Evaluating transosseous anchorless repair for arthroscopic rotator cuff surgery: a comparative study with double row anchor repair.

Background: This retrospective observational study compared outcomes of arthroscopic rotator cuff surgery using double row anchor repair (DRR) versus transosseous anchorless repair (TAR) in patients with small to large full-thickness rotator cuff tears.

Methods: A total of 42 patients underwent DRR (n=20) or TAR (n=22) between January 2022 and May 2023. Patients were matched based on age, sex, body mass index, and tear severity.

Estimating best nanomaterial for energy harvesting through reinforcement learning DQN coupled with fuzzy PROMETHEE under road-based conditions.

Energy harvesters based on nanomaterials are getting more and more popular, but on their way to commercial availability, some crucial issues still need to be solved. The objective of the study is to select an appropriate nanomaterial. Using features of the Reinforcement Deep Q-Network (DQN) in conjunction with Fuzzy PROMETHEE, the proposed model, we present in this work a hybrid fuzzy approach to selecting appropriate materials for a vehicle-environmental-hazardous substance (EHS) combination that operates in roadways and under traffic conditions.

Implementing heuristic-based multiscale depth-wise separable adaptive temporal convolutional network for ambient air quality prediction using real time data.

In many emerging nations, rapid industrialization and urbanization have led to heightened levels of air pollution. This sudden rise in air pollution, which affects global sustainability and human health, has become a significant concern for citizens and governments. While most current methods for predicting air quality rely on shallow models and often yield unsatisfactory results, our study explores a deep architectural model for forecasting air quality.

Targeted protein degradation via intramolecular bivalent glues.

Targeted protein degradation is a pharmacological modality that is based on the induced proximity of an E3 ubiquitin ligase and a target protein to promote target ubiquitination and proteasomal degradation. This has been achieved either via proteolysis-targeting chimeras (PROTACs)-bifunctional compounds composed of two separate moieties that individually bind the target and E3 ligase, or via molecular glues that monovalently bind either the ligase or the target. Here, using orthogonal genetic screening, biophysical characterization and structural reconstitution, we investigate the mechanism of action of bifunctional degraders of BRD2 and BRD4, termed intramolecular bivalent glues (IBGs), and find that instead of connecting target and ligase in trans as PROTACs do, they simultaneously engage and connect two adjacent domains of the target protein in cis.

RNA polymerase II promotes the organization of chromatin following DNA replication.

Understanding how chromatin organisation is duplicated on the two daughter strands is a central question in epigenetics. In mammals, following the passage of the replisome, nucleosomes lose their defined positioning and transcription contributes to their re-organisation. However, whether transcription plays a greater role in the organization of chromatin following DNA replication remains unclear.

Step-Economical Mechanosynthesis of Hybrid Azoles: Deciphering Their π-Orbital and Pharmacological Characteristics.

A hybrid pharmacophore strategy for unifying 1,2,3-triazole with 1,2,4-triazole cores to prepare mixed triazoles was accomplished by a ball-milling approach. The developed chemistry works under the catalysis of cupric oxide nanoparticles with salient features like one-jar operation, lower number of synthetic steps, catalyst recyclability, time-dependent product control, and good overall yields. π-Orbital properties based on theoretical calculations supported the suitability of these molecules for pharmacological screening.

Mechanosynthesis of Triazolyl-bis(indolyl)methane Pharmacophores via Gold Catalysis: A Prelude to Their Molecular Electronic Properties and Biological Potency.

Chemical structures possessing both 1,2,3-triazole and bis(indolyl)methane fragments gained considerable interest in drug synthesis owing to their established biological efficacies. However, 1,2,3-triazoles linked at the bridging position of bis(indolyl)methane is a logical and unexplored design approach. In this regard, nine new triazolyl-bis(indolyl)methane conjugates under AuCl catalyzed ball-milling conditions were accomplished.

Structure and mechanism of the type I-G CRISPR effector.

Type I CRISPR systems are the most common CRISPR type found in bacteria. They use a multisubunit effector, guided by crRNA, to detect and bind dsDNA targets, forming an R-loop and recruiting the Cas3 enzyme to facilitate target DNA destruction, thus providing immunity against mobile genetic elements. Subtypes have been classified into families A-G, with type I-G being the least well understood.

A non-canonical scaffold-type E3 ligase complex mediates protein UFMylation.

Protein UFMylation, i.e., post-translational modification with ubiquitin-fold modifier 1 (UFM1), is essential for cellular and endoplasmic reticulum homeostasis.

Acute depletion of the ARID1A subunit of SWI/SNF complexes reveals distinct pathways for activation and repression of transcription.

The ARID1A subunit of SWI/SNF chromatin remodeling complexes is a potent tumor suppressor. Here, a degron is applied to detect rapid loss of chromatin accessibility at thousands of loci where ARID1A acts to generate accessible minidomains of nucleosomes. Loss of ARID1A also results in the redistribution of the coactivator EP300.

Efficient and Rapid Analysis of Polysomes and Ribosomal Subunits in Cells and Tissues Using Ribo Mega-SEC.

Polysome profile analysis is a popular method for separating polysomes and ribosomal subunits and is typically achieved using a sucrose density gradient (SDG). This has remained the gold standard method since ribosomes were first discovered; however, this method is time-consuming and requires multiple steps from making the gradient and long ultracentrifugation to collecting and analyzing the fractions. Each of these steps in the SDG workflow can introduce potential technical variation that affects the reproducibility of gradient profiles between samples.

Survival of primary amebic meningoencephalitis by : First reported case from Tamil Nadu, South India.

A case of primary amebic meningoencephalitis (PAM) in a 47-year-old male is described. The disease may have been contracted during bathing. The source of water was from a pond.

