A gene expression study on strains of Nostoc (Cyanobacteria) revealing antimicrobial activity under mixotrophic conditions

Cyanobacteria are well known for their production of a multitude of highly allelopathic compounds. These products have features such as incorporation of non-proteinogenic amino acids which are characteristics of peptides biosynthesized by non-ribosomal peptide synthetases (NRPSs). Some of these peptides have acetate-derived moieties, suggesting that their biosynthesis also involves polyketide synthases (PKSs). Among the photosynthetic microorganisms, cyanobacteria belonging to the genus Nostoc are regarded as good candidates for producing biologically active secondary metabolites. Aiming at the maximization in the production of natural product, we compared autotrophic, and mixotrophic growth at high light intensity of two Nostoc species in relation to the production of bioactive compounds with the antimicrobial activity at different source of sugar. Glucose was shown to be the best substrate for the production of high natural product when compared with sucrose. Also, the rate of biomass production and antimicrobial activity was reaching ~2.0 to 2.5 and ~1.5 times greater than that of the autotrophic and sucrose grown cultures, respectively. Also, we conduct a combined NRPSs and PKSs polymerase chain reaction (PCR). The sequences presented in this study was deposited in GenBank and had accession numbers JF795278 and JF795279 (NRPS A domains) and JF795280 and JF795281 (PKS KS domains). Computer modeling and phylogenetic analysis was conducted to predict the putative amino acid recognized by the unknown adenylation domain in the NRPS sequences. This study highlights the importance of environmental and nutrimental factors in maximization of antibiotic production of two Nostoc species.Keywords: Peptide synthetase gene, polyketide synthase gene, Nostoc, secondary metabolites, mixotrophic condition

Biochemical responses of Alfalfa (Medicago sativa L.) cultivars subjected to NaCl salinity stress

This investigation was conducted to determine NaCl salinity effects on antioxidant enzyme s activities, reducing sugar contents and lipid peroxidation in two alfalfa cultivars. Plants grown in solution cultures were subjected to 0, 100, 150 and 200 mM solutions of sodium chloride. Yazdi and Diabolourde alfalfa were used as tolerant and sensitive cultivars, respectively, in a germination experiment under similar conditions. Results show that the amount of reducing sugars and the activities of peroxidase (POD), catalase (CAT), ascorbate peroxidase (APX) and superoxide dismutase (SOD) enzymes increased with the increase in salt concentration. However, SOD activities decreased at high salt concentrations. The increase in the activities of antioxidant enzymes in response to salt treatments was higher in the tolerant cultivar. The results also show that salt treatment provoked an oxidative stress in both cultivars, as shown by the increase in lipid peroxidation. However, the level of lipid peroxidation was higher in the sensitive cultivar. The increase in antioxidant activities could also be a response to the cellular damage induced by NaCl. It seems that the tolerant cultivar has a better mechanism to cope with the deleterious effects ROS produced under salt stress.Key words: Alfalfa, antioxidant enzymes, malondialdehyde, salt stress

Contemporary multicenter outcomes of continent cutaneous ileocecocystoplasty in the adult population over a 10-year period: A Neurogenic Bladder Research Group study

AIMS: Evidence is sparse on the long-term outcomes of continent cutaneous ileocecocystoplasty (CCIC). We hypothesized that obesity, laparoscopic/robotic approach, and concomitant surgeries would affect morbidity after CCIC and aimed to evaluate the outcomes of CCIC in adults in a multicenter contemporary study. METHODS: We retrospectively reviewed the charts of adult patients from sites in the Neurogenic Bladder Research Group undergoing CCIC (2007-2017) who had at least 6 months of follow-up. We evaluated patient demographics, surgical details, 90-day complications, and follow-up surgeries. the Mann-Whitney U test was used to compare continuous variables and χ² and Fisher\u27s Exact tests were used to compare categorical variables. RESULTS: We included 114 patients with a median age of 41 years. The median postoperative length of stay was 8 days. At 3 months postoperatively, major complications occurred in 18 (15.8%), and 24 patients (21.1%) were readmitted. During a median follow-up of 40 months, 48 patients (42.1%) underwent 80 additional related surgeries. Twenty-three patients (20.2%) underwent at least one channel revision, most often due to obstruction (15, 13.2%) or incontinence (4, 3.5%). Of the channel revisions, 10 (8.8%) were major and 14 (12.3%) were minor. Eleven patients (9.6%) abandoned the catheterizable channel during the follow-up period. Obesity and laparoscopic/robotic surgical approach did not affect outcomes, though concomitant surgery was associated with a higher rate of follow-up surgeries. CONCLUSIONS: In this contemporary multicenter series evaluating CCIC, we found that the short-term major complication rate was low, but many patients require follow-up surgeries, mostly related to the catheterizable channel

