Differential in vitro infection of neural cells by astroviruses

Encephalitis remains a diagnostic conundrum in humans as over 50% of cases are managed without the identification of an etiology. Astroviruses have been detected from the central nervous system of mammals in association with disease, suggesting that this family of RNA viruses could be responsible for cases of some neurological diseases that are currently without an ascribed etiology. However, there are significant barriers to understanding astrovirus infection as the capacity of these viruses to replicate in nervous system cells in vitro has not been determined. We describe primary and immortalized cultured cells of the nervous system that support infection by astroviruses. These results further corroborate the role of astroviruses in causing neurological diseases and will serve as an essential model to interrogate the neuropathogenesis of astrovirus infection.Recent advances in unbiased pathogen discovery have implicated astroviruses as pathogens of the central nervous system (CNS) of mammals, including humans. However, the capacity of astroviruses to be cultured in CNS-derived cells in vitro has not been reported to date. Both astrovirus VA1/HMO-C (VA1; mamastrovirus 9) and classic human astrovirus 4 (HAstV4; mamastrovirus 1) have been previously detected from cases of human encephalitis. We tested the ability of primary human neurons, primary human astrocytes, and other immortalized human nervous system cell lines (SK-N-SH, U87 MG, and SW-1088) to support infection and replication of these two astrovirus genotypes. Primary astrocytes and SK-N-SH cells supported the full viral life cycle of VA1 with a >100-fold increase in viral RNA levels during a multistep growth curve, detection of viral capsid, and a >100-fold increase in viral titer. Primary astrocytes were permissive with respect to HAstV4 infection and replication but did not yield infectious virus, suggesting abortive infection. Similarly, abortive infection of VA1 was observed in SW-1088 and U87 MG cells. Elevated expression of the chemokine CXCL10 was detected in VA1-infected primary astrocytes and SK-N-SH cells, suggesting that VA1 infection can induce a proinflammatory host response. These findings establish an in vitro cell culture model that is essential for investigation of the basic biology of astroviruses and their neuropathogenic potential

Constraint checking during error recovery

The system-level software onboard a spacecraft is responsible for recovery from communication, power, thermal, and computer-health anomalies that may occur. The recovery must occur without disrupting any critical scientific or engineering activity that is executing at the time of the error. Thus, the error-recovery software may have to execute concurrently with the ongoing acquisition of scientific data or with spacecraft maneuvers. This work provides a technique by which the rules that constrain the concurrent execution of these processes can be modeled in a graph. An algorithm is described that uses this model to validate that the constraints hold for all concurrent executions of the error-recovery software with the software that controls the science and engineering activities of the spacecraft. The results are applicable to a variety of control systems with critical constraints on the timing and ordering of the events they control

Willingness to Pay for Water Availability in Northwest Arkansas

Resource /Energy Economics and Policy,

RyR1-targeted drug discovery pipeline integrating FRET-based high-throughput screening and human myofiber dynamic Ca2+ assays.

Elevated cytoplasmic [Ca2+] is characteristic in severe skeletal and cardiac myopathies, diabetes, and neurodegeneration, and partly results from increased Ca2+ leak from sarcoplasmic reticulum stores via dysregulated ryanodine receptor (RyR) channels. Consequently, RyR is recognized as a high-value target for drug discovery to treat such pathologies. Using a FRET-based high-throughput screening assay that we previously reported, we identified small-molecule compounds that modulate the skeletal muscle channel isoform (RyR1) interaction with calmodulin and FK506 binding protein 12.6. Two such compounds, chloroxine and myricetin, increase FRET and inhibit [3H]ryanodine binding to RyR1 at nanomolar Ca2+. Both compounds also decrease RyR1 Ca2+ leak in human skinned skeletal muscle fibers. Furthermore, we identified compound concentrations that reduced leak by > 50% but only slightly affected Ca2+ release in excitation-contraction coupling, which is essential for normal muscle contraction. This report demonstrates a pipeline that effectively filters small-molecule RyR1 modulators towards clinical relevance

Current dark matter annihilation constraints from CMB and low-redshift data

Updated constraints on the dark matter cross section and mass are presented combining cosmic microwave background (CMB) power spectrum measurements from Planck, WMAP9, ACT, and SPT as well as several low-redshift data sets (BAO, HST, and supernovae). For the CMB data sets, we combine WMAP9 temperature and polarization data for l ≤ 431 with Planck temperature data for 432 ≤ l ≤ 2500, ACT and SPT data for l > 2500, and Planck CMB four-point lensing measurements. We allow for redshift-dependent energy deposition from dark matter annihilation by using a “universal" energy absorption curve. We also include an updated treatment of the excitation, heating, and ionization energy fractions and provide an updated deposition efficiency factors (f[subscript eff]) for 41 different dark matter models. Assuming perfect energy deposition (f[subscript eff] = 1) and a thermal cross section, dark matter masses below 26 GeV are excluded at the 2σ level. Assuming a more generic efficiency of f[subscript eff] = 0.2, thermal dark matter masses below 5 GeV are disfavored at the 2σ level. These limits are a factor of ∼2 improvement over those from WMAP9 data alone. These current constraints probe, but do not exclude, dark matter as an explanation for reported anomalous indirect detection observations from AMS-02/PAMELA and the Fermi gamma-ray inner-Galaxy data. They also probe relevant models that would explain anomalous direct detection events from CDMS, CRESST, CoGeNT, and DAMA, as originating from a generic thermal weakly interacting massive particle. Projected constraints from the full Planck release should improve the current limits by another factor of ∼2 but will not definitely probe these signals. The proposed CMB Stage IV experiment will more decisively explore the relevant regions and improve upon the Planck constraints by another factor of ∼2.Stony Brook University-Brookhaven National Laboratory (Research Initiatives Seed Grant 37298, Project 1111593)United States. Dept. of Energy (Cooperative Research Agreement Contract DE-FG02-05ER41360

Prenatal Stress: A Predictor of Childhood Behavior Disorders

Background: Behavior disorders in children are disruptive to the lives of those who are close to the child and can affect life in the home, school or social setting. One theory is that maternal prenatal psychosocial stress can potentiate such disruptive behavior. Several animal studies have found a correlation between prenatal stress and child development. This systematic review evaluates observational studies of prenatal psychosocial stress in humans and the behavior of their offspring. Does psychosocial stress in pregnant mothers lead to behavior disorders in their children? Method: An extensive search of medical literature was conducted using databases of Medline Ovid, Web of Science, CINAHL, and Google Scholar using the keywords: child behavior disorders, life change events, pregnancy and psychosocial stress. Studies meeting exclusion and inclusion criteria were evaluated for quality using the GRADE system. Results: Three observational studies were thoroughly evaluated and are included in this review. One study found a correlation between prenatal stress and temperament and problem behaviors of toddlers. One study suggests evidence supports a link between prenatal bereavement and the development of ADHD in offspring. One in vitro fertilization study examined the nature vs. nurture question by comparing genetically related mothers to genetically unrelated mothers, and assessing the correlation between prenatal stress and behavior problems of their offspring. Conclusion: Each study suggests the correlation between prenatal psychosocial stress and behavior disorders in children but each study has some level of limitation leading to inconclusive evidence. Understanding the correlation between prenatal stress and child behavior, medical providers could aid in preventing the behavior problems. Identifying those mothers who are stressed and providing them with resources to alleviate the stress could potentially mitigate the undesired behavior in the child. More studies are needed to examine the theory that prenatal stress effects behavior development in children