A single-cell strategy for the identification of intronic variants related to mis-splicing in pancreatic cancer.

Most clinical diagnostic and genomic research setups focus almost exclusively on coding regions and essential splice sites, thereby overlooking other non-coding variants. As a result, intronic variants that can promote mis-splicing events across a range of diseases, including cancer, are yet to be systematically investigated. Such investigations would require both genomic and transcriptomic data, but there currently exist very few datasets that satisfy these requirements.

Boswellic acid formulations are not suitable for treatment of pediatric high-grade glioma due to tumor promoting potential.

Background And Aim: Pediatric high-grade gliomas (pedHGG) comprise a very poor prognosis. Thus, parents of affected children are increasingly resorting to complementary and alternative medicine (CAM), among those Boswellia extracts. However, nothing is known about the therapeutic effectiveness of their active substances, Boswellic acids (BA) in pedHGG.

Prdm12 represses the expression of the visceral neuron determinants Phox2a/b in developing somatosensory ganglia.

Prdm12 is a transcriptional regulator essential for the emergence of the somatic nociceptive lineage during sensory neurogenesis. The exact mechanisms by which Prdm12 promotes nociceptor development remain, however, poorly understood. Here, we report that the trigeminal and dorsal root ganglia hypoplasia induced by the loss of involves Bax-dependent apoptosis and that it is accompanied by the ectopic expression of the visceral sensory neuron determinants and , which is, however, not sufficient to impose a complete fate switch in surviving somatosensory neurons.

Single-cell transcriptomics reveal extracellular vesicles secretion with a cardiomyocyte proteostasis signature during pathological remodeling.

Aberrant Wnt activation has been reported in failing cardiomyocytes. Here we present single cell transcriptome profiling of hearts with inducible cardiomyocyte-specific Wnt activation (β-cat) as well as with compensatory and failing hypertrophic remodeling. We show that functional enrichment analysis points to an involvement of extracellular vesicles (EVs) related processes in hearts of β-cat mice.

A novel single-cell RNA-sequencing approach and its applicability connecting genotype to phenotype in ageing disease.

Single cell multi-omics analysis has the potential to yield a comprehensive understanding of the cellular events that underlie the basis of human diseases. The cardinal feature to access this information is the technology used for single-cell isolation, barcoding, and sequencing. Most currently used single-cell RNA-sequencing platforms have limitations in several areas including cell selection, documentation and library chemistry.

Prdm12 modulates pain-related behavior by remodeling gene expression in mature nociceptors.

Prdm12 is a conserved epigenetic transcriptional regulator that displays restricted expression in nociceptors of the developing peripheral nervous system. In mice, Prdm12 is required for the development of the entire nociceptive lineage. In humans, PRDM12 mutations cause congenital insensitivity to pain, likely because of the loss of nociceptors.

WNT11/ROR2 signaling is associated with tumor invasion and poor survival in breast cancer.

Background: Breast cancer has been associated with activation of the WNT signaling pathway, although no driver mutations in WNT genes have been found yet. Instead, a high expression of the alternative WNT receptor ROR2 was observed, in particular in breast cancer brain metastases. However, its respective ligand and downstream signaling in this context remained unknown.

Biallelic variants in YRDC cause a developmental disorder with progeroid features.

The highly conserved YrdC domain-containing protein (YRDC) interacts with the well-described KEOPS complex, regulating specific tRNA modifications to ensure accurate protein synthesis. Previous studies have linked the KEOPS complex to a role in promoting telomere maintenance and controlling genome integrity. Here, we report on a newborn with a severe neonatal progeroid phenotype including generalized loss of subcutaneous fat, microcephaly, growth retardation, wrinkled skin, renal failure, and premature death at the age of 12 days.

CHARGE syndrome and related disorders: a mechanistic link.

CHARGE syndrome is an autosomal dominant malformation disorder caused by pathogenic variants in the chromatin remodeler CHD7. Affected are craniofacial structures, cranial nerves and multiple organ systems. Depending on the combination of malformations present, its distinction from other congenital disorders can be challenging.

