Pre-monsoon Zonal Wind Index over Tibetan Plateau and sub-seasonal Indian summer monsoon rainfall variability

In this paper, by using the Principal Component Analysis (PCA) technique monthly zonal wind indices over Tibetan Plateau (25°N-45°N, 75-105°E) (TP) at 200 hPa have been constructed for the period 1948-2006. These indices are referred as Tibetan Zonal Wind Index (TZWI). The relationship between the TZWI and Indian summer monsoon rainfall on monthly basis has been studied by the correlation analysis. From the analysis, it is observed that pre-monsoon months (April and May) of TZWI show the significant inverse relationship with June and July rainfall over India respectively. The study may be useful for forecasting rainfall activity in June and July months, which are crucial months from the agricultural point of view

Dexmedetomidine premedication in cataract surgery under topical anaesthesia: to assess patient and surgeon satisfaction

Background: Dexmedetomidine is a potent non-opioid analgesic that may enhance analgesia for cataract surgery under topical anaesthesia. This study was undertaken to assess sedation and analgesia provided by dexmedetomidine and evaluating patients’ satisfication. Secondary aims were: (1) To study the effect of dexmedetomidine in decreasing the intraocular pressure. (2) The impact on surgeons' satisfaction. (3) Hemodynamic effectsMethods: We conducted a prospective randomized study on ASA I/II patients presenting for cataract surgery under topical anesthesia. Patients were randomly assigned to two groups: group D received dexmedetomidine premedication 1 mcg/kg over 10 minutes and group C received saline at the same rate. Sedation and pain score, intraocular pressure, patient and surgeon satisfaction score and hemodynamics were monitored and compared.Results: There was a significant increase in sedation assessed by the Ramsay sedation score at all times in group D after receiving dexmedetomidine (p< 0.0001). However, pain scores (numeric rating scale) were similar in both groups (p>0.05). Dexmedetomidine decreased the intraocular pressure and the difference was statistically highly significant (p< 0.0001). Group D had better patient and surgeon satisfaction score as against group C (p=0.0001). Noticably, the incidence of dry mouth was higher in group D. Hemodynamic parameters were well maintained in both groups with no adverse events in either group. Conclusions: Dexmedetomidine can be used safely for cataract surgery under topical anesthesia surgery. Administration of dexmedetomidine was associated with better patient and surgeon satisfaction

Brunner Gland Hamartoma: A Rare Incidental Finding on Autopsy

Brunner gland hamartoma (BGH), is a very rare benign tumor of the duodenum. It is usually asymptomatic and detected incidentally by endoscopy or other imaging modality. But, the definitive diagnosis is only by histopathological examination. We report an autopsy case in which a duodenal mass was found incidentally which was then confirmed histologically as Brunner gland hamartoma and the cause of death in this case was cerebral haemorrhage

Materials design by evolutionary optimization of functional groups in metal-organic frameworks

A genetic algorithm that efficiently optimizes a desired physical or functional property in metal-organic frameworks (MOFs) by evolving the functional groups within the pores has been developed. The approach has been used to optimize the CO₂ uptake capacity of 141 experimentally characterized MOFs under conditions relevant for postcombustion CO₂ capture. A total search space of 1.65 trillion structures was screened, and 1035 derivatives of 23 different parent MOFs were identified as having exceptional CO₂ uptakes of >3.0 mmol/g (at 0.15 atm and 298 K). Many well-known MOF platforms were optimized, with some, such as MIL-47, having their CO₂ adsorption increase by more than 400%. The structures of the high-performing MOFs are provided as potential targets for synthesis.: We thank the Natural Sciences and Engineering Research Council of Canada, Carbon Management Canada, and Canada Research Chairs Program for financial support and Compute Canada and the Canada Foundation for Innovation for computing resource

A Review of Vrushya Dravyas of Guduchyadi Varga of Bhavaprakasha Nighantu

Bhavaprakasha Nighantu, an important lexicon of Ayurveda consists of 23 Vargas where Guduchyadi Varga is one among them which consists of 190 drugs. Among them 28 drugs are attributed to Vrushya property. As Infertility has emerged as one of the most common health issues that many young couples are facing, there is a great demand for the treatment of infertility. While, the herbal therapies are better positioned to offer more holistic approaches to improve reproductive health. So here an attempt is made to screen the Vrushya Dravyas mentioned in Guduchyadi Varga of  Bhavaprakasha Nighantu with their Rasa, Guna, Veerya, Vipaka

LAT1 (SLC7A5) and CD98hc (SLC3A2) complex dynamics revealed by single-particle cryo-EM

Solute carriers are a large class of transporters that play key roles in normal and disease physiology. Among the solute carriers, heteromeric amino-acid transporters (HATs) are unique in their quaternary structure. LAT1–CD98hc, a HAT, transports essential amino acids and drugs across the blood–brain barrier and into cancer cells. It is therefore an important target both biologically and therapeutically. During the course of this work, cryo-EM structures of LAT1–CD98hc in the inward-facing conformation and in either the substrate-bound or apo states were reported to 3.3–3.5 Å resolution [Yan et al. (2019), Nature (London), 568, 127–130]. Here, these structures are analyzed together with our lower resolution cryo-EM structure, and multibody 3D auto-refinement against single-particle cryo-EM data was used to characterize the dynamics of the interaction of CD98hc and LAT1. It is shown that the CD98hc ectodomain and the LAT1 extracellular surface share no substantial interface. This allows the CD98hc ectodomain to have a high degree of movement within the extracellular space. The functional implications of these aspects are discussed together with the structure determination

Impact of medication and psychological behaviour assessment by community pharmacists in type 2 diabetes mellitus patients after hospital stay

