Sequence-specific Photomodification Of Dna By An Oligonucleotide-phenanthrodihydrodioxin Conjugate

We introduce a new member of a family of photochemically active oligonucleotide conjugates. A Phenanthrodihydrodioxin (PDHD)-based agent was synthesized and covalently linked to a 5\u27-end of the 9-mer oligonucleotide via a hexamethylene linker. The conjugate hybridized to a complementary 30-nucleotide-long target and efficiently cleaved it in a sequence specific manner. Up to 67% of target was specifically damaged (51% cross-links and 16% direct cleavage). While the photosensitizer alone nonspecifically damaged only Gs in a single-stranded target, its conjugate cross-linked to and damaged also A, T, and C sites in a target in agreement with duplex and tripler formation

Persistent Correlation of Ghrelin Plasma Levels with Body Mass Index Both in Stable Weight Conditions and during Gastric-bypass-induced Weight Loss

Background: Studies done on serial changes in plasma ghrelin levels after gastric bypass (GBP) have yielded contrasting results since decreased, unchanged, or increased levels have been reported in the literature. This study investigates whether or not GBP has an inhibitory effect on fasting ghrelin levels independently of weight loss. Methods: Fasting ghrelin levels were measured in 115 stable body weight females, classified as normal body weight (NW; body mass index (BMI) 50kg/m2). Results: Each obese subgroup showed significantly lower ghrelin levels as compared to both NW (p < 0.0001) and OW subjects (p < 0.05 or 0.005); however, no significant differences were observed within the three obese subgroups. Forty-nine obese patients underwent a GBP. Plasma ghrelin, measured at 3, 6, and 12months after GBP, significantly increased from the sixth month on (p < 0.0001). When patients were classified, at each postoperative time point, according to their actual BMI, ghrelin was significantly (p = 0.0002) related to postoperative BMI and not significantly different from ghrelin measured in stable body weight conditions. Conclusions: Fasting ghrelin displays an inversely significant correlation with BMI in both stable body weight conditions and after GBP. No evidence was found that GBP had an effect on fasting ghrelin levels, independent of weight los

Correlation entropy of synaptic input-output dynamics

The responses of synapses in the neocortex show highly stochastic and nonlinear behavior. The microscopic dynamics underlying this behavior, and its computational consequences during natural patterns of synaptic input, are not explained by conventional macroscopic models of deterministic ensemble mean dynamics. Here, we introduce the correlation entropy of the synaptic input-output map as a measure of synaptic reliability which explicitly includes the microscopic dynamics. Applying this to experimental data, we find that cortical synapses show a low-dimensional chaos driven by the natural input pattern.Comment: 7 pages, 6 Figures (7 figure files

Upregulation of peroxisome proliferator-activated receptor gamma coactivator gene ( PGC1A ) during weight loss is related to insulin sensitivity but not to energy expenditure

Aims/hypothesis: We investigated whether skeletal muscle peroxisome proliferator-activated receptor gamma coactivator-1 (PGC1A; also known as PPARGC1A) and its target mitofusin-2 (MFN2), as well as carnitine palmitoyltransferase-1 (CPT1; also known as carnitine palmitoyltransferase 1A [liver] [CPT1A]) and uncoupling protein (UCP)3, are involved in the improvement of insulin resistance and/or in the modification of energy expenditure during surgically induced massive weight loss. Materials and methods: Seventeen morbidly obese women (mean BMI: 45.9 ± 4kg/m2) were investigated before, and 3 and 12months after, Roux-en-Y gastric bypass (RYGB). We evaluated insulin sensitivity by the euglycaemic-hyperinsulinaemic clamp, energy expenditure and substrate oxidation by indirect calorimetry, and muscle mRNA expression by PCR. Results: Post-operatively, PGC1A was enhanced at 3 (p = 0.02) and 12months (p = 0.03) as was MFN2 (p = 0.008 and p = 0.03 at 3 and 12months respectively), whereas UCP3 was reduced (p = 0.03) at 12months. CPT1 did not change. The expression of PGC1A and MFN2 were strongly (p < 0.0001) related. Insulin sensitivity, which increased after surgery (p = 0.002 at 3, p = 0.003 at 12months), was significantly related to PGC1A and MFN2, but only MFN2 showed an independent influence in a multiple regression analysis. Energy expenditure was reduced at 3months post-operatively (p = 0.001 vs before RYGB), remaining unchanged thereafter until 12months. CPT1 and UCP3 were not significantly related to the modifications of energy expenditure or of lipid oxidation rate. Conclusions/interpretation: Weight loss upregulates PGC1A, which in turn stimulates MFN2 expression. MFN2 expression significantly and independently contributes to the improvement of insulin sensitivity. UCP3 and CPT1 do not seem to influence energy expenditure after RYG

Neutral-Donor-Bound-Exciton Complexes in ZnO Crystals

Neutral-donor–bound-exciton transitions have been observed in ZnO. The isolated neutral donors are made up of defect pair complexes. The neutral-donor nature of these pair complexes was determined from magneticfield measurements and from two-electron transitions. Excited states of the neutral-donor bound excitons were observed in the form of rotator states analogous to rotational states of the H2 molecule

