The ERBB2 c.1795C>T, p.Arg599Cys variant is associated with left ventricular outflow tract obstruction defects in humans.

Non-syndromic congenital heart defects (CHDs) are occasionally familial and left ventricular outflow tract obstruction (LVOTO) defects are among the subtypes with the highest hereditability. The aim of this study was to evaluate the pathogenicity of a heterozygous ERBB2 variant c.1795C>T, p.

Novel heterozygous SPI1c.538C>T p.(Leu180Phe) variant causes PU.1 haploinsufficiency leading to agammaglobulinemia.

PU.1 is an Ets family transcription factor crucial for hematopoietic cell fate. Complete PU.

Nuclear Factor I Family Members are Key Transcription Factors Regulating Gene Expression.

The Nuclear Factor I (NFI) family of transcription factors (TFs) plays key roles in cellular differentiation, proliferation, and homeostasis. As such, NFI family members engage in a large number of interactions with other proteins and chromatin. However, despite their well-established significance, the NFIs' interactomes, their dynamics, and their functions have not been comprehensively examined.

Tensin-2 interactomics reveals interaction with GAPDH and a phosphorylation-mediated regulatory role in glycolysis.

Integrin adaptor proteins, like tensin-2, are crucial for cell adhesion and signaling. However, the function of tensin-2 beyond localizing to focal adhesions remain poorly understood. We utilized proximity-dependent biotinylation and Strep-tag affinity proteomics to identify interaction partners of tensin-2 in Flp-In 293 T-REx cells.

Disruption of KLHL6 Fuels Oncogenic Antigen Receptor Signaling in B-Cell Lymphoma.

Pathomechanisms that activate oncogenic B-cell receptor (BCR) signaling in diffuse large B-cell lymphoma (DLBCL) are largely unknown. Kelch-like family member 6 (KLHL6) encoding a substrate-adapter for Cullin-3-RING E3 ubiquitin ligase with poorly established targets is recurrently mutated in DLBCL. By applying high-throughput protein interactome screens and functional characterization, we discovered that KLHL6 regulates BCR by targeting its signaling subunits CD79A and CD79B.

Distinct functions for the paralogous RBM41 and U11/U12-65K proteins in the minor spliceosome.

Here, we identify RBM41 as a novel unique protein component of the minor spliceosome. RBM41 has no previously recognized cellular function but has been identified as a paralog of U11/U12-65K, a known unique component of the U11/U12 di-snRNP. Both proteins use their highly similar C-terminal RRMs to bind to 3'-terminal stem-loops in U12 and U6atac snRNAs with comparable affinity.

IUPHAR ECR review: Cancer-related anorexia-cachexia in cancer patients: Pathophysiology and treatment.

Cancer-related anorexia-cachexia (CRAC) comprises one of the most common syndromes of advanced cancer patients. The prevalence of CRAC increases from 50% to 80% before death. CRAC is associated not only with impaired quality of life in patients and family members but also with shorter survival.

Mirtazapine versus megestrol acetate in treatment of anorexia-cachexia in advanced cancer patients: a randomized, double-blind trial.

Objective: Cancer-related anorexia-cachexia comprises one of the most common syndromes of advanced cancer patients. The management of cancer-related anorexia-cachexia is a great challenge in clinical practice. There are no definite practice guidelines yet for the prevention and treatment of cancer-related anorexia-cachexia.

Interaction network of human early embryonic transcription factors.

Embryonic genome activation (EGA) occurs during preimplantation development and is characterized by the initiation of de novo transcription from the embryonic genome. Despite its importance, the regulation of EGA and the transcription factors involved in this process are poorly understood. Paired-like homeobox (PRDL) family proteins are implicated as potential transcriptional regulators of EGA, yet the PRDL-mediated gene regulatory networks remain uncharacterized.

CMGC Kinases in Health and Cancer.

CMGC kinases, encompassing cyclin-dependent kinases (CDKs), mitogen-activated protein kinases (MAPKs), glycogen synthase kinases (GSKs), and CDC-like kinases (CLKs), play pivotal roles in cellular signaling pathways, including cell cycle regulation, proliferation, differentiation, apoptosis, and gene expression regulation. The dysregulation and aberrant activation of these kinases have been implicated in cancer development and progression, making them attractive therapeutic targets. In recent years, kinase inhibitors targeting CMGC kinases, such as CDK4/6 inhibitors and BRAF/MEK inhibitors, have demonstrated clinical success in treating specific cancer types.

Biallelic NFATC1 mutations cause an inborn error of immunity with impaired CD8+ T-cell function and perturbed glycolysis.

The nuclear factor of activated T cells (NFAT) family of transcription factors plays central roles in adaptive immunity in murine models; however, their contribution to human immune homeostasis remains poorly defined. In a multigenerational pedigree, we identified 3 patients who carry germ line biallelic missense variants in NFATC1, presenting with recurrent infections, hypogammaglobulinemia, and decreased antibody responses. The compound heterozygous NFATC1 variants identified in these patients caused decreased stability and reduced the binding of DNA and interacting proteins.

Construction of Fusion Protein for Enhanced Small RNA Loading to Extracellular Vesicles.

Extracellular vesicles (EVs) naturally carry cargo from producer cells, such as RNA and protein, and can transfer these messengers to other cells and tissue. This ability provides an interesting opportunity for using EVs as delivery vehicles for therapeutic agents, such as for gene therapy. However, endogenous loading of cargo, such as microRNAs (miRNAs), is not very efficient as the copy number of miRNAs per EV is quite low.

Heterozygous premature termination in zinc-finger domain of Krüppel-like factor 2 gene associates with dysregulated immunity.

Krüppel-like factor 2 (KLF2) is a transcription factor with significant roles in development, maturation, differentiation, and proliferation of several cell types. In immune cells, KLF2 regulates maturation and trafficking of lymphocytes and monocytes. KLF2 participates in regulation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway.

Physical and functional interactome atlas of human receptor tyrosine kinases.

Much cell-to-cell communication is facilitated by cell surface receptor tyrosine kinases (RTKs). These proteins phosphorylate their downstream cytoplasmic substrates in response to stimuli such as growth factors. Despite their central roles, the functions of many RTKs are still poorly understood.

Sustainable Biocomposites from Recycled Bale Wrap Plastic and Agave Fiber: Processing and Property Evaluation.

Plastic recycling to make sustainable materials is considered one of the biggest initiatives toward a greener environment and socioeconomic development. This research aims to investigate the properties of a blend of recycled bale wrap linear low-density polyethylene (rLLDPE) and polypropylene (PP) (rLLDPE/PP 50:50 wt % matrix), which was further reinforced with 25 wt % agave fiber prepared by injection-molding. Different ratios of a combined industrial compatibilizer (maleic anhydride-grafted PP/PE) were used (1-3 wt %), which were compared with a synthesized compatibilizer made from maleic anhydride-PP/rLLDPE in terms of mechanical and thermomechanical properties of the biocomposites.

Epigenetic alterations in mesenchymal stem cells by osteosarcoma-derived extracellular vesicles.

Extracellular vesicles (EVs) are central to intercellular communication and play an important role in cancer progression and development. Osteosarcoma (OS) is an aggressive bone tumour, characterized by the presence of malignant mesenchymal cells. The specific tumour-driving genetic alterations that are associated with OS development are currently poorly understood.