Toward a simulation approach for alkene ring-closing metathesis : scope and limitations of a model for RCM

A published model for revealing solvent effects on the ring-closing metathesis (RCM) reaction of di-Et diallylmalonate 7 has been evaluated over a wider range of conditions, to assess its suitability for new applications. Unfortunately, the model is too flexible and the published rate consts. do not agree with exptl. studies in the literature. However, by fixing the values of important rate consts. and restricting the concn. ranges studied, useful conclusions can be drawn about the relative rates of RCM of different substrates, precatalyst concn. can be simulated accurately and the effect of precatalyst loading can be anticipated. Progress has also been made toward applying the model to precatalyst evaluation, but further modifications to the model are necessary to achieve much broader aims

The Effect of Bifidobacterium on Reducing Symptomatic Abdominal Pain in Patients with Irritable Bowel Syndrome: A Systematic Review

Probiotics, specifically Bifidobacteria, may improve abdominal pain in patients with irritable bowel syndrome (IBS); however, results from randomised controlled trials (RCTs) are conflicting. Here, we systematically reviewed the efficacy of Bifidobacteria on abdominal pain in IBS. We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register from inception to 20 May 2019, without language or date restrictions. The search strategy comprised of the combination of three concepts: supplementation, abdominal pain, and IBS. Inclusion criteria included double-blind placebo-controlled RCTs featuring Bifidobacteria supplementation in Rome-diagnosed IBS patients. A total of 8 RCTs involving a total of 1045 patients with Rome diagnosed IBS were included. The dose of total Bifidobacteria ranged from 106 to > 1011 cfu (colony-forming unit) and duration of supplementation ranged between 2 and 8 weeks. Bifidobacteria was delivered through either intake of fermented milk products, encapsulation or via a malted milk beverage, with all studies assessing abdominal pain via a visual analogue Likert scale. From the studies included, 50% (n = 4) of studies found a statistically significant improvement in abdominal pain following Bifidobacteria supplementation compared to placebo, 38% (n = 3) of studies found non-significant improvements and 12% (n = 1) showed a statistically significant dose-response effect of improvement. The evidence shows a heterogeneity of effect for Bifidobacteria dependent upon strain, dosage and delivery method. While not all studies demonstrate significant improvements in abdominal pain, none of the selected studies reported an increase in pain or other adverse effects

A Meta-Analysis of Probiotic Efficacy for Gastrointestinal Diseases

Background: Meta-analyses on the effects of probiotics on specific gastrointestinal diseases have generally shown positive effects on disease prevention and treatment; however, the relative efficacy of probiotic use for treatment and prevention across different gastrointestinal diseases, with differing etiology and mechanisms of action, has not been addressed. Methods/Principal Findings: We included randomized controlled trials in humans that used a specified probiotic in the treatment or prevention of Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, Antibiotic Associated Diarrhea, Traveler’s Diarrhea, or Necrotizing Enterocolitis. Random effects models were used to evaluate efficacy as pooled relative risks across the eight diseases as well as across probiotic species, single vs. multiple species, patient ages, dosages, and length of treatment. Probiotics had a positive significant effect across all eight gastrointestinal diseases with a relative risk of 0.58 (95 % (CI) 0.51–0.65). Six of the eight diseases: Pouchitis, Infectious diarrhea, Irritable Bowel Syndrome, Helicobacter pylori, Clostridium difficile Disease, and Antibiotic Associated Diarrhea, showed positive significant effects. Traveler’s Diarrhea and Necrotizing Enterocolitis did not show significant effects of probiotcs. Of the 11 species and species mixtures, all showed positive significant effects except for Lactobacillus acidophilus, Lactobacillus plantarum, and Bifidobacterium infantis. Across all diseases and probiotic species, positive significant effects of probiotics were observed for all age groups, single vs. multiple species, and treatment lengths

Ulcerative colitis and irritable bowel patients exhibit distinct abnormalities of the gut microbiota

