HV 11423: The Coolest Supergiant in the SMC

We call attention to the fact that one of the brightest red supergiants in the SMC has recently changed its spectral type from K0-1 I (December 2004) to M4 I (December 2005) and back to K0-1 I (September 2006). An archival spectrum from the Very Large Telescope reveals that the star was even cooler (M4.5-M5 I) in December 2001. By contrast, the star was observed to be an M0 I in both October 1978 and October 1979. The M4-5 I spectral types is by far the latest type seen for an SMC supergiant, and its temperature in that state places it well beyond the Hayashi limit into a region of the H-R diagram where the star should not be in hydrostatic equilibrium. The star is variable by nearly 2 mag in V, but essentially constant in K. Our modeling of its spectral energy distribution shows that the visual extinction has varied during this time, but that the star has remained essentially constant in bolometric luminosity. We suggest that the star is currently undergoing a period of intense instability, with its effective temperature changing from 4300 K to 3300 K on the time-scale of months. It has one of the highest 12-micron fluxes of any RSG in the SMC, and we suggest that the variability at V is due primarily to changes in effective temperature, and secondly, due to changes in the local extinction due to creation and dissipation of circumstellar dust. We speculate that the star may be nearing the end of its life.Comment: Accepted by the Astrophysical Journa

Signal transducer and activator of transcription-5 mediates neuronal apoptosis induced by inhibition of Rac GTPase activity.

In several neuronal cell types, the small GTPase Rac is essential for survival. We have shown previously that the Rho family GTPase inhibitor Clostridium difficile toxin B (ToxB) induces apoptosis in primary rat cerebellar granule neurons (CGNs) principally via inhibition of Rac GTPase function. In the present study, incubation with ToxB activated a proapoptotic Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, and a pan-JAK inhibitor protected CGNs from Rac inhibition. STAT1 expression was induced by ToxB; however, CGNs from STAT1 knock-out mice succumbed to ToxB-induced apoptosis as readily as wild-type CGNs. STAT3 displayed enhanced tyrosine phosphorylation following treatment with ToxB, and a reputed inhibitor of STAT3, cucurbitacin (JSI-124), reduced CGN apoptosis. Unexpectedly, JSI-124 failed to block STAT3 phosphorylation, and CGNs were not protected from ToxB by other known STAT3 inhibitors. In contrast, STAT5A tyrosine phosphorylation induced by ToxB was suppressed by JSI-124. In addition, roscovitine similarly inhibited STAT5A phosphorylation and protected CGNs from ToxB-induced apoptosis. Consistent with these results, adenoviral infection with a dominant negative STAT5 mutant, but not wild-type STAT5, significantly decreased ToxB-induced apoptosis of CGNs. Finally, chromatin immunoprecipitation with a STAT5 antibody revealed increased STAT5 binding to the promoter region of prosurvival Bcl-xL. STAT5 was recruited to the Bcl-xL promoter region in a ToxB-dependent manner, and this DNA binding preceded Bcl-xL down-regulation, suggesting transcriptional repression. These data indicate that a novel JAK/STAT5 proapoptotic pathway significantly contributes to neuronal apoptosis induced by the inhibition of Rac GTPase

Unweaving the population structure and genetic diversity of Canadian shrub willow

Perennial shrub willow are increasingly being promoted in short-rotation coppice systems as biomass feedstocks, for phytoremediation applications, and for the diverse ecosystem services that can accrue. This renewed interest has led to widespread willow cultivation, particularly of non-native varieties. However, Canadian willow species have not been widely adopted and their inherent diversity has not yet been thoroughly investigated. In this study, 324 genotypes of Salix famelica and Salix eriocephala collected from 33 sites of origin were analyzed using 26,016 single nucleotide polymorphisms to reveal patterns of population structure and genetic diversity. Analyses by Bayesian methods and principal component analysis detected five main clusters that appeared to be largely shaped by geoclimatic variables including mean annual precipitation and the number of frost-free days. The overall observed (HO) and expected (HE) heterozygosity were 0.126 and 0.179, respectively. An analysis of molecular variance revealed that the highest genetic variation occurred within genotypes (69%), while 8% of the variation existed among clusters and 23% between genotypes within clusters. These findings provide new insights into the extent of genetic variation that exists within native shrub willow species which could be leveraged in pan-Canadian willow breeding programs.Fil: Murphy, Emily K. University of British Columbia. Faculty of Forestry. Department of Wood Science; CanadáFil: Cappa, Eduardo Pablo. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Soolanayakanahally, Raju Y. Agriculture and Agri-Food Canada. Indian Head Research Farm; Canadá. Agriculture and Agri-Food Canada. Saskatoon Research and Development Centre; Canadá.Fil: El-Kassaby, Yousry A. University of British Columbia. Faculty of Forestry. Department of Forest and Conservation Sciences; CanadáFil: Parkin, Isobel A.P. Agriculture and Agri-Food Canada. Saskatoon Research and Development Centre; Canadá.Fil: Schroeder, William R. Agriculture and Agri-Food Canada. Indian Head Research Farm; CanadáFil: Mansfield, Shawn D. University of British Columbia. Faculty of Forestry. Department of Wood Science; Canad

