Genetic diversity, social structure, and conservation value of the elephants of the Nakai Plateau, Lao PDR, based on non-invasive sampling

The Lao People??s Democratic Republic (PDR) may have the largest Asian elephant population in Indochina. However, elephants on Lao PDR??s Nakai Plateau are potentially threatened by the construction of a hydropower dam that will flood important habitat. We conducted a non-invasive genetic study of elephants in this region to provide baseline data on genetic diversity and social structure prior to dam construction. For the 102 elephants we detected, values of observed heterozygosity (0.711) and allelic diversity (8.0 alleles/locus) at microsatellite loci were higher than those found in elephant populations in India and Vietnam, while mitochondrial diversity (haplotype diversity 0.741; nucleotide diversity 0.011) was similar to that reported for the Lao/Vietnam region. Six mitochondrial haplotypes were detected, representing both major clades previously reported in this species. Relatedness estimates between females and young detected near each other are consistent with familial relationships, and relatedness estimates between adult males and females suggest male locational dispersal. Since family group structure appears to be intact in the Nakai region, these elephants will likely move as relatively large family groups in response to habitat disturbance. These results have positive implications for the viability of the elephant population in this region, demonstrate its conservation significance, and will be valuable for predicting and monitoring the effects of the hydropower dam over time.     

MHC mismatch inhibits neurogenesis and neuron maturation in stem cell allografts

Background

The role of histocompatibility and immune recognition in stem cell transplant therapy has been controversial, with many reports arguing that undifferentiated stem cells are protected from immune recognition due to the absence of major histocompatibility complex (MHC) markers. This argument is even more persuasive in transplantation into the central nervous system (CNS) where the graft rejection response is minimal.

Methodology/Principal Findings

In this study, we evaluate graft survival and neuron production in perfectly matched vs. strongly mismatched neural stem cells transplanted into the hippocampus in mice. Although allogeneic cells survive, we observe that MHC-mismatch decreases surviving cell numbers and strongly inhibits the differentiation and retention of graft-derived as well as endogenously produced new neurons. Immune suppression with cyclosporine-A did not improve outcome but non-steroidal anti-inflammatory drugs, indomethacin or rosiglitazone, were able to restore allogeneic neuron production, integration and retention to the level of syngeneic grafts.

Conclusions/Significance

These results suggest an important but unsuspected role for innate, rather than adaptive, immunity in the survival and function of MHC-mismatched cellular grafts in the CNS.     

A Pilot Randomized Controlled Trial of a Clinic and Home‐Based Behavioral Intervention to Decrease Obesity in Preschoolers

We evaluated the efficacy of a 6‐month clinic and home‐based behavioral intervention (Learning about Activity and Understanding Nutrition for Child Health; LAUNCH) to reduce obesity in preschool children ≥95th BMI percentile compared to enhanced standard of care (Pediatrician Counseling; PC). LAUNCH was a family‐based behavioral intervention that taught parents to use child behavior management strategies to increase healthy eating and activity for their children and themselves. PC presented the same diet and activity recommendations, but was delivered in a one‐time PC session. Eighteen children aged 2–5 years (mean 4.71 ± 1.01) with an average BMI percentile of 98 (±1.60) and an overweight parent were randomized to LAUNCH or PC. Assessments were conducted at baseline, 6 months (end of LAUNCH treatment) and 12 months (6 months following LAUNCH treatment). LAUNCH showed a significantly greater decrease on the primary outcomes of child at month 6 (post‐treatment) BMI z (?0.59 ± 0.17), BMI percentile (?2.4 ± 1.0), and weight gain (?2.7 kg ± 1.2) than PC and this difference was maintained at follow‐up (month 12). LAUNCH parents also had a significantly greater weight loss (?5.5 kg ± 0.9) at month 6 and 12 (?8.0 kg ± 3.5) than PC parents. Based on the data from this small sample, an intensive intervention that includes child behavior management strategies to improve healthy eating and activity appears more promising in reducing preschool obesity than a low intensity intervention that is typical of treatment that could be delivered in primary care.     

c-Rel deficiency increases caspase-4 expression and leads to ER stress and necrosis in EBV-transformed cells

