Analysis of the Genome of the Sexually Transmitted Insect Virus Helicoverpa zea Nudivirus 2

The sexually transmitted insect virus Helicoverpa zea nudivirus 2 (HzNV-2) was determined to have a circular double-stranded DNA genome of 231,621 bp coding for an estimated 113 open reading frames (ORFs). HzNV-2 is most closely related to the nudiviruses, a sister group of the insect baculoviruses. Several putative ORFs that share homology with the baculovirus core genes were identified in the viral genome. However, HzNV-2 lacks several key genetic features of baculoviruses including the late transcriptional regulation factor, LEF-1 and the palindromic hrs, which serve as origins of replication. The HzNV-2 genome was found to code for three ORFs that had significant sequence homology to cellular genes which are not generally found in viral genomes. These included a presumed juvenile hormone esterase gene, a gene coding for a putative zinc-dependent matrix metalloprotease, and a major facilitator superfamily protein gene; all of which are believed to play a role in the cellular proliferation and the tissue hypertrophy observed in the malformation of reproductive organs observed in HzNV-2 infected corn earworm moths, Helicoverpa zea

The novel ORFV protein ORFV113 activates LPA-p38 signaling

Viruses have evolved mechanisms to subvert critical cellular signaling pathways that regulate a wide range of cellular functions, including cell differentiation, proliferation and chemotaxis, and innate immune responses. Here, we describe a novel ORFV protein, ORFV113, that interacts with the G protein-coupled receptor Lysophosphatidic acid receptor 1 (LPA1). Consistent with its interaction with LPA1, ORFV113 enhances p38 kinase phosphorylation in ORFV infected cells in vitro and in vivo, and in cells transiently expressing ORFV113 or treated with soluble ORFV113. Infection of cells with virus lacking ORFV113 (OVIA82Δ113) significantly decreased p38 phosphorylation and viral plaque size. Infection of cells with ORFV in the presence of a p38 kinase inhibitor markedly diminished ORFV replication, highlighting importance of p38 signaling during ORFV infection. ORFV113 enhancement of p38 activation was prevented in cells in which LPA1 expression was knocked down and in cells treated with LPA1 inhibitor. Infection of sheep with OV-IA82Δ113 led to a strikingly attenuated disease phenotype, indicating that ORFV113 is a major virulence determinant in the natural host. Notably, ORFV113 represents the first viral protein that modulates p38 signaling via interaction with LPA1 receptor

Total Sitting Time and Sitting Pattern in Postmenopausal Women Differ by Hispanic Ethnicity and are Associated With Cardiometabolic Risk Biomarkers.

Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with cardiometabolic risk were explored in overweight/obese postmenopausal women (n=518; mean±SD age 63±6 years; mean body mass index 31.4±4.8 kg/m2). Accelerometer data were processed using validated machine-learned algorithms to measure total daily sitting time and mean sitting bout duration (an indicator of sitting behavior pattern). Multivariable linear regression was used to compare sitting among Hispanic women (n=102) and non-Hispanic women (n=416) and tested associations with cardiometabolic risk biomarkers. Hispanic women sat, on average, 50.3 minutes less/day than non-Hispanic women (P<0.001) and had shorter (3.6 minutes less, P=0.02) mean sitting bout duration. Among all women, longer total sitting time was deleteriously associated with fasting insulin and triglyceride concentrations, insulin resistance, body mass index and waist circumference; longer mean sitting bout duration was deleteriously associated with fasting glucose and insulin concentrations, insulin resistance, body mass index and waist circumference. Exploratory interaction analysis showed that the association between mean sitting bout duration and fasting glucose concentration was significantly stronger among Hispanic women than non-Hispanic women (P-interaction=0.03). Conclusions Ethnic differences in 2 objectively measured parameters of sitting behavior, as well as detrimental associations between parameters and cardiometabolic biomarkers were observed in overweight/obese older women. The detrimental association between mean sitting bout duration and fasting glucose may be greater in Hispanic women than in non-Hispanic women. Corroboration in larger studies is warranted

Nine years of in situ soil warming and topography impact the temperature sensitivity and basal respiration rate of the forest floor in a Canadian boreal forest

