Hypertension and Diabetes as a risk factor for dementia: a cross sectional study

Background: A relation between possible cardiovascular risk factors (hypertension and diabetes) and dementia has been studied in the past and an association has been documented, in spite of some studies pointing to the contrary. Our purpose is to analyze the relation between these risk factors and dementia and add some information to the existing concept and will try to conceptualize the pathogenesis of dementia.Methods: This was a cross sectional study. Patients were recruited from amongst those presenting to our department by convenient consecutive sampling method after taking consent. Five hundred patients of different types of dementia were enrolled. Hypertension was diagnosed using JNC7 criteria. World health organization (WHO) diagnostic criteria were used to diagnose diabetes mellitus. The open Epi software version 3 was used to find the absolute values after preparing 2×2 table. Continuous quantitative data were analyzed using chi square test. Odds ratio and Risk ratio were also calculated. For all statistical tests, a p Value less than 0.05 was taken to indicate significance.Results: Study provides the strong positive association of hypertension (HTN) and diabetes mellitus (DM) with vascular dementia (VaD) but the relationship of these risk factors were not positively correlated with other dementia. Conclusions: Positive association of these risk factors with vascular dementia were found but not with the other types of dementia

An immunostimulatory glycolipid that blocks SARS-CoV-2, RSV, and influenza infections in vivo

Prophylactic vaccines for SARS-CoV-2 have lowered the incidence of severe COVID-19, but emergence of viral variants that are antigenically distinct from the vaccine strains are of concern and additional, broadly acting preventive approaches are desirable. Here, we report on a glycolipid termed 7DW8-5 that exploits the host innate immune system to enable rapid control of viral infections in vivo. This glycolipid binds to CD1d on antigen-presenting cells and thereby stimulates NKT cells to release a cascade of cytokines and chemokines. The intranasal administration of 7DW8-5 prior to virus exposure significantly blocked infection by three different authentic variants of SARS-CoV-2, as well as by respiratory syncytial virus and influenza virus, in mice or hamsters. We also found that this protective antiviral effect is both host-directed and mechanism-specific, requiring both the CD1d molecule and interferon-[Formula: see text]. A chemical compound like 7DW8-5 that is easy to administer and cheap to manufacture may be useful not only in slowing the spread of COVID-19 but also in responding to future pandemics long before vaccines or drugs are developed

Isolation and characterization of IgM from Bengal goat blood serum

ABSTRACT Isolation of IgM from Bengal goat blood serum was carried out by centrifugation of the collected serum to eliminate the blood corpuscles and purity of serum was affirmed by the absence of pellets. Purified serum was obtained by ammonium sulphate precipitation. The isolated IgM obtained through dialysis, was quantified through silica gel chromatography using phosphate buffer saline (PBS) as a solvent with varied pH and obtained different fractions (namely I, II, III, IV and V). Quantification of protein was carried out by Lowry method and the molecular weight was determined by SDS-PAGE with a standard marker. The presence of IgM was confirmed by Immunodiffusion and Immuno Dot Blot. The results of the experiment suggest that Fractions I, II and III contain more stressed protein which has some similarity with ovalbumin. The resulting colour intensity obtained on performing Immuno Dot Blot using IgM as primary antibody, demonstrates that Fraction II contains maximum concentration of stressed protein

Weighted gene co-expression network analysis of nitrogen (N)-responsive genes and the putative role of G-quadruplexes in N use efficiency (NUE) in rice

