Genomic plasticity associated with antimicrobial resistance in Vibrio cholerae.

The Bay of Bengal is known as the epicenter for seeding several devastating cholera outbreaks across the globe. Vibrio cholerae, the etiological agent of cholera, has extraordinary competency to acquire exogenous DNA by horizontal gene transfer (HGT) and adapt them into its genome for structuring metabolic processes, developing drug resistance, and colonizing the human intestine. Antimicrobial resistance (AMR) in V. cholerae has become a global concern. However, little is known about the identity of the resistance traits, source of AMR genes, acquisition process, and stability of the genetic elements linked with resistance genes in V. cholerae Here we present details of AMR profiles of 443 V. cholerae strains isolated from the stool samples of diarrheal patients from two regions of India. We sequenced the whole genome of multidrug-resistant (MDR) and extensively drug-resistant (XDR) V. cholerae to identify AMR genes and genomic elements that harbor the resistance traits. Our genomic findings were further confirmed by proteome analysis. We also engineered the genome of V. cholerae to monitor the importance of the autonomously replicating plasmid and core genome in the resistance profile. Our findings provided insights into the genomes of recent cholera isolates and identified several acquired traits including plasmids, transposons, integrative conjugative elements (ICEs), pathogenicity islands (PIs), prophages, and gene cassettes that confer fitness to the pathogen. The knowledge generated from this study would help in better understanding of V. cholerae evolution and management of cholera disease by providing clinical guidance on preferred treatment regimens.DBT Indi

3'-N-alkylamino-3'-deoxy-ara-uridines: a new class of potential inhibitors of ribonuclease A and angiogenin

In this study, we report the inhibition of ribonuclease A (RNase A) by certain aminonucleosides. This is the first such instance of the use of this group of compounds to investigate the inhibitory activity of this protein. The compounds synthesized have been tested for their ability to inhibit the ribonucleolytic activity of RNase A by an agarose gel-based assay. A tRNA precipitation assay and inhibition kinetic studies with cytidine 2',3'-cyclic monophosphate as the substrate have also been conducted for two of the compounds. Results indicate substantial inhibitory activity with inhibition association constants in the micromolar range. The experimental studies have been substantiated by docking of the aminonucleoside ligands to RNase A using AutoDock. We find that the ligands preferentially bind to the active site of the protein molecule with a favorable free energy of binding. The study has been extended to a member of the ribonuclease superfamily, angiogenin, which is a potent inducer of blood vessel formation. We show that the aminonucleosides act as potent inhibitors of angiogenin induced angiogenesis

Aflibercept vs. dexamethasone implant for recalcitrant diabetic macular edema in pseudophakic eyes – 1-year outcomes from a quazi-randomized study in India

Purpose: To assess the safety and efficacy of intravitreal Aflibercept (IVA) versus dexamethasone (DEX) implant for treating recalcitrant diabetic macular edema (DME) in pseudophakic eyes at 1-year follow-up. Design: Retrospective comparative case series. Participants: Data of all patients diagnosed with DME between January 2019 and December 2021, who underwent 4-monthly doses of intravitreal ranibizumab but had persistent DME [central macular thickness (CMT) within 10% of baseline value] were extracted from a computerized database. Of these, only pseudophakic eyes that underwent either IVA or DEX implant and had at least 1-year follow-up were included for analysis. Methods: DEX implant was preferred before December 2020 and IVA after this time point. In the IVA group, patients were followed up every month while DEX were followed at least every 3 months. Reinjections were considered when vision dropped by at least 1 Snellen’s line or CMT increased by at least 10% from the previous visit in both groups. Main Outcome Measures: Comparison of change in vision and CMT at 1-year follow-up in DEX versus IVA groups. Results: Eighty-four eyes of 84 patients aged 54.4 + 4.4 years were included, 39 (46%) received DEX and 45 (54%) received IVA. Groups were comparable for baseline vision and CMT. Vision improved equally in both groups from 0.83 + 0.15 logMAR to 0.52 + 0.10 logMAR at 3 months (P 3-line improvement in vision. The CMT reduction was also comparable between groups (-169 + 51 in DEX vs. -174 + 49 in IVA, P = 0.67). More eyes in the IVA group required >3 injections (91% vs. 69% in DEX, P = 0.01). The IOP was significantly higher at 6 and 9 months in the DEX group and 5 eyes (13%) required IOP lowering medications. Conclusion: In pseudophakic eyes with recalcitrant DME not responding to ranibizumab, switching to IVA or DEX implant results in equal visual improvement and CMT reduction. Though >3-line improvement occurs more frequently with IVA, this comes at the expense of a greater number of injections and follow-up visits

