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1.
Chappuis F Sundar S Hailu A Ghalib H Rijal S Peeling RW Alvar J Boelaert M 《Nature reviews. Microbiology》2007,5(11):873-882
Visceral leishmaniasis (VL) is a systemic protozoan disease that is transmitted by phlebotomine sandflies. Poor and neglected populations in East Africa and the Indian sub-continent are particularly affected. Early and accurate diagnosis and treatment remain key components of VL control. In addition to improved diagnostic tests, accurate and simple tests are needed to identify treatment failures. Miltefosine, paromomycin and liposomal amphotericin B are gradually replacing pentavalent antimonials and conventional amphotericin B as the preferred treatments in some regions, but in other areas these drugs are still being evaluated in both mono- and combination therapies. New diagnostic tools and new treatment strategies will only have an impact if they are made widely available to patients. 相似文献
2.
Duangporn Jamsai Sewa Rijal Deborah M. Bianco Anne E. O'Connor Donna J. Merriner Stephanie J. Smith Gerard M. Gibbs Moira K. O'Bryan 《Biology of the cell / under the auspices of the European Cell Biology Organization》2010,102(2):93-106
Background information. CRISP2 (cysteine‐rich secretory protein 2) is a sperm acrosome and tail protein with the ability to regulate Ca2+ flow through ryanodine receptors. Based on these properties, CRISP2 has a potential role in fertilization through the regulation of ion signalling in the acrosome reaction and sperm motility. The purpose of the present study was to determine the expression, subcellular localization and the role in spermatogenesis of a novel CRISP2‐binding partner, which we have designated SHTAP (sperm head and tail associated protein). Results. Using yeast two‐hybrid screens of an adult testis expression library, we identified SHTAP as a novel mouse CRISP2‐binding partner. Sequence analysis of all Shtap cDNA clones revealed that the mouse Shtap gene is embedded within a gene encoding the unrelated protein NSUN4 (NOL1/NOP2/Sun domain family member 4). Five orthologues of the Shtap gene have been annotated in public databases. SHTAP and its orthologues showed no significant sequence similarity to any known protein or functional motifs, including NSUN4. Using an SHTAP antiserum, multiple SHTAP isoforms (~20–87 kDa) were detected in the testis, sperm, and various somatic tissues. Interestingly, only the ~26 kDa isoform of SHTAP was able to interact with CRISP2. Furthermore, yeast two‐hybrid assays showed that both the CAP (CRISP/antigen 5/pathogenesis related‐1) and CRISP domains of CRISP2 were required for maximal binding to SHTAP. SHTAP protein was localized to the peri‐acrosomal region of round spermatids, and the head and tail of the elongated spermatids and sperm tail where it co‐localized with CRISP2. During sperm capacitation, SHTAP and the SHTAP—CRISP2 complex appeared to be redistributed within the head. Conclusions. The present study is the first report of the identification, annotation and expression analysis of the mouse Shtap gene. The redistribution observed during sperm capacitation raises the possibility that SHTAP and the SHTAP—CRISP2 complex play a role in the attainment of sperm functional competence. 相似文献
3.
Lymphangiogenesis is a common phenomenon observed during inflammation and engraftment of transplants, but its precise role in the immune response and underlying mechanisms of regulation remain poorly defined. Here we showed that in response to injury and autoimmunity, lymphangiogenesis occurred around islets and played a key role in the islet inflammation in mice. Vascular endothelial growth factors receptor 3 (VEGFR3) is specifically involved in lymphangiogenesis, and blockade of VEGFR3 potently inhibited lymphangiogenesis in both islets and the draining LN during multiple low-dose streptozotocin (MLDS) induced autoimmune insulitis, which resulted in less T cell infiltration, preservation of islets and prevention of the onset of diabetes. In addition to their well-known conduit function, lymphatic endothelial cells (LEC) also produced chemokines in response to inflammation. These LEC attracted two distinct CX3CR1(hi) and LYVE-1(+) macrophage subsets to the inflamed islets and CX3CR1(hi) cells were influenced by LEC to differentiate into LYVE-1(+) cells closely associated with lymphatic vessels. These observations indicate a linkage among lymphangiogenesis and myeloid cell inflammation during insulitis. Thus, inhibition of lymphangiogenesis holds potential for treating insulitis and autoimmune diabetes. 相似文献
4.
