Membrane Binding and Cholesterol Sensing Motif in FtsZ: A Novel Mode of Membrane Recruitment for Bacterial FtsZ.

Cell division in bacteria is initiated by constriction of the Z-ring comprising two essential proteins, FtsZ and FtsA. Though the essential function of the Z-ring in bacterial division has been established, the precise roles of FtsZ and FtsA in the constriction process remain elusive. Due to the minimal number of components, FtsZ/FtsA in cell wall-less bacteria is an ideal model system for obtaining mechanistic insights into Z-ring constriction in the absence of a cell wall synthesis machinery.

Pharmacological restriction of genomic binding sites redirects PU.1 pioneer transcription factor activity.

Transcription factor (TF) DNA-binding dynamics govern cell fate and identity. However, our ability to pharmacologically control TF localization is limited. Here we leverage chemically driven binding site restriction leading to robust and DNA-sequence-specific redistribution of PU.

Universal penalized regression (Elastic-net) model with differentially methylated promoters for oral cancer prediction.

Background: DNA methylation showed notable potential to act as a diagnostic marker in many cancers. Many studies proposed DNA methylation biomarker in OSCC detection, while most of these studies are limited to specific cohorts or geographical location. However, the generalizability of DNA methylation as a diagnostic marker in oral cancer across different geographical locations is yet to be investigated.

Copper-induced pro-apoptotic response and its alleviation by Quercetin through autophagic modulation in HEPG2 cells.

Background: Recent studies indicated that the liver is susceptible to Cu-induced stress as it stores and distributes the metal to other cellular organelles. To counteract the hepatocytic damage, a known polyphenol, quercetin, was employed for its remarkable antioxidant properties. Thus, the study aimed to assess quercetin's potency against Cu-induced toxicity in HEPG2 cells.

Quercetin alleviates 6-OHDA-caused apoptosis in SH-SY5Y cells.

Aim: This study is primarily designed to investigate the potential neuroprotective effects of polyphenol against 6-OHDAcaused neurotoxicity on SH-SY5Y cells.

Materials And Methods: Cytotoxic effect of 6-OHDA and valuable role of quercetin, myricetin and kaempferol on SH-SY5Y cells were analyzed by MTT assay. Generation of 6-OHDA-stimulated reactive oxygen species (ROS) was measured using DCFDA fluorescence dye.

Isolation and characterization of mercury and multidrug-resistant Citrobacter freundii strains from tannery effluents in Kolkata, India.

Mercury (Hg) is one of the most potent toxic heavy metals that distresses livestock, humans, and ecological health. Owing to uncontrolled exposure to untreated tannery industrial effluents, metals such as Hg are increasing in nature and are, therefore, becoming a global concern. As a result, understanding the thriving microflora in that severe condition and their characteristics becomes immensely important.

Dynamics of interdomain rotation facilitates FtsZ filament assembly.

FtsZ, the tubulin homolog essential for bacterial cell division, assembles as the Z-ring at the division site, and directs peptidoglycan synthesis by treadmilling. It is unclear how FtsZ achieves kinetic polarity that drives treadmilling. To obtain insights into fundamental features of FtsZ assembly dynamics independent of peptidoglycan synthesis, we carried out structural and biochemical characterization of FtsZ from the cell wall-less bacteria, Spiroplasma melliferum (SmFtsZ).

An Old Dog Has a New Trick: Somatic Exonic Deletions in RUNX1 Are Frequent in AML.

Somatic loss-of-function RUNX1 mutations in acute myeloid leukemia (AML) include missense, nonsense, and frameshift mutations, whereas germline RUNX1 variants in RUNX1-FPDMM also include large exonic deletions. Alternative variant detection approaches revealed that large exonic deletions in RUNX1 are also common in sporadic AML, which has implications for patient stratification and therapeutic decision-making. See related article by Eriksson et al.

A mechanism of salt bridge-mediated resistance to FtsZ inhibitor PC190723 revealed by a cell-based screen.

Bacterial cell division proteins, especially the tubulin homologue FtsZ, have emerged as strong targets for developing new antibiotics. Here, we have utilized the fission yeast heterologous expression system to develop a cell-based assay to screen for small molecules that directly and specifically target the bacterial cell division protein FtsZ. The strategy also allows for simultaneous assessment of the toxicity of the drugs to eukaryotic yeast cells.

Performance assessment of genomic island prediction tools with an improved version of Design-Island.

Genomic Islands (GIs) play an important role in the evolution and adaptation of prokaryotes. The origin and extent of ecological diversity of prokaryotes can be analyzed by comparing GIs across closely or distantly related prokaryotes. Understanding the importance of GI and to study the bacterial evolution, several GI prediction tools have been generated.

Comparative genomics analysis of statistically significant genomic islands of Helicobacter pylori strains for better understanding the disease prognosis.

Bacterial virulence factors are often located in their genomic islands (GIs). Helicobacter pylori, a highly diverse organism is reported to be associated with several gastrointestinal diseases like, gastritis, gastric cancer (GC), peptic ulcer, duodenal ulcer (DU) etc. A novel similarity score (Sm)-based comparative analysis with GIs of 50 H.

