease suggests an effective treatment for an incurable, sometimes life-threatening illness is within reach, the scientists said.

The research was published in the New England Journal of Medicine.

Sarcoidosis is an inflammatory disease that affects multiple organs in the body. While some sarcoidosis patients recover without treatment, others suffer damage to the lungs, heart, lymph nodes, skin, and other organs. Current treatments, including steroids, are not reliably effective for the skin and can cause serious side effects.

Based on clues gleaned from prior studies, the Yale team decided to try the arthritis medication tofacitinib. The drug, a Jak inhibitor, blocks a pathway known as Jak-STAT. The lead author, Brett King, M.D., has pioneered the use of Jak inhibitors to treat other intractable skin diseases, including vitiligo, alopecia areata, and eczema.

For several months, a 48-year-old female patient was treated with the drug, a twice-daily pill. The researchers observed that her skin lesions nearly disappeared. They also performed RNA sequencing on biopsied skin from the patient before and during treatment. "Before treatment, we were able to show that the Jak-STAT pathway is activated," King said. "During treatment, not only does her skin disease go away, but there is no activation of the pathway."

"We plan to evaluate the activation of the Jak-STAT pathway in the lung fluid and blood of over 200 patients with pulmonary and multiorgan sarcoidosis," said co-author Nkiruka Emeagwali. These are big steps toward understanding a disease that has been a mystery for years, the researchers said.

The findings are being tested further by the Yale team in a clinical trial. If confirmed, they could represent a breakthrough for sarcoidosis patients, King noted.

"A frequently awful disease, which to date has no reliably effective therapy, may now be targeted with Jak inhibitors," he said. "We have a relatively safe medicine that works."

Other Yale authors are William Damsky, Durga Thakral, and Anjela Galan.

Credit: 
Yale University

Fish bones yield new tool for tracking coal ash contamination

image: Duke University scientists are using trace element isotopes from fish ear bones to identify and track coal ash contamination in lakes that serve as cooling ponds for coal-fired power plants, such as Sutton Lake in eastern North Carolina.

Image: 
Jessica Brandt, Duke Univ.

DURHAM, N.C. -- A Duke University study shows that trace elements in a fish's ear bones can be used to identify and track coal ash contamination in the waters where it lived.

"Calcified structures -- or otoliths -- found in a fish's inner ear are known to store a lot of life history information, including chemical and physical records of the fish's age, natal habitat and migration patterns," said Jessica Brandt, lead author of the paper and a 2018 PhD graduate of Duke's Nicholas School of the Environment. "We've shown that otoliths also capture the signatures of contaminants that have affected the fish's ecosystems."

Brant and her team found that strontium isotope ratios in the otoliths of fish from two North Carolina lakes -- both of which had received effluents from coal ash ponds at nearby power plants -- matched the strontium isotope ratios in samples collected from sediment at the bottom of the lakes.

"This shows otoliths can be used as biogenic tracers to assess the potential for ecological impacts of coal ash waste streams in affected waters," said Brandt, who is now a postdoctoral researcher with the U.S. Geological Survey. "While strontium behaves differently than the toxic elements in coal ash effluents, it helps us connect high levels of those elements back to the contamination source."

Strontium is a naturally occurring trace element in coal that retains unique isotopic ratios even after the coal is burned and coal ash comes into contact with an aquatic environment.

Past studies have used strontium isotope ratios to track coal ash's impacts on water quality, "but this is the first time we've been able to prove they can also be used as fingerprints to track coal ash's impacts in living organisms," said Avner Vengosh, professor of geochemistry and water quality at Duke's Nicholas School, who coauthored the study.

"This definitely shows the strontium in the fish must be from coal ash contamination," Vengosh said.

The Duke team published its peer-reviewed findings Nov. 21 in the journal Environmental Science & Technology Letters.

