Recent advances in the chemical synthesis of sugar-nucleotides

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Petrogenesis of the Lalezar granitoid intrusions (Kerman Province – Iran)

The Lalezar granitoids crop out within volcanic successions of the Urumieh-Dokhtar Magmatic Assemblage (UDMA). These granitoids have a range from gabbro-diorites to granites in composition. The mineral compositions of the most felsic rocks are characterized by the abundances of Na-plagioclase, quartz, alkali feldspar, biotite and hornblende. In the gabbro-diorite rocks, plagioclase (Ca-rich), hornblende, biotite and clinopyroxene are the most common minerals. Major element geochemical data show that the Lalezar granitoids are mostly metaluminous, although the most felsic members (granites) attain slightly peraluminous compositions and that they have features typical of high-K calc-alkaline rocks. In primitive mantle-normalized trace element spider diagrams, the analysed samples display strong enrichment in LILE compared to HFSE, accompanied by negative anomalies of Nb,Ta and Ti. REE chondrite-normalized plots show moderate LREE enrichment with slight to strong negative Eu anomalies. Rb–Sr geochronological data, mainly dependent on the Sr isotopic composition of biotite, was obtained in two samples and it points to 15-16 Ma. As a probable, age for the emplacement of the studied intrusives. Initial 87Sr/86Sr ratios and ƐNdi values range from 0.70495 to 0.70565 from +3.1 to +1.5 respectively, which fit into a supra-subduction mantle wedge source for the parental melts and indicates that, in general, crustal contribution for magma diversification was not relevant. Geochemical and isotopic evidence reveal that the Lalezar intrusions are cogenetic I-type granitoids which were generated in a continental arc setting, in agreement with models previously presented in the UDMA

Recent advances in the enzymatic synthesis of sugar-nucleotides using nucleotidylyltransferases and glycosyltransferases

Sugar-nucleotides are imperative to carbohydrate metabolism and glycoconjugate biosynthesis. Enzymatic methods to access these key materials offer a powerful alternative to traditional chemical synthesis routes. Herein we review recent advances in the enzymatic pyrophosphorylation of glycosyl 1-phosphates for the provision of both native and modified sugar-nucleotides

The extracellular vesicles-derived from mesenchymal stromal cells: A new therapeutic option in regenerative medicine

ABSTRACT Mesenchymal stem cells (MSCs) are adult multipotent cells that due to their ability to homing to damaged tissues and differentiate into specialized cells, are remarkable cells in the field of regenerative medicine. It's suggested that the predominant mechanism of MSCs in tissue repair might be related to their paracrine activity. The utilization of MSCs for tissue repair is initially based on the differentiation ability of these cells; however now it has been revealed that only a small fraction of the transplanted MSCs actually fuse and survive in host tissues. Indeed, MSCs supply the microenvironment with the secretion of soluble trophic factors, survival signals and the release of extracellular vesicles (EVs) such as exosome. Also, the paracrine activity of EVs could mediate the cellular communication to induce cell- differentiation/self-renewal. Recent findings suggest that EVs released by MSCs may also be critical in the physiological function of these cells. This review provides an overview of MSC-derived extracellular vesicles as a hopeful opportunity to advance novel cell-free therapy strategies that might prevail over the obstacles and risks associated with the use of native or engineered stem cells. EVs are very stable; they can pass the biological barriers without rejection and can shuttle bioactive molecules from one cell to another, causing the exchange of genetic information and reprogramming of the recipient cells. Moreover, extracellular vesicles may provide therapeutic cargo for a wide range of diseases and cancer therapy. Key Words: Mesenchymal Stem Cells, Extracellular vesicles, Exosome, Regenerative medicine

