Selenoprotein P Status Correlates to Cancer-Specific Mortality in Renal Cancer Patients

Selenium (Se) is an essential trace element for selenoprotein biosynthesis. Selenoproteins have been implicated in cancer risk and tumor development. Selenoprotein P (SePP) serves as the major Se transport protein in blood and as reliable biomarker of Se status in marginally supplied individuals. Among the different malignancies, renal cancer is characterized by a high mortality rate. In this study, we aimed to analyze the Se status in renal cell cancer (RCC) patients and whether it correlates to cancer-specific mortality. To this end, serum samples of RCC patients (n = 41) and controls (n = 21) were retrospectively analyzed. Serum Se and SePP concentrations were measured by X-ray fluorescence and an immunoassay, respectively. Clinical and survival data were compared to serum Se and SePP concentrations as markers of Se status by receiver operating characteristic (ROC) curve and Kaplan-Meier and Cox regression analyses. In our patients, higher tumor grade and tumor stage at diagnosis correlated to lower SePP and Se concentrations. Kaplan-Meier analyses indicated that low Se status at diagnosis (SePP<2.4 mg/l, bottom tertile of patient group) was associated with a poor 5-year survival rate of 20% only. We conclude that SePP and Se concentrations are of prognostic value in RCC and may serve as additional diagnostic biomarkers identifying a Se deficit in kidney cancer patients potentially affecting therapy regimen. As poor Se status was indicative of high mortality odds, we speculate that an adjuvant Se supplementation of Se-deficient RCC patients might be beneficial in order to stabilize their selenoprotein expression hopefully prolonging their survival. However, this assumption needs to be rigorously tested in prospective clinical trials.     

Bioprocess in-line monitoring using Raman spectroscopy and Indirect Hard Modeling (IHM): A simple calibration yields a robust model

To increase the process productivity and product quality of bioprocesses, the in-line monitoring of critical process parameters is highly important. For monitoring substrate, metabolite, and product concentrations, Raman spectroscopy is a commonly used Process Analytical Technology (PAT) tool that can be applied in-situ and non-invasively. However, evaluating bioprocess Raman spectra with a robust state-of-the-art statistical model requires effortful model calibration. In the present study, we in-line monitored a glucose to ethanol fermentation by Saccharomyces cerevisiae (S. cerevisiae) using Raman spectroscopy in combination with the physics-based Indirect Hard Modeling (IHM) and showed successfully that IHM is an alternative to statistical models with significantly lower calibration effort. The IHM prediction model was developed and calibrated with only 16 Raman spectra in total, which did not include any process spectra. Nevertheless, IHM's root mean square errors of prediction (RMSEPs) for glucose (3.68 g/L) and ethanol (1.69 g/L) were comparable to the prediction quality of similar studies that used statistical models calibrated with several calibration batches. Despite our simple calibration, we succeeded in developing a robust model for evaluating bioprocess Raman spectra.     

Disagreement between Human Papillomavirus Assays: An Unexpected Challenge for the Choice of an Assay in Primary Cervical Screening

We aimed to determine the disagreement in primary cervical screening between four human papillomavirus assays: Hybrid Capture 2, cobas, CLART, and APTIMA. Material from 5,064 SurePath samples of women participating in routine cervical screening in Copenhagen, Denmark, was tested with the four assays. Positive agreement between the assays was measured as the conditional probability that the results of all compared assays were positive given that at least one assay returned a positive result. Of all 5,064 samples, 1,679 (33.2%) tested positive on at least one of the assays. Among these, 41% tested positive on all four. Agreement was lower in women aged ≥30 years (30%, vs. 49% at <30 years), in primary screening samples (29%, vs. 38% in follow-up samples), and in women with concurrent normal cytology (22%, vs. 68% with abnormal cytology). Among primary screening samples from women aged 30–65 years (n = 2,881), 23% tested positive on at least one assay, and 42 to 58% of these showed positive agreement on any compared pair of the assays. While 4% of primary screening samples showed abnormal cytology, 6 to 10% were discordant on any pair of assays. A literature review corroborated our findings of considerable disagreement between human papillomavirus assays. This suggested that the extent of disagreement in primary screening is neither population- nor storage media-specific, leaving assay design differences as the most probable cause. The substantially different selection of women testing positive on the various human papillomavirus assays represents an unexpected challenge for the choice of an assay in primary cervical screening, and for follow up of in particular HPV positive/cytology normal women.     

