Homozygous carriers of the TCF7L2 rs7903146 T-allele show altered postprandial response in triglycerides and triglyceride-rich lipoproteins

The TCF7L2 rs7903146 T-allele shows the strongest association with type 2 diabetes (T2D) among common gene variants. The aim of this study was to assess circulating levels of metabolites following a meal test in individuals carrying the high risk rs790346 TT genotype (cases) and low-risk CC genotype (controls). Sixty-two men were recruited based on TCF7L2 genotype, 31 were TT carriers and 31 were age- and BMI-matched CC carriers. All participants consumed a test meal after 12 hours of fasting. Metabolites were measured using proton nuclear magnetic resonance (NMR) spectroscopy. Metabolomic profiling of TCF7L2 carriers were performed for 141 lipid estimates. TT carriers had lower fasting levels of L-VLDL-L (total lipids in large very low density lipoproteins, p = 0.045), L-VLDL-CE (cholesterol esters in large VLDL, p = 0.03), and L-VLDL-C (total cholesterol in large VLDL, p = 0.045) compared to CC carriers. Additionally, TT carriers had lower postprandial levels of total triglycerides (TG) (q = 0.03), VLDL-TG (q = 0.05, including medium, small and extra small, q = 0.048, q = 0.0009, q = 0.04, respectively), HDL-TG (triglycerides in high density lipoproteins q = 0.037) and S-HDL-TG (q = 0.00003). In conclusion, TT carriers show altered postprandial triglyceride response, mainly influencing VLDL and HDL subclasses suggesting a genotype-mediated effect on hepatic lipid regulation

The performance of beta type stirling engine using different fuel

Stirling engine categorized as external combustion engine which defined as a closed-cycle regenerative heat engine to perform the conversion of energy into the mechanical power. The thermal efficiency of the Stirling cycle always is the main criterion, and the literature showed its efficiency of energy conversion is consider relatively as high as the Carnot cycle. Although the Stirling engine consists of great versatility for energy sources, however still inadequate efforts were done for the development of the Stirling engine that is powered by combustion fuel, since generally the engine is fueled by renewable energy which is inapplicable by the public. Therefore, the objectives to fill up the research gaps are to simulate the operation condition of Beta type Stirling engine by manipulated the use of different fuels with the assistant of MATLAB then compared with the outcome of a reference model to validate the outcome and to acquire the optimum performance of the engine, and any index that brings a reputation for the development of the Stirling engine. Compression ratio, and the temperature of the heater that affected by the specifications of Stirling engine design and effective volume of the heater, respectively act as the major element that manipulated the final power output. A higher compression ratio of 18 and power output of 315.88 Watts can be obtained with smaller clearance between the engine primary components, besides the heater temperature that achieves 855.75 K and thermal efficiency of 64.93% is affected by the usage of appropriate combustion fuel as gasoline and bigger effective volume of the heater

Performance improvement in mobile air conditioning system using Al2O3/PAG nanolubricant

This paper presents the investigation of Al2O3/PAG nanolubricant performance for a compact vehicle mobile air conditioning (MAC) system. The Al2O3/PAG nanolubricant in this study is prepared by using two-step preparation method and stabilized using 4-Step UV–Vis Spectral Absorbency Analysis. An enhancement in the coefficient of performance (COP), reduction in compressor work, and enhancement in the cooling capacity of MAC employing Al2O3/PAG nanolubricant are recorded up to 31%, 26% and 32%, respectively, for 0.010% volume concentration. The current MAC performance is compared with MAC employing SiO2/PAG nanolubricant from previous study. The comparison shows that the Al2O3/PAG nanolubricant has better performance in term of cooling capacity, compressor work, and COP at an average of 6%, 8%, and 33%, respectively. Therefore, the finding from this study suggests Al2O3/PAG nanolubricant with a volume concentration of 0.010% as an optimum and best performance nanolubricant for MAC systems

Identifying factors associated with sedentary time after stroke. Secondary analysis of pooled data from nine primary studies.

