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Background: Previous observational studies have demonstrated a connection between the risk of Type 2 diabetes mellitus (T2DM) and gastrointestinal problems brought on by Helicobacter pylori (H. pylori) infection. However, little is understood about how these factors impact on T2DM. Method: This study used data from the GWAS database on H. pylori antibodies, gastroduodenal ulcers, chronic gastritis, gastric cancer, T2DM and information on potential mediators: obesity, glycosylated hemoglobin (HbA1c) and blood glucose levels. Using univariate Mendelian randomization (MR) and multivariate MR (MVMR) analyses to evaluate the relationship between H. pylori and associated gastrointestinal diseases with the risk of developing of T2DM and explore the presence of mediators to ascertain the probable mechanisms. Results: Genetic evidence suggests that H. pylori IgG antibody (P = 0.006, b = 0.0945, OR = 1.0995, 95% CI = 1.023–1.176), H. pylori GroEL antibody (P = 0.028, OR = 1.033, 95% CI = 1.004–1.064), gastroduodenal ulcers (P = 0.019, OR = 1.036, 95% CI = 1.006–1.068) and chronic gastritis (P = 0.005, OR = 1.042, 95% CI = 1.012–1.074) are all linked to an increased risk of T2DM, additionally, H. pylori IgG antibody is associated with obesity (P = 0.034, OR = 1.03, 95% CI = 1.002–1.055). The results of MVMR showed that the pathogenic relationship between H. pylori GroEL antibody and gastroduodenal ulcer in T2DM is mediated by blood glucose level and obesity, respectively. Conclusion: Our study found that H. pylori IgG antibody, H. pylori GroEL antibody, gastroduodenal ulcer and chronic gastritis are all related to t T2DM, and blood glucose level and obesity mediate the development of H. pylori GroEL antibody and gastroduodenal ulcer on T2DM, respectively. These findings may inform new prevention and intervention strategies for T2DM. [ABSTRACT FROM AUTHOR]

The halophyte Suaeda salsa displayed strong resistance to salinity. Up to date, molecular mechanisms underlying tolerance of S. salsa to salinity have not been well understood. In the present study, S. salsa seedlings were treated with 30‰ salinity and then leaves and roots were subjected to Illumina sequencing. Compared with the control, 68,599 and 77,250 unigenes were significantly differentially expressed in leaves and roots in saline treatment, respectively. KEGG enrichment analyses indicated that photosynthesis process, carbohydrate, lipid and amino acid metabolisms were all downregulated in saline treatment, which should inhibit growth of S. salsa. Expression levels of Na+/H+ exchanger, V-H+ ATPase, choline monooxygenase, potassium and chloride channels were upregulated in saline treatment, which could relieve reduce over-accumulation of Na+ and Cl-. Fe-SOD, glutathione, L-ascorbate and flavonoids function as antioxidants in plants. Genes in relation to them were all upregulated, suggesting that S. salsa initiated various antioxidant mechanisms to tolerate high salinity. Besides, plant hormones, especially auxin, ethylene and jasmonic acid signaling transduction pathways were all upregulated in response to saline treatment, which were important to gene regulations of ion transportation and antioxidation. These changes might comprehensively contribute to tolerance of S. salsa to salinity. Overall, the present study provided new insights to understand the mechanisms underlying tolerance to salinity in halophytes. [ABSTRACT FROM AUTHOR]

