Anatomical Variations in the Position of Vermiform Appendix – A Cadaveric Study

Appendicitis is one of the most common clinical conditions which require emergency surgery. Variations in the anatomical position of vermiform appendix can result in different clinical presentations. This study was carried on 50 human cadavers irrespective of sex and age from the department of anatomy over a periods of 10 months. In the present study the commonest position was retrocaecal(38%), followed by pelvic(28%), postileal(20%), subcaecal(10%) and midinguinal(4%). Preileal variety was not found. A thorough knowledge of normal anatomy and variations in the position of vermiform appendix is very important for the surgeons while performing abdominal surgeries in adult, children and infants as it helps them to make optimal diagnosis of various pathological conditions related to this organ and treat accordingly.

Effect of replacement of Caspian Sea gammarus meal by partial kilka fish meal on growth performance, feed conversion ratio and survival of juveniles of rainbow trout (Oncorhynchus mykiss)

The effects of using different of gammarus meal levels (0, 5, 10 and 20%) instead of kilk fish meal as a protein source on growth performance, feed conversion ratio and survival of rainbow trout (Oncorhynchus mykiss) fingerlings were studied over 8 weeks. Rainbow trout fingerlings (mean body weight 5.48 ± 0.32g) were reared in a completely randomized design with three replications in the same conditions. Based on the results, no significant difference was observed in the final length and weight and specific growth rate among treatments. Increase of gammarus meal in diet led to increase of feed conversion ratio and decrease of survival, but the difference was not significant among treatments. Commercial analysis showed that the cost price of feed increased with increase of gammarus meal in diet, significantly. Thus, results of our study showed that adding up to 10% of gammarus meal instead of kilka fish meal in rainbow trout fingerlings diet is suitable, considering gammarus abundance in the shores of south Caspian Sea and lack of significance in difference on growth, feed conversion ratio and survival

Effects of different levels of Daphnia and Artemia extracts on food acceptability and growth factor rates of beluga (Huso huso Linnaeus, 1758)

In a 30 day feeding trial, Daphnia and Artemia extracts were added to diets of juvenile Beluga (Huso huso) at different levels to evaluate its effects on growth and survival rate of the fish. The trial was carried out in aquaculture research center of the Gorgan University, during which three different dietary levels of extracts (1:25, 1: 50 and 1:100) were used in 250 liter PVC tanks filled with about 125 liters of water. A total of 20 juvenile Beluga with an average weight of 5 plus or minus 0.2g each was stocked in tanks and were fed 4 meals a day. Growth and survival factors were analyzed at the end of the trial period. The results showed that the addition of extracts in diets led to improvement of body weight increase, weight increase percentage, specific growth rate (SGR), daily growth rate (DGR), daily growth index (DGI), condition factor (CF), price index (PI) and decrease of food conversion ratio (FCR) compared to the control treatment. The best improvement of growth index was achieved at the dietary level 1:50 Artemia extracts. There was no significant difference (P>0.05) in survival among treatments

Primary culture of ovarian follicular cells of Sterlet, Acipenser ruthenus to develop an in vitro system

The aim of the present study was to develop an in vitro system for functional investigation of ovarian follicular cells in Sterlet, Acipenser ruthenus. Oocytes for the primary culture were obtained from the ovaries of a 6 years old Sterlet 729 g in weight and 47 cm in total length. The oocytes were in advanced vitellogenesis stage (PI >10). A part of the ovary (containing about 300 follicles) was removed, ovarian follicles isolated by manually removing those from the interstitial tissue and washed with sterile phosphate buffered saline (PBS) containing antibiotics and Amphotericin B. Follicular cells were separated by treating oocytes with 0.25% trypsin-EDTA in Ca2+ and Mg2+ free PBS and cultured in medium L-15 supplemented with 20% FBS, streptomycin sulphate (Gibco, 100 mg.ml-1), penicillin G potassium (Gibco, 100 IU.ml-1) and Amphotericin B (Gibco, 2.5 mg.ml-1) at 22 °C. The concentrations of Testosterone (T), Estradiol-17β (E2), Progesterone (P4) and 17α-hydroxyprogestron (17αOHP) in the medium were measured at days 3, 5 & 7 by the Enzyme-Linked Immunosorbent Assay. According to the results, the ovarian follicular cells of Sterlet proliferated in L-15 medium were steroidogenically active as expressed by the secretion of T, E2, P4 & 17αOHP. Testosterone was the dominant hormone secreted by cultivated follicular cells, which was correlated closely with the end of vitellogenesis in the isolated oocytes. Decrease in production of these hormones was greater at days 3 & 4 in comparison with those at days 5 & 6. By successfully culturing ovarian follicular cells of Sterlet in L-15 culture medium, an in vitro system was developed which enables functional studies to be carried out similar to the in vivo situation in the ovarian follicles

