939. STROBILANTHES GLUTINOSA

Strobilanthes glutinosa is described and illustrated. It is a winter‐flowering species native to the foothills of the northwestern Himalayas. Although frost sensitive, it appears to flourish as a cultivated plant in shaded places enjoying a mild moist climate.     

Cultivable fungi present in deep-sea sediments of Antarctica: taxonomy,diversity, and bioprospecting of bioactive compounds

Extremophiles - We accessed the culturable mycobiota present in marine sediments at different depths in Antarctica Ocean. Acremonium fusidioides, Penicillium allii-sativi, Penicillium chrysogenum,...     

Nucleic Acid Tools for Invasive Fungal Disease Diagnosis

Current Fungal Infection Reports - This review has incorporated the knowledge and experience of the leads of each of the laboratory working parties of the fungal PCR initiative in order to provide...     

Are you what you eat? A highly transient and prey‐influenced gut microbiome in the grey house spider Badumna longinqua

Stable core microbial communities have been described in numerous animal species and are commonly associated with fitness benefits for their hosts. Recent research, however, highlights examples of species whose microbiota are transient and environmentally derived. Here, we test the effect of diet on gut microbial community assembly in the spider Badumna longinqua. Using 16S rRNA gene amplicon sequencing combined with quantitative PCR, we analyzed diversity and abundance of the spider's gut microbes, and simultaneously characterized its prey communities using nuclear rRNA markers. We found a clear correlation between community similarity of the spider's insect prey and gut microbial DNA, suggesting that microbiome assembly is primarily diet‐driven. This assumption is supported by a feeding experiment, in which two types of prey—crickets and fruit flies—both substantially altered microbial diversity and community similarity between spiders, but did so in different ways. After cricket consumption, numerous cricket‐derived microbes appeared in the spider's gut, resulting in a rapid homogenization of microbial communities among spiders. In contrast, few prey‐associated bacteria were detected after consumption of fruit flies; instead, the microbial community was remodelled by environmentally sourced microbes, or abundance shifts of rare taxa in the spider's gut. The reshaping of the microbiota by both prey taxa mimicked a stable core microbiome in the spiders for several weeks post feeding. Our results suggest that the spider's gut microbiome undergoes pronounced temporal fluctuations, that its assembly is dictated by the consumed prey, and that different prey taxa may remodel the microbiota in drastically different ways.     

Analysis of chemometric models applied to Raman spectroscopy for monitoring key metabolites of cell culture

The Food and Drug Administration (FDA) initiative of Process Analytical Technology (PAT) encourages the monitoring of biopharmaceutical manufacturing processes by innovative solutions. Raman spectroscopy and the chemometric modeling tool partial least squares (PLS) have been applied to this aim for monitoring cell culture process variables. This study compares the chemometric modeling methods of Support Vector Machine radial (SVMr), Random Forests (RF), and Cubist to the commonly used linear PLS model for predicting cell culture components—glucose, lactate, and ammonia. This research is performed to assess whether the use of PLS as standard practice is justified for chemometric modeling of Raman spectroscopy and cell culture data. Model development data from five small-scale bioreactors (2 × 1 L and 3 × 5 L) using two Chinese hamster ovary (CHO) cell lines were used to predict against a manufacturing scale bioreactor (2,000 L). Analysis demonstrated that Cubist predictive models were better for average performance over PLS, SVMr, and RF for glucose, lactate, and ammonia. The root mean square error of prediction (RMSEP) of Cubist modeling was acceptable for the process concentration ranges of glucose (1.437 mM), lactate (2.0 mM), and ammonia (0.819 mM). Interpretation of variable importance (VI) results theorizes the potential advantages of Cubist modeling in avoiding interference of Raman spectral peaks. Predictors/Raman wavenumbers (cm⁻¹) of interest for individual variables are X1139–X1141 for glucose, X846–X849 for lactate, and X2941–X2943 for ammonia. These results demonstrate that other beneficial chemometric models are available for use in monitoring cell culture with Raman spectroscopy.     

