Skeletal muscle glucose uptake during treadmill exercise in neuronal nitric oxide synthase-μ knockout mice

Nitric oxide influences intramuscular signaling that affects skeletal muscle glucose uptake during exercise. The role of the main NO-producing enzyme isoform activated during skeletal muscle contraction, neuronal nitric oxide synthase-μ (nNOSμ), in modulating glucose uptake has not been investigated in a physiological exercise model. In this study, conscious and unrestrained chronically catheterized nNOSμ+/+ and nNOSμ−/− mice either remained at rest or ran on a treadmill at 17 m/min for 30 min. Both groups of mice demonstrated similar exercise capacity during a maximal exercise test to exhaustion (17.7 ± 0.6 vs. 15.9 ± 0.9 min for nNOSμ+/+ and nNOSμ−/−, respectively, P &gt; 0.05). Resting and exercise blood glucose levels were comparable between the genotypes. Very low levels of NOS activity were detected in skeletal muscle from nNOSμ−/− mice, and exercise increased NOS activity only in nNOSμ+/+ mice (4.4 ± 0.3 to 5.2 ± 0.4 pmol·mg−1·min−1, P &lt; 0.05). Exercise significantly increased glucose uptake in gastrocnemius muscle (5- to 7-fold) and, surprisingly, more so in nNOSμ−/− than in nNOSμ+/+ mice ( P &lt; 0.05). This is in parallel with a greater increase in AMPK phosphorylation during exercise in nNOSμ−/− mice. In conclusion, nNOSμ is not essential for skeletal muscle glucose uptake during exercise, and the higher skeletal muscle glucose uptake during exercise in nNOSμ−/− mice may be due to compensatory increases in AMPK activation. </jats:p

Selective scattering between Floquet-Bloch and Volkov states in a topological insulator

The coherent optical manipulation of solids is emerging as a promising way to engineer novel quantum states of matter. The strong time periodic potential of intense laser light can be used to generate hybrid photon-electron states. Interaction of light with Bloch states leads to Floquet-Bloch states which are essential in realizing new photo-induced quantum phases. Similarly, dressing of free electron states near the surface of a solid generates Volkov states which are used to study non-linear optics in atoms and semiconductors. The interaction of these two dynamic states with each other remains an open experimental problem. Here we use Time and Angle Resolved Photoemission Spectroscopy (Tr-ARPES) to selectively study the transition between these two states on the surface of the topological insulator Bi2Se3. We find that the coupling between the two strongly depends on the electron momentum, providing a route to enhance or inhibit it. Moreover, by controlling the light polarization we can negate Volkov states in order to generate pure Floquet-Bloch states. This work establishes a systematic path for the coherent manipulation of solids via light-matter interaction.Comment: 21 pages, 6 figures, final version to appear in Nature Physic

A semiconductor source of triggered entangled photon pairs?

The realisation of a triggered entangled photon source will be of great importance in quantum information, including for quantum key distribution and quantum computation. We show here that: 1) the source reported in ``A semiconductor source of triggered entangled photon pairs''[1. Stevenson et al., Nature 439, 179 (2006)]} is not entangled; 2) the entanglement indicators used in Ref. 1 are inappropriate, relying on assumptions invalidated by their own data; and 3) even after simulating subtraction of the significant quantity of background noise, their source has insignificant entanglement.Comment: 5 pages in pre-print format, 1 tabl

Metabolic changes of salicylic acid-elicited Catharanthus roseus cell suspension cultures monitored by NMR-based metabolomics

The effect of salicylic acid (SA) on the metabolic profile of Catharanthus roseus suspension cells throughout a time course (0, 6, 12, 24, 48 and 72 h after treatment) was investigated using NMR spectroscopy and multivariate data analysis. When compared to control cell lines, SA-treated cells showed a high level of sugars (glucose and sucrose) up to 48 h after treatment, followed by a dynamic change in amino acids, phenylpropanoids, and tryptamine. Additionally, one compound—2,5-dihydroxybenzoic-5-O-glucoside—was detected solely in SA-treated cells

Glucose-6-phosphate dehydrogenase contributes to the regulation of glucose uptake in skeletal muscle

