Large enhancement of the thermopower in Nax_xCoO2_2 at high Na doping

Research on the oxide perovskites has uncovered electronic properties that are strikingly enhanced compared with those in conventional metals. Examples are the high critical temperatures of the cuprate superconductors and the colossal magnetoresistance in the manganites. The conducting layered cobaltate $\rm Na_xCoO_2$ displays several interesting electronic phases as $x$ is varied including water-induced superconductivity and an insulating state that is destroyed by field. Initial measurements showed that, in the as-grown composition, $\rm Na_xCoO_2$ displays moderately large thermopower $S$ and conductivity $\sigma$. However, the prospects for thermoelectric cooling applications faded when the figure of merit $Z$ was found to be small at this composition (0.6$<x<$0.7). Here we report that, in the poorly-explored high-doping region $x>$0.75, $S$ undergoes an even steeper enhancement. At the critical doping $x_p\sim$ 0.85, $Z$ (at 80 K) reaches values $\sim$40 times larger than in the as-grown crystals. We discuss prospects for low-temperature thermoelectric applications.Comment: 6 pages, 7 figure

Survey of Nutrition Management Practices in Centers for Pediatric Intestinal Rehabilitation

Background: Nutrition management of pediatric intestinal failure (IF) requires interdisciplinary coordination of parenteral nutrition (PN) and enteral nutrition (EN) support. Nutrition strategies used by specialists in pediatric intestinal rehabilitation to promote gut adaptation and manage complications have not been previously summarized. Methods: A practice survey was distributed to members of the dietitian subgroup of the American Society for Parenteral and Enteral Nutrition Pediatric Intestinal Failure Section. The survey included 24 open‐ended questions related to PN and enteral feeding strategies, nutrition management of PN‐associated liver disease, and laboratory monitoring. Results: Dietitians from 14 centers completed the survey. Management components for patients at risk for cholestasis were consistent and included fat minimization, trace element modification, avoiding PN overfeeding, and providing EN. Parenteral amino acid solutions designed for infants/young children are used in patients <1 or 2 years of age. Trace minerals are dosed individually in 10 of 14 centers. Eleven centers prescribe a continuous infusion of breast milk or elemental formula 1–2 weeks after resection while 3 centers determine the formula type by the extent of resection. Most (86%) centers do not have a protocol for initiating oral/motor therapy. Laboratory panel composition varied widely by center. The selection and frequency of use depended on clinical variables, including cholestatic status, exclusive vs partial PN dependence, postrepletion verification vs routine monitoring, intestinal anatomy, and acuity of care. Conclusion: EN and PN management strategies are relatively consistent among U.S. centers. Collaborative initiatives are necessary to define better practices and establish laboratory monitoring guidelines.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145220/1/ncp10040_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145220/2/ncp10040.pd

Proteomic Analysis of Neisseria gonorrhoeae Biofilms Shows Shift to Anaerobic Respiration and Changes in Nutrient Transport and Outermembrane Proteins

Neisseria gonorrhoeae, the causative agent of gonorrhea, can form biofilms in vitro and in vivo. In biofilms, the organism is more resistant to antibiotic treatment and can serve as a reservoir for chronic infection. We have used stable isotope labeling by amino acids in cell culture (SILAC) to compare protein expression in biofilm and planktonic organisms. Two parallel populations of N. gonorrhoeae strain 1291, which is an arginine auxotroph, were grown for 48 h in continuous-flow chambers over glass, one supplemented with 13C6-arginine for planktonic organisms and the other with unlabeled arginine for biofilm growth. The biofilm and planktonic cells were harvested and lysed separately, and fractionated into three sequential protein extracts. Corresponding heavy (H) planktonic and light (L) biofilm protein extracts were mixed and separated by 1D SDS-PAGE gels, and samples were extensively analyzed by liquid chromatography-mass spectrometry. Overall, 757 proteins were identified, and 152 unique proteins met a 1.5-fold cutoff threshold for differential expression with p-values <0.05. Comparing biofilm to planktonic organisms, this set included 73 upregulated and 54 downregulated proteins. Nearly a third of the upregulated proteins were involved in energy metabolism, with cell envelope proteins making up the next largest group. Of the downregulated proteins, the largest groups were involved in protein synthesis and energy metabolism. These proteomics results were compared with our previously reported results from transcriptional profiling of gonococcal biofilms using microarrays. Nitrite reductase and cytochrome c peroxidase, key enzymes required for anaerobic growth, were detected as highly upregulated in both the proteomic and transcriptomic datasets. These and other protein expression changes observed in the present study were consistent with a shift to anaerobic respiration in gonococcal biofilms, although changes in membrane proteins not explicitly related to this shift may have other functions