Electrochemical Evaluation of Dopant Energetics and the Modulation of Ultrafast Carrier Dynamics in Cu-Doped CdSe Nanocrystals

Cyclic voltammetric and femtosecond transient absorption (TA) measurements on Cu⁺-doped CdSe nanocrystals (NCs) were utilized to reveal the energetics of the electroactive Cu⁺ dopant with respect to the band energies of CdSe NC host and the influence of Cu in tuning the carrier dynamics, respectively. Oxidation–reduction peaks due to an electroactive dopant within CdSe NC host have been traced to determine its energy level which was correlated to the dopant emission energy and Stokes shift. The low doping density of Cu does not significantly alter the band structure of CdSe as the shape of the TA spectra remains similar before and after doping. However, Cu⁺ acts as a hole localizing center decoupling the electronic wave function from the hole leading to slower Auger-assisted electron cooling in doped NCs. As hole localization to Cu⁺ is the primary step for dopant emission, in the presence of hole quenchers (aminophenols) the dopant emission gets drastically quenched. Interestingly, once hole is captured by Cu⁺ due to strong affinity for electron, external quenchers (nitrophenols) are unable to capture the electron as confirmed from steady state and time-resolved measurements establishing the role of Cu as an internal sensitizer for the charge carriers

Intraband Electron Cooling Mediated Unprecedented Photocurrent Conversion Efficiency of CdS_<i>x</i>Se_1–<i>x</i> Alloy QDs: Direct Correlation between Electron Cooling and Efficiency

Composition and size dependent band gap engineering with longer excited state charge carrier lifetime assist CdS_<i>x</i>Se_1–<i>x</i> alloy semiconductor quantum dots (QDs) as a promising candidate for quantum dot solar cell (QDSC). Colloidal CdS_<i>x</i>Se_1–<i>x</i> alloy QDs were synthesized using the hot injection method where a stoichiometric mixture of S-TOP and Se-TOP were injected at 270 °C in a mixture of Cd-oleate. The electron decoupled from hole in the alloyed structure due to delocalization of electron in electronically quasi type-II graded CdS_<i>x</i>Se_1–<i>x</i> alloyed structure. As a result, intraband electron cooling time increases from 100s of fs to sub 10 ps time scale in the alloyed graded structure. Extremely slow electron cooling time (∼8 ps) and less charge recombination (∼50% in >2 ns) as compared to both CdS and CdSe QDs are found to be beneficial for charge carrier extraction in QD solar cells. Using polysulfide electrolyte and Cu₂S-deposited ITO glass plates as photocathode, the efficiency of the QD solar cell was measured to be 1.1 (±0.07)% for CdS, 3.36 (±0.1)% for CdSe, and 3.95 (±0.12)% for CdS_0.7Se_0.3 QDs. An additional nonepitaxial CdS quasi-shell followed by ZnS passivation layer (TiO₂/ CdS_0.7Se_0.3 /quasi-CdS/ZnS) was deposited on top of the CdS_0.7Se_0.3 film which showed a photo current conversion efficiency (PCE) of 4.5 (±0.18) %. The overall 14% increase of PCE is due to the quasi CdS shell helps to separate more electrons through passivating the surface states of TiO₂