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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 vidD resulted in increased production of sterigmatocystin. Together, these results show that VidD is required for proper fungal growth, development, and sterigmatocystin production in A. nidulans. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Spinal muscular atrophy (SMA) is caused by the mutation or deletion of the survival motor neuron 1 (SMN1) gene. Only ∼10% of the products of SMN2, a paralogue of SMN1, are functional full-length SMN (SMN-FL) proteins, whereas SMN2 primarily produces alternatively spliced transcripts lacking exon 7. Reduced SMN protein levels in SMA patients lead to progressive degeneration of spinal motor neurons (MNs). In this study, we report an advanced platform based on an SMN2 splicing-targeting approach for SMA drug screening and validation using an SMN2 splicing reporter cell line and an in vitro human SMA model through induced pluripotent stem cell (iPSC) technology. Through drug screening using a robust cell-based luciferase assay to quantitatively measure SMN2 splicing, the small-molecule candidate compound rigosertib was identified as an SMN2 splicing modulator that led to enhanced SMN protein expression. The therapeutic potential of the candidate compound was validated in MN progenitors differentiated from SMA patient-derived iPSCs (SMA iPSC-pMNs) as an in vitro human SMA model, which recapitulated the biochemical and molecular phenotypes of SMA, including lower levels of SMN-FL transcripts and protein, enhanced cell death, and reduced neurite length. The candidate compound exerted strong splicing correction activity for SMN2 and potently alleviated the disease-related phenotypes of SMA iPSC-pMNs by modulating various cellular and molecular abnormalities. Our combined screening platform representing a pMN model of human SMA provides an efficient and reliable drug screening system and is a promising resource for drug evaluation and the exploration of drug modes of action. [ABSTRACT FROM AUTHOR]

Objective: To investigate the efficacy of double inversion recovery (DIR) sequence for evaluating the synovium of the femoro-patellar joint without contrast enhancement (CE).Methods: Two radiologists independently evaluated the axial DIR and CE T1-weighted fat-saturated (CET1FS) images of 33 knees for agreement; the visualisation and distribution of the synovium were evaluated using a four-point visual scaling system at each of the five levels of the femoro-patellar joint and the location of the thickest synovium. The maximal synovial thickness at each sequence was measured by consensus.Results: The interobserver agreement was good (κ = 0.736) for the four-point scale, and was excellent for the location of the thickest synovium on DIR and CET1FS (κ = 0.955 and 0.954). The intersequential agreement for the area with the thickest synovium was also excellent (κ = 0.845 and κ = 0.828). The synovial thickness on each sequence showed excellent correlation (r = 0.872).Conclusion: The DIR showed as good a correlation as CET1FS for the evaluation of the synovium at the femoro-patellar joint. DIR may be a useful MR technique for evaluating the synovium without CE.Key Points: • DIR can be useful for evaluating the synovium of the femoro-patellar joint. • Interobserver and intersequential agreements between DIR and CET1FS were good. • Mean thickness of the synovium was significantly different between two sequences. [ABSTRACT FROM AUTHOR]

Recently, there has been increasing research to discover genomic biomarkers, haplotypes, and potentially other variables that together contribute to the development of diseases. Single Nucleotide Polymorphisms (SNPs) are the most common form of genomic variations and they can represent an individual’s genetic variability in greatest detail. Genome-wide association studies (GWAS) of SNPs, high-dimensional case-control studies, are among the most promising approaches for identifying disease causing variants. METU-SNP software is a Java based integrated desktop application specifically designed for the prioritization of SNP biomarkers and the discovery of genes and pathways related to diseases via analysis of the GWAS case-control data. Outputs of METU-SNP can easily be utilized for the downstream biomarkers research to allow the prediction and the diagnosis of diseases and other personalized medical approaches. Here, we introduce and describe the system functionality and architecture of the METU-SNP. We believe that the METU-SNP will help researchers with the reliable identification of SNPs that are involved in the etiology of complex diseases, ultimately supporting the development of personalized medicine approaches and targeted drug discoveries

