Observation of an Isotope Shift in the Superconducting Transition Temperature of La\u3csub\u3e1.85\u3c/sub\u3eSr\u3csub\u3e0.15\u3c/sub\u3eCuO\u3csub\u3e4\u3c/sub\u3e

An oxygen isotope shift is observed in superconducting La1.85Sr0.15CuO4 when 18O is substituted partially for 16O; the superconducting transition temperature Tc is lowered by 0.3 to 1.0 K in different samples. We examine these results using conventioanl phonon-mediated BCS theory and conclude that, for La1.85Sr0.15CuO4, phonons play an important role in the pairing mechanism

Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease. © 2013 McEvoy et al

Infective endocarditis caused by Salmonella enteritidis in a dialysis patient: a case report and literature review

BackgroundInfective endocarditis is significantly more common in haemodialysis patients as compared with the general population, the causative pathogen is generally Staphylococcus aureus; there have been no previously reported cases of infective endocarditis caused by a Salmonella species in haemodialysis patients.Case presentationWe report the case of a 68 year-old woman on haemodialysis who developed infective endocarditis as a result of Salmonella enteritidis. Although we treated the patient with ceftriaxone combined with ciprofloxacin, infective endocarditis was not detected early enough and unfortunately developed into cerebral septic emboli, which ultimately resulted in death.ConclusionAlthough there are several reports that Salmonella endocarditis without cardiac failure can be successfully treated with antibiotics alone, early surgical intervention is essential for some cases to prevent life-threatening complications. Transesophageal echocardiography should be performed in any patient with high clinical suspicion of infective endocarditis. To the best of our knowledge, this is the first case-report of Salmonella endocarditis in a haemodialysis patient

Novel Protein-Protein Interactions Inferred from Literature Context

We have developed a method that predicts Protein-Protein Interactions (PPIs) based on the similarity of the context in which proteins appear in literature. This method outperforms previously developed PPI prediction algorithms that rely on the conjunction of two protein names in MEDLINE abstracts. We show significant increases in coverage (76% versus 32%) and sensitivity (66% versus 41% at a specificity of 95%) for the prediction of PPIs currently archived in 6 PPI databases. A retrospective analysis shows that PPIs can efficiently be predicted before they enter PPI databases and before their interaction is explicitly described in the literature. The practical value of the method for discovery of novel PPIs is illustrated by the experimental confirmation of the inferred physical interaction between CAPN3 and PARVB, which was based on frequent co-occurrence of both proteins with concepts like Z-disc, dysferlin, and alpha-actinin. The relationships between proteins predicted by our method are broader than PPIs, and include proteins in the same complex or pathway. Dependent on the type of relationships deemed useful, the precision of our method can be as high as 90%. The full set of predicted interactions is available in a downloadable matrix and through the webtool Nermal, which lists the most likely interaction partners for a given protein. Our framework can be used for prioritizing potential interaction partners, hitherto undiscovered, for follow-up studies and to aid the generation of accurate protein interaction maps

Calpain 3 Is a Rapid-Action, Unidirectional Proteolytic Switch Central to Muscle Remodeling

Calpain 3 (CAPN3) is a cysteine protease that when mutated causes Limb Girdle Muscular Dystrophy 2A. It is thereby the only described Calpain family member that genetically causes a disease. Due to its inherent instability little is known of its substrates or its mechanism of activity and pathogenicity. In this investigation we define a primary sequence motif underlying CAPN3 substrate cleavage. This motif can transform non-related proteins into substrates, and identifies >300 new putative CAPN3 targets. Bioinformatic analyses of these targets demonstrate a critical role in muscle cytoskeletal remodeling and identify novel CAPN3 functions. Among the new CAPN3 substrates are three E3 SUMO ligases of the Protein Inhibitor of Activated Stats (PIAS) family. CAPN3 can cleave PIAS proteins and negatively regulates PIAS3 sumoylase activity. Consequently, SUMO2 is deregulated in patient muscle tissue. Our study thus uncovers unexpected crosstalk between CAPN3 proteolysis and protein sumoylation, with strong implications for muscle remodeling

Integrated Profiling of MicroRNAs and mRNAs: MicroRNAs Located on Xq27.3 Associate with Clear Cell Renal Cell Carcinoma

Background: With the advent of second-generation sequencing, the expression of gene transcripts can be digitally measured with high accuracy. The purpose of this study was to systematically profile the expression of both mRNA and miRNA genes in clear cell renal cell carcinoma (ccRCC) using massively parallel sequencing technology. Methodology: The expression of mRNAs and miRNAs were analyzed in tumor tissues and matched normal adjacent tissues obtained from 10 ccRCC patients without distant metastases. In a prevalence screen, some of the most interesting results were validated in a large cohort of ccRCC patients. Principal Findings: A total of 404 miRNAs and 9,799 mRNAs were detected to be differentially expressed in the 10 ccRCC patients. We also identified 56 novel miRNA candidates in at least two samples. In addition to confirming that canonical cancer genes and miRNAs (including VEGFA, DUSP9 and ERBB4; miR-210, miR-184 and miR-206) play pivotal roles in ccRCC development, promising novel candidates (such as PNCK and miR-122) without previous annotation in ccRCC carcinogenesis were also discovered in this study. Pathways controlling cell fates (e. g., cell cycle and apoptosis pathways) and cell communication (e. g., focal adhesion and ECM-receptor interaction) were found to be significantly more likely to be disrupted in ccRCC. Additionally, the results of the prevalence screen revealed that the expression of a miRNA gene cluster located on Xq27.3 was consistently downregulated in at least 76.7% of similar to 50 ccRCC patients. Conclusions: Our study provided a two-dimensional map of the mRNA and miRNA expression profiles of ccRCC using deep sequencing technology. Our results indicate that the phenotypic status of ccRCC is characterized by a loss of normal renal function, downregulation of metabolic genes, and upregulation of many signal transduction genes in key pathways. Furthermore, it can be concluded that downregulation of miRNA genes clustered on Xq27.3 is associated with ccRCC

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Simple scoring system to predict in-hospital mortality after surgery for infective endocarditis

BACKGROUND: Aspecific scoring systems are used to predict the risk of death postsurgery in patients with infective endocarditis (IE). The purpose of the present study was both to analyze the risk factors for in-hospital death, which complicates surgery for IE, and to create a mortality risk score based on the results of this analysis. METHODS AND RESULTS: Outcomes of 361 consecutive patients (mean age, 59.1\ub115.4 years) who had undergone surgery for IE in 8 European centers of cardiac surgery were recorded prospectively, and a risk factor analysis (multivariable logistic regression) for in-hospital death was performed. The discriminatory power of a new predictive scoring system was assessed with the receiver operating characteristic curve analysis. Score validation procedures were carried out. Fifty-six (15.5%) patients died postsurgery. BMI >27 kg/m2 (odds ratio [OR], 1.79; P=0.049), estimated glomerular filtration rate 55 mm Hg (OR, 1.78; P=0.032), and critical state (OR, 2.37; P=0.017) were independent predictors of in-hospital death. A scoring system was devised to predict in-hospital death postsurgery for IE (area under the receiver operating characteristic curve, 0.780; 95% CI, 0.734-0.822). The score performed better than 5 of 6 scoring systems for in-hospital death after cardiac surgery that were considered. CONCLUSIONS: A simple scoring system based on risk factors for in-hospital death was specifically created to predict mortality risk postsurgery in patients with IE