Biomechanics of human fetal hearts with critical aortic stenosis

Critical aortic stenosis (AS) of the fetal heart causes a drastic change in the cardiac biomechanical environment. Consequently, a substantial proportion of such cases will lead to a single-ventricular birth outcome. However, the biomechanics of the disease is not well understood. To address this, we performed Finite Element (FE) modelling of the healthy fetal left ventricle (LV) based on patient-specific 4D ultrasound imaging, and simulated various disease features observed in clinical fetal AS to understand their biomechanical impact. These features included aortic stenosis, mitral regurgitation (MR) and LV hypertrophy, reduced contractility, and increased myocardial stiffness. AS was found to elevate LV pressures and myocardial stresses, and depending on severity, can drastically decrease stroke volume and myocardial strains. These effects are moderated by MR. AS alone did not lead to MR velocities above 3 m/s unless LV hypertrophy was included, suggesting that hypertrophy may be involved in clinical cases with high MR velocities. LV hypertrophy substantially elevated LV pressure, valve flow velocities and stroke volume, while reducing LV contractility resulted in diminished LV pressure, stroke volume and wall strains. Typical extent of hypertrophy during fetal AS in the clinic, however, led to excessive LV pressure and valve velocity in the FE model, suggesting that reduced contractility is typically associated with hypertrophy. Increased LV passive stiffness, which might represent fibroelastosis, was found to have minimal impact on LV pressures, stroke volume, and wall strain. This suggested that fibroelastosis could be a by-product of the disease progression and does not significantly impede cardiac function. Our study demonstrates that FE modelling is a valuable tool for elucidating the biomechanics of congenital heart disease and can calculate parameters which are difficult to measure, such as intraventricular pressure and myocardial stresses

The month of July: an early experience with pandemic influenza A (H1N1) in adults with cystic fibrosis

<p>Abstract</p> <p>Background</p> <p>Pandemic Influenza A (H1N1) 2009 is a novel viral infection that emerged in March 2009. This is the first report addressing the clinical course of patients with cystic fibrosis (CF) and H1N1 infection.</p> <p>Methods</p> <p>All patients with an influenza-like illness (ILI) attending our adult centre during July 2009 were identified. Baseline respiratory function, nutritional status, approach to management and short-term clinical course were recorded.</p> <p>Results</p> <p>Most patients experienced a mild course and were able to be managed with antiviral agents as an outpatient. Robust infection control policies were implemented to limit transmission of H1N1 infection within our CF centre. Patients with severe lung disease, poor baseline nutritional reserve and presenting with more than 48 hours of ILI experienced a more severe course. Prompt antiviral therapy within the first 48 hours of illness may have been important in improving outcomes.</p> <p>Conclusions</p> <p>This observational study demonstrates that most adults with CF with H1N1 infection had mild clinical courses and recovered rapidly.</p

Nucleosome mobilization by ISW2 requires the concerted action of the ATPase and SLIDE domains

The ISWI family of ATP-dependent chromatin remodelers represses transcription by changing nucleosome positioning. The interactions with extranucleosomal DNA and the requirement of a minimal length of extranucleosomal DNA by ISWI mediate the spacing of nucleosomes. ISW2 from Saccharomyces cerevisiae, a member of the ISWI family, has a conserved domain called SLIDE (SANT-like ISWI domain), whose binding to extranucleosomal DNA ~19 bp from the edge of nucleosomes is required for efficiently pushing DNA into nucleosomes and maintaining the unidirectional movement of nucleosomes, as reported here. Loss of SLIDE binding does not perturb ATPase domain binding to the SHL2 site of nucleosomes or its initial movement of DNA inside of nucleosomes. ISW2 has therefore two distinct roles in mobilizing nucleosomes, with the ATPase domain translocating and moving DNA inside nucleosomes, and the SLIDE domain facilitating the entry of linker DNA into nucleosomes

Clustering of cardio-metabolic risk factors in parents of adolescents with type 1 diabetes and microalbuminuria