Objectives : The aim of study was to evaluate the effect of Herbal medicine on post stroke cognitive deficit. Methods : All groups were treated with acupunture treatment, moxa treatment, herbal medicines, physical and occupational therapy for 4 weeks, additionally cardiotonic pills(CP) were taken in the cardiotonic pills group. The effect of treatment was assessed using Verval fluency, MMSE-KC, Word List Immediate Recall test. Statistical significance was achived if the probability was less than 5%(p,0.05). Results : Verval fluency, MMSE-KC, Word List Immediate Recall test scores increased in both group. MMSEKC, Word List Immediate Recall test scores were significantly increased in the CP group. Verval fluency, MMSE-KC, Word List Immediate Recall test scores were significantly increased in the control group. In the Verval fluency, MMSE-KC, Word List Immediate Recall test of the CP group more increased compared to the control group. There were no significant differences between two groups. In the CP group, the scores of the infarction group more increased compared to the hemorrhage group. Conclusions : According to the these results, herbal medicines are effective to improve post stroke cognitive-deficit. Futher studies are needed to know cardiotonic pills in the ischemic stroke.

Methods for the rapid removal of chemical warfare agents are of critical importance. In this work, a porous activated carbon material (C-PAC) was prepared from chitosan flakes via single-step potassium carbonate (K2CO3) activation for the prompt adsorption of dimethyl methylphosphonate (DMMP). C-PAC samples were prepared using different carbonization temperatures (350, 550, and 750 °C) at a constant K2CO3/chitosan ratio (1:2) and using different activator ratios (K2CO3/chitosan ratios of 1:0.5, 1:1, 1:2, and 1:3) at 750 °C. Furthermore, we evaluated the effect of preparation conditions on the adsorption capacities of the various C-PAC materials for DMMP under ambient conditions (25 °C). Notably, for the C-PAC material prepared at 750 °C using a K2CO3/chitosan ratio of 1:2, the DMMP adsorption was saturated at approximately 412 mg·g−1 carbon after 48 h. The good performance of this material makes it a potential candidate for use in remedial applications or protective gear. [ABSTRACT FROM AUTHOR]

Lysosomes are cytoplasmic compartments that contain many acid hydrolases and play critical roles in the metabolism of a wide range of macromolecules. Deficiencies in lysosomal enzyme activities cause genetic diseases, called lysosomal storage disorders (LSDs). Many mutations have been identified in the genes responsible for LSDs, and the identification of mutations is required for the accurate molecular diagnoses. Here, we analyzed cell lines that were derived from two different LSDs, GM1 gangliosidosis and sialidosis. GM1 gangliosidosis is caused by mutations in the GLB1 gene that encodes β-galactosidase. A lack of β-galactosidase activity leads to the massive accumulation of GM1 ganglioside, which results in neurodegenerative pathology. Mutations in the NEU1 gene that encodes lysosomal sialidase cause sialidosis. Insufficient activity of lysosomal sialidase progressively increases the accumulation of sialylated molecules, and various clinical symptoms, including mental retardation, appear. We sequenced the entire coding regions of GLB1 and NEU1 in GM1 gangliosidosis and sialidosis patient cells, respectively. We found the novel mutations p.E186A in GLB1 and p.R347Q in NEU1, as well as many other mutations that have been previously reported. We also demonstrated that patient cells containing the novel mutations showed the molecular phenotypes of the corresponding disease. Further structural analysis suggested that these novel mutation sites are highly conserved and important for enzyme activity. [ABSTRACT FROM AUTHOR]

Polar tip growth in plants occurs only in root hairs and pollen tubes. In particular, root hair growth is considered very important in the growth of plants, as it is critical for water and nutrient absorption. Polar tip growth is regulated by various factors, including plant hormones such as abscisic acid (ABA) and gibberellin (GA) and cell wall modifications. We aimed to elucidate the effects and mechanisms on tip growth of a novel gene containing the domain of unknown function (DUF) 3511. We found that Protein Involved in Tip Elongation (PITE) is involved in root hair development in rice (Oryza sativa L.). PITE protein was observed in the plasma membrane and cytoplasm of root hairs. Pite mutants generated by the CRISPR/Cas9 system showed a shorter root hair phenotype compared to the wild type. Through RNA sequencing and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis, we found that the expression of genes that affect cell wall rigidity and GA metabolism-related genes were differently regulated in pite mutants. PITE could interact with acyl transferase and haloacid dehalogenase-like hydrolase (HAD9) in the nucleus and cytoplasm. Our study suggests that PITEs containing the DUF3511 domain regulate root hair growth in rice by mediating the expression of genes that can regulate cell wall rigidity or cause changes in GA metabolism through interactors such as HAD9., (© 2024 Scandinavian Plant Physiology Society.)

