Role of the Anaphase-Promoting Complex Activator Cdh1 in the Virulence of .

is a globally distributed human fungal pathogen that can cause cryptococcal meningitis with high morbidity and mortality. In this study, we identified an anaphase-promoting complex (APC) activator, Cdh1, and examined its impact on the virulence of . Our subcellular localization analysis revealed that Cdh1 is situated in the nucleus of .

Roles of Different Signaling Pathways in Virulence.

is a widespread fungal pathogen that can infect the human central nervous system (CNS) and cause fungal meningitis, leading to hundreds of thousands of deaths worldwide each year. Previous studies have demonstrated that many signal transduction pathways are crucial for the morphological development and virulence of . In this review, data from over 116 research articles have been compiled to show that many signaling pathways control various characteristics of , individually or in association with other pathways, and to establish strong links among them to better understand pathogenesis.

Mechanisms and Virulence Factors of Dissemination to the Central Nervous System.

Cryptococcosis is a prevalent fungal infection of the central nervous system (CNS) caused by , a yeast with a polysaccharide capsule in the basidiomycete group. Normally, infects the respiratory tract and then breaches the blood-brain barrier (BBB), leading to meningitis or meningoencephalitis, which leads to hundreds of thousands of deaths each year. Although the mechanism by which infiltrates the BBB to invade the brain has yet to be fully understood, research has revealed that can cross the BBB using transcellular penetration, paracellular traversal, and infected phagocytes (the "Trojan horse" mechanism).

Interplay between acetylation and ubiquitination of imitation switch chromatin remodeler Isw1 confers multidrug resistance in .

poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for and multidrug resistance in . Cells with the disrupted gene exhibited profound resistance to multiple antifungal drugs.

Ubiquitin Degradation of the AICAR Transformylase/IMP Cyclohydrolase Ade16 Regulates the Sexual Reproduction of .

F-box protein is a key protein of the SCF E3 ubiquitin ligase complex, responsible for substrate recognition and degradation through specific interactions. Previous studies have shown that F-box proteins play crucial roles in sexual reproduction. However, the molecular mechanism by which F-box proteins regulate sexual reproduction in is unclear.

Antifungal therapy: Novel drug delivery strategies driven by new targets.

In patients with compromised immunity, invasive fungal infections represent a significant cause of mortality. Given the limited availability and drawbacks of existing first-line antifungal drugs, there is a growing interest in exploring novel targets that could facilitate the development of new antifungal agents or enhance the effectiveness of conventional ones. While previous studies have extensively summarized new antifungal targets inherent in fungi for drug development purposes, the exploration of potential targets for novel antifungal drug delivery strategies has received less attention.

Ubiquitin proteolysis of a CDK-related kinase regulates titan cell formation and virulence in the fungal pathogen Cryptococcus neoformans.

Fungal pathogens often undergo morphological switches, including cell size changes, to adapt to the host environment and cause disease. The pathogenic yeast Cryptococcus neoformans forms so-called 'titan cells' during infection. Titan cells are large, polyploid, display alterations in cell wall and capsule, and are more resistant to phagocytosis and various types of stress.

The intrinsically disordered region from PP2C phosphatases functions as a conserved CO sensor.

Carbon dioxide not only plays a central role in the carbon cycle, but also acts as a crucial signal in living cells. Adaptation to changing CO concentrations is critical for all organisms. Conversion of CO to HCO by carbonic anhydrase and subsequent HCO-triggered signalling are thought to be important for cellular responses to CO (refs.

Role of F-box Protein Cdc4 in Fungal Virulence and Sexual Reproduction of .

is an opportunistic yeast-like pathogen that mainly infects immunocompromised individuals and causes fatal meningitis. Sexual reproduction can promote the exchange of genetic material between different strains of , which is one of the reasons leading to the emergence of highly pathogenic and drug-resistant strains of . Although much research has been done on the regulation mechanism of sexual reproduction, there are few studies on the sexual reproduction regulation of by the ubiquitin-proteasome system.

The Vacuolar Morphogenesis Protein Vam6-Like Protein Vlp1 Is Required for Pathogenicity of .

is an encapsulated yeast pathogen that infects immunocompromised patients to cause fungal meningitis, resulting in hundreds of thousands of deaths each year. F-box protein Fbp1, the key component of the E3 ubiquitin ligase, plays a critical role in fungal development and virulence in fungal pathogens. In this study, we identified a potential substrate of Fbp1, the vacuolar morphogenesis protein Vam6-like protein Vlp1, and evaluated its role in virulence in .

The Effect of Accessory Pathway Location on Cardiac Function in Adult Patients with Wolff-Parkinson-White Syndrome.

Introduction: The relationship between ventricular pre-excitation and left ventricular dysfunction has been described in the absence of sustained supraventricular tachycardia in a series of case reports. However, there have been no systematic studies about the effect of ventricular pre-excitation on cardiac function in adult patients with different accessory pathway locations.

Methods And Results: Patients were divided into four groups based on the type and location of their accessory pathway: septal, right free wall, left free wall, and concealed.

A Predicted Mannoprotein Cmp1 Regulates Fungal Virulence in .

