Coxsackievirus B3 infection early in pregnancy induces congenital heart defects through suppression of fetal cardiomyocyte proliferation

Background Coxsackievirus B (CVB) is the most common cause of viral myocarditis. It targets cardiomyocytes through coxsackie and adenovirus receptor, which is highly expressed in the fetal heart. We hypothesized CVB3 can precipitate congenital heart defects when fetal infection occurs during critical window of gestation. Methods and Results We infected C57Bl/6 pregnant mice with CVB3 during time points in early gestation (embryonic day [E] 5, E7, E9, and E11). We used different viral titers to examine possible dose-response relationship and assessed viral loads in various fetal organs. Provided viral exposure occurred between E7 and E9, we observed characteristic features of ventricular septal defect (33.6%), abnormal myocardial architecture resembling noncompaction (23.5%), and double-outlet right ventricle (4.4%) among 209 viable fetuses examined. We observed a direct relationship between viral titers and severity of congenital heart defects, with apparent predominance among female fetuses. Infected dams remained healthy; we did not observe any maternal heart or placental injury suggestive of direct viral effects on developing heart as likely cause of congenital heart defects. We examined signaling pathways in CVB3-exposed hearts using RNA sequencing, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, and immunohistochemistry. Signaling proteins of the Hippo, tight junction, transforming growth factor-β1, and extracellular matrix proteins were the most highly enriched in CVB3-infected fetuses with ventricular septal defects. Moreover, cardiomyocyte proliferation was 50% lower in fetuses with ventricular septal defects compared with uninfected controls. Conclusions We conclude prenatal CVB3 infection induces congenital heart defects. Alterations in myocardial proliferate capacity and consequent changes in cardiac architecture and trabeculation appear to account for most of observed phenotypes

Predictability of the Arctic sea ice edge

Skillful sea ice forecasts from days to years ahead are becoming increasingly important for the operation and planning of human activities in the Arctic. Here we analyze the potential predictability of the Arctic sea ice edge in six climate models. We introduce the integrated ice-edge error (IIEE), a user-relevant verification metric defined as the area where the forecast and the “truth” disagree on the ice concentration being above or below 15%. The IIEE lends itself to decomposition into an absolute extent error, corresponding to the common sea ice extent error, and a misplacement error. We find that the often-neglected misplacement error makes up more than half of the climatological IIEE. In idealized forecast ensembles initialized on 1 July, the IIEE grows faster than the absolute extent error. This means that the Arctic sea ice edge is less predictable than sea ice extent, particularly in September, with implications for the potential skill of end-user relevant forecasts

A case of persistent human pegivirus infection in two separate pregnancies of a woman

Human pegivirus (HPgV) is best known for persistent, presumably non-pathogenic, infection and a propensity to co-infect with human immunodeficiency virus or hepatitis C virus. However, unique attributes, such as the increased risk of malignancy or immune modulation, have been recently recognized for HPgV. We have identified a unique case of a woman with high levels HPgV infection in two pregnancies, which occurred 4 years apart and without evidence of human immunodeficiency virus or hepatitis C virus infection. The second pregnancy was complicated by congenital heart disease. A high level of HPgV infection was detected in the maternal blood from different trimesters by RT-PCR and identified as HPgV type 1 genotype 2 in both pregnancies. In the second pregnancy, the decidua and intervillous tissue of the placenta were positive for HPgV by PCR but not the chorion or cord blood (from both pregnancies), suggesting no vertical transmission despite high levels of viremia. The HPgV genome sequence was remarkably conserved over the 4 years. Using VirScan, sera antibodies for HPgV were detected in the first trimester of both pregnancies. We observed the same anti-HPgV antibodies against the non-structural NS5 protein in both pregnancies, suggesting a similar non-E2 protein humoral immune response over time. To the best of our knowledge, this is the first report of persistent HPgV infection involving placental tissues with no clear indication of vertical transmission. Our results reveal a more elaborate viral-host interaction than previously reported, expand our knowledge about tropism, and opens avenues for exploring the replication sites of this virus

Experimental study of double beta decay modes using a CdZnTe detector array

An array of sixteen 1 cm^3 CdZnTe semiconductor detectors was operated at the Gran Sasso Underground Laboratory (LNGS) to further investigate the feasibility of double-beta decay searches with such devices. As one of the double-beta decay experiments with the highest granularity the 4 x 4 array accumulated an overall exposure of 18 kg days. The setup and performance of the array is described. Half-life limits for various double-beta decay modes of Cd, Zn and Te isotopes are obtained. No signal has been found, but several limits beyond 10^20 years have been performed. They are an order of magnitude better than those obtained with this technology before and comparable to most other experimental approaches for the isotopes under investigation. An improved limit for the beta^+/EC decay of Te 120 is given.Comment: 6 pages, 5 figure