Living phosphatic stromatolites in a low‐phosphorus environment: Implications for the use of phosphorus as a proxy for phosphate levels in paleo‐systems

In the geological record, fossil phosphatic stromatolites date back to the Great Oxidation Event in the Paleoproterozoic, but living phosphatic stromatolites have not been described previously. Here, we report on cyanobacterial stromatolites in a supratidal freshwater environment at Cape Recife, South African southern coast, precipitating Ca carbonate alternating with episodes of Ca phosphate deposition. In their structure and composition, the living stromatolites from Cape Recife closely resemble their fossilized analogues, showing phosphatic zonation, microbial casts, tunnel structures and phosphatic crusts of biogenic origin. The microbial communities appear to be also similar to those proposed to have formed fossil phosphatic stromatolites. Phosphatic domains in the material from Cape Recife are spatially and texturally associated with carbonate precipitates, but form distinct entities separated by sharp boundaries. Electron Probe Micro‐Analysis shows that Ca/P ratios and the overall chemical compositions of phosphatic precipitates are in the range of octacalcium phosphate, amorphous tricalcium phosphate and apatite. The coincidence in time of the emergence of phosphatic stromatolites in the fossil record with a major episode of atmospheric oxidation led to the assumption that at times of increased oxygen release the underlying increased biological production may have been linked to elevated phosphorus availability. The stromatolites at Cape Recife, however, form in an environment where ambient phosphorus concentrations do not exceed 0.28 μM, one to two orders of magnitude below the previously predicted minimum threshold of >5 μM for biogenic phosphate precipitation in paleo‐systems. Accordingly, we contest the previously proposed suitability of phosphatic stromatolites as a proxy for high ambient phosphate concentrations in supratidal to shallow ocean settings in earth history.     

Erectile Dysfunction Severity as a Risk Marker for Cardiovascular Disease Hospitalisation and All-Cause Mortality: A Prospective Cohort Study

Background

Erectile dysfunction is an emerging risk marker for future cardiovascular disease (CVD) events; however, evidence on dose response and specific CVD outcomes is limited. This study investigates the relationship between severity of erectile dysfunction and specific CVD outcomes.

Methods and Findings

We conducted a prospective population-based Australian study (the 45 and Up Study) linking questionnaire data from 2006–2009 with hospitalisation and death data to 30 June and 31 Dec 2010 respectively for 95,038 men aged ≥45 y. Cox proportional hazards models were used to examine the relationship of reported severity of erectile dysfunction to all-cause mortality and first CVD-related hospitalisation since baseline in men with and without previous CVD, adjusting for age, smoking, alcohol consumption, marital status, income, education, physical activity, body mass index, diabetes, and hypertension and/or hypercholesterolaemia treatment. There were 7,855 incident admissions for CVD and 2,304 deaths during follow-up (mean time from recruitment, 2.2 y for CVD admission and 2.8 y for mortality). Risks of CVD and death increased steadily with severity of erectile dysfunction. Among men without previous CVD, those with severe versus no erectile dysfunction had significantly increased risks of ischaemic heart disease (adjusted relative risk [RR] = 1.60, 95% CI 1.31–1.95), heart failure (8.00, 2.64–24.2), peripheral vascular disease (1.92, 1.12–3.29), “other” CVD (1.26, 1.05–1.51), all CVD combined (1.35, 1.19–1.53), and all-cause mortality (1.93, 1.52–2.44). For men with previous CVD, corresponding RRs (95% CI) were 1.70 (1.46–1.98), 4.40 (2.64–7.33), 2.46 (1.63–3.70), 1.40 (1.21–1.63), 1.64 (1.48–1.81), and 2.37 (1.87–3.01), respectively. Among men without previous CVD, RRs of more specific CVDs increased significantly with severe versus no erectile dysfunction, including acute myocardial infarction (1.66, 1.22–2.26), atrioventricular and left bundle branch block (6.62, 1.86–23.56), and (peripheral) atherosclerosis (2.47, 1.18–5.15), with no significant difference in risk for conditions such as primary hypertension (0.61, 0.16–2.35) and intracerebral haemorrhage (0.78, 0.20–2.97).

