Observation of Cabibbo-suppressed and W-exchange Lambda_c^+ baryon decays

We present measurements of the Cabibbo-suppressed decays Lambda_c^+ --> Lambda0 K+ and Lambda_c^+ --> Sigma0 K+ (both first observations), Lambda_c^+ --> Sigma+ K+ pi- (seen with large statistics for the first time), Lambda_c^+ --> p K+ K- and Lambda_c^+ --> p phi (measured with improved accuracy). Improved branching ratio measurements for the decays Lambda_c^+ --> Sigma+ K+ K- and Lambda_c^+ --> Sigma+ phi, which are attributed to W-exchange diagrams, are shown. We also present the first evidence for Lambda_c^+ --> Xi(1690)^0 K+ and set an upper limit on the non-resonant decay Lambda_c^+ --> Sigma+ K+ K-. This analysis was performed using 32.6 fb^{-1} of data collected by the Belle detector at the asymmetric e+ e- collider KEKB.Comment: Submitted to Phys. Lett. B. v2: A small correction to the Authorlist was made. An earlier version of this analysis was released as BELLE-CONF-0130, hep-ex/010800

Structural basis for arginine glycosylation of host substrates by bacterial effector proteins

The bacterial effector proteins SseK and NleB glycosylate host proteins on arginine residues, leading to reduced NF-κB-dependent responses to infection. Salmonella SseK1 and SseK2 are E. coli NleB1 orthologs that behave as NleB1-like GTs, although they differ in protein substrate specificity. Here we report that these enzymes are retaining glycosyltransferases composed of a helix-loop-helix (HLH) domain, a lid domain, and a catalytic domain. A conserved HEN motif (His-Glu-Asn) in the active site is important for enzyme catalysis and bacterial virulence. We observe differences between SseK1 and SseK2 in interactions with substrates and identify substrate residues that are critical for enzyme recognition. Long Molecular Dynamics simulations suggest that the HLH domain determines substrate specificity and the lid-domain regulates the opening of the active site. Overall, our data suggest a front-face SNi mechanism, explain differences in activities among these effectors, and have implications for future drug development against enteric pathogens

Different contribution of extent of myocardial injury to left ventricular systolic and diastolic function in early reperfused acute myocardial infarction

BACKGROUND: We sought to investigate the influence of the extent of myocardial injury on left ventricular (LV) systolic and diastolic function in patients after reperfused acute myocardial infarction (AMI). METHODS: Thirty-eight reperfused AMI patients underwent cardiac magnetic resonance (CMR) imaging after percutaneous coronary revascularization. The extent of myocardial edema and scarring were assessed by T2 weighted imaging and late gadolinium enhancement (LGE) imaging, respectively. Within a day of CMR, echocardiography was done. Using 2D speckle tracking analysis, LV longitudinal, circumferential strain, and twist were measured. RESULTS: Extent of LGE were significantly correlated with LV systolic functional indices such as ejection fraction (r��=��-0.57, p��<��0.001), regional wall motion score index (r��=��0.52, p��=��0.001), and global longitudinal strain (r��=��0.56, p��<��0.001). The diastolic functional indices significantly correlated with age (r��=��-0.64, p��<��0.001), LV twist (r��=��-0.39, p��=��0.02), average non-infarcted myocardial circumferential strain (r��=��-0.52, p��=��0.001), and LV end-diastolic wall stress index (r��=��-0.47, p��=��0.003 with e') but not or weakly with extent of LGE. In multivariate analysis, age and non-infarcted myocardial circumferential strain independently correlated with diastolic functional indices rather than extent of injury. CONCLUSIONS: In patients with timely reperfused AMI, not only extent of myocardial injury but also age and non-infarcted myocardial function were more significantly related to LV chamber diastolic function.ope

Robot-Assisted Radical Prostatectomy:Modified Ultradissection Reduces pT2 Positive Surgical Margins on the Bladder Neck