<p><b>Background</b>: High levels of sedentary time increases the risk of cardiovascular disease, including recurrent stroke.</p> <p><b>Objective</b>: This study aimed to identify factors associated with high sedentary time in community-dwelling people with stroke.</p> <p><b>Methods</b>: For this data pooling study, authors of published and ongoing trials that collected sedentary time data, using the activPAL monitor, in community-dwelling people with stroke were invited to contribute their raw data. The data was reprocessed, algorithms were created to identify sleep-wake time and determine the percentage of waking hours spent sedentary. We explored demographic and stroke-related factors associated with total sedentary time and time in uninterrupted sedentary bouts using unique, both univariable and multivariable, regression analyses.</p> <p><b>Results</b>: The 274 included participants were from Australia, Canada, and the United Kingdom, and spent, on average, 69% (SD 12.4) of their waking hours sedentary. Of the demographic and stroke-related factors, slower walking speeds were significantly and independently associated with a higher percentage of waking hours spent sedentary (p = 0.001) and uninterrupted sedentary bouts of <i>>30</i> and <i>>60 min</i> (p = 0.001 and p = 0.004, respectively). Regression models explained 11–19% of the variance in total sedentary time and time in prolonged sedentary bouts.</p> <p><b>Conclusion</b>: We found that variability in sedentary time of people with stroke was largely unaccounted for by demographic and stroke-related variables. Behavioral and environmental factors are likely to play an important role in sedentary behavior after stroke. Further work is required to develop and test effective interventions to address sedentary behavior after stroke.</p

The role of lipids in mechanosensation

Acknowledgements: This work was supported by Wellcome Trust grants WT092552MA (J.H.N. and I.R.B.), Senior Investigator Award WT100209MA (J.H.N.), 093228 (T.K.S.) and 092970 (M.S.P.S.), and Biotechnology and Biological Sciences Research Council grants BB/I019855/1 (M.S.P.S.), BB/H017917/1 (J.H.N. and I.R.B.) and BB/J009784/1 (H.B.). We acknowledge the Diamond Light Source for beam time. I.R.B. is supported as a Leverhulme Emeritus Fellow. J.H.N. is supported as a Royal Society Wolfson Merit Award holder and as a 1000 Talent Scholar at Sichuan University. A.C.E.D. was supported by an Engineering and Physical Sciences Research Council Systems Biology Doctoral Training Centre student fellowship. We thank R. Phillips, A. Lee and S. Conway for helpful discussions.Peer reviewedPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprintPostprin

How β-Lactam Antibiotics Enter Bacteria: A Dialogue with the Porins

BACKGROUND:Multi-drug resistant (MDR) infections have become a major concern in hospitals worldwide. This study investigates membrane translocation, which is the first step required for drug action on internal bacterial targets. beta-lactams, a major antibiotic class, use porins to pass through the outer membrane barrier of Gram-negative bacteria. Clinical reports have linked the MDR phenotype to altered membrane permeability including porin modification and efflux pump expression. METHODOLOGY/PRINCIPAL FINDINGS: Here influx of beta-lactams through the major Enterobacter aerogenes porin Omp36 is characterized. Conductance measurements through a single Omp36 trimer reconstituted into a planar lipid bilayer allowed us to count the passage of single beta-lactam molecules. Statistical analysis of each transport event yielded the kinetic parameters of antibiotic travel through Omp36 and distinguishable translocation properties of beta-lactams were quantified for ertapenem and cefepime. Expression of Omp36 in an otherwise porin-null bacterial strain is shown to confer increases in the killing rate of these antibiotics and in the corresponding bacterial susceptibility. CONCLUSIONS/SIGNIFICANCE: We propose the idea of a molecular "passport" that allows rapid transport of substrates through porins. Deciphering antibiotic translocation provides new insights for the design of novel drugs that may be highly effective at passing through the porin constriction zone. Such data may hold the key for the next generation of antibiotics capable of rapid intracellular accumulation to circumvent the further development MDR infections

Association of Ketone Body Levels With Hyperglycemia and Type 2 Diabetes in 9,398 Finnish Men