LMP1-mediated activation of nuclear factor of kappaB (NF-κB) is critical for the ligand independent proliferation and cell survival of in vitro EBV-transformed lymphoblastoid cell lines (LCLs). Previous experiments revealed that a majority of LMP1-dependent responses are regulated by NF-κB. However, the extent that individual NF-κB family members are required for these responses, in particular, c-Rel, whose expression is restricted to mature hematopoietic cells, remains unclear. Here we report that low c-Rel expression in LCLs derived from a patient with hyper-IgM syndrome (Pt1), resulted in defects in proliferation and cell survival. In contrast to studies that associated loss of NF-κB with increased apoptosis, Pt1 LCLs failed to initiate apoptosis and alternatively underwent autophagy and necrotic cell death. Whereas the proliferation defect appeared linked to a c-Rel-associated decrease in c-myc expression, identified pro-survival and pro-apoptotic targets were expressed at or near control levels consistent with the absence of apoptosis. Ultrastructural examination of Pt1 LCLs revealed a high level of cellular and ER stress that was further supported by gene expression profiling showing the upregulation of several genes involved in stress and inflammation. Apoptosis-independent cell death was accompanied by increased expression of the inflammatory marker, caspase-4. Using gene overexpression and siRNA knockdown we demonstrated that levels of c-Rel directly modulated expression of caspase-4 as well as other ER stress genes. Overall, these findings reveal the importance of c-Rel in maintaining LCL viability and that decreased expression results in ER stress and a default response leading to necrotic cell death.     

EBP2 plays a key role in Epstein-Barr virus mitotic segregation and is regulated by aurora family kinases

Epstein-Barr virus (EBV) genomes persist indefinitely in latently infected human cells, in part due to their ability to stably segregate during cell division. This process is mediated by the viral EBNA1 protein, which tethers the viral episomes to the cellular mitotic chromosomes. We have previously identified a mitotic chromosomal protein, human EBNA1 binding protein 2 (hEBP2), which binds to EBNA1 and enables EBNA1 to partition EBV-based plasmids in Saccharomyces cerevisiae. Using an RNA silencing approach, we show that hEBP2 is essential for the proliferation of human cells and that repression of hEBP2 severely decreases the ability of EBNA1 and EBV-based plasmids to bind mitotic chromosomes. When expressed in yeast, hEBP2 undergoes the same cell cycle-regulated association with the mitotic chromatin as in human cells, and using yeast temperature-sensitive mutant strains, we found that the attachment of hEBP2 to mitotic chromosomes was dependent on the Ipl1 kinase. Both RNA silencing of the Ipl1 orthologue in human cells (Aurora B) and specific inhibition of the Aurora B kinase activity with a small molecule confirmed a role for this kinase in enabling hEBP2 binding to human mitotic chromosomes, suggesting that this kinase can regulate EBV segregation.     

Reference ranges for hemolymph chemistries from Elliptio complanata of North Carolina

Hemolymph chemistries may be useful nonlethal measures of bivalve health. The prognostic value of hemolymph, however, depends on a comparison of chemistry results to reference ranges from healthy individuals. Currently, knowledge of expected hemolymph values in healthy and unhealthy freshwater mussels is extremely limited. The purpose of this study was to develop a set of reference ranges for clinical evaluation of hemolymph from a freshwater mussel species common to southeastern USA. We collected hemolymph from 380 Elliptio complanata from 19 apparently healthy populations from northwest of Raleigh, North Carolina, during May through July 2001. We present reference ranges for hemolymph parameters ammonia, glucose, calcium, magnesium, phosphorus, aspartate aminotransferase (AST), bicarbonate, protein and cell count, and for tissue glycogen. We compare the subpopulations of mussels from regions with an agricultural riparian buffer to those surrounded predominantly by forested lands. We further present correlations noted between hemolymph chemistries and physical or physiologic parameters. The only statistically significant differences between populations contiguous to agricultural and forested lands were in hemolymph calcium and glucose concentrations. Other statistically significant correlations identified were between gravidity and hemolymph protein concentration and tissue glycogen content, as well as between gravidity and parasite burden, and between shell length and hemolymph glucose, AST, calcium and bicarbonate concentrations. The results of this study will aid the interpretation of health measures from populations of E. complanata of similar geographic and seasonal origin.     

Prevalence of antibodies to Toxoplasma gondii in raccoons (Procyon lotor) from an urban area of Northern Virginia

Raccoons (Procyon lotor) are intermediate hosts for Toxoplasma gondii, and clinical toxoplasmosis in raccoons has been reported. A 2-yr serological survey was conducted to determine the prevalence of antibodies to T. gondii in raccoons collected from Fairfax County, Virginia, a suburban/urban area outside Washington, D.C. Serum samples from 256 raccoons were examined for T. gondii antibodies at a 1:50 dilution using the modified direct agglutination test. Results indicated that 216 (84.4%) of the raccoons had been exposed to T. gondii. Our results indicate that raccoons in this area of Virginia are frequently exposed to T. gondii. Domestic cats were common in the study area and may have served as a source of oocysts for raccoons and the food items of raccoons.