Background: Workplace violence is a widely-reported phenomenon among healthcare providers and negatively affects quality of care and treatment. This study aims to understand the potential factors related to HCV through the experiences of women who have undergone a pregnancy termination due to fetal anomaly. Methods: Qualitative interview was used to collect data in this case study. Forty-one pregnant women who decided to terminate their pregnancy due to fetal anomaly were recruited from four Chinese hospital facilities, including three general hospitals and one specialty hospital in Changsha, Hunan, China. In-depth interviews were conducted from May to September 2017. Content analysis was used to analyze the data. Results: Several potential factors related to violence in healthcare facilities were identified, including preventive factors, which possibly relieve healthcare violence; and negative experiences, which potentially related to healthcare violence. Preventive factors include healthcare providers gaining patient trust with detailed observation, expressing patient-centered care through discreet behavior, and showing patience and professionalism. Factors related to violence include busy work schedules, hurried visits, mechanized process, patients’ scant medical knowledge and mental distress. Conclusions: This study highlights potential factors related to healthcare violence. The results will be submitted to the Chinese government’s policy making department in order to improve the healthcare system. We also suggest several important strategies to prevent HCV in a healthcare setting, both in China and globally. [ABSTRACT FROM AUTHOR]

Isoalantolactone has recently been revealed to induce apoptosis in several types of cancer. However, little is reported on its anti-tumor potential on human lung cancer. Our present study was designed to investigate its effects on human lung squamous carcinoma SK-MES-1 cells. We found that Isoalantolactone induced cellular and DNA morphological changes and decreased the viability of SK-MES-1 cells. It significantly inhibited the growth of SK-MES-1 cells through apoptosis in a dose-dependent manner via activation of p53. It also induced cell cycle arrest at G1 phase. It can down-regulate Bcl-2 and up-regulate Bax, to induce dissipation of mitochondrial membrane potential and generation of reactive oxygen species. Caspase-3 was also activated by Isoalantolactone, with the cleavage of poly (ADP-ribose) polymerase. Our results reveal that Isoalantolactone induces intrinsic apoptosis in SK-MES-1 cells through p53 signaling pathway, which suggests that Isoalantolactone could be a potential leading compound for future development of anti-lung cancer drugs. [ABSTRACT FROM AUTHOR]

Objective: To explore the potential damaging effect of chronic pelvic inflammation on ovarian reserve. Design: Case-control study. Patients: A total of 122 women with bilateral tubal occlusion, diagnosed by hysterosalipingography (HSG) and 217 women with normal fallopians were recruited. Measurements: Serum anti-Mullerian hormone (AMH), basic follicle-stimulating hormone (FSH), luteining hormone (LH), estradiol (E2), and testosterone (T) were measured; and antral follicle counts (AFCs) were recorded. Results: Significantly lower level of AMH was observed in women with bilateral tubal occlusion compared to control group [2.62 (2.95) ng/ml vs. 3.37 (3.11) ng/ml, P = 0.03], and the difference remained after adjustment of BMI (Padjust = 0.04). However, no statistical difference was found in the levels of FSH [7.00 (2.16) IU/L vs. 6.74 (2.30) IU/L], LH [4.18 (1.52) IU/L vs. 4.63 (2.52) IU/L], E2 [35.95 (20.40) pg/ml vs. 34.90 (17.85) pg/ml], T [25.07±11.46 ng/dl vs. 24.84±12.75 ng/dl], and AFC [6.00 (4.00) vs. 7.00 (4.00)] between two groups (p>0.05). Conclusions: Women with bilateral tubal occlusion showed decreased AMH level, suggesting that chronic pelvic inflammation may diminish ovarian reserve. More caution should be paid when evaluating the detriment of PID on female fertility. [ABSTRACT FROM AUTHOR]

