Explaining International Trends in Mortality on Hemodialysis Through Changes in Hemodialysis Practices in the Dialysis Outcomes and Practice Patterns Study (DOPPS).

Rationale & Objective: Case-mix adjusted hemodialysis mortality has decreased since 1998. Many factors that influence mortality may have contributed to this trend, and these associations may differ by continental region. We studied changes in hemodialysis facility practices over time and their potential role in mediating changes in patient survival.

A force-sensitive mutation reveals a non-canonical role for dynein in anaphase progression.

The diverse roles of the dynein motor in shaping microtubule networks and cargo transport complicate in vivo analysis of its functions significantly. To address this issue, we have generated a series of missense mutations in Drosophila Dynein heavy chain. We show that mutations associated with human neurological disease cause a range of defects, including impaired cargo trafficking in neurons.

Evidence for long-term efficacy of a membrane filtration device in rural villages in Ghana.

Drinking water contaminated by pathogenic micro-organisms increases the risk of infectious gastrointestinal disease which could potentially lead to acute kidney injury and even death, particularly amongst the young and the elderly. Earlier studies have shown a substantial reduction in the incidence of diarrheal disease over a period of one year using a polysulfone membrane water gravity-powered water filtration device. The current report is a continuation of these studies to assess the long-term effects of the innovative method on diarrheal incidence rates over a 4-year follow-up period.

The pleiotropic functions of Pri smORF peptides synchronize leg development regulators.

The last decade witnesses the emergence of the abundant family of smORF peptides, encoded by small ORF (<100 codons), whose biological functions remain largely unexplored. Bioinformatic analyses here identify hundreds of putative smORF peptides expressed in Drosophila imaginal leg discs. Thanks to a functional screen in leg, we found smORF peptides involved in morphogenesis, including the pioneer smORF peptides Pri.

A temperature-tolerant CRISPR base editor mediates highly efficient and precise gene editing in .

CRISPR nucleases generate a broad spectrum of mutations that includes undesired editing outcomes. Here, we develop optimized C-to-T base editing systems for the generation of precise loss- or gain-of-function alleles in and identify temperature as a crucial parameter for efficiency. We find that a variant of the widely used APOBEC1 deaminase has attenuated activity at 18° to 29°C and shows considerable dose-dependent toxicity.

The weakness of senescent dermal fibroblasts.

Skin is the largest human organ with easily noticeable biophysical manifestations of aging. As human tissues age, there is chronological accumulation of biophysical changes due to internal and environmental factors. Skin aging leads to decreased elasticity and the loss of dermal matrix integrity via degradation.

A force-sensitive mutation reveals a spindle assembly checkpoint-independent role for dynein in anaphase progression.

The cytoplasmic dynein-1 (dynein) motor organizes cells by shaping microtubule networks and moving a large variety of cargoes along them. However, dynein's diverse roles complicate studies of its functions significantly. To address this issue, we have used gene editing to generate a series of missense mutations in Dynein heavy chain (Dhc).

A global genetic interaction network by single-cell imaging and machine learning.

Cellular and organismal phenotypes are controlled by complex gene regulatory networks. However, reference maps of gene function are still scarce across different organisms. Here, we generated synthetic genetic interaction and cell morphology profiles of more than 6,800 genes in cultured Drosophila cells.

Ageing-induced shrinkage of intervessel pit membranes in xylem of modifies its mechanical properties as revealed by atomic force microscopy.

Bordered pit membranes of angiosperm xylem are anisotropic, mesoporous media between neighbouring conduits, with a key role in long distance water transport. Yet, their mechanical properties are poorly understood. Here, we aim to quantify the stiffness of intervessel pit membranes over various growing seasons.

USP47 deubiquitylates Groucho/TLE to promote Wnt-β-catenin signaling.

The Wnt-β-catenin signal transduction pathway is essential for embryonic development and adult tissue homeostasis. Wnt signaling converts TCF from a transcriptional repressor to an activator in a process facilitated by the E3 ligase XIAP. XIAP-mediated monoubiquitylation of the transcriptional corepressor Groucho (also known as TLE) decreases its affinity for TCF, thereby allowing the transcriptional coactivator β-catenin to displace it on TCF.

Fluid volume management in hemodialysis: never give up!

