A Single-Cell Atlas of Porcine Skeletal Muscle Reveals Mechanisms That Regulate Intramuscular Adipogenesis.

Porcine skeletal muscle development is closely linked to meat production efficiency and quality. The accumulation of porcine intramuscular fat is influenced by the hyperplasia and hypertrophy of adipocytes within the muscle. However, the cellular profiles corresponding to the two stages of muscle development remain undetermined.

Interferon signalling and non-canonical inflammasome activation promote host protection against multidrug-resistant Acinetobacter baumannii.

Multidrug-resistant (MDR) Acinetobacter baumannii are of major concern worldwide due to their resistance to last resort carbapenem and polymyxin antibiotics. To develop an effective treatment strategy, it is critical to better understand how an A. baumannii MDR bacterium interacts with its mammalian host.

Epigenetic modulation via the C-terminal tail of H2A.Z.

H2A.Z-nucleosomes are present in both euchromatin and heterochromatin and it has proven difficult to interpret their disparate roles in the context of their stability features. Using an in situ assay of nucleosome stability and DT40 cells expressing engineered forms of the histone variant we show that native H2A.

Recommendations for defining disturbed flow as laminar, transitional, or turbulent in assays of hemostasis and thrombosis: communication from the ISTH SSC Subcommittee on Biorheology.

Blood flow is vital to life, yet disturbed flow has been linked to atherosclerosis, thrombosis, and endothelial dysfunction. The commonly used hemodynamic descriptor "disturbed flow" found in disease and medical devices is not clearly defined in many studies. However, the specific flow regime-laminar, transitional, or turbulent-can have very different effects on hemostasis, thrombosis, and vascular health.

Whole exome sequencing in patients with childhood-onset systemic lupus erythematosus: Results from a Croatian national study.

The purpose of this study was to identify new and low-frequency gene variants using whole exome sequencing (WES) in patients with childhood-onset systemic lupus erythematosus (cSLE), that may be involved in the pathogenesis of SLE. We performed WES on selected 17 trios (in some cases including other informative family members) in which the proband presented with severe, atypical clinical features, resistance to conventional therapy, a family pattern of occurrence and/or syndromic characteristics. After performing WES and analysis of gene variants, 17 novel and/or low-frequency variants were identified in 7 patients.

Exploring the Utility of Cell-Penetrating Peptides as Vehicles for the Delivery of Distinct Antimalarial Drug Cargoes.

The devastating impact of malaria includes significant mortality and illness worldwide. Increasing resistance of the causative parasite, Plasmodium, to existing antimalarial drugs underscores a need for additional compounds with distinct modes of action in the therapeutic development pipeline. Here we showcase peptide-drug conjugates (PDCs) as an attractive compound class, in which therapeutic or lead antimalarials are chemically conjugated to cell-penetrating peptides.

SRSF6 modulates histone-chaperone HIRA splicing to orchestrate AR and E2F activity in prostate cancer.

Despite novel therapeutic strategies, advanced-stage prostate cancer (PCa) remains highly lethal, pointing out the urgent need for effective therapeutic strategies. While dysregulation of the splicing process is considered a cancer hallmark, the role of certain splicing factors remains unknown in PCa. This study focuses on characterizing the levels and role of SRSF6 in this disease.

Molecular mechanisms of emerging inflammasome complexes and their activation and signaling in inflammation and pyroptosis.

Inflammasomes are multi-protein complexes that assemble within the cytoplasm of mammalian cells in response to pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), driving the secretion of the pro-inflammatory cytokines IL-1β and IL-18, and pyroptosis. The best-characterized inflammasome complexes are the NLRP3, NAIP-NLRC4, NLRP1, AIM2, and Pyrin canonical caspase-1-containing inflammasomes, and the caspase-11 non-canonical inflammasome. Newer inflammasome sensor proteins have been identified, including NLRP6, NLRP7, NLRP9, NLRP10, NLRP11, NLRP12, CARD8, and MxA.

Protocol for the processing, cryopreservation, and biobanking of patient-derived cells and tissues.

Biobanking of patient-derived specimens offers unique opportunities for retrospective testing that could potentially contribute to diagnosing and evaluating clinical conditions, advancing personalized medicine and translational biomedical discovery. In this protocol, we detail the collection, processing, and cryopreservation of peripheral blood, bone marrow, and lymph nodes from patients with hematological malignancies. This protocol can be used for multiomics to gain cellular and molecular insights into blood cancers and to test the therapeutic potential of compounds for translational biomedical research.

SETD1B mutations confer apoptosis resistance and BCL2 independence in B cell lymphoma.

The translocation t(14;18) activates BCL2 and is considered the initiating genetic lesion in most follicular lymphomas (FL). Surprisingly, FL patients fail to respond to the BCL2 inhibitor, Venetoclax. We show that mutations and deletions affecting the histone lysine methyltransferase SETD1B (KMT2G) occur in 7% of FLs and 16% of diffuse large B cell lymphomas (DLBCL).

Vision loss and diabetic retinopathy prevalence and risk among a cohort of Indigenous and non-Indigenous Australians with type 2 diabetes receiving renal haemodialysis treatment: The retinopathy in people currently on renal dialysis (RiPCORD) study.