We investigated the association of the levels of ketone bodies (KBs) with hyperglycemia and with 62 genetic risk variants regulating glucose levels or type 2 diabetes in the population-based Metabolic Syndrome in Men (METSIM) study, including 9,398 Finnish men without diabetes or newly diagnosed type 2 diabetes. Increasing fasting and 2-h plasma glucose levels were associated with elevated levels of acetoacetate (AcAc) and β-hydroxybutyrate (BHB). AcAc and BHB predicted an increase in the glucose area under the curve in an oral glucose tolerance test, and AcAc predicted the conversion to type 2 diabetes in a 5-year follow-up of the METSIM cohort. Impaired insulin secretion, but not insulin resistance, explained these findings. Of the 62 single nucleotide polymorphisms associated with the risk of type 2 diabetes or hyperglycemia, the glucose-increasing C allele of GCKR significantly associated with elevated levels of fasting BHB levels. Adipose tissue mRNA expression levels of genes involved in ketolysis were significantly associated with insulin sensitivity (Matsuda index). In conclusion, high levels of KBs predicted subsequent worsening of hyperglycemia, and a common variant of GCKR was significantly associated with BHB levels

Photosensitizer Drug Delivery via an Optical Fiber

: An optical fiber has been developed with a maneuverable miniprobe tip that sparges O2 gas and photodetaches pheophorbide (sensitizer) molecules. Singlet oxygen is produced at the probe tip surface which reacts with an alkene spacer group releasing sensitizer upon fragmentation of a dioxetane intermediate. Optimal sensitizer photorelease occurred when the probe tip was loaded with 60 nmol sensitizer, where crowding of the pheophorbide molecules and self-quenching were kept to a minimum. The fiber optic tip delivered pheophorbide molecules and singlet oxygen to discrete locations. The 60 nmol sensitizer was delivered into petrolatum; however, sensitizer release was less efficient in toluene-d8 (3.6 nmol) where most had remained adsorbed on the probe tip, even after the covalent alkene spacer bond had been broken. The results open the door to a new area of fiber optic-guided sensitizer delivery for the potential photodynamic therapy of hypoxic structures requiring cytotoxic control

The microaerophilic microbiota of de-novo paediatric inflammatory bowel disease: the BISCUIT study

&lt;p&gt;Introduction: Children presenting for the first time with inflammatory bowel disease (IBD) offer a unique opportunity to study aetiological agents before the confounders of treatment. Microaerophilic bacteria can exploit the ecological niche of the intestinal epithelium; Helicobacter and Campylobacter are previously implicated in IBD pathogenesis. We set out to study these and other microaerophilic bacteria in de-novo paediatric IBD.&lt;/p&gt; &lt;p&gt;Patients and Methods: 100 children undergoing colonoscopy were recruited including 44 treatment naïve de-novo IBD patients and 42 with normal colons. Colonic biopsies were subjected to microaerophilic culture with Gram-negative isolates then identified by sequencing. Biopsies were also PCR screened for the specific microaerophilic bacterial groups: Helicobacteraceae, Campylobacteraceae and Sutterella wadsworthensis.&lt;/p&gt; &lt;p&gt;Results: 129 Gram-negative microaerophilic bacterial isolates were identified from 10 genera. The most frequently cultured was S. wadsworthensis (32 distinct isolates). Unusual Campylobacter were isolated from 8 subjects (including 3 C. concisus, 1 C. curvus, 1 C. lari, 1 C. rectus, 3 C. showae). No Helicobacter were cultured. When comparing IBD vs. normal colon control by PCR the prevalence figures were not significantly different (Helicobacter 11% vs. 12%, p = 1.00; Campylobacter 75% vs. 76%, p = 1.00; S. wadsworthensis 82% vs. 71%, p = 0.312).&lt;/p&gt; &lt;p&gt;Conclusions: This study offers a comprehensive overview of the microaerophilic microbiota of the paediatric colon including at IBD onset. Campylobacter appear to be surprisingly common, are not more strongly associated with IBD and can be isolated from around 8% of paediatric colonic biopsies. S. wadsworthensis appears to be a common commensal. Helicobacter species are relatively rare in the paediatric colon.&lt;/p&gt