The researchers collected surface water and sediment-based pore water samples from two North Carolina lakes -- Mayo Lake and Sutton Lake -- that were historically impounded to provide cooling water for nearby power plants and to receive their effluents. Sutton Lake was the site of a large coal ash leak into the adjacent Cape Fear River after Hurricane Florence caused flooding this fall.

The researchers also collected surface and pore water samples from two sites located upstream from the lakes, and from two other lakes -- Lake Tillery and Lake Waccamaw -- that are not associated with coal ash waste streams. The samples were then analyzed in the laboratory, along with the otoliths of largemouth bass from each of the lakes.

"Strontium isotope ratios in the largemouth bass otoliths overlapped with ratios in corresponding sediment pore waters at all lakes and reservoirs, which is compelling evidence that otoliths can serve as biogenic tracers of coal ash effluents," said Richard Di Giulio, the Sally Kleberg Professor of Environmental Toxicology at Duke, who co-authored the study.

Strontium isotope ratios in surface water samples from the lakes didn't always match those in the fish otoliths and pore water samples, Di Giulio explained, but this could be because surface water ratios are more variable over time.

"This study's finding demonstrate that otolith studies can add to our existing research efforts," said Brandt. "Water-based strontium isotope tracers only give us information about coal ash impacts at a particular point in time, but because otoliths continuously grow over a fish's lifetime, we could use time-series analyses of otoliths to determine the timing of waste stream discharges or spills going back several years. This represents an emerging and important new direction in environmental toxicology and water-quality research."

Credit: 
Duke University

Trees' enemies help tropical forests maintain their biodiversity

image: Tropical forest diversity.

Image: 
Oregon State University

CORVALLIS, Ore. - Scientists have long struggled to explain how tropical forests can maintain their staggering diversity of trees without having a handful of species take over - or having many other species die out.

The answer, researchers say, lies in the soil found near individual trees, where natural "enemies" of tree species reside. These enemies, including fungi and arthropods, attack and kill many of the seeds and seedlings near the host tree, preventing local recruitment of trees of that same species.

Also playing a key role in the tropical forest dynamic are seed dispersers. Seeds from individual trees that are carried a distance away - often by rodents, mammals or birds - have a chance to get established because the fungi and arthropods in the new region target different species. This restriction of tree recruitment near the adult trees creates a long-term stabilizing effect that favors rare species and hinders common ones, the researchers say.

Overturning previous theory, the researchers demonstrate that these interactions with enemies are important enough to maintain the incredible diversity of tropical forests. Results of the study are being published this week in Proceedings of the National Academy of Sciences (PNAS).

"In many North American forests, trees compete for space and some have a niche that allows them to outcompete others," said Taal Levi, an Oregon State University ecologist and lead author on the study. "Douglas-firs are the species that grow best after a fire. Hemlock thrives in the shade and grows well under a canopy. Some species do well at elevation.

"But in the tropics, all of the tree species appear to have a similar competitive advantage. There is an abundance of species, but few individuals of each species. The chances of blinking out should be high. But there has to be a mechanism that keeps one species from becoming common, becoming dominant. And it is these natural enemies that have a high host-specificity."

Egbert Leigh, of the Smithsonian Tropical Research Institute, best described the diversity of tropical forests in one statement: "How can a half square-kilometer (of forest) in Borneo or Amazonia contain as many tree species as 4.2 million kilometers of temperate zone forest in Europe, North American and Asia combined?"

Levi said some tropical forests have as many as 1,000 different tree species living in the same general area. The idea of natural enemies restricting the recruitment of juvenile trees is not new, he said, and in fact was posited nearly a half-century ago by two scientists in what has become known as the Janzen-Connell hypothesis.

Although Janzen-Connell effects should prevent one species from taking over, they don't explain or predict how a thousand tree species can be maintained together. In fact, previous researchers suggested that the Janzen-Connell effects could only maintain a very few species, and thus were relatively unimportant to the overall maintenance of tropical forest diversity.

