The mRNA-capping enzyme localizes to stress granules in the cytoplasm and maintains cap homeostasis of target mRNAs.

The model of RNA stability has undergone a transformative shift with the revelation of a cytoplasmic capping activity that means a subset of transcripts are recapped autonomously of their nuclear counterparts. The present study demonstrates nucleo-cytoplasmic shuttling of the mRNA-capping enzyme (CE, also known as RNA guanylyltransferase and 5'-phosphatase; RNGTT), traditionally acknowledged for its nuclear localization and functions, elucidating its contribution to cytoplasmic capping activities. A unique nuclear export sequence in CE mediates XPO1-dependent nuclear export of CE. Notably, during sodium arsenite-induced oxidative stress, cytoplasmic CE (cCE) congregates within stress granules (SGs). Through an integrated approach involving molecular docking and subsequent co-immunoprecipitation, we identify eIF3b, a constituent of SGs, as an interactive associate of CE, implying that it has a potential role in guiding cCE to SGs. We measured the cap status of specific mRNA transcripts from U2OS cells that were non-stressed, stressed and recovered from stress, which indicated that cCE-target transcripts lost their caps during stress but remarkably regained cap stability during the recovery phase. This comprehensive study thus uncovers a novel facet of cytoplasmic CE, which facilitates cellular recovery from stress by maintaining cap homeostasis of target mRNAs.

Colloidal Atomic Layer Deposition on Nanocrystals Using Ligand-Modified Precursors.

Atomic layer deposition (ALD) is a method to grow thin metal oxide layers on a variety of materials for applications spanning from electronics to catalysis. Extending ALD to colloidally stable nanocrystals promises to combine the benefits of thin metal oxide coatings with the solution processability of the nanocrystals. However, challenges persist in applying this method, which relate to finding precursors that promote the growth of the metal oxide while preserving colloidal stability throughout the process. Herein, we introduce a colloidal ALD method to coat nanocrystals with amorphous metal oxide shells using metal and oxygen precursors that act as colloidal stabilizing ligands. Our scheme involves metal-amide precursors modified with solubilizing groups and oleic acid as the oxygen source. The growth of the oxide is self-limiting and proceeds in a layer-by-layer fashion. Our protocol is generalizable and intrinsically scalable. Potential applications in display, light detection, and catalysis are envisioned.

Biomechanical trade-offs in the pelvic floor constrain the evolution of the human birth canal.

Compared with most other primates, humans are characterized by a tight fit between the maternal birth canal and the fetal head, leading to a relatively high risk of neonatal and maternal mortality and morbidities. Obstetric selection is thought to favor a spacious birth canal, whereas the source for opposing selection is frequently assumed to relate to bipedal locomotion. Another, yet underinvestigated, hypothesis is that a more expansive birth canal suspends the soft tissue of the pelvic floor across a larger area, which is disadvantageous for continence and support of the weight of the inner organs and fetus. To test this "pelvic floor hypothesis," we generated a finite element model of the human female pelvic floor and varied its radial size and thickness while keeping all else constant. This allowed us to study the effect of pelvic geometry on pelvic floor deflection (i.e., the amount of bending from the original position) and tissue stresses and stretches. Deflection grew disproportionately fast with increasing radial size, and stresses and stretches also increased. By contrast, an increase in thickness increased pelvic floor stiffness (i.e., the resistance to deformation), which reduced deflection but was unable to fully compensate for the effect of increasing radial size. Moreover, larger thicknesses increase the intra-abdominal pressure necessary for childbirth. Our results support the pelvic floor hypothesis and evince functional trade-offs affecting not only the size of the birth canal but also the thickness and stiffness of the pelvic floor.

Effect of short-term exposure to high-altitude hypoxic climate on feed-intake, blood glucose level and physiological responses of native and non-native goat.