Every hemodialysis session starts with the question of how much fluid should be removed, which can currently not be answered precisely. Herein, we first revisit the "probing-dry-weight" concept, using the historical example of Tassin/France (practicing also "long, slow dialysis"): Mortality outcomes were, in the 1980s, better than registry data, but are nowadays similar to European average. In view of the negative primary end point in a recent trial on dry weight assessment, based on lung ultrasound-guided evaluation of fluid excess in the lungs, and a meta-analysis of prospective studies failing to show that bioimpedance-based interventions for correction of volume overload had a direct effect on all-cause mortality, we ask how to ever move forward.

Tissue-Specific CRISPR-Cas9 Screening in Drosophila.

Over the last century research in Drosophila has resulted in many fundamental contributions to our understanding of the biology of multicellular organisms. Many of these breakthroughs have been based on the identification of novel gene functions in large-scale genetic screens. However, conventional forward-genetic screens have been limited by the random nature of mutagenesis and difficulties in mapping causal mutations, while reverse-genetic RNAi screens suffer from incomplete knockdown of gene expression.

Evaluation of TEM methods for their signature of the number of layers in mono- and few-layer TMDs as exemplified by MoS and MoTe.

In mono- and few-layer 2D materials, the exact number of layers is a critical parameter, determining the materials' properties and thus their performance in future nano-devices. Here, we evaluate in a systematic manner the signature of exfoliated free-standing mono- and few-layer MoS and MoTe in TEM experiments such as high-resolution transmission electron microscopy, electron energy-loss spectroscopy, and 3D electron diffraction. A reference for the number of layers has been determined by optical contrast and AFM measurements on a substrate.

Reduced adhesion of aged intestinal stem cells contributes to an accelerated clonal drift.

Upon aging, the function of the intestinal epithelium declines with a concomitant increase in aging-related diseases. ISCs play an important role in this process. It is known that ISC clonal dynamics follow a neutral drift model.

Sex-Specific Differences in Mortality and Incident Dialysis in the Chronic Kidney Disease Outcomes and Practice Patterns Study.

Introduction: More men than women start kidney replacement therapy (KRT) although the prevalence of chronic kidney disease (CKD) is higher in women than men. We therefore aimed at analyzing sex-specific differences in clinical outcomes among 8237 individuals with CKD in stages 3 to 5 from Brazil, France, Germany, and the United States participating in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDopps).

Methods: Fine and Gray models, evaluating the effect of sex on time to events, were adjusted for age, Black race (model A); plus diabetes, cardiovascular disease, albuminuria (model B); plus estimated glomerular filtration rate (eGFR) slope during the first 12 months after enrollment and first eGFR after enrollment (model C).

Influence of ROCK Pathway Manipulation on the Actin Cytoskeleton Height.

The actin cytoskeleton with its dynamic properties serves as the driving force for the movement and division of cells and gives the cell shape and structure. Disorders in the actin cytoskeleton occur in many diseases. Deeper understanding of its regulation is essential in order to better understand these biochemical processes.

Conditional CRISPR-Cas Genome Editing in to Generate Intestinal Tumors.

CRISPR-Cas has revolutionized genetics and extensive efforts have been made to enhance its editing efficiency by developing increasingly more elaborate tools. Here, we evaluate the CRISPR-Cas9 system in to assess its ability to induce stem cell-derived tumors in the intestine. We generated conditional tissue-specific CRISPR knockouts using different Cas9 expression vectors with guide RNAs targeting the BMP, Notch, and JNK pathways in intestinal progenitors such as stem cells (ISCs) and enteroblasts (EBs).

Albumin Microspheres as "Trans-Ferry-Beads" for Easy Cell Passaging in Cell Culture Technology.

Protein hydrogels represent ideal materials for advanced cell culture applications, including 3D-cultivation of even fastidious cells. Key properties of fully functional and, at the same time, economically successful cell culture materials are excellent biocompatibility and advanced fabrication processes allowing their easy production even on a large scale based on affordable compounds. Chemical crosslinking of bovine serum albumin (BSA) with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) in a water-in-oil emulsion with isoparaffinic oil as the continuous phase and sorbitan monooleate as surfactant generates micro-meter-scale spherical particles.

European hemodialysis patient satisfaction with phosphate binders is associated with serum phosphorus levels: the Dialysis Outcomes and Practice Patterns Study.

Background: Hemodialysis (HD) patients are commonly prescribed phosphate binders (PBs) to manage serum phosphorus levels, as hyperphosphatemia is strongly associated with poorer survival. Nonadherence with the PB prescription is associated with elevated serum phosphorus levels. We studied associations between patient satisfaction with their PB and serum phosphorus levels and mortality rates.