A Homozygous Deep Intronic Variant Causes Von Willebrand Factor Deficiency and Lack of Endothelial-Specific Secretory Organelles,Weibel–Palade Bodies

A type 3 von Willebrand disease (VWD) index patient (IP) remains mutation-negative after completion of the conventional diagnostic analysis, including multiplex ligation-dependent probe amplification and sequencing of the promoter, exons, and flanking intronic regions of the VWF gene (VWF). In this study, we intended to elucidate causative mutation through next-generation sequencing (NGS) of the whole VWF (including complete intronic region), mRNA analysis, and study of the patient-derived endothelial colony-forming cells (ECFCs). The NGS revealed a variant in the intronic region of VWF (997 + 118 T > G in intron 8), for the first time. The bioinformatics assessments (e.g., SpliceAl) predicted this variant creates a new donor splice site (ss), which could outcompete the consensus 5′ donor ss at exon/intron 8. This would lead to an aberrant mRNA that contains a premature stop codon, targeting it to nonsense-mediated mRNA decay. The subsequent quantitative real-time PCR confirmed the virtual absence of VWF mRNA in IP ECFCs. Additionally, the IP ECFCs demonstrated a considerable reduction in VWF secretion (~6% of healthy donors), and they were devoid of endothelial-specific secretory organelles, Weibel–Palade bodies. Our findings underline the potential of NGS in conjunction with RNA analysis and patient-derived cell studies for genetic diagnosis of mutation-negative type 3 VWD patients.     

Sensitivity analysis for predicting continuous fields of tree-cover and fractional land-cover distributions in cloud-prone areas

The use of multi-temporal datasets, such as vegetation index time series or phenological metrics, for improved classification and regression performance is well established in the remote-sensing science community. However, the usefulness of such information is less apparent for areas with distinct wet season periods and heavily concentrated cloud cover. In view of this, this study examines the potential of multi-temporal datasets for the estimation of sub-pixel land-cover fractions and percentage tree cover in an area having distinct wet and dry seasons. Prediction is based on a regression tree algorithm in combination with linear least-squares regression planes, which relate multi-spectral and multi-temporal satellite data from the Moderate-Resolution Imaging Spectroradiometer (MODIS) sensor to sub-pixel land-cover proportions and percentage tree cover, derived from high-resolution land-cover maps. Furthermore, several versions of the latter were produced using different classification approaches to evaluate the sensitivity of the response variable on overall prediction accuracy. The results were evaluated according to absolute accuracy levels and according to their long-term inter-annual robustness by applying the regression models to MODIS data over a period of 11 years. The best regression model based on dry season information only estimated continuous fields of percentage tree cover with a prediction error of less than 7% and an inter-annual variability of less than 4% over a time period of 11 years. The inclusion of intra-annual information did not contribute to any improvements in model accuracy compared to information from the dry season alone, and furthermore, deteriorated inter-annual robustness of model predictions. In addition, it has been shown that the quality of the response variable in the training data had significant effects on overall accuracy.     

Antimicrobial proteinaceous compounds obtained from bifidobacteria: from production to their application

Antimicrobial proteinaceous compounds such as bacteriocins or bacteriocin-like compounds produced by bifidobacteria are largely unknown but have been found to have potent antimicrobial activities toward closely related bacteria and undesirable harmful microorganisms. They are useful in the fields of food preservation or safety, health care, and pharmaceutical applications. The inhibition activity of these substances has been reported to be strain-dependent. Binding to the epithelial cell on the gastrointestinal surfaces is one of the important factors of resident microflora to colonize the intestine. Certain Bifidobacterium strains are able to produce substances that compete and prevent pathogenic bacteria from adhering to the receptors on epithelial cells of intestinal surfaces. The potential probiotic effects of bifidobacteria is well known in the human ecosystem and their production of antimicrobial peptides can contribute to elucidate the precise mechanisms by which bifidobacteria can dominate the intestinal microbiota and achieve their probiotic function. This paper presents a review of the antimicrobial proteinaceous compounds produced by various Bifidobacterium strains, the attempts made to purify them, their characterization, identification and useful applications.     

Three compartment bioimpedance spectroscopy in the nutritional assessment and the outcome of patients with advanced or end stage kidney disease: What have we learned so far?

Bioimpedance spectroscopy (BIS) is an easily applicable tool to assess body composition. The three compartment model BIS (3C BIS) conventionally expresses body composition as lean tissue index (LTI) (lean tissue mass [LTM]/height in meters squared) and fat tissue index (FTI) (adipose tissue mass/height in meters squared), and a virtual compartment reflecting fluid overload (FO). It has been studied extensively in relation to diagnosis and treatment guidance of fluid status disorders in patients with advanced‐stage or end‐stage renal disease. It is the aim of this article to provide a narrative review on the relevance of 3C BIS in the nutritional assessment in this population. At a population level, LTI decreases after the start of hemodialysis, whereas FTI increases. LTI below the 10th percentile is a consistent predictor of outcome whereas a low FTI is predominantly associated with outcome when combined with a low LTI. Recent research also showed the connection between low LTI, inflammation, and FO, which are cumulatively associated with an increased mortality risk. However, studies toward nutritional interventions based on BIS data are still lacking in this population. In conclusion, 3C BIS, by disentangling the components of body mass index, has contributed to our understanding of the relevance of abnormalities in different body compartments in chronic kidney disease patients, and appears to be a valuable prognostic tool, at least at a population level. Studies assessing the effect of BIS guided nutritional intervention could further support its use in the daily clinical care for renal patients.     

Acylhydrazones as Reversible Covalent Crosslinkers for Self‐Healing Polymers

The utilization of dynamic covalent and noncovalent bonds in polymeric materials offers the possibility to regenerate mechanical damage, inflicted on the material, and is therefore of great interest in the field of self‐healing materials. For the design of a new class of self‐healing materials, methacrylate containing copolymers with acylhydrazones as reversible covalent crosslinkers are utilized. The self‐healing polymer networks are obtained by a bulk polymerization of an acylhydrazone crosslinker and commercially available methacrylates as comonomers to fine‐tune the T_g of the systems. The influence of the amount of acylhydrazone crosslinker and the self‐healing behavior of the polymers is studied in detail. Furthermore, the basic healing mechanism and the corresponding mechanical properties are analyzed.