Drug related problem (DRPs) is a key factor which will affect the outcome of therapy and safety. The aim of the present study is to assess the DRPs in T2DM patients and psychological aspects of patients by community pharmacists to observe the rate of DRP. Prospective randomized controlled intervention study involved T2DM patients and conducted in two community pharmacies at Kanpur from January 2012 to December 2012. The assessment of DRPs was based on the PCNE. Changes in HBA1C, LDL, BP, foot examinations, changes medical and medication utilization were studied. Using as control group, received usual care, and interventional group provided, intervened with use of the STG. Researcher provided the knowledge to community pharmacists and patients. Baseline and interventional data were collected at 0,3,6,9 and 12 months. Over 12 month study, participants’ average HBA1C reduced from 8.9% at initial visit to 7.5%. During this time, the eye examination rate was raised from 31% to 48%, and the foot examination rate was raised from 35% to 50%. It may be concluded that the intervention of pharmacists showed very less significant influence on any of the intermediate health outcomes in T2DM.Keywords: Type 2 Diabetes Mellitus, Drug related problems , PCNE classification, Medication review, Psychological behavior

The expanding toolkit for structural biology: synchrotrons, X-ray lasers and cryoEM

Structural biology continues to benefit from an expanding toolkit, which is helping to gain unprecedented insight into the assembly and organization of multi-protein machineries, enzyme mechanisms and ligand/inhibitor binding. The combination of results from X-ray free-electron lasers (XFELs), modern synchrotron crystallographic beamlines and cryo-electron microscopy (cryoEM) is proving to be particularly powerful. The highly brilliant undulator beamlines at modern synchrotron facilities have empowered the crystallographic revolution of high-throughput structure determination at high resolution. The brilliance of the X-rays at these crystallographic beamlines has enabled this to be achieved using microcrystals, but at the expense of an increased absorbed X-ray dose and a consequent vulnerability to radiation-induced changes. The advent of serial femtosecond crystallography (SFX) with X-ray free-electron lasers provides a new opportunity in which damage-free structures can be obtained from much smaller crystals (2 µm) and more complex macromolecules, including membrane proteins and multi-protein complexes. For redox enzymes, SFX provides a unique opportunity by providing damage-free structures at both cryogenic and ambient temperatures. The promise of being able to visualize macromolecular structures and complexes at high resolution without the need for crystals using X-rays has remained a dream, but recent technological advancements in cryoEM have made this come true and hardly a month goes by when the structure of a new/novel macromolecular assembly is not revealed. The uniqueness of cryoEM in providing structural information for multi-protein complexes, particularly membrane proteins, has been demonstrated by examples such as respirasomes. The synergistic use of cryoEM and crystallography in lead-compound optimization is highlighted by the example of the visualization of antimalarial compounds in cytochrome bc1. In this short review, using some recent examples including our own work, we share the excitement of these powerful structural biology methods

Dimeric structures of quinol-dependent nitric oxide reductases (qNORs) revealed by cryo–electron microscopy

Quinol-dependent nitric oxide reductases (qNORs) are membrane-integrated, iron-containing enzymes of the denitrification pathway, which catalyze the reduction of nitric oxide (NO) to the major ozone destroying gas nitrous oxide (N2O). Cryo–electron microscopy structures of active qNOR from Alcaligenes xylosoxidans and an activity-enhancing mutant have been determined to be at local resolutions of 3.7 and 3.2 Å, respectively. They unexpectedly reveal a dimeric conformation (also confirmed for qNOR from Neisseria meningitidis) and define the active-site configuration, with a clear water channel from the cytoplasm. Structure-based mutagenesis has identified key residues involved in proton transport and substrate delivery to the active site of qNORs. The proton supply direction differs from cytochrome c–dependent NOR (cNOR), where water molecules from the cytoplasm serve as a proton source similar to those from cytochrome c oxidase

The active form of quinol-dependent Nitric Oxide reductase (qNOR) from Neisseria meningitidis is a dimer

Neisseria meningitidis is carried by nearly a billion humans, causing developmental impairment and over 100 000 deaths a year. A quinol-dependent nitric oxide reductase (qNOR) plays a critical role in the survival of the bacterium in the human host. X-ray crystallographic analyses of qNOR, including that from N. meningitidis (NmqNOR) reported here at 3.15 Å resolution, show monomeric assemblies, despite the more active dimeric sample being used for crystallization. Cryo-electron microscopic analysis of the same chromatographic fraction of NmqNOR, however, revealed a dimeric assembly at 3.06 Å resolution. It is shown that zinc (which is used in crystallization) binding near the dimer-stabilizing TMII region contributes to the disruption of the dimer. A similar destabilization is observed in the monomeric (∼85 kDa) cryo-EM structure of a mutant (Glu494Ala) qNOR from the opportunistic pathogen Alcaligenes (Achromobacter) xylosoxidans, which primarily migrates as a monomer. The monomer–dimer transition of qNORs seen in the cryo-EM and crystallographic structures has wider implications for structural studies of multimeric membrane proteins. X-ray crystallographic and cryo-EM structural analyses have been performed on the same chromatographic fraction of NmqNOR to high resolution. This represents one of the first examples in which the two approaches have been used to reveal a monomeric assembly in crystallo and a dimeric assembly in vitrified cryo-EM grids. A number of factors have been identified that may trigger the destabilization of helices that are necessary to preserve the integrity of the dimer. These include zinc binding near the entry of the putative proton-transfer channel and the preservation of the conformational integrity of the active site. The mutation near the active site results in disruption of the active site, causing an additional destabilization of helices (TMIX and TMX) that flank the proton-transfer channel helices, creating an inert monomeric enzyme