Mixed kelp with foliose red seaweeds, sponges and ascidians on sheltered tide-swept infralittoral rock

Mit dieser Publikation liegt erstmalig eine repräsentative Erhebung zur Verbreitung der verschiedenen Bodenbearbeitungssysteme und der technischen Ausstattung in sächsischen Landwirtschaftsbetrieben vor. Die Entscheidungsgründe bezüglich der Bodenbearbeitung aus Sicht des Bodenschutzes und der Verunkrautung sind vielfältig. Bezogen auf die Ackerfläche der befragten Betriebe werden in Sachsen rund 43 % dauerhaft pfluglos bestellt und nur 7 % dauerhaft gepflügt. Auf rund 50 % der Ackerfläche wird wechselnd in unterschiedlicher Häufigkeit mit oder ohne Pflug gearbeitet. Redaktionsschluss: 04.03.202

Evidence for anti-angiogenic and pro-survival functions of the cerebral cavernous malformation protein 3

Mutations in CCM1, CCM2, or CCM3 lead to cerebral cavernous malformations, one of the most common hereditary vascular diseases of the brain. Endothelial cells within these lesions are the main disease compartments. Here, we show that adenoviral CCM3 expression inhibits endothelial cell migration, proliferation, and tube formation while downregulation of endogenous CCM3 results in increased formation of tube-like structures. Adenoviral CCM3 expression does not induce apoptosis under normal endothelial cell culture conditions but protects endothelial cells from staurosporine-induced cell death. Tyrosine kinase activity profiling suggests that CCM3 supports PDPK-1/Akt-mediated endothelial cell quiescence and survival

A two-hit mechanism causes cerebral cavernous malformations: complete inactivation of CCM1, CCM2 or CCM3 in affected endothelial cells

Cavernous vascular malformations occur with a frequency of 1:200 and can cause recurrent headaches, seizures and hemorrhagic stroke if located in the brain. Familial cerebral cavernous malformations (CCMs) have been associated with germline mutations in CCM1/KRIT1, CCM2 or CCM3/PDCD10. For each of the three CCM genes, we here show complete localized loss of either CCM1, CCM2 or CCM3 protein expression depending on the inherited mutation. Cavernous but not adjacent normal or reactive endothelial cells of known germline mutation carriers displayed immunohistochemical negativity only for the corresponding CCM protein but not for the two others. In addition to proving loss of function at the protein level, our data are the first to demonstrate endothelial cell mosaicism within cavernous tissues and provide clear pathogenetic evidence that the endothelial cell is the cell of disease origin

VEGF receptors on PC12 cells mediate transient activation of ERK1/2 and Akt: comparison of nerve growth factor and vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) and endostatin are angiogenic and anti-angiogenic molecules, respectively, that have been implicated in neurogenesis and neuronal survival. Using alkaline phosphatase fusion proteins, we show that the PC12 neuronal cell line contains cell membrane receptors for VEGF but not for endostatin and the collagen XV endostatin homologue. Immunocytochemistry confirmed that proliferating and differentiated PC12 cells express VEGF receptors 1, 2 and neuropilin-1. While no functional effects of VEGF on PC12 cell proliferation and differentiation could be observed, a slight VEGF-induced reduction of caspase-3 activity in differentiated apoptotic PC12 cells was paralleled by transient activation of ERK1/2 and Akt. In direct comparison, nerve growth factor proved to be a strikingly more potent neuroprotective agent than VEGF

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics

Schons M, Pilgram L, Reese J-P, et al. The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics. European Journal of Epidemiology . 2022.The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON's goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36-62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON's design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584. © 2022. The Author(s)

Winner's Curse Correction and Variable Thresholding Improve Performance of Polygenic Risk Modeling Based on Genome-Wide Association Study Summary-Level Data