Little is known about the repertoire of cellular factors involved in the replication of pathogenic alphaviruses. To uncover molecular regulators of alphavirus infection, and to identify candidate drug targets, we performed a high-content imaging-based siRNA screen. We revealed an actin-remodeling pathway involving Rac1, PIP5K1- α, and Arp3, as essential for infection by pathogenic alphaviruses. Infection causes cellular actin rearrangements into large bundles of actin filaments termed actin foci. Actin foci are generated late in infection concomitantly with alphavirus envelope (E2) expression and are dependent on the activities of Rac1 and Arp3. E2 associates with actin in alphavirus-infected cells and co-localizes with Rac1–PIP5K1-α along actin filaments in the context of actin foci. Finally, Rac1, Arp3, and actin polymerization inhibitors interfere with E2 trafficking from the trans-Golgi network to the cell surface, suggesting a plausible model in which transport of E2 to the cell surface is mediated via Rac1- and Arp3-dependent actin remodeling. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arterial hypertension is usually fatal due to right ventricular failure and is frequently associated with co-existing left ventricular dysfunction. Endothelin-1 is a powerful pro-fibrotic mediator and vasoconstrictor that is elevated in pulmonary arterial hypertension. Endothelin receptor blockers are commonly used as pulmonary vasodilators, however their effect on biventricular injury, remodeling and function, despite elevated isolated right ventricular afterload is unknown. Methods: Elevated right ventricular afterload was induced by progressive pulmonary artery banding. Seven rabbits underwent pulmonary artery banding without macitentan; 13 received pulmonary artery banding + macitentan; and 5 did not undergo inflation of the pulmonary artery band (sham-operated controls). Results: Right and left ventricular collagen content was increased with pulmonary artery banding compared to sham-operated controls and ameliorated by macitentan. Right ventricular fibrosis signaling (connective tissue growth factor and endothelin-1 protein levels); extra-cellular matrix remodeling (matrix-metalloproteinases 2 and 9), apoptosis and apoptosis-related peptides (caspases 3 and 8) were increased with pulmonary artery banding compared with sham-operated controls and decreased with macitentan. Conclusion: Isolated right ventricular afterload causes biventricular fibrosis, right ventricular apoptosis and extra cellular matrix remodeling, mediated by up-regulation of endothelin-1 and connective tissue growth factor signaling. These pathological changes are ameliorated by dual endothelin receptor blockade despite persistent elevated right ventricular afterload. [ABSTRACT FROM AUTHOR]

Many marine bacteria secrete exopolysaccharides (EPSs) that have important ecological and physiological functions. Numerous nutritional and environmental factors influence bacterial EPS production. However, the regulatory mechanisms of EPS production are poorly understood. The deep-sea Bacteroidetes bacterium Zunongwangia profunda SM-A87 can produce high quantities of EPS, and its EPS production is enhanced significantly by lactose. Here, we studied the reasons behind the significant advantage that lactose has over other carbon sources in EPS production in SM-A87. RNA-seq technologies were used to study lactose-regulated genes in SM-A87. The expression level of genes within the EPS gene cluster was up-regulated when lactose was added. Supplement of lactose also influenced the expression of genes located outside the EPS gene cluster that are also involved in EPS biosynthesis. The major glycosyl components of SM-A87 EPS are mannose, glucose and galactose. Genomic metabolic pathway analyses showed that the EPS precursor GDP-mannose can be synthesized from glucose, while the precursor UDP-glucose must be synthesized from galactose. Lactose can provide glucose and galactose simultaneously and prevent glucose inhibition. Lactose can also greatly stimulate the growth of SM-A87. Taken together, lactose acts not only as an inducer but also as a carbohydrate source for EPS production. This research broadens our knowledge of the regulation of EPS production in marine bacteria. [ABSTRACT FROM AUTHOR]

Ferns usually have relatively lower photosynthetic potential than angiosperms. However, it is unclear whether low photosynthetic potential of ferns is linked to leaf water supply. We hypothesized that there is an evolutionary association of leaf water transport capacity with photosynthesis and stomatal density in ferns. In the present study, a series of functional traits relating to leaf anatomy, hydraulics and physiology were assessed in 19 terrestrial and 11 epiphytic ferns in a common garden, and analyzed by a comparative phylogenetics method. Compared with epiphytic ferns, terrestrial ferns had higher vein density (Dvein), stomatal density (SD), stomatal conductance (gs), and photosynthetic capacity (Amax), but lower values for lower epidermal thickness (LET) and leaf thickness (LT). Across species, all traits varied significantly, but only stomatal length (SL) showed strong phylogenetic conservatism. Amax was positively correlated with Dvein and gs with and without phylogenetic corrections. SD correlated positively with Amax, Dvein and gs, with the correlation between SD and Dvein being significant after phylogenetic correction. Leaf water content showed significant correlations with LET, LT, and mesophyll thickness. Our results provide evidence that Amax of the studied ferns is linked to leaf water transport capacity, and there was an evolutionary association between water supply and demand in ferns. These findings add new insights into the evolutionary correlations among traits involving carbon and water economy in ferns. [ABSTRACT FROM AUTHOR]