Rice is an important target to improve crop nitrogen (N) use efficiency (NUE), and the identification and shortlisting of the candidate genes are still in progress. We analyzed data from 16 published N-responsive transcriptomes/microarrays to identify, eight datasets that contained the maximum number of 3020 common genes, referred to as N-responsive genes. These include different classes of transcription factors, transporters, miRNA targets, kinases and events of post-translational modifications. A Weighted gene co-expression network analysis (WGCNA) with all the 3020 N-responsive genes revealed 15 co-expression modules and their annotated biological roles. Protein-protein interaction network analysis of the main module revealed the hub genes and their functional annotation revealed their involvement in the ubiquitin process. Further, the occurrences of G-quadruplex sequences were examined, which are known to play important roles in epigenetic regulation but are hitherto unknown in N-response/NUE. Out of the 3020 N-responsive genes studied, 2298 contained G-quadruplex sequences. We compared these N-responsive genes containing G-quadruplex sequences with the 3601 genes we previously identified as NUE-related (for being both N-responsive and yield-associated). This analysis revealed 389 (17%) NUE-related genes containing G-quadruplex sequences. These genes may be involved in the epigenetic regulation of NUE, while the rest of the 83% (1811) genes may regulate NUE through genetic mechanisms and/or other epigenetic means besides G-quadruplexes. A few potentially important genes/processes identified as associated with NUE were experimentally validated in a pair of rice genotypes contrasting for NUE. The results from the WGCNA and G4 sequence analysis of N-responsive genes helped identify and shortlist six genes as candidates to improve NUE. Further, the hitherto unavailable segregation of genetic and epigenetic gene targets could aid in informed interventions through genetic and epigenetic means of crop improvement

A null mutation of the neuronal sodium channel NaV1.6 disrupts action potential propagation and excitation‐contraction coupling in the mouse heart

Evidence supports the expression of brain‐type sodium channels in the heart. Their functional role, however, remains controversial. We used global NaV1.6‐null mice to test the hypothesis that NaV1.6 contributes to the maintenance of propagation in the myocardium and to excitation‐contraction (EC) coupling. We demonstrated expression of transcripts encoding full‐length NaV1.6 in isolated ventricular myocytes and confirmed the striated pattern of NaV1.6 fluorescence in myocytes. On the ECG, the PR and QRS intervals were prolonged in the null mice, and the Ca2+ transients were longer in the null cells. Under patch clamping, at holding potential (HP) = –120 mV, the peak INa was similar in both phenotypes. However, at HP = –70 mV, the peak INa was smaller in the nulls. In optical mapping, at 4 mM [K+]o, 17 null hearts showed slight (7%) reduction of ventricular conduction velocity (CV) compared to 16 wild‐type hearts. At 12 mM [K+]o, CV was 25% slower in a subset of 9 null vs. 9 wild‐type hearts. These results highlight the importance of neuronal sodium channels in the heart, whereby NaV1.6 participates in EC coupling, and represents an intrinsic depolarizing reserve that contributes to excitation.—Noujaim, S. F., Kaur, K., Milstein, M., Jones, J. M., Furspan, P., Jiang, D., Auerbach, D. S., Herron, T., Meisler, M. H., Jalife, J. A null mutation of the neuronal sodium channel NaV1.6 disrupts action potential propagation and excitation‐contraction coupling in the mouse heart. FASEB J. 26, 63–72 (2012). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154524/1/fsb2fj10179770.pd

The bovine lactation genome: insights into the evolution of mammalian milk

Comparison of milk protein and mammary genes in the bovine genome with those from other mammals gives insights into the evolution of lactation

Presolar He and Ne Isotopes in Single Circumstellar SiC Grains

Noble gas isotopes in presolar silicon carbide (SiC) dust grains from primitive meteorites provide, together with major element isotopic compositions, insight into the nucleosynthetic output of different types of evolved stars >4.5 Gyr ago. We report here new results from helium and neon isotopic analyses of single presolar SiC grains with sizes between 0.6 and 6.3 μm using an ultrahigh sensitivity mass spectrometer. These noble gas studies were complemented by an ion microprobe study (NanoSIMS) of Si, C, and N isotopic compositions of the same grains. About 40%, or 46 of the 110 grains analyzed, contain nucleosynthetic 22Ne and/or 4He from their parent stars above our mass spectrometer's detection limit. We discuss the possible stellar sources using isotopic ratios as constraints combined with new model predictions for low- to intermediate-mass (1.5, 2, 3, and 5 M☉) asymptotic giant branch (AGB) stars of different metallicities (1, 1/2, 1/3, and 1/6 Z☉). Most SiC grains are of the mainstream type and originated in low-mass AGB stars. We find a higher-than-expected percentage of A/B type grains, with some containing 22Ne and/or 4He. In addition, we find one noble gas-rich nova grain candidate, one supernova grain (X-type grain), and one 22Ne-rich X- or Z-type grain candidate

