Posterior Cruciate Ligament Avulsion Fracture of Tibia: Fixation with Screw and Augmentation Using Ethibond Suture for Improved Clinical Outcomes.

Introduction: The posterior cruciate ligament (PCL) is a vital structure in knee biomechanics, and its avulsion fractures present a unique challenge. This prospective cohort study was conducted at Grant Government Medical College and JJ Hospital, Mumbai, aimed to assess the clinical outcomes of open reduction and internal fixation (ORIF) utilizing cancellous screws and ethibond suture augmentation for PCL avulsion fractures. PCL avulsion fractures often result from traumatic incidents, such as road traffic accidents, and are associated with complications if left untreated.

Laparoscopic uretero-ileal substitution preserving the natural anti-reflux mechanism: A case report.

Ureteral strictures constitute one of the most common sequelae of impacted ureteral stones. Uretero-ileal substitution is an established treatment for long benign ureteral strictures, measuring more than 2 cm, which are incurable by other less invasive treatment options. One of the common drawbacks of this procedure is its extensive nature and the urine reflux into the newly constructed ileal segment, resulting in urine stagnation and precipitation of urinary tract infections.

Structures of heat shock factor trimers bound to DNA.

Heat shock factor 1 (HSF1) and 2 (HSF2) play distinct but overlapping regulatory roles in maintaining cellular proteostasis or mediating cell differentiation and development. Upon activation, both HSFs trimerize and bind to heat shock elements (HSEs) present in the promoter region of target genes. Despite structural insights gained from recent studies, structures reflecting the physiological architecture of this transcriptional machinery remains to be determined.

Chemogenomics identifies acetyl-coenzyme A synthetase as a target for malaria treatment and prevention.

We identify the Plasmodium falciparum acetyl-coenzyme A synthetase (PfAcAS) as a druggable target, using genetic and chemical validation. In vitro evolution of resistance with two antiplasmodial drug-like compounds (MMV019721 and MMV084978) selects for mutations in PfAcAS. Metabolic profiling of compound-treated parasites reveals changes in acetyl-CoA levels for both compounds.

Substrate and Stereochemical Control of Peptidoglycan Cross-Linking by Transpeptidation by PBP1B.

Penicillin binding proteins (PBPs) catalyzing transpeptidation reactions that stabilize the peptidoglycan component of the bacterial cell wall are the targets of β-lactams, the most clinically successful antibiotics to date. However, PBP-transpeptidation enzymology has evaded detailed analysis, because of the historical unavailability of kinetically competent assays with physiologically relevant substrates and the previously unappreciated contribution of protein cofactors to PBP activity. By re-engineering peptidoglycan synthesis, we have constructed a continuous spectrophotometric assay for transpeptidation of native or near native peptidoglycan precursors and fragments by PBP1B, allowing us to (a) identify recognition elements of transpeptidase substrates, (b) reveal a novel mechanism of stereochemical editing within peptidoglycan transpeptidation, (c) assess the impact of peptidoglycan substrates on β-lactam targeting of transpeptidation, and (d) demonstrate that both substrates have to be bound before transpeptidation occurs.

Structure-Guided Enhancement of Selectivity of Chemical Probe Inhibitors Targeting Bacterial Seryl-tRNA Synthetase.

Aminoacyl-tRNA synthetases are ubiquitous and essential enzymes for protein synthesis and also a variety of other metabolic processes, especially in bacterial species. Bacterial aminoacyl-tRNA synthetases represent attractive and validated targets for antimicrobial drug discovery if issues of prokaryotic versus eukaryotic selectivity and antibiotic resistance generation can be addressed. We have determined high-resolution X-ray crystal structures of the and seryl-tRNA synthetases in complex with aminoacyl adenylate analogues and applied a structure-based drug discovery approach to explore and identify a series of small molecule inhibitors that selectively inhibit bacterial seryl-tRNA synthetases with greater than 2 orders of magnitude compared to their human homologue, demonstrating a route to the selective chemical inhibition of these bacterial targets.

Phase Transfer Ceria-Supported Nanocatalyst for Nitrile Hydration Reaction.

