Grazing sheep on pastures with tansy ragwort ( L.) - results of a two-year study on ingested pyrrolizidine alkaloids and transfer into animal organs.

Tansy ragwort ( L.) growing in animal pasture may pose a risk to humans due to the potential transfer of pyrrolizidine alkaloids (PAs) into food of animal origin. Here, we investigated what amount of PAs corresponds to the amount of ragwort consumed by sheep on a pasture and whether the ingested PAs are transferred into edible tissue.

The unique functions of Runx1 in skeletal muscle maintenance and regeneration are facilitated by an ETS interaction domain.

The conserved Runt-related (RUNX) transcription factor family are master regulators of developmental and regenerative processes. Runx1 and Runx2 are expressed in satellite cells (SCs) and in skeletal myotubes. Here, we examined the role of Runx1 in mouse satellite cells to determine the role of Runx1 during muscle differentiation.

Knock-Out of IKKepsilon Ameliorates Atherosclerosis and Fatty Liver Disease by Alterations of Lipid Metabolism in the PCSK9 Model in Mice.

The inhibitor-kappaB kinase epsilon (IKKε) represents a non-canonical IκB kinase that modulates NF-κB activity and interferon I responses. Inhibition of this pathway has been linked with atherosclerosis and metabolic dysfunction-associated steatotic liver disease (MASLD), yet the results are contradictory. In this study, we employed a combined model of hepatic PCSK9 overexpression and a high-fat diet for 16 weeks to induce atherosclerosis and liver steatosis.

Sulfonylureas exert antidiabetic action on adipocytes by inhibition of PPARγ serine 273 phosphorylation.

Objective: Sulfonylureas (SUs) are still among the mostly prescribed antidiabetic drugs with an established mode of action: release of insulin from pancreatic β-cells. In addition, effects of SUs on adipocytes by activation of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) have been described, which might explain their insulin-sensitizing potential observed in patients. However, there is a discrepancy between the impact of SUs on antidiabetic action and their rather moderate in vitro effect on PPARγ transcriptional activity.

Human cytomegalovirus infection coopts chromatin organization to diminish TEAD1 transcription factor activity.

Human cytomegalovirus (HCMV) infects up to 80% of the world's population. Here, we show that HCMV infection leads to widespread changes in human chromatin accessibility and chromatin looping, with hundreds of thousands of genomic regions affected 48 hours after infection. Integrative analyses reveal HCMV-induced perturbation of Hippo signaling through drastic reduction of TEAD1 transcription factor activity.

Shared and distinct interactions of type 1 and type 2 Epstein-Barr Nuclear Antigen 2 with the human genome.

Background: There are two major genetic types of Epstein-Barr Virus (EBV): type 1 (EBV-1) and type 2 (EBV-2). EBV functions by manipulating gene expression in host B cells, using virus-encoded gene regulatory proteins including Epstein-Barr Nuclear Antigen 2 (EBNA2). While type 1 EBNA2 is known to interact with human transcription factors (hTFs) such as RBPJ, EBF1, and SPI1 (PU.

Reduced Nephron Endowment in Six2-TGCtg Mice Is Due to Six3 Misexpression by Aberrant Enhancer-Promoter Interactions in the Transgene.

Key Points: Aberrant enhancer–promoter interactions detected by Hi-C drive ectopic expression of in the Six2TGCtg line. Disruption of in the Six2TGCtg line restores nephron number, implicating SIX3 interference with SIX2 function in nephron progenitor cell renewal.

Background: Lifelong kidney function relies on the complement of nephrons generated during mammalian development from a mesenchymal nephron progenitor cell population.

The unique function of Runx1 in skeletal muscle differentiation and regeneration is mediated by an ETS interaction domain.

The conserved Runt-related (RUNX) transcription factor family are well-known master regulators of developmental and regenerative processes. and are both expressed in satellite cells (SC) and skeletal myotubes. Conditional deletion of in adult SC negatively impacted self-renewal and impaired skeletal muscle maintenance.

Distinct molecular mechanisms contribute to the reduction of melanoma growth and tumor pain after systemic and local depletion of alpha-Synuclein in mice.

Epidemiological studies show a coincidence between Parkinson's disease (PD) and malignant melanoma. It has been suggested that this relationship is due, at least in part, to modulation of alpha-Synuclein (αSyn/Snca). αSyn oligomers accumulate in PD, which triggers typical PD symptoms, and in malignant melanoma, which increases the proliferation of tumor cells.

Reduced nephron endowment in the common mouse line is due to misexpression by aberrant enhancer-promoter interactions in the transgene.

Unlabelled: Lifelong kidney function relies on the complement of nephrons generated during mammalian development from a mesenchymal nephron progenitor cell (NPC) population. Low nephron endowment confers increased susceptibility to chronic kidney disease. We asked whether reduced nephron numbers in the popular transgenic mouse line was due to disruption of a regulatory gene at the integration site or to ectopic expression of a gene(s) contained within the transgene.

Horses' rejection behaviour towards the presence of Senecio jacobaea L. in hay.

