Impact of Th1 CD4 Follicular Helper T Cell Skewing on Antibody Responses to an HIV-1 Vaccine in Rhesus Macaques.

Generating durable humoral immunity through vaccination depends upon effective interactions of follicular helper T (Tfh) cells with germinal center (GC) B cells. Th1 polarization of Tfh cells is an important process shaping the success of Tfh-GC B cell interactions by influencing costimulatory and cytokine-dependent Tfh help to B cells. However, the question remains as to whether adjuvant-dependent modulation of Tfh cells enhances HIV-1 vaccine-induced antienvelope (anti-Env) antibody responses. We investigated whether an HIV-1 vaccine platform designed to increase the number of Th1-polarized Tfh cells enhances the magnitude and quality of anti-Env antibodies. Utilizing a novel interferon-induced protein 10 (IP-10)-adjuvanted HIV-1 DNA prime followed by a monophosphoryl lipid A and QS-21 (MPLA+QS-21)-adjuvanted Env protein boost (DIP-10 PALFQ) in macaques, we observed higher anti-Env serum IgG titers with greater cross-clade reactivity, specificity for V1V2, and effector functions than in macaques primed with DNA lacking IP-10 and boosted with MPLA-plus-alum-adjuvanted Env protein (DPALFA) The DIP-10 PALFQ vaccine regimen elicited higher anti-Env IgG1 and lower IgG4 antibody levels in serum, showing for the first time that adjuvants can dramatically impact the IgG subclass profile in macaques. The DIP-10 PALFQ regimen also increased vaginal and rectal IgA antibodies to a greater extent. Within lymph nodes, we observed augmented GC B cell responses and the promotion of Th1 gene expression profiles in GC Tfh cells. The frequency of GC Tfh cells correlated with both the magnitude and avidity of anti-Env serum IgG. Together, these data suggest that adjuvant-induced stimulation of Th1-Tfh cells is an effective strategy for enhancing the magnitude and quality of anti-Env antibody responses.IMPORTANCE The results of the RV144 trial demonstrated that vaccination could prevent HIV transmission in humans and that longevity of anti-Env antibodies may be key to this protection. Efforts to improve upon the prime-boost vaccine regimen used in RV144 have indicated that booster immunizations can increase serum anti-Env antibody titers but only transiently. Poor antibody durability hampers efforts to develop an effective HIV-1 vaccine. This study was designed to identify the specific elements involved in the immunological mechanism necessary to produce robust HIV-1-specific antibodies in rhesus macaques. By clearly defining immune-mediated pathways that improve the magnitude and functionality of the anti-HIV-1 antibody response, we will have the foundation necessary for the rational development of an HIV-1 vaccine

Synthesis, Optical and Electrical Properties of ZnFe2O4 Nanocomposites

ZnFe2O4 nanocomposites have been prepared by a simple co‐precipitation method. The prepared samples were characterized by Scanning Electron Microscopy (SEM), Powder X‐ray Diffraction (XRD), Energy Disperse X‐ray Analysis (EDX), Transmission electron microscopy (TEM) and UV‐visible absorption spectral techniques. Conductivity measurements show a transition from ferrimagnetism to paramagnetism. The enhancement in fluorescence spectra shows that there is an electronic transition to an exciting level. In UV‐Vis spectra, the peak observed at 647nm indicates ZnFe2O4 nanocomposites are a photoactive compound. The above results suggest that these nanomateria

Modulation of macro and micronutrients to enhance lipid production by <i>Scenedesmus abundans</i> in a flat-panel photobioreactor under outdoor natural sunlight

The present study investigates the effect of macro- and micronutrients on photoautotrophic lipid production from Scenedesmus abundans. An optimized lipid medium has been formulated using one-at-a-time variation of macronutrients and a study of micronutrient interactions. Both single-stage and two-stage strategies were used for simultaneous production of lipid and exopolysaccharide (EPS) in medium-scale photobioreactors (PBRs) using the optimized lipid medium. In the single-stage cultivation 32% fatty acid methyl ester (FAME, biodiesel) was achieved, whereas only 12.6% FAME was observed in two-stage PBR. A FAME titer of 1.16 g/L with overall FAME productivity of 32 mg/L/day and 280 mg/L EPS was achieved using the single-stage strategy. Further, under diurnal natural sunlight and outdoor conditions, a FAME content of 46%, with 1.28 g/L of FAME and 27 mg/L/day FAME productivity, and 155 mg/L EPS were achieved using the single-stage strategy in 2 L medium-scale flat-panel PBRs. Apart from high biodiesel and EPS production, this microalgal strain also has the ability to carry out natural autoflocculation with high efficiency. The strain could be exploited for high lipid content under outdoor cultivation without photoinhibition. Micronutrients have effects on lipid accumulation in Scenedesmus abundans. Scenedesmus abundans produced high biodiesel content (46% of DCW) under natural sunlight. Simultaneous synthesis of multiproducts by this candidate paves the way for biorefining.</p

