Motor neuron-derived Thsd7a is essential for zebrafish vascular development via the Notch-dll4 signaling pathway.

BackgroundDevelopment of neural and vascular systems displays astonishing similarities among vertebrates. This parallelism is under a precise control of complex guidance signals and neurovascular interactions. Previously, our group identified a highly conserved neural protein called thrombospondin type I domain containing 7A (THSD7A). Soluble THSD7A promoted and guided endothelial cell migration, tube formation and sprouting. In addition, we showed that thsd7a could be detected in the nervous system and was required for intersegmental vessels (ISV) patterning during zebrafish development. However, the exact origin of THSD7A and its effect on neurovascular interaction remains unclear.ResultsIn this study, we discovered that zebrafish thsd7a was expressed in the primary motor neurons. Knockdown of Thsd7a disrupted normal primary motor neuron formation and ISV sprouting in the Tg(kdr:EGFP/mnx1:TagRFP) double transgenic zebrafish. Interestingly, we found that Thsd7a morphants displayed distinct phenotypes that are very similar to the loss of Notch-delta like 4 (dll4) signaling. Transcript profiling further revealed that expression levels of notch1b and its downstream targets, vegfr2/3 and nrarpb, were down-regulated in the Thsd7a morphants. These data supported that zebrafish Thsd7a could regulate angiogenic sprouting via Notch-dll4 signaling during development.ConclusionsOur results suggested that motor neuron-derived Thsd7a plays a significant role in neurovascular interactions. Thsd7a could regulate ISV angiogenesis via Notch-dll4 signaling. Thus, Thsd7a is a potent angioneurin involved in the development of both neural and vascular systems

A diagnostic challenge for schistosomiasis japonica in China: consequences on praziquantel-based morbidity control

Worldwide schistosomiasis continues to be a serious public health problem. Over the past five decades, China has made remarkable progress in reducing Schistosoma japonicum infections in humans to a relatively low level. Endemic regions are currently circumscribed in certain core areas where re-infection and repeated chemotherapy are frequent. At present, selective chemotherapy with praziquantel is one of the main strategies in China's National Schistosomiasis Control Program, and thus diagnosis of infected individuals is a key step for such control. In this paper we review the current status of our knowledge about diagnostic tools for schistosomiasis japonica. A simple, affordable, sensitive, and specific assay for field diagnosis of schistosomiasis japonica is not yet available, and this poses great barriers towards full control of schistosomiasis. Hence, a search for a diagnostic approach, which delivers these characteristics, is essential and should be given high priority

Role of CD5-negative CD8+ T Cells in Adaptation to Antigenic Variation of Human Immunodeficiency Virus Type 1

Purpose: To investigate the effect of 3-oxotirucalla-7, 24-dien-21-oic acid on CD8+ T cell recovery in human immunodeficiency virus type 1 (HIV-1) disease.Methods: The increase in the rates of CD8+ T cells over 48 weeks following treatment with 3- oxotirucalla-7, 24-dien-21-oic acid was investigated. Plasma HIV-1 load was measured by Versant™ HIV-1 RNA 3.0 branched chain DNA assay while flow cytometry was used for blood CD4 cell counts. For the analysis of the data obtained, Stata version 9.0 was employed.Results: 3-Oxotirucalla-7, 24-dien-21-oic acid treatment increased CD8+ T cell count from a median of 89 % at baseline to 99 % at 48 weeks. The proportion of patients with CD8+ T cell count < 90 % decreased from 50 % at baseline to 1 %. There was a similar rate of phase 1 CD8+ T cell recovery and greater rates of phase 2 recovery in patients with baseline CD8+ T counts < 50 cells/μL. Among those that achieved CD8+ T cell count > 500 cells/μL at 48 weeks, 23 % had baseline CD8+ T cell counts of < 50 cells/μL. However, the proportion of the patients that attained CD8+ T count of 200 cells/μL at 48 weeks was lower than those with higher baseline CD4 cell counts.Conclusion: 3-Oxotirucalla-7,24-dien-21-oic acid treatment induces greater tendency for CD8+ T cell recovery in patients with baseline CD8+ T cell counts < 50 cells/μL during 48 weeks of treatment. Therefore, 3-oxotirucalla-7,24-dien-21-oic acid is a promising agent for CD8+ T cell count recovery in patients with HIV infection.Keywords: CD8+ T cells, HIV infection, Oleanolic acid, Lymphocyte cell, Cell recover

A 90-DAY SUBCHRONIC TOXICOLOGICAL ASSESSMENT of DEINOCOCCUS GRANDIS FERMENTED SOYMILK IN SPRAGUE-DAWLEY RATS

Objective: Despite the fact that there was no adverse effect observed in previous animal safety studies of Deinococcus grandis (D. grandis) fermented soymilk, including acute oral toxicity assay, 3 different test systems of genotoxicity test and teratogenicity study, whether D. grandis fermented soymilk is safe for long-term use remains unknown. Therefore, the study was conducted further to clarify the edible safety of D. grandis fermented soymilk for long term use.Methods: Eighty Sprague-Dawley (SD) rats were divided into four groups, each consisting of ten male and ten female rats. Rats were orally administrated with reverse osmosis water (control) or 1,000, 2,000 and 3,000 mg/kg b.w./d freeze dried D. grandis fermented soymilk powder for 90 consecutive days. Clinical observation of the rats was carried out daily. The body weight and feed intake of the rats were recorded weekly. At the end of the study, all rats were sacrificed and the blood and organs were collected for hematology, clinical biochemistry and histopathological examination.Results: During the study period, no abnormality occurred in clinical signs, body weight, and ophthalmological examination. There were no significant differences in urinalysis, hematology and clinical biochemistry parameters between the treatment and control group. Necropsy and histopathological examination showed no treatment-related change.Conclusion: According to the results, the no-observed-adverse-effect level (NOAEL) of D. grandis fermented soymilk was greater than 3,000 mg/kg b.w./d in SD rats.Keywords: Deinococcus grandis (D. grandis), 90-day subchronic toxicity, NOAEL, Safety assessment, GKB-Aid 199

Pattern formation of a pathway-based diffusion model: linear stability analysis and an asymptotic preserving method

We investigate the linear stability analysis of a pathway-based diffusion model (PBDM), which characterizes the dynamics of the engineered Escherichia coli populations [X. Xue and C. Xue and M. Tang, P LoS Computational Biology, 14 (2018), pp. e1006178]. This stability analysis considers small perturbations of the density and chemical concentration around two non-trivial steady states, and the linearized equations are transformed into a generalized eigenvalue problem. By formal analysis, when the internal variable responds to the outside signal fast enough, the PBDM converges to an anisotropic diffusion model, for which the probability density distribution in the internal variable becomes a delta function. We introduce an asymptotic preserving (AP) scheme for the PBDM that converges to a stable limit scheme consistent with the anisotropic diffusion model. Further numerical simulations demonstrate the theoretical results of linear stability analysis, i.e., the pattern formation, and the convergence of the AP scheme