The development of skeletal muscle insulin resistance is an early physiological defect, yet the intracellular mechanisms accounting for this metabolic defect remained unresolved. Here, we have examined the role of glucose-6-phosphate dehydrogenase (G6PDH) activity in the pathogenesis of insulin resistance in skeletal muscle. Methods Multiple mouse disease states exhibiting insulin resistance and glucose intolerance, as well as obese humans defined as insulin-sensitive, insulin-resistant, or pre-diabetic, were examined. Results We identified increased glucose-6-phosphate dehydrogenase (G6PDH) activity as a common intracellular adaptation that occurs in parallel with the induction of insulin resistance in skeletal muscle and is present across animal and human disease states with an underlying pathology of insulin resistance and glucose intolerance. We observed an inverse association between G6PDH activity and nitric oxide synthase (NOS) activity and show that increasing NOS activity via the skeletal muscle specific neuronal (n)NOS&mu; partially suppresses G6PDH activity in skeletal muscle cells. Furthermore, attenuation of G6PDH activity in skeletal muscle cells via (a) increased nNOS&mu;/NOS activity, (b) pharmacological G6PDH inhibition, or (c) genetic G6PDH inhibition increases insulin-independent glucose uptake. Conclusions We have identified a novel, previously unrecognized role for G6PDH in the regulation of skeletal muscle glucose metabolism. <br /

Regulation of Adipose Tissue Stromal Cells Behaviors by Endogenic Oct4 Expression Control

BACKGROUND: To clarify the role of the POU domain transcription factor Oct4 in Adipose Tissue Stromal Cells (ATSCs), we investigated the regulation of Oct4 expression and other embryonic genes in fully differentiated cells, in addition to identifying expression at the gene and protein levels. The ATSCs and several immature cells were routinely expressing Oct4 protein before and after differentiating into specific lineages. METHODOLOGY/PRINCIPAL FINDINGS AND CONCLUSIONS: Here, we demonstrated the role of Oct4 in ATSCs on cell proliferation and differentiation. Exogenous Oct4 improves adult ATSCs cell proliferation and differentiation potencies through epigenetic reprogramming of stemness genes such as Oct4, Nanog, Sox2, and Rex1. Oct4 directly or indirectly induces ATSCs reprogramming along with the activation of JAK/STAT3 and ERK1/2. Exogenic Oct4 introduced a transdifferentiation priority into the neural lineage than mesodermal lineage. Global gene expression analysis results showed that Oct4 regulated target genes which could be characterized as differentially regulated genes such as pluripotency markers NANOG, SOX2, and KLF4 and markers of undifferentiated stem cells FOXD1, CDC2, and EPHB1. The negatively regulated genes included FAS, TNFR, COL6A1, JAM2, FOXQ1, FOXO1, NESTIN, SMAD3, SLIT3, DKK1, WNT5A, BMP1, and GLIS3 which are implicated in differentiation processes as well as a number of novel genes. Finally we have demonstrated the therapeutic utility of Oct4/ATSCs were introduced into the mouse traumatic brain, engrafted cells was more effectively induces regeneration activity with high therapeutic modality than that of control ATSCs. Engrafted Oct4/ATSCs efficiently migrated and transdifferentiated into action potential carrying, functionally neurons in the hippocampus and promoting the amelioration of lesion cavities

STK295900, a Dual Inhibitor of Topoisomerase 1 and 2, Induces G<inf>2</inf> Arrest in the Absence of DNA Damage

STK295900, a small synthetic molecule belonging to a class of symmetric bibenzimidazoles, exhibits antiproliferative activity against various human cancer cell lines from different origins. Examining the effect of STK295900 in HeLa cells indicates that it induces G2 phase arrest without invoking DNA damage. Further analysis shows that STK295900 inhibits DNA relaxation that is mediated by topoisomerase 1 (Top 1) and topoisomerase 2 (Top 2) in vitro. In addition, STK295900 also exhibits protective effect against DNA damage induced by camptothecin. However, STK295900 does not affect etoposide-induced DNA damage. Moreover, STK295900 preferentially exerts cytotoxic effect on cancer cell lines while camptothecin, etoposide, and Hoechst 33342 affected both cancer and normal cells. Therefore, STK295900 has a potential to be developed as an anticancer chemotherapeutic agent. © 2013 Kim et al

