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

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

Minimal Hepatic Encephalopathy in Patients with Alcohol Related and Non-alcoholic Steatohepatitis Related Cirrhosis by Psychometric Hepatic Cephalopathy Score and Critical Flicker Frequency

Background: alcohol may have additional neurotoxic ill-effects in patients with alcohol related cirrhosis apart from hepatic encephalopathy. We aimed to evaluate minimal hepatic encephalopathy (MHE) with Psychometric Hepatic Encephalopathy (PHES) score and Critical Flicker Frequency (CFF) in alcohol (ALD) and non-alcoholic steatohepatitis related (NASH) related cirrhosis. Methods: 398 patients were screened between March 2016 and December 2018; of which 71 patients were included in ALD group and 69 in NASH group. All included patients underwent psychometric tests which included number connection test A and B (NCT-A and NCT-B), serial dot test (SDT), digit symbol test (DST), line tracing test (LTT) and CFF. MHE was diagnosed when their PHES was <-4. Results: the prevalence of MHE was significantly higher in ALD group compared to NASH (69.01% vs 40.58%; P=0.007). The performance of individual psychometric tests was significantly poorer in ALD (P<0.05). Overall sensitivity and specificity of CFF was 76.62% (95%CI 65.59 – 85.52) and 46.03% (95%CI 33.39 – 59.06) respectively. Mean CFF was significantly lower in ALD than NASH (37.07 (SD 2.37) vs 39.05 (SD 2.40), P=0.001); also in presence of MHE (36.95 (SD 2.04) vs 37.96 (SD 1.87), P=0.033) and absence of MHE (37.34 (SD 3.01) vs 39.79 (SD 2.46), P=0.001). Conclusion: MHE is significantly more common in patients with ALD cirrhosis than NASH counterparts. Overall CFF values are less in alcohol related cirrhosis than NASH related cirrhosis, even in presence or absence of MHE. We recommend additional caution in managing MHE in ALD cirrhosis

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

Chronic SIV-induced neuroinflammation disrupts CCR7+CD4+ T cell immunosurveillance in the rhesus macaque brain

CD4+ T cells survey and maintain immune homeostasis in the brain, yet their differentiation states and functional capabilities remain unclear. Our approach, combining single-cell transcriptomic analysis, ATAC-Seq, spatial transcriptomics, and flow cytometry, revealed a distinct subset of CCR7+ CD4+ T cells resembling lymph node central memory (TCM) cells. We observed chromatin accessibility at the CCR7, CD28, and BCL-6 loci, defining molecular features of TCM. Brain CCR7+ CD4+ T cells exhibited recall proliferation and interleukin-2 production ex vivo, showcasing their functional competence. We identified the skull bone marrow as a local niche for these cells alongside CNS border tissues. Sequestering TCM cells in lymph nodes using FTY720 led to reduced CCR7+ CD4+ T cell frequencies in the cerebrospinal fluid, accompanied by increased monocyte levels and soluble markers indicating immune activation. In macaques chronically infected with SIVCL757 and experiencing viral rebound due to cessation of antiretroviral therapy, a decrease in brain CCR7+ CD4+ T cells was observed, along with increased microglial activation and initiation of neurodegenerative pathways. Our findings highlight a role for CCR7+ CD4+ T cells in CNS immune surveillance, and their decline during chronic SIV highlights their responsiveness to neuroinflammation

Additional file 2 of Neuroinflammatory transcriptional programs induced in rhesus pre-frontal cortex white matter during acute SHIV infection

Additional file 2: Table S2. Normalized Read Counts. Normalized read counts in units of Log2 Counts per Million (CPM). Sample IDs are listed in row 1 and correspond to Code in Table S1. Corresponding Gene.stable.ID and Gene names are listed in columns 1 and 2

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

Monoclonal antibodies protect aged rhesus macaques from SARS-CoV-2-induced immune activation and neuroinflammation.

Anti-viral monoclonal antibody (mAb) treatments may provide immediate but short-term immunity from coronavirus disease 2019 (COVID-19) in high-risk populations, such as people with diabetes and the elderly; however, data on their efficacy in these populations are limited. We demonstrate that prophylactic mAb treatment blocks viral replication in both the upper and lower respiratory tracts in aged, type 2 diabetic rhesus macaques. mAb infusion dramatically curtails severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-mediated stimulation of interferon-induced chemokines and T&nbsp;cell activation, significantly reducing development of interstitial pneumonia. Furthermore, mAb infusion significantly dampens the greater than 3-fold increase in SARS-CoV-2-induced effector CD4 T&nbsp;cell influx into the cerebrospinal fluid. Our data show that neutralizing mAbs administered preventatively to high-risk populations may mitigate the adverse inflammatory consequences of SARS-CoV-2 exposure

SARS-CoV-2 induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques.

CD4 T follicular helper (Tfh) cells are important for the generation of durable and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center (GC) response is an important question as we investigate&nbsp;vaccine induced&nbsp;immunity against COVID-19. Here, we report that SARS-CoV-2 infection in rhesus macaques, either infused with convalescent plasma, normal plasma, or receiving no infusion, resulted in transient accumulation of pro-inflammatory monocytes and proliferating Tfh cells with a Th1 profile in peripheral blood. CD4 helper cell responses skewed predominantly toward a Th1 response in blood, lung, and lymph nodes. SARS-CoV-2 Infection induced GC Tfh cells specific for the SARS-CoV-2 spike and nucleocapsid proteins, and a corresponding early appearance of antiviral serum IgG antibodies. Collectively, the data show induction of GC responses in a rhesus model of mild COVID-19