The Effect of Epstein-Barr Virus Latent Membrane Protein 2 Expression on the Kinetics of Early B Cell Infection

Infection of human B cells with wild-type Epstein-Barr virus (EBV) in vitro leads to activation and proliferation that result in efficient production of lymphoblastoid cell lines (LCLs). Latent Membrane Protein 2 (LMP2) is expressed early after infection and previous research has suggested a possible role in this process. Therefore, we generated recombinant EBV with knockouts of either or both protein isoforms, LMP2A and LMP2B (Δ2A, Δ2B, Δ2A/Δ2B) to study the effect of LMP2 in early B cell infection. Infection of B cells with Δ2A and Δ2A/Δ2B viruses led to a marked decrease in activation and proliferation relative to wild-type (wt) viruses, and resulted in higher percentages of apoptotic B cells. Δ2B virus infection showed activation levels comparable to wt, but fewer numbers of proliferating B cells. Early B cell infection with wt, Δ2A and Δ2B viruses did not result in changes in latent gene expression, with the exception of elevated LMP2B transcript in Δ2A virus infection. Infection with Δ2A and Δ2B viruses did not affect viral latency, determined by changes in LMP1/Zebra expression following BCR stimulation. However, BCR stimulation of Δ2A/Δ2B cells resulted in decreased LMP1 expression, which suggests loss of stability in viral latency. Long-term outgrowth assays revealed that LMP2A, but not LMP2B, is critical for efficient long-term growth of B cells in vitro. The lowest levels of activation, proliferation, and LCL formation were observed when both isoforms were deleted. These results suggest that LMP2A appears to be critical for efficient activation, proliferation and survival of EBV-infected B cells at early times after infection, which impacts the efficient long-term growth of B cells in culture. In contrast, LMP2B did not appear to play a significant role in these processes, and long-term growth of infected B cells was not affected by the absence of this protein. © 2013 Wasil et al

Mitochondrial genome deletions and minicircles are common in lice (Insecta: Phthiraptera)

Background The gene composition, gene order and structure of the mitochondrial genome are remarkably stable across bilaterian animals. Lice (Insecta: Phthiraptera) are a major exception to this genomic stability in that the canonical single chromosome with 37 genes found in almost all other bilaterians has been lost in multiple lineages in favour of multiple, minicircular chromosomes with less than 37 genes on each chromosome. Results Minicircular mt genomes are found in six of the ten louse species examined to date and three types of minicircles were identified: heteroplasmic minicircles which coexist with full sized mt genomes (type 1); multigene chromosomes with short, simple control regions, we infer that the genome consists of several such chromosomes (type 2); and multiple, single to three gene chromosomes with large, complex control regions (type 3). Mapping minicircle types onto a phylogenetic tree of lice fails to show a pattern of their occurrence consistent with an evolutionary series of minicircle types. Analysis of the nuclear-encoded, mitochondrially-targetted genes inferred from the body louse, Pediculus, suggests that the loss of mitochondrial single-stranded binding protein (mtSSB) may be responsible for the presence of minicircles in at least species with the most derived type 3 minicircles (Pediculus, Damalinia). Conclusions Minicircular mt genomes are common in lice and appear to have arisen multiple times within the group. Life history adaptive explanations which attribute minicircular mt genomes in lice to the adoption of blood-feeding in the Anoplura are not supported by this expanded data set as minicircles are found in multiple non-blood feeding louse groups but are not found in the blood-feeding genus Heterodoxus. In contrast, a mechanist explanation based on the loss of mtSSB suggests that minicircles may be selectively favoured due to the incapacity of the mt replisome to synthesize long replicative products without mtSSB and thus the loss of this gene lead to the formation of minicircles in lice

Tallness is associated with risk of testicular cancer: evidence for the nutrition hypothesis