The capsule of the fungal pathogen consists of glucuronoxylomannan (GXM), glucuronoxylomannogalactan (GXMGal), and mannoproteins (MPs). MPs are a kind of glycoproteins with low content but high immunogenicity, which can stimulate the immune protection of the host. However, there is not much information about the role of mannoproteins in virulence of the human fungal pathogen .

Electrophysiological manifestations of rare supra-ventricular tachycardias with concealed nodo-ventricular fibers.

Purpose: To clarify the electrophysiological mechanism of supra-ventricular tachycardias (SVT) with concealed nodo-ventricular (NV) fibers.

Methods: We studied the intra-cardiac electrograms during electrophysiological study (EPS) of three cases of SVT which concerned concealed NV fibers. Electrophysiological maneuvers including right ventricular apex entrainments, RS2 stimuli, adenosine triphosphate injection and so on were done for differential diagnosis before ablation.

Autophagy Regulates Fungal Virulence and Sexual Reproduction in .

Autophagy (macroautophagy) is an evolutionarily conserved degradation pathway involved in bulk degradation of cytoplasmic organelles, old protein, and other macromolecules and nutrient recycling during starvation. Extensive studies on functions of autophagy-related genes have revealed that autophagy plays a role in cell differentiation and pathogenesis of pathogenic fungi. In this study, we identified and characterized 14 core autophagy machinery genes (s) in .

Zinc Finger Proteins in the Human Fungal Pathogen .

Zinc is one of the essential trace elements in eukaryotes and it is a critical structural component of a large number of proteins. Zinc finger proteins (ZNFs) are zinc-finger domain-containing proteins stabilized by bound zinc ions and they form the most abundant proteins, serving extraordinarily diverse biological functions. In recent years, many ZNFs have been identified and characterized in the human fungal pathogen , a fungal pathogen causing fatal meningitis mainly in immunocompromised individuals.

The CysHis zinc finger protein Zfp1 regulates sexual reproduction and virulence in Cryptococcus neoformans.

Cryptococcus neoformans is a ubiquitous yeast pathogen that often infects the human central nervous system (CNS) to cause meningitis in immunocompromised individuals. Although numerous signaling pathways and factors important for fungal sexual reproduction and virulence have been investigated, their precise mechanism of action remains to be further elucidated. In this study, we identified and characterized a novel zinc finger protein Zfp1 that regulates fungal sexual reproduction and virulence in C.

Recombinant leptin attenuates abdominal aortic aneurysm formation in angiotensin II-infused apolipoprotein E-deficient mice.

Vascular disease can manifest as stenotic plaques or ectatic aneurysms. Human abdominal aortic aneurysms (AAA) comprise an inflammatory disease characterized by the predominance of T helper type 2 (Th2) cytokine expression. Leptin has been clearly demonstrated to play an important role in regulating Th0 cell to Th1.

Role of the inositol pyrophosphate multikinase Kcs1 in Cryptococcus inositol metabolism.

Cryptococcus neoformans is the most common cause of deadly fungal meningitis. This fungus has a complex inositol acquisition and utilization system, and our previous studies have shown the importance of inositol utilization in cryptococcal development and virulence. However, how inositol utilization is regulated in this fungus remains unknown.

The F-Box Protein Fbp1 Shapes the Immunogenic Potential of .

is the main etiologic agent of cryptococcal meningitis and causes a significant number of deadly infections per year. Although it is well appreciated that host immune responses are crucial for defense against cryptococcosis, our understanding of factors that control the development of effective immunity to this fungus remains incomplete. In previous studies, we identified the F-box protein Fbp1 as a novel determinant of virulence.

Comparative proteomic analysis of differentially expressed proteins in the Bombyx mori fat body during the microsporidia Nosema bombycis infection.

Nosema bombycis is an obligate intracellular parasite, which can cause pébrine disease. To investigate the effects of N. bombycis infection, 5th-instar silkworms were challenged with N.

Crystal structure of Gib2, a signal-transducing protein scaffold associated with ribosomes in Cryptococcus neoformans.

The atypical Gβ-like/RACK1 Gib2 protein promotes cAMP signalling that plays a central role in regulating the virulence of Cryptococcus neoformans. Gib2 contains a seven-bladed β transducin structure and is emerging as a scaffold protein interconnecting signalling pathways through interactions with various protein partners. Here, we present the crystal structure of Gib2 at a 2.

Cryptococcus inositol utilization modulates the host protective immune response during brain infection.

Background: Cryptococcus neoformans is the most common cause of fungal meningitis among individuals with HIV/AIDS, which is uniformly fatal without proper treatment. The underlying mechanism of disease development in the brain that leads to cryptococcal meningoencephalitis remains incompletely understood. We have previously demonstrated that inositol transporters (ITR) are required for Cryptococcus virulence.

Fbp1-mediated ubiquitin-proteasome pathway controls Cryptococcus neoformans virulence by regulating fungal intracellular growth in macrophages.

Cryptococcus neoformans is a human fungal pathogen that often causes lung and brain infections in immunocompromised patients, with a high fatality rate. Our previous results showed that an F-box protein, Fbp1, is essential for Cryptococcus virulence independent of the classical virulence factors, suggesting a novel virulence control mechanism. In this study, we show that Fbp1 is part of the ubiquitin-proteasome system, and we further investigated the mechanism of Fbp1 function during infection.