23 research outputs found
An Iterative Approach for Model Selection in A Class of Semiparametric Models
A novel algorithm to simultaneously select and estimate the Single-Index Varying Coefficient models
Electrothermal combined optimization on notch in air-cooled high-speed permanent-magnet generator
A 30kVA, 96000rpm, air cooled high-speed permanent magnetic generator (HSPMG) is investigated in this paper. Considering effects on both the magnetic circuit and heat transfer paths comprehensively, the stator slot notch in this HSPMG is optimized. First, by using the time-stepping finite element method, the transient electromagnetic fields of HSPMG is numerically calculated, and the electromagnetic losses in different components are obtained. Then, after the determination of other mechanical losses in such a machine, a three-dimensional fluid-thermal coupling calculation model is established, and the working temperature distribution in the HSPMG is studied. Thus, the electromagnetic-fluid-thermal coupling analysis method on the HSPMG is proposed, by using which the influences of machine notch height on machine magnetic circuit and cooling air flowing path are investigated. Meanwhile, both the electromagnetic performance and the temperature distribution in HSPMG with different stator notch height are studied, and a series of analytical equations are deduced to describe the variations of machine performances with stator notch. By using the proposed unbalance relative weighting method, the notch height is optimized to enhance the performance of HSPMG. The obtained conclusions could provide reference for HSPMG electromagnetic calculation, cooling system design, and optimization design
Jump-seq: Genome-Wide Capture and Amplification of 5-Hydroxymethylcytosine Sites
5-Hydroxymethylcytosine
(5hmC) arises from the oxidation of 5-methylcytosine
(5mC) by Fe2+ and 2-oxoglutarate-dependent 10–11
translocation (TET) family proteins. Substantial levels of 5hmC accumulate
in many mammalian tissues, especially in neurons and embryonic stem
cells, suggesting a potential active role for 5hmC in epigenetic regulation
beyond being simply an intermediate of active DNA demethylation. 5mC
and 5hmC undergo dynamic changes during embryogenesis, neurogenesis,
hematopoietic development, and oncogenesis. While methods have been
developed to map 5hmC, more efficient approaches to detect 5hmC at
base resolution are still highly desirable. Herein, we present a new
method, Jump-seq, to capture and amplify 5hmC in genomic DNA. The
principle of this method is to label 5hmC by the 6-N3-glucose moiety and connect a hairpin DNA oligonucleotide carrying
an alkyne group to the azide-modified 5hmC via Huisgen cycloaddition
(click) chemistry. Primer extension starts from the hairpin motif
to the modified 5hmC site and then continues to “land”
on genomic DNA. 5hmC sites are inferred from genomic DNA sequences
immediately spanning the 5-prime junction. This technology was validated,
and its utility in 5hmC identification was confirmed
Activation of the 5-hydroxytryptamine 4 receptor ameliorates tight junction barrier dysfunction in the colon of type 1 diabetic mice
Hyperglycemia drives dysfunction of the intestinal barrier. 5-Hydroxytryptaine 4 receptor (5-HT4R) agonists have been considered therapeutics for constipation in clnic. However, the roles of 5-HT4R activation in mucosa should be fully realized. Here, we investigate the effects of 5-HT4R activation on diabetes-induced disruption of the tight junction (TJ) barrier in the colon. Not surprisingly, the TJ barrier in diabetic mice with or without 5-HT4R is tremendously destroyed, as indicated by increased serum fluorescein isothiocyanate (FITC)-dextran and decreased transepithelial electrical resistance (TER). Simultaneously, decreased expressions of TJ proteins are shown in both wild-type (WT) and 5-HT4R knockout (KO) mice with diabetes. Notably, chronic treatment with intraperitoneal injection of a 5-HT4R agonist in WT mice with diabetes repairs the TJ barrier and promotes TJ protein expressions, including occludin, claudin-1 and ZO-1, in the colon, whereas a 5-HT4R agonist does not improve TJ barrier function or TJ protein expressions in 5-HT4R KO mice with diabetes. Furthermore, stimulation of 5-HT4R inhibits diabetes-induced upregulation of myosin light chain kinase (MLCK), Rho-associated coiled coil protein kinase 1 (ROCK1), and phosphorylated myosin light chain (p-MLC), which are key molecules that regulate TJ integrity, in the colonic mucosa of WT mice. However, such action induced by a 5-HT4R agonist is not observed in 5-HT4R KO mice with diabetes. These findings indicate that 5-HT4R activation may restore TJ integrity by inhibiting the expressions of MLCK, ROCK1 and p-MLC, improving epithelial barrier function in diabetes
Asymmetric Reprogramming Capacity of Parental Pronuclei in Mouse Zygotes