The exposure to high altitude and cold stress poses challenges in maintaining normal physiological standards and body homeostasis in non-native animals. To enhance our understanding of the physiology of native and non-native goats in high-altitude environments, we conducted a comparative study to examine the impact of natural hypoxic and cold stress conditions on their feed intake (FIT) and associated changes in physiological responses, including plasma glucose concentration (PGC). The study took place at an altitude of 3505.2 m above mean sea level and involved twenty-two healthy females from two different breeds of goats. This study was conducted over a period of 56 days after the arrival of non-native Black Bengal goats (BBN) and compared with native Changthangi (CHAN) goats. Both groups were extensively reared in a natural high-altitude and cold-stress environment in Leh, India, and were subjected to defined housing and management practices. The parameters evaluated included FIT, PGC, respiration rate, heart rate, pulse rate, and rectal temperature. High altitudes had a significant (p < 0.05) impact on FIT, PGC, respiration rate, heart rate, pulse rate, and rectal temperature in BBN, whereas these parameters remained stable in CHAN throughout the study period. Additionally, the detrimental effects of high-altitude stress were more pronounced in non-native goats compared to native goats. These findings suggest that physiological responses in non-native goats tend to stabilize after an initial period of adverse effects in high-altitude environments. Based on the physiological responses and glucose concentration, it is recommended to pay special attention to the nutrition of non-native goats for up to the third week (21 days) after their arrival in high-altitude areas.

Voltage-Driven Chemical Reactions Enable the Synthesis of Tunable Liquid Ga-Metal Nanoparticles.

Nanosized particles of liquid metals are emerging materials that hold promise for applications spanning from microelectronics to catalysis. Yet, knowledge of their chemical reactivity is largely unknown. Here, we study the reactivity of liquid Ga and Cu nanoparticles under the application of a cathodic voltage. We discover that the applied voltage and the spatial proximity of these two particle precursors dictate the reaction outcome. In particular, we find that a gradual voltage ramp is crucial to reduce the native oxide skin of gallium and enable reactive wetting between the Ga and Cu nanoparticles; instead, a voltage step causes dewetting between the two. We determine that the use of liquid Ga/Cu nanodimer precursors, which consist of an oxide-covered Ga domain interfaced with a metallic Cu domain, provides a more uniform mixing and results in more homogeneous reaction products compared to a physical mixture of Ga and Cu NPs. Having learned this, we obtain CuGa2 alloys or solid@liquid CuGa2@Ga core@shell nanoparticles by tuning the stoichiometry of Ga and Cu in the nanodimer precursors. These products reveal an interesting complementarity of thermal and voltage-driven syntheses to expand the compositional range of bimetallic NPs. Finally, we extend the voltage-driven synthesis to the combination of Ga with other elements (Ag, Sn, Co, and W). By rationalizing the impact of the native skin reduction rate, the wetting properties, and the chemical reactivity between Ga and other metals on the results of such voltage-driven chemical manipulation, we define the criteria to predict the outcome of this reaction and set the ground for future studies targeting various applications for multielement nanomaterials based on liquid Ga.

Description of Photodegradation Mechanisms and Structural Characteristics in Carbon@Titania Yolk-Shell Nanostructures by XAS.

Carbon@titania yolk-shell nanostructures are successfully synthesized at different calcination conditions. These unique structure nanomaterials can be used as a photocatalyst to degrade the emerging water pollutant, acetaminophen (paracetamol). The photodegradation analysis studies have shown that the samples with residual carbon nanospheres have improved the photocatalytic efficiency. The local electronic and atomic structure of the nanostructures are analyzed by X-ray absorption spectroscopy (XAS) measurements. The spectra confirm that the hollow shell has an anatase phase structure, slight lattice distortion, and variation in Ti 3d orbital orientation. In situ XAS measurements reveal that the existence of amorphous carbon nanospheres inside the nano spherical shell inhibit the recombination of electron-hole pairs; more mobile holes are formed in the p-d hybridized bands near the Fermi surface and enables the acceleration of the carries that significantly enhance the photodegradation of paracetamol under UV-visible irradiation. The observed charge transfer process from TiO2  hybridized orbital to the carbon nanospheres reduces the recombination rate of electrons and holes, thus increasing the photocatalytic efficiency.

Variability in the Responses of Hepatitis B Virus D-Subgenotypes to Antiviral Therapy: Designing Pan-D-Subgenotypic Reverse Transcriptase Inhibitors.

