The bromodomain and extraterminal (BET) domain family of proteins binds to acetylated lysines on histones and regulates gene transcription. Recently, BET inhibitors (BETi) have been developed that ...show promise as potent anticancer drugs against various solid and hematological malignancies. Here we show that the structurally novel and orally bioavailable BET inhibitor RVX2135 inhibits proliferation and induces apoptosis of lymphoma cells arising in Myc-transgenic mice in vitro and in vivo. We find that BET inhibition exhibits broad transcriptional effects in Myc-transgenic lymphoma cells affecting many transcription factor networks. By examining the genes induced by BETi, which have largely been ignored to date, we discovered that these were similar to those induced by histone deacetylase inhibitors (HDACi). HDACi also induced cell-cycle arrest and cell death of Myc-induced murine lymphoma cells and synergized with BETi. Our data suggest that BETi sensitize Myc-overexpressing lymphoma cells partly by inducing HDAC-silenced genes, and suggest synergistic and therapeutic combinations by targeting the genetic link between BETi and HDACi.
Although rurality is often treated as an aspect of diversity, researchers disagree regarding whether the traditional rural values of self-reliance, distrust of outsiders, religiosity, centrality of ...family, and fatalism continue to differentiate rural versus urban undergraduates. The present study examined 1) whether differences in these values exist between rural and urban college students in the United States and 2) whether these rural values might mediate the association between geographic remoteness and posttraumatic stress symptom (PTSS) severity. College undergraduates in the United States who reported experiencing traumatic and/or stressful events (N = 213) completed measures of these constructs through an online survey. T-test results indicated that rural respondents had significantly higher levels of PTSS severity and distrust of outsiders and significantly lower levels of religiosity when compared with urban participants. After controlling for gender, distrust of outsiders and religiosity also emerged as significant mediators of the relationship between geographic remoteness and PTSS severity. Thus, despite research that highlights differences based on geographic location, similarities and differences exist for rural and urban undergraduates in the United States with regard to traditionally rural values. For rural undergraduate clients presenting with trauma symptoms, our results suggest that building trust and religious and/or spiritual self-care may be particularly critical.
Objective
Rural areas in the Southern United States are characterized by certain cultural values that may delay or prevent mental health service utilization. The present study examined a four‐stage ...chain of serial mediation where higher levels of general self‐reliance would be related to greater levels of public stigma, which would in turn be related to higher levels of self‐stigma, followed by greater self‐reliance about managing mental health problems, and finally, more negative attitudes toward seeking help from psychologists.
Method
Community members who lived in rural counties in the Southern United States (N = 783) completed measures of these constructs online.
Results
Mediation analyses supported a direct association between general self‐reliance and attitudes toward help‐seeking that was explained in serial by higher levels of public stigma, self‐stigma, and mental health self‐reliance.
Conclusions
Clinical implications for rural practitioners are suggested including instilling policy changes, increasing provider visibility, and addressing barriers in therapy.
Methods
Adults seeking behavioral health or medical treatment (N = 158) were recruited from a community healthcare agency and a residential support program in the southeastern United States.
Results
...Individuals who reported interpersonal trauma had significantly higher total PTS severity and symptom clusters. No significant difference was found in perceived PTG based on trauma type. No significant curvilinear relationship between PTS and perceived PTG was found. A significant negative linear relationship was observed between PTS and perceived PTG for non‐interpersonal trauma, but not interpersonal trauma.
Conclusion
Trauma type may influence the PTS and perceived PTG relationship and, while associated with PTS, seems less important to reporting of perceived PTG.
Food waste presents a complex global problem that involves multiple actors and institutions within the aggregate food marketing system. Food waste occurs across food production and distribution, as ...well as at the hands of the consumer. In this research, the authors focus on waste that occurs across what is termed the "squander sequence," which describes waste that occurs from consumer behaviors at the preacquisition, acquisition, consumption, and disposition stages. The authors set forth a behavioral theory-based agenda to explain food waste in the squander sequence with the ultimate goals of encouraging future research to uncover the psychological underpinnings of consumer-level food waste and of deriving transformative consumer solutions to this substantive issue.
•Inversion tillage increased soil porosity but decreased soil water retention.•Organic management increased soil water holding capacity compared to conventional management.•Soil properties had ...contrasting effects on root growth and microbial diversity.•Meso-porosity was positively associated with microbial diversity.•Fungal diversity was strongly correlated to soil water content in macropores.