The pathogenesis of testicular germ cell tumours (GCTs) is potentially influenced by high-energy nutrition during infancy. As adult height is a proxy for childhood nutrition, we investigated the role of nutrition in GCT pathogenesis by comparing stature of patients with healthy men. In a matched case–control study, 6415 patients with GCT were compared with healthy army conscripts (1:6 matching modus) with regard to height (cm) and body mass index (BMI; kg/m2). Statistical analysis involved tabulation of descriptive height measures and BMI. Conditional logistic regression models were used to quantify the association of GCT with height, with odds ratios (OR) adjusted for BMI. The literature was searched for studies on stature in GCT patients. Body size is significantly associated with risk of GCT, very tall men (>195 cm) having a GCT risk of OR=3.35 (95% confidence intervals (CI): 2.88–3.90; adjusted). Short stature is protective (OR=0.798; 95% CI: 0.68–0.93). Both histologic subgroups are associated with tallness. Of 16 previous reports, 7 were confirmative, 5 had null and 4 equivocal results. The association of stature with GCT risk accords with the nutrition hypothesis of GCT. This study expands the current view of GCT tumorigenesis by suggesting that high-calorie intake in childhood promotes GCT precursors originating in utero

Simvastatin decreases the level of heparin-binding protein in patients with acute lung injury

Background: Heparin-binding protein is released by neutrophils during inflammation and disrupts the integrity of the alveolar and capillary endothelial barrier implicated in the development of acute lung injury and systemic organ failure. We sought to investigate whether oral administration of simvastatin to patients with acute lung injury reduces plasma heparin-binding protein levels and improves intensive care unit outcome. Methods: Blood samples were collected from patients with acute lung injury with 48 h of onset of acute lung injury (day 0), day 3, and day 7. Patients were given placebo or 80 mg simvastatin for up to 14 days. Plasma heparin-binding protein levels from patients with acute lung injury and healthy volunteers were measured by ELISA. Results: Levels of plasma heparin-binding protein were significantly higher in patients with acute lung injury than healthy volunteers on day 0 (p = 0.011). Simvastatin 80 mg administered enterally for 14 days reduced plasma level of heparin-binding protein in patients. Reduced heparin-binding protein was associated with improved intensive care unit survival. Conclusions: A reduction in heparin-binding protein with simvastatin is a potential mechanism by which the statin may modify outcome from acute lung injury

Glucose and glutamine fuel protein O-GlcNAcylation to control T cell self-renewal and malignancy

Sustained glucose and glutamine transport are essential for activated T lymphocytes to support ATP and macromolecule biosynthesis. We now show that glutamine and glucose also fuel an indispensible dynamic regulation of intracellular protein O-GlcNAcylation at key stages of T cell development, transformation and differentiation. Glucose and glutamine are precursors of UDP-GlcNAc, a substrate for cellular glycosyltransferases. Immune activated T cells contained higher concentrations of UDP-GlcNAc and increased intracellular protein O-GlcNAcylation controlled by the enzyme O-GlcNAc glycosyltransferase as compared to naïve cells. We identified Notch, the T cell antigen receptor and c-Myc as key controllers of T cell protein O-GlcNAcylation, via regulation of glucose and glutamine transport. Loss of O-GlcNAc transferase blocked T cell progenitor renewal, malignant transformation, and peripheral T cell clonal expansion. Nutrient-dependent signaling pathways regulated by O-GlcNAc glycosyltransferase are thus fundamental for T cell biology

Relationship between nano-architectured Ti1−xCux thin film and electrical resistivity for resistance temperature detectors