The ability of activated T cells to present foreign antigens through the MHC class II pathway has been shown in the case of human, rat and mouse T cells. In the present study, the ability of activated T cells to present their endogenous TCR in association with MHC class II molecules to CD4+ T cells was shown. Upon activation mouse T cells downregulate their surface TCR, which are degraded into peptides in endosomal/lysosomal compartments. The idiopeptides (peptides derived from the variable region of the TCR) are presented to cognate anti-idiotypic CD4+ T cells, resulting in activation and proliferation of these cells. Interaction of idiotypic and anti-idiotypic T cells brought about by presentation of TCR idiopeptide may have important implications for T-cell vaccination and perpetuation of T-cell memory not requiring persisting antigen or long-lived memory cells. 相似文献
5.
Upadhaya AR Lungrin I Yamaguchi H Fändrich M Thal DR 《Journal of cellular and molecular medicine》2012,16(2):287-295
Alzheimer's disease (AD) is characterized by the aggregation and deposition of amyloid β protein (Aβ) in the brain. Soluble Aβ oligomers are thought to be toxic. To investigate the predominant species of Aβ protein that may play a role in AD pathogenesis, we performed biochemical analysis of AD and control brains. Sucrose buffer-soluble brain lysates were characterized in native form using blue native (BN)-PAGE and also in denatured form using SDS-PAGE followed by Western blot analysis. BN-PAGE analysis revealed a high-molecular weight smear (>1000 kD) of Aβ(42) -positive material in the AD brain, whereas low-molecular weight and monomeric Aβ species were not detected. SDS-PAGE analysis, on the other hand, allowed the detection of prominent Aβ monomer and dimer bands in AD cases but not in controls. Immunoelectron microscopy of immunoprecipitated oligomers and protofibrils/fibrils showed spherical and protofibrillar Aβ-positive material, thereby confirming the presence of high-molecular weight Aβ (hiMWAβ) aggregates in the AD brain. In vitro analysis of synthetic Aβ(40) - and Aβ(42) preparations revealed Aβ fibrils, protofibrils, and hiMWAβ oligomers that were detectable at the electron microscopic level and after BN-PAGE. Further, BN-PAGE analysis exhibited a monomer band and less prominent low-molecular weight Aβ (loMWAβ) oligomers. In contrast, SDS-PAGE showed large amounts of loMWAβ but no hiMWAβ(40) and strikingly reduced levels of hiMWAβ(42) . These results indicate that hiMWAβ aggregates, particularly Aβ(42) species, are most prevalent in the soluble fraction of the AD brain. Thus, soluble hiMWAβ aggregates may play an important role in the pathogenesis of AD either independently or as a reservoir for release of loMWAβ oligomers. 相似文献
6.
Kuan-Ying A. Huang Tiong Kit Tan Ting-Hua Chen Chung-Guei Huang Ruth Harvey Saira Hussain Cheng-Pin Chen Adam Harding Javier Gilbert-Jaramillo Xu Liu Michael Knight Lisa Schimanski Shin-Ru Shih Yi-Chun Lin Chien-Yu Cheng Shu-Hsing Cheng Yhu-Chering Huang Tzou-Yien Lin Jia-Tsrong Jan Che Ma William James Rodney S. Daniels John W. McCauley Pramila Rijal Alain R. Townsend 《PLoS pathogens》2021,17(12)
7.