Soil structure is important for plant growth and ecosystem functioning, and provides habitat for a wide range of soil biota. So far, very few studies directly compared the effects of three main farming practices (conventional, organic and conservation agriculture) on soil structure and soil physical properties. Here, we collected undisturbed soil cores from the FArming System and Tillage long-term field experiment (FAST) near Zurich (Switzerland). This trial compares the effects of conventional tillage, conventional no-tillage, organic tillage and non-inversion reduced tillage under organic farming since 2009. We assessed 28 soil chemical and physical properties and related them to root and microbial biomass as well as to the diversity of bacteria and fungi. Tillage decreased bulk density (−14 %) and penetration resistance (−40 %) compared to no/reduce-tillage, potentially promoting a facilitative environment for plant root growth. Water holding capacity varied among systems, being the lowest in conventional tillage and highest (+10 %) in organic reduced tillage. We observed that microbial biomass and rhizosphere microbial diversity was positively associated with water holding capacity and the occurrence of mesopores. The presence of mesopores could provide additional niche space for microbes possibly explaining its positive effect on microbial diversity. Soil microbial biomass and rhizosphere microbial diversity were higher in plots subjected to soil conservation practices, indicating that tillage has a detrimental effect on soil microbes. Our work demonstrates that organic, conventional and conservation agriculture create contrasting soil physical environments. This work highlights the trade-off between creating a facilitative environment for root growth by tillage and maintaining complex and diverse soil microhabitats for microbes under conservation agriculture.
Objective
After combat, veterans may experience mental health symptomology and attempt to make meaning from their experiences. The present study qualitatively examined the mental health effects of ...deployment and meaning‐making among Operation Iraqi Freedom (OIF) or Operation Enduring Freedom (OEF) veterans.
Method
OIF/OEF veterans who were exposed to combat (N = 14) participated in semi‐structured interviews to assess how their perspectives had changed post‐deployment. Most participants (86%) were male, with a mean age of 30.
Results
Veterans described issues post‐combat that caused psychological distress or promoted distancing from others. Veterans also discussed factors that could promote or hinder meaning‐making, including perceptions of growth, changed global beliefs, and disillusionment. Finally, veterans described psychological reactions to death, which could be related to moral injury.
Conclusion
Mental health concerns, meaning‐making, and consideration of mortality appear to characterize veterans’ experiences post‐deployment. These constructs may be important for clinicians to consider when working with OIF/OEF veterans.
Objective
Combat‐exposed veterans risk encountering events that disrupt beliefs. To facilitate reduced discrepancy between prior beliefs and current trauma appraisals, veterans may engage in a ...process of meaning‐making. Meaning‐making can lead to positive outcomes, such as integrating the traumatic event into one's life narrative or adapting global meaning (meaning made) or elicit distress. Given these potentially different outcomes, this study examined potential correlates of posttraumatic stress symptom (PTSS) severity and meaning made, including relationship attachment dimensions of anxiety and avoidance, and difficulties with emotion regulation, while controlling for combat exposure.
Method
Veterans receiving mental health services at a Veterans Affairs (VA) Medical Center and a VA community‐based outpatient clinic (N = 130) completed measures through a paper‐and‐pencil survey. Almost all participants (92%) were male, with a mean age of 55.92 years.
Results
In terms of meaning made, lower levels of attachment anxiety and emotional clarity (an aspect of emotion regulation) predicted higher meaning made. In terms of PTSS severity, higher attachment avoidance, attachment anxiety, and difficulties engaging in goal‐directed behavior (an aspect of emotion regulation) significantly predicted higher PTSS severity.
Conclusion
Aspects of both attachment style and emotion regulation difficulties affect meaning made and PTSS severity. These constructs may be especially relevant for clinicians working with veterans to help PTSS and support meaning made postcombat.
G6PC2 is predominantly expressed in pancreatic islet β-cells where it encodes a glucose-6-phosphatase catalytic subunit that modulates the sensitivity of insulin secretion to glucose by opposing the ...action of glucokinase, thereby regulating fasting blood glucose (FBG). Prior studies have shown that the G6pc2 promoter alone is unable to confer sustained islet-specific gene expression in mice, suggesting the existence of distal enhancers that regulate G6pc2 expression. Using information from both mice and humans and knowledge that single nucleotide polymorphisms (SNPs) both within and near G6PC2 are associated with variations in FBG in humans, we identified several putative enhancers 3' of G6pc2. One region, herein referred to as enhancer I, resides in the 25th intron of Abcb11 and binds multiple islet-enriched transcription factors. CRISPR-mediated deletion of enhancer I in C57BL/6 mice had selective effects on the expression of genes near the G6pc2 locus. In isolated islets, G6pc2 and Spc25 expression were reduced ∼50%, and Gm13613 expression was abolished, whereas Cers6 and nostrin expression were unaffected. This partial reduction in G6pc2 expression enhanced islet insulin secretion at basal glucose concentrations but did not affect FBG or glucose tolerance in vivo, consistent with the absence of a phenotype in G6pc2 heterozygous C57BL/6 mice.
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