The purpose of this study was to compare the positive surgical margin (PSM) rates of 2 techniques of robot-assisted radical prostatectomy (RARP) for pT2 (localized) prostate cancer. A retrospective analysis was conducted of 361 RARP cases, performed from May 2005 to September 2008 by a single surgeon (KHR) at our institution (Yonsei University College of Medicine). In the conventional technique, the bladder neck was transected first. In the modified ultradissection, the lateral border of the bladder neck was dissected and then the bladder neck was transected while the detrusor muscle of the bladder was well visualized. Perioperative characteristics and outcomes and PSM rates were analyzed retrospectively for pT2 patients (n＝217), focusing on a comparison of those undergoing conventional (n＝113) and modified ultradissection (n＝104) techniques. There was no difference between the conventional and modified ultradissection group in mean age, BMI, PSA, prostate volume, biopsy Gleason score, and DʼAmico prognostic criteria distributions. The mean operative time was shorter (p＜0.001) and the estimated blood loss was less (p＜0.01) in the modified ultradissection group. The PSM rate for the bladder neck was significantly reduced by modified ultradissection, from 6.2% to 0% (p＜0.05). In conclusion, modified ultradissection reduces the PSM rate for the bladder neck

Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10-6<P<10-4) in a test for GxETS interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10-7 in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10-7 and P = 1.98×10-7 in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP. © 2014 Wu et al

ARHGDIA mutations cause nephrotic syndrome via defective RHO GTPase signaling

Nephrotic syndrome (NS) is divided into steroid-sensitive (SSNS) and -resistant (SRNS) variants. SRNS causes end-stage kidney disease, which cannot be cured. While the disease mechanisms of NS are not well understood, genetic mapping studies suggest a multitude of unknown single-gene causes. We combined homozygosity mapping with whole-exome resequencing and identified an ARHGDIA mutation that causes SRNS. We demonstrated that ARHGDIA is in a complex with RHO GTPases and is prominently expressed in podocytes of rat glomeruli. ARHGDIA mutations (R120X and G173V) from individuals with SRNS abrogated interaction with RHO GTPases and increased active GTP-bound RAC1 and CDC42, but not RHOA, indicating that RAC1 and CDC42 are more relevant to the pathogenesis of this SRNS variant than RHOA. Moreover, the mutations enhanced migration of cultured human podocytes; however, enhanced migration was reversed by treatment with RAC1 inhibitors. The nephrotic phenotype was recapitulated in arhgdia-deficient zebrafish. RAC1 inhibitors were partially effective in ameliorating arhgdia-associated defects. These findings identify a single-gene cause of NS and reveal that RHO GTPase signaling is a pathogenic mediator of SRNS.ope

Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats

Peer reviewe

Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma

Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator). Here, we show that the combined action of CHIR99021 and forskolin converted malignant glioma into fully differentiated neurons with no malignant characteristics; inhibited the proliferation of malignant glioma; and significantly down-regulated gene ontology and gene expression profiles related to cell division, gliogenesis, and angiogenesis in small molecule-induced neurons. In vivo, the combined action of CHIR99021 and forskolin markedly delayed neurological deficits and significantly reduced the tumor volume. We suggest that reprogramming technology may be a potential treatment strategy replacing the therapeutic paradigm of traditional treatment of malignant glioma, and a combination molecule comprising a GSK3 inhibitor and a cAMP inducer could be the next generation of anticancer drugs

The Impact of the Goods and Services Tax on Mortgage Costs: Evidence from Australian Mortgage Corporations

so, which corresponds with the introduction of the Goods and Services Tax (GST) in July 2000. To what extent the GST has impacted mortgage costs is the research question. This study investigates the GST impact on the mortgage costs of Australian mortgage corporations. Using data of mortgage corporations operating in Australia, we perform t-tests and multivariate regression analysis to examine the GST effects on mortgage yield spreads. The empirical results clearly indicate that mortgage corporations increased their mortgage charges in the post-GST periods significantly beyond the magnitude of the GST. Furthermore, the lenders started to increase the yield spreads before and continued to increase the spreads after the implementation of the GST, indicating the rise in mortgage costs was not a one-off surge. The findings offer insights into mortgage costs and have significant policy implications and wider economic relevance.Griffith Business School, Department of Accounting, Finance and EconomicsFull Tex

A case of hippocampal sclerosis diagnosed as cortical dysplasia due to preoperative brain MRI finding

Hippocampal sclerosis (HS) is one of the most common features of intractable temporal lobe epilepsy. Generally it can be identified through brain magnetic resonance imaging (MRI) with high degree of sensitivity and specificity. Typical brain MRI findings of HS are hippocampal atrophy with hyperintense signal confined to the lesion. On the other hand cortical dysplasia exhibits blurring of the gray-white matter junction and abnormal white matter signal intensity. We present a case where preoperative brain MRI strongly suggested the presence of diffuse cortical dysplasia in the left temporal lobe but postoperative pathology revealed the temporal lesion to be unremarkable except for hippocampal sclerosis