Egg Parasitism of \u3ci\u3eScirpophaga incertulas\u3c/i\u3e Walker (Lepidoptera:Pyralidae) by Hymenopterous Parasitoids in IRRI Rice Fields

We surveyed the IRRI farm to determine the extent of parasitization of yellow stemborer egg masses. The egg masses were randomly collected at weekly intervals from July to October 1984 from rice fields, 15-20 days after transplanting, and brought to the laboratory for collection of emerging parasites. Three species of hymenopterous parasitoids—Tetrasticus schoenobii, Telenomus rowani, and Trichogramma japonicum—were found from 700 egg masses. We introduced a method to calculate percent parasitism as based on parasite biology and behaviour. Among the three species, the combination of T. rowani and T. japonicum was the highest multiparasitization of yellow stem borer egg masses, and T. rowani, a solitary parasite had the highest number based on immature and adult stages counted. However, T. schoenobii may be the most efficient parasite because two to four host eggs are needed to complete the larval period, and it took 10-14 days for one generation

Efficacy of Metreleptin in Obese Patients With Type 2 Diabetes: Cellular and Molecular Pathways Underlying Leptin Tolerance

Objective: Metreleptin has been efficacious in improving metabolic control in patients with lipodystrophy, but its efficacy has not been tested in obese patients with type 2 diabetes. Research Design and Methods: We studied the role of leptin in regulating the endocrine adaptation to long-term caloric deprivation and weight loss in obese diabetic subjects over 16 weeks in the context of a double-blinded, placebo–controlled, randomized trial. We then performed detailed interventional and mechanistic signaling studies in humans in vivo, ex vivo, and in vitro. Results: In obese patients with diabetes, metreleptin administration for 16 weeks did not alter body weight or circulating inflammatory markers but reduced HbA$_{1c}$ marginally (8.01 $\pm$ 0.93–7.96 $\pm$ 1.12, P = 0.03). Total leptin, leptin-binding protein, and antileptin antibody levels increased, limiting free leptin availability and resulting in circulating free leptin levels of $\sim$50 ng/mL. Consistent with clinical observations, all metreleptin signaling pathways studied in human adipose tissue and peripheral blood mononuclear cells were saturable at $\sim$50 ng/mL, with no major differences in timing or magnitude of leptin-activated STAT3 phosphorylation in tissues from male versus female or obese versus lean humans in vivo, ex vivo, or in vitro. We also observed for the first time that endoplasmic reticulum (ER) stress in human primary adipocytes inhibits leptin signaling. Conclusions: In obese patients with diabetes, metreleptin administration did not alter body weight or circulating inflammatory markers but reduced HbA$_{1c}$ marginally. ER stress and the saturable nature of leptin signaling pathways play a key role in the development of leptin tolerance in obese patients with diabetes

Variation in the provision and practice of implant-based breast reconstruction in the UK: Results from the iBRA national practice questionnaire

Introduction The introduction of biological and synthetic meshes has revolutionised the practice of implant-based breast reconstruction (IBBR) but evidence for effectiveness is lacking. The iBRA (implant Breast Reconstruction evAluation) study is a national trainee-led project that aims to explore the practice and outcomes of IBBR to inform the design of a future trial. We report the results of the iBRA National Practice Questionnaire (NPQ) which aimed to comprehensively describe the provision and practice of IBBR across the UK. Methods A questionnaire investigating local practice and service provision of IBBR developed by the iBRA Steering Group was completed by trainee and consultant leads at breast and plastic surgical units across the UK. Summary data for each survey item were calculated and variation between centres and overall provision of care examined. Results 81 units within 79 NHS-hospitals completed the questionnaire. Units offered a range of reconstructive techniques, with IBBR accounting for 70% (IQR:50–80%) of participating units' immediate procedures. Units on average were staffed by 2.5 breast surgeons (IQR:2.0–3.0) and 2.0 plastic surgeons (IQR:1.0–3.0) performing 35 IBBR cases per year (IQR:20-50). Variation was demonstrated in the provision of novel different techniques for IBBR especially the use of biological (n = 62) and synthetic (n = 25) meshes and in patient selection for these procedures. Conclusions The iBRA-NPQ has demonstrated marked variation in the provision and practice of IBBR in the UK. The prospective audit phase of the iBRA study will determine the safety and effectiveness of different approaches to IBBR and allow evidence-based best practice to be explored