The forest floor of boreal forest stores large amounts of organic C that may react to a warming climate and increased N deposition. It is therefore crucial to assess the impact of these factors on the temperature sensitivity of this C pool to help predict future soil CO2 emissions from boreal forest soils to the atmosphere. In this study, soil warming (+2–4°C) and canopy N addition (CNA; +0.30–0.35 kg·N·ha-1·yr-1) were replicated along a topographic gradient (upper, back and lower slope) in a boreal forest in Quebec, Canada. After nine years of treatment, the forest floor was collected in each plot, and its organic C composition was characterized through solid-state 13C nuclear magnetic resonance (NMR) spectroscopy. Forest floor samples were incubated at four temperatures (16, 24, 32 and 40°C) and respiration rates (RR) measured to assess the temperature sensitivity of forest floor RR (Q10 = e10k) and basal RR (B). Both soil warming and CNA had no significant effect on forest floor chemistry (e.g., C, N, Ca and Mg content, amount of soil organic matter, pH, chemical functional groups). The NMR analyses did not show evidence of significant changes in the forest floor organic C quality. Nonetheless, a significant effect of soil warming on both the Q10 of RR and B was observed. On average, B was 72% lower and Q10 45% higher in the warmed, versus the control plots. This result implies that forest floor respiration will more strongly react to changes in soil temperature in a future warmer climate. CNA had no significant effect on the measured soil and respiration parameters, and no interaction effects with warming. In contrast, slope position had a significant effect on forest floor organic C quality. Upper slope plots had higher soil alkyl C:O-alkyl C ratios and lower B values than those in the lower slope, across all different treatments. This result likely resulted from a relative decrease in the labile C fraction in the upper slope, characterized by lower moisture levels. Our results point towards higher temperature sensitivity of RR under warmer conditions, accompanied by an overall down-regulation of RR at low temperatures (lower B). Since soil C quantity and quality were unaffected by the nine years of warming, the observed patterns could result from microbial adaptations to warming

Identification of T-cell epitopes in African swine fever virus CD2v and C-type lectin proteins.

African swine fever (ASF) is an emerging disease threat for the swine industry worldwide. No ASF vaccine is available, and progress is hindered by lack of knowledge concerning the extent of ASF virus (ASFV) strain diversity and the viral antigens conferring type-specific protective immunity in pigs. Previously, we demonstrated that ASFV serotype-specific proteins CD2v (EP402R) and/or C-type lectin (EP153R) are important for protection against homologous ASF infection. Here, we identified six discrete T-cell epitope regions present on CD2v and C-type lectin using IFN-γ ELISpot assay and PBMCs from ASF immune animals, indicating cellular reactivity to these proteins in the context of ASFV infection and protective immunity. Notably, three of the epitope regions map to previously described serotype-specific signature regions of these proteins. Improved understanding of ASFV protective antigens, relevant epitopes and their diversity in nature will facilitate ASFV subunit vaccine design and development

Migratory shorebird adheres to Bergmann’s Rule by responding to environmental conditions through the annual lifecycle

The inverse relationship between body size and environmental temperature is a widespread ecogeographic pattern. However, the underlying forces that produce this pattern are unclear in many taxa. Expectations are particularly unclear for migratory species, as individuals may escape environmental extremes and reorient themselves along the environmental gradient. In addition, some aspects of body size are largely fixed while others are environmentally flexible and may vary seasonally. Here, we used a long-term dataset that tracked multiple populations of the migratory piping plover Charadrius melodus across their breeding and non-breeding ranges to investigate ecogeographic patterns of phenotypically flexible (body mass) and fixed (wing length) size traits in relation to latitude (Bergmann’s Rule), environmental temperature (heat conservation hypothesis), and migratory distance. We found that body mass was correlated with both latitude and temperature across the breeding and non-breeding ranges, which is consistent with predictions of Bergmann’s Rule and heat conservation. However, wing length was correlated with latitude and temperature only on the breeding range. This discrepancy resulted from low migratory connectivity across seasons and the tendency for individuals with longer wings to migrate farther than those with shorter wings. Ultimately, these results suggest that wing length may be driven more by conditions experienced during the breeding season or tradeoffs related to migration, whereas body mass is modified by environmental conditions experienced throughout the annual lifecycle

