Bacterial Rps3 counters oxidative and UV stress by recognizing and processing AP-sites on mRNA via a novel mechanism.

Lesions and stable secondary structures in mRNA severely impact the translation efficiency, causing ribosome stalling and collisions. Prokaryotic ribosomal proteins Rps3, Rps4 and Rps5, located in the mRNA entry tunnel, form the mRNA helicase center and unwind stable mRNA secondary structures during translation. However, the mechanism underlying the detection of lesions on translating mRNA is unclear.

Cognitive and Behavioral Profile of Patients with Amyotrophic Lateral Sclerosis Spectrum in the Indian Context.

Introduction: Amyotrophic lateral sclerosis (ALS) is characterized by motor, cognitive, and behavioral impairment. There is a paucity of evidence about the cognitive/behavioral features of ALS patients from India. We aimed to investigate the cognitive/behavioral profile of ALS spectrum disorders in the Indian context.

Myotonic Dystrophy Type 1 (DM1): Clinical Characteristics and Disease Progression in a Large Cohort.

Background: DM1 is a multisystem disorder caused by expansion of a CTG triplet repeat in the 3' non-coding region of DMPK. Neuropsychological consequences and sleep abnormalities are important associations in DM1.

Objective: To describe the clinical phenotype, disease progression and characterize the sleep alterations and cognitive abnormalities in a sub-set of patients.

Cryo-EM structures of Uba7 reveal the molecular basis for ISG15 activation and E1-E2 thioester transfer.

ISG15 plays a crucial role in the innate immune response and has been well-studied due to its antiviral activity and regulation of signal transduction, apoptosis, and autophagy. ISG15 is a ubiquitin-like protein that is activated by an E1 enzyme (Uba7) and transferred to a cognate E2 enzyme (UBE2L6) to form a UBE2L6-ISG15 intermediate that functions with E3 ligases that catalyze conjugation of ISG15 to target proteins. Despite its biological importance, the molecular basis by which Uba7 catalyzes ISG15 activation and transfer to UBE2L6 is unknown as there is no available structure of Uba7.

Redox oscillations destabilize and mobilize colloidal soil organic carbon.

The onset of oxic-anoxic events in soil induces biogeochemical processes that may have profound influences on the fate and transport of soil organic carbon (OC). An 18-wk long laboratory soil column study was conducted to investigate the influence of static oxic (SO), static anoxic (SA), or redox oscillation (RO) events on the release of OC. Column leachate samples were collected after 9-wk and 18-wk of incubations and separated into dissolved (<2.

Regulation of futile ligation during early steps of BER in M. tuberculosis is carried out by a β-clamp-XthA-LigA tri-component complex.

The Class-II AP-endonuclease (XthA) is a mycobacterial DNA base excision repair (BER) pathway enzyme that functions in the initial steps. It acts on DNA substrates that contain abasic sites to create nicks with 3'-hydroxyl (OH) and 5'-deoxyribose phosphate (5'-dRP) moieties. The NAD-dependent DNA ligase (LigA) is the terminal player in mycobacterial BER and seals such nicks efficiently.

Drug targeting Nsp1-ribosomal complex shows antiviral activity against SARS-CoV-2.

The SARS-CoV-2 non-structural protein 1 (Nsp1) contains an N-terminal domain and C-terminal helices connected by a short linker region. The C-terminal helices of Nsp1 (Nsp1-C-ter) from SARS-CoV-2 bind in the mRNA entry channel of the 40S ribosomal subunit and blocks mRNA entry, thereby shutting down host protein synthesis. Nsp1 suppresses host immune function and is vital for viral replication.

Disrupted structural connectome and neurocognitive functions in Duchenne muscular dystrophy: classifying and subtyping based on Dp140 dystrophin isoform.

Objective: Neurocognitive disabilities in Duchenne muscular dystrophy (DMD) children beginning in early childhood and distal DMD gene deletions involving disruption of Dp140 isoform are more likely to manifest significant neurocognitive impairments. MRI data analysis techniques like brain-network metrics can provide information on microstructural integrity and underlying pathophysiology.

Methods: A prospective study on 95 participants [DMD = 57, and healthy controls (HC) = 38].

Salt bridges at the subdomain interfaces of the adenylation domain and active-site residues of Mycobacterium tuberculosis NAD-dependent DNA ligase A (MtbLigA) are important for the initial steps of nick-sealing activity.

NAD-dependent DNA ligase (LigA) is the principal bacterial ligase and catalyses a multistep ligation reaction. The adenylation (AdD) domain at the N-terminus consists of subdomains 1a and 1b, where subdomain 1a is unique to LigA. Small-angle X-ray scattering and X-ray diffraction studies were used to probe changes in the relative spatial dispositions of the two subdomains during the adenylation reaction.

[Fe-S] biogenesis and unusual assembly of the ISC scaffold complex in the Plasmodium falciparum mitochondrion.

The malaria parasite harbors two [Fe-S] biogenesis pathways of prokaryotic origin-the SUF and ISC systems in the apicoplast and mitochondrion, respectively. While the SUF machinery has been delineated, there is little experimental evidence on the ISC pathway. We confirmed mitochondrial targeting of Plasmodium falciparum ISC proteins followed by analyses of cysteine desulfurase, scaffold, and [Fe-S]-carrier components.

Emetine suppresses SARS-CoV-2 replication by inhibiting interaction of viral mRNA with eIF4E.

Emetine is a FDA-approved drug for the treatment of amebiasis. Previously we demonstrated the antiviral efficacy of emetine against some RNA and DNA viruses. In this study, we evaluated the in vitro antiviral efficacy of emetine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and found it to be a low nanomolar (nM) inhibitor.