The effect of insulin on cardiac autonomic balance predicts weight reduction after gastric bypass

Aims/hypothesis: The aim of this study was to assess the predictive role of autonomic reactivity in body weight loss induced by gastric bypass. Methods: A group of 22 morbidly obese subjects, who were due to undergo a gastric bypass, were submitted, before surgery, to a euglycaemic-hyperinsulinaemic clamp, during which a continuous recording of the ECG was performed. The effect of insulin on cardiac autonomic balance was evaluated by performing power spectral analysis of heart rate variability. The low-to-high frequency ratio was calculated before and during the clamp and its modifications were expressed as % delta low-to-high frequency ratio (%Δ L: H). Results: Preoperative %Δ L: H showed a significant (p=0.0009, r 2=0.43), positive relationship to the reduction of body weight, measured 1 year after surgery and expressed as % excess weight loss (% EWL). Preoperative BMI was also significantly (p=0.0009, r 2=0.43) negatively related to the 12-month % EWL. In a multiple regression analysis, %Δ L: H remained a significant (p=0.003), independent predictor of body weight loss, even when preoperative BMI or age, % fat mass, insulinaemia and glucose disposal were taken into account. Conclusions/interpretation: The best correction of excess body weight was achieved by those obese subjects who had a preserved capacity to shift their cardiac autonomic balance towards a sympathetic prevalence in response to an euglycaemic-hyperinsulinaemic clamp. Further studies are needed to elucidate the mechanisms through which the autonomic nervous system influences weight reductio

Is Environmental Improvement in Automotive Component Design Highly Constrained?

This article investigates the influence of environmental, cost, and performance requirements on the design and management of automotive components through a case study involving instrument panels. To address the question of whether the environmental improvement of an instrument panel (IP) is highly constrained, a lifecycle inventory analysis is used to characterize the major environmental burdens associated with a generic IP defined from an average of three midsized vehicle models. A life-cycle cost analysis is also conducted to understand the market forces operating in the domains of the original equipment manufacturer; consumer; and end-of-life (EOL) vehicle managen. This study indicates that the existing set of environmental requirements, in conjunction with current cost drivers and the large set of manufacturing and use phase functional performance requirements, highly constrain opportunities for environmental improvement Specific improvement strategies-lightweighting, elimination of the painting operation, and reduction in material complexity-are examined in the context of existing system requirements. The near-term forecast for improvements is not optimistic. Innovation will continue in a slow and piecemeal fashion until requirements affecting the total vehicle system are significantly changedPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72780/1/jiec.1998.2.2.103.pd

Weight and metabolic effects of cpap in obstructive sleep apnea patients with obesity

<p>Abstract</p> <p>Background</p> <p>Obstructive sleep apnea (OSA) is associated with obesity, insulin resistance (IR) and diabetes. Continuous positive airway pressure (CPAP) rapidly mitigates OSA in obese subjects but its metabolic effects are not well-characterized. We postulated that CPAP will decrease IR, ghrelin and resistin and increase adiponectin levels in this setting.</p> <p>Methods</p> <p>In a pre- and post-treatment, within-subject design, insulin and appetite-regulating hormones were assayed in 20 obese subjects with OSA before and after 6 months of CPAP use. Primary outcome measures included glucose, insulin, and IR levels. Other measures included ghrelin, leptin, adiponectin and resistin levels. Body weight change were recorded and used to examine the relationship between glucose regulation and appetite-regulating hormones.</p> <p>Results</p> <p>CPAP effectively improved hypoxia. However, subjects had increased insulin and IR. Fasting ghrelin decreased significantly while leptin, adiponectin and resistin remained unchanged. Forty percent of patients gained weight significantly. Changes in body weight directly correlated with changes in insulin and IR. Ghrelin changes inversely correlated with changes in IR but did not change as a function of weight.</p> <p>Conclusions</p> <p>Weight change rather than elimination of hypoxia modulated alterations in IR in obese patients with OSA during the first six months of CPAP therapy.</p

Tropical forcing of increased Southern Ocean climate variability revealed by a 140-year subantarctic temperate reconstruction

Occupying 14% of the world’s surface, the Southern Ocean plays a fundamental role in global climate, ocean circulation, carbon cycling and Antarctic ice-sheet stability. Unfortunately, high interannual variability and a dearth of instrumental observations before the 1950s limits our understanding of how marine-atmosphere-ice domains interact on multi-decadal timescales and the impact of anthropogenic forcing. Here we integrate climate-sensitive tree growth with ocean and atmospheric observations on southwest Pacific subantarctic islands that lie at the boundary of polar and subtropical climates (52–54˚S). Our annually-resolved temperature reconstruction captures regional change since the 1870s and demonstrates a significant increase in variability from the mid-twentieth century, a phenomenon predating the observational record. Climate reanalysis and modelling shows a parallel change in tropical Pacific sea surface temperatures that generate an atmospheric Rossby wave train which propagates across a large part of the Southern Hemisphere during the austral spring and summer