Complexes of Cobalt(II) with Schiff Bases Derived from Salicylaldehyde & Some Amino Acids

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Synthesis and structure characterization of two cadmium coordination polymers based on μ2-bridging bidentate hydrazine ligand

Synthesis, single crystal structures, spectral and thermal characteristics of two cadmium coordination polymers, viz., [Cd(NO3)2(N2H4)2] (1) [Cd(C3H2O4)(N2H4)] (where C3H2O4 is malonate) (2) are reported. The μ2-bridging bidentate binding mode of the crystallographically unique hydrazine ligands in (1) leads to a one-dimensional polymeric structure extending along c axis. The central Cd(II) in (2) exhibits hepta-coordination and is bonded to a unique malonate anion which exhibits a μ3-bridging pentadentate coordination, extending the structure along the a axis. The bridging bidentate binding of the crystallographically independent hydrazine ligand extends along b axis resulting in a 2-D structure

A Randomised Controlled Trial Comparing Ketamine versus Fentanyl for Procedural Sedation in the Emergency Department for Adults with Isolated Extremity Injury

Introduction: Alleviating pain and anxiety of patients during procedures is an essential skill for an Emergency Physician (EP). Several sedatives and dissociative agents are used for PSA (Procedural Sedation and Analgesia). In this study, we aimed to compare two drugs that is, ketamine and fentanyl for procedural sedation in adults with isolated limb injuries in the Emergency Department (ED). Materials and methods: In this prospective, randomised controlled interventional trial, patients aged between 18 to 65 years with isolated extremity injury requiring PSA in the ED were recruited. A total of 200 subjects were included in the study and randomly allocated to either the fentanyl (n=100) or the ketamine (n=100) group. Patients were blinded to the intervention and subsequently premedicated with Midazolam. Following this, they received either ketamine or fentanyl based on the group they were allocated to. Vital signs, including but not limited to the level of sedation, were measured at predetermined time intervals. A Modified Aldrete Score of >8 was used as a criterion for disposition from the ED. Data were collected in a pre-designed proforma. We aimed to compare the effectiveness as well as ascertain the safety profile of the two drugs for PSA in the ED. Results: There was no significant difference between the two groups when age, gender, mechanism of injury and comorbidities were compared. We found that there was no statistically significant difference between the two groups when blood pressure, respiratory rate and depth of sedation were compared. In both groups, there was a significant decrease in pain on the Numerical Rating Scale (NRS) following drug administration from 8 to 3 (p<0.001). Patients in the fentanyl group had an increased incidence of transient oxygen desaturation (p<0.001). Vomiting was more common in the ketamine group (p<0.001). Conclusion: PSA is a safe and efficacious procedure for patients undergoing painful procedures in ED. Patients in both the groups maintained hemodynamic stability throughout the procedure. From our study, we were able to conclude that both ketamine and fentanyl are similar in efficacy for PSA in the ED for adults with isolated limb injuries. In addition, no significant cardiovascular adverse events were noted in either group in our study

Tight Junction-Related Barrier Contributes to the Electrophysiological Asymmetry across Vocal Fold Epithelium

Electrophysiological homeostasis is indispensable to vocal fold hydration. We investigate tight junction (TJ)-associated components, occludin and ZO-1, and permeability with or without the challenge of a permeability-augmenting agent, histamine. Freshly excised ovine larynges are obtained from a local abattoir. TJ markers are explored via reverse transcriptase polymerase chain reaction (RT-PCR). Paracellular permeabilities are measured in an Ussing system. The gene expression of both TJ markers is detected in native ovine vocal fold epithelium. Luminal histamine treatment significantly decreases transepithelial resistance (TER) (N = 72, p<0.01) and increases penetration of protein tracer (N = 35, p<0.001), respectively, in a time-, and dose-dependent fashion. The present study demonstrates that histamine compromises TJ-related paracellular barrier across vocal fold epithelium. The detection of TJ markers indicates the existence of typical TJ components in non-keratinized, stratified vocal fold epithelium. The responsiveness of paracellular permeabilities to histamine would highlight the functional significance of this TJ-equivalent system to the electrophysiological homeostasis, which, in turn, regulates the vocal fold superficial hydration