Structure based identification of first-in-class fragment inhibitors that target the NMN pocket of M. tuberculosis NAD-dependent DNA ligase A.

NAD-dependent DNA ligase (LigA) is the essential replicative ligase in bacteria and differs from ATP-dependent counterparts like the human DNA ligase I (HligI) in several aspects. LigA uses NAD as the co-factor while the latter uses ATP. Further, the LigA carries out enzymatic activity with a single divalent metal ion in the active site while ATP-dependent ligases use two metal ions.

M. tuberculosis class II apurinic/ apyrimidinic-endonuclease/3'-5' exonuclease (XthA) engages with NAD+-dependent DNA ligase A (LigA) to counter futile cleavage and ligation cycles in base excision repair.

Class-II AP-endonuclease (XthA) and NAD+-dependent DNA ligase (LigA) are involved in initial and terminal stages of bacterial DNA base excision repair (BER), respectively. XthA acts on abasic sites of damaged DNA to create nicks with 3'OH and 5'-deoxyribose phosphate (5'-dRP) moieties. Co-immunoprecipitation using mycobacterial cell-lysate, identified MtbLigA-MtbXthA complex formation.

Deciphering the Nature of Caffeic Acid to Inhibit the HSA Aggregation Induced by Glyoxal.

Background: Under certain circumstances, the path for protein folding deviates and attains an alternative path forming misfolded states, which are the key precursors for protein aggregation. Protein aggregation is associated with variety of diseases and leads to the cytotoxicity. These protein aggregate related diseases have been untreated so far.

Quantification and molecular characterization of organo-mineral associations as influenced by redox oscillations.

Organo-mineral association is one of the most important stabilization mechanisms of soil organic matter. However, few studies have been conducted to assess the retention, transformation, and transportation of colloids (1-1000 nm) and associated organic carbon (OC) in soil. Given the particularly significant role that wetland soils play in carbon storage and cycling, we quantified the dynamics of organo-mineral association within colloidal size range by conducting three consecutive 35-day redox (reduction-oxidation) oscillation experiments using a wetland soil.

Glycation induced conformational transitions in cystatin proceed to form biotoxic aggregates: A multidimensional analysis.

Hyperglycaemic conditions facilitate the glycation of serum proteins which may have predisposition to aggregation and thus lead to complications. The current study investigates the glycation induced structural and functional modifications of chickpea cystatin (CPC) as well as biological toxicity of the modified protein forms, using CPC-glucose as a model system. Several structural intermediates were formed during the incubation of CPC with glucose (day 4, 8, 12, & 16) as revealed by circular dichroism (CD), altered intrinsic fluorescence, and high ANS binding.

Modification of chickpea cystatin by reactive dicarbonyl species: Glycation, oxidation and aggregation.

Reactive dicarbonyl species such as methylglyoxal (MGO) and glyoxal (GO) have recently received extensive attention due to their high reactivity and ability to modify biological substances such as proteins, phospholipids, and DNA. In case of proteins these reactive species mainly react with lysine and arginine residues to form AGEs, oxidative products, and aggregates. Chickpea cystatin (CPC) was incubated with varying concentrations of glyoxal and methylglyoxal which caused, along with altered secondary and tertiary structures, glycation, functional inactivation, altered redox state, cross-linking and high-molecular-mass aggregation.

Biochemical characterization and novel inhibitor identification of Endonuclease VIII 2 (Rv3297).

Nei2 (Rv3297) is a DNA Base Excision Repair (BER) glycosylase that is essential for survival of in primates. We show that MtbNei2 is a bifunctional glycosylase that specifically acts on oxidized pyrimidine-containing single-stranded, double-stranded, 5'/3' fork and bubble DNA substrates. MtbNei2 possesses Uracil DNA glycosylase activity unlike Nei.

PeMtb: A Database of MHC Antigenic Peptide of Mycobacterium tuberculosis.

Background: For design of a subunit vaccine for tuberculosis, identification of antigenic Tcell epitope is of utmost importance. Several MHC prediction server are available that can accurately predict antigenic peptide of variable lengths. However, peptides predicted from one server not necessarily are predicted form another server, thus creating a confusing situation for scientists to choose a best epitope.

Analysing Cytochrome c Aggregation and Fibrillation upon Interaction with Acetonitrile: an in Vitro Study.

The propensity of native state to form aggregated and fibrillar assemblies is a hallmark of amyloidosis. Our study was focused at analyzing the aggregation and fibrillation tendency of cytochrome c in presence of an organic solvent i.e.

Oral administration of oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver.

Cisplatin (CP) is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application.

Rifampicin Induced Aggregation of Ovalbumin: Malicious Behaviour of Antibiotics.

Molecular modeling deciphered the site of interaction of rifampicin in the structure of ovalbumin at a site which is surrounded by residues Glu-214, Asp-98, Pro-85, Asp-91 and Asp-47. Isothermal calorimetric analysis determined the thermodynamic parameters i.e.

Memory, executive function and language function are similarly impaired in both temporal and extra temporal refractory epilepsy-A prospective study.

Introduction: Cognitive impairment has long been recognized as a co-morbidity or sequel to refractory epilepsy. This study was conducted to evaluate the degree and selectivity of involvement of memory, language and executive functions performance among patients with temporal (TLE) versus extratemporal epilepsy (ETLE).

Methods: We prospectively enrolled adolescent and adult patients with medically refractory focal epilepsy, who had undergone pre-surgical evaluation.