Objective To evaluate the association between a clustering of cardio-metabolic risk factors in parents and the development of microalbuminuria (MA) in their offspring with childhood-onset type 1 diabetes (T1D). Methods The study population comprised 53 parents (mean age [±SD]: 56.7±6.2 years) of 35 T1D young people with MA (MA+) and 86 parents (age: 56.1±6.3 years) of 50 matched offspring with normoalbuminuria (MA–), who underwent clinical, biochemical and cardiovascular imaging assessments. The primary study endpoint was the difference between parents from the MA+ and MA− groups in a cardio-metabolic risk score, calculated as the average value of the standardized measures (z-scores) for waist circumference, blood pressure, fasting glucose, insulin, HDL-cholesterol and triglycerides levels. Cardiovascular parameters, including carotid intima-media thickness (cIMT), flow-mediated dilatation (FMD) and pulse wave velocity (PWV), were also assessed. A DXA scan was performed to assess body composition. Results The cardio-metabolic risk score was significantly higher in parents of MA+ compared to parents of MA− offspring (mean [95% CI]: 1.066[0.076; 2.056] vs −0.268[−0.997; 0.460], P = .03). Parents of MA+ offspring had slightly higher values of waist circumference, lipids, insulin and blood pressure, although only diastolic blood pressure was statistically different between the 2 groups (P = .0085). FMD, cIMT, PWV (all P > .3), and DXA parameters (all P > .2) were not significantly different between the 2 groups. Conclusions Parents of young offspring with childhood-onset T1D and MA showed an abnormal metabolic profile, reflected by a calculated risk score. The finding supports the role of a familial predisposition to risk of developing diabetic nephropathy.The study was supported by a grant from Diabetes UK (09/0003859). P.H.T. was financially supported by Academy of Finland (decision 130171); The Diabetes Research Foundation, Finland; Foundation for Pediatric Research, Finland; The Alma and K. A. Snellman Foundation, Oulu, Finland; and The Finnish Medical Foundation

Clustering of cardio-metabolic risk factors in parents of adolescents with type 1 diabetes and microalbuminuria

OBJECTIVE: To evaluate the association between a clustering of cardio‐metabolic risk factors in parents and the development of microalbuminuria (MA) in their offspring with childhood‐onset type 1 diabetes (T1D). METHODS: The study population comprised 53 parents (mean age [±SD]: 56.7±6.2 years) of 35 T1D young people with MA (MA+) and 86 parents (age: 56.1±6.3 years) of 50 matched offspring with normoalbuminuria (MA–), who underwent clinical, biochemical and cardiovascular imaging assessments. The primary study endpoint was the difference between parents from the MA+ and MA− groups in a cardio‐metabolic risk score, calculated as the average value of the standardized measures (z‐scores) for waist circumference, blood pressure, fasting glucose, insulin, HDL‐cholesterol and triglycerides levels. Cardiovascular parameters, including carotid intima‐media thickness (cIMT), flow‐mediated dilatation (FMD) and pulse wave velocity (PWV), were also assessed. A DXA scan was performed to assess body composition. RESULTS: The cardio‐metabolic risk score was significantly higher in parents of MA+ compared to parents of MA− offspring (mean [95% CI]: 1.066[0.076; 2.056] vs −0.268[−0.997; 0.460], P = .03). Parents of MA+ offspring had slightly higher values of waist circumference, lipids, insulin and blood pressure, although only diastolic blood pressure was statistically different between the 2 groups (P = .0085). FMD, cIMT, PWV (all P > .3), and DXA parameters (all P > .2) were not significantly different between the 2 groups. CONCLUSIONS: Parents of young offspring with childhood‐onset T1D and MA showed an abnormal metabolic profile, reflected by a calculated risk score. The finding supports the role of a familial predisposition to risk of developing diabetic nephropathy

Immunological assays for chemokine detection in in-vitro culture of CNS cells

Herein we review the various methods currently in use for determining the expression of chemokines by CNS cells in vitro. Chemokine detection assays are used in conjuction with one another to provide a comprehensive, biologically relevant assessment of the chemokines which is necessary for correct data interpretation of a specific observed biological effect. The methods described include bioassays for soluble chemokine receptors, RNA extraction, RT-PCR, Real - time quantitative PCR, gene array analysis, northern blot analysis, Ribonuclease Protection assay, Flow cytometry, ELISPOT, western blot analysis, and ELISA. No single method of analysis meets the criteria for a comprehensive, biologically relevant assessment of the chemokines, therefore more than one assay might be necessary for correct data interpretation, a choice that is based on development of a scientific rationale for the method with emphasis on the reliability and relevance of the method

Genetic and Proteomic Approaches to Identify Cancer Drug Targets

While target-based small-molecule discovery has taken centre-stage in the pharmaceutical industry, there are many cancer-promoting proteins not easily addressed with a traditional target-based screening approach. In order to address this problem, as well as to identify modulators of biological states in the absence of knowing the protein target of the state switch, alternative phenotypic screening approaches, such as gene expression-based and high-content imaging, have been developed. With this renewed interest in phenotypic screening, however, comes the challenge of identifying the binding protein target(s) of small-molecule hits. Emerging technologies have the potential to improve the process of target identification. In this review, we discuss the application of genomic (gene expression-based), genetic (short hairpin RNA and open reading frame screening), and proteomic approaches to protein target identification