A5027504599- Genetics and Neurodevelopmental Disorders
- Ion Transport and Channel Regulation
- Genomics and Rare Diseases
- Ion channel regulation and function
- Biomedical Research and Pathophysiology
- Cellular transport and secretion
- RNA and protein synthesis mechanisms
- Antimicrobial Peptides and Activities
- COVID-19 and Mental Health
- Congenital heart defects research
- Biochemical and Structural Characterization
- Erythrocyte Function and Pathophysiology
- Neuroscience and Neuropharmacology Research
- Nitric Oxide and Endothelin Effects
- Neonatal Health and Biochemistry
- Cardiomyopathy and Myosin Studies
- Diabetes Management and Research
- Bladder and Urothelial Cancer Treatments
- Muscle Physiology and Disorders
- Pharmacology and Obesity Treatment
- Adipokines, Inflammation, and Metabolic Diseases
- Microbial Natural Products and Biosynthesis
- Sexual Differentiation and Disorders
- Genomic variations and chromosomal abnormalities
- Muscle metabolism and nutrition
Forschungsinstitut Havelhöhe
2022
Humboldt-Universität zu Berlin
2021
Charité - Universitätsmedizin Berlin
2014-2021
Freie Universität Berlin
2021
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
2010-2020
Max Delbrück Center
2010-2020
Leipzig University
2014
Broad Institute
2014
Leibniz Institute for Neurobiology
2012
Babraham Institute
2012
Summary Purpose The management of epilepsy in children is particularly challenging when seizures are resistant to antiepileptic medications, or undergo many changes seizure type over time, have comorbid cognitive, behavioral, motor deficits. Despite efforts classify such epilepsies based on clinical and electroencephalographic criteria, never receive a definitive etiologic diagnosis. Whole exome sequencing ( WES ) proving be highly effective method for identifying de novo variants that cause...
X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, large number families mapping to remained unresolved suggesting that more XLID or loci are yet be Here, we investigated 405 with XLID. We employed massively parallel sequencing all exons index males. The majority these males were previously tested negative for copy variations mutations subset known by...
Abstract Proline‐rich antimicrobial peptides (PrAMPs) have been investigated and optimized by several research groups companies as promising lead compounds to treat systemic infections caused Gram‐negative bacteria. PrAMPs, such apidaecins oncocins, enter the bacteria kill them apparently through inhibition of specific targets without a lytic effect on membranes. Both oncocins were shown bind with nanomolar dissociation constants 70S ribosome. In apidaecins, at least two C‐terminal residues...
During lysosomal acidification, proton-pump currents are thought to be shunted by a chloride ion (Cl-) channel, tentatively identified as ClC-7. Surprisingly, recent data suggest that ClC-7 instead mediates Cl-/proton (H+) exchange. We generated mice carrying point mutation converting into an uncoupled (unc) Cl- conductor. Despite maintaining conductance and normal pH, these Clcn7(unc/unc) showed storage disease like lacking However, their osteopetrosis was milder, they lacked coat color...
Chloride Balancing Act The ionic composition of the cytosol and intracellular organelles must be regulated in face ongoing membrane traffic into out cell. Now, two papers address consequences a change transport phenotype an Cl − protein from coupled exchanger to passive conductor (see Perspective by Smith Schwappach ). Novarino et al. (p. 1398 , published online 29 April) investigated consequence knock-in uncoupled ClC-5 transporter mouse. knock-out mouse this endosomal kidney has severe...
Rationale : Vascular wall stretch is the major stimulus for myogenic response of small arteries to pressure. The molecular mechanisms are elusive, but recent findings suggest that G protein–coupled receptors can elicit a response. Objective To determine whether angiotensin II type 1 (AT R) in vascular smooth muscle cells exert mechanosensitivity and identify downstream ion channel mediators vasoconstriction. Methods Results We used mice deficient AT R signaling molecules putative targets,...
Titin, the largest protein known to date, has been linked sarcomere assembly and function through its elastic adaptor signaling domains. Titin's M-line region contains a unique kinase domain that proposed regulate via substrate titin cap (T-cap). In this study, we use M line–deficient mouse show initial of does not depend on titin's or phosphorylation T-cap by kinase. Rather, is required form continuous filament provide mechanical stability embryonic sarcomere. Even without integrating into...
Variants in CLCN4, which encodes the chloride/hydrogen ion exchanger CIC-4 prominently expressed brain, were recently described to cause X-linked intellectual disability and epilepsy. We present detailed phenotypic information on 52 individuals from 16 families with CLCN4-related disorder: 5 affected females 2 males a de novo variant CLCN4 (6 previously unreported) 27 males, 3 15 asymptomatic female carriers 9 inherited variants (4 unreported). Intellectual ranged borderline profound....