The folate antagonist methotrexate diminishes replication of the coronavirus SARS-CoV-2 and enhances the antiviral efficacy of remdesivir in cell culture models.

The search for successful therapies of infections with the coronavirus SARS-CoV-2 is ongoing. We tested inhibition of host cell nucleotide synthesis as a promising strategy to decrease the replication of SARS-CoV-2-RNA, thus diminishing the formation of virus progeny. Methotrexate (MTX) is an established drug for cancer therapy and to induce immunosuppression.

Transcriptome Analysis of Hypoxic Lymphatic Endothelial Cells Indicates Their Potential to Contribute to Extracellular Matrix Rearrangement.

Lymphedema (LE) affects millions of people worldwide. It is a chronic progressive disease with massive development of fibrosclerosis when untreated. There is no pharmacological treatment of lymphedema.

Impact of myocardial fibrosis on left ventricular remodelling, recovery, and outcome after transcatheter aortic valve implantation in different haemodynamic subtypes of severe aortic stenosis.

Aims: Myocardial fibrosis (MF) might represent a key player in pathophysiology of heart failure in aortic stenosis (AS). We aimed to assess its impact on left ventricular (LV) remodelling, recovery, and mortality after transcatheter aortic valve implantation (TAVI) in different AS subtypes.

Methods And Results: One hundred patients with severe AS were prospectively characterized clinically and echocardiographically at baseline (BL), 6 months, 1 year, and 2 years following TAVI.

Reconstruction of Different Modes of WNT Dependent Protein Networks from Time Series Protein Quantification.

Protein signaling networks are crucial cornerstones in cellular responses. Deregulation causes various diseases, including cancer. One pathway that is frequently deregulated in cancer is the WNT signaling pathway.

Comparative proteomics reveals a diagnostic signature for pulmonary head-and-neck cancer metastasis.

Patients with head-and-neck cancer can develop both lung metastasis and primary lung cancer during the course of their disease. Despite the clinical importance of discrimination, reliable diagnostic biomarkers are still lacking. Here, we have characterised a cohort of squamous cell lung (SQCLC) and head-and-neck (HNSCC) carcinomas by quantitative proteomics.

Modelling of Spray Flames with Doubly Conditional Moment Closure.

Simulations of a pilot-stabilised flame in a uniformly dispersed ethanol spray are performed using a Doubly Conditional Moment Closure (DCMC) model. The DCMC equation for spray combustion is derived, using the mixture fraction and the reaction progress variable as conditioning variables, including droplet evaporation and differential diffusion terms. A set of closure sub-models is suggested to allow for a first, preliminary application of the DCMC model to the test case presented here.

Plant-soil feedbacks: a comparative study on the relative importance of soil feedbacks in the greenhouse versus the field.

Interactions between plants and soil microorganisms influence individual plant performance and thus plant-community composition. Most studies on such plant-soil feedbacks (PSFs) have been performed under controlled greenhouse conditions, whereas no study has directly compared PSFs under greenhouse and natural field conditions. We grew three grass species that differ in local abundance in grassland communities simultaneously in the greenhouse and field on field-collected soils either previously conditioned by these species or by the general grassland community.

Topological insulators in magnetic fields: quantum Hall effect and edge channels with a nonquantized θ term.

We investigate how a magnetic field induces one-dimensional edge channels when the two-dimensional surface states of three-dimensional topological insulators become gapped. The Hall effect, measured by contacting those channels, remains quantized even in situations where the θ term in the bulk and the associated surface Hall conductivities, σ(xy)(S), are not quantized due to the breaking of time-reversal symmetry. The quantization arises as the θ term changes by ±2πn along a loop around n edge channels.

Emergent Lorentz symmetry with vanishing velocity in a critical two-subband quantum wire.

We consider a quantum wire with two subbands of spin-polarized electrons in the presence of strong interactions. We focus on the quantum phase transition when the second subband starts to get filled as a function of gate voltage. Performing a one-loop renormalization group analysis of the effective Hamiltonian, we identify the critical fixed-point theory as a conformal field theory having an enhanced SU(2) symmetry and central charge 3/2.