The Study of Newborns with Congenital Gastrointestinal Tract Obstruction

Introduction: Gastrointestinal Tract Obstruction (GITO) is one of the most common causes of surgical emergencies in newborns. Management of these patients depends on the site of obstruction, associated anomalies, the time of diagnosis and the surgery. Aim: The purpose of this study was to evaluate clinical manifestations, associated anomalies and the outcome of these patients with GITO admitted to Imam Reza and Razi Hospitals of Kermanshah. Material and Methods: This is an observational study, which is conducted to investigate all the newborns, admitted to the Neonatal Intensive Care Unit (NICU) of Imam Reza & Razi Hospital of Kermanshah during ten years from 2002 to 2012 with diagnosis of GITO. The history of the newborn, operation records and case records of the patients in addition to clinical and paraclinical conditions and their pathological results were studied. Results: During the study period, 235 cases of GITO were investigated. Among them, 63 were admitted with imperforate anus, 62 with Hirschsprung's disease, 52 with esophageal atresia, 9 with ileal atresia, 17 with jejunal atresia, and 16 with duodenal obstruction and 6 with colonic atresia. The most common symptoms at the time of admission were abdominal distension in 108, absence of meconial defecation in 85, and bile vomiting in 42 cases. 189 (80.4%) of newborns were operated. The overall mortality rate of newborns under study was 31.2%. The highest rate of mortality was observed in newborns with esophageal atresia 61.5%. Conclusion: The results of the present study showed that approximately 5% of the cases admitted to NICU suffered from congenital GITO. Considering the high number of cases and the increased probability of death in these patients, close attention, better management and treatment of these patients seems crucial

Chemical and enzymatic synthesis of the alginate sugar nucleotide building block: GDP-d-mannuronic acid

Highlights Sugarnucleotide synthesis. Chemical and enzymatic access to GDP-d-ManA. Evaluation of protected and free uronate 1-phosphates for pyrophosphorylation

Geochronology, isotope geochemistry and tectonomagmatic setting of the Lalezar granitoids (Urumieh-Dokhtar Volcanic Belt, Iran)

The Lalezar granitoids crop out within the Urumieh-Dokhtar Volcanic Belt, which is the largest volcanic belt in Central Iran. These granitoids have intruded into the Eocene volcano-sedimentary rocks and range from gabbro-diorites to granites in composition, with dominance of diorites and tonalites. Two of the least altered samples, 5-ln-7 and 23-ln-6, were selected for Rb–Sr geochronology. Biotite (Bt), hornblende (Hbl) and plagioclase (Pl) separates were obtained from both samples. For sample 5-ln-7, using the data from the whole-rock and the three mineral separates, a 87Sr/86Sr vs. 87Rb/86Sr correlation corresponding to a 14.6±5.8 Ma age is obtained, with initial 87Sr/86Sr=0.7055. However, the MSWD has a very large value (376). This is due to the fact that Hbl composition plots deviated from the alignement defined by WR, Pl and Bt, suggesting that some disturbance took place. Under the petrographic microscope, the amphibole grains in this sample show some low temperature alteration, as testified by chloritization and oxidation, which makes plausible that a late enrichment in radiogenic Sr could have affected hornblende. If Hbl is discarded, the result now is a 15.0±0.4 Ma Bt-Pl-WR isochron, with MSWD=2.4 and initial 87Sr/86Sr=0.70517. Considering the errors, both results (with and without Hbl) overlap, which suggests that there was Sr isotope equilibrium at an age of ca. 15 Ma (most likely during igneous crystallization). In the 87Sr/86Sr vs. 87Rb/86Sr diagram for sample 23-ln-6, the line obtained with Bt-Hbl-Pl-WR has a slope indicating an age of 15.8±1.6 Ma. The MSWD value is 18 and the initial 87Sr/86Sr ratio is 0.70533. The MSWD shows that the correlation is not perfect, and, as in the previous case, it probably reflects some minor alteration; once again, Hbl plots above the line that passes through WR, Pl and Bt. Taking the errors into account, the ages calculated for 23-ln-6 and 5-ln-7 overlap each other, suggesting that this set of data is geochronologically meaningful. Therefore, and considering that the studied rocks are shallow intrusives which should have not undergone a long cooling period, the obtained 15-16 Ma ages are probably dating the intrusive events. For isotope geochemistry, Sr and Nd isotopic compositions were determined for 14 whole-rock samples. Assuming an age of 15 Ma, initial 87Sr/86Sr and εNd values vary in restricted ranges from 0.70495 to 0.70565 and from +3.1 to +1.5, respectively. In the εNdi versus (87Sr/86Sr)i diagram, this cluster plots to the right of the so-called mantle array and overlaps the field of island-arc basalts. The limited range of Sr and Nd isotopic compositions suggest that the Lalezar intrusions are co-genetic, deriving from the same parental magmas essentially by magmatic differentiation processes. Taking into account the IAB-like isotopic compositions of the studied rocks, the parental magmas may have been formed by partial melting in a supra-subduction mantle wedge. The occurrence of gabbrodioritic rocks in the Lalezar suite provides additional evidence in favour of an origin of the parental magmas by melting of mantle peridotites, rather than by melting of mafic crust

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase.