Journal of Clinical and Diagnostic Research [serial online

ABSTRACT Purpose The incidence of Extended Spectrum β -Lactamase (ESBL) producing strains among clinical Klebsiella species and Escherichia coli isolates has been steadily increasing over the past years. ESBL producing organisms pose a major problem for clinical therapeutics. Identifying organisms that are ESBL producers are a major challenge for the clinical microbiology laboratory. An attempt was therefore made to study ESBL production and multidrug resistance in clinical isolates of K.pneumoniae and E.coli at a hospital in Mangalore. Method ESBL production and multidrug resistance was studied in a total of 228 isolates of K.pneumoniae and E.coli which were obtained from various clinical samples during one year period from January to December 2008. Identification of the isolates was done based on cultural characteristics and reactions in standard biochemical tests. All the isolates were tested for antimicrobial susceptibility by the disk diffusion technique according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The screening for ESBL production was done by the phenotypic confirmatory test using ceftazidime discs in the presence and absence of clavulanic acid. Result All the isolates showed resistance or decreased susceptibility to at least one of the third generation cephalosporins (ceftazidime, cefotaxime, ceftriaxone) which were used for the study. ESBL production was noted in 59.65% of the isolates tested. ESBL production was detected in 51.47% strains of E.coli and 48.53% strains of K.pneumoniae (70% of E.coli isolated from urine samples and 75% of K.pneumoniae isolated from exudates samples were ESBL producers). All the isolates were found to be sensitive to the antibiotic, imipenem. Sensitivity of E.coli to piperacillin-tazobactum (Pt) and cefaperazone-sulbactum (Cfs) was 100%, whereas K.pneumoniae showed 98% sensitive to Pt and 88% sensitive to Cfs. Conclusion The study has shown an increase in the incidence of ESBL producing E.coli and K.pneumoniae strains in Mangalore. The prevalence of ESBL and multidrug resistant strains constitute a serious threat to the current β-lactam therapy. Tests for the detection of ESBL producing bacteria should be carried out at all diagnostic centers routinely and the use of third generation cephalosporins should be restricted. This can reduce the prevalence of ESBL producing organisms

Asian Journal of Agricultural Extension, Economics & Sociology

Not AvailableBuilding an effective online course requires an understanding of learning analytics. The study assumes significance in the COVID 19 pandemic situation as there is a sudden surge in online courses. Analysis of the online course using the data generated from the Moodle Learning Management System (LMS), Google Forms and Google Analytics was carried out to understand the tenants of an effective online course. About 515 learners participated in the initial pre-training needs & expectations? survey and 472 learners gave feedback at the end, apart from the real-time data generated from LMS and Google Analytics during the course period. This case study analysed online learning behaviour and the supporting learning environment and suggest critical factors to be at the centre stage in the design and development of online courses; leads to the improved online learning experience and thus the quality of education. User needs, quality of resources and effectiveness of online courses are equally important in taking further online courses

Additional file 1 of Neuroinflammatory transcriptional programs induced in rhesus pre-frontal cortex white matter during acute SHIV infection

Additional file 1: Fig. S1. Ranked genes by median normalized read counts in units of Log2 counts per million (Log2CPM) in the subcortical white matter of the pre-frontal cortex (PFCw), and gray matter of the superior temporal sulcus (STS), caudate nucleus (CN), and hippocampus (HP) of uninfected animals. Dotted lines indicate location of marker genes associated with neurons (MAP2), astrocytes (GFAP), microglia (P2RY12), and oligodendrocytes (MOG) within ranked distribution. Fig. S2. T-stochastic neighborhood embedding analysis (t-SNE) of gene expression profiles from the pre-frontal cortex white matter (black), superior temporal sulcus (blue), caudate nucleus (red), and hippocampus (green) of uninfected animals. Outlier sample [Animal 43661 pre-frontal cortex white matter] is included. Symbols represent individual animals. Circles indicate 95% confidence intervals. Fig. S3. Regional eigengene expression and corresponding top fifteen most significantly enriched (p < 0.01 by Fisher’s exact test) biological processes GO terms within region specific modules (PFCw-specific [MEmagenta, MEmidnightblue], STS-specific [MEtan], CN-specific [MEpurple, MEred], HP-specific [MEsalmon]) determined by weighted gene co-expression network analysis from uninfected animals. *p < 0.05 by linear mixed effects model (region effect). Boxplots represent quartiles. Fig. S4. Normalized read counts of genes encoding for chemokines in the STS (blue), PFCw (black), CN (red), and HP (green) of uninfected animals. Expression levels are displayed in normalized read counts in units of Log2 counts per million (Log2CPM). Brackets indicate structural chemokine classes. Fig. S5. Log2 Fold change of genes regulating inflammatory processes and synaptic functions between SHIV infected and uninfected animals in all brain regions (gray), STS (blue), and PFCw (red). Dotted line indicates a fold change of 1. Fig. S6. T-stochastic neighborhood embedding (t-SNE) analysis of gene expression profiles from SHIV infected and uninfected animals. (Left) t-SNE plot indicates clustering of gene expression profiles by region and SHIV infection status (SHIV infected [pink], uninfected [black]) with removal of outlier sample [Animal 43661 Pre-frontal cortex white matter]. (Right) t-SNE plot shows all samples including the outlier with data points indicating regions (pre-frontal cortex white matter (P), superior temporal sulcus [S], caudate nucleus [C], hippocampus [H]) and infection status (color) and individual animals (symbols). Circles indicate 95% confidence intervals. Fig. S7 Expression levels of genes (expressed as normalized read counts in units of Log2 Counts per million [CPM]) related to synaptic functions, endoplasmic reticulum stress, and ATP synthase subunits in the PFCw of SHIV infected (red) and uninfected (gray) animals. Violin plots indicate quartiles. P values determined by linear mixed effects model. Table S1 Animal/Sample Data. Animal information—Animal ID, Sex, Age, SHIV infection status, and medical cull rationale. Sample Information—Sample ID, Sample Code, Tissue identity, Tissue weight (mg), purified RNA absorbance ratios (A260/A280 and A260/A230), and sample RNA yield. Table S3. Reagents used for flow cytometric analysis