Reap the crop wild relatives for breeding future crops

Crop wild relatives (CWRs) have provided breeders with several 'game-changing' traits or genes that have boosted crop resilience and global agricultural production. Advances in breeding and genomics have accelerated the identification of valuable CWRs for use in crop improvement. The enhanced genetic diversity of breeding pools carrying optimum combinations of favorable alleles for targeted crop-growing regions is crucial to sustain genetic gain. In parallel, growing sequence information on wild genomes in combination with precise gene-editing tools provide a fast-track route to transform CWRs into ideal future crops. Data-informed germplasm collection and management strategies together with adequate policy support will be equally important to improve access to CWRs and their sustainable use to meet food and nutrition security targets

Interplay between REST and nucleolin transcription factors: a key mechanism in the overexpression of genes upon increased phosphorylation

Non-malignant cells can be transformed via the activation of kinases that control degradation of neural-restrictive silencer factor (REST). Here, we identify a mechanism that contributes to the activation of genes, expression of which is controlled by responsive elements containing overlapping binding sites for REST and nucleolin. We demonstrate that both phosphorylated and non-phosphorylated nucleolin-bound DNA; however, only phosphorylated nucleolin successfully competed with either full-length REST or a REST-derived DNA-binding peptide, REST68, for binding to the overlapping binding sites. We show that this interplay between the two transcription factors regulates the activation of cell survival and immunomodulatory genes in tumors and non-malignant cells with activated protein kinase C, which is accompanied with alterations in cell proliferation and apoptosis. We propose a model for the regulation of these genes, which brings a new insight into the molecular mechanisms that control cellular transformation driven by activation of protein kinases

Cross-Sample Validation Provides Enhanced Proteome Coverage in Rat Vocal Fold Mucosa

The vocal fold mucosa is a biomechanically unique tissue comprised of a densely cellular epithelium, superficial to an extracellular matrix (ECM)-rich lamina propria. Such ECM-rich tissues are challenging to analyze using proteomic assays, primarily due to extensive crosslinking and glycosylation of the majority of high Mr ECM proteins. In this study, we implemented an LC-MS/MS-based strategy to characterize the rat vocal fold mucosa proteome. Our sample preparation protocol successfully solubilized both proteins and certain high Mr glycoconjugates and resulted in the identification of hundreds of mucosal proteins. A straightforward approach to the treatment of protein identifications attributed to single peptide hits allowed the retention of potentially important low abundance identifications (validated by a cross-sample match and de novo interpretation of relevant spectra) while still eliminating potentially spurious identifications (global single peptide hits with no cross-sample match). The resulting vocal fold mucosa proteome was characterized by a wide range of cellular and extracellular proteins spanning 12 functional categories

IRF4 transcription factor-dependent CD11b+ dendritic cells in human and mouse control mucosal IL-17 cytokine responses.

Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24(+)CD64(-) DCs and contaminating CSF-1R-dependent CD24(-)CD64(+) macrophages. Functionally, loss of CD24(+)CD11b(+) DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24(+)CD11b(+) DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies

Cadherin exits the junction by switching its adhesive bond

Intercellular traction forces or lateral alignment of cadherin molecules can influence adherens junction dynamics by altering the cadherin dimerization interface

A potential new, stable state of the E-cadherin strand-swapped dimer in solution

E-cadherin is a transmembrane glycoprotein that facilitates inter-cellular adhesion in the epithelium. The ectodomain of the native structure is comprised of five repeated immunoglobulin-like domains. All E-cadherin crystal structures show the protein in one of three alternative conformations: a monomer, a strand-swapped trans homodimer and the so-called X-dimer, which is proposed to be a kinetic intermediate to forming the strand-swapped trans homodimer. However, previous studies have indicated that even once the trans strand-swapped dimer is formed, the complex is highly dynamic and the E-cadherin monomers may reorient relative to each other. Here, molecular dynamics simulations have been used to investigate the stability and conformational flexibility of the human E-cadherin trans strand-swapped dimer. In four independent, 100 ns simulations, the dimer moved away from the starting structure and converged to a previously unreported structure, which we call the Y-dimer. The Y-dimer was present for over 90% of the combined simulation time, suggesting that it represents a stable conformation of the E-cadherin dimer in solution. The Y-dimer conformation is stabilised by interactions present in both the trans strand-swapped dimer and X-dimer crystal structures, as well as additional interactions not found in any E-cadherin dimer crystal structures. The Y-dimer represents a previously unreported, stable conformation of the human E-cadherin trans strand-swapped dimer and suggests that the available crystal structures do not fully capture the conformations that the human E-cadherin trans homodimer adopts in solution