Background: Senecio jacobaea contains pyrrolizidine alkaloids that can induce severe hepatic intoxication in horses, either acute when ingested in high amounts or chronic when consumed over a long period. The aim of this study was to determine horses' rejection behaviour towards the presence of Senecio jacobaea in hay when fed ad libitum. We hypothesized that adult horses can sort Senecio jacobaea out of the contaminated hay when hay is fed ad libitum.

Rejection behaviour of horses for hay contaminated with meadow saffron (Colchicum autumnale L.).

Background: Extensively used grasslands are frequently utilised for hay production for equines. Especially, extensive meadows have a great variety of plant species, which may include plants that are poisonous for equines such as meadow saffron (Colchicum autumnale L.).

Runx1 shapes the chromatin landscape via a cascade of direct and indirect targets.

Runt-related transcription factor 1 (Runx1) can act as both an activator and a repressor. Here we show that CRISPR-mediated deletion of Runx1 in mouse metanephric mesenchyme-derived mK4 cells results in large-scale genome-wide changes to chromatin accessibility and gene expression. Open chromatin regions near down-regulated loci enriched for Runx sites in mK4 cells lose chromatin accessibility in Runx1 knockout cells, despite remaining Runx2-bound.

[Prevalence of hypophosphatasia in adult patients in rheumatology].

Background: Hypophosphatasia (HPP) is a genetic disorder caused by one or more mutations in the alkaline phosphatase (ALP) gene, responsible for encoding tissue-specific ALP and for the mineralization process.

Objective: Identification of the prevalence of HPP in rheumatology patients.

Material And Methods: Medical records of all adult rheumatology patients with pathologically low total ALP levels (<35 U/L) treated in the Department of Rheumatology at the Clinic of Internal Medicine III, University Hospital Bonn between January 2017 and June 2019, were retrospectively examined for clinical signs as well as for results of genetic tests for HPP.

Hypersensitivity in patients receiving metal implants: a scoping review protocol.

Objective: The objective of this scoping review is to gather the available evidence on metal hypersensitivity to determine the extent of the problem and identify gaps in the evidence about screening practices.

Introduction: Hypersensitivity to metal was first reported in 1966. Since this time, the use of metal in prosthetic devices has increased with an associated rise in reported hypersensitivity reaction to other metals.

Metal hypersensitivity screening among frontline healthcare workers-A descriptive study.

Aims And Objectives: The study aims were to (a) assess allergy screening practices, (b) determine the awareness of metal hypersensitivity among frontline healthcare workers and (c) examine perceived barriers to implementing metal hypersensitivity screening into clinical practice.

Background: Adverse device-related events, such as hypersensitivity to metals, are well documented in the literature. Hypersensitivity to metal is a type IV T-cell-mediated reaction that can occur after cardiac, orthopaedic, dental, gynaecological and neurosurgical procedures where a device with metal components is implanted into the body.

When You Can't R.I.O.T., R.I.O.: Tele-assessment for School Psychologists.

The acronym R.I.O.

Notch dimerization and gene dosage are important for normal heart development, intestinal stem cell maintenance, and splenic marginal zone B-cell homeostasis during mite infestation.

Cooperative DNA binding is a key feature of transcriptional regulation. Here we examined the role of cooperativity in Notch signaling by CRISPR-mediated engineering of mice in which neither Notch1 nor Notch2 can homo- or heterodimerize, essential for cooperative binding to sequence-paired sites (SPS) located near many Notch-regulated genes. Although most known Notch-dependent phenotypes were unaffected in Notch1/2 dimer-deficient mice, a subset of tissues proved highly sensitive to loss of cooperativity.

Laboratory Limitations of Excluding Hereditary Protein C Deficiency by Chromogenic Assay: Discrepancies of Phenotype and Genotype.

Protein C (PC) deficiency is associated with an increased risk for venous thromboembolism (VTE). In daily practice, exclusion of a hereditary PC deficiency is often based on a single determination of PC activity, by either clotting time-based or mostly chromogenic assay. However, diagnosis of hereditary PC deficiency is challenging due to several laboratory and clinical limitations.

Enhancer architecture sensitizes cell specific responses to gene dose via a bind and discard mechanism.

Notch pathway haploinsufficiency can cause severe developmental syndromes with highly variable penetrance. Currently, we have a limited mechanistic understanding of phenotype variability due to gene dosage. Here, we unexpectedly found that inserting an enhancer containing pioneer transcription factor sites coupled to Notch dimer sites can induce a subset of haploinsufficiency phenotypes in with wild type gene dose.

Engaging Patients in Primary Care Quality Improvement Initiatives: Facilitators and Barriers.

Health care transformation calls for patient engagement in quality improvement (PEQI), yet practice participation remains low. This pilot study of 8 primary care clinics at 7 statewide locations sought to determine the most effective strategies for disseminating a previously successful single-system PEQI intervention. Qualitative data were obtained through site visits, interviews, observations, and journaling.

The effect of α-and δ-tocopherol-lipoic acid ester co-drugs on the response of the rabbit bladder to in vitro ischemia/reperfusion.

Objective: Obstructive bladder dysfunction (OBD) caused by benign prostatic hyperplasia is a common medical problem in ageing men. As the prostate enlarges and compresses the urethra, the bladder wall thickness and the bladder is termed "compensated" because its function is still relatively normal. Subsequently, bladder function begins to fail and this change is termed "decompensation.