miRNAs as Regulators of Antidiabetic Effects of Fucoidans

open access articleDiabetes mellitus is a metabolic disease with a high mortality rate worldwide. MicroRNAs (miRNAs), and other small noncoding RNAs, serve as endogenous gene regulators through binding to specific sequences in RNA and modifying gene expression toward up- or down-regulation. miRNAs have become compelling therapeutic targets and play crucial roles in regulating the process of insulin resistance. Fucoidan has shown potential function as an a-amylase inhibitor, which may be beneficial in the management of type 2 diabetes mellitus. In recent years, many studies on fucoidan focused on the decrease in blood glucose levels caused by ingesting low-glucose food or glucose-lowering components. However, the importance of miRNAs as regulators of antidiabetic effects was rarely recognized. Hence, this review emphasizes the antidiabetic mechanisms of fucoidan through regulation of miRNAs. Fucoidan exerts a vital antidiabetic effect by regulation of miRNA expression and thus provides a novel biological target for future research

Let us conserve and exchange seeds: celebrating traditional crop diversity of the Nepali lowlands

A seed fair is an activity to create awareness about and appreciate local crop diversity, exchange seed and related knowledge, and celebrate farmers’ efforts to conserve agrobiodiversity. It takes considerable time and effort to organize a seed fair. This brief describes the seed fair organized at the Agyauli Community Seedbank, Nawalparasi in the southern region of Nepal. About 30 members of 10 community seedbanks from the terai (the southern lowland) region of Nepal came together for this. Apart from exchanging seeds of traditional crop varieties, they also shared stories about the socio-cultural, religious, spiritual, nutritional and medicinal values of their varieties. The recent formal registration of the Community Seed Banks Association of Nepal (CSBAN) was also celebrated

Chemical determinants of occupational hypersensitivity pneumonitis

Background: Workplace inhalational exposures to low molecular weight (LMW) chemicals cause hypersensitivity pneumonitis (HP) as well as the more common manifestation of respiratory hypersensitivity, occupational asthma (OA). Aims: To explore whether chemical causation of HP is associated with different structural and physico-chemical determinants from OA. Methods: Chemical causes of human cases of HP and OA were identified from searches of peer-reviewed literature up to the end of 2011. Each chemical was categorised according to whether or not it had been the attributed cause of at least one case of HP. The predicted asthma hazard was determined for each chemical using a previously developed quantitative structure-activity relationship (QSAR) model. The chemicals in both sets were independently and ‘blindly’ analysed by an expert in mechanistic chemistry for a qualitative prediction of protein cross-linking potential and determination of lipophilicity (log Kow). Results: Ten HP causing chemicals were identified and had a higher median QSAR predicted asthma hazard than the control group of 101 OA causing chemicals (p < 0.005). Nine of ten HP causing chemicals were predicted to be protein cross-linkers compared to 24/92 controls (p<0.0001). The distributions of log Kow indicated higher values for the HP list (median 3.47) compared to controls (median 0.81) (p < 0.05). Conclusion: These findings suggest that chemicals capable of causing HP tend to have higher predicted asthma hazard, are more lipophilic and are more likely to be protein cross-linkers than those causing OA. Key words: hypersensitivity pneumonitis, occupational chemicals, occupational respiratory disease, toxic inhalatio

Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure

Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota, characterized by persistently low diversity, dominance of pathogenic bacteria within the Enterobacteriaceae family, and a paucity of strictly anaerobic taxa including Veillonella relative to infants with appropriate postnatal growth. Metabolomic profiling of infants with growth failure demonstrated elevated serum acylcarnitines, fatty acids, and other byproducts of lipolysis and fatty acid oxidation. Machine learning algorithms for normal maturation of the microbiota and metabolome among infants with appropriate growth revealed a pattern of delayed maturation of the microbiota and metabolome among infants with growth failure. Collectively, we identified novel microbial and metabolic features of growth failure in preterm infants and potentially modifiable targets for intervention

Influence of initial stress distribution on liquefaction-induced settlement of shallow foundations

During earthquakes, saturated sandy soils may generate significant excess pore pressures and approach a state of liquefaction. Structures founded on shallow foundations above such soils may consequently undergo large settlements. Recent case history analysis has shown that the stress imposed by the foundation is a key factor in the estimation of such settlements. However, the case history data showed that although increasing bearing pressure caused an increase in settlements as expected, this was only true up to a point, and that very heavy structures appeared to settle less than some lighter structures. This work aims to investigate these counter-intuitive results by means of controlled experimental testing using a geotechnical centrifuge. Results of the centrifuge tests show that the trend derived from case histories is correct and that liquefaction-induced settlements peak for a given bearing stress (90 kPa for the models tested) and reduce for greater applied stresses. Further, by analysis of excess pore pressure distributions beneath the foundations it is shown that the main factor inhibiting pore pressure generation beneath the footings is not so much the confining pressure as the in-situ static shear stress around the edge of the foundation. This is supported by element test data from the literature. When this initial static shear stress is so high that the applied cyclic shear stress cannot exceed it (i.e. the direction of shear stress does not reverse) then pore pressure generation is greatly reduced, thus causing the observed reduction in expected settlements.All data created during this research are openly available from the University of Dundee repository Discovery at http://doi.org/10.15132/10000116</p

Deep-coverage whole genome sequences and blood lipids among 16,324 individuals.