Recent heritability analyses have indicated that genome-wide association studies (GWAS) have the potential to improve genetic risk prediction for complex diseases based on polygenic risk score (PRS), a simple modelling technique that can be implemented using summary-level data from the discovery samples. We herein propose modifications to improve the performance of PRS. We introduce threshold-dependent winner's-curse adjustments for marginal association coefficients that are used to weight the single-nucleotide polymorphisms (SNPs) in PRS. Further, as a way to incorporate external functional/annotation knowledge that could identify subsets of SNPs highly enriched for associations, we propose variable thresholds for SNPs selection. We applied our methods to GWAS summary-level data of 14 complex diseases. Across all diseases, a simple winner's curse correction uniformly led to enhancement of performance of the models, whereas incorporation of functional SNPs was beneficial only for selected diseases. Compared to the standard PRS algorithm, the proposed methods in combination led to notable gain in efficiency (25-50% increase in the prediction R2) for 5 of 14 diseases. As an example, for GWAS of type 2 diabetes, winner's curse correction improved prediction R2 from 2.29% based on the standard PRS to 3.10% (P = 0.0017) and incorporating functional annotation data further improved R2 to 3.53% (P = 2×10-5). Our simulation studies illustrate why differential treatment of certain categories of functional SNPs, even when shown to be highly enriched for GWAS-heritability, does not lead to proportionate improvement in genetic risk-prediction because of non-uniform linkage disequilibrium structure

Molecular mechanisms of neurodegeneration in cathepsin B- and L- deficient brains

Kathepsin B und L sind lysosomale Cysteinproteasen, die mit einer Reihe von pathologischen Prozessen, wie z. B. Cancerogenese, Tumorangiogenese und Neurodegeneration in Verbindung gebracht werden. Dennoch sind bis jetzt nur wenige Proteinsubstrate beschrieben. Ausserdem sind die Mechanismen der Regulation von Zellproliferation, -invasion und -apoptose durch Kathepsin B und L weitgehend unverstanden. Ein kombinierter Mangel beider Kathepsine führt zu einer frühzeitigen Neurodegeneration in Mäusen, die an neuronale Lipofuszinosen beim Menschen erinnert. In der vorliegenden Studie wurden Unterschiede in der Proteinzusammensetzung von wildtypischen und doppelt-defizienten Gehirnlysosomen quantifiziert. Eine Kombination von subzellulärer Fraktionierung und LC-MS/MS unter Verwendung einer isobarischen Markierung (iTraqTM) erlaubte uns die gleichzeitige Untersuchung von zerebralen Lysosomen aus Wildtyp und Kathepsin B-/-L-/- Mäusen. Ingesamt waren 19 Proteine signifikant erhöht in Kathepsin B-/-L-/- Lysosomen. Die meisten erhöhten Proteine wurden der neuronalen Biosynthese, regenerierenden bzw. endozytotischen oder lysosomalen Kompartimenten zugeordnet. Der Anstieg von Calcyon, dem Delta/Notch- verwandten epidermalen Wachstumsfaktor-Rezeptor (DNER), Neurochondrin, Phospholipase D3, Rab14, Cathepsin D und Apolipoprotein E lässt eine potentielle Rolle von Kathepsin B und L im Axonwachstum und der Synapsenbildung während der postnatalen Entwicklung des Zentralnervensystems vermuten.Cathepsins B and L are lysosomal cysteine proteases which have been implicated in a variety of pathological processes such as cancer, tumor angiogenesis, and neurodegeneration. However, only a few protein substrates have thus far been described and the mechanisms by which cathepsins B and L regulate cell proliferation, invasion, and apoptosis are poorly understood. Combined deficiency of both cathepsins results in early-onset neurodegeneration in mice reminiscent of neuronal ceroid lipofuscinoses in humans. Therefore, we intended to quantify protein changes in brain lysosomes of double deficient mice. A combination of subcellular fractionation and LC-MS/MS using isobaric tagging for relative and absolute quantitation (iTRAQTM) allowed us to simultaneously assess wildtype and cathepsin B-/-L-/- cerebral lysosomes. Altogether, 19 different proteins were significantly increased in cathepsin B-/-L-/- lysosomes. Most elevated proteins had previously been localized to neuronal biosynthetic, recycling/endocytic or lysosomal compartments. The increase of calcyon, the Delta/Notch-like epidermal growth factor-related receptor, neurochondrin, phospholipase D3, Rab14, cathepsin D, and apolipoprotein E suggests a potential role for cathepsins B and L in axon outgrowth and synapse formation during postnatal development of the central nervous system