Identification of diarrheagenic Escherichia coli isolated from infants and children in Dar es Salaam, Tanzania

<p>Abstract</p> <p>Background</p> <p>Relatively few studies have been done in Tanzania to detect and classify diarrheagenic <it>Escherichia coli </it>(DEC) strains among children with diarrhea. This study aimed at investigating DEC among children in Dar es Salaam aged less than five years hospitalized due to acute/persistent diarrhea.</p> <p>Methods</p> <p>DEC were isolated from stool samples collected from two hundred and eighty children with acute/persistent diarrhea at Muhimbili National Hospital and Ilala and Mwananyamala Municipal Hospitals in Dar es Salaam. A multiplex PCR system method was used to detect a species specific gene for <it>E.coli </it>and ten different virulence genes for detection of five pathogroups of DEC namely enteroaggregative- (EAEC), enteropathogenic- (EPEC), enterotoxigenic- (ETEC), enteroinvasive- (EIEC) and enterohemorghagic- <it>Escherichia coli </it>(EHEC).</p> <p>Results</p> <p>Sixty-four patients (22.9%) harbored DEC. Forty-one of them (14.6%) were categorized as EAEC. Most of the EAEC (82.9%) were classified as typical EAEC possessing the <it>aggR </it>gene, and 92.6% carried the <it>aat </it>gene. Isolates from thirteen patients were EPEC (4.6%) and most of these (92.3%) were typical EPEC with both <it>eae </it>and <it>bfpA </it>genes. Ten isolates were identified as ETEC (3.6%) with only the heat stable toxin; either <it>st1a </it>or <it>st1b </it>but not both. Age wise, EAEC and EPEC were significantly more prevalent among the age group 0–6 months (p < 0.05). Genes for EHEC (<it>stx</it>₁and <it>stx</it>₂) and EIEC <it>(ial</it>) were not detected in this study group.</p> <p>Conclusion</p> <p>The results show a high proportion of DEC among Tanzanian children with diarrhea, with typical EAEC and typical EPEC predominating. The use of primers for both variants of ST1 (st1a and st1b) increased the sensitivity for detection of ETEC strains.</p

Single-cell RNA-seq supports a developmental hierarchy in human oligodendroglioma

Although human tumours are shaped by the genetic evolution of cancer cells, evidence also suggests that they display hierarchies related to developmental pathways and epigenetic programs in which cancer stem cells (CSCs) can drive tumour growth and give rise to differentiated progeny. Yet, unbiased evidence for CSCs in solid human malignancies remains elusive. Here we profile 4,347 single cells from six IDH1 or IDH2 mutant human oligodendrogliomas by RNA sequencing (RNA-seq) and reconstruct their developmental programs from genome-wide expression signatures. We infer that most cancer cells are differentiated along two specialized glial programs, whereas a rare subpopulation of cells is undifferentiated and associated with a neural stem cell expression program. Cells with expression signatures for proliferation are highly enriched in this rare subpopulation, consistent with a model in which CSCs are primarily responsible for fuelling the growth of oligodendroglioma in humans. Analysis of copy number variation (CNV) shows that distinct CNV sub-clones within tumours display similar cellular hierarchies, suggesting that the architecture of oligodendroglioma is primarily dictated by developmental programs. Subclonal point mutation analysis supports a similar model, although a full phylogenetic tree would be required to definitively determine the effect of genetic evolution on the inferred hierarchies. Our single-cell analyses provide insight into the cellular architecture of oligodendrogliomas at single-cell resolution and support the cancer stem cell model, with substantial implications for disease management

Gap Junctions and Epileptic Seizures – Two Sides of the Same Coin?