Pathogenicity of Pythium species to maize

AbstractPythium isolates from diseased and dead bait plants of maize and cress grown in compost or various soils (maize fields, parkland under deciduous trees, grassland) were characterised and tested for pathogenicity to maize (Zea mays L.). In pot tests performed under controlled conditions, pathogenicity of the isolates to maize was apparent by reduction of root and shoot growth, whereas damping-off of maize seedlings was less frequent. Contrarily, pea seedlings were killed by pathogenic Pythium isolates. Pythium isolates from diseased maize seedlings and pathogenic strains from other gramineous plants (P. phragmitis, P. aff.phragmitis, P. catenulatum) were not necessarily more virulent to maize compared to isolates originating from dicotyledonous plants (cress). The most virulent isolates originated from compost and caused a reduction of maize shoot growth of up to 60%. Phylogenetic analysis revealed that they were very closely related to P. ultimum var. ultimum and P. arrhenomanes, respectively. Isolates originating from maize fields, grassland and parkland under deciduous trees, a reference culture of P. arrhenomanes and strains of P. phragmitis, P. aff. phragmitis and P. catenulatum with known pathogenicity on reed were non-pathogenic on maize. Isolates from compost, and from maize fields generally had a higher temperature optimum for mycelial growth (30 °C) and a faster growth rate (1.5–2.0 mm h−1) compared to the isolates from parkland under deciduous trees and grassland soil (20–25 °C, ~1.0 mm h−1), respectively. This study indicates a potential impact of pathogenic Pythium on maize plants even in the absence of visible symptoms

The preliminary design of a scaled Composite UHBR Fan for a wind tunnel test campaign

AbstractThe ambition of the CA3ViAR project is to design an open test case fan that experiences instability mechanisms, which are representative for ultra-high bypass ratio (UHBR) fans of civil aircrafts, and to perform a comprehensive experimental investigation to measure aerodynamic, aeroelastic and aeroacoustic performance in a wide range of operational conditions. Experimental tests will be performed in the Propulsion-Test-Facility (PTF) of the Institute of Jet Propulsion and Turbomachinery (IFAS) of Technische Universität Braunschweig, Germany. The final objective of the project is to provide an open test case for the entire research community, with geometries, numerical and experimental results to establish a new reference for composite UHBR fan design. This will support the development of new methods and tools for the development of safer, lighter and more efficient composite fans for greener UHBR engines. In this work the preliminary design of the low transonic fan (LTF) to be used as test article, whose main requirement is to be operated in a safe and controlled way in conditions of aerodynamic and/or aeroelastic instability during wind tunnel operations, is presented. More in particular, consolidated aerodynamic design, strategy adopted to drive the structural design, flutter analysis taking into account acoustic reflection at the intake, dynamic and stress analyses, as well as aeroacoustic measurement optimization are presented and discussed. The preliminary mechanical design of composite blades and the rotor hub, together with the rotor instrumentation and related studies to embed sensors in the composite blades, are also part of this article, and complemented by manufacturing trials and demonstration tests give the full picture of all the project activities up to the preliminary design review

Pediatrics

OBJECTIVESTo describe the prevalence and secular trends of high weight-for-length among infants (ages, 3\u201323 months) in the biennial US Department of Agriculture Women, Infants, and Children Program and Participants Characteristic (WIC-PC) Survey from 2000 through 2014 (n = 16 927 120).METHODSWeight-for-length was considered to be \u201chigh\u201d if it was 652 SDs above the sex-and age-specific median in the World Health Organization growth standards. Poisson regression was used to calculate adjusted prevalence ratios.RESULTSThe overall prevalence of high weight-for-length increased from 13.4% in 2000 to 14.5% in 2004, remained constant until 2010, and then decreased by >2 percentage points (to 12.3%) through 2014. The prevalence of high weight-for-length was associated with sex (higher among boys), race-ethnicity (highest among American Indians/Alaskan Natives), and with both age (positive) and family income (inverse). The secular trends, however, were fairly similar within categories of these variables. From 2010 to 2014, the prevalence of high weight-for-length decreased in 40 states and 3 (of 5) US territories, with the largest decreases seen in Puerto Rico ( 129 percentage points) and Kentucky ( 127 percentage points), and the largest increase (+2 percentage points) seen in West Virginia.CONCLUSIONSAlthough the current results cannot be considered representative of infants in the populations, the prevalence of a high weight-for-length has decreased among infants in WIC-PC since 2010. These decreases were similar across categories of most characteristics, but there were substantial differences across jurisdictions, possibly reflecting differences in policy and local programs that target maternal and infant health.20162018-01-01T00:00:00ZCC999999/Intramural CDC HHS/United States27965380PMC5359001777

Hypoxia as a therapy for mitochondrial disease

Defects in the mitochondrial respiratory chain (RC) underlie a spectrum of human conditions, ranging from devastating inborn errors of metabolism to aging. We performed a genome-wide Cas9-mediated screen to identify factors that are protective during RC inhibition. Our results highlight the hypoxia response, an endogenous program evolved to adapt to limited oxygen availability. Genetic or small-molecule activation of the hypoxia response is protective against mitochondrial toxicity in cultured cells and zebrafish models. Chronic hypoxia leads to a marked improvement in survival, body weight, body temperature, behavior, neuropathology, and disease biomarkers in a genetic mouse model of Leigh syndrome, the most common pediatric manifestation of mitochondrial disease. Further preclinical studies are required to assess whether hypoxic exposure can be developed into a safe and effective treatment for human diseases associated with mitochondrial dysfunction.National Institute of Mental Health (U.S.) (Grant 5DP1-MH100706)National Institute of Mental Health (U.S.) (Grant 1R01-MH110049)National Institute of Neurological Diseases and Stroke (U.S.) (Grant 5R01DK097768-03