Effect of different levels of Azolla meal on growth performance and digestibility of common carp (Cyprinus carpio)

In this study, the effects of different dietary levels of Azolla meal were investigated on growth performance and digestibility of common carp (Cyprinus carpio) fingerlings during 60 days. Five experimental diets approximately iso-protein (30%) and isolipidic (10%), were formulated with different levels of Azolla meal consisting of 0, 15, 25, 35 and 45%, respectively. In each experimental treatment, triplicate groups of common Carp fingerlings (16.5± 0.2 g) were used in a completely randomized design. Twenty fish were assigned to each experimental unit and stocked in 300 L tank. The results showed that the use of Azolla meal up to 15% had no negative effect on growth performance. The growth of fish was reduced significantly with increasing Azolla meal level of more than 15% of diet. Based on results, the apparent digestibility coefficients (ADC) of dry matter decreased with increasing Azolla meal in diets. The highest ADC of protein was observed in control treatment. However, no significant difference was observed between the treatment 2 (diet with 15% Azolla meal) and control (without Azolla meal) for ADC of protein. In general, results of the present study showed that Azolla meal can be used up to 15% in Cyprinus carpio diet

Structural analysis of phosphoribosyltransferase-mediated cell wall precursor synthesis in Mycobacterium tuberculosis

In Mycobacterium tuberculosis, Rv3806c is a membrane-bound phosphoribosyltransferase (PRTase) involved in cell wall precursor production. It catalyses pentosyl phosphate transfer from phosphoribosyl pyrophosphate to decaprenyl phosphate, to generate 5-phospho-β-ribosyl-1-phosphoryldecaprenol. Despite Rv3806c being an attractive drug target, structural and molecular mechanistic insight into this PRTase is lacking. Here we report cryogenic electron microscopy structures for Rv3806c in the donor- and acceptor-bound states. In a lipidic environment, Rv3806c is trimeric, creating a UbiA-like fold. Each protomer forms two helical bundles, which, alongside the bound lipids, are required for PRTase activity in vitro. Mutational and functional analyses reveal that decaprenyl phosphate and phosphoribosyl pyrophosphate bind the intramembrane and extramembrane cavities of Rv3806c, respectively, in a distinct manner to that of UbiA superfamily enzymes. Our data suggest a model for Rv3806c-catalysed phosphoribose transfer through an inverting mechanism. These findings provide a structural basis for cell wall precursor biosynthesis that could have potential for anti-tuberculosis drug development.</p

DprE2 is a molecular target of the anti-tubercular nitroimidazole compounds pretomanid and delamanid

Abstract Mycobacterium tuberculosis is one of the global leading causes of death due to a single infectious agent. Pretomanid and delamanid are new antitubercular agents that have progressed through the drug discovery pipeline. These compounds are bicyclic nitroimidazoles that act as pro-drugs, requiring activation by a mycobacterial enzyme; however, the precise mechanisms of action of the active metabolite(s) are unclear. Here, we identify a molecular target of activated pretomanid and delamanid: the DprE2 subunit of decaprenylphosphoribose-2’-epimerase, an enzyme required for the synthesis of cell wall arabinogalactan. We also provide evidence for an NAD-adduct as the active metabolite of pretomanid. Our results highlight DprE2 as a potential antimycobacterial target and provide a foundation for future exploration into the active metabolites and clinical development of pretomanid and delamanid

Structure of the priming arabinosyltransferase AftA required for AG biosynthesis of Mycobacterium tuberculosis.