Biodiversity of mangrove ecosystems is difficult to assess, at least partly due to lack of genetic verification of morphologybased documentation of species. Natural hybridization, on the one hand, plays an important role in evolution as a source of novel gene combinations and a mechanism of speciation. However, on the other hand, recurrent introgression allows gene flow between species and could reverse the process of genetic differentiation among populations required for speciation. To understand the dynamic evolutionary consequences of hybridization, this study examines genomic structure of hybrids and parental species at the population level. In the Indo-West Pacific, Bruguiera is one of the dominant mangrove genera and species ranges overlap extensively with one another. Morphological intermediates between sympatric Bruguiera gymnorrhiza and Bruguiera sexangula have been reported as a variety of B. sexangula or a new hybrid species, B. 6 rhynchopetala. However, the direction of hybridization and extent of introgression are unclear. A large number of speciesspecific inter-simple sequence repeat (ISSR) markers were found in B. gymnorrhiza and B. sexangula, and the additive ISSR profiling of B. 6 rhynchopetala ascertained its hybrid status and identified its parental origin. The varying degree of scatterness among hybrid individuals in Principal Coordinate Analysis and results from NewHybrids analysis indicate that B. 6rhynchopetala comprises different generations of introgressants in addition to F1s. High genetic relatedness between B. x rhynchopetala and B. gymnorrhiza based on nuclear and chloroplast sequences suggests preferential hybrid backcrosses to B. gymnorrhiza. We conclude that B. x rhynchopetala has not evolved into an incipient hybrid species, and its persistence can be explained by recurrent hybridization and introgression. Genomic data provide insights into the hybridization dynamics of mangrove plants. Such information can assist in biodiversity assessment by helping detect novel taxa and/or define species boundaries. [ABSTRACT FROM AUTHOR]

Background:Avian reovirus (ARV) causes arthritis, tenosynovitis, runting-stunting syndrome (RSS), malabsorption syndrome (MAS) and immunosuppression in chickens. σB is one of the major structural proteins of ARV, which is able to induce group-specific antibodies against the virus. Methods and Results:The present study described the identification of two linear B-cell epitopes in ARV σB through expressing a set of partially overlapping and consecutive truncated peptides spanning σB screened with two monoclonal antibodies (mAbs) 1F4 and 1H3-1.The data indicated that 21KTPACW26 (epitope A) and 32WDTVTFH38 (epitope B) were minimal determinants of the linear B cell epitopes. Antibodies present in the serum of ARV-positive chickens recognized the minimal linear epitopes in Western blot analyses. By sequence alignment analysis, we determined that the epitopes A and B were not conserved among ARV, duck reovirus (DRV) and turkey reovirus (TRV) strains. Western blot assays, confirmed that epitopes A and B were ARV-specific epitopes, and they could not react with the corresponding peptides of DRV and TRV. Conclusions and Significance:We identified 21KTPACW26 and 32WDTVTFH38 as σB -specific epitopes recognized by mAbs 1F4 and 1H3-1, respectively. The results in this study may have potential applications in development of diagnostic techniques and epitope-based marker vaccines against ARV groups. [ABSTRACT FROM AUTHOR]