Ti1−xCux thin films were produced by the glancing angle deposition technique (GLAD) for resistance temperature measurements. The deposition angle was fixed at α = 0° to growth columnar structures and α = 45° to growth zigzag structures. The Ti-to-Cu atomic concentration was tuned from 0 to 100 at.% of Cu in order to optimize the temperature coefficient of resistance (TCR) value. Increasing the amount of Cu in the Ti1−xCux thin films, the electrical conductivity was gradually changed from 4.35 to 7.87 × 105 Ω−1 m−1. After thermal “stabilization,” the zigzag structures of Ti1−xCux films induce strong variation of the thermosensitive response of the materials and exhibited a reversible resistivity versus temperature between 35 and 200 °C. The results reveal that the microstructure has an evident influence on the overall response of the films, leading to values of TCR of 8.73 × 10−3 °C−1 for pure copper films and of 4.38 × 10−3 °C−1 for a films of composition Ti0.49Cu0.51. These values are very close to the ones reported for the bulk platinum (3.93 × 10−3 °C−1), which is known to be one of the best material available for these kind of temperature-related applications. The non-existence of hysteresis in the electrical response of consecutive heating and cooling steps indicates the viability of these nanostructured zigzag materials to be used as thermosensitive sensors.Portuguese Foundation for Science and Technology (FCT) in the framework of the Strategic Funding UID/FIS/04650/2013 and Project PTDC/EEI-SII/5582/2014. A. Ferreira and C. Lopes thanks the FCT for Grant SFRH/BPD/102402/2014 and SFRH/BD/103373/2014. The authors thank financial support from the Basque Government Industry Department under the ELKARTEK Programinfo:eu-repo/semantics/publishedVersio

Home on the Range: Factors Explaining Partial Migration of African Buffalo in a Tropical Environment

Partial migration (when only some individuals in a population undertake seasonal migrations) is common in many species and geographical contexts. Despite the development of modern statistical methods for analyzing partial migration, there have been no studies on what influences partial migration in tropical environments. We present research on factors affecting partial migration in African buffalo (Syncerus caffer) in northeastern Namibia. Our dataset is derived from 32 satellite tracking collars, spans 4 years and contains over 35,000 locations. We used remotely sensed data to quantify various factors that buffalo experience in the dry season when making decisions on whether and how far to migrate, including potential man-made and natural barriers, as well as spatial and temporal heterogeneity in environmental conditions. Using an information-theoretic, non-linear regression approach, our analyses showed that buffalo in this area can be divided into 4 migratory classes: migrants, non-migrants, dispersers, and a new class that we call “expanders”. Multimodel inference from least-squares regressions of wet season movements showed that environmental conditions (rainfall, fires, woodland cover, vegetation biomass), distance to the nearest barrier (river, fence, cultivated area) and social factors (age, size of herd at capture) were all important in explaining variation in migratory behaviour. The relative contributions of these variables to partial migration have not previously been assessed for ungulates in the tropics. Understanding the factors driving migratory decisions of wildlife will lead to better-informed conservation and land-use decisions in this area

Habitat quality, configuration and context effects on roe deer fecundity across a forested landscape mosaic

Effective landscape-scale management of source-sink deer populations will be strengthened by understanding whether local variation in habitat quality drives heterogeneity in productivity. We related female roe deer Capreolus capreolus fecundity and body mass to habitat composition and landscape context, separately for adults and yearlings, using multi-model inference (MMI) applied to a large sample of individuals (yearlings: fecundity=202, body mass=395; adults: fecundity=908, body mass=1669) culled during 2002-2015 from an extensive (195 km2) heterogeneous forest landscape. Adults were heavier (inter-quartile, IQ, effect size=+0.5kg) when culled in buffers comprising more arable lands while contrary to our prediction no effects on body mass of grassland, young forest or access to vegetation on calcareous soil were found. Heavier adults were more fertile (IQ effect size, +12% probability of having two embryos instead of one or zero). Counter-intuitively, adults with greater access to arable lands were less fecund (IQ effect of arable: -7% probability of having two embryos, instead of one or zero), and even accounting for greater body mass of adults with access to arable, their modelled fecundity was similar to or lower than that of adults in the forest interior. In contrast, effects of grassland, young forest and calcareous soil did not receive support. Yearling body mass had an effect on fecundity twice that found in adults (+23% probability of having one additional embryo), but yearling body mass and fecundity were not affected by any candidate habitat or landscape variables. Effect of arable lands on body mass and fecundity were small, with little variance explained (Coefficient of Variation of predicted fecundity across forest sub-regions=0.03 for adults). More variance in fecundity was attributed to other differences between forest management sub-regions (modelled as random effects), suggesting other factors might be important. When analysing source-sink population dynamics to support management, an average value of fecundity can be appropriate across a heterogeneous forest landscape