Article2 March 2020Open Access Source DataTransparent process Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration Stefanie Weinert Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany Max-Delbrück-Centrum Medizin (MDC), Search for more papers by this author Niclas Gimber orcid.org/0000-0001-9456-3063 Dorothea Deuschel Till Stuhlmann Dmytro Puchkov Zohreh Farsi Carmen F Ludwig Gaia Novarino Karen I López-Cayuqueo Rosa Planells-Cases...
Abstract Background: Congenital adrenal hyperplasia (CAH) is a frequent autosomal recessive disease, with wide range of clinical manifestations, most commonly attributable to mutations in the 21-hydroxylase gene (CYP21). Large deletions, large conversions, small 8-basepair deletion, and eight point CYP21 account for ∼95% all enzyme deficiencies. We developed new strategy rapid analysis. Methods: DNA samples from 40 CAH patients previously genotyped by direct sequencing were reanalyzed...
Inactivation of the mainly endosomal 2Cl(-)/H(+)-exchanger ClC-5 severely impairs endocytosis in renal proximal tubules and underlies human kidney stone disorder Dent's disease. In heterologous expression systems, interaction E3 ubiquitin ligases WWP2 Nedd4-2 with a "PY-motif" cytoplasmic C terminus stimulates its internalization from plasma membrane may influence receptor-mediated endocytosis. We asked whether this is relevant vivo generated mice which PY-motif was destroyed by point...
The bacterial protein DnaK promotes folding of newly synthesized polypeptide chains, refolding misfolded proteins, and trafficking. Assisted is especially important under stress conditions induced by antibiotic therapies reducing the desired bactericidal effects. supposedly targeted proline-rich antimicrobial peptides (PrAMPs), but Escherichia coli ΔdnaK mutants wild type strains are equally susceptible indicating further intracellular targets, such as 70S ribosome. Crystal structures...
With the coronavirus disease 2019 (COVID-19) cases peaking and health systems reaching their limits in winter 2020/21, schools remained closed many countries. To better understand teachers’ risk perception, we conducted a survey Germany. Participants were recruited through various associations invited to take part cross-sectional COVID-19-specific online survey. Descriptive statistical analysis was performed. Factors associated with fears of contracting severe acute respiratory syndrome type...
Abstract Background With COVID-19 cases peaking, vaccination programs starting and health systems reaching their limits in winter 2020/21, schools remained closed many countries despite ever-recurring debates. To better understand teachers’ fear of infection risk perception we conducted a survey Germany. Methods Participants were recruited through various associations invited to take part cross-sectional specific online survey. Anonymous demographic self-reported data collected from those...
Evidence suggests that Post/Long-COVID (PLC) is associated with a reduced health-related quality of life, however little knowledge exists on the risk factors contribute to PLC. The objective this prospective real-world data study was evaluate PLC using national online survey data. Adjusted multivariable regression analyses were performed software R. Between 14 April and 15 June 2021, 99 registered individuals reported have suffered from symptoms most common fatigue, dyspnoea, decreased...
Abstract Prolinreiche antimikrobielle Peptide (PrAMPs) wurden bereits von mehreren Forschungsgruppen und Firmen als vielversprechende Leitverbindungen zur Behandlung systemischer Infektionen mit Gram‐negativen Bakterien untersucht optimiert. PrAMPs, wie Apidaecine Oncocine, dringen in ein töten diese wahrscheinlich durch Inhibition spezifischer Zielstrukturen, ohne lytische Wirkung auf die Membranen. Wir zeigen hier, dass Oncocine Dissoziationskonstanten im nanomolaren Bereich an das...
Abstract Proteins of the CLC gene family assemble to homo‐ or sometimes heterodimers and either function as Cl – channels /H + ‐exchangers. proteins are present in all phyla. Detailed structural information is available from crystal structures bacterial algal CLCs. Mammals express nine genes, four which encode five 2Cl Two accessory β‐subunits known: (1) barttin (2) Ostm1. ClC‐Ka ClC‐Kb need barttin, whereas Ostm1 required for lysosomal ClC‐7 ‐exchanger. ClC‐1, ‐2, ‐Ka ‐Kb reside plasma...
Wall stretch is a major stimulus for the myogenic response of small arteries to pressure. Recent findings suggest that G protein‐coupled receptors can elicit response. Our aim was determine if angiotensin II type 1 (AT1R) in vascular smooth muscle cells (VSMC) exert mechanosensitivity and identify downstream ion channel mediators vasoconstriction. We used mice deficient AT1R signaling molecules putative targets, namely AT1R, angiotensinogen, TRPC6 channels or subtypes KCNQ (Kv7) gene family...