Large-scale deep-coverage whole-genome sequencing (WGS) is now feasible and offers potential advantages for locus discovery. We perform WGS in 16,324 participants from four ancestries at mean depth &gt;29X and analyze genotypes with four quantitative traits-plasma total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides. Common variant association yields known loci except for few variants previously poorly imputed. Rare coding variant association yields known Mendelian dyslipidemia genes but rare non-coding variant association detects no signals. A high 2M-SNP LDL-C polygenic score (top 5th percentile) confers similar effect size to a monogenic mutation (~30 mg/dl higher for each); however, among those with severe hypercholesterolemia, 23% have a high polygenic score and only 2% carry a monogenic mutation. At these sample sizes and for these phenotypes, the incremental value of WGS for discovery is limited but WGS permits simultaneous assessment of monogenic and polygenic models to severe hypercholesterolemia

Differences between <i>Trypanosoma brucei gambiense</i> groups 1 and 2 in their resistance to killing by Trypanolytic factor 1

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The three sub-species of &lt;i&gt;Trypanosoma brucei&lt;/i&gt; are important pathogens of sub-Saharan Africa. &lt;i&gt;T. b. brucei&lt;/i&gt; is unable to infect humans due to sensitivity to trypanosome lytic factors (TLF) 1 and 2 found in human serum. &lt;i&gt;T. b. rhodesiense&lt;/i&gt; and &lt;i&gt;T. b. gambiense&lt;/i&gt; are able to resist lysis by TLF. There are two distinct sub-groups of &lt;i&gt;T. b. gambiense&lt;/i&gt; that differ genetically and by human serum resistance phenotypes. Group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; have an invariant phenotype whereas group 2 show variable resistance. Previous data indicated that group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; are resistant to TLF-1 due in-part to reduced uptake of TLF-1 mediated by reduced expression of the TLF-1 receptor (the haptoglobin-hemoglobin receptor (&lt;i&gt;HpHbR&lt;/i&gt;)) gene. Here we investigate if this is also true in group 2 parasites.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methodology:&lt;/b&gt; Isogenic resistant and sensitive group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; were derived and compared to other T. brucei parasites. Both resistant and sensitive lines express the &lt;i&gt;HpHbR&lt;/i&gt; gene at similar levels and internalized fluorescently labeled TLF-1 similar fashion to &lt;i&gt;T. b. brucei&lt;/i&gt;. Both resistant and sensitive group 2, as well as group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt;, internalize recombinant APOL1, but only sensitive group 2 parasites are lysed.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Our data indicate that, despite group 1 &lt;i&gt;T. b. gambiense&lt;/i&gt; avoiding TLF-1, it is resistant to the main lytic component, APOL1. Similarly group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; is innately resistant to APOL1, which could be based on the same mechanism. However, group 2 &lt;i&gt;T. b. gambiense&lt;/i&gt; variably displays this phenotype and expression does not appear to correlate with a change in expression site or expression of &lt;i&gt;HpHbR&lt;/i&gt;. Thus there are differences in the mechanism of human serum resistance between &lt;i&gt;T. b. gambiense&lt;/i&gt; groups 1 and 2.&lt;/p&gt

Numerical modelling of transient cyclic vertical loading of suction caissons in sand

This paper presents numerical investigations of the monotonic and cyclic behaviours of suction caissons upon vertical transient loading. Both drained and partially drained conditions are investigated. Monotonic compression and traction simulations are carried out to qualitatively compare results with the literature and validate the model. They highlight the different modes of reaction of the caisson to both compression and traction loading. A sensitivity analysis points out the strong influence of some parameters on the resistance of the caisson but also on the failure mechanism. The transient behaviour of the caisson upon different kinds of cyclic load signals is analysed. Results reproduce the settlement and pore water pressure accumulations observed during experiments. The influence of the key design parameters on the settlement accumulation is also assessed. Finally a cyclic diagram is proposed to describe the evolution of the final settlement upon different magnitudes of loading

How the other half lives: CRISPR-Cas's influence on bacteriophages

CRISPR-Cas is a genetic adaptive immune system unique to prokaryotic cells used to combat phage and plasmid threats. The host cell adapts by incorporating DNA sequences from invading phages or plasmids into its CRISPR locus as spacers. These spacers are expressed as mobile surveillance RNAs that direct CRISPR-associated (Cas) proteins to protect against subsequent attack by the same phages or plasmids. The threat from mobile genetic elements inevitably shapes the CRISPR loci of archaea and bacteria, and simultaneously the CRISPR-Cas immune system drives evolution of these invaders. Here we highlight our recent work, as well as that of others, that seeks to understand phage mechanisms of CRISPR-Cas evasion and conditions for population coexistence of phages with CRISPR-protected prokaryotes.Comment: 24 pages, 8 figure