Adherence to the updated guidelines for the prevention of perinatal Group B streptococcal disease

In 2010, the Centers for Disease Control and Prevention updated the Guidelines for the Prevention of Perinatal Group B Streptococcal (GBS) Disease. Previous studies of adherence to GBS guidelines have focused on the treatment of carriers of GBS. Our objective was to determine whether there was any difference in adherence to the guidelines for screening and treatment of women who delivered at our institution between the beginning of 2011 and the end of 2011 as the revised guidelines were published in November 2010. Our secondary outcome was to determine whether any differences in adherence occurred between prenatal provider types (OB/Gyn, Certified Nurse Midwives, and Family Practice)

Epidural Hematoma Following Cervical Spine Surgery.

STUDY DESIGN: A multicentered retrospective case series. OBJECTIVE: To determine the incidence and circumstances surrounding the development of a symptomatic postoperative epidural hematoma in the cervical spine. METHODS: Patients who underwent cervical spine surgery between January 1, 2005, and December 31, 2011, at 23 institutions were reviewed, and all patients who developed an epidural hematoma were identified. RESULTS: A total of 16 582 cervical spine surgeries were identified, and 15 patients developed a postoperative epidural hematoma, for a total incidence of 0.090%. Substantial variation between institutions was noted, with 11 sites reporting no epidural hematomas, and 1 site reporting an incidence of 0.76%. All patients initially presented with a neurologic deficit. Nine patients had complete resolution of the neurologic deficit after hematoma evacuation; however 2 of the 3 patients (66%) who had a delay in the diagnosis of the epidural hematoma had residual neurologic deficits compared to only 4 of the 12 patients (33%) who had no delay in the diagnosis or treatment (P = .53). Additionally, the patients who experienced a postoperative epidural hematoma did not experience any significant improvement in health-related quality-of-life metrics as a result of the index procedure at final follow-up evaluation. CONCLUSION: This is the largest series to date to analyze the incidence of an epidural hematoma following cervical spine surgery, and this study suggest that an epidural hematoma occurs in approximately 1 out of 1000 cervical spine surgeries. Prompt diagnosis and treatment may improve the chance of making a complete neurologic recovery, but patients who develop this complication do not show improvements in the health-related quality-of-life measurements

Utility of Seated Lateral Radiographs in the Diagnosis and Classification of Lumbar Degenerative Spondylolisthesis

STUDY DESIGN: Retrospective cohort study. PURPOSE: Our goal was to determine which radiographic images are most essential for degenerative spondylolisthesis (DS) classification and instability detection. OVERVIEW OF LITERATURE: The heterogeneity in DS requires multiple imaging views to evaluate vertebral translation, disc space, slip angle, and instability. However, there are several restrictions on frequently used imaging perspectives such as flexion-extension and upright radiography. METHODS: We assessed baseline neutral upright, standing flexion, seated lateral radiographs, and magnetic resonance imaging (MRI) for patients identified with spondylolisthesis from January 2021 to May 2022 by a single spine surgeon. DS was classified by Meyerding and Clinical and Radiographic Degenerative Spondylolisthesis classifications. A difference of \u3e10° or \u3e8% between views, respectively, was used to characterize angular and translational instability. Analysis of variance and paired chi-square tests were utilized to compare modalities. RESULTS: A total of 136 patients were included. Seated lateral and standing flexion radiographs showed the greatest slip percentage (16.0% and 16.7%), while MRI revealed the lowest (12.2%, p0.05). Translational instability was shown to be more prevalent when associated with seated lateral or standing flexion than when combined with neutral upright (31.5% vs. 20.2%, p =0.041; and 28.1% vs. 14.6%, p =0.014, respectively). There were no differences between seated lateral or standing flexion in the detection of instability (all p \u3e0.20). CONCLUSIONS: Seated lateral radiographs are appropriate alternatives for standing flexion radiographs. Films taken when standing up straight do not offer any more information for DS detection. Rather than standing flexion-extension radiographs, instability can be detected using an MRI, which is often performed preoperatively, paired with a single seated lateral radiograph

