Unveiling the Functions of the VosA-VelB Target Gene vidD inAspergillus nidulans

The velvet regulators VosA and VelB are primarily involved in spore maturation and dormancy. Previous studies found that the VosA-VelB hetero-complex coordinates certain target genes that are related to fungal differentiation and conidial maturation in Aspergillus nidulans. Here, we characterized the VosA/VelB-inhibited developmental gene vidD in A. nidulans.Phenotypic analyses demonstrated that the vidD deleted mutant exhibited defect fungal growth, a reduced number of conidia, and delayed formation of sexual fruiting bodies. The deletion of vidD decreased the amount of conidial trehalose, increased the sensitivity against heat stress, and reduced the conidial viability. Moreover, the absence of vidDresulted in increased production of sterigmatocystin. Together, these results show that vidD is required for proper fungal growth, development, and sterigmatocystin production in A. nidulans.

Genetic Manipulation and Transformation Methods for Aspergillus spp

Species of the genus Aspergillus have a variety of effects on humans and have been considered industrial cell factories due to their prominent ability for manufacturing several products such as heterologous proteins, secondary metabolites, and organic acids. Scientists are trying to improve fungal strains and re-design metabolic processes through advanced genetic manipulation techniques and gene delivery systems to enhance their industrial efficiency and utility. In this review, we describe the current status of the genetic manipulation techniques and transformation methods for species of the genus Aspergillus. The host strains, selective markers, and experimental materials required for the genetic manipulation and fungal transformation are described in detail. Furthermore, the advantages and disadvantages of these techniques are described.

Unveiling the Functions of the VosA-VelB Target Gene vidD inAspergillus nidulans

The velvet regulators VosA and VelB are primarily involved in spore maturation and dormancy. Previous studies found that the VosA-VelB hetero-complex coordinates certain target genes that are related to fungal differentiation and conidial maturation in Aspergillus nidulans. Here, we characterized the VosA/VelB-inhibited developmental gene vidD in A. nidulans.Phenotypic analyses demonstrated that the vidD deleted mutant exhibited defect fungal growth, a reduced number of conidia, and delayed formation of sexual fruiting bodies. The deletion of vidD decreased the amount of conidial trehalose, increased the sensitivity against heat stress, and reduced the conidial viability. Moreover, the absence of vidDresulted in increased production of sterigmatocystin. Together, these results show that vidD is required for proper fungal growth, development, and sterigmatocystin production in A. nidulans.

Genetic Manipulation and Transformation Methods for Aspergillus spp

Species of the genus Aspergillus have a variety of effects on humans and have been considered industrial cell factories due to their prominent ability for manufacturing several products such as heterologous proteins, secondary metabolites, and organic acids. Scientists are trying to improve fungal strains and re-design metabolic processes through advanced genetic manipulation techniques and gene delivery systems to enhance their industrial efficiency and utility. In this review, we describe the current status of the genetic manipulation techniques and transformation methods for species of the genus Aspergillus. The host strains, selective markers, and experimental materials required for the genetic manipulation and fungal transformation are described in detail. Furthermore, the advantages and disadvantages of these techniques are described.

Conserved Roles of MonA in Fungal Growth and Development in Aspergillus Species

MonA is a subunit of a guanine nucleotide exchange factor that is important for vacuole passing and autophagy processes in eukaryotes. In this study, we characterized the function of MonA, an orthologue of Saccharomyces cerevisiae Mon1, in the model fungus Aspergillus nidulans and a toxigenic fungus A. flavus. In A. nidulans, the absence of AnimonA led to decreased fungal growth, reduced asexual reproduction, and defective cleistothecia production. In addition, AnimonA deletion mutants exhibited decreased spore viability, had reduced trehalose contents in conidia, and were sensitive to thermal stress. In A. flavus, deletion of AflmonA caused decreased fungal growth and defective production of asexual spores and sclerotia structures. Moreover, the absence of monA affected vacuole morphology in both species. Taken together, these results indicate that MonA plays conserved roles in controlling fungal growth, development and vacuole morphology in A. nidulans and A. flavus.