Migratory shorebird adheres to Bergmann’s Rule by responding to environmental conditions through the annual lifecycle

The inverse relationship between body size and environmental temperature is a widespread ecogeographic pattern. However, the underlying forces that produce this pattern are unclear in many taxa. Expectations are particularly unclear for migratory species, as individuals may escape environmental extremes and reorient themselves along the environmental gradient. In addition, some aspects of body size are largely fixed while others are environmentally flexible and may vary seasonally. Here, we used a long-term dataset that tracked multiple populations of the migratory piping plover Charadrius melodus across their breeding and non-breeding ranges to investigate ecogeographic patterns of phenotypically flexible (body mass) and fixed (wing length) size traits in relation to latitude (Bergmann’s Rule), environmental temperature (heat conservation hypothesis), and migratory distance. We found that body mass was correlated with both latitude and temperature across the breeding and non-breeding ranges, which is consistent with predictions of Bergmann’s Rule and heat conservation. However, wing length was correlated with latitude and temperature only on the breeding range. This discrepancy resulted from low migratory connectivity across seasons and the tendency for individuals with longer wings to migrate farther than those with shorter wings. Ultimately, these results suggest that wing length may be driven more by conditions experienced during the breeding season or tradeoffs related to migration, whereas body mass is modified by environmental conditions experienced throughout the annual lifecycle

Ciliary Abnormalities Due to Defects in the Retrograde Transport Protein DYNC2H1 in Short-Rib Polydactyly Syndrome

The short-rib polydactyly (SRP) syndromes are a heterogenous group of perinatal lethal skeletal disorders with polydactyly and multisystem organ abnormalities. Homozygosity by descent mapping in a consanguineous SRP family identified a genomic region that contained DYNC2H1, a cytoplasmic dynein involved in retrograde transport in the cilium. Affected individuals in the family were homozygous for an exon 12 missense mutation that predicted the amino acid substitution R587C. Compound heterozygosity for one missense and one null mutation was identified in two additional nonconsanguineous SRP families. Cultured chondrocytes from affected individuals showed morphologically abnormal, shortened cilia. In addition, the chondrocytes showed abnormal cytoskeletal microtubule architecture, implicating an altered microtubule network as part of the disease process. These findings establish SRP as a cilia disorder and demonstrate that DYNC2H1 is essential for skeletogenesis and growth

Neuromotor tolerability and behavioural characterisation of cannabidiolic acid, a phytocannabinoid with therapeutic potential for anticipatory nausea

Rationale: Anticipatory nausea (AN) is a poorly controlled side-effect experienced by chemotherapy patients. Currently, pharmacotherapy is restricted to benzodiazepine anxiolytics, which have limited efficacy, significant sedative effects, and induce dependency. The non-psychoactive phytocannabinoid, cannabidiolic acid (CBDA), has shown considerable efficacy in pre-clinical AN models, however determination of its neuromotor tolerability profile is crucial to justify clinical investigation. Provisional evidence for appetite-stimulating properties also requires detailed investigation. Objectives: To assess the tolerability of CBDA in locomotor activity, motor coordination and muscular strength tests, and additionally for ability to modulate feeding behaviours. Methods: Male Lister hooded rats administered CBDA (0.05-5 mg/kg; p.o.) were assessed in habituated open field (for locomotor activity), static beam and grip strength tests. A further study investigated whether these CBDA doses modulated normal feeding behaviour. Finally, evidence of anxiolytic-like effects in the habituated open field prompted testing of 5 mg/kg CBDA for anxiolytic-like activity in unhabituated open field, light/dark box and novelty-supressed feeding (NSF) tests. Results: CBDA had no adverse effects upon performance in any neuromotor tolerability test, however anxiolytic-like behaviour was observed in the habituated open field. Normal feeding behaviours were unaffected by any dose. CBDA (5 mg/kg) abolished the increased feeding latency in the NSF test induced by the 5-HT1AR antagonist, WAY-100,635, indicative of anxiolytic-like effects, but had no effect on anxiety-like behaviour in the novel open field or light/dark box. Conclusions: CBDA is very well tolerated and devoid of the sedative side-effect profile of benzodiazepines, justifying its clinical investigation as a novel AN treatment