Nucleos(t)ide analogues entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are recommended as first-line monotherapies for chronic hepatitis B (CHB). Multiple HBV genotypes/subgenotypes have been described, but their impact on treatment response remains largely elusive. We investigated the effectiveness of ETV/TDF on HBV/D-subgenotypes, D1/D2/D3/D5, studied the structural/functional differences in subgenotype-specific reverse transcriptase (RT) domains of viral polymerase, and identified novel molecules with robust inhibitory activity on various D-subgenotypes. Transfection of Huh7 cells with full-length D1/D2/D3/D5 and in vitro TDF/ETV susceptibility assays demonstrated that D1/D2 had greater susceptibility to TDF/ETV while D3/D5 exhibited poorer response. Additionally, HBV load was substantially reduced in TDF-treated CHB patients carrying D1/D2 but minimally reduced in D3/D5-infected patients. Comparison of RT sequences of D-subgenotypes led to identification of unique subgenotype-specific residues, and molecular modeling/docking/simulation studies depicted differential bindings of TDF/ETV to the active site of their respective RTs. Replacement of signature residues in D3/D5 HBV clones with corresponding amino acids seen in D1/D2 improved their susceptibility to TDF/ETV. Using high throughput virtual screening, we identified N(9)-[3-fluoro-2-(phosphonomethoxy)propyl] (FPMP) derivatives of purine bases, including N6-substituted (S)-FPMP derivative of 2,6-diaminopurine (DAP) (OB-123-VK), as potential binders of RT of different D-subgenotypes. We synthesized (S)-FPMPG prodrugs (FK-381-FEE/FK-381-SEE/FK-382) and tested their effectiveness along with OB-123-VK. Both OB-123-VK and FK-381-FEE exerted similar antiviral activities against all D-subgenotypes, although FK-381-FEE was more potent. Our study highlighted the natural variation in therapeutic response of D1/D2/D3/D5 and emphasized the need for HBV subgenotype determination before treatment. Novel molecules described here could benefit future design/discovery of pan-D-subgenotypic inhibitors. IMPORTANCE Current treatment of chronic hepatitis B relies heavily on nucleotide/nucleoside analogs in particular, tenofovir disoproxil fumarate (TDF) and entecavir (ETV) to keep HBV replication under control and prevent end-stage liver diseases. However, it was unclear whether the therapeutic effects of TDF/ETV differ among patients infected with different HBV genotypes and subgenotypes. HBV genotype D is the most widespread of all HBV genotypes and multiple D-subgenotypes have been described. We here report that different subgenotypes of HBV genotype-D exhibit variable response toward TDF and ETV and this could be attributed to naturally occurring amino acid changes in the reverse transcriptase domain of the subgenotype-specific polymerase. Further, we identified novel molecules and also synthesized prodrugs that are equally effective on different D-subgenotypes and could facilitate management of HBV/D-infected patients irrespective of D-subgenotype.

Death registration coverage 2019-2021, India.

Objective: To investigate coverage and factors associated with death registration in India. Methods: We used data from the Indian National Family Health Survey 2019-2021. Based on responses of eligible household members, we estimated death registration in 84 390 deaths in all age groups across the country. We used multilevel logistic regression analysis to determine sociodemographic variables associated with death registration at state, district and individual levels. Findings: Nationally, 70.8% (59 748/84 390) of deaths were registered. Of 707 districts in our study period, 122 and 53 districts had death registration levels less than 40% in females and males, respectively. The likelihood of death registration was significantly lower for females than males (adjusted odds ratios, aOR: 0.61; 95% confidence interval, CI: 0.59-0.64). Death registration increased significantly with age of the deceased person, with the highest odds in 35-49-year-olds (aOR: 5.05; 95% CI: 4.58-5.57) compared with 0-4-year-olds. Death registration was less likely among rural households, disadvantaged castes, the poorest wealth quintile, Muslims and households without a below poverty level card. Higher education was associated with higher death registration with the greatest likelihood of registration in households with a member with post-secondary school education (aOR: 1.54; 95% CI: 1.42-1.66). District-level factors were not significantly associated with death registration. Conclusion: Sociodemographic characteristics of the deceased person were significantly associated with death registration. Strategies to raise awareness of death registration procedures among disadvantaged population groups and the introduction of a mobile telephone application for death registration are recommended to improve death registration in India.

Spectrum, Outcomes, and Mortality Predictors of Acute Kidney Injury among Non-COVID-19 Patients during COVID-19 Pandemic: Data from Four Intensive Care Units.