It has been demonstrated that reprogramming factors are sequestered in the pronuclei of zygotes after fertilization, because zygotes enucleated at the M phase instead of interphase of the first mitosis can support the development of cloned embryos. However, the contribution of the parental pronucleus derived from either the sperm or the oocyte in reprogramming remains elusive. Here, we demonstrate that the parental pronuclei have asymmetric reprogramming capacities and that the reprogramming factors reside predominantly in the male pronucleus. As a result, only female pronucleus-depleted (FPD) mouse zygotes can reprogram somatic cells to a pluripotent state and support the full-term development of cloned embryos; male pronucleus-depleted (MPD) zygotes fail to support somatic cell reprogramming. We further demonstrate that fusion of an additional male pronucleus into a zygote greatly enhances reprogramming efficiency. Our data provide a clue to further identify critical reprogramming factors in the male pronucleus
Protein Expression Landscape of Mouse Embryos during Pre-implantation Development
Pre-implantation embryo development is an intricate and precisely regulated process orchestrated by maternally inherited proteins and newly synthesized proteins following zygotic genome activation. Although genomic and transcriptomic studies have enriched our understanding of the genetic programs underlying this process, the protein expression landscape remains unexplored. Using quantitative mass spectrometry, we identified nearly 5,000 proteins from 8,000 mouse embryos of each stage (zygote, 2-cell, 4-cell, 8-cell, morula, and blastocyst). We found that protein expression in zygotes, morulas, and blastocysts is distinct from 2- to 8-cell embryos. Analysis of protein phosphorylation identified critical kinases and signal transduction pathways. We highlight key factors and their important roles in embryo development. Combined analysis of transcriptomic and proteomic data reveals coordinated control of RNA degradation, transcription, and translation and identifies previously undefined exon-junction-derived peptides. Our study provides an invaluable resource for further mechanistic studies and suggests core factors regulating pre-implantation embryo development
Eubacterium rectale is a potential marker of altered gut microbiota in psoriasis and psoriatic arthritis
ABSTRACTPrevious studies have profiled the gut microbiota among psoriatic patients compared to that among healthy individuals. However, a comprehensive understanding of the magnitude, direction, and detailed compositional and functional profiles remains limited. Additionally, research exploring the gut microbiota in the context of both plaque psoriasis (PsO) and psoriatic arthritis (PsA) is lacking. To assess the taxonomic and functional characteristics of the gut microbiota in PsO and PsA patients and investigate potential links between the gut microbiota and disease pathogenesis. We collected fecal samples from 70 psoriatic patients (44 PsO and 26 PsA) and 25 age- and gender-matched healthy controls (HC) and employed deep metagenomic sequencing to characterize their gut microbiota. We noted significant alternations in the gut microbiota compositions of both PsO and PsA patients compared to those of HC. Despite limited effect sizes in alpha diversity (12.3% reduction of microbial richness but unchanged evenness in psoriatic patients) and beta diversity (disease accounts for 3.5% of total variations), we consistently observed substantial reductions of Eubacterium rectale in both PsO and PsA patients, with PsA patients exhibiting even lower levels of E. rectale than PsO patients. Additionally, two Alistipes species were also depleted in psoriatic patients. These microorganisms are known to play crucial roles in carbohydrate metabolism pathways, mainly producing short-chain fatty acids with anti-inflammatory effects. Overall, our observations supplemented the profiling of altered gut microbiota in patients with PsO and PsA at the species level and described a link between the dominant short-chain fatty acid-producing bacterial species and systemic immunity in psoriatic patients.IMPORTANCEIn this observational clinical study with sufficient sample size and metagenomic sequencing to profile the gut microbiota, we identified consistent signals of the depleted abundance of Eubacterium rectale and related functional genes among psoriatic patients, including those with psoriatic arthritis. E. rectale may serve as an ecologically important functional unit in the gut microbiota, holding potential as a diagnostic marker and target for therapeutic interventions to achieve lasting effects. Our findings provide comprehensive gut microbiota profiling in psoriasis, resolving previous contradictions and generating new hypotheses for further investigation. These insights may significantly impact psoriasis management and related conditions