Chromatin remodelling comes into focus.

ATP-dependent chromatin remodelling enzymes are molecular machines that act to reconfigure the structure of nucleosomes. Until recently, little was known about the structure of these enzymes. Recent progress has revealed that their interaction with chromatin is dominated by ATPase domains that contact DNA at favoured locations on the nucleosome surface.

Prospects of siRNA cocktails as tools for modifying multiple gene targets in the injured spinal cord.

Unlabelled: Gene silencing through RNA interference (RNAi) has been touted as a boon for identifying potential therapies for difficult-to-treat pathologies. In this regard, siRNA-mediated gene silencing for tackling the multifaceted pathophysiology of spinal cord injury seemed promising. The genes caspase 3 and sarm1 were targeted in the present study, using siRNAs in a rodent model of spinal cord injury, as the feasibility of concomitant silencing of more than one gene had not been previously attempted.

Melioidosis-Series of Seven Cases from Madurai, Tamil Nadu, India.

Unlabelled: We describe a case series of seven culture proven melioidosis patients presenting during 2014 to 2016 in Madurai, south Tamilnadu. Skin, soft tissue, bone and joint infections were common. All of them were middle aged men except one case.

Nucleosome remodelling: structural insights into ATP-dependent remodelling enzymes.

ATP-dependent chromatin remodelling enzymes play a fundamental role in determining how nucleosomes are organised, and render DNA sequences accessible to interacting proteins, thereby enabling precise regulation of eukaryotic genes. Remodelers conserved from yeast to humans are classified into four families based on the domains and motifs present in their ATPase subunits. Insights into overall assembly and the mode of interaction to the nucleosome by these different families of remodelers remained limited due to the complexity of obtaining structural information on these challenging samples.

Efficient analysis of mammalian polysomes in cells and tissues using Ribo Mega-SEC.

We describe Ribo Mega-SEC, a powerful approach for the separation and biochemical analysis of mammalian polysomes and ribosomal subunits using Size Exclusion Chromatography and uHPLC. Using extracts from either cells, or tissues, polysomes can be separated within 15 min from sample injection to fraction collection. Ribo Mega-SEC shows translating ribosomes exist predominantly in polysome complexes in human cell lines and mouse liver tissue.

Structure of the chromatin remodelling enzyme Chd1 bound to a ubiquitinylated nucleosome.

ATP-dependent chromatin remodelling proteins represent a diverse family of proteins that share ATPase domains that are adapted to regulate protein-DNA interactions. Here, we present structures of the Chd1 protein engaged with nucleosomes in the presence of the transition state mimic ADP-beryllium fluoride. The path of DNA strands through the ATPase domains indicates the presence of contacts conserved with single strand translocases and additional contacts with both strands that are unique to Snf2 related proteins.

Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity.

Ubiquitination is initiated by transfer of ubiquitin (Ub) from a ubiquitin-activating enzyme (E1) to a ubiquitin-conjugating enzyme (E2), producing a covalently linked intermediate (E2-Ub) . Ubiquitin ligases (E3s) of the 'really interesting new gene' (RING) class recruit E2-Ub via their RING domain and then mediate direct transfer of ubiquitin to substrates . By contrast, 'homologous to E6-AP carboxy terminus' (HECT) E3 ligases undergo a catalytic cysteine-dependent transthiolation reaction with E2-Ub, forming a covalent E3-Ub intermediate.

Seroprevalence of transfusion transmissible infections among blood donors by chemiluminescent assay in a tertiary care centre.

Introduction: Blood transfusion is a life saving measure, but also carries risk of transfusion transmitted infections (TTIs). In spite of improved donor screening, risk of transmission of TTIs still remains a major concern. Stringent screening of blood not only ensures safe supply of blood and blood products, but also gives us an idea about prevalence of TTIs among general population.

The Ndc80 complex targets Bod1 to human mitotic kinetochores.

Regulation of protein phosphatase activity by endogenous protein inhibitors is an important mechanism to control protein phosphorylation in cells. We recently identified Biorientation defective 1 (Bod1) as a small protein inhibitor of protein phosphatase 2A containing the B56 regulatory subunit (PP2A-B56). This phosphatase controls the amount of phosphorylation of several kinetochore proteins and thus the establishment of load-bearing chromosome-spindle attachments in time for accurate separation of sister chromatids in mitosis.

Parkin-phosphoubiquitin complex reveals cryptic ubiquitin-binding site required for RBR ligase activity.

RING-between-RING (RBR) E3 ligases are a class of ubiquitin ligases distinct from RING or HECT E3 ligases. An important RBR ligase is Parkin, mutations in which lead to early-onset hereditary Parkinsonism. Parkin and other RBR ligases share a catalytic RBR module but are usually autoinhibited and activated via distinct mechanisms.

Structural reorganization of the chromatin remodeling enzyme Chd1 upon engagement with nucleosomes.

The yeast Chd1 protein acts to position nucleosomes across genomes. Here, we model the structure of the Chd1 protein in solution and when bound to nucleosomes. In the apo state, the DNA-binding domain contacts the edge of the nucleosome while in the presence of the non-hydrolyzable ATP analog, ADP-beryllium fluoride, we observe additional interactions between the ATPase domain and the adjacent DNA gyre 1.

Comparative cytotoxic and genotoxic effects of permethrin and its nanometric form on human erythrocytes and lymphocytes in vitro.

The research on the novel pesticides such as nanopesticides has become inevitable to control the mosquito population. Nanopermethrin (NP), one of such kind was formulated in pesticide loaded oil-in-water (o/w) microemulsion by rapid evaporation. Even though NP possess improved efficacy against the target pests, the toxicological investigation on the human or mammalian system remains unexplored.