PspA adopts an ESCRT-III-like fold and remodels bacterial membranes

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Enhanced Directed Radiative Surface Plasmon Emission from Periodically Corrugated Noble Metal Films

Plasmonics - Massively enhanced directed radiation emission from periodically corrugated thin gold and silver films at the surface plasmon resonance is reported. The optical setup comprises...     

Time-dependent propagators for stochastic models of gene expression: an analytical method

The inherent stochasticity of gene expression in the context of regulatory networks profoundly influences the dynamics of the involved species. Mathematically speaking, the propagators which describe the evolution of such networks in time are typically defined as solutions of the corresponding chemical master equation (CME). However, it is not possible in general to obtain exact solutions to the CME in closed form, which is due largely to its high dimensionality. In the present article, we propose an analytical method for the efficient approximation of these propagators. We illustrate our method on the basis of two categories of stochastic models for gene expression that have been discussed in the literature. The requisite procedure consists of three steps: a probability-generating function is introduced which transforms the CME into (a system of) partial differential equations (PDEs); application of the method of characteristics then yields (a system of) ordinary differential equations (ODEs) which can be solved using dynamical systems techniques, giving closed-form expressions for the generating function; finally, propagator probabilities can be reconstructed numerically from these expressions via the Cauchy integral formula. The resulting ‘library’ of propagators lends itself naturally to implementation in a Bayesian parameter inference scheme, and can be generalised systematically to related categories of stochastic models beyond the ones considered here.

     

Progress in Definition,Prevention and Treatment of Fungal Infections in Cystic Fibrosis

Cystic fibrosis (CF) is a chronic lethal multi-system condition; however, most of the morbidity and mortality is dependent on the status of the respiratory system. Progressive respiratory decline is mediated by chronic infection and inflammation, punctuated by important acute events known as pulmonary exacerbations which can lead to accelerated decline. The main bacterial species causing infections include Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae and Achromobacter xylosoxidans. In addition to bacteria, fungi are detected in a significant number of patients. The impact of fungal colonization of the airways is still not completely elucidated, but an increasing body of evidence suggests an important role for moulds and yeasts. Although fungal infections are rare, fungi can cause severe pneumonia requiring appropriate targeted treatment. The most common fungi in respiratory samples of patients with CF are Aspergillus fumigatus, Aspergillus terreus and Scedosporium species for filamentous fungi, and yeasts such as Candida albicans and Candida glabrata. Therapeutic strategies depend on the detected fungus and the underlying clinical status of the patient. The antifungal therapy can range from a simple monotherapy up to a combination of three different drugs. Treatment course may be indicated in some patients for two weeks and in others for up to six months, and in rare cases even longer. New antifungal drugs have been developed and are being tested in clinical studies offering the hope of therapeutic alternatives to existing drugs. Identifying relevant risk factors and diagnostic criteria for fungal colonization and infection is crucial to enabling an adequate prevention, diagnosis and treatment.     

Organization of Patient Management and Fungal Epidemiology in Cystic Fibrosis

The achievement of a better life for cystic fibrosis (CF) patients is mainly caused by a better management and infection control over the last three decades. Herein, we want to summarize the cornerstones for an effective management of CF patients and to give an overview of the knowledge about the fungal epidemiology in this clinical context in Europe. Data from a retrospective analysis encompassing 66,616 samples from 3235 CF patients followed-up in 9 CF centers from different European countries are shown.     

Anaerobic biotransformation of hexachlorocyclohexane isomers by <Emphasis Type="Italic">Dehalococcoides</Emphasis> species and an enrichment culture

The biotransformation of hexachlorocyclohexane isomers (HCH) by two Dehalococcoides mccartyi strains (195 and BTF08) and an enrichment culture was investigated and compared to conversion by the obligate anaerobic strain Clostridium pasteurianum strain DSMZ 525. The D. mccartyi strains preferentially transformed γ-HCH over α-HCH and δ-HCH isomers while β-HCH biotransformation was not significant. In case of the enrichment culture, γ-HCH was preferentially transformed over the δ-HCH, β-HCH and α-HCH isomers. Major observed metabolites in both cases were tetrachlorocyclohexene and as end products monochlorobenzene (MCB) and benzene. Dechlorination of the γ-HCH isomer was linked to an increase in cell numbers for strain 195. γ-HCH transformation was linked to considerable carbon stable isotope fractionation with the enrichment factor ε_c?=???5.5?±?0.8‰ for D. mccartyi strain 195, ε_c?=???3.1?±?0.4‰ for the enrichment culture and ε_c?=???4.1?±?0.6‰ for co-metabolic transformation by C. pasteurianum.