Inhibition of the Notch signal transducer CSL by Pkc53E-mediated phosphorylation to fend off parasitic immune challenge in .

Notch signalling activity regulates hematopoiesis in and vertebrates alike. Parasitoid wasp infestation of larvae, however, requires a timely downregulation of Notch activity to allow the formation of encapsulation-active blood cells. Here, we show that the CSL transcription factor Suppressor of Hairless [Su(H)] is phosphorylated at Serine 269 in response to parasitoid wasp infestation.

Systematic review of variables that moderate and/or mediate the relationship between child maltreatment and adverse outcomes: a study protocol.

Introduction: Child maltreatment (CM) is associated with adverse cognitive, behavioural, physical and social outcomes that often continue until adulthood. Systematic reviews on mediators and moderators of this relationship mostly investigate childhood adversities in general or only with regard to an adult population, single outcomes or single forms of maltreatment. The purpose of this review is to synthesise the evidence of variables that mediate and/or moderate the relationship between CM and diverse outcomes.

Numerous Serine/Threonine Kinases Affect Blood Cell Homeostasis in .

Blood cells in serve primarily innate immune responses. Various stressors influence blood cell homeostasis regarding both numbers and the proportion of blood cell types. The principle molecular mechanisms governing hematopoiesis are conserved amongst species and involve major signaling pathways like Notch, Toll, JNK, JAK/Stat or RTK.

CRISPR/Cas9-mediated nexilin deficiency interferes with cardiac contractile function in zebrafish in vivo.

Nexilin (NEXN) plays a crucial role in stabilizing the sarcomeric Z-disk of striated muscle fibers and, when mutated, leads to dilated cardiomyopathy in humans. Due to its early neonatal lethality in mice, the detailed impact of the constitutive homozygous NEXN knockout on heart and skeletal muscle morphology and function is insufficiently investigated. Here, we characterized a constitutive homozygous CRISPR/Cas9-mediated nexn knockout zebrafish model.

Zebrafish as model system for the biological characterization of CK1 inhibitors.

The CK1 family is involved in a variety of physiological processes by regulating different signaling pathways, including the Wnt/β-catenin, the Hedgehog and the p53 signaling pathways. Mutations or dysregulation of kinases in general and of CK1 in particular are known to promote the development of cancer, neurodegenerative diseases and inflammation. There is increasing evidence that CK1 isoform specific small molecule inhibitors, including CK1δ- and CK1ε-specific inhibitors of Wnt production (IWP)-based small molecules with structural similarity to benzimidazole compounds, have promising therapeutic potential.

Hdac1-deficiency affects the cell cycle axis Cdc25-Cdk1 causing impaired G2/M phase progression and reduced cardiomyocyte proliferation in zebrafish.

Zebrafish have the ability to fully regenerate their hearts after injury since cardiomyocytes subsequently dedifferentiate, re-enter cell cycle, and proliferate to replace damaged myocardial tissue. Recent research identified the reactivation of dormant developmental pathways during cardiac regeneration in adult zebrafish, suggesting pro-proliferative pathways important for developmental heart growth to be also critical for regenerative heart growth after injury. Histone deacetylase 1 (Hdac1) was recently shown to control both, embryonic as well as adult regenerative cardiomyocyte proliferation in the zebrafish model.

Hydroxylation of the NOTCH1 intracellular domain regulates Notch signaling dynamics.

Notch signaling plays a pivotal role in the development and, when dysregulated, it contributes to tumorigenesis. The amplitude and duration of the Notch response depend on the posttranslational modifications (PTMs) of the activated NOTCH receptor - the NOTCH intracellular domain (NICD). In normoxic conditions, the hydroxylase FIH (factor inhibiting HIF) catalyzes the hydroxylation of two asparagine residues of the NICD.

[Requirements of good medical care for victims of violence and quality-assured "confidential securing of evidence". A qualitative study among physicians in Northrhine-Westphalia].

Background: Sexual and domestic violence against women and young girls are widespread and can lead to significant psychological, psychosocial and health consequences for the victims. "Confidential Securing of Evidence" ("vertrauliche Spurensicherung", VSS) offers victims the opportunity to have the consequences of the violent acts they have suffered documented without primary police involvement, thus gaining time for decision-making. However, VSS and, in general, the care for victims of violence pose special challenges to physicians.

Histone deacetylase 1 controls cardiomyocyte proliferation during embryonic heart development and cardiac regeneration in zebrafish.

In contrast to mammals, the zebrafish maintains its cardiomyocyte proliferation capacity throughout adulthood. However, neither the molecular mechanisms that orchestrate the proliferation of cardiomyocytes during developmental heart growth nor in the context of regeneration in the adult are sufficiently defined yet. We identified in a forward genetic N-ethyl-N-nitrosourea (ENU) mutagenesis screen the recessive, embryonic-lethal zebrafish mutant baldrian (bal), which shows severely impaired developmental heart growth due to diminished cardiomyocyte proliferation.

Long-Chain Acyl-Carnitines Interfere with Mitochondrial ATP Production Leading to Cardiac Dysfunction in Zebrafish.

