Environmental Factors and Male Infertility

A significant decrease in human fertility has been observed in the last 50 years. Approximately 15% of couples of reproductive age have fertility problems and about half of these cases are because of male factors. A growing body of evidence suggests that environmental factors play an important role in the causes of male infertility. Our environment is contaminated by natural and synthetic chemicals, which could interact with the endocrine system, resulting in the reduction of human fertility. Studies carried out in recent years have proven that endocrine-disrupting chemicals may disturb fertility of men. Improper lifestyle factors such as smoking, alcohol consumption, high temperature, radiation also have negative impact on male fertility. This chapter is an overview of recent developments about the importance of endocrine-disrupting chemicals and lifestyle factors’ effects on sperm counts and male fertility in human

Infection and Infertility

Infection is a multifactorial process, which can be induced by a virus, bacterium, or parasite. It may cause many diseases, including obesity, cancer, and infertility. In this chapter, we focus our attention on the association of infection and fertility alteration. Numerous studies have suggested that genetic polymorphisms influencing infection are associated with infertility. So we also review the genetic influence on infection and risk of infertility

Oxytocin and Pregnancy

Oxytocin, an important neuropeptide, exerts a wide influence on the central nervous system and the peripheral tissues. In the central nervous system, the oxytocin gene expression is mainly shown to be present in neurons in the hypothalamic paraventricular and supraoptic nuclei. Oxytocin gene also transcribes in the peripheral tissues such as uterus, placenta, and amnion. Oxytocin receptors can be founded in many tissues in humans, like the uterine, ovary, testis, kidney, and so on. And just in the same tissue, due to the variation of physiology factors, the amount of oxytocin changes a lot. Oxytocin secretion is closely linked with pregnancy advancing. During labor, the contractions of uterine smooth muscles and oxytocin secretion are inseparable. Moreover, oxytocin is also responsible for stimulating milk ejection after parturition. Oxytocin is associated with many diseases. Poor regulation of oxytocin may cause postpartum depression and infantile autism. In terms of physiology, fatal heart failure and gestational hypertension are concerned with oxytocin level. In this chapter, we will discuss the oxytocin in pregnancy as well as its clinical applications

Identification of DNA motif pairs on paired sequences based on composite heterogeneous graph

MotivationThe interaction between DNA motifs (DNA motif pairs) influences gene expression through partnership or competition in the process of gene regulation. Potential chromatin interactions between different DNA motifs have been implicated in various diseases. However, current methods for identifying DNA motif pairs rely on the recognition of single DNA motifs or probabilities, which may result in local optimal solutions and can be sensitive to the choice of initial values. A method for precisely identifying DNA motif pairs is still lacking.ResultsHere, we propose a novel computational method for predicting DNA Motif Pairs based on Composite Heterogeneous Graph (MPCHG). This approach leverages a composite heterogeneous graph model to identify DNA motif pairs on paired sequences. Compared with the existing methods, MPCHG has greatly improved the accuracy of motifs prediction. Furthermore, the predicted DNA motifs demonstrate heightened DNase accessibility than the background sequences. Notably, the two DNA motifs forming a pair exhibit functional consistency. Importantly, the interacting TF pairs obtained by predicted DNA motif pairs were significantly enriched with known interacting TF pairs, suggesting their potential contribution to chromatin interactions. Collectively, we believe that these identified DNA motif pairs held substantial implications for revealing gene transcriptional regulation under long-range chromatin interactions

Adsorption Mechanism of Cu-Doped SnO 2

The content of hydrogen is a key quantity in condition assessment and fault diagnosis of power transformer. Based on the density functional theory (DFT), the adsorption mechanism of Cu-doped SnO2 surface toward H2 has been systematically studied in this work. Firstly, the relaxation, the bond length, and overlap population of both the pure and Cu-doped SnO2 are computed. To determine the optimal doping position, the formation energies of four potential sites (i.e., Sn5c, Sn6c, Sn5c-s, and Sn6c-s) are then compared with each other. The adsorption energy and the electronic structure of SnO2 surface are analysed and discussed in detail. Furthermore, to estimate the partial atomic charges and the electrical conductance, the Mulliken population analysis is also performed. It has been found that the bridge oxygen is the most favourable position. The partial density of states of H2 after adsorption is broadened and shifted close to the Fermi level. A large amount of charges would be transferred and then released back into its conduction band, leading to the reduction of resistance and the enhancement of sensitivity toward H2. The results of this work provide references for SnO2-based sensor design