Quercetin Attenuates Copper-Induced Apoptotic Cell Death and Endoplasmic Reticulum Stress in SH-SY5Y Cells by Autophagic Modulation.

An increase in anthropogenic activities results in metal contamination in the ecosystem which has proven to be a major health risk in humans, as they make entry into cellular organelles via agricultural products. Copper (Cu) is one such metal that acts as an essential cofactor for the activity of several enzymes, one being the cytochrome c oxidase. The increasing number of evidence suggests a substantial correlation of Cu overload with neurodegenerative disorders, including Parkinson's disease (PD).

Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission.

The recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has the capability of gaining rapid mutations as the virus spreads.

A novel microRNA boosts hyper-β-oxidation of fatty acids in liver by impeding CEP350-mediated sequestration of PPARα and thus restricts chronic hepatitis C.

Imbalance in lipid metabolism induces steatosis in liver during Chronic hepatitis C (CHC). Contribution of microRNAs in regulating lipid homoeostasis and liver disease progression is well established using small RNA-transcriptome data. Owing to the complexity in the development of liver diseases, the existence and functional importance of yet undiscovered regulatory miRNAs in disease pathogenesis was explored in this study using the unmapped sequences of the transcriptome data of HCV-HCC liver tissues following miRDeep2.

Neuroprotective Role of Quercetin on Rotenone-Induced Toxicity in SH-SY5Y Cell Line Through Modulation of Apoptotic and Autophagic Pathways.

The detrimental impact on the food chain due to the overuse of rotenone is partly responsible for alpha-synuclein (α-syn) mediated neurotoxicity. It is hypothesized that rotenone overdose leads to cytosolic proteopathy resulting in modulation of apoptosis and autophagic pathways. The aim of our study is to explore the neuroprotective role of quercetin, a beneficial polyphenol against rotenone-induced neurotoxicity in dopaminergic human SH-SY5Y cell lines.

The exosome encapsulated microRNAs as circulating diagnostic marker for hepatocellular carcinoma with low alpha-fetoprotein.

Diagnosis of hepatocellular carcinoma (HCC) remains challenging to clinicians, particularly in a patient with low alpha-fetoprotein. Here, in silico, ex vivo and in vitro data were combined to identify liver-specific exosomal miRNAs as an early diagnostic marker for HCC. Transcriptome profiling for mRNA and small RNA in same HCV-HCC and normal liver tissues followed by cross-validation of 41 deregulated miRNAs (log FoldChange > 1.

Glutathione deficiency-elicited reprogramming of hepatic metabolism protects against alcohol-induced steatosis.

Depletion of glutathione (GSH) is considered a critical pathogenic event promoting alcohol-induced lipotoxicity. We recently show that systemic GSH deficiency in mice harboring a global disruption of the glutamate-cysteine ligase modifier subunit (Gclm) gene confers protection against alcohol-induced steatosis. While several molecular pathways have been linked to the observed hepatic protection, including nuclear factor erythroid 2-related factor 2 and AMP-activated protein kinase pathways, the precise mechanisms are yet to be defined.

Comparative RNA-seq analysis reveals dys-regulation of major canonical pathways in ERG-inducible LNCaP cell progression model of prostate cancer.

Prostate Cancer (CaP) is the second leading cause of cancer related death in USA. In human CaP, gene fusion between androgen responsive regulatory elements at the 5'-untranslated region of TMPRSS2 and ETS-related genes (ERG) is present in at least 50% of prostate tumors. Here we have investigated the unique cellular transcriptome associated with over-expression of ERG in ERG-inducible LNCaP cell model system of human CaP.

Altered Levels of Long NcRNAs Meg3 and Neat1 in Cell And Animal Models Of Huntington's Disease.

Altered expression levels of protein-coding genes and microRNAs have been implicated in the pathogenesis of Huntington's disease (HD). The involvement of other ncRNAs, especially long ncRNAs (lncRNA), is being realized recently and the related knowledge is still rudimentary. Using small RNA sequencing and PCR arrays we observed perturbations in the levels of 12 ncRNAs in HD mouse brain, eight of which had human homologs.

Associations of ERAP1 coding variants and domain specific interaction with HLA-C∗06 in the early onset psoriasis patients of India.

Interferon-γ-induced aminopeptidase ERAP1 trims peptides within the endoplasmic reticulum so that they can be loaded onto MHC class I and presented to the CD8 T-cells. ERAP1 association and its interaction with HLA-C∗06 is controversial across different populations. We have investigated the association and possible functional role of non-synonymous SNPs at different exons of ERAP1 (rs26653: Arg127Pro, rs30187: Lys528Arg and rs27044: Gln730Glu) and their interactions with HLA-C∗06 in psoriasis.

Genome-wide DNA methylation profile identified a unique set of differentially methylated immune genes in oral squamous cell carcinoma patients in India.

Background: Oral squamous cell carcinoma (OSCC) is one of the common malignancies in Southeast Asia. Epigenetic changes, mainly the altered DNA methylation, have been implicated in many cancers. Considering the varied environmental and genotoxic exposures among the Indian population, we conducted a genome-wide DNA methylation study on paired tumor and adjacent normal tissues of ten well-differentiated OSCC patients and validated in an additional 53 well-differentiated OSCC and adjacent normal samples.