Instead, Levi and his colleagues from the University of Florida, Oregon State, and James Cook University in Australia says this close relationship between trees and their natural enemies is the key to tropical forest diversity. They found that if fungi, arthropods and other natural enemies produce even small zones around trees where a new tree of the same species cannot establish, then the very high levels of tree diversity observed in tropical forests can be maintained almost indefinitely.

"There is a 'seed shadow' around adult trees and some escape the curve and get out, allowing recruitment in other areas until the host-specific enemies get established in the new location," Levi said. "That's why it is critically important to maintain the biodiversity of birds and mammals in these forests, or recruitment eventually will decline - especially in over-hunted areas."

Levi is in Oregon State's Department of Fisheries and Wildlife, in the College of Agricultural Sciences.

Credit: 
Oregon State University

Pitt-led research describes how neurons could disconnect from each other in Huntington's disease

PITTSBURGH, Dec. 24, 2018 - A hallmark of neurodegenerative diseases like Huntington's is the progressive death of nerve cells in the brain. The cells don't die quickly, though. They first start to disconnect from each other because their neurites -- long finger-like extensions that make connections all through the brain -- become smaller.

Now, using animal models and nerve cells grown in the lab, researchers from the University of Pittsburgh School of Medicine suggest a new mechanism dubbed "neuritosis" that might explain neurons shrinking in Huntington's and other neurodegenerative diseases, opening new targets for therapy. The study is published this week in the journal Proceedings of the National Academy of Sciences.

"Neuritosis is a process that hasn't been recognized or described until now and could play a very important role in normal brain development, aging and neurodegenerative disease," said senior author Robert Friedlander, M.D., chair and Walter E. Dandy Professor of Neurosurgery and Neurobiology at Pitt's School of Medicine.

It all started when Sergei Baranov, Ph.D., a staff scientist in Friedlander's lab, noticed an interesting phenomenon in mouse nerve cells that he was growing in the lab.

"Their mitochondria, the cellular powerhouses, weren't working as well at the neurite ends" said Baranov. Then, when the researchers looked at neurons in the spinal cords of mice, they found the same phenomenon. "Other researchers must have noticed this as well, but we were able to visualize it and suggest the potential cause as well as outcome," he noted.

The researchers found that when proteins in mitochondria at the ends of neurites were damaged by normal wear and tear, newer ones weren't coming in to replace them as quickly as they did for mitochondria near the nucleus. This made them function less efficiently, which activated 'executioner' enzymes called caspases and ultimately led to neurites withering away.

Friedlander and his team called this neuritosis, a variation on apoptosis, the cell death process that involves caspase activation. "It's quite intuitive, once we discovered how it works," said Friedlander. "Neuronal projections are really long and the farther you are from the nucleus, which is the central factory, the harder it gets to repair and replenish the cellular machinery, making the ends more vulnerable to even small stresses."

The researchers then wanted to understand whether neuritosis plays a role in neurodegenerative disease, and they had reason to suspect that it does. Previous work in Friedlander's lab showed that mutations in huntingtin, the protein linked to Huntington's, interferes with the same protein supply chain that breaks down in neuritosis.

To test their hunch, Friedlander's team used genetically modified mice that carried a mutant version of the human huntingtin protein. These mice exhibit symptoms of the disease, including accelerated neuronal death. Their findings were similar to what they had seen in the cells, but more pronounced. There were fewer mitochondria at the ends, and what remained was more dysfunctional than in normal neurons. There was also more activation of caspases, and increased levels of cell death.

"It's quite likely that neuritosis happens in nerve cells normally and doesn't result in cell death, but in neurodegenerative diseases, there are higher levels of stress to the already vulnerable neurite ends, which could push neuritosis over the edge and lead to cells dying," said Friedlander. "If we can somehow find a way to keep mitochondria at nerve ends healthy, it may be beneficial in treating neurodegenerative diseases."

