Trust as a mediator in the relationship between childhood sexual abuse and IL-6 level in adulthood

Childhood sexual abuse (CSA) has been shown to predict the coupling of depression and inflammation in adulthood. Trust within intimate relationships, a core element in marital relations, has been shown to predict positive physical and mental health outcomes, but the mediating role of trust in partners in the association between CSA and inflammation in adulthood requires further study. The present study aimed to examine the impact of CSA on inflammatory biomarkers (IL-6 and IL-1β) in adults with depression and the mediating role of trust. A cross-sectional survey data set of adults presenting with mood and sleep disturbance was used in the analysis. CSA demonstrated a significant negative correlation with IL-6 level (r = -0.28, p<0. 01) in adults with clinically significant depression, while trust showed a significant positive correlation with IL-6 level (r = 0.36, p < .01). Sobel test and bootstrapping revealed a significant mediating role for trust between CSA and IL-6 level. CSA and trust in partners were revealed to have significant associations with IL-6 level in adulthood. Counterintuitively, the directions of association were not those expected. Trust played a mediating role between CSA and adulthood levels of IL-6. Plausible explanations for these counterintuitive findings are discussed

Statistical identification of gene association by CID in application of constructing ER regulatory network

<p>Abstract</p> <p>Background</p> <p>A variety of high-throughput techniques are now available for constructing comprehensive gene regulatory networks in systems biology. In this study, we report a new statistical approach for facilitating <it>in silico </it>inference of regulatory network structure. The new measure of association, coefficient of intrinsic dependence (CID), is model-free and can be applied to both continuous and categorical distributions. When given two variables X and Y, CID answers whether Y is dependent on X by examining the conditional distribution of Y given X. In this paper, we apply CID to analyze the regulatory relationships between transcription factors (TFs) (X) and their downstream genes (Y) based on clinical data. More specifically, we use estrogen receptor α (ERα) as the variable X, and the analyses are based on 48 clinical breast cancer gene expression arrays (48A).</p> <p>Results</p> <p>The analytical utility of CID was evaluated in comparison with four commonly used statistical methods, Galton-Pearson's correlation coefficient (GPCC), Student's <it>t</it>-test (STT), coefficient of determination (CoD), and mutual information (MI). When being compared to GPCC, CoD, and MI, CID reveals its preferential ability to discover the regulatory association where distribution of the mRNA expression levels on X and Y does not fit linear models. On the other hand, when CID is used to measure the association of a continuous variable (Y) against a discrete variable (X), it shows similar performance as compared to STT, and appears to outperform CoD and MI. In addition, this study established a two-layer transcriptional regulatory network to exemplify the usage of CID, in combination with GPCC, in deciphering gene networks based on gene expression profiles from patient arrays.</p> <p>Conclusion</p> <p>CID is shown to provide useful information for identifying associations between genes and transcription factors of interest in patient arrays. When coupled with the relationships detected by GPCC, the association predicted by CID are applicable to the construction of transcriptional regulatory networks. This study shows how information from different data sources and learning algorithms can be integrated to investigate whether relevant regulatory mechanisms identified in cell models can also be partially re-identified in clinical samples of breast cancers.</p> <p>Availability</p> <p>the implementation of CID in R codes can be freely downloaded from <url>http://homepage.ntu.edu.tw/~lyliu/BC/</url>.</p

The Slow-Releasing Hydrogen Sulfide Donor, GYY4137, Exhibits Novel Anti-Cancer Effects In Vitro and In Vivo

The slow-releasing hydrogen sulfide (H2S) donor, GYY4137, caused concentration-dependent killing of seven different human cancer cell lines (HeLa, HCT-116, Hep G2, HL-60, MCF-7, MV4-11 and U2OS) but did not affect survival of normal human lung fibroblasts (IMR90, WI-38) as determined by trypan blue exclusion. Sodium hydrosulfide (NaHS) was less potent and not active in all cell lines. A structural analogue of GYY4137 (ZYJ1122) lacking sulfur and thence not able to release H2S was inactive. Similar results were obtained using a clonogenic assay. Incubation of GYY4137 (400 µM) in culture medium led to the generation of low (<20 µM) concentrations of H2S sustained over 7 days. In contrast, incubation of NaHS (400 µM) in the same way led to much higher (up to 400 µM) concentrations of H2S which persisted for only 1 hour. Mechanistic studies revealed that GYY4137 (400 µM) incubated for 5 days with MCF-7 but not IMR90 cells caused the generation of cleaved PARP and cleaved caspase 9, indicative of a pro-apoptotic effect. GYY4137 (but not ZYJ1122) also caused partial G2/M arrest of these cells. Mice xenograft studies using HL-60 and MV4-11 cells showed that GYY4137 (100–300 mg/kg/day for 14 days) significantly reduced tumor growth. We conclude that GYY4137 exhibits anti-cancer activity by releasing H2S over a period of days. We also propose that a combination of apoptosis and cell cycle arrest contributes to this effect and that H2S donors should be investigated further as potential anti-cancer agents