Background: Both leaf attributes and stomatal traits are linked to water economy in land plants. However, it is unclear whether these two components are associated evolutionarily., Methodology/principal Findings: In characterizing the possible effect of phylogeny on leaf attributes and stomatal traits, we hypothesized that a correlated evolution exists between the two. Using a phylogenetic comparative method, we analyzed 14 leaf attributes and stomatal traits for 17 species in Paphiopedilum. Stomatal length (SL), stomatal area (SA), upper cuticular thickness (UCT), and total cuticular thickness (TCT) showed strong phylogenetic conservatism whereas stomatal density (SD) and stomatal index (SI) were significantly convergent. Leaf vein density was correlated with SL and SD whether or not phylogeny was considered. The lower epidermal thickness (LET) was correlated positively with SL, SA, and stomatal width but negatively with SD when phylogeny was not considered. When this phylogenetic influence was factored in, only the significant correlation between SL and LET remained., Conclusion/significance: Our results support the hypothesis for correlated evolution between stomatal traits and vein density in Paphiopedilum. However, they do not provide evidence for an evolutionary association between stomata and leaf thickness. These findings lend insight into the evolution of traits related to water economy for orchids under natural selection.

Copy number variants (CNVs) are known to cause Mendelian forms of Parkinson disease (PD), most notably in SNCA and PARK2. PARK2 has a recessive mode of inheritance; however, recent evidence demonstrates that a single CNV in PARK2 (but not a single missense mutation) may increase risk for PD. We recently performed a genome-wide association study for PD that excluded individuals known to have either a LRRK2 mutation or two PARK2 mutations. Data from the Illumina370Duo arrays were re-clustered using only white individuals with high quality intensity data, and CNV calls were made using two algorithms, PennCNV and QuantiSNP. After quality assessment, the final sample included 816 cases and 856 controls. Results varied between the two CNV calling algorithms for many regions, including the PARK2 locus (genome-wide p = 0.04 for PennCNV and p = 0.13 for QuantiSNP). However, there was consistent evidence with both algorithms for two novel genes, USP32 and DOCK5 (empirical, genome-wide p-values<0.001). PARK2 CNVs tended to be larger, and all instances that were molecularly tested were validated. In contrast, the CNVs in both novel loci were smaller and failed to replicate using real-time PCR, MLPA, and gel electrophoresis. The DOCK5 variation is more akin to a VNTR than a typical CNV and the association is likely caused by artifact due to DNA source. DNA for all the cases was derived from whole blood, while the DNA for all controls was derived from lymphoblast cell lines. The USP32 locus contains many SNPs with low minor allele frequency leading to a loss of heterozygosity that may have been spuriously interpreted by the CNV calling algorithms as support for a deletion. Thus, only the CNVs within the PARK2 locus could be molecularly validated and associated with PD susceptibility.

The Esx-1 (type VII) secretion system is a major virulence determinant of pathogenic mycobacteria, including Mycobacterium marinum. However, the molecular events and host-pathogen interactions underlying Esx-1-mediated virulence in vivo remain unclear. Here we address this problem in a non-lethal mouse model of M. marinum infection that allows detailed quantitative analysis of disease progression. M. marinum established local infection in mouse tails, with Esx-1-dependent formation of caseating granulomas similar to those formed in human tuberculosis, and bone deterioration reminiscent of skeletal tuberculosis. Analysis of tails infected with wild type or Esx-1-deficient bacteria showed that Esx-1 enhanced generation of proinflammatory cytokines, including the secreted form of IL-1beta, suggesting that Esx-1 promotes inflammasome activation in vivo. In vitro experiments indicated that Esx-1-dependent inflammasome activation required the host NLRP3 and ASC proteins. Infection of wild type and ASC-deficient mice demonstrated that Esx-1-dependent inflammasome activation exacerbated disease without restricting bacterial growth, indicating a host-detrimental role of this inflammatory pathway in mycobacterial infection. These findings define an immunoregulatory role for Esx-1 in a specific host-pathogen interaction in vivo, and indicate that the Esx-1 secretion system promotes disease and inflammation through its ability to activate the inflammasome.