Motif distribution in genomes gives insights into gene clustering and co-regulation.

We read the genome as proteins in the cell would - by studying the distributions of 5-6 base motifs of DNA in the whole genome or smaller stretches such as parts of, or whole chromosomes. This led us to some interesting findings about motif clustering and chromosome organization. It is quite clear that the motif distribution in genomes is not random at the length scales we examined: 1 kb to entire chromosomes.

Alphavirus infection triggers selective cytoplasmic translocation of nuclear RBPs with moonlighting antiviral roles.

RNA is a central molecule for viruses; however, the interactions that viral RNA (vRNA) establishes with the host cell is only starting to be elucidated. Here, we determine the ribonucleoprotein (RNP) composition of the prototypical arthropod-borne Sindbis virus (SINV). We show that SINV RNAs engage with hundreds of cellular proteins, including a group of nuclear RNA-binding proteins (RBPs) with unknown roles in infection.

Targeting LLT1 as a potential immunotherapy option for cancer patients non-responsive to existing checkpoint therapies in multiple solid tumors.

Background: High levels of LLT1 expression have been found in several cancers, where it interacts with CD161 on NK cells to facilitate tumor immune escape. Targeting LLT1 could potentially relieve this inhibitory signal and enhance anti-tumor responses mediated through NK cells. Using the 'The Cancer Genome Atlas' (TCGA) database, we investigated the role of LLT1 in the tumor microenvironment (TME) across various cancers.

High-affinity biomolecular interactions are modulated by low-affinity binders.

The strength of molecular interactions is characterized by their dissociation constants (K). Only high-affinity interactions (K ≤ 10 M) are extensively investigated and support binary on/off switches. However, such analyses have discounted the presence of low-affinity binders (K > 10 M) in the cellular environment.

Psidium guajav-mediated zinc oxide nanoparticles as a multifunctional, microbicidal, antioxidant and antiproliferative agent against destructive pathogens.

Bio-inspired zinc oxide nanoparticles are gaining immense interest due to their safety, low cost, biocompatibility, and broad biological properties. In recent years, much research has been focused on plant-based nanoparticles, mainly for their eco-friendly, facile, and non-toxic character. Hence, the current study emphasized a bottom-up synthesis of zinc oxide nanoparticles (ZnO NPs) from Psidium guajava aqueous leaf extract and evaluation of its biological properties.

Investigating the effect of acidic and basic precipitation on the antibacterial activity of ZnO nanoparticles against Gram-negative and Gram-positive bacteria.

In the present work, acidic (direct) and basic precipitation (indirect) methods were used to demonstrate the influence of the mode of precipitation on the structural properties of ZnO nanoparticles (NPs). Four samples of ZnO nanoparticles were prepared, two samples each mode of precipitation. DZOa and IZOa were the aged samples prepared acidic and basic precipitation methods, and DZOwa and IZOwa were processed without aging.

Identification of sequence determinants for the ABHD14 enzymes.

Over the course of evolution, enzymes have developed remarkable functional diversity in catalyzing important chemical reactions across various organisms, and understanding how new enzyme functions might have evolved remains an important question in modern enzymology. To systematically annotate functions, based on their protein sequences and available biochemical studies, enzymes with similar catalytic mechanisms have been clustered together into an enzyme superfamily. Typically, enzymes within a superfamily have similar overall three-dimensional structures, conserved catalytic residues, but large variations in substrate recognition sites and residues to accommodate the diverse biochemical reactions that are catalyzed within the superfamily.

Characterizing the relationship between coronavirus disease 2019 (COVID-19) and central-line-associated bloodstream infection (CLABSI) and assessing the impact of a nursing-focused CLABSI reduction intervention during the COVID-19 pandemic.

Objective: To examine the impact of SARS-CoV-2 infection on CLABSI rate and characterize the patients who developed a CLABSI. We also examined the impact of a CLABSI-reduction quality-improvement project in patients with and without COVID-19.