ATOMS : ALMA Three-millimeter Observations of Massive Star-forming regions - XI. From inflow to infall in hub-filament systems

We investigate the presence of hub-filament systems in a large sample of 146 active proto-clusters, using (HCO+)-C-13 J = 1-0 molecular line data obtained from the ATOMS survey. We find that filaments are ubiquitous in proto-clusters, and hub-filament systems are very common from dense core scales (similar to 0.1 pc) to clump/cloud scales (similar to 1-10 pc). The proportion of proto-clusters containing hub-filament systems decreases with increasing dust temperature (T-d) and luminosity-to-mass ratios (L/M) of clumps, indicating that stellar feedback from H ii regions gradually destroys the hub-filament systems as proto-clusters evolve. Clear velocity gradients are seen along the longest filaments with a mean velocity gradient of 8.71 km s(-1) pc(-1) and a median velocity gradient of 5.54 km s(-1) pc(-1). We find that velocity gradients are small for filament lengths larger than similar to 1 pc, probably hinting at the existence of inertial inflows, although we cannot determine whether the latter are driven by large-scale turbulence or large-scale gravitational contraction. In contrast, velocity gradients below similar to 1 pc dramatically increase as filament lengths decrease, indicating that the gravity of the hubs or cores starts to dominate gas infall at small scales. We suggest that self-similar hub-filament systems and filamentary accretion at all scales may play a key role in high-mass star formation.Peer reviewe

Coenzyme Q10 Reduces Ethanol-Induced Apoptosis in Corneal Fibroblasts

Dilute ethanol (EtOH) is a widely used agent to remove the corneal epithelium during the modern refractive surgery. The application of EtOH may cause the underlying corneal fibroblasts to undergo apoptosis. This study was designed to investigate the protective effect and potential mechanism of the respiratory chain coenzyme Q10 (CoQ10), an electron transporter of the mitochondrial respiratory chain and a ubiquitous free radical scavenger, against EtOH-induced apoptosis of corneal fibroblasts. Corneal fibroblasts were pretreated with CoQ10 (10 µM) for 2 h, followed by exposure to different concentrations of EtOH (0.4, 2, 4, and 20%) for 20 s. After indicated incubation period (2–12 h), MTT assay was used to examine cell viability. Treated cells were further assessed by flow cytometry to identify apoptosis. Reactive oxygen species (ROS) and the change in mitochondrial membrane potential were assessed using dichlorodihydrofluorescein diacetate/2′,7′-dichlorofluorescein (DCFH-DA/DCF) assays and flow-cytometric analysis of JC-1 staining, respectively. The activity and expression of caspases 2, 3, 8, and 9 were evaluated with a colorimetric assay and western blot analysis. We found that EtOH treatment significantly decreased the viability of corneal fibroblasts characterized by a higher percentage of apoptotic cells. CoQ10 could antagonize the apoptosis inducing effect of EtOH. The inhibition of cell apoptosis by CoQ10 was significant at 8 and 12 h after EtOH exposure. In EtOH-exposed corneal fibroblasts, CoQ10 pretreatment significantly reduced mitochondrial depolarization and ROS production at 30, 60, 90, and 120 min and inhibited the activation and expression of caspases 2 and 3 at 2 h after EtOH exposure. In summary, pretreatment with CoQ10 can inhibit mitochondrial depolarization, caspase activation, and cell apoptosis. These findings support the proposition that CoQ10 plays an antiapoptotic role in corneal fibroblasts after ethanol exposure

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

ATOMS : ALMA Three-millimeter Observations of Massive Star-forming regions - I. Survey description and a first look at G9.62+0.19

