The correlation analysis of gear tooth broken-pitting compound fault and single fault based on Laplacian Eigenmaps

Gear break and pitting are two common faults in transmission system, when these two faults coexist and form a compound fault, the damage speed and frequency of gear transmission system will be greatly increased. Taking the gear fault-pitting compound fault as the object, the dynamic model of gear single fault and compound fault is established, and the vibration characteristics of gear single fault, pitting single fault and broken tooth-pitting compound fault signal are analyzed. The characteristic manifolds of the intrinsic dimension space in the case of gear single failure and compound fault are extracted by using the Laplacian Eigenmaps algorithm, the evolution trend of single fault and compound fault in the overlapping region of the feature space, the degree of correlation and the curvature of the fault circle core are analyzed and obtained. The study found that with the deepening of the fault severity, the overlapping area of fault circle between compound fault and single fault become smaller gradually, that is, the degree of correlation become weakened, tooth broken single fault and compound fault can be identified in mid-late stage of fault, while the pitting single fault and compound fault are in the late stage. The experimental results of gearbox compound fault correlation show that the conclusion of the simulation analysis is correct and effective, which provides a new idea for the diagnosis of mechanical complex faults

Defective Expression of Mitochondrial, Vacuolar H+-ATPase and Histone Genes in a C. elegans Model of SMA

Spinal muscular atrophy (SMA) is a severe motor neuron degenerative disease caused by loss-of-function mutations in the survival motor neuron gene SMN1. It is widely posited that defective gene expression underlies SMA. However, the identities of these affected genes remain to be elucidated. By analyzing the transcriptome of a Caenorhabditis elegans SMA model at the pre-symptomatic stage, we found that the expression of numerous nuclear encoded mitochondrial genes and vacuolar H+-ATPase genes was significantly down-regulated, while that of histone genes was significantly up-regulated. We previously showed that the uaf-1 gene, encoding key splicing factor U2AF large subunit, could affect the behavior and lifespan of smn-1 mutants. Here, we found that smn-1 and uaf-1 interact to affect the recognition of 3′ and 5′ splice sites in a gene-specific manner. Altogether, our results suggest a functional interaction between smn-1 and uaf-1 in affecting RNA splicing and a potential effect of smn-1 on the expression of mitochondrial and histone genes

Insights into the functional role of tea microbes on tea growth, quality and resistance against pests and diseases

Tea is an economical and most widely used beverage across the globe owing to its unique fragrance and flavor. Plant microbe interaction has emerged as an important topic which got the attention of scientists to improve plant performance. Tea microbes remained a prominent research topic for scientists over the years as tea microbes helps in nutrient cycling and stress management which in turn improve the tea growth, yield and quality. The roots of tea plants are colonized by various microbes including arbuscular mycorrhizal fungi (AMF), bacterial communities, and endophytes increase root growth, development and nutrient uptake which in turn improve tea growth, yield and quality. These microbes also increase the concentration of nutrients, amino acids, soluble proteins, flavonoids, catechuic acid, glucose, fructose, sucrose contents caffeine, and polyphenols concentration in tea plants. Besides this, these microbes also protect the tea plants from harmful pest and diseases which in turn leads to an appreciable improvement in plant growth and development. The most important goal of any farming system is to establish a system with production of maximum food while minimizing impacts on the environment. The present review article highlights the role of various microbes in improving the growth, yield and quality of tea plants. In addition, we also discussed the research gaps to improve our understanding about the role of tea microbes in improving tea growth, yield, pest and diseases resistance. We believe that this review will provide a better insight into the existing knowledge of tea microbes in improving tea growth and yield

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

The Caenorhabditis elegans Gene mfap-1 Encodes a Nuclear Protein That Affects Alternative Splicing

RNA splicing is a major regulatory mechanism for controlling eukaryotic gene expression. By generating various splice isoforms from a single pre–mRNA, alternative splicing plays a key role in promoting the evolving complexity of metazoans. Numerous splicing factors have been identified. However, the in vivo functions of many splicing factors remain to be understood. In vivo studies are essential for understanding the molecular mechanisms of RNA splicing and the biology of numerous RNA splicing-related diseases. We previously isolated a Caenorhabditis elegans mutant defective in an essential gene from a genetic screen for suppressors of the rubberband Unc phenotype of unc-93(e1500) animals. This mutant contains missense mutations in two adjacent codons of the C. elegans microfibrillar-associated protein 1 gene mfap-1. mfap-1(n4564 n5214) suppresses the Unc phenotypes of different rubberband Unc mutants in a pattern similar to that of mutations in the splicing factor genes uaf-1 (the C. elegans U2AF large subunit gene) and sfa-1 (the C. elegans SF1/BBP gene). We used the endogenous gene tos-1 as a reporter for splicing and detected increased intron 1 retention and exon 3 skipping of tos-1 transcripts in mfap-1(n4564 n5214) animals. Using a yeast two-hybrid screen, we isolated splicing factors as potential MFAP-1 interactors. Our studies indicate that C. elegans mfap-1 encodes a splicing factor that can affect alternative splicing.National Natural Science Foundation (China) (Grant 30971639)United States. National Institutes of Health (Grant GM24663