The present study elaborates the catalytic effect of rare-earth metal oxides (SmO and LaO) over ceria as a support phase transfer catalyst. The synthesized catalysts have been subjected to different characterization techniques, such as field-emission scanning electron microscopy, high-resolution transmission electron microscopy, powder X-ray diffraction, N adsorption-desorption (BET surface analysis), temperature-programmed desorption study (NH/CO-TPD), Fourier transform infrared, Raman analysis, and X-ray photoelectron spectroscopy to get better insights into the catalytic activity of the catalysts for hydration of nitrile.

The role of the jaw subdomain of peptidoglycan glycosyltransferases for lipid II polymerization.

Bacterial peptidoglycan glycosyltransferases (PGT) catalyse the essential polymerization of lipid II into linear glycan chains required for peptidoglycan biosynthesis. The PGT domain is composed of a large head subdomain and a smaller jaw subdomain and can be potently inhibited by the antibiotic moenomycin A (MoeA). We present an X-ray structure of the MoeA-bound monofunctional PGT enzyme, revealing electron density for a second MoeA bound to the jaw subdomain as well as the PGT donor site.

Structural basis for DNA recognition by the transcription regulator MetR.

MetR, a LysR-type transcriptional regulator (LTTR), has been extensively studied owing to its role in the control of methionine biosynthesis in proteobacteria. A MetR homodimer binds to a 24-base-pair operator region of the met genes and specifically recognizes the interrupted palindromic sequence 5'-TGAA-N5-TTCA-3'. Mechanistic details underlying the interaction of MetR with its target DNA at the molecular level remain unknown.

Purification, crystallization and preliminary X-ray diffraction analysis of the 23S rRNA methyltransferase RlmJ from Escherichia coli.

Methyltransferase RlmJ uses the cofactor S-adenosylmethionine to methylate the exocyclic nitrogen N6 of nucleotide A2030 in 23S rRNA during ribosome assembly in Escherichia coli. RlmJ with a C-terminal hexahistidine tag was overexpressed in E. coli and purified as a monomer using Ni(2+)-affinity and size-exclusion chromatography.

Structural and functional insights into the molecular mechanism of rRNA m6A methyltransferase RlmJ.

RlmJ catalyzes the m(6)A2030 methylation of 23S rRNA during ribosome biogenesis in Escherichia coli. Here, we present crystal structures of RlmJ in apo form, in complex with the cofactor S-adenosyl-methionine and in complex with S-adenosyl-homocysteine plus the substrate analogue adenosine monophosphate (AMP). RlmJ displays a variant of the Rossmann-like methyltransferase (MTase) fold with an inserted helical subdomain.

Energetic pathway sampling in a protein interaction domain.

The affinity and specificity of protein-ligand interactions are influenced by energetic crosstalk within the protein domain. However, the molecular details of such intradomain allostery are still unclear. Here, we have experimentally detected and computationally predicted interaction pathways in the postsynaptic density 95/discs large/zonula occludens 1 (PDZ)-peptide ligand model system using wild-type and circularly permuted PDZ proteins.

Tolerance of protein folding to a circular permutation in a PDZ domain.

Circular permutation is a common molecular mechanism for evolution of proteins. However, such re-arrangement of secondary structure connectivity may interfere with the folding mechanism causing accumulation of folding intermediates, which in turn can lead to misfolding. We solved the crystal structure and investigated the folding pathway of a circularly permuted variant of a PDZ domain, SAP97 PDZ2.

Crystal structure of RlmM, the 2'O-ribose methyltransferase for C2498 of Escherichia coli 23S rRNA.

RlmM (YgdE) catalyzes the S-adenosyl methionine (AdoMet)-dependent 2'O methylation of C2498 in 23S ribosomal RNA (rRNA) of Escherichia coli. Previous experiments have shown that RlmM is active on 23S rRNA from an RlmM knockout strain but not on mature 50S subunits from the same strain. Here, we demonstrate RlmM methyltransferase (MTase) activity on in vitro transcribed 23S rRNA and its domain V.

Imaging manifestations in Proteus syndrome: an unusual multisystem developmental disorder.

In this review we use images from an 11-year-old male to describe Proteus syndrome, a complex disorder with multisystem involvement and great clinical variability. Our aim is to enhance recognition of the typical imaging findings, which can aid diagnosis of this rare condition.