We demonstrated that Fe/Cr doped and pH-modified CeO 2 nanoparticles (NPs) exhibit enhanced photocatalytic performance as compared to bare CeO 2 NPs, using photocatalytic degradation. To assess the toxicity level of these double-modified CeO 2 NPs on the human skin, they were introduced into HaCaT cells. The results of our conventional cellular toxicity assays (neutral red uptake and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide for assays) indicated that Cr@CeO x NPs prompt severe negative effects on the viability of human cells. Moreover, the results obtained by scanning transmission X-ray microscopy and bio-transmission electron microscope analysis showed that most of the NPs were localized outside the nucleus of the cells. Thus, serious genetic toxicity was unlikely. Overall, this study highlights the need to prevent the development of Cr@CeO x NP toxicity. Moreover, further research should aim to improve the photocatalytic properties and activity of these NPs while accounting for their stability issues.

Background/aim: Thyroid cancer is the most common type of endocrine cancer and its incidence and mortality are increasing. However, few studies on the molecular factors related to its poor prognosis have been performed. The aim of our study was to identify a poor prognostic factor for thyroid cancer to reduce its overtreatment, recurrence, and mortality., Materials and Methods: The present study is a retrospective study of 55 patients who were diagnosed with papillary thyroid cancer and operated in Korea from September 2013 to November 2015., Results: Mts1 is a member of the S100 protein family and is involved in tumor progression and metastasis. Mts1 was highly expressed in patients with thyroid cancer and high Mts1 levels were related to poor prognoses such as lymph node metastasis., Conclusion: Mts1 is associated with aggressive pathological features in thyroid cancer, and may be a poor prognostic factor for thyroid cancer., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Calcineurin modulates environmental stress survival and virulence of the human fungal pathogen Cryptococcus neoformans Previously, we identified 44 putative calcineurin substrates, and proposed that the calcineurin pathway is branched to regulate targets including Crz1, Pbp1, and Puf4 in C. neoformans In this study, we characterized Had1, which is one of the putative calcineurin substrates belonging to the ubiquitously conserved haloacid dehalogenase β-phosphoglucomutase protein superfamily. Growth of the had1 ∆ mutant was found to be compromised at 38° or higher. In addition, the had1 ∆ mutant exhibited increased sensitivity to cell wall perturbing agents, including Congo Red and Calcofluor White, and to an endoplasmic reticulum stress inducer dithiothreitol. Virulence studies revealed that the had1 mutation results in attenuated virulence compared to the wild-type strain in a murine inhalation infection model. Genetic epistasis analysis revealed that Had1 and the zinc finger transcription factor Crz1 play roles in parallel pathways that orchestrate stress survival and fungal virulence. Overall, our results demonstrate that Had1 is a key regulator of thermotolerance, cell wall integrity, and virulence of C. neoformans ., (Copyright © 2018 Jung et al.)

Recurrent copy number variations (CNVs) of human 16p11.2 have been associated with a variety of developmental/neurocognitive syndromes. In particular, deletion of 16p11.2 is found in patients with autism, developmental delay, and obesity. Patients with deletions or duplications have a wide range of clinical features, and siblings carrying the same deletion often have diverse symptoms. To study the consequence of 16p11.2 CNVs in a systematic manner, we used chromosome engineering to generate mice harboring deletion of the chromosomal region corresponding to 16p11.2, as well as mice harboring the reciprocal duplication. These 16p11.2 CNV models have dosage-dependent changes in gene expression, viability, brain architecture, and behavior. For each phenotype, the consequence of the deletion is more severe than that of the duplication. Of particular note is that half of the 16p11.2 deletion mice die postnatally; those that survive to adulthood are healthy and fertile, but have alterations in the hypothalamus and exhibit a "behavior trap" phenotype-a specific behavior characteristic of rodents with lateral hypothalamic and nigrostriatal lesions. These findings indicate that 16p11.2 CNVs cause brain and behavioral anomalies, providing insight into human neurodevelopmental disorders.