Design: Retrospective cohort analysis.

A novel intervention: Implementation of a neutropenic infection-prevention bundle and audit tool in an oncology unit.

Infectious complications are a significant cause of morbidity and mortality in patients with chemotherapy-induced neutropenia. Specific infection control practices targeting this patient population are widely endorsed, but little guidance exists on how to implement and monitor compliance with these practices. At our institution, we increased compliance with infection control measures by using a bundled neutropenic precaution (NP) audit and feedback tool.

Transmission risk of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) to healthcare personnel following unanticipated exposure to aerosol-generating procedures: Experience from epidemiologic investigations at an academic medical center.

Healthcare personnel (HCP) with unprotected exposures to aerosol-generating procedures (AGPs) on patients with coronavirus disease 2019 (COVID-19) are at risk of infection with severe acute respiratory coronavirus virus 2 (SARS-CoV-2). A retrospective review at an academic medical center demonstrated an infection rate of <1% among HCP involved in AGPs without a respirator and/or eye protection.

Real-World Impact of the Accelerate PhenoTest BC Kit on Patients With Bloodstream Infections in the Improving Outcomes and Antimicrobial Stewardship Study: A Quasiexperimental Multicenter Study.

Background: Bloodstream infections (BSIs) are a leading cause of morbidity and mortality. The Improving Outcomes and Antimicrobial Stewardship study seeks to evaluate the impact of the Accelerate PhenoTest BC Kit (AXDX) on antimicrobial use and clinical outcomes in BSIs.

Methods: This multicenter, quasiexperimental study compared clinical and antimicrobial stewardship metrics, prior to and after implementation of AXDX, to evaluate the impact this technology has on patients with BSIs.

Packpred: Predicting the Functional Effect of Missense Mutations.

Predicting the functional consequences of single point mutations has relevance to protein function annotation and to clinical analysis/diagnosis. We developed and tested Packpred that makes use of a multi-body clique statistical potential in combination with a depth-dependent amino acid substitution matrix (FADHM) and positional Shannon entropy to predict the functional consequences of point mutations in proteins. Parameters were trained over a saturation mutagenesis data set of T4-lysozyme (1,966 mutations).

Peptide bond planarity constrains hydrogen bond geometry and influences secondary structure conformations.

An extensive database study of hydrogen bonds in different protein environments showed systematic variations in donor-acceptor-acceptor antecedent angle () and donor-acceptor distance. Protein environments were characterized by depth (distance of amino acids from bulk solvent), secondary structure, and whether the donor/acceptor belongs to the main chain (MC) or side chain (SC) of amino acids. The MC-MC hydrogen bonds (whether in secondary structures or not) have angles tightly restricted to a value of around 155°, which was distinctly different from other angles.

On and off controls within dynein-dynactin on native cargoes.

The dynein-dynactin nanomachine transports cargoes along microtubules in cells. Why dynactin interacts separately with the dynein motor and also with microtubules is hotly debated. Here we disrupted these interactions in a targeted manner on phagosomes extracted from cells, followed by optical trapping to interrogate native dynein-dynactin teams on single phagosomes.

Methods for Molecular Modelling of Protein Complexes.

Biological processes are often mediated by complexes formed between proteins and various biomolecules. The 3D structures of such protein-biomolecule complexes provide insights into the molecular mechanism of their action. The structure of these complexes can be predicted by various computational methods.

The miRISC component AGO2 has multiple binding sites for Nup358 SUMO-interacting motif.

Micro-RNA mediated suppression of mRNA translation represents a major regulatory mode of post-transcriptional gene expression. Recently, the nucleoporin Nup358 was shown to interact with AGO protein, a key component of miRNA-induced silencing complex (miRISC), and facilitate the coupling of miRISC with target mRNA. Previous results suggested that SUMO-interacting motifs (SIMs) present on Nup358 mediate interaction with AGO protein.

Observation of an Unusually Large IR Red-Shift in an Unconventional S-H···S Hydrogen-Bond.

