Myotubularin-related protein-6 silencing protects mice from Leishmania donovani infection.

The protozoan parasite Leishmania donovani resides within mammalian macrophages and alters its antigen-presenting functions to negatively regulate host-protective T cell responses. This negative regulation of human T cell responses in vitro is attributed to myotubularin-related protein-6 (MTMR6), an ion channel-associated phosphatase. As mouse and human MTMR6 share homology, we studied whether MTMR6 silencing by lentivirally expressed MTMR6shRNA (Lv-MTMR6shRNA) reduced Leishmania growth in macrophages and whether MTMR6 silencing in Leishmania-susceptible BALB/c mice reduced the infection and reinstated host-protective T cell functions.

Advantage of neuroeducation in managing mass psychogenic illness among rural school children in Nepal.

Introduction: Mass psychogenic illness (MPI), also known as mass hysteria (MH), is a mental health disorder that frequently occurs in Nepal. It primarily affects female students in government high schools and occurs during the course of the school day over a few days without corresponding organic causes.

Purpose Of The Study: This study set out to evaluate and give neuroeducation with the goal of preventing and/or managing MPI after documenting the existing state of knowledge regarding MPI.

Development of the Antileishmanial Vaccine.

Search for an efficacious antileishmanial vaccine has led to clinical trials of numerous vaccine candidates in the past few decades. As no promising candidate has emerged from these studies, novel vaccine modalities and vaccine assessment techniques are still emerging for antileishmanial vaccine development. Briefly, this chapter discusses: (a) history and timeline of antileishmanial vaccine development; (b) techniques utilized for developing whole-parasite and subunit-based antileishmanial vaccine formulations, and (c) immunogenicity and post-challenge protective efficacy assessment of vaccine candidates.

Mechanism of noncoding RNA-associated N-methyladenosine recognition by an RNA processing complex during IgH DNA recombination.

Immunoglobulin heavy chain (IgH) locus-associated G-rich long noncoding RNA (SμGLT) is important for physiological and pathological B cell DNA recombination. We demonstrate that the METTL3 enzyme-catalyzed N-methyladenosine (mA) RNA modification drives recognition and 3' end processing of SμGLT by the RNA exosome, promoting class switch recombination (CSR) and suppressing chromosomal translocations. The recognition is driven by interaction of the MPP6 adaptor protein with nuclear mA reader YTHDC1.

LmjF.36.3850, a novel hypothetical Leishmania major protein, contributes to the infection.

Leishmania is a protozoan parasite that resides in mammalian macrophages and inflicts the disease known as leishmaniasis. Although prevalent in 88 countries, an anti-leishmanial vaccine remains elusive. While comparing the virulent and avirulent L.

Residue-Specific Message Encoding in CD40-Ligand.

CD40-Ligand (CD40L)-CD40 interaction regulates immune responses against pathogens, autoantigens, and tumor and transplantation antigens. Single amino acid mutations within the 115-155 amino acids stretch, which is responsible for CD40L functions, result in XIgM syndrome. We hypothesize that each of these amino acids of CD40L encodes specific message that, when decoded by CD40 signaling, induces a specific profile of functions.

Development and Characterization of an Avirulent Strain.

causes cutaneous leishmaniasis. An antileishmanial vaccine for humans is unavailable. In this study, we report development of two attenuated strains-5ASKH-HP and LV39-HP-by continuous culture (high passage) of the corresponding virulent strains (low passage).

Ras isoforms selectively regulate antigen-specific immune response.

H-/K-Ras and N-Ras isoforms were proposed to lack functional specificities due to similarity in 1-165 amino acids. As recent studies implied Ras isoform-specific developmental effects, we examined their functional specificity using Leishmania major infection, anti-hapten antibody response and carrier-specific T cell response. While N-Ras overexpression increased L.

A Leishmania donovani dominant-negative mutant for eIF2α kinase LdeK1 elicits host-protective immune response.

Dominant-negative mutation of LdeK1 gene, an eIF2α kinase from Leishmania donovani, revealed its role in translation regulation in response to nutrient starvation earlier. However, whether the kinase influences the infectivity of the parasites which naturally encounters nutrient deprivation during its life cycle was interesting to investigate. Both in vitro and in vivo experiments resulted in decrease of the parasite burden in peritoneal macrophages and in splenic/ hepatic load, respectively.

Prevalence of Color Blindness in Undergraduates of Kathmandu University.

Introduction: Color blindness is X-linked recessive inherited disorder that occurs mostly in males and is transmitted through females. Many people with color blindness may remain undetected. Thus the present study aims to evaluate the incidence of color blindness among undergraduates of Kathmandu University.

Visual Evoked Potentials in Primary Open Angle Glaucoma.

Background And Aims: Visual evoked potentials (VEPs) assess the integrity of the visual pathways from the optic nerve to the occipital cortex. Optic disc cupping and visual field loss have been associated with prolongation of latency of VEP in primary open angle glaucoma (POAG).

Methods: Pattern reversal and flash VEP tests were done in consenting 20 primary open angle glaucoma eyes and 40 normal control eyes.

Neuroscience Symposium and Workshop on SAAPCON-2016, Nepal.

Physiological Society of Nepal, with support from the South Asian Association of Physiologists (SAAP), organized the 5th Biennial Conference of the South Asian Association of Physiologists in conjunction with the 2nd Annual Conference of Physiological Society of Nepal. The purpose of this conference is to bring the scientists, researchers, and students from the South Asian countries in one platform to share and discuss the recent advances and achievements in the field of physiology. Since physiology is the backbone of medical science which deals with the functions of the human body, the theme of the conference was given as "Redefining health in nature.

Inhibition of CD40-induced N-Ras activation reduces leishmania major infection.

Leishmania major is a parasite that resides and replicates in macrophages. We previously showed that the parasite enhanced CD40-induced Raf-MEK-ERK signaling but inhibited PI3K-MKK-p38MAPK signaling to proleishmanial effects. As Raf and PI3K have a Ras-binding domain but exert opposite effects on Leishmania infection, we examined whether Ras isoforms had differential roles in Leishmania infection.

The host-protective effect of arabinosylated lipoarabinomannan against Leishmania donovani infection is associated with restoration of IFN-γ responsiveness.

Visceral leishmaniasis (VL), which is endemic as a major infectious disease in the tropical and subtropical countries, is caused by a protozoan parasite Leishmania donovani. At present, restricted treatment options and lack of vaccines intensify the problem of controlling VL. Therefore, finding a novel immunoprophylactic or therapeutic principle is a pressing need.

Pegylated bisacycloxypropylcysteine, a diacylated lipopeptide ligand of TLR6, plays a host-protective role against experimental Leishmania major infection.

TLRs recognize pathogen-expressed Ags and elicit host-protective immune response. Although TLR2 forms heterodimers with TLR1 or TLR6, recognizing different ligands, differences in the functions of these heterodimers remain unknown. In this study, we report that in Leishmania major-infected macrophages, the expression of TLR1 and TLR2, but not TLR6, increased; TLR2-TLR2 association increased, but TLR2-TLR6 association diminished.