Identification and characterization of a 25-lncRNA prognostic signature for early recurrence in hepatocellular carcinoma

Background Early recurrence is the major cause of poor prognosis in hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) are deeply involved in HCC prognosis. In this study, we aimed to establish a prognostic lncRNA signature for HCC early recurrence. Methods The lncRNA expression profile and corresponding clinical data were retrieved from total 299 HCC patients in TCGA database. LncRNA candidates correlated to early recurrence were selected by differentially expressed gene (DEG), univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses. A 25-lncRNA prognostic signature was constructed according to receiver operating characteristic curve (ROC). Kaplan-Meier and multivariate Cox regression analyses were used to evaluate the performance of this signature. ROC and nomogram were used to evaluate the integrated models based on this signature with other independent clinical risk factors. Gene set enrichment analysis (GSEA) was used to reveal enriched gene sets in the high-risk group. Tumor infiltrating lymphocytes (TILs) levels were analyzed with single sample Gene Set Enrichment Analysis (ssGSEA). Immune therapy response prediction was performed with TIDE and SubMap. Chemotherapeutic response prediction was conducted by using Genomics of Drug Sensitivity in Cancer (GDSC) pharmacogenomics database. Results Compared to low-risk group, patients in high-risk group showed reduced disease-free survival (DFS) in the training (p < 0.0001) and validation cohort (p = 0.0132). The 25-lncRNA signature, AFP, TNM and vascular invasion could serve as independent risk factors for HCC early recurrence. Among them, the 25-lncRNA signature had the best predictive performance, and combination of those four risk factors further improves the prognostic potential. Moreover, GSEA showed significant enrichment of “E2F TARGETS”, “G2M CHECKPOINT”, “MYC TARGETS V1” and “DNA REPAIR” pathways in the high-risk group. In addition, increased TILs were observed in the low-risk group compared to the high-risk group. The 25-lncRNA signature negatively associates with the levels of some types of antitumor immune cells. Immunotherapies and chemotherapies prediction revealed differential responses to PD-1 inhibitor and several chemotherapeutic drugs in the low- and high-risk group. Conclusions Our study proposed a 25-lncRNA prognostic signature for predicting HCC early recurrence, which may guide postoperative treatment and recurrence surveillance in HCC patients

Regulation of Budding Yeast Mating-Type Switching Donor Preference by the FHA Domain of Fkh1

During Saccharomyces cerevisiae mating-type switching, an HO endonuclease-induced double-strand break (DSB) at MAT is repaired by recombining with one of two donors, HMLα or HMRa, located at opposite ends of chromosome III. MATa cells preferentially recombine with HMLα; this decision depends on the Recombination Enhancer (RE), located about 17 kb to the right of HML. In MATα cells, HML is rarely used and RE is bound by the MATα2-Mcm1 corepressor, which prevents the binding of other proteins to RE. In contrast, in MATa cells, RE is bound by multiple copies of Fkh1 and a single copy of Swi4/Swi6. We report here that, when RE is replaced with four LexA operators in MATa cells, 95% of cells use HMR for repair, but expression of a LexA-Fkh1 fusion protein strongly increases HML usage. A LexA-Fkh1 truncation, containing only Fkh1's phosphothreonine-binding FHA domain, restores HML usage to 90%. A LexA-FHA-R80A mutant lacking phosphothreonine binding fails to increase HML usage. The LexA-FHA fusion protein associates with chromatin in a 10-kb interval surrounding the HO cleavage site at MAT, but only after DSB induction. This association occurs even in a donorless strain lacking HML. We propose that the FHA domain of Fkh1 regulates donor preference by physically interacting with phosphorylated threonine residues created on proteins bound near the DSB, thus positioning HML close to the DSB at MAT. Donor preference is independent of Mec1/ATR and Tel1/ATM checkpoint protein kinases but partially depends on casein kinase II. RE stimulates the strand invasion step of interchromosomal recombination even for non-MAT sequences. We also find that when RE binds to the region near the DSB at MATa then Mec1 and Tel1 checkpoint kinases are not only able to phosphorylate histone H2A (γ-H2AX) around the DSB but can also promote γ-H2AX spreading around the RE region

