Boron abundance and solar neutrino spectrum distortion

The presence of neutrinos from Boron decay in the flux observed on Earth is attested by the observation of their energy spectrum. Possible distortions of the spectrum investigated in current detectors are often interpreted in terms of evidence in favour or against various schemes of neutrino oscillations. We stress here that a distortion of the spectrum at high energies could also result from an increase in the ratio of neutrinos originating from ($^3$He+p) and $^8$B reactions. While a $^8$B neutrino depletion would contribute to this effect, an increase in the Hep contribution seems also needed to reproduce the preliminary data.Comment: 8 pages, 2 figures; abstract and introduction rewritten to match the conclusions bette

Protein processing characterized by a gel-free proteomics approach

We describe a method for the specific isolation of representative N-terminal peptides of proteins and their proteolytic fragments. Their isolation is based on a gel-free, peptidecentric proteomics approach using the principle of diagonal chromatography. We will indicate that the introduction of an altered chemical property to internal peptides holding a free α-N-terminus results in altered column retention of these peptides, thereby enabling the isolation and further characterization by mass spectrometry of N-terminal peptides. Besides pointing to changes in protein expression levels when performing such proteome surveys in a differential modus, protease specificity and substrate repertoires can be allocated since both are specified by neo-N-termini generated after a protease cleavage event. As such, our gel-free proteomics technology is widely applicable and amenable for a variety of proteome-driven protease degradomics research

Recessive osteogenesis imperfecta caused by LEPRE1 mutations: clinical documentation and identification of the splice form responsible for prolyl 3-hydroxylation

Abstract: Background: Recessive forms of osteogenesis imperfecta (OI) may be caused by mutations in LEPRE1, encoding prolyl 3-hydroxylase-1 (P3H1) or in CRTAP, encoding cartilage associated protein. These proteins constitute together with cyclophilin B (CyPB) the prolyl 3-hydroxylation complex that hydroxylates the Pro986 residue in both the type I and type II collagen alpha 1-chains. Methods: We screened LEPRE1, CRTAP and PPIB (encoding CyPB) in a European/Middle Eastern cohort of 20 lethal/severe OI patients without a type I collagen mutation. Results: Four novel homozygous and compound heterozygous mutations were identified in LEPRE1 in four probands. Two probands survived the neonatal period, including one patient who is the eldest reported patient (17(7/12) years) so far with P3H1 deficiency. At birth, clinical and radiologic features were hardly distinguishable from those in patients with autosomal dominant (AD) severe/lethal OI. Follow-up data reveal that the longer lived patients develop a severe osteochondrodysplasia that overlaps with, but has some distinctive features from, AD OI. A new splice site mutation was identified in two of the four probands, affecting only one of three LEPRE1 mRNA splice forms, detected in this study. The affected splice form encodes a 736 amino acid (AA) protein with a "KDEL'' endoplasmic reticulum retention signal. While western blotting and immunocytochemical analysis of fibroblast cultures revealed absence of this P3H1 protein, mass spectrometry and SDS-urea-PAGE data showed severe reduction of alpha 1(I) Pro986 3-hydroxylation and overmodification of type I (pro) collagen chains in skin fibroblasts of the patients. Conclusion: These findings suggest that the 3-hydroxylation function of P3H1 is restricted to the 736AA splice form

Editorial: Management of right ventricular failure: pathophysiology, medical treatment and use of ventricular assist devices

Left ventricular assist device; Advanced heart failure; Right ventricular failureDispositiu d'assistència ventricular esquerre; Insuficiència cardíaca avançada; Insuficiència del ventricle dretDispositivo de asistencia ventricular izquierda; Insuficiencia cardíaca avanzada; Insuficiencia del ventrículo derech

The effect of climate type on timescales of drought propagation in an ensemble of global hydrological models

Drought is a natural hazard that occurs at many temporal and spatial scales and has severe environmental and socioeconomic impacts across the globe. The impacts of drought change as drought evolves from precipitation deficits to deficits in soil moisture or streamflow. Here, we quantified the time taken for drought to propagate from meteorological drought to soil moisture drought and from meteorological drought to hydrological drought. We did this by cross-correlating the Standardized Precipitation Index (SPI) against standardized indices (SIs) of soil moisture, runoff, and streamflow from an ensemble of global hydrological models (GHMs) forced by a consistent meteorological dataset. Drought propagation is strongly related to climate types, occurring at sub-seasonal timescales in tropical climates and at up to multi-annual timescales in continental and arid climates. Winter droughts are usually related to longer SPI accumulation periods than summer droughts, especially in continental and tropical savanna climates. The difference between the seasons is likely due to winter snow cover in the former and distinct wet and dry seasons in the latter. Model structure appears to play an important role in model variability, as drought propagation to soil moisture drought is slower in land surface models (LSMs) than in global hydrological models, but propagation to hydrological drought is faster in land surface models than in global hydrological models. The propagation time from SPI to hydrological drought in the models was evaluated against observed data at 127 in situ streamflow stations. On average, errors between observed and modeled drought propagation timescales are small and the model ensemble mean is preferred over the use of a single model. Nevertheless, there is ample opportunity for improvement as substantial differences in drought propagation are found at 10% of the study sites. A better understanding and representation of drought propagation in models may help improve seasonal drought forecasting as well as constrain drought variability under future climate scenarios