Suppression subtractive hybridization coupled with microarray analysis to examine differential expression of genes in virus infected cells

High throughput detection of differential expression of genes is an efficient means of identifying genes and pathways that may play a role in biological systems under certain experimental conditions. There exist a variety of approaches that could be used to identify groups of genes that change in expression in response to a particular stimulus or environment. We here describe the application of suppression subtractive hybridization (SSH) coupled with cDNA microarray analysis for isolation and identification of chicken transcripts that change in expression on infection of host cells with a paramyxovirus. SSH was used for initial isolation of differentially expressed transcripts, a large-scale validation of which was accomplished by microarray analysis. The data reveals a large group of regulated genes constituting many biochemical pathways that could serve as targets for future investigations to explore their role in paramyxovirus pathogenesis. The detailed methods described herein could be useful and adaptable to any biological system for studying changes in gene expression

Kinesin-based transport of ectoplasmic specializations and localization of dynamin 3 in the testis

The Sertoli cell cytoskeleton plays a number of roles including intracellular transport, maintenance of cell shape, and formation of adhesion junctions. During spermatogenesis, the cytoskeleton plays a number of roles to ensure the proper formation of spermatids in the seminiferous epithelium. The epithelium is composed of the spermatogenic cells as well as Sertoli cells. Sertoli cells act as nurse cells and provide support and nourishment to the developing spermatids. The spermatids are attached to Sertoli cells through actin-rich adhesion complexes known as ectoplasmic specializations. During spermatogenesis, these junctions and the associated spermatids are hypothesized to be transported along polarized microtubule tracts in the Sertoli cell to the base of the seminiferous epithelium before retreating back to the apex of the epithelial tissue. Upon reaching the apex of the tissue, the ectoplasmic specializations are disassembled and spermatids are released into the lumen of the seminiferous epithelium. The study of this junction transport and disassembly will help to better understand mechanisms of spermatogenesis. Recent work has provided evidence that a dynein motor protein is the likely mechanism which transports the spermatid/ectoplasmic specialization junction to the apex of the epithelium. In addition, past work using mRNA GeneChip data arrays has identified the Rab6KIFL kinesin to be highly expressed in Sertoli cells. In chapter 2 of this thesis, I present evidence that antibodies raised against the Rab6KIFL protein are associated with ectoplasmic specializations and that this motor may be involved in spermatid entrenchment. Results indicate localization of antibodies at ectoplasmic specializations at times of spermatogenesis when entrenchment occurs and localization of antibodies on the cytoplasmic face of ectoplasmic specializations. In chapter 3 of this thesis I demonstrate that dynamin 3 is present at tubulobulbar complexes and when transfected into eGFP-nectin-2y MDCK cells tube like structures form. Dynamin 3 is highly expressed in testis however its function has been unexplored. Here I demonstrate that dynamin 3 may facilitate formation of these structures. The findings summarized in this thesis are integrated around the predominant subject of adhesion junction transport and disassembly. This work provides insight into mechanisms involved in spermatid translocation and release during spermatogenesis.Medicine, Faculty ofGraduat

BIOINFORMATICS APPLICATIONS NOTE Genome analysis ExPrimer: to design primers from exon–exon junctions

Summary: ExPrimer is a web-based computer program to design primers mainly from a specified exon–exon junction (E-E-jn) of a gene of interest. The tool suggests the optimum primer-pair(s) of which the right (reverse) primer represents a particular E-E-jn of the mRNA. The ‘product length ’ decides the location of the left primer. The results also include all other primer pairs considered and their ‘scores’. ExPrimer can use the NCBI BLASTn program for sequence specificity of primers. The tool is useful in many areas of molecular biology research that involve hybridization of short sequences with mRNA or cDNA. Availability