Protective Effect of Silent Mating Type Information Regulation 2 Homolog 1 on TGF-β1 Pathway via mTOR in Diabetic Nephropathy

Objective: To demonstrate whether the expression of silent mating type information regulation 2 homolog 1 (SIRT1) affects the level of TGF-β1 and Smad3 in HEK293 cells through regulating mTOR. Methods: First, recombinant plasmids DNA (rSIRT1) and siRNA targeting SIRT1 were constructed which were transfected into Human Embryonic Kidney 293 cell (HEK293) cells, respectively. Then, the generation of intracellular ROS in cells was examined by flow cytometry using the oxidation-sensitive probe. Last, the expressions of TGF-β1, smad3, P53, mTOR, p-mTOR, LC3-I and LC3-II in cells were detected to observe the effect of SIRT1 on TGF-β1 Pathway by western blot analysis. Results: We demonstrated that overexpressing of SIRT1 may decrease TGF-β1 and Smad3 expression in HEK293 cells through regulating mTOR. In addition, the result is the opposite when SIRT1 was silent in HEK293 cells. Conclusions: SIRT1 is closely related to TGF-β1/Smad3 pathway that correlates with the regulation of mTOR and ROS generation and causes diabetic nephropathy. The available evidence implies that SIRT1 has great potential as a clinical target for the prevention and treatment of renal fibrosis in the development of DN.

Mating Type Alleles, Female Fertility and Genetic Diversity of Magnaporthe grisea Populations Pathogenic to Rice fromSome Asian Countries

Five hundred and twenty-two isolates of Magnaporthe grisea isolated from rice in 5 Asian countries were characterized for their mating type by crossing them with 4 hermaphroditic isolates(KA3 and TH12: MAT1.1; Guy11 and TH16: MAT1. 2). Among them, 41% were MAT1.1 and 25% were MAT1. 2. The remaining 34% did not produce perithecia with any of the 4 hermaphroditic testers. In Bangladesh, India, Nepal, Vietnam and in most provinces of China, both mating types were present. Only one mating type was found in 3 provinces and 1 city of China. Almost all the isolates had very low fertility, as they were in general female sterile and sometimes also male sterile. Hermaphroditic isolates were recovered from the 5 countries. In these countries, they represented between 13% and 75% of the isolates. In Zhejiang, Guizhou, Guangdong, Hunan, Yunnan and Hubei provinces of China, hermaphroditic isolates represented between 6% and 67%. The genetic diversity of 143 isolates from these countries and provinces, where hermaphroditic isolates had been collected, was analyzed using SCAR markers. Genetic diversity was high and population structure did not resemble classical clonal structure described in most rice growing regions. The existence of sexual reproduction in the field, localization of a center of diversity in China, and migration between countries were discussed in this paper.

Mating Genotype Analysis of Ganoderma lucidum Populations

[Objective] The mating genotype was studied and compared with esterase isozyme of Ganoderma lucidum populations between groups in order to clarify their differences in genetic relationship analysis. [Method] OWE-SOJ technique was applied to identify standard mating types and determinate mating genotype between groups of monokaryons isolates from 24 G. lucidum stains. Genetic relationships were analyzed by combined group mating genotype determination with esterase isozyme assay. [Result] All strains of G. lucidum could be divided into 7 large groups of the mating genotype. Four alleles of A factor, four alleles of B factor and one mixed alleles of A factor were found in this study. Distorted segregation ratio among monokaryon mycelia of G. lucidum had been observed in four kinds of mat- ing types to some extent. Twenty-eight different types of enzyme bands were determined in esterase isozyme test, Twenty-four strains of G. lucidum could be divided into 9 large groups through the cluster analysis when the genetic similarity coefficient was 0.73214. Comparing the results of mating genotype analysis and esterase isozyme analysis, it showed great similarity. [Conclusion] Mating genotype analysis could be used as an important supplementary method for strain identification and genetic diversity research.

Targeting the core of neurodegeneration:FoxO,mTOR,and SIRT1

The global increase in lifespan noted not only in developed nations,but also in large developing countries parallels an observed increase in a significant number of noncommunicable diseases,most notable neurodegenerative disorders.Neurodegenerative disorders present a number of challenges for treatment options that do not resolve disease progression.Furthermore,it is believed by the year 2030,the services required to treat cognitive disorders in the United States alone will exceed$2 trillion annually.Mammalian forkhead transcription factors,silent mating type information regulation 2 homolog 1(Saccharomyces cerevisiae),the mechanistic target of rapamycin,and the pathways of autophagy and apoptosis offer exciting avenues to address these challenges by focusing upon core cellular mechanisms that may significantly impact nervous system disease.These pathways are intimately linked such as through cell signaling pathways involving protein kinase B and can foster,sometimes in conjunction with trophic factors,enhanced neuronal survival,reduction in toxic intracellular accumulations,and mitochondrial stability.Feedback mechanisms among these pathways also exist that can oversee reparative processes in the nervous system.However,mammalian forkhead transcription factors,silent mating type information regulation 2 homolog 1,mechanistic target of rapamycin,and autophagy can lead to cellular demise under some scenarios that may be dependent upon the precise cellular environment,warranting future studies to effectively translate these core pathways into successful clinical treatment strategies for neurodegenerative disorders.

Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

Throughout the globe,diabetes mellitus（DM） is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder.DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy.The mechanistic target of rapamycin（m TOR） is a promising agent for the development of novel regenerative strategies for the treatment of DM.m TOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis,insulin resistance,insulin secretion,stem cell proliferation and differentiation,pancreatic β-cell function,and programmed cell death with apoptosis and autophagy.m TOR is central element for the protein complexes m TOR Complex 1（m TORC1） and m TOR Complex 2（m TORC2） and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase（PI 3-K）,protein kinase B（Akt）,AMP activated protein kinase（AMPK）,silent mating type information regulation 2 homolog 1（Saccharomyces cerevisiae）（SIRT1）,Wnt1 inducible signaling pathway protein 1（WISP1）,and growth factors.As a result,m TOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease.Future studies directed to elucidate the delicate balance m TOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.

Stimulation Study of Gene Pyramiding inAnimals by Marker-Assisted Selection

This gene pyramiding strategy is based on the idea of efficiently pyramiding genes of interest by crosses and selection to obtain a population with favorable alleles from different breeds or lines, which is called an ideal population. We investigate impacts of some factors on the pyramiding efficiencies by simulation. These factors include selection strategies （the breeding value selection, the molecular scores selection and the index selection）, proportion selected （2, 10 and 20%）, recombination rates between adjacent target genes （0.1, 0.3 and 0.5） and different mating types （the random mating and the positive assortative mating avoiding sib mating）. The results show that： （1） The more recombination rate and the lower proportion male selected, the better pyramiding efficiency; （2） the ideal population is obtained via various selection strategies, while different selection strategies are suitable for different breeding objectives. From the perspective of pyramiding target genes merely, the molecular scores selection is the best one, for the purpose of pyramiding target genes and recovering genetic background of the target trait, the index selection is the best one, while from the saving cost point of view, the breeding value selection is the best one; （3） the positive assortative mating is more efficient for gene pyramiding compared with the random mating in the terms of the number of generations of intercross for getting the ideal population.

A Preliminary Investigation on Phenotypic Characteristics of Phytophthora infestans from Guizhou Province

Abstract [ Objective ] This study aimed to investigate the phenotypic characteristics of Phytophthora infestans from Guizhou Province. The metalaxyl resistance, mating type and isozyme genotype of 292 P. infestans strains isolated from Guizhou Province were analyzed. [ Result] Metalaxyl-resistant P. infestans strains were found in different areas of Guizhou Province. Resistant, moderately resistant and susceptible strains accounted for 35.62% , 33.90% and 30.48% , re- spectively. Both mating types A1 and A2 were found, which accounted for 65.38% and 34.62%, respectively. P. infestans strains isolated from Guizhou Province mainly belonged to Gpi genotypes 100/100 and 100/100/111, accounting for 50.68% and 43.84%, respectively. [ Conclusion] This study provides the theoretical basis for the prevention and control of potato late blight in Guizhou Province.

Cardiovascular and nonalcoholic fatty liver disease:Sharing common ground through SIRT1 pathways

As a non-communicable disease,cardiovascular disorders have become the lea-ding cause of death for men and women.Of additional concern is that cardio-vascular disease is linked to chronic comorbidity disorders that include nonal-coholic fatty liver disease(NAFLD).NAFLD,also termed metabolic-dysfunction-associated steatotic liver disease,is the greatest cause of liver disease throughout the world,increasing in prevalence concurrently with diabetes mellitus(DM),and can progress to nonalcoholic steatohepatitis that leads to cirrhosis and liver fi-brosis.Individuals with metabolic disorders,such as DM,are more than two times likely to experience cardiac disease,stroke,and liver disease that includes NAFLD when compared individuals without metabolic disorders.Interestingly,cardiovascular disorders and NAFLD share a common underlying cellular me-chanism for disease pathology,namely the silent mating type information regu-lation 2 homolog 1(SIRT1;Saccharomyces cerevisiae).SIRT1,a histone deacetylase,is linked to metabolic pathways through nicotinamide adenine dinucleotide and can offer cellular protection though multiple avenues,including trophic factors such as erythropoietin,stem cells,and AMP-activated protein kinase.Translating SIRT1 pathways into clinical care for cardiovascular and hepatic disease can offer significant hope for patients,but further insights into the complexity of SIRT1 pathways are necessary for effective treatment regimens.