<p>Abstract</p> <p>Background</p> <p>Previous studies suggest a link between gut microbiota and the development of ulcerative colitis (UC) and irritable bowel syndrome (IBS). Our aim was to investigate any quantitative differences in faecal bacterial compositions in UC and IBS patients compared to healthy controls, and to identify individual bacterial species that contribute to these differences.</p> <p>Methods</p> <p>Faecal microbiota of 13 UC patients, 11 IBS patients and 22 healthy volunteers were analysed by PCR-Denaturing Gradient Gel Electrophoresis (DGGE) using universal and Bacteroides specific primers. The data obtained were normalized using in-house developed statistical method and interrogated by multivariate approaches. The differentiated bands were excised and identified by sequencing the V3 region of the 16S rRNA genes.</p> <p>Results</p> <p>Band profiles revealed that number of predominant faecal bacteria were significantly different between UC, IBS and control group (p < 10^-4). By assessing the mean band numbers in UC (37 ± 5) and IBS (39 ± 6), compared to the controls (45 ± 3), a significant decrease in bacterial species is suggested (p = 0.01). There were no significant differences between IBS and UC. Biodiversity of the bacterial species was significantly lower in UC (μ = 2.94, σ = 0.29) and IBS patients (μ = 2.90, σ = 0.38) than controls (μ = 3.25, σ = 0.16; p = 0.01). Moreover, similarity indices revealed greater biological variability of predominant bacteria in UC and IBS compared to the controls (median Dice coefficients 76.1% (IQR 70.9 - 83.1), 73.8% (IQR 67.0 - 77.5) and 82.9% (IQR 79.1 - 86.7) respectively). DNA sequencing of discriminating bands suggest that the presence of <it>Bacteroides vulgatus, B. ovatus, B. uniformis</it>, and <it>Parabacteroides sp</it>. in healthy volunteers distinguishes them from IBS and UC patients. DGGE profiles of Bacteroides species revealed a decrease of Bacteroides community in UC relative to IBS and controls.</p> <p>Conclusion</p> <p>Molecular profiling of faecal bacteria revealed abnormalities of intestinal microbiota in UC and IBS patients, while different patterns of Bacteroides species loss in particular, were associated with UC and IBS.</p

Comparative analysis of Neph gene expression in mouse and chicken development

Neph proteins are evolutionarily conserved members of the immunoglobulin superfamily of adhesion proteins and regulate morphogenesis and patterning of different tissues. They share a common protein structure consisting of extracellular immunoglobulin-like domains, a transmembrane region, and a carboxyl terminal cytoplasmic tail required for signaling. Neph orthologs have been widely characterized in invertebrates where they mediate such diverse processes as neural development, synaptogenesis, or myoblast fusion. Vertebrate Neph proteins have been described first at the glomerular filtration barrier of the kidney. Recently, there has been accumulating evidence suggesting a function of Neph proteins also outside the kidney. Here we demonstrate that Neph1, Neph2, and Neph3 are expressed differentially in various tissues during ontogenesis in mouse and chicken. Neph1 and Neph2 were found to be amply expressed in the central nervous system while Neph3 expression remained localized to the cerebellum anlage and the spinal cord. Outside the nervous system, Neph mRNAs were also differentially expressed in branchial arches, somites, heart, lung bud, and apical ectodermal ridge. Our findings support the concept that vertebrate Neph proteins, similarly to their Drosophila and C. elegans orthologs, provide guidance cues for cell recognition and tissue patterning in various organs which may open interesting perspectives for future research on Neph1-3 controlled morphogenesis

Low potency toxins reveal dense interaction networks in metabolism

Background The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved. In this paper I address the extent to which biochemistry is restricted to a small fraction of the chemical space of possible chemicals, a restricted subset that I call Biochemical Space. I explore evidence that this restriction is at least in part due to selection again specific structures, and suggest a mechanism by which this occurs. Results Chemicals that contain structures that our outside Biochemical Space (UnBiological groups) are more likely to be toxic to a wide range of organisms, even though they have no specifically toxic groups and no obvious mechanism of toxicity. This correlation of UnBiological with toxicity is stronger for low potency (millimolar) toxins. I relate this to the observation that most chemicals interact with many biological structures at low millimolar toxicity. I hypothesise that life has to select its components not only to have a specific set of functions but also to avoid interactions with all the other components of life that might degrade their function. Conclusions The chemistry of life has to form a dense, self-consistent network of chemical structures, and cannot easily be arbitrarily extended. The toxicity of arbitrary chemicals is a reflection of the disruption to that network occasioned by trying to insert a chemical into it without also selecting all the other components to tolerate that chemical. This suggests new ways to test for the toxicity of chemicals, and that engineering organisms to make high concentrations of materials such as chemical precursors or fuels may require more substantial engineering than just of the synthetic pathways involved