Properties of local interactions and their potential value in complementing genome-wide association studies

Local interactions between neighbouring SNPs are hypothesized to be able to capture variants missing from genome-wide association studies (GWAS) via haplotype effects but have not been thoroughly explored. We have used a new high-throughput analysis tool to probe this underexplored area through full pair-wise genome scans and conventional GWAS in diastolic and systolic blood pressure and six metabolic traits in the Northern Finland Birth Cohort 1966 (NFBC1966) and the Atherosclerosis Risk in Communities study cohort (ARIC). Genome-wide significant interactions were detected in ARIC for systolic blood pressure between PLEKHA7 (a known GWAS locus for blood pressure) and GPR180 (which plays a role in vascular remodelling), and also for triglycerides as local interactions within the 11q23.3 region (replicated significantly in NFBC1966), which notably harbours several loci (BUD13, ZNF259 and APOA5) contributing to triglyceride levels. Tests of the local interactions within the 11q23.3 region conditional on the top GWAS signal suggested the presence of two independent functional variants, each with supportive evidence for their roles in gene regulation. Local interactions captured 9 additional GWAS loci identified in this study (3 significantly replicated) and 73 from previous GWAS (24 in the eight traits and 49 in related traits). We conclude that the detection of local interactions requires adequate SNP coverage of the genome and that such interactions are only likely to be detectable between SNPs in low linkage disequilibrium. Analysing local interactions is a potentially valuable complement to GWAS and can provide new insights into the biology underlying variation in complex traits

Acquired resistance to oxaliplatin is not directly associated with increased resistance to DNA damage in SK-N-ASrOXALI4000, a newly established oxaliplatin-resistant sub-line of the neuroblastoma cell line SK-N-AS

The formation of acquired drug resistance is a major reason for the failure of anti-cancer therapies after initial response. Here, we introduce a novel model of acquired oxaliplatin resistance, a sub-line of the non-MYCN-amplified neuroblastoma cell line SK-N-AS that was adapted to growth in the presence of 4000 ng/mL oxaliplatin (SK-N-ASrOXALI4000). SK-N-ASrOXALI4000 cells displayed enhanced chromosomal aberrations compared to SK-N-AS, as indicated by 24-chromosome fluorescence in situ hybridisation. Moreover, SK-N-ASrOXALI4000 cells were resistant not only to oxaliplatin but also to the two other commonly used anti-cancer platinum agents cisplatin and carboplatin. SK-N-ASrOXALI4000 cells exhibited a stable resistance phenotype that was not affected by culturing the cells for 10 weeks in the absence of oxaliplatin. Interestingly, SK-N-ASrOXALI4000 cells showed no cross resistance to gemcitabine and increased sensitivity to doxorubicin and UVC radiation, alternative treatments that like platinum drugs target DNA integrity. Notably, UVC-induced DNA damage is thought to be predominantly repaired by nucleotide excision repair and nucleotide excision repair has been described as the main oxaliplatin-induced DNA damage repair system. SK-N-ASrOXALI4000 cells were also more sensitive to lysis by influenza A virus, a candidate for oncolytic therapy, than SK-N-AS cells. In conclusion, we introduce a novel oxaliplatin resistance model. The oxaliplatin resistance mechanisms in SK-N-ASrOXALI4000 cells appear to be complex and not to directly depend on enhanced DNA repair capacity. Models of oxaliplatin resistance are of particular relevance since research on platinum drugs has so far predominantly focused on cisplatin and carboplatin

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group