Amy D. Marshall

Posttraumatic Stress Disorder Symptoms, Physiological Reactivity, Alcohol Problems, and Aggression Among Military Veterans

This study examined the association between posttraumatic stress disorder (PTSD) symptomatology and aggressive behavior among a sample of male Vietnam veterans (N = 1,328). Results indicated that the hyperarousal PTSD symptom cluster evidenced the strongest positive association with aggression at the bivariate level when compared with the other PTSD symptom clusters. When the PTSD symptom clusters were examined together as predictors, hyperarousal symptoms evidenced a significant positive relationship with aggression, and avoidance/numbing symptoms were negatively associated with aggression. Examination of potential mediators indicated that hyperarousal symptoms were directly associated with aggression and indirectly related to aggression via alcohol problems. Reexperiencing symptoms were associated with aggression only indirectly and through their positive association with physiological reactivity and negative association with alcohol problems. Study results highlight the complexity of the relationship between PTSD symptoms and aggression, and suggest possible mechanisms explaining this association.

Posttraumatic Stress Disorder, Anger, and Partner Abuse Among Vietnam Combat Veterans

The authors examined interrelationships among posttraumatic stress disorder (PTSD) symptomatology, anger, and partner abuse perpetration among a sample of 60 combat veterans. Compared with PTSD-negative participants, PTSD-positive participants reported higher state anger across time and neutral and trauma prime conditions and higher anger reactivity during the trauma prime condition. PTSD-positive participants also exhibited more anger reactivity during the trauma prime than during the neutral condition. The same pattern of results was not found for anxiety reactivity during trauma memory activation. PTSD symptoms were associated with physical assault and psychological aggression perpetration, and trait anger mediated these relationships. Findings indicate a heightened anger response among PTSD-positive veterans and suggest the salience of dispositional components of anger in abuse perpetration in this population.

ASCT2/SLC1A5 controls glutamine uptake and tumour growth in triple-negative basal-like breast cancer

Alanine, serine, cysteine-preferring transporter 2 (ASCT2; SLC1A5) mediates uptake of glutamine, a conditionally essential amino acid in rapidly proliferating tumour cells. Uptake of glutamine and subsequent glutaminolysis is critical for activation of the mTORC1 nutrient-sensing pathway, which regulates cell growth and protein translation in cancer cells. This is of particular interest in breast cancer, as glutamine dependence is increased in high-risk breast cancer subtypes. Pharmacological inhibitors of ASCT2-mediated transport significantly reduced glutamine uptake in human breast cancer cell lines, leading to the suppression of mTORC1 signalling, cell growth and cell cycle progression. Notably, these effects were subtype-dependent, with ASCT2 transport critical only for triple-negative (TN) basal-like breast cancer cell growth compared with minimal effects in luminal breast cancer cells. Both stable and inducible shRNA-mediated ASCT2 knockdown confirmed that inhibiting ASCT2 function was sufficient to prevent cellular proliferation and induce rapid cell death in TN basal-like breast cancer cells, but not in luminal cells. Using a bioluminescent orthotopic xenograft mouse model, ASCT2 expression was then shown to be necessary for both successful engraftment and growth of HCC1806 TN breast cancer cells in vivo. Lower tumoral expression of ASCT2 conferred a significant survival advantage in xenografted mice. These responses remained intact in primary breast cancers, where gene expression analysis showed high expression of ASCT2 and glutamine metabolism-related genes, including GLUL and GLS, in a cohort of 90 TN breast cancer patients, as well as correlations with the transcriptional regulators, MYC and ATF4. This study provides preclinical evidence for the feasibility of novel therapies exploiting ASCT2 transporter activity in breast cancer, particularly in the high-risk basal-like subgroup of TN breast cancer where there is not only high expression of ASCT2, but also a marked reliance on its activity for sustained cellular proliferation.

Family-of-Origin Maltreatment, Posttraumatic Stress Disorder Symptoms, Social Information Processing Deficits, and Relationship Abuse Perpetration

In this study, the authors examined the interrelations among family-of-origin maltreatment variables, posttraumatic stress disorder (PTSD) symptoms, social information processing deficits, and male-to-female psychological and physical intimate relationship abuse perpetration in adulthood among a community sample of 164 men and their partners. In bivariate analyses, higher family-of-origin childhood parental rejection was associated with the perpetration of psychological and physical abuse in adulthood, and childhood exposure to interparental violence was also associated with adult psychological abuse perpetration. Structural equation modeling analyses indicated that when childhood variables and other study variables were considered together, only childhood parental rejection was associated with the abuse perpetration outcomes, and these effects were indirect through PTSD symptoms and social information processing deficits. Results indicate a need for further investigation into the mechanisms accounting for the impact of early maltreatment on the development of abusive intimate relationship behavior.

Intimate Partner Aggression Reporting Concordance and Correlates of Agreement Among Men With Alcohol use Disorders and Their Female Partners

This study examined relationship aggression reporting concordance among 303 men with alcohol use disorders and their female partners enrolled in couples-based alcohol abuse treatment. Agreement for physical and psychological aggression was generally consistent with, or higher than, concordance rates reported among other populations. Men’s antisocial personality disorder characteristics were the strongest predictor of higher concordance for male- and female-perpetrated aggression. Higher alcohol problem severity, poorer relationship adjustment, and higher psychopathic personality features were associated with better concordance in some analyses. Women reported experiencing more physical aggression than men reported perpetrating, and women reported perpetrating more psychological aggression than men reported experiencing. Findings highlight the importance of obtaining aggression reports from both partners and the need for research investigating methods for improving concordance.