In the human heart, the energy supplied by the production of ATP is predominately accomplished by ß-oxidation in mitochondria, using fatty acids (FAs) as the primary fuel. Long-chain acylcarnitines (LCACs) are intermediate forms of FA transport that are essential for FA delivery from the cytosol into mitochondria. Here, we analyzed the impact of the LCACs C18 and C18:1 on mitochondrial function and, subsequently, on heart functionality in the in vivo vertebrate model system of zebrafish ().

Phospho-Site Mutations in Transcription Factor Suppressor of Hairless Impact Notch Signaling Activity During Hematopoiesis in .

The highly conserved Notch signaling pathway controls a multitude of developmental processes including hematopoiesis. Here, we provide evidence for a novel mechanism of tissue-specific Notch regulation involving phosphorylation of CSL transcription factors within the DNA-binding domain. Earlier we found that a phospho-mimetic mutation of the CSL ortholog Suppressor of Hairless [Su(H)] at Ser impedes DNA-binding.

Spen deficiency interferes with Connexin 43 expression and leads to heart failure in zebrafish.

Genome-wide association studies identified Spen as a putative modifier of cardiac function, however, the precise function of Spen in the cardiovascular system is not known yet. Here, we analyzed for the first time the in vivo role of Spen in zebrafish and found that targeted Spen inactivation led to progressive impairment of cardiac function in the zebrafish embryo. In addition to diminished cardiac contractile force, Spen-deficient zebrafish embryos developed bradycardia, atrioventricular block and heart chamber fibrillation.

An RBPJ- Model Reveals Dependence of RBPJ Protein Stability on the Formation of Transcription-Regulator Complexes.

Notch signaling activity governs widespread cellular differentiation in higher animals, including humans, and is involved in several congenital diseases and different forms of cancer. Notch signals are mediated by the transcriptional regulator RBPJ in a complex with activated Notch (NICD). Analysis of Notch pathway regulation in humans is hampered by a partial redundancy of the four Notch receptor copies, yet RBPJ is solitary, allowing its study in model systems.

Characterisation of Victims Of Violence in the A & E Department and Analysis of the Acceptance of a Medico-Legal Expertise Centre After its Implementation vs. Multi-Year Consolidation.

Background: People who have become victims of domestic or public violence often suffer long-term physical, psychological and social impairment. Due to physical injury, the first contact with the health care system is frequently an A & E Department. Thus, physicians and especially surgeons play a key role in detecting victims of domestic or public violence.

["Because we feel, we have to do something" - Barriers in the prevention of violence and key areas requiring action : A qualitative interview study with professional nurses and managers in the field of elderly care].

Background: In recent years, politics and society have shown an increasing interest in the prevention of violence. Despite the scientific studies and prevention programs that have been conducted over the past few years, there is no indication that the prevalence of violence in elderly care is falling. A high number of unreported cases may still be assumed.

[Dealing with victims of domestic violence. Suggestions for daily practice].

The recognition of victims of violence and their treatment in medical facilities is a subject which has been covered for several years in a number of ways. In medicine and in other disciplines, the focus of research, publication, and practical work has been on the quality of care provided. Guidelines for the treatment of victims of violence have been developed and needs have been assessed.

Pulmonary and coronary foreign particle embolism after central venous injection of liquid nutrition.

A man was found dead in his nursing bed. The responsible assistant nurse explained that she had administered liquid nutrition (Isosource Energy Fibre 500 ml) via perfusion pump into the Hickman catheter, insisting that the Hickman catheter was a percutaneous endoscopic gastric tube. Autopsy findings were unspecific and could not reveal the cause of death.

Persistence of biological traces at inside parts of a firearm from a case of multiple familial homicide.

Backspatter from wounds caused by contact shots against a biological target had before been shown to be propelled into firearms' barrels where they can persist and be retrieved from as relevant forensic evidence. Herein, that insight was applied to the investigation of a case of multiple familial homicide with a firearm. Samples of backspatter were collected from the firearm using DNA-free swabs.

Quality improvement of fingerprints of decayed corpses by local thanatopractical processing (Thanatoprint).

Thanatopractical processing allows morphological reconstruction of even advanced decayed bodies. By extracting fluids from the body's tissue antemortem tenseness and volume can be restored. If bodies are partly subject to thanatopractical processing in the hand region ("Thanatoprint"), fingerprints of high quality can be gathered even in cases of advanced decay.

Accidental mechanical asphyxia of children in Germany between 2000 and 2008.

Accidents constitute one of the greatest risks to children, yet there are few medical reports that discuss the subject of accidental asphyxia. However, a systematic analysis of all documented cases in Germany over the years 2000-2008 has now been conducted, aiming at identifying patterns of accidental asphyxia, deducing findings, defining avoidance measures and recommending ways of increasing product safety and taking possible precautions. The analysis is based on a detailed retrospective analysis of all 91 relevant autopsy reports from 24 different German forensic institutes.

[Examination of live victims of violent crimes at the Institutes of Legal Medicine of Hanover, Cologne and Leipzig].

During the last few years the importance of clinical forensic medicine has increased within the field itself, but also in interdisciplinary cooperation. Although examinations of live victims play a substantial role in the every-day work of most German forensic scientists, the number of data published on their frequency and the type of offence for which they were performed is small. For this reason a comparison of the data from the Institutes of Legal Medicine in Hanover, Cologne and Leipzig was carried out.