Credit: 
University of Pittsburgh Schools of the Health Sciences

New insights into pion condensation and the formation of neutron stars

In 1973, Russian physicist A.B. Migdal predicted the phenomenon of pion condensation above a critical, extremely high--several times higher than that for normal matter-- nuclear density. Although this condensation has never been observed, it is expected to play a key role in the rapid cooling process of the core of neutron stars. These city-size heavy stellar objects are so dense that on Earth, one teaspoonful would weigh a billion tons.
Recently, researchers from the RIKEN Nishina Center for Accelerator-Based Science and Kyushu University, performing an experiment at the RIKEN RI Beam Factory on a very neutron-rich tin isotope, investigated whether this process could really occur in neutron stars having the mass of about 1.4 times that of our Sun. Similar investigations were conducted previously on stable isotopes, such as 90Zr or 208Pb, but this time the researchers decided to study the case of 132Sn, an isotope of tin. This doubly magic unstable nucleus has a fairly simple structure that makes the theoretical calculations easily compared to other isotopes with similar mass. Furthermore, 132Sn with its large neutron excess (it consists of 50 protons and 82 neutrons) provides better conditions than the stable isotopes for extending this study towards the pure neutron matter in the neutron stars.
A secondary cocktail beam containing 132Sn was produced by projectile fragmentation of a uranium primary beam colliding with thick a beryllium target. Then, a liquid hydrogen target was irradiated with 132Sn. Resulting in the collective excitation of the neutrons and protons of the tin nuclei, with the neutron spin and proton spin oscillating out of phase. This excitation mode, called "giant resonance", is suitable for studying the short-range interactions that, while being crucial in the onset of pion condensation, are complex and extremely difficult to measure.
According to Masaki Sasano from RIKEN Nishina Center, who is one of the first authors of this study, their result, which was published in the Physical Review Letters journal, shows that the pion condensation should occur at around two times normal nuclear density, which can be realized in a neutron star with a mass of 1.4 times that of the Sun. Sasano said that in order to understand the possibility of the pion condensation fully, they plan to extend these unique studies of giant resonances to other neutron-rich nuclei that are far beyond the stability line, having large neutron-proton asymmetry.
The work was done by an international collaboration led by RIKEN, Kyushu University, and the University of Michigan.

Credit: 
RIKEN

NASA's GPM satellite examines weakening Tropical Cyclone Kenanga

image: GPM observed powerful storms south of Kenanga's center on Dec. 20, still producing very heavy rainfall at the rate of 214 mm (8.4 inches) per hour in that area. The rainfall in the northern half of the storm had decreased significantly. The storm tops of the eyewall which had remained intact on the western side of the cyclone were reaching heights of 12.7 km (7.9 miles).

Image: 
NASA/JAXA, Hal Pierce

Tropical Cyclone Kenanga is now on a weakening trend and NASA's GPM core satellite provided a look at the rainfall and cloud heights within the storm.

On December 20, 2018, NASA's Global Precipitation Measurement mission or GPM core observatory satellite passed over the Tropical Cyclone Kenanga and captured the storm beginning to weaken as predicted. The GPM satellite had an excellent view of the Kenanga when the tropical cyclone's maximum sustained winds were at 90 knots (103.5 mph). GPM's pass showed the eye of the storm, visible the day before, had since filled in.

GPM's instruments including the Microwave Imager (GMI) and the Dual-Frequency Precipitation Radar (DPR) revealed that the powerful storms south of Kenanga's center are still producing very heavy rainfall at the rate of 214 mm (8.4 inches) per hour in that area. The rainfall in the northern half of the storm had decreased significantly. This GPM 3-D view of Kenanga is looking southwest and was derived by the DPR Ku Band of the radar on the satellite. It showed extremely powerful storms south of Kenanga's deteriorating eye were returning very strong reflectivity values which help to map the severity of the storm and the rainfall totals. The storm tops of the eyewall which had remained intact on the western side of the cyclone were reaching heights of 12.7 km (7.9 miles).