Introduction: The data of acute kidney injury (AKI), that is, community-acquired AKI (CA-AKI) and hospital-acquired AKI (HA-AKI) among non-COVID patients from intensive care units (ICU) during the coronavirus disease-2019 (COVID-19) pandemic are scarce. We planned to study the change in the profile of such patients compared to the pre-pandemic era. Materials and methods: This prospective observational study was conducted at four ICUs dealing with non-COVID patients at a government hospital in North India, and was aimed at assessing outcomes, and mortality predictors of AKI among non-COVID patients during the COVID-19 pandemic. Renal and patient survival at ICU transfer-out and hospital discharge, ICU and hospital stay duration, mortality predictors, and dialysis requirement at discharge were evaluated. The current or previous COVID-19 infection, previous AKI or chronic kidney disease (CKD), organ donors, and organ transplant patients were excluded. Results: Among the 200 non-COVID-19 AKI patients, diabetes mellitus (DM), primary hypertension, and cardiovascular diseases were the predominant comorbidities in descending order. The commonest cause of AKI was severe sepsis, followed by systemic infections and post-surgery patients. Dialysis requirements at ICU admission during ICU stay and above 30 days were seen in 20.5, 47.5, and 6.5% of patients, respectively. Incidence of CA-AKI and HA-AKI was 1.24:1, whereas dialysis requirement above 30 days was 0.85:1, respectively. The 30-day mortality was 42%. Hepatic dysfunction [hazard ratio (HR): 3.471], septicemia (HR: 3.342), age above 60 years (HR: 4.000), higher sequential organ failure assessment (SOFA) score (HR: 1.107; p = 0.001), anemia (p = 0.003), and low serum iron (p = 0.001) were important mortality predictors in AKI. Conclusion: Compared to the pre-COVID era, CA-AKI was more common than HA-AKI due to restricted elective surgeries during the COVID-19 pandemic. Acute kidney injury with multiorgan involvement and hepatic dysfunction, elderly age with higher SOFA score and sepsis were predictors of adverse renal and patient outcomes. How to cite this article: Singh B, Dogra PM, Sood V, Singh V, Katyal A, Dhawan M, et al. Spectrum, Outcomes, and Mortality Predictors of Acute Kidney Injury among Non-COVID-19 Patients during COVID-19 Pandemic: Data from Four Intensive Care Units. Indian J Crit Care Med 2023;27(2):119-126.

Interface Dynamics in Ag-Cu3P Nanoparticle Heterostructures.

Earth-abundant transition metal phosphides are promising materials for energy-related applications. Specifically, copper(I) phosphide is such a material and shows excellent photocatalytic activity. Currently, there are substantial research efforts to synthesize well-defined metal-semiconductor nanoparticle heterostructures to enhance the photocatalytic performance by an efficient separation of charge carriers. The involved crystal facets and heterointerfaces have a major impact on the efficiency of a heterostructured photocatalyst, which points out the importance of synthesizing potential photocatalysts in a controlled manner and characterizing their structural and morphological properties in detail. In this study, we investigated the interface dynamics occurring around the synthesis of Ag-Cu3P nanoparticle heterostructures by a chemical reaction between Ag-Cu nanoparticle heterostructures and phosphine in an environmental transmission electron microscope. The major product of the Cu-Cu3P phase transformation using Ag-Cu nanoparticle heterostructures with a defined interface as a template preserved the initially present Ag{111} facet of the heterointerface. After the complete transformation, corner truncation of the faceted Cu3P phase led to a physical transformation of the nanoparticle heterostructure. In some cases, the structural rearrangement toward an energetically more favorable heterointerface has been observed and analyzed in detail at the atomic level. The herein-reported results will help better understand dynamic processes in Ag-Cu3P nanoparticle heterostructures and enable facet-engineered surface and heterointerface design to tailor their physical properties.

Towards Non-stick Silk: Tuning the Hydrophobicity of Silk Fibroin Protein.