Systemic Stimulation of TLR2 Impairs Neonatal Mouse Brain Development

Background: Inflammation is associated with perinatal brain injury but the underlying mechanisms are not completely characterized. Stimulation of Toll-like receptors (TLRs) through specific agonists induces inflammatory responses that trigger both innate and adaptive immune responses. The impact of engagement of TLR2 signaling pathways on the neonatal brain is still unclear. The aim of this study was to investigate the potential effect of a TLR2 agonist on neonatal brain development. Methodology/Principal Findings: Mice were injected intraperitoneally (i.p.) once a day from postnatal day (PND) 3 to PND11 with endotoxin-free saline, a TLR2 agonist Pam$_{3}$CSK$_{4}$ (5 mg/kg) or Lipopolysaccharide (LPS, 0.3 mg/kg). Pups were sacrificed at PND12 or PND53 and brain, spleen and liver were collected and weighed. Brain sections were stained for brain injury markers. Long-term effects on memory function were assessed using the Trace Fear Conditioning test at PND50. After 9 days of Pam$_{3}$CSK$_{4}$ administration, we found a decreased volume of cerebral gray matter, white matter in the forebrain and cerebellar molecular layer that was accompanied by an increase in spleen and liver weight at PND12. Such effects were not observed in Pam$_{3}$CSK$_{4}$-treated TLR 2-deficient mice. Pam$_{3}$CSK$_{4}$-treated mice also displayed decreased hippocampus neuronal density, and increased cerebral microglia density, while there was no effect on caspase-3 or general cell proliferation at PND12. Significantly elevated levels of IL-1β, IL-6, KC, and MCP-1 were detected after the first Pam$_{3}$CSK$_{4}$ injection in brain homogenates of PND3 mice. Pam$_{3}$CSK$_{4}$administration did not affect long-term memory function nor the volume of gray or white matter. Conclusions/Significance: Repeated systemic exposure to the TLR2 agonist Pam$_{3}$CSK$_{4}$ can have a short-term negative impact on the neonatal mouse brain

Editing the genome of chicken primordial germ cells to introduce alleles and study gene function

With continuing advances in genome sequencing technology, the chicken genome assembly is now better annotated with improved accuracy to the level of single nucleotide polymorphisms. Additionally, the genomes of other birds such as the duck, turkey and zebra finch have now been sequenced. A great opportunity exists in avian biology to use genome editing technology to introduce small and defined sequence changes to create specific haplotypes in chicken to investigate gene regulatory function, and also perform rapid and seamless transfer of specific alleles between chicken breeds. The methods for performing such precise genome editing are well established for mammalian species but are not readily applicable in birds due to evolutionary differences in reproductive biology. A significant leap forward to address this challenge in avian biology was the development of long-term culture methods for chicken primordial germ cells (PGCs). PGCs present a cell line in which to perform targeted genetic manipulations that will be heritable. Chicken PGCs have been successfully targeted to generate genetically modified chickens. However, genome editing to introduce small and defined sequence changes has not been demonstrated in any avian species. To address this deficit, the application of CRISPR/Cas9 and short oligonucleotide donors in chicken PGCs for performing small and defined sequence changes was investigated in this thesis. Specifically, homology-directed DNA repair (HDR) using oligonucleotide donors along with wild-type CRISPR/Cas9 (SpCas9-WT) or high fidelity CRISPR/Cas9 (SpCas9-HF1) was investigated in cultured chicken PGCs. The results obtained showed that small sequences changes ranging from a single to a few nucleotides could be precisely edited in many loci in chicken PGCs. In comparison to SpCas9-WT, SpCas9-HF1 increased the frequency of biallelic and single allele editing to generate specific homozygous and heterozygous genotypes. This finding demonstrates the utility of high fidelity CRISPR/Cas9 variants for performing sequence editing with high efficiency in PGCs. Since PGCs can be converted into pluripotent stem cells that can potentially differentiate into many cell types from the three germ layers, genome editing of PGCs can, therefore, be used to generate PGC-derived avian cell types with defined genetic alterations to investigate the host-pathogen interactions of infectious avian diseases. To investigate this possibility, the chicken ANP32A gene was investigated as a target for genetic resistance to avian influenza virus in PGC-derived chicken cell lines. Targeted modification of ANP32A was performed to generate clonal lines of genome-edited PGCs. Avian influenza minigenome replication assays were subsequently performed in the ANP32A-mutant PGC-derived cell lines. The results verified that ANP32A function is crucial for the function of both avian virus polymerase and human-adapted virus polymerase in chicken cells. Importantly, an asparagine to isoleucine mutation at position 129 (N129I) in chicken ANP32A failed to support avian influenza polymerase function. This genetic change can be introduced into chickens and validated in virological studies. Importantly, the results of my investigation demonstrate the potential to use genome editing of PGCs as an approach to generate many types of unique cell models for the study of avian biology. Genome editing of PGCs may also be applied to unravel the genes that control the development of the avian germ cell lineage. In the mouse, gene targeting has been extensively applied to generate loss-of-function mouse models to use the reverse genetics approach to identify key genes that regulate the migration of specified PGCs to the genital ridges. Avian PGCs express similar cytokine receptors as their mammalian counterparts. However, the factors guiding the migration of avian PGCs are largely unknown. To address this, CRISPR/Cas9 was used in this thesis to generate clonal lines of chicken PGCs with loss-of-function deletions in the CXCR4 and c-Kit genes which have been implicated in controlling mouse PGC migration. The results showed that CXCR4-deficient PGCs are absent from the gonads whereas c-Kit-deficient PGCs colonise the developing gonads in reduced numbers and are significantly reduced or absent from older stages. This finding shows a conserved role for CXCR4 and c-Kit signalling in chicken PGC development. Importantly, other genes suspected to be involved in controlling the development of avian germ cells can be investigated using this approach to increase our understanding of avian reproductive biology. Finally, the methods developed in this thesis for editing of the chicken genome may be applied in other avian species once culture methods for the PGCs from these species are develope

MS Replication Project: Engelbrecht-Wiggans & Katok (2008) Replication

Recordings of stimuli for MS replication project -- Engelbrecht-Wiggans & Katok (2008) replication. Laboratory sessions