Participatory Landscape Planning: The case of the "Westvaardersplassen" in the Netherlands

Although it has been recognised that a stakeholder approach is important in effective landscape planning, a lack of objective methods which include stakeholder opinions in planning projects exists. In this paper we describe a new experimental method for creating landscape planning maps based on stakeholder opinions. During interviews, stakeholders are asked to rate the suitability of individual landscape elements and to visualise their ideal landscape plan. The results of the interview are then used to create a new landscape plan for the area. This method is illustrated by means of a case study in the Netherlands in which four stakeholders were included: the municipality, an agricultural organisation, the water board and a nature conservation organisation. In addition, a sensitivity analysis was performed in order to determine the robustness of the proposed method. Changing weights given to the individual stakeholders did not have a significant influence on the resulting landscape plan, indicating that this is a promising method for participatory landscape planning

Improved Microarray-Based Decision Support with Graph Encoded Interactome Data

In the past, microarray studies have been criticized due to noise and the limited overlap between gene signatures. Prior biological knowledge should therefore be incorporated as side information in models based on gene expression data to improve the accuracy of diagnosis and prognosis in cancer. As prior knowledge, we investigated interaction and pathway information from the human interactome on different aspects of biological systems. By exploiting the properties of kernel methods, relations between genes with similar functions but active in alternative pathways could be incorporated in a support vector machine classifier based on spectral graph theory. Using 10 microarray data sets, we first reduced the number of data sources relevant for multiple cancer types and outcomes. Three sources on metabolic pathway information (KEGG), protein-protein interactions (OPHID) and miRNA-gene targeting (microRNA.org) outperformed the other sources with regard to the considered class of models. Both fixed and adaptive approaches were subsequently considered to combine the three corresponding classifiers. Averaging the predictions of these classifiers performed best and was significantly better than the model based on microarray data only. These results were confirmed on 6 validation microarray sets, with a significantly improved performance in 4 of them. Integrating interactome data thus improves classification of cancer outcome for the investigated microarray technologies and cancer types. Moreover, this strategy can be incorporated in any kernel method or non-linear version of a non-kernel method

Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF

Several pathological processes, such as sepsis and inflammatory bowel disease (IBD), are associated with impairment of intestinal epithelial barrier. Here, we investigated the role of matrix metalloproteinase MMP13 in these diseases. We observed that MMP13(-/-) mice display a strong protection in LPS- and caecal ligation and puncture-induced sepsis. We could attribute this protection to reduced LPS-induced goblet cell depletion, endoplasmic reticulum stress, permeability and tight junction destabilization in the gut of MMP13(-/-) mice compared to MMP13(+/+) mice. Both in vitro and in vivo, we found that MMP13 is able to cleave pro-TNF into bioactive TNF. By LC-MS/MS, we identified three MMP13 cleavage sites, which proves that MMP13 is an alternative TNF sheddase next to the TNF converting enzyme TACE. Similarly, we found that the same mechanism was responsible for the observed protection of the MMP13(-/-) mice in a mouse model of DSS-induced colitis. We identified MMP13 as an important mediator in sepsis and IBD via the shedding of TNF. Hence, we propose MMP13 as a novel drug target for diseases in which damage to the gut is essential

Immundefekte bei chronischer Rhinosinusitis : eine bedeutende und oft unterschätzte Ursache

Background Chronic rhinosinusitis (CRS) is one of the most frequent chronic diseases. Among these patients the prevalence of immune defects is higher than in the healthy general population. Methods A selective review of the literature was carried out in PubMed and Medline covering the period between 2008 and 2019. Additionally, recent German publications in journals not listed in the abovementioned databases were analyzed. Results The diagnostic workflow with respect to the immunodeficiency consists of a detailed anamnesis and physical examination, laboratory tests and the antibody reaction to polysaccharide vaccines and antigens. Beside antibiotic treatment, vaccinations and immunoglobulin replacement are available. Notwithstanding the above, functional endoscopic surgery of the paranasal sinuses should be performed according to guideline recommendations. Conclusion Patients with CRS who do not sufficiently respond to conservative and surgical treatment should be checked for underlying immunodeficiencies