Mon1 Is Essential for Fungal Virulence and Stress Survival in Cryptococcus neoformans

Mon1 is a guanine nucleotide exchange factor subunit that activates the Ypt7 Rab GTPase and is essential for vacuole trafficking and autophagy in eukaryotic organisms. Here, we identified and characterized the function of Mon1, an ortholog of Saccharomyces cerevisiae Mon1, in a human fungal pathogen, Cryptococcus neoformans. Mutation in mon1 resulted in hypersensitivity to thermal stress. The mon1 deletion mutant exhibited increased sensitivity to cell wall and endoplasmic reticulum stress. However, the mon1 deletion mutant showed more resistance to the antifungal agent fluconazole. In vivo studies demonstrated that compared to the wild-type strain, the mon1 deletion mutant attenuated virulence in the Galleria mellonella insect model. Moreover, the mon1 deletion mutant was avirulent in the murine inhalation model. These results demonstrate that Mon1 plays a crucial role in stress survival and pathogenicity in C. neoformans.

Correlates of N-acetylaspartate and Cognitive Dysfunctions in Drug-naive Patients with Obsessive-compulsive Disorder: A Proton MRSI Study / 신경정신의학

OBJECTIVES: Reductions of N-acetylaspartate (NAA), a putative marker of neuronal viability, within the subcortical structures in patients with obsessive-compulsive disorder (OCD) are well documented. However, there has been no report of the NAA level in cortical structures. The authors used proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess potential reductions of NAA in the frontal white matter, prefrontal gray matter, parietal gray and white matter, and the cingulate in drugnaive patients with OCD and explored the relationship between the brain metabolites and the degree to the dysfunction on the neuropsychological performances. METHODS : Thirteen drug-naive patients who met DSM-IV criteria for OCD and 13 healthy age-, sex-, handness- matched control subjects were studied. Subjects underwent MRI and 1H-MRSI and the peaks of NAA, creatine+phosphocreatine (Cr), and choline-containing compounds (Cho) were measured. Differences between patients and control subjects were tested for each metabolite ratio, and the relations between metabolite ratios and clinical symptoms, neuropsychological performances were examined. RESULTS : Upon comparison with normal controls, NAA/Cr ratio was significantly reduced in patients for the prefrontal gray matter, frontal white matter and anterior cingulate. There was no difference in Cho/Cr or NAA/Cho in any region. Also, a significant positive correlation was found between prefrontal NAA/Cr ratio and the delayed recall score of the Rey-Osterrieth Complex Figure Test in patients with OCD. CONCLUSION : The reduced NAA/Cr ratio in the prefrontal gray matter and frontal white matter suggests that OCD patients have lower neuronal viability than normal comparisons and it may be related to impaired organizational strategies in patients with OCD. These results support a role for the frontal-subcortical circuitry in a neurobiologic model of OCD.

Cognitive Dysfunctions in Patients with Obsessive-Compulsive Disorder: Two-Year Treatment Follow-up / 신경정신의학

OBJECTIVES: The purpose of this study was to investigate the changes of cognitive dysfunctions in patients with obsessive compulsive disorder (OCD) over the two-year of pharmacological treatment. METHODS: The thirty-three OCD patients and thirteen normal subjects were administered the neuropsychological tests and clinical evaluations twice (at the baseline and two-year). RESULTS: In spite of the two-year treatment, the accuracy of delayed recall on the Rey-Osterrieth Complex Figure Tests (RCFT), the numbers of responses on the category and letter test of Controlled Oral Word Association Test (COWA), the response time on the Trail Making Test part A (TMT-A) remained significantly impaired in the OCD patients compared with the normal controls. CONCLUSION: These findings suggest that the cognitive dysfunctions such as visuospatial memory and verbal fluency might be the underlying persisting neuropathophysiology of OCD.

Cognitive Dysfunctions in Patients with Obsessive-Compulsive Disorder: Two-Year Treatment Follow-up / 신경정신의학

OBJECTIVES: The purpose of this study was to investigate the changes of cognitive dysfunctions in patients with obsessive compulsive disorder (OCD) over the two-year of pharmacological treatment. METHODS: The thirty-three OCD patients and thirteen normal subjects were administered the neuropsychological tests and clinical evaluations twice (at the baseline and two-year). RESULTS: In spite of the two-year treatment, the accuracy of delayed recall on the Rey-Osterrieth Complex Figure Tests (RCFT), the numbers of responses on the category and letter test of Controlled Oral Word Association Test (COWA), the response time on the Trail Making Test part A (TMT-A) remained significantly impaired in the OCD patients compared with the normal controls. CONCLUSION: These findings suggest that the cognitive dysfunctions such as visuospatial memory and verbal fluency might be the underlying persisting neuropathophysiology of OCD.