Aims: Diabetic nephropathy, vision loss and diabetic retinopathy (DR) are frequent comorbidities among individuals with type 2 diabetes (T2D). The Retinopathy in People Currently On Renal Dialysis (RiPCORD) study sought to examine the epidemiology and risk of vision impairment (VI) and DR among a cohort of Indigenous and non-Indigenous Australians with T2D currently receiving haemodialysis for end-stage renal failure (ESRF).

Methods: A total of 106 Indigenous and 109 non-Indigenous Australians were recruited in RiPCORD across five haemodialysis centres in urban and remote settings.

Innate immune sensing of cell death in disease and therapeutics.

Innate immunity, cell death and inflammation underpin many aspects of health and disease. Upon sensing pathogens, pathogen-associated molecular patterns or damage-associated molecular patterns, the innate immune system activates lytic, inflammatory cell death, such as pyroptosis and PANoptosis. These genetically defined, regulated cell death pathways not only contribute to the host defence against infectious disease, but also promote pathological manifestations leading to cancer and inflammatory diseases.

Mouse guanylate-binding proteins of the chromosome 3 cluster do not mediate antiviral activity in vitro or in mouse models of infection.

Dynamin-like GTPase proteins, including myxoma (Mx) and guanylate-binding proteins (GBPs), are among the many interferon stimulated genes induced following viral infections. While studies report that human (h)GBPs inhibit different viruses in vitro, few have convincingly demonstrated that mouse (m)GBPs mediate antiviral activity, although mGBP-deficient mice have been used extensively to define their importance in immunity to diverse intracellular bacteria and protozoa. Herein, we demonstrate that individual (overexpression) or collective (knockout (KO) mice) mGBPs of the chromosome 3 cluster (mGBPchr3) do not inhibit replication of five viruses from different virus families in vitro, nor do we observe differences in virus titres recovered from wild type versus mGBPchr3 KO mice after infection with three of these viruses (influenza A virus, herpes simplex virus type 1 or lymphocytic choriomeningitis virus).

Mining human clinical waste as a rich source of stem cells for neural regeneration.

Neural diseases are challenging to treat and are regarded as one of the major causes of disability and morbidity in the world. Stem cells can provide a solution, by offering a mechanism to replace damaged circuitry. However, obtaining sufficient cell sources for neural regeneration remains a significant challenge.

Multifunctional histone variants in genome function.

Histones are integral components of eukaryotic chromatin that have a pivotal role in the organization and function of the genome. The dynamic regulation of chromatin involves the incorporation of histone variants, which can dramatically alter its structural and functional properties. Contrary to an earlier view that limited individual histone variants to specific genomic functions, new insights have revealed that histone variants exert multifaceted roles involving all aspects of genome function, from governing patterns of gene expression at precise genomic loci to participating in genome replication, repair and maintenance.

Enhancing the Intrinsic Antiplasmodial Activity and Improving the Stability and Selectivity of a Tunable Peptide Scaffold Derived from Human Platelet Factor 4.

The control of malaria, a disease caused by parasites that kills over half a million people every year, is threatened by the continual emergence and spread of drug resistance. Therefore, new molecules with different mechanisms of action are needed in the antimalarial drug development pipeline. Peptides developed from host defense molecules are gaining traction as anti-infectives due to theood of inducing drug resistance.

CX-5461 Preferentially Induces Top2α-Dependent DNA Breaks at Ribosomal DNA Loci.

While genotoxic chemotherapeutic agents are among the most effective tools to combat cancer, they are often associated with severe adverse effects caused by indiscriminate DNA damage in non-tumor tissue as well as increased risk of secondary carcinogenesis. This study builds on our previous work demonstrating that the RNA Polymerase I (Pol I) transcription inhibitor CX-5461 elicits a non-canonical DNA damage response and our discovery of a critical role for Topoisomerase 2α (Top2α) in the initiation of Pol I-dependent transcription. Here, we identify Top2α as a mediator of CX-5461 response in the murine Eµ- B lymphoma model whereby sensitivity to CX-5461 is dependent on cellular Top2α expression/activity.

Evaluation of and anticancer activities of potassium koetjapate: a solubility improved formulation of koetjapic acid against human colon cancer.

Background And Purpose: The previous work on koetjapic acid (KA) isolated from showed its efficacy towards colorectal cancer however KA has poor water solubility which poses the biggest hindrance to its efficacy. In the present paper, an attempt was made to study the anti-colon cancer efficacy of KA's potassium salt . potassium koetjapate (KKA) applying and methods.

Mastering Death: The Roles of Viral Bcl-2 in dsDNA Viruses.

Proteins of the Bcl-2 family regulate cellular fate via multiple mechanisms including apoptosis, autophagy, senescence, metabolism, inflammation, redox homeostasis, and calcium flux. There are several regulated cell death (RCD) pathways, including apoptosis and autophagy, that use distinct molecular mechanisms to elicit the death response. However, the same proteins/genes may be deployed in multiple biochemical pathways.

NCF4 attenuates colorectal cancer progression by modulating inflammasome activation and immune surveillance.

The spatiotemporal regulation of inflammasome activation remains unclear. To examine the mechanism underlying the assembly and regulation of the inflammasome response, here we perform an immunoprecipitation-mass spectrometry analysis of apoptosis-associated speck-like protein containing a CARD (ASC) and identify NCF4/1/2 as ASC-binding proteins. Reduced NCF4 expression is associated with colorectal cancer development and decreased five-year survival rate in patients with colorectal cancer.