Cytotoxic T Lymphocyte Antigen 4 Haploinsufficiency Presenting As Refractory Celiac-Like Disease: Case Report

Primary immunodeficiency may present with treatment-refractory enteropathy. We present two patients with celiac/celiac-like disease diagnosed in early childhood and refractory to the gluten-free diet. One patient had features of multi-system autoimmunity, whereas the other had celiac-like disease as an isolated clinical finding. Both patients underwent genetic testing given disease refractoriness and were ultimately diagnosed with cytotoxic T lymphocyte antigen 4 (CTLA4) haploinsufficiency. They are both now in complete clinical and endoscopic remission on abatacept. CTLA4 haploinsufficiency has incomplete penetrance and significant phenotypic heterogeneity but should be considered in the differential diagnosis of refractory celiac/celiac-like disease, as treatment implications are significant

Genome-wide meta-analysis identifies eight new susceptibility loci for cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (SCC) is one of the most common cancers in the United States. Previous genome-wide association studies (GWAS) have identified 14 single nucleotide polymorphisms (SNPs) associated with cutaneous SCC. Here, we report the largest cutaneous SCC meta-analysis to date, representing six international cohorts and totaling 19,149 SCC cases and 680,049 controls. We discover eight novel loci associated with SCC, confirm all previously associated loci, and perform fine mapping of causal variants. The novel SNPs occur within skin-specific regulatory elements and implicate loci involved in cancer development, immune regulation, and keratinocyte differentiation in SCC susceptibility

Lineage-specific dynamic and pre-established enhancer–promoter contacts cooperate in terminal differentiation

Chromosome conformation is an important feature of metazoan gene regulation; however, enhancer–promoter contact remodeling during cellular differentiation remains poorly understood. To address this, genome-wide promoter capture Hi-C (CHi-C) was performed during epidermal differentiation. Two classes of enhancer–promoter contacts associated with differentiation-induced genes were identified. The first class ('gained') increased in contact strength during differentiation in concert with enhancer acquisition of the H3K27ac activation mark. The second class ('stable') were pre-established in undifferentiated cells, with enhancers constitutively marked by H3K27ac. The stable class was associated with the canonical conformation regulator cohesin, whereas the gained class was not, implying distinct mechanisms of contact formation and regulation. Analysis of stable enhancers identified a new, essential role for a constitutively expressed, lineage-restricted ETS-family transcription factor, EHF, in epidermal differentiation. Furthermore, neither class of contacts was observed in pluripotent cells, suggesting that lineage-specific chromatin structure is established in tissue progenitor cells and is further remodeled in terminal differentiation

HPV16 E7-Dependent Transformation Activates NHE1 through a PKA-RhoA-Iinduced Inhibition of p38alpha

Background: Neoplastic transformation originates from a large number of different genetic alterations. Despite this genetic variability, a common phenotype to transformed cells is cellular alkalinization. We have previously shown in human keratinocytes and a cell line in which transformation can be turned on and followed by the inducible expression of the E7 oncogene of human papillomavirus type 16 (HPV16), that intracellular alkalinization is an early and essential physiological event driven by the up-regulation of the Na/H-+(+) exchanger isoform 1 (NHE1) and is necessary for the development of other transformed phenotypes and the in vivo tumor formation in nude mice.Methodology: Here, we utilize these model systems to elucidate the dynamic sequence of alterations of the upstream signal transduction systems leading to the transformation-dependent activation of NHE1.Principal Findings: We observe that a down-regulation of p38 MAPK activity is a fundamental step in the ability of the oncogene to transform the cell. Further, using pharmacological agents and transient transfections with dominant interfering, constitutively active, phosphorylation negative mutants and siRNA strategy to modify specific upstream signal transduction components that link HPV16 E7 oncogenic signals to up-regulation of the NHE1, we demonstrate that the stimulation of NHE1 activity is driven by an early rise in cellular cAMP resulting in the down-stream inhibition of p38 MAPK via the PKA-dependent phosphorylation of the small G-protein, RhoA, and its subsequent inhibition.Conclusions: All together these data significantly improve our knowledge concerning the basic cellular alterations involved in oncogene-driven neoplastic transformation

Genome-Wide Expression Profiling of Five Mouse Models Identifies Similarities and Differences with Human Psoriasis

Development of a suitable mouse model would facilitate the investigation of pathomechanisms underlying human psoriasis and would also assist in development of therapeutic treatments

SS18 Together with Animal-Specific Factors Defines Human BAF-Type SWI/SNF Complexes

Contains fulltext : 94049.pdf (publisher's version ) (Open Access