Arabinogalactan (AG) is an essential cell wall component in mycobacterial species, including the deadly human pathogen Mycobacterium tuberculosis. It plays a pivotal role in forming the rigid mycolyl-AG-peptidoglycan core for in vitro growth. AftA is a membrane-bound arabinosyltransferase and a key enzyme involved in AG biosynthesis which bridges the assembly of the arabinan chain to the galactan chain. It is known that AftA catalyzes the transfer of the first arabinofuranosyl residue from the donor decaprenyl-monophosphoryl-arabinose to the mature galactan chain (i.e., priming); however, the priming mechanism remains elusive. Herein, we report the cryo-EM structure of Mtb AftA. The detergent-embedded AftA assembles as a dimer with an interface maintained by both the transmembrane domain (TMD) and the soluble C-terminal domain (CTD) in the periplasm. The structure shows a conserved glycosyltransferase-C fold and two cavities converging at the active site. A metal ion participates in the interaction of TMD and CTD of each AftA molecule. Structural analyses combined with functional mutagenesis suggests a priming mechanism catalyzed by AftA in Mtb AG biosynthesis. Our data further provide a unique perspective into anti-TB drug discovery. </p

Fluorescent mannosides serve as acceptor substrates for glycosyltransferase and sugar-1-phosphate transferase activities in <i>Euglena gracilis</i> membranes

Synthetic hexynyl α-D-mannopyranoside and its α-1,6-linked disaccharide counterpart were fluorescently labelled through CuAAC click chemistry with 3-azido-7-hydroxycoumarin. The resulting triazolyl-coumarin adducts, which were amenable to analysis by TLC, HPLC and mass spectrometry, proved to be acceptor substrates for α-1,6-ManT activities in mycobacterial membranes, as well as α- and β-GalT activities in trypanosomal membranes, benchmarking the potential of the fluorescent acceptor approach against earlier radiochemical assays. Following on to explore the glycobiology of the benign protozoan alga Euglena gracilis, α-1,3- and α-1,2-ManT activities were detected in membrane preparations, along with GlcT, Glc-P-T and GlcNAc-P-T activities. These studies serve to demonstrate the potential of readily accessible fluorescent glycans as substrates for exploring carbohydrate active enzymes

Identification of Novel Mt-Guab2 Inhibitor Series Active against M. tuberculosis

Tuberculosis (TB) remains a leading cause of mortality worldwide. With the emergence of multidrug resistant TB, extensively drug resistant TB and HIV-associated TB it is imperative that new drug targets be identified. The potential of Mycobacterium tuberculosis inosine monophosphate dehydrogenase (IMPDH) as a novel drug target was explored in the present study. IMPDH exclusively catalyzes the conversion of inosine monophosphate (IMP) to xanthosine monophosphate (XMP) in the presence of the cofactor nicotinamide adenine dinucleotide (NAD+). Although the enzyme is a dehydrogenase, the enzyme does not catalyze the reverse reaction i.e. the conversion of XMP to IMP. Unlike other bacteria, M. tuberculosis harbors three IMPDH-like genes, designated as Mt-guaB1, Mt-guaB2 and Mt-guaB3 respectively. Of the three putative IMPDH's, we previously confirmed that Mt-GuaB2 was the only functional ortholog by characterizing the enzyme kinetically. Using an in silico approach based on designed scaffolds, a series of novel classes of inhibitors was identified. The inhibitors possess good activity against M. tuberculosis with MIC values in the range of 0.4 to 11.4 µg mL−1. Among the identified ligands, two inhibitors have nanomolar Kis against the Mt-GuaB2 enzyme