Silk fibroin protein is a biomaterial with excellent biocompatibility and low immunogenicity. These properties have catapulted the material as a leader for extensive use in stents, catheters, and wound dressings. Modulation of hydrophobicity of silk fibroin protein to further expand the scope and utility however has been elusive. We report that installing perfluorocarbon chains on the surface of silk fibroin transforms this water-soluble protein into a remarkably hydrophobic polymer that can be solvent-cast. A clear relationship emerged between fluorine content of the modified silk and film hydrophobicity. Water contact angles of the most decorated silk fibroin protein exceeded that of Teflon®. We further show that water uptake in prefabricated silk bars is dramatically reduced, extending their lifetimes, and maintaining mechanical integrity. These results highlight the power of chemistry under moderate conditions to install unnatural groups onto the silk fibroin surface and will enable further exploration into applications of this versatile biomaterial.

Swift catalytic reduction of hazardous pollutants by new generation microgels.

In this manuscript, we report for the first time a new generation microgel synthesis without using any divinyl functionalized cross-linker. A new generation less crosslinked microgel structure has been achieved by optimizing the amount of N-hydroxy methyl acrylamide (NHMA) and using a fixed amount of styrene (St), acrylic acid (AA) and N-vinyl pyrrolidone (NVP) via a free radical emulsion solution polymerization technique. Poly(NHMA) works as a hydrophilic as well as a crosslinking agent. Furthermore, microgels have been upgraded into a composite by incorporation of Ag nanoparticles for catalytic reduction applications. Microgels and their composites have been characterized by EDAX, FT-IR, particle size analyzer, SEM, TEM, TGA, UV-vis spectroscopy and XRD. Methylene blue (MB) dye and p-nitrophenol (PNP) were chosen as model hazardous pollutants for catalytic reduction applications. Microgels efficiently adsorb both pollutants over the surface and microgel_Ag composites dramatically reduced both pollutants in the non-toxic form at room temperature by using smaller doses of NaBH4.

Newly designed acrylamide derivative-based pH-responsive hydrogel-urease bioconjugates: synthesis and catalytic urea hydrolysis.

Jack bean urease, the first nickel metalloenzyme, and crystallized enzymes have historical significance due to their several applications in the biomedical and other fields. For the first time, cross-linker free pH-responsive hydrogel-urease bioconjugates have been reported. Without the use of divinyl benzene or divinyl acrylamide derivatives, urease was immobilized inside the hydrogel matrix and various grades of bioconjugates were synthesized. The hydrogel-urease bioconjugate exhibits excellent swelling-deswelling and pH-responsive characteristics without affecting the urease enzyme. The pH-responsive bioconjugates were characterized by FT-IR, powder XRD, SEM, TGA, and UV-vis spectroscopy. Urea hydrolysis and enzyme affinity have been investigated at pH 4, pH 7, and pH 11 using bioconjugates and free urease. At basic pH, BCs showed excellent enzyme activity. In summary, this technique is effective for stabilizing biomacromolecules at different pHs for a variety of real applications.

The Use of Computational Geometry Techniques to Resolve the Issues of Coverage and Connectivity in Wireless Sensor Networks.

Wireless Sensor Networks (WSNs) enhance the ability to sense and control the physical environment in various applications. The functionality of WSNs depends on various aspects like the localization of nodes, the strategies of node deployment, and a lifetime of nodes and routing techniques, etc. Coverage is an essential part of WSNs wherein the targeted area is covered by at least one node. Computational Geometry (CG) -based techniques significantly improve the coverage and connectivity of WSNs. This paper is a step towards employing some of the popular techniques in WSNs in a productive manner. Furthermore, this paper attempts to survey the existing research conducted using Computational Geometry-based methods in WSNs. In order to address coverage and connectivity issues in WSNs, the use of the Voronoi Diagram, Delaunay Triangulation, Voronoi Tessellation, and the Convex Hull have played a prominent role. Finally, the paper concludes by discussing various research challenges and proposed solutions using Computational Geometry-based techniques.

Role of Regulatory Proteins Involved in Iron Homeostasis in Pulmonary Tuberculosis Patients and Their Household Contacts.