The influence of the computerised cognitive training Cogpack on the cognitive functions of alcohol-dependent male patients in in-patient withdrawal treatment

Die vorliegende Studie basiert auf der Fragestellung, dass in der klinischen Literatur häufig die Rede von neuropsychologischen Beeinträchtigungen bei alkoholabhängigen Patienten ist. In diesem Zusammenhang wird die zentrale Bedeutung neuropsychologischer Therapie postuliert. Dabei wird auch die zunehmende Wichtigkeit von computergestütztem neuropsychologischem Training zur Steigerung der kognitiven Fähigkeiten von Alkoholikern diskutiert. Deshalb war das Ziel dieser Studie zu untersuchen, ob sich mit Hilfe des computergestützten Hirnleistungstrainings Cogapck bei männlichen alkoholabhängigen Patienten in stationärer Entwöhnungsbehandlung kognitive Leistungssteigerungen in einer für diese Untersuchung zusammengestellten neuropsychologischen Testbatterie nachweisen lassen.The present study is based on the research issue that in clinical literature it is often talked about neuropsychological impairment in alcohol-dependent patients. In this context, the key importance of neuropsychological therapy is posited. At the same time, the increasing importance of computerised neuropsychological training for the enhancement of cognitive abilities of alcoholics is discussed. Thus it was the goal of this study to examine if by means of the computerised cognitive training Cogpack it is possible to prove an enhancement of cognitive abilities in male alcohol-dependent patients in in-patient withdrawal treatment using a neuropsychological test battery constructed specifically for this study

Ecosystem house:

Lebewesen begleiten den Menschen, seitdem er sich in abgetrennten Bereichen vor Gefahren und der Witterung schützt. Durch den Eintrag von Feuchtigkeit in modernen Gebäuden werden das Artenspektrum und die Biomasse in Räumen deutlich erhöht. Nach der feuchteabhängigen Besiedelung durch Schimmelpilze und Bakterien werden gebildete „Schimmelrasen“ von Milben, Staubläusen und Silberfischchen beweidet. Die Bedeutung von Milben, Staubläusen und Silberfischchen als Bioindikatoren für Feuchte-/Schimmelschäden wird bis heute unterschätzt. Der Einsatz eines Schimmelspürhundes kann als weiterer und weiterführender Baustein einer tierischen Bioindikatorkette für Schimmelschäden gewertet werden: Mit dieser Methodik wurden neue Erkenntnisse über unsere Innenraumqualitäten gewonnen. Im Routineeinsatz liefern Schimmelspürhunde, wenn auch mit großen Qualitätsunterschieden, wesentliche Entscheidungsgrundlagen für das Erkennen und fachgerechte Sanieren von Feuchte-/Schimmelschäden.Living organisms have accompanied humans ever since they have sheltered in secluded areas from danger and the elements. The introduction of moisture into modern buildings significantly increases the species spectrum and biomass in rooms. After the moisture-dependent colonisation by moulds and bacteria, formed “mould lawns” are grazed by mites, dust lice and silverfish. The importance of mites, dust lice and silverfish as bioindicators of moisture/mould damage is still underestimated today. The use of a mould sniffing dog can be seen as a further and more advanced component of an animal bioindicator chain for mould  damage: With this methodology, new insights into our indoor qualities have been gained. In routine use, mould sniffer dogs – albeit with great differences in quality – provide essential bases for decision-making for the detection and professional remediation of damp/mould damage