Systematic Triple-Mutant Analysis Uncovers Functional Connectivity between Pathways Involved in Chromosome Regulation

Genetic interactions reveal the functional relationships between pairs of genes. In this study, we describe a method for the systematic generation and quantitation of triple mutants, termed Triple Mutant Analysis (TMA). We have used this approach to interrogate partially redundant pairs of genes in S. cerevisiae, including ASF1 and CAC1, two histone chaperones. After subjecting asf1Δ cac1Δ to TMA, we found that the Swi/Snf Rdh54 protein, compensates for the absence of Asf1 and Cac1. Rdh54 more strongly associates with the chromatin apparatus and the pericentromeric region in the double mutant. Moreover, Asf1 is responsible for the synthetic lethality observed in cac1Δ strains lacking the HIRA-like proteins. A similar TMA was carried out after deleting both CLB5 and CLB6, cyclins that regulate DNA replication, revealing a strong functional connection to chromosome segregation. This approach can reveal functional redundancies that cannot be uncovered using traditional double mutant analyses

POSTSYNTHESIS OF TITANIUM INCORPORATED WITH AMINO-FUNCTIONALIZATION UIO-66 FOR ENHANCING CO2 UPTAKE

Metal-organic frameworks (MOFs) are promising nanomaterials with unprecedented capacity to store small molecules. Titanium cooperated with NH2-UiO-66 were prepared via post synthesis modifications approach and their structures and properties were characterized by X-raydiffraction,Fourier transform infrared spectroscopy, thermogravimetric analysis, nitrogen adsorption isotherms, and scanning electron microscopy. The resultant titanium cooperated with NH2-UiO-66 showed excellent performance for CO2 adsorption via the formation of oxo-bridged hetero-Zr-Ti clusters. This result clearly demonstrates that the smaller Ti ions exchanged with the Zr ions of NH2-UiO-66 may decrease the pore sizes within the framework to be closer to the ideal pore sizes for CO2 adsorption

Association Analysis between the Polymorphisms of HSD11B1 and H6PD and Risk of Polycystic Ovary Syndrome in Chinese Population.

To evaluate whether single nucleotide polymorphisms of HSD11B1 (rs846908) and H6PD (rs6688832 and rs17368528) are associated with polycystic ovary syndrome (PCOS) in Chinese population.A case-control study was implemented to investigate the association between HSD11B1 and H6PD polymorphisms and PCOS. Patients with PCOS (n = 335) and controls (n = 354) were recruited in this study. Genetic variants of HSD11B1 (rs846908) and H6PD (rs6688832 and rs17368528) were analyzed by TaqMan method.We found a significantly 0.79-fold lower risk of G allele of rs6688832 in control group compared with the patients with PCOS (adjusted OR, 0.79; 95%CI = 0.63-0.99; P = 0.040). Additionally, significant difference in the levels of follicle stimulating hormone (FSH) was observed between AA and AG genotype in rs6688832. The rs6688832 AG genotype was associated with lower level of FSH (P = 0.039) and higher risk of hyperandrogenism (P = 0.016) in patients with PCOS. When all subjects were divided into different subgroups according to age and body mass index (BMI), we found that the frequency of G allele of rs6688832 was significantly higher in controls than that in PCOS patients in the subgroup of BMI > 23 (adjusted OR, 0.70; 95% CI = 0.50-0.98; P = 0.037).Our findings showed a statistical association between H6PD rs6688832 and PCOS risk in Chinese population. The G allele of rs6688832 in H6PD might exert potential genetic protective role against the development of PCOS, especially in overweight women. PCOS patients with AG genotype of rs6688832 might confer risk to the phenotype of hyperandrogenemia of PCOS