Early identification and treatment of active tuberculosis disease among high risk household contacts could limit new transmission and better clinical outcome, thus decreasing TB burden. Host iron homeostasis is an important yet underevaluated factor in pathophysiology of tuberculosis (TB). One such protein is hepcidin which internalizes ferroportin (membrane iron transporter), thus inhibiting iron export from macrophages which is utilised by bacteria leading to disease severity. Iron homeostasis markers were evaluated in 50 pulmonary tuberculosis patients (PTB) and their household contacts to assess their utility as biomarkers for TB development. Altered iron homeostasis with significantly lower haemoglobin levels despite optimum serum iron levels was observed in PTB compared to household contacts and healthy controls pointing towards anaemia of inflammation. Higher serum hepcidin with lower ferroportin expression and hence higher ferritin levels was seen in PTB compared to both household contacts and healthy controls due to IL-6 induced hepcidin production in TB. Transferrin levels were found to be significantly lower in PTB and household contacts as compared to healthy controls owing to higher ferritin levels in PTB group. Upon infection, regulation of iron absorption is disturbed via increased hepcidin levels leading to ferroportin internalization and thus inhibition of iron export from macrophages which may lead to favourable M.tb. survival and multiplication leading to tuberculosis. Some of these markers could be assessed for early identification and treatment of active tuberculosis among high risk household contacts limiting new transmission and better clinical outcome, thus decreasing TB burden.

A plastid-localized bona fide geranylgeranyl diphosphate synthase plays a necessary role in monoterpene indole alkaloid biosynthesis in Catharanthus roseus.

In plants, geranylgeranyl diphosphate (GGPP, C20 ) synthesized by GGPP synthase (GGPPS) serves as precursor for vital metabolic branches including specialized metabolites. Here, we report the characterization of a GGPPS (CrGGPPS2) from the Madagascar periwinkle (Catharanthus roseus) and demonstrate its role in monoterpene (C10 )-indole alkaloids (MIA) biosynthesis. The expression of CrGGPPS2 was not induced in response to methyl jasmonate (MeJA), and was similar to the gene encoding type-I protein geranylgeranyltransferase_ß subunit (CrPGGT-I_ß), which modulates MIA formation in C. roseus cell cultures. Recombinant CrGGPPS2 exhibited a bona fide GGPPS activity by catalyzing the formation of GGPP as the sole product. Co-localization of fluorescent protein fusions clearly showed CrGGPPS2 was targeted to plastids. Downregulation of CrGGPPS2 by virus-induced gene silencing (VIGS) significantly decreased the expression of transcription factors and pathway genes related to MIA biosynthesis, resulting in reduced MIA. Chemical complementation of CrGGPPS2-vigs leaves with geranylgeraniol (GGol, alcoholic form of GGPP) restored the negative effects of CrGGPPS2 silencing on MIA biosynthesis. In contrast to VIGS, transient and stable overexpression of CrGGPPS2 enhanced the MIA biosynthesis. Interestingly, VIGS and transgenic-overexpression of CrGGPPS2 had no effect on the main GGPP-derived metabolites, cholorophylls and carotenoids in C. roseus leaves. Moreover, silencing of CrPGGT-I_ß, similar to CrGGPPS2-vigs, negatively affected the genes related to MIA biosynthesis resulting in reduced MIA. Overall, this study demonstrated that plastidial CrGGPPS2 plays an indirect but necessary role in MIA biosynthesis. We propose that CrGGPPS2 might be involved in providing GGPP for modifying proteins of the signaling pathway involved in MIA biosynthesis.

Whole-exome analyses of congenital muscular dystrophy and congenital myopathy patients from India reveal a wide spectrum of known and novel mutations.

BACKGROUND AND PURPOSE: Congenital muscular dystrophies (CMDs) and congenital myopathies (CMs) are a group of genetically and clinically heterogeneous degenerative primary muscle disorders with onset at birth or during infancy. Due to vast heterogeneity, clinical examination and protein-based analyses often fail to identify the genetic causes of these diseases. The aim of this study was to genetically diagnose a cohort of 36 difficult-to-diagnose CMD and CM cases of Indian origin using next-generation sequencing methods. METHODS: Whole-exome sequencing (WES) was performed to identify pathogenic mutations in previously reported CMD and CM-related genes using variant calling and stringent variant filtration process. Subsequently, in silico homology modelling and molecular dynamics simulations (MDS) studies were undertaken for a number of novel and missense variants. RESULTS: A total of 33 and 21 rare and deleterious mutations were identified in 28 genes previously reported in CMD and CM based on OMIM, ClinVar and Orphanet, respectively. We could accurately diagnose 54% patients (n = 12/22) in the CMD group and 35% patients (n = 5/14) in the CM group. Furthermore, MDS studies for mutations located in LMNA, LAMA2 and RYR1 suggest that the wild-type proteins are more stable than their mutant counterparts, implying a potential mechanism of pathogenesis. CONCLUSION: The WES findings led us to identify reported as well as novel variants for the first time in Indian patients with CMD and CM. This allowed us to achieve an accurate genetic diagnosis, which was difficult using conventional diagnostic tools. Transferring these WES findings to clinical practice will help guide clinical care of the affected patients and inform genetic counselling.