GPM is a joint mission between NASA and the Japan Aerospace Exploration Agency, JAXA.

On Dec. 21 at 10 a.m. EST (1500 UTC) Tropical Cyclone Kenanga was located approximately 672 nautical miles southeast of Diego Garcia and has tracked westward. Maximum sustained winds dropped to 60 knots (69 mpg/111 kph), so it is now a tropical storm.

The Joint Typhoon Warning Center predicts that Kenanga will continue to weaken rapidly as the dry air within the storm gets colder and heavier causing downdrafts. It is the dry air higher aloft that contributes to stronger convective wind gusts and therefore stronger storms. Kenanga is forecast to dissipate in the next 72 hours as it tracks within the northeast periphery of Tropical Cyclone Cilida.

Credit: 
NASA/Goddard Space Flight Center

Camera trap study reveals the hidden lives of island carnivores

image: A gray wolf in 2015 on Stockton Island, Wisconsin.

Image: 
Photo courtesy Max Allen/Erik Olson/Tim Van Deelen

CHAMPAIGN, Ill. -- Researchers placed 160 cameras on 19 of the 22 Apostle Islands in northern Wisconsin to see which carnivores were living there. After taking more than 200,000 photos over a period of three years, the team discovered that several mammalian predators are living on various islands in this remote archipelago in Lake Superior.

Reported in the journal Community Ecology, the study reveals a thriving community of carnivores, with some doing better than others on islands that differ in size and proximity to the mainland.

The researchers put motion-activated cameras on each of the islands studied, at a density of one camera per square kilometer. Over time, the camera traps recorded 10 of 12 Wisconsin land carnivores, including American martens, black bears, bobcats, coyotes, fishers, gray foxes, gray wolves, raccoons, red foxes and weasels. The cameras also captured images of semiaquatic carnivores mink and river otters, as well as raptors, small rodents, squirrels, songbirds and waterfowl.

"This is one of the first studies to focus on the carnivore community in an island system," said Illinois Natural History Survey wildlife ecologist Max Allen, who led the new research with Morgan Farmer and Tim Van Deelen at the University of Wisconsin, and Erik Olson from Northland College. "The area is remote and difficult to access, with rough water in summer and variable ice conditions in winter, so the carnivore community had never been studied."

The INHS is a division of the Prairie Research Institute at the University of Illinois at Urbana-Champaign.

The research offers new insights into a phenomenon known as island biogeography, which describes the distribution and diversity of species in territories with distinct boundaries that can act as obstacles to inward and outward migration.

"Most research on island biogeography has been conducted in tropical marine systems that have innately high levels of biodiversity and few carnivores," Allen said. The new study is unique in that it examines carnivores in a remote island system in a temperate locale, he said.

"We were surprised to find an intact carnivore community - including gray wolves and American martens - on these islands," Allen said. "We found more carnivore species on islands that were larger and/or closer to the mainland."

Black bears were found on 13 of the islands examined. They appeared to prefer bigger islands that were closer to other islands. Gray wolves, however, were seen only on one of the 19 islands studied. These differences may have to do with the animals' diets and habits. Bears tend to be solitary and eat a variety of foods, while wolves are social, with more specialized diets. The latter tend to prey on ungulates like deer.

The researchers were surprised to find that some smaller carnivores, such as weasels and American martens, appeared to prefer life on islands further from the mainland.

The carnivores may swim from island to island or use ice bridges that form in winter between the islands. Documented declines in the duration of lake ice as a result of climate change may hinder the movement of carnivores between islands and to and from the mainland, Allen said.

"The study offers a first glimpse of the top predators making a living on the Apostle Islands," Allen said. "It's pretty exciting to be the first to document species in an area, especially a wild and remote piece of land in the National Park Service."

Credit: 
University of Illinois at Urbana-Champaign, News Bureau