Effect of quercetin on histamine induced gastric ulcers in male guinea pigs

Background: Peptic ulcer disease is the most prevalent gastrointestinal diseases caused by an imbalance between gastric stimulant or aggressive factors and the mucosal defensive factors. The defence of flavonoids against the tissue oxidative stress is being proved in various animal models for wide pharmacological effects. The aim of the present study is to evaluate the anti-oxidant effect of quercetin in histamine induced gastric ulcers.Methods: Male guinea pigs were divided into 4 groups (n=6). Group I includes normal control. Group 2, 3 and 4 were induced gastric ulcers with histamine as intraperitoneal (IP) injection. Group 2 serves as the gastric ulcer control. Group 3 and Group 4 are pre-treated with quercetin 200 mg/kg per orally (PO) and ranitidine 100 mg/kg PO respectively 45mins before histamine injection. After 4 hours of histamine injection, the animals were sacrificed to collect blood samples and stomach tissue for estimation of plasma and tissue antioxidant levels.Results: On estimation of antioxidant levels both in plasma and stomach tissues the SOD and CAT levels increased in the Group 3 and 4 significantly and also a significant reduction in MDA levels were noted in the Group 3 and 4 compared to the gastric ulcer control group.Conclusions: Hence, with flavonoids quercetin utilization in histamine induced gastric ulcers, the antioxidants showed comparative levels with ranitidine treatment groups. So a permanent cure for the chronic gastric ulcers could be proved in further studies as this is the milestone, tough to achieve in general clinical practice

Nuclear Factor 90 uses an ADAR2-like binding mode to recognize specific bases in dsRNA

Nuclear factors 90 and 45 (NF90 and NF45) form a protein complex involved in the post-transcriptional control of many genes in vertebrates. NF90 is a member of the dsRNA binding domain (dsRBD) family of proteins. RNA binding partners identified so far include elements in 3′ untranslated regions of specific mRNAs and several non-coding RNAs. In NF90, a tandem pair of dsRBDs separated by a natively unstructured segment confers dsRNA binding activity. We determined a crystal structure of the tandem dsRBDs of NF90 in complex with a synthetic dsRNA. This complex shows surprising similarity to the tandem dsRBDs from an adenosine-to-inosine editing enzyme, ADAR2 in complex with a substrate RNA. Residues involved in unusual base-specific recognition in the minor groove of dsRNA are conserved between NF90 and ADAR2. These data suggest that, like ADAR2, underlying sequences in dsRNA may influence how NF90 recognizes its target RNAs

Yeast Ssd1 is a non-enzymatic member of the RNase II family with an alternative RNA recognition interface

Ssd1, a conserved fungal RNA-binding protein, is important in stress responses, cell division and virulence. Ssd1 is closely related to Dis3L2 of the RNase II family of nucleases, but lacks catalytic activity and likely suppresses translation of bound mRNAs. Previous studies identified RNA motifs enriched in Ssd1-associated transcripts, yet the sequence requirements for Ssd1 binding are not defined. Here, we identify precise binding sites of Ssd1 on RNA using in vivo cross-linking and cDNA analysis. These sites are enriched in 5′ untranslated regions of a subset of mRNAs encoding cell wall proteins. We identified a conserved bipartite motif that binds Ssd1 with high affinity in vitro. Active RNase II enzymes have a characteristic, internal RNA binding path; the Ssd1 crystal structure at 1.9 Å resolution shows that remnants of regulatory sequences block this path. Instead, RNA binding activity has relocated to a conserved patch on the surface of the protein. Structure-guided mutations of this surface prevent Ssd1 from binding RNA in vitro and phenocopy Ssd1 deletion in vivo. These studies provide a new framework for understanding the function of a pleiotropic post-transcriptional regulator of gene expression and give insights into the evolution of regulatory and binding elements in the RNase II family

A Self-Adaptive Trajectory Optimization Algorithm Using Fuzzy Logic for Mobile Edge Computing System Assisted by Unmanned Aerial Vehicle

The advancement of the Internet of Things (IoT) and the availability of wide cloud services have led to the horizon of edge computing paradigm which demands for processing the data at the edge of the network. The development of 5G technology has led to the increased usage of IoT-based devices and the generation of a large volume of data followed by increased data traffic, which is difficult to process by the mobile edge computing (MEC) platform. The latest inventions related to unmanned aerial vehicles (UAVs) helps to assist and replace the edge servers used for MEC. In the present work, the objective is to develop self-adaptive trajectory optimization algorithm (STO) which is a multi-objective optimization algorithm used to solve the vital objectives associated with the above scenario of a UAV-assisted MEC system. The objectives identified are minimizing the energy consumed by the MEC and minimizing the process emergency indicator, where the process emergency indicator implies the urgency level of a particular process. Finding the optimal values for these conflicting objectives will help to further efficiently apply UAV for MEC systems. A self-adaptive multi-objective differential evolution-based trajectory optimization algorithm (STO) is proposed, where a pool of trial vector generation strategies is extended. The strategies and the crossover rate associated with a differential evolution (DE) algorithm are self-adapted using fuzzy systems to improve the population diversity. The experimentation is planned to be conducted on hundreds of IoT device instances considered to be fixed on the ground level and to evaluate the performance of the proposed algorithm for a single unmanned aerial vehicle-assisted mobile edge computing system