Sufferers of cystic fibrosis are at significant risk of contracting chronic bacterial lung infections. The dominant pathogen in these cases is mucoid Pseudomonas aeruginosa. Such infections are characterised by overproduction of the exopolysaccharide alginate. We present herein the design and chemoenzymatic synthesis of sugar nucleotide tools to probe a critical enzyme within alginate biosynthesis, GDP-mannose dehydrogenase (GMD). We first synthesise C6-modified glycosyl 1-phosphates, incorporating 6-amino, 6-chloro and 6-sulfhydryl groups, followed by their evaluation as substrates for enzymatic pyrophosphorylative coupling. The development of this methodology enables access to GDP 6-chloro-6-deoxy-ᴅ-mannose and its evaluation against GMD

Determination of optimum dosage of Ovaprim injectionon artificial spawning efficiency of Esox lucius

This project was conducted to goal of optimum dosage determination of ovaprim injection to artificial spawning efficiency of Esox lucius. The research implemented by 4 treatments with 3 replicates for each ones. 3 female and 6 male brooders injected in each replicate. The animals in 1, 2 and 3 treatments injected by 10, 20 and 30 µg/kg BW, respectively, and 4th treatment as a control injected with 4 mg/kg BW pituitary gland extract. Average weight of brooders were 1361±521, 1376±954, 1009±160 and 1100 ±422 g in 1, 2, 3 and 4 treatments in females and 689±145, 734±197, 547±118 and 794±238 g in males, respectively. In addition, positive response percent to hormone injection were measured 77.8 ±19.24 , 88.9 ± 19.24 , 55.5 ±50.91 and 55.5 ± 19.24 % in 1, 2, 3 and 4 treatments in female and 94.4 ± 9.58, 88.9 ±19.26 , 83.3±28.86 and 88.9 ± 19.26 % in male brooders, respectively, but there was no significant different between all of treatments (p<0.05). Incubation period from fertilization till hatching step in 7 to 15 ˚C was 5 to 10 days with average of 7±1.5 days. Fertilization content was in 1 to 4 treatments measured 87.1±10, 88.04±7.7, 83.9±5.2 and 72.4±19.7 %, respectively and also the treatments didn’t show any different significantly together (p<0.05). Average percentage of eyed eggs 66.6±15.9 in treat 1, 61.2±22.3 in treat 2, 58.3±10.7 in treat 3 and 56.1±15.04 in treat 4, without any significant different between of them (p<0.05). Hatching of eggs mean were measured 27.41±19.8 in treat 1, 39.53±26.9 in treat 2, 95.18±5.6 in treat 3 and 26.78±12.4 in treat 4, and significant different observed between of them too (p<0.05).In the other hand, mean percent of larvae with active feeding in these treatments were measured 18.77±14.6, 20.1±8.51, 55.6±11.6 and 14.51±7.72 as the treatments had significant different (p<0.05). Also, the best temperature and dosage injection of ovaprim hormone was 9 to 12.5 ˚C and 20µg/kg BW, respectively. The end of trial, from 103740 larvae introduced to earthen pond obtained 8000 fingerlings with weight of 2.68±0.6 g and length of 6.96±0.51 cm

New entity of adult ultra-short coeliac disease: the first international cohort and case–control study

Background: Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD. Methods: Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease. Findings: Patients with USCD (n=137, median age 27 years, IQR 21–43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1–5.9) vs 12.6×ULN (IQR 3.3–18.3), p<0.001). Patients: with USCD had the same number of symptoms overall (median 3 (IQR 2–4) vs 3 (IQR 1–4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006). Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4. At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440–2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2–1.4) vs 0.7 ULN (IQR 0.2–2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms. Interpretation: Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup