The impact of MAFLD on coronary plaque characteristics and physiologic status: a coronary CT angiography study.

Rationale And Objectives: Metabolic dysfunction-associated fatty liver disease (MAFLD) is linked to an increased risk of cardiovascular events. Our study sought to determine the impact of MAFLD on both the anatomy and function of coronary plaques.

Materials And Methods: A total of 203 participants (including 728 plaques) with suspected coronary artery disease (CAD) who underwent coronary CT angiography (CCTA) and abdominal ultrasound were prospectively enrolled.

Crosstalk Between Metabolism and Immune Activity Reveals Four Subtypes With Therapeutic Implications in Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma (ccRCC) is characterized by metabolic dysregulation and distinct immunological signatures. The interplay between metabolic and immune processes in the tumor microenvironment (TME) causes the complexity and heterogeneity of immunotherapy responses observed during ccRCC treatment. Herein, we initially identified two distinct metabolic subtypes (C1 and C2 subtypes) and immune subtypes (I1 and I2 subtypes) based on the occurrence of differentially expressed metabolism-related prognostic genes and immune-related components.

Ras1 and Ras2 play antagonistic roles in regulating cellular cAMP level, stationary-phase entry and stress response in Candida albicans.

The GTPase Ras1 activates the yeast-to-hypha transition in Candida albicans by activating cAMP synthesis. Here, we have characterized Ras2. Ras2 belongs to a group of atypical Ras proteins in some fungal species that share poor identity with other Ras GTPases with many variations in conserved motifs thought to be crucial for Ras-associated activities.

Phosphorylation of Rga2, a Cdc42 GAP, by CDK/Hgc1 is crucial for Candida albicans hyphal growth.

Cyclin-dependent kinases (CDKs) control yeast morphogenesis, although how they regulate the polarity machinery remains unclear. The dimorphic fungus Candida albicans uses Cdc28/Hgc1, a CDK/cyclin complex, to promote persistent actin polarization for hyphal growth. Here, we report that Rga2, a GTPase-activating protein (GAP) of the central polarity regulator Cdc42, undergoes Hgc1-dependent hyperphosphorylation.

Candida albicans hyphal morphogenesis occurs in Sec3p-independent and Sec3p-dependent phases separated by septin ring formation.

The growing tips of Candida albicans hyphae are sites of polarized exocytosis. Mammalian septins have been implicated in regulating exocytosis and C. albicans septins are known to localize at hyphal tips, although their function here is unknown.

Critical role of DNA checkpoints in mediating genotoxic-stress-induced filamentous growth in Candida albicans.

The polymorphic fungus Candida albicans switches from yeast to filamentous growth in response to a range of genotoxic insults, including inhibition of DNA synthesis by hydroxyurea (HU) or aphidicolin (AC), depletion of the ribonucleotide-reductase subunit Rnr2p, and DNA damage induced by methylmethane sulfonate (MMS) or UV light (UV). Deleting RAD53, which encodes a downstream effector kinase for both the DNA-replication and DNA-damage checkpoint pathways, completely abolished the filamentous growth caused by all the genotoxins tested. Deleting RAD9, which encodes a signal transducer of the DNA-damage checkpoint, specifically blocked the filamentous growth induced by MMS or UV but not that induced by HU or AC.

The F-box protein Grr1 regulates the stability of Ccn1, Cln3 and Hof1 and cell morphogenesis in Candida albicans.

Both G1 and mitotic cyclins have been implicated in regulating Candida albicans filamentous growth. We have investigated the functions of Grr1 whose orthologue in Saccharomyces cerevisiae is known to mediate ubiquitin-dependent degradation of the G1 cyclins Cln1 and Cln2. Here, we report that deleting C.

The formin family protein CaBni1p has a role in cell polarity control during both yeast and hyphal growth in Candida albicans.

Formins are conserved eukaryotic proteins playing key roles in regulating cell polarity. We have characterized the roles of a formin CaBni1p in the polymorphic fungus Candida albicans. CaBni1p localized persistently to hyphal tips during hyphal growth but to distinct growth sites at different cell cycle stages during yeast growth.

CaSPA2 is important for polarity establishment and maintenance in Candida albicans.

Saccharomyces cerevisiae Spa2p is a component of polarisome that controls cell polarity. Here, we have characterized the role of its homologue, CaSpa2p, in the polarized growth in Candida albicans. During yeast growth, GFP-tagged CaSpa2p localized to distinct growth sites in a cell cycle-dependent manner, while during hyphal growth it persistently localized to hyphal tips throughout the cell cycle.

Characterization and functional analysis of the siderophore-iron transporter CaArn1p in Candida albicans.

Siderophores are small organic compounds with high affinity for ferric iron. Microorganisms commonly acquire iron via siderophore secretion and uptake. Here we report the characterization of the siderophore transporter CaArn1p in the fungal pathogen Candida albicans.