Correlation between biofilm production and multiple drug resistance in imipenem resistant clinical isolates of Acinetobacter baumannii

Purpose: To study the qualitative and quantitative methods for the investigation of biofilm formation and to examine the correlation between biofilm and antibiotic resistance among the clinical isolates of Acinetobacter baumannii . We also verified the association between biofilm and presence of extended spectrum β-lactamases, particularly, bla PER-1 . Methods: A total of 55 isolates were subjected to susceptibility testing by disc diffusion method for 13 clinically relevant antibiotics. Screening for biofilm production was done by both qualitative and quantitative methods through tube and microtitre plate assay respectively. The presence of bla PER-1 was checked by PCR. Results: A. baumannii isolates showed very high resistance (>75%) to imipenem, cephotaxime, amikacin and ciprofloxacin. Only cefoperazone, netillin and norfloxacin were found to be effective agents. Results of microtitre and tube methods were concordant with 34 isolates (62%) showing biofilm formation. Resistance to four antibiotics such as amikacin (82% vs. 17.6%, P < 0.001), cephotaxime (88% vs. 11%, P P < 0.001), ciprofloxacin (70% vs. 29%, P =0.005) and aztreonam (38% vs. 11%, P =0.039) was comparatively higher among biofilm producers than non-biofilm producers. Microtitre assay additionally detected 14 weakly adherent isolates. Only 11 isolates had bla PER-1 gene and among these two were strong biofilm producers, while remaining were weakly adherent isolates. Conclusion: Microtitre plate method was found to be a more sensitive method for biofilm detection. This study demonstrates a high propensity among the clinical isolates of A. baumannii to form biofilm and a significant association of biofilms with multiple drug resistance. Presence of bla PER-1 appears to be more critical for cell adherence than for biofilm formation

Structural and Functional Organization of the Ska Complex, a Key Component of the Kinetochore-Microtubule Interface

The Ska complex is an essential mitotic component required for accurate cell division in human cells. It is composed of three subunits that function together to establish stable kinetochore-microtubule interactions in concert with the Ndc80 network. We show that the structure of the Ska core complex is a W-shaped dimer of coiled coils, formed by intertwined interactions between Ska1, Ska2, and Ska3. The C-terminal domains of Ska1 and Ska3 protrude at each end of the homodimer, bind microtubules in vitro when connected to the central core, and are essential in vivo. Mutations disrupting the central coiled coil or the dimerization interface result in chromosome congression failure followed by cell death. The Ska complex is thus endowed with bipartite and cooperative tubulin-binding properties at the ends of a 350 Å-long molecule. We discuss how this symmetric architecture might complement and stabilize the Ndc80-microtubule attachments with analogies to the yeast Dam1/DASH complex

Molecular Mechanisms for the RNA-Dependent ATPase Activity of Upf1 and Its Regulation by Upf2

International audienc

Structure of SALL4 zinc-finger domain reveals link between AT-rich DNA binding and Okihiro syndrome

Spalt-like 4 (SALL4) maintains vertebrate embryonic stem cell identity and is required for the development of multiple organs, including limbs. Mutations in SALL4 are associated with Okihiro syndrome and SALL4 is also a known target of thalidomide. SALL4 protein has a distinct preference for AT-rich sequences, recognised by a pair of zinc fingers at the C-terminus. However, unlike many characterised zinc finger proteins, SALL4 shows flexible recognition with many different combinations of AT-rich sequences being targeted. SALL4 interacts with the NuRD corepressor complex which potentially mediates repression of AT-rich genes. We present a crystal structure of SALL4 C-terminal zinc fingers with an AT-rich DNA sequence, which shows that SALL4 uses small hydrophobic and polar side chains to provide flexible recognition in the major groove. Missense mutations reported in patients that lie within the C-terminal zinc fingers reduced overall binding to DNA but not the preference for AT-rich sequences. Furthermore, these mutations altered association of SALL4 with AT-rich genomic sites, providing evidence that these mutations are likely pathogenic. ## Complementary datasets ## Datasets in this repository complement additional datasets that are deposited in public databases: * Coordinates and structure factors are deposited in the Protein Data Bank: accession 8A4I; * SAXS data are deposited in the small angle scattering database (SASDB): accessions SASDP64 (SALL4 ZFC4); SASDP74 (DNA); SASDP84 (SALL4 ZFC4 + DNA); * HT-SELEX data are deposited at Array express: accession E-MTAB-11519