Monitoring trends in socioeconomic health inequalities: it matters how you measure

<p>Abstract</p> <p>Background</p> <p>Odds ratio (OR), a relative measure for health inequality, has frequently been used in prior studies for presenting inequality trends in health and health behaviors. Since OR is not a good approximation of prevalence ratio (PR) when the outcome prevalence is quite high, an important problem may arise when OR trends are used in data in which the outcome variable (e.g., smoking or ill-health) is of relatively high prevalence and varies significantly over time. This study is to compare time trends of odds ratio (OR) and prevalence ratio (PR) for examining time trends in socioeconomic inequality in smoking.</p> <p>Methods</p> <p>A total of 147,805 subjects (71,793 men and 76,017 women) aged 25–64 from three Social Statistics Surveys of Korea from 1999 to 2006 were analyzed. Socioeconomic position indicators were occupational class and education.</p> <p>Results</p> <p>While there were no significant p values for trend in ORs of occupational class among men, trends for PRs were significant. In women, p values for OR trends were similar to those for PR trends. In males, RII by log-binomial regression showed a significant increasing tendency while RII by logistic regression was stable between years. In females, trends of RIIs by logistic regression and log-binomial regression produced a similar level of p values.</p> <p>Conclusion</p> <p>Different methods of measuring trends in socioeconomic health inequalities may lead to different conclusions about whether relative inequalities are increasing or decreasing. Trends in ORs may overstate or understate trends in relative inequality in health when the outcome is of relatively high prevalence and that prevalence varies significantly with time.</p

Overcoming challenges of translating deep- learning models for glioblastoma: the ZGBM consortium

Objective: To report imaging protocol and scheduling variance in routine care of glioblastoma patients in order to demonstrate challenges of integrating deep-learning models in glioblastoma care pathways. Additionally, to understand the most common imaging studies and image contrasts to inform the development of potentially robust deep-learning models. Methods: MR imaging data were analysed from a random sample of five patients from the prospective cohort across five participating sites of the ZGBM consortium. Reported clinical and treatment data alongside DICOM header information were analysed to understand treatment pathway imaging schedules. Results: All sites perform all structural imaging at every stage in the pathway except for the presurgical study, where in some sites only contrast-enhanced T 1-weighted imaging is performed. Diffusion MRI is the most common non-structural imaging type, performed at every site. Conclusion: The imaging protocol and scheduling varies across the UK, making it challenging to develop machine-learning models that could perform robustly at other centres. Structural imaging is performed most consistently across all centres. Advances in knowledge: Successful translation of deep-learning models will likely be based on structural post-treatment imaging unless there is significant effort made to standardise non-structural or peri-operative imaging protocols and schedules

Molecular characterization of partial-open reading frames 1a and 2 of the human astroviruses in South Korea

Human astroviruses (HAstVs) are among the major causes of gastroenteritis in South Korea. In this study, the partial regions of the open reading frame (ORF) 1a and ORF2 genes of HAstVs from gastroenteritis patients in nine hospitals were sequenced, and the molecular characterization of the viruses was revealed. 89 partial nucleotide sequences of ORF1a and 88 partial nucleotide sequences of ORF2 were amplified from 120 stool specimens. Phylogenetic analysis showed that most of the nucleotide sequences of ORF1a and ORF2 were grouped with HAstV type 1 but had evolutionary genetic distance compared with the reference sequences, such as the HAstV-1 prototype, Dresden strain, and Oxford strain. According to the phylogenetic analysis, some nucleotide sequences including SE0506041, SE0506043, and SE0506058, showed the discrepancy of the genotypes, but there was no proof of recombination among the HAstV types. In conclusion, this study showed that the dominant HAstV isolated from the Seoul metropolitan area in 2004-2005 was HAstV type 1, and that Korean HAstV-1 had the genetic distance in evolution compared with the reference sequences of HAstVs. Lots of nucleotide sequences of the ORF1a and ORF2 genes of HAstV will be useful for studying for the control and prevention of HAstV gastroenteritis in South Korea