The ATOMS, standing for ALMA Three-millimeter Observations of Massive Star-forming regions, survey has observed 146 active star-forming regions with ALMA band 3, aiming to systematically investigate the spatial distribution of various dense gas tracers in a large sample of Galactic massive clumps, to study the roles of stellar feedback in star formation, and to characterize filamentary structures inside massive clumps. In this work, the observations, data analysis, and example science of the ATOMS survey are presented, using a case study for the G9.62+0.19 complex. Toward this source, some transitions, commonly assumed to trace dense gas, including CS J = 2-1, HCO+ J = 1-0, and HCN J = 1-0, are found to show extended gas emission in low-density regions within the clump; less than 25 per cent of their emission is from dense cores. SO, CH3OH, (HCN)-C-13, and HC3N show similar morphologies in their spatial distributions and reveal well the dense cores. Widespread narrow SiO emission is present (over similar to 1 pc), which may be caused by slow shocks from large-scale colliding flows or HII regions. Stellar feedback from an expanding HII region has greatly reshaped the natal clump, significantly changed the spatial distribution of gas, and may also account for the sequential high-mass star formation in the G9.62+0.19 complex. The ATOMS survey data can be jointly analysed with other survey data, e.g. MALT90, Orion B, EMPIRE, ALMA IMF, and ALMAGAL, to deepen our understandings of 'dense gas' star formation scaling relations and massive protocluster formation.Peer reviewe

ATOMS : ALMA three-millimeter observations of massive star-forming regions - III. Catalogues of candidate hot molecular cores and hyper/ultra compact H II regions

A correction has been published: Monthly Notices of the Royal Astronomical Society, Volume 511, Issue 1, March 2022, Pages 501–505, https://doi.org/10.1093/mnras/stac039We have identified 453 compact dense cores in 3mm continuum emission maps in the ALMA Three-millimetre Observations of Massive Star-forming regions survey, and compiled three catalogues of high-mass star-forming cores. One catalogue, referred to as hyper/ultra compact (H/UC)-HII catalogue, includes 89 cores that enshroud H/UC HII regions as characterized by associated compact H40 alpha emission. A second catalogue, referred to as pure s-cHMC, includes 32 candidate hot molecular cores (HMCs) showing rich spectra (N >= 20 lines) of complex organic molecules (COMs) and not associated with H/UC-HII regions. The third catalogue, referred to as pure w-cHMC, includes 58 candidate HMCs with relatively low levels of COM richness and not associated with H/UC-Hii regions. These three catalogues of dense cores provide an important foundation for future studies of the early stages of high-mass star formation across the Milky Way. We also find that nearly half of H/UC-HII cores are candidate HMCs. From the number counts of COM-containing and H/UC-HII cores, we suggest that the duration of high-mass protostellar cores showing chemically rich features is at least comparable to the lifetime of H/UC-HII regions. For cores in the H/UC-HII catalogue, the width of the H40 alpha line increases as the core size decreases, suggesting that the non-thermal dynamical and/or pressure line-broadening mechanisms dominate on the smaller scales of the H/UC-HII cores.Peer reviewe

ATOMS : ALMA three-millimeter observations of massive star-forming regions - II. Compact objects in ACA observations and star formation scaling relations

We report studies of the relationships between the total bolometric luminosity (L-bol or L-TIR) and the molecular line luminosities of J = 1 - 0 transitions of (HCN)-C-13, (HCO+)-C-13, HCN, and HCO+ with data obtained from ACA observations in the 'ATOMS' survey of 146 active Galactic star-forming regions. The correlations between L-bol and molecular line luminosities L-mol' of the four transitions all appear to be approximately linear. Line emission of isotopologues shows as large scatters in L-bol-L-mol' relations as their main line emission. The log(L-bol/L-mol') for different molecular line tracers have similar distributions. The L-bol-to-L-mol' ratios do not change with galactocentric distances (R-GC) and clump masses (M-clump). The molecular line luminosity ratios (HCN-to-HCO+, (HCN)-C-13-to-(HCO+)-C-13, HCN-to-(HCN)-C-13, and HCO+-to-(HCO+)-C-13) all appear constant against L-bol, dust temperature (T-d), M-clump, and R-GC. Our studies suggest that both the main lines and isotopologue lines are good tracers of the total masses of dense gas in Galactic molecular clumps. The large optical depths of main lines do not affect the interpretation of the slopes in star formation relations. We find that the mean star formation efficiency (SFE) of massive Galactic clumps in the 'ATOMS' survey is reasonably consistent with other measures of the SFE for dense gas, even those using very different tracers or examining very different spatial scales.Peer reviewe