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A liposome based nanosensor Lipo-1 for efficient detection of copper, cyanide (CN-) and ATP in a pure aqueous medium has been described. Lipo-1 shows a fluorescence ON-OFF response with copper. However, Lipo-1.Cu (Lipo-1 and copper ensemble) was used for the OFF-ON detection of ATP with nM and CN- with μM detection levels, lower than the WHO permissible level for safe drinking. Lipo-1 has better and enhanced binding properties over the counter organic amphiphilic compound Bzimpy-LC, which is not soluble in water. The significant changes in the emission spectra in the presence of Cu2+, CN- and ATP ions, as variable inputs, are used to construct INHIBIT and OR logic operations in a nano-scale environment. The fluorescent detection of CN- ions with Lipo-1.Cu was used to develop an enzyme assay for β-glucosidase using amygdalin as the substrate. β-Glucosidase enzymatic activity was monitored by the emission OFF-ON signal of the probe Lipo-1.Cu by CN- detection. This approach could be an efficient method for developing a fluorescence-based β-glucosidase enzyme assay. Axitinib supplier A switch ON luminescence response, low detection limit, fast response, 100% aqueous solution, biocompatibility, multi-analyte detection, and improved sensitivity and selectivity of Bzimpy-LC in lipid bilayer membranes are the main features of the nanoprobe Lipo-1. These properties give it a clear advantage for analytical applications.

Clozapine is the gold standard in the management of treatment-resistant schizophrenia. Despite its clinically proven efficacy clozapine utilization is variable globally and published evidence is suggestive of its underutilization. Research from the Arab region on clozapine utilization is limited. The aim of our descriptive observational study was to evaluate the prescribing practice of clozapine and its sociodemographic and clinical corelates in the State of Qatar.

The study is a retrospective case-note review of all patients maintained on clozapine, in the calendar year 2020. Data were collected on sociodemographic characteristics of the patients; antipsychotic trials before initiating clozapine; and clinical characteristics of the patients, including their diagnoses leading to prescription of clozapine, duration of illness, psychiatric hospitalizations, and co-morbidities.

During the study period, 100 patients were maintained on clozapine. Patients were mostly Qatari and non-Qatari Arab males. Prescricant delay in Clozapine initiation despite its clinical superiority.

First study on Clozapine utilization from the Middle-East and North-Africa region. This study examined prescribing of clozapine in a national cohort of patients in Qatar. Provides insight into sociodemographic and clinical correlates of clozapine prescribing in a country with 90% migrants. Limited by the completeness of the information contained in the patients' medical charts.