Synthesis of a Series of a Few Hydrosulfide Complexes of Cu(I). A µ3-SH-Bridged Rare Cubane-like Tetramer Showing Efficient Catalytic Activity toward Azide-Alkyne Cycloaddition.

A cubane-like tetranuclear hydrosulfido complex of Cu(I), [Cu4(SH)4(PPh3)4] (1), has been synthesized by the reaction of Cu(NO3)2·3H2O, NaSCOPh, and Cu(PPh3)2NO3 and characterized structurally. Complex 1 represents the first example of crystallographically characterized µ3-SH-bridged cubanoid hydrosulfide. By direct reactions of [(PPh3)2Cu(NO3)] and NaSH, neutral hydrosulfide complexes [Cu(SH)(PPh3)2]·C6H6 (2), [Cu2(SH)2(PPh3)3] (3), and [Cu2(SH)2(PPh3)4] (4) have also been synthesized and structurally characterized. Complex 2 is monomeric with a terminal hydrosulfide ligand. The other two, 3 and 4, are µ2-SH-bridged unsymmetrical and symmetrical dinuclear complexes, respectively. In the symmetric one (4), both Cu(I) ions are tetrahedrally coordinated while in the unsymmetric one (3), one Cu(I) ion is tetrahedral and the other one has a trigonal-planar coordination geometry. The catalytic activity of a hydrosulfido complex in a "click" azide-alkyne cycloaddition reaction has been explored for the first time, and complex 1 is found to be an efficient catalyst for the regioselective synthesis of glycoconjugate triazoles.

PresRAT: a server for identification of bacterial small-RNA sequences and their targets with probable binding region.

Bacterial small-RNA (sRNA) sequences are functional RNAs, which play an important role in regulating the expression of a diverse class of genes. It is thus critical to identify such sRNA sequences and their probable mRNA targets. Here, we discuss new procedures to identify and characterize sRNA and their targets via the introduction of an integrated online platform 'PresRAT'. PresRAT uses the primary and secondary structural attributes of sRNA sequences to predict sRNA from a given sequence or bacterial genome. PresRAT also finds probable target mRNAs of sRNA sequences from a given bacterial chromosome and further concentrates on the identification of the probable sRNA-mRNA binding regions. Using PresRAT, we have identified a total of 66,209 potential sRNA sequences from 292 bacterial genomes and 2247 potential targets from 13 bacterial genomes. We have also implemented a protocol to build and refine 3D models of sRNA and sRNA-mRNA duplex regions and generated 3D models of 50 known sRNAs and 81 sRNA-mRNA duplexes using this platform. Along with the server part, PresRAT also contains a database section, which enlists the predicted sRNA sequences, sRNA targets, and their corresponding 3D models with structural dynamics information.

"Shunt Pumping Test": role of practice on an experimental model.

PURPOSE: To ascertain the benefits of practicing shunt pumping test on a validated experimental model. METHODS: A validated experimental model of shunt was used and 25 medical professionals were asked to assess the block in the model where artificial blocks were created. The assessment was repeated after the participants had practiced on the same model. The performance of participants before and after practice was compared and statistically evaluated. RESULTS: The ability to predict the status of shunt showed an improvement in all scenarios after practice. The odds ratio for predicting a blocked shunt before and after practice was 7.25 (95% credible interval: 1.50-21.01). The odds ratio for predicting a functional shunt before and after practice was 8.81 (95% credible interval of 1.64 to 13.65). CONCLUSION: Practicing on the experimental model significantly improves the ability to predict the status of shunt. Training of primary caregivers on similar shunt models based on the shunts used in respective centers can improve an early detection of shunt block and reduce reliance on more invasive and expensive evaluation modalities.