Withania somnifera (WS) or its psychotropic preparation is known to play a critical role in morphine, alcohol and benzodiazepines addiction. This study investigates the role of WS in acute ethanol and withdrawal from chronic ethanol consumption using elevated plus maze paradigm in rats. Acute administration of ethanol (1.5-2 g/kg, ip) triggered anxiolytic effect and withdrawal from prolonged ethanol (9% v/v ethanol, 15 days) consumption elicited enhanced behavioral despair (anxiety). Acute administration of WS (50 mg/kg, oral) potentiated the anxiolytic action of subeffective dose of ethanol (0.5 or 1 g/kg, ip). Moreover, the ethanol withdrawal anxiety was markedly antagonized in dose dependent manner by WS at 200 and 500 mg/kg or higher dose of ethanol (2.5 g/kg). However, co-administration of subeffective doses of WS (50 mg/kg, oral) and ethanol also attenuated withdrawal-induced anxiety due to chronic ethanol (9% v/v ethanol, 15 days) consumption. The results suggest the protective effect of WS in the management of ethanol withdrawal reactions. 相似文献
8.
Decuypere S Vanaerschot M Rijal S Yardley V Maes L de Doncker S Chappuis F Dujardin JC 《Parasitology》2008,135(2):183-194
Gene expression profiling is increasingly used in the field of infectious diseases for characterization of host, pathogen and the nature of their interaction. The purpose of this study was to develop a robust, standardized method for comparative expression profiling and molecular characterization of Leishmania donovani clinical isolates. The limitations and possibilities associated with expression profiling in intracellular amastigotes and promastigotes were assessed through a series of comparative experiments in which technical and biological parameters were scrutinized. On a technical level, our results show that it is essential to use parasite harvesting procedures that involve minimal disturbance of the parasite's environment in order to 'freeze' gene expression levels instantly; this is particularly a delicate task for intracellular amastigotes and for specific 'sensory' genes. On the biological level, we demonstrate that gene expression levels fluctuate during in vitro development of both intracellular amastigotes and promastigotes. We chose to use expression-curves rather than single, specific, time-point measurements to capture this biological variation. Intracellular amastigote protocols need further refinement, but we describe a first generation tool for high-throughput comparative molecular characterization of patients' isolates, based on the changing expression profiles of promastigotes during in vitro differentiation. 相似文献
9.
Geometry of tapered fiber sensors critically affects the response of an evanescent field sensor to cell suspensions. Single-mode fibers (nominally at 1300 nm) were tapered to symmetric or asymmetric tapers with diameters in the range of 3–20 μm, and overall lengths of 1–7 mm. Their transmission characteristics in air, water and in the presence of Escherichia coli (JM101 strain) at concentrations of 100, 1000, 7000 and 7 million cells/mL were measured in the 400–800 nm range and gave rich spectral data that lead to the following conclusions. (1) No change in transmission was observed due to E. coli with tapers that showed no relative change in transmission in water compared to air. (2) Tapers that exhibited a significant difference in transmission in water compared to air gave weak response to the presence of the E. coli. Of these, tapers with low waist diameters (6 μm) showed sensitivity to E. coli at 7000 cells/mL and higher concentration. (3) Tapers that showed modest difference in water transmission compared to air, and those that had small waist diameters gave excellent response to E. coli at 100–7000 cells/mL. In addition, mathematical modeling showed that: (1) at low wavelength (470 nm) and small waist diameter (6 μm), transmission with water in the waist region is higher than in air. (2) Small changes in waist diameter (0.05 μm) can cause larger changes in transmission at 470 nm than at 550 nm at waist diameter of 6 μm. (3) For the same overall geometry, a 5.5 μm diameter taper showed larger refractive index sensitivity compared to a 6.25 μm taper at 470 nm. 相似文献
10.
Dinesh DS Das ML Picado A Roy L Rijal S Singh SP Das P Boelaert M Coosemans M 《PLoS neglected tropical diseases》2010,4(10):e859