A multi-locus phylogenetic evaluation of Diaporthe (Phomopsis)

The genus Diaporthe(Phomopsis)includes important plant pathogenic fungi with wide host ranges and geographic distributions.In the present study,phylogenetic species recognition in Diaporthe is re-evaluated using a multi-locus phylogeny based on a combined data matrix of rDNA ITS,and partial sequences from the translation elongation factor 1-α(EF 1-α),βtubulin(TUB)and calmodulin(CAL)molecular markers.DNA sequences of available extype cultures have been included,providing a multi-locus backbone tree for future studies on Diaporthe.Four utilizable loci were analyzed individually and in combination,and ITS,EF 1-αand multi-locus phylogenetic trees are presented.The phylogenetic tree inferred by combined analysis of four loci provided the best resolution for species as compared to single gene analysis.Notes are provided for nine species previously known in Phomopsis that are transferred to Diaporthe in the present study.The unraveling of cryptic species complexes of Diaporthe based on Genealogical Concordance Phylogenetic Species Recognition(GCPSR)is emphasized.

Genome Assembly and Pathway Analysis of Edible Mushroom Agrocybe cylindracea

Agrocybe cylindracea,an edible mushroom,is widely cultivated for its abundance of nutrients and flavor,and many of its metabolites are reported to have beneficial roles,such as medicinal effects on tumors and chronical illnesses.However,the lack of genomic information has hindered further molecular studies on this fungus.Here,we present a genome assembly of A.cylindracea together with comparative genomics and pathway analyses of Agaricales species.The draft,generated from both next-generation sequencing(NGS)and single-molecule real-time(SMRT)sequencing platforms to overcome high genetic heterozygosity,is composed of a56.5 Mb sequence and 15,384 predicted genes.This mushroom possesses a complex reproductive system,including tetrapolar heterothallic and secondary homothallic mechanisms,and harbors several hydrolases and peptidases for gradual and effective degradation of various carbon sources.Our pathway analysis reveals complex processes involved in the biosynthesis of polysaccharides and other active substances,including B vitamins,unsaturated fatty acids,and N-acetylglucosamine.RNA-seq data show that A.cylindracea stipes tend to synthesize carbohydrate for carbon sequestration and energy storage,whereas pilei are more active in carbon utilization and unsaturated fatty acid biosynthesis.These results reflect diverse functions of the two anatomical structures of the fruiting body.Our comprehensive genomic and transcriptomic data,as well as preliminary comparative analyses,provide insights into the molecular details of the medicinal effects in terms of active compounds and nutrient components.

Mate-recognition and species boundaries in the ascomycetes

Reproductive gene evolution is commonly invoked as a source of reproductive isolation during speciation.This possibility has not been adequately explored in the Ascomycota,the most species-rich fungal phylum.The mechanisms of mate-recognition in this group are relatively simple:a“mating type”locus determines reproductive mode and sexual compatibility,and two pheromone/receptor pairs control sexual attraction.However,ascomycete reproductive genes can experience unique and interesting evolutionary forces,which could lead to rapid divergence.In this review,we examine the mechanisms of sexual interaction in ascomycetes and explore current evidence as to whether these mechanisms allow for species-specificity in mate-recognition.We discuss the evolutionary forces that can drive reproductive gene divergence,how these may apply in the world of ascomycetes,and their possible consequences for speciation.

Diversity and delimitation of Rhizopus microsporus

Rhizopus microsporus has been used for centuries in the production of oriental fermented foods,but the species is also known as a toxin producer and from severe human infections.To study the diversity and species delimitation of Rhizopus microsporus,48 isolates from the reference collection of the CBS-KNAW Fungal Biodiversity Centre,comprising nine environmental,ten clinical,and 23 foodborne strains,in addition to six strains from unknown sources and representing all existing varieties of the species,were examined.Sequence diversity was based on the internal transcribed spacer(ITS),and on a part of the actin(ACT)and translation elongation factor 1-α(TEF)genes.Differences in physiological properties were assessed including temperature relationships.Spore morphology was studied,mating type tests were performed,and MALDI-ToF profiles were generated.Clinical and food-associated strains as well as members of different varieties mated successfully and consequently they belong to a single biological species.Molecular differences did not match with any other parameter investigated.Based on these results the varieties of Rhizopus microsporus are reduced to synonyms.