The cancer-testis antigen BORIS phenocopies the tumor suppressor CTCF in normal and neoplastic cells

BORIS and CTCF are paralogous, multivalent 11‐zinc finger transcription factors that play important roles in organizing higher‐order chromatin architecture. BORIS is a cancer‐testis antigen with a poorly defined function in cancer, although it has been hypothesized to exhibit oncogenic properties. CTCF, however, has been postulated as a candidate tumor suppressor. We collated the genetic lesions in BORIS and CTCF from multiple cancers identified using high‐throughput genomics. In BORIS, nonsense and missense mutations are evenly distributed. In CTCF, recurrent mutations are mostly clustered in the conserved zinc finger domain and at residues critical for contacting DNA and zinc ion co‐ordination. Three missense mutations are common to both proteins. We used an inducible lentivector to express wildtype BORIS or CTCF in primary cells and cancer cell lines in order to define their functional differences. Both BORIS and CTCF caused a significant decrease in cell proliferation and clonogenic capacity, without alteration of specific cell cycle phases. Both BORIS and CTCF conferred protective effects in primary cells and some cancer cells during UV damage‐induced apoptosis. Using a bioluminescent MCF‐7 orthotopic breast cancer model in vivo, we demonstrated that CTCF and BORIS suppressed breast cancer growth. These findings provide further evidence that CTCF behaves as a tumor suppressor, and show BORIS has a similar growth inhibitory effect in vitro and in vivo. Hence, acquired zinc finger mutations may disrupt these functions, thereby contributing to tumor growth and development.

Genetic alterations of m 6 A regulators predict poorer survival in acute myeloid leukemia

Methylation of N6 adenosine (m6A) is known to be important for diverse biological processes including gene expression control, translation of protein, and messenger RNA (mRNA) splicing. However, its role in the development of human cancers is poorly understood. By analyzing datasets from the Cancer Genome Atlas Research Network (TCGA) acute myeloid leukemia (AML) study, we discover that mutations and/or copy number variations of m6A regulatory genes are strongly associated with the presence of TP53 mutations in AML patients. Further, our analyses reveal that alterations in m6A regulatory genes confer a worse survival in AML. Our work indicates that genetic alterations of m6A regulatory genes may cooperate with TP53 and/or its regulator/downstream targets in the pathogenesis and/or maintenance of AML.

The Relationship of Intimate Partner Aggression to Head Injury, Executive Functioning, and Intelligence.

Measures of head injury, executive functioning, and intelligence were given to a community sample composed of 102 male perpetrators of intimate partner aggression (IPA) and 62 nonaggressive men. A history of head injury and lower mean score on a measure of verbal intelligence were associated with the frequency of male-perpetrated physical IPA as reported by male perpetrators and their female partners. Lower mean scores on a measure of verbal intelligence also predicted frequency of psychological IPA perpetration. Using the perpetrator subtypes outlined by Holtzworth-Munroe et al. (2000), analyses revealed that compared with other groups, the most severely aggressive subtypes (i.e., borderline-dysphoric and generally violent-antisocial) were the most likely to report a history of head injury and to have significantly lower mean scores on a neuropsychological test of verbal intelligence. The possible role of neuropsychological factors in IPA perpetration and implications for prevention and intervention programs are discussed.

LAT1 is a putative therapeutic target in endometrioid endometrial carcinoma.

l‐type amino acid transporters (LAT1‐4) are expressed in various cancer types and are involved in the uptake of essential amino acids such as leucine. Here we investigated the expression of LAT1‐4 in endometrial adenocarcinoma and evaluated the contribution of LATs to endometrial cancer cell growth. Analysis of human gene expression data showed that all four LAT family members are expressed in endometrial adenocarcinomas. LAT1 was the most highly expressed, and showed a significant increase in both serous and endometrioid subtypes compared to normal endometrium. Endometrioid patients with the highest LAT1 levels exhibited the lowest disease‐free survival. The pan‐LAT inhibitor BCH led to a significant decrease in cell growth and spheroid area in four endometrial cancer cell lines tested in vitro. Knockdown of LAT1 by shRNA inhibited cell growth in HEC1A and Ishikawa cells, as well as inhibiting spheroid area in HEC1A cells. These data show that LAT1 plays an important role in regulating the uptake of essential amino acids such as leucine into endometrial cancer cells. Increased ability of BCH compared to LAT1 shRNA at inhibiting Ishikawa spheroid area suggests that other LAT family members may also contribute to cell growth. LAT1 inhibition may offer an effective therapeutic strategy in endometrial cancer patients whose tumours exhibit high LAT1 expression.

Stressors Experienced by Women Within Marine Corps Families: A Qualitative Study of Discourse Within an Online Forum

The social constructionist perspective frames this exploration of the socioemotional and relational aspects of stress experienced by significant others of active duty Marines. Interpretive methods were applied to data from an online forum for Marine Corps wives, fiancées, and girlfriends. Open coding revealed six stressors: (a) stuck in a state of flux, (b) going through changes, (c) relational uncertainty, (d) loneliness, (e) alienation, and (f) anxiety related to deployment. Axial coding revealed three properties underlying these stressors: (a) issues of control and helplessness, (b) concerns over privileging individual or relational goals, and (c) the matter of locus of blame.