Conclusions

These findings give support for CVD risk assessment in men with erectile dysfunction who have not already undergone assessment. The utility of erectile dysfunction as a clinical risk prediction tool requires specific testing. Please see later in the article for the Editors'' Summary     

Site-Specific Phosphorylation of the DNA Damage Response Mediator Rad9 by Cyclin-Dependent Kinases Regulates Activation of Checkpoint Kinase 1

The mediators of the DNA damage response (DDR) are highly phosphorylated by kinases that control cell proliferation, but little is known about the role of this regulation. Here we show that cell cycle phosphorylation of the prototypical DDR mediator Saccharomyces cerevisiae Rad9 depends on cyclin-dependent kinase (CDK) complexes. We find that a specific G2/M form of Cdc28 can phosphorylate in vitro the N-terminal region of Rad9 on nine consensus CDK phosphorylation sites. We show that the integrity of CDK consensus sites and the activity of Cdc28 are required for both the activation of the Chk1 checkpoint kinase and its interaction with Rad9. We have identified T125 and T143 as important residues in Rad9 for this Rad9/Chk1 interaction. Phosphorylation of T143 is the most important feature promoting Rad9/Chk1 interaction, while the much more abundant phosphorylation of the neighbouring T125 residue impedes the Rad9/Chk1 interaction. We suggest a novel model for Chk1 activation where Cdc28 regulates the constitutive interaction of Rad9 and Chk1. The Rad9/Chk1 complex is then recruited at sites of DNA damage where activation of Chk1 requires additional DDR–specific protein kinases.     

Discovery Analysis of TCGA Data Reveals Association between Germline Genotype and Survival in Ovarian Cancer Patients

Background

Ovarian cancer remains a significant public health burden, with the highest mortality rate of all the gynecological cancers. This is attributable to the late stage at which the majority of ovarian cancers are diagnosed, coupled with the low and variable response of advanced tumors to standard chemotherapies. To date, clinically useful predictors of treatment response remain lacking. Identifying the genetic determinants of ovarian cancer survival and treatment response is crucial to the development of prognostic biomarkers and personalized therapies that may improve outcomes for the late-stage patients who comprise the majority of cases.

Methods

To identify constitutional genetic variations contributing to ovarian cancer mortality, we systematically investigated associations between germline polymorphisms and ovarian cancer survival using data from The Cancer Genome Atlas Project (TCGA). Using stage-stratified Cox proportional hazards regression, we examined 650,000 SNP loci for association with survival. We additionally examined whether the association of significant SNPs with survival was modified by somatic alterations.

Results

Germline polymorphisms at rs4934282 (AGAP11/C10orf116) and rs1857623 (DNAH14) were associated with stage-adjusted survival ( = 1.12e-07 and 1.80e-07, FDR  = 1.2e-04 and 2.4e-04, respectively). A third SNP, rs4869 (C10orf116), was additionally identified as significant in the exome sequencing data; it is in near-perfect LD with rs4934282. The associations with survival remained significant when somatic alterations.

Conclusions

Discovery analysis of TCGA data reveals germline genetic variations that may play a role in ovarian cancer survival even among late-stage cases. The significant loci are located near genes previously reported as having a possible relationship to platinum and taxol response. Because the variant alleles at the significant loci are common (frequencies for rs4934282 A/C alleles = 0.54/0.46, respectively; rs1857623 A/G alleles = 0.55/0.45, respectively) and germline variants can be assayed noninvasively, our findings provide potential targets for further exploration as prognostic biomarkers and individualized therapies.     

Factors Associated with Post-Seasonal Serological Titer and Risk Factors for Infection with the Pandemic A/H1N1 Virus in the French General Population

The CoPanFlu-France cohort of households was set up in 2009 to study the risk factors for infection by the pandemic influenza virus (H1N1pdm) in the French general population. The authors developed an integrative data-driven approach to identify individual, collective and environmental factors associated with the post-seasonal serological H1N1pdm geometric mean titer, and derived a nested case-control analysis to identify risk factors for infection during the first season. This analysis included 1377 subjects (601 households). The GMT for the general population was 47.1 (95% confidence interval (CI): 45.1, 49.2). According to a multivariable analysis, pandemic vaccination, seasonal vaccination in 2009, recent history of influenza-like illness, asthma, chronic obstructive pulmonary disease, social contacts at school and use of public transports by the local population were associated with a higher GMT, whereas history of smoking was associated with a lower GMT. Additionally, young age at inclusion and risk perception of exposure to the virus at work were identified as possible risk factors, whereas presence of an air humidifier in the living room was a possible protective factor. These findings will be interpreted in light of the longitudinal analyses of this ongoing cohort.