First study on Clozapine utilization from the Middle-East and North-Africa region. This study examined prescribing of clozapine in a national cohort of patients in Qatar. Provides insight into sociodemographic and clinical correlates of clozapine prescribing in a country with 90% migrants. Limited by the completeness of the information contained in the patients' medical charts.Background and Objectives Brain damage which has been induced by radiation generally occurs in radiotherapeutics patient. Stem cells transplantation represents a vital applicant for alleviating neurodegenerative disorders. This work aims at exploring the potential of bone marrow derived mesenchymal stem cells (BM-MSCs) on brain injury induced by γ radiation in mice and the possible underlying mechanisms were elucidated. Materials & Methods Mice were allocated into three groups; Group I (Control), Group II (Irradiated control) where mice submitted to 5 Gy of whole body γ radiation, Group III (Irradiated + BM-MSCs) where mice were intravenouslyinjected of BM-MSCs at a dose of 106 cells/mice 24 hours following irradiation. Animals were sacrificed 28 days following exposure to γ radiation. Results It was observed that BM-MSCs therapy provided a valuable tissue repair as evidenced by reduction in inflammatory mediators including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), nuclear factor kappa (NF-κβ), interferon gamma (IFN γ) and monocyte chemoattractant protein-1 (MCP-1) associated with decreased levels of transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF) in brain tissues of irradiated mice. Furthermore, neuronal apoptosis was declined in brain tissues of BM-MSCs group as remarkable inhibition of caspase-3 and Bax accompanied by elevation of Bcl-2 proteins expression. These results were supported by histopathological investigation. Conclusions In conclusion, BM-MSCs could display a vital rule in alleviating brain injury in radio-therapeutic patients.The Kv family of voltage-gated potassium channels regulate neuronal excitability. The biophysical characteristics of Kv channels can be matched to the needs of different neurons by forming homotetrameric or heterotetrameric channels within one of four subfamilies. The cytoplasmic tetramerization (T1) domain plays a major role in dictating the compatibility of different Kv subunits. The only Kv subfamily lacking a representative structure of the T1 domain is the Kv2 family. Here, X-ray crystallography was used to solve the structure of the human Kv2.1 T1 domain. The structure is similar to those of other T1 domains, but surprisingly formed a pentamer instead of a tetramer. In solution the Kv2.1 T1 domain also formed a pentamer, as determined by inline SEC-MALS-SAXS and negative-stain electron microscopy. The Kv2.1 T1-T1 interface involves electrostatic interactions, including a salt bridge formed by the negative charges in a previously described CDD motif, and inter-subunit coordination of zinc. It is shown that zinc binding is important for stability. In conclusion, the Kv2.1 T1 domain behaves differently from the other Kv T1 domains, which may reflect the versatility of Kv2.1, which can assemble with the regulatory KvS subunits and scaffold ER-plasma membrane contacts.Transient protein-protein interactions between cis-acting acyltransferase (AT) and acyl carrier protein (ACP) domains are critical for the catalysis and processivity of modular polyketide synthases (mPKSs), but are challenging for structural characterization due to the intrinsically weak binding affinity. Here, a stable complex of cis-acting AT and ACP domains from the ninth module of the salinomycin mPKS was obtained using a maleimide cross-linker and the structure of the complex was determined at 2.6 Å resolution. The crystal structure shows that the AT in combination with the ketosynthase (KS)-to-AT linker forms a C-shaped architecture to embrace the ACP. The large hydrolase subdomain of the AT serves as a major binding platform for the ACP, while the small ferredoxin-like subdomain of the AT and the KS-to-AT linker cooperate with each other to constrain binding of the ACP. The importance of interface residues in cis-acting AT-ACP interactions was confirmed by mutagenesis assays. The interaction mode observed in the cis-acting AT-ACP complex is completely different from those observed in trans-acting AT-ACP complexes, where the ACP primarily contacts the small domain of the AT. The complex structure provides detailed mechanistic insights into AT-ACP recognition in cis-AT mPKSs.Hen egg-white lysozyme (HEWL) is an enzymatic protein with two acidic amino acids, Glu35 and Asp52, in its active site. Glu35 acts as a proton donor to the substrate and Asp52 interacts with the positively charged substrate, suggesting different protonation states of these residues. However, neutron crystallographic studies thus far have not provided a consistent picture of the protonation states of these residues. Only one study succeeded in observing the active protonation states of Glu35 and Asp52 in the triclinic crystal system. However, their active states in the most widely studied tetragonal crystal system are still unknown. The application of the D/H contrast technique in neutron crystallography improves the ability to locate exchangeable D/H atoms in proteins. In the present study, D2O and H2O solvent crystals were prepared. Each neutron data set was collected for only five days by combining a time-of-flight diffractometer (iBIX) and the spallation neutron source at the Japan Proton Accelerator Research Complex. The D/H contrast map provided better visualization of the D/H atoms in HEWL than the conventional neutron scattering length density map. The neutron D/H contrast map demonstrated the alternative protonation of the OE1 and OE2 atoms in the carboxyl group of Glu35. This alternative protonation occurs in the absence of a substrate, where high selectivity of the protonation site does not occur. In this case, only the OE1-HE1 bond attacks the substrate in an equilibrium between OE1-HE1 and OE2-HE2, or the H+ ion of the OE2-HE2 bond moves to the OE1 atom just before or after substrate binding to initiate the catalytic reaction. In contrast, the carboxyl group of Asp52 is not protonated. Protonation of the carboxyl group was not observed for other Asp and Glu residues. These results are consistent with results from NMR spectroscopy and explain the protonation states at the active site in the apo form of HEWL.In macromolecular crystallography, radiation damage limits the amount of data that can be collected from a single crystal. It is often necessary to merge data sets from multiple crystals; for example, small-wedge data collections from micro-crystals, in situ room-temperature data collections and data collection from membrane proteins in lipidic mesophases. Whilst the indexing and integration of individual data sets may be relatively straightforward with existing software, merging multiple data sets from small wedges presents new challenges. The identification of a consensus symmetry can be problematic, particularly in the presence of a potential indexing ambiguity. Furthermore, the presence of non-isomorphous or poor-quality data sets may reduce the overall quality of the final merged data set. To facilitate and help to optimize the scaling and merging of multiple data sets, a new program, xia2.multiplex, has been developed which takes data sets individually integrated with DIALS and performs symmetry analysis, scaling and merging of multi-crystal data sets. xia2.multiplex also performs analysis of various pathologies that typically affect multi-crystal data sets, including non-isomorphism, radiation damage and preferential orientation. After the description of a number of use cases, the benefit of xia2.multiplex is demonstrated within a wider autoprocessing framework in facilitating a multi-crystal experiment collected as part of in situ room-temperature fragment-screening experiments on the SARS-CoV-2 main protease.Prolyl oligopeptidases (POPs) are atypical serine proteases that are unique in their involvement in the maturation and degradation of prolyl-containing peptide hormones and neuropeptides. They are potential pharmaceutical targets for the treatment of several neurodegenerative disorders, such as Alzheimer's disease. In this study, the catalytic and substrate-regulatory mechanisms of a novel bacterial POP from Microbulbifer arenaceous (MaPOP) were investigated. The crystal structure revealed that the catalytic triad of MaPOP was covered by the central tunnel of an unusual β-propeller domain. The tunnel not only provided the sole access to the active site for oligopeptides, but also protected large structured peptides or proteins from accidental proteolysis. The enzyme was able to cleave angiotensin I specifically at the carboxyl side of the internal proline residue, but could not hydrolyze long-chain bovine insulin B in vitro. Like the ligand-free structure, MaPOP bound to the transition-state analog inhibitor ZPR was also in a closed state, which was not modulated by the common `latching loop' found in other POPs.