Electrical synapses (gap junctions) play a pivotal role in the synchronization of neuronal ensembles which also makes them likely agonists of pathological brain activity. Although large body of experimental data and theoretical considerations indicate that coupling neurons by electrical synapses promotes synchronous activity (and thus is potentially epileptogenic), some recent evidence questions the hypothesis of gap junctions being among purely epileptogenic factors. In particular, an expression of inter-neuronal gap junctions is often found to be higher after the experimentally induced seizures than before. Here we used a computational modeling approach to address the role of neuronal gap junctions in shaping the stability of a network to perturbations that are often associated with the onset of epileptic seizures. We show that under some circumstances, the addition of gap junctions can increase the dynamical stability of a network and thus suppress the collective electrical activity associated with seizures. This implies that the experimentally observed post-seizure additions of gap junctions could serve to prevent further escalations, suggesting furthermore that they are a consequence of an adaptive response of the neuronal network to the pathological activity. However, if the seizures are strong and persistent, our model predicts the existence of a critical tipping point after which additional gap junctions no longer suppress but strongly facilitate the escalation of epileptic seizures. Our results thus reveal a complex role of electrical coupling in relation to epileptiform events. Which dynamic scenario (seizure suppression or seizure escalation) is ultimately adopted by the network depends critically on the strength and duration of seizures, in turn emphasizing the importance of temporal and causal aspects when linking gap junctions with epilepsy

Single-Cell Transcriptional Analysis of Normal, Aberrant, and Malignant Hematopoiesis in Zebrafish

Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, the lack of cell surface antibodies has compelled researchers to use fluorescent transgenic reporter lines to label specific blood cell fractions. However, these approaches are limited by the availability of transgenic lines and fluorescent protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish to define erythroid, myeloid, B, and T cell lineages. We also used our approach to identify hematopoietic stem and progenitor cells and a novel NK-lysin 4+ cell type, representing a putative cytotoxic T/NK cell. Our platform also quantified hematopoietic defects in rag2E450fs mutant fish and showed that these fish have reduced T cells with a subsequent expansion of NK-lysin 4+ cells and myeloid cells. These data suggest compensatory regulation of the innate immune system in rag2E450fs mutant zebrafish. Finally, analysis of Myc-induced T cell acute lymphoblastic leukemia showed that cells are arrested at the CD4+/CD8+ cortical thymocyte stage and that a subset of leukemia cells inappropriately reexpress stem cell genes, including bmi1 and cmyb. In total, our experiments provide new tools and biological insights into single-cell heterogeneity found in zebrafish blood and leukemia

R5-SHIV Induces Multiple Defects in T Cell Function during Early Infection of Rhesus Macaques Including Accumulation of T Reg Cells in Lymph Nodes

Background: HIV-1 is a pathogen that T cell responses fail to control. HIV-1gp120 is the surface viral envelope glycoprotein that interacts with CD4 T cells and mediates entry. HIV-1gp120 has been implicated in immune dysregulatory functions that may limit anti-HIV antigen-specific T cell responses. We hypothesized that in the context of early SHIV infection, immune dysregulation of antigen-specific T-effector cell and regulatory functions would be detectable and that these would be associated or correlated with measurable concentrations of HIV-1gp120 in lymphoid tissues. Methods: Rhesus macaques were intravaginally inoculated with a Clade C CCR5-tropic simian-human immunodeficiency virus, SHIV-1157ipd3N4. HIV-1gp120 levels, antigen-specificity, levels of apoptosis/anergy and frequency and function of Tregs were examined in lymph node and blood derived T cells at 5 and 12 weeks post inoculation. Results/Conclusions: We observed reduced responses to Gag in CD4 and gp120 in CD8 lymph node-derived T cells compared to the peripheral blood at 5 weeks post-inoculation. Reduced antigen-specific responses were associated with higher levels of PD-1 on lymph node-derived CD4 T cells as compared to peripheral blood and uninfected lymph node-derived CD4 T cells. Lymph nodes contained increased numbers of Tregs as compared to peripheral blood, which positively correlated with gp120 levels; T regulatory cell depletion restored CD8 T cell responses to Gag but not to gp120. HIV gp120 was also able to induce T regulatory cell chemotaxis in a dose-dependent, CCR5-mediated manner. These studies contribute to our broader understanding of the ways in which HIV-1 dysregulates T cell function and localization during early infection