The S-H···S non-covalent interaction is generally known as an extremely unconventional weak hydrogen-bond in the literature. The present gas-phase spectroscopic investigation shows that the S-H···S hydrogen-bond can be as strong as any conventional hydrogen-bond in terms of the IR red-shift in the stretching frequency of the hydrogen-bond donor group. Herein, the strength of the S-H···S hydrogen-bond has been determined by measuring the red-shift (∼150 cm) of the S-H stretching frequency in a model complex of 2-chlorothiophenol and dimethyl sulfide using isolated gas-phase IR spectroscopy coupled with quantum chemistry calculations.

Combining Information from Crosslinks and Monolinks in the Modeling of Protein Structures.

Monolinks are produced in a chemical crosslinking mass spectrometry experiment and are more abundant than crosslinks. They convey residue exposure information, but so far have not been used in the modeling of protein structures. Here, we present the Monolink Depth Score (MoDS), for assessing structural models based on the depth of monolinked residues, corresponding to their distance to the nearest bulk water.

A knowledge-based scoring function to assess quaternary associations of proteins.

Motivation: The elucidation of all inter-protein interactions would significantly enhance our knowledge of cellular processes at a molecular level. Given the enormity of the problem, the expenses and limitations of experimental methods, it is imperative that this problem is tackled computationally. In silico predictions of protein interactions entail sampling different conformations of the purported complex and then scoring these to assess for interaction viability.

Predicting and designing therapeutics against the Nipah virus.

Despite Nipah virus outbreaks having high mortality rates (>70% in Southeast Asia), there are no licensed drugs against it. In this study, we have considered all 9 Nipah proteins as potential therapeutic targets and computationally identified 4 putative peptide inhibitors (against G, F and M proteins) and 146 small molecule inhibitors (against F, G, M, N, and P proteins). The computations include extensive homology/ab initio modeling, peptide design and small molecule docking.

Introducing a nursing maintenance bundle for patients with pulmonary arterial catheters.

We undertook a quality improvement project to address challenges with pulmonary artery catheter (PAC) line maintenance in a setting of low-baseline central-line infection rates. We observed a subsequent reduction in Staphylococcal PAC line infections and a trend toward a reduction in overall PAC infection rates over 1 year.

Optimizing utilization of beta-lactam surgical prophylaxis through implementation of a structured allergy assessment tool in a presurgical clinic.

In patients with β-lactam allergies, administration of non-β-lactam surgical prophylaxis is associated with increased risk of infection. Although many patients self-report β-lactam allergies, most are unconfirmed or mislabeled. A quality improvement process, utilizing a structured β-lactam allergy tool, was implemented to improve the utilization of preferred β-lactam surgical prophylaxis.

Structural insights of a cellobiose dehydrogenase enzyme from the basidiomycetes fungus Termitomyces clypeatus.

Filamentous fungi secrete various oxidative enzymes to degrade the glycosidic bonds of polysaccharides. Cellobiose dehydrogenase (CDH) (E.C.

Water-Mediated Selenium Hydrogen-Bonding in Proteins: PDB Analysis and Gas-Phase Spectroscopy of Model Complexes.

High-resolution X-ray crystallography and two-dimensional NMR studies demonstrate that water-mediated conventional hydrogen-bonding interactions (N-H···N, O-H···N, etc.) bridging two or more amino acid residues contribute to the stability of proteins and protein-ligand complexes. In this work, we have investigated single water-mediated selenium hydrogen-bonding interactions (unconventional hydrogen-bonding) between amino acid residues in proteins through extensive protein data bank (PDB) analysis coupled with gas-phase spectroscopy and quantum chemical calculation of a model complex consisting of indole, dimethyl selenide, and water.

Protein Interaction Z Score Assessment (PIZSA): an empirical scoring scheme for evaluation of protein-protein interactions.

Our web server, PIZSA (http://cospi.iiserpune.ac.