Fully Ab Initio Approach to Inelastic Atom-Surface Scattering.

We introduce a fully ab initio theory for inelastic scattering of any atom from any surface exciting single phonons, and apply the theory to helium scattering from Nb(100). The key aspect making our approach general is a direct first-principles evaluation of the scattering atom-electron vertex. By correcting misleading results from current state-of-the-art theories, this fully ab initio approach will be critical in guiding and interpreting experiments that adopt next-generation, nondestructive atomic beam scattering.

Distal and Proximal Minority Stressors on Patterns of Tobacco and Cannabis Use Among Young Bisexual Women.

BACKGROUND: Bisexual women have high rates of tobacco and cannabis use, but few studies have examined co-use behavior in this population. Although the role of distal minority stressors (eg, discrimination) on substance use has been examined, fewer studies have examined proximal minority stressors (eg, negative sexual identity self-schemas). The current study was a secondary data analysis that examined patterns of tobacco and cannabis use, and the role of distal (instability of bisexuality, sexual irresponsibility of bisexual people, and hostility toward bisexual people) and proximal (illegitimacy of bisexuality, anticipated binegativity, internalized binegativity, and identity affirmation) bisexual-specific minority stressors among bisexual women. METHODS: Participants were 224 young (aged 18-30 years old) self-identified bisexual women who reported on their past 30-day tobacco and cannabis use and completed measures of distal and proximal bisexual-specific minority stressors. Participants were categorized into one of 4 patterns: no use, tobacco use only, cannabis use only, and tobacco and cannabis co-use. RESULTS: The most common pattern of past 30-day use was tobacco and cannabis co-use (39.1%). Results from a multinomial logistic regression revealed that bisexual women who reported higher illegitimacy of bisexuality, a proximal minority stressor, were significantly more likely to engage in tobacco and cannabis co-use, relative to no use. DISCUSSION: Bisexual women have particularly high rates of substance use, with tobacco and cannabis co-use as the most common pattern. Incorporating the role of proximal minority stressors, and specifically, beliefs about the legitimacy of bisexuality, may be an important target of substance use interventions for bisexual women.

Normative Perceptions of Sexual Behavior and Alcohol Use among Bisexual Women.

Background: As compared to heterosexual and lesbian women, bisexual women report higher rates of alcohol, other substance use, and risky sexual behavior, and they experience more negative outcomes from these behaviors. Descriptive norms (i.e., perceptions of others' behavior) are an important predictor of risky behaviors, but scant research has examined whether bisexual women's perceptions of other bisexual women's alcohol use and sexual behavior are associated with their own alcohol or drug use during sex. Objectives: Consequently, the present study examined (1) whether perceived sex norms were related to engagement in sex and (2) the relative influence of drinking and sex norms on engaging in sex while drinking among bisexual women. Method: Data were collected from 225 self-identified bisexual women who completed an online survey about their typical weekly alcohol use, engagement in alcohol or drug use during sex in the past 30 days, and normative perceptions of drinking and sexual behavior. Results: Regression models demonstrated both sexual norms and drinking frequency norms were positively associated with alcohol or drug use during sex. In addition, only perceived norms of other bisexual women, compared to perceived norms of lesbian and heterosexual women, predicted engagement in sex. Conclusions: Bisexual women may be susceptible to normative perceptions, given their connectedness to a marginalized social group. Thus, alcohol prevention and intervention efforts aimed at reducing risky consequences among bisexual women should specifically consider drinking and sexual norms of other bisexual women.

Impulsivity, sex-related alcohol expectancies, alcohol use, and sexual risk-taking among bisexual women.

BACKGROUND AND OBJECTIVES: According to the acquired preparedness model, personality traits, such as impulsivity, may influence the learning process, contributing to heightened expectations surrounding risky behaviors (i.e., alcohol use, sexual risk-taking). As bisexual women demonstrate heightened risk for hazardous alcohol- and sex-related behaviors, the present study examined a sequential pathway, whereby the relation between impulsivity and sexual risk-taking is mediated through sex-related alcohol expectancies and alcohol use. METHODS: Data were collected from 225 self-identified cisgender, bisexual women between the ages of 18 and 30 years (M = 22.77, SD = 3.45), who participated in an online survey. Participants reported on impulsivity, sex-related alcohol expectancies, alcohol use, and experiences of sexual risk-taking. RESULTS: Results revealed that sex-related alcohol expectancies and alcohol use sequentially mediated the relation between impulsivity and sexual risk-taking. Thus, greater impulsivity was related to greater sexual risk-taking through heightened sex-related alcohol expectancies and elevated alcohol use. DISCUSSION AND CONCLUSIONS: Findings from this study highlight mechanisms associated with risky drinking and sexual behaviors among this at-risk population. Such information could aid the development of more efficacious prevention and intervention programs aimed at reducing consequences associated with alcohol use and sexual risk-taking among bisexual women. SCIENTIFIC SIGNIFICANCE: Bisexual women are at heightened risk for alcohol-related problems, including sexual risk-taking. Findings from the current study identify impulsivity and sex-related alcohol expectancies as independent and integrative predictors of such risky behaviors. Incorporation of these constructs may aid in the development of more efficacious clinical methods aimed at bettering health outcomes among bisexual women.

Dimensions of binegativity differentially predict drinking to cope motivations and alcohol use severity among bisexual women.

Research indicates that bisexual women experience greater stigmatization and discrimination compared to lesbian women. Such oppression is described as binegativity and is associated with alcohol use among bisexual women. Specifically, previous research has suggested that bisexual women may drink to cope in an effort to self-medicate from experiences of binegativity. Although substantial research has been conducted with regard to drinking behaviors among at-risk groups, research has yet to identify which specific types of binegativity may be most predictive of drinking outcomes among bisexual women. Consequently, the present study sought to examine the predictive utility of three dimensions of binegativity: (a) sexual orientation instability (e.g., the perception of bisexuality as an illegitimate sexual orientation), (b) sexual irresponsibility (e.g., the stereotype that bisexual persons are oversexualized or sexually promiscuous), and (c) interpersonal hostility (e.g., the alienation and uncomfortability with bisexual identification), on drinking to cope motivations and alcohol use severity. Participants were 225 self-identified bisexual women between the ages of 18 and 30 years (Mean = 22.77, SD = 3.45) who participated in a larger study about health behaviors among bisexual women. Multiple regressions revealed that, compared to other binegativity dimensions, sexual irresponsibility was the strongest predictor of typical alcohol use, drinking to cope motivations, and alcohol use severity. Thus, bisexual women who are stereotyped to be sexually promiscuous are at particular risk for problematic alcohol use. Prevention and intervention efforts should target stress associated with experiences of oversexualized stigmatizations, in an effort to reduce alcohol-related risk among bisexual women. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Mindfulness to Manage Moral Injury: Rationale and development of a live online 7-week group intervention for veterans with moral injury.

Background: Military service puts service members at risk for moral injury. Moral injury is an array of symptoms (e.g., guilt, shame, anger) that develop from events that violate or transgress one's moral code. Objective: We describe adaption of in-person mindfulness training program, Mindfulness to Manage Chronic Pain (MMCP), to address symptoms of moral injury to be delivered live via the web. We discuss how we will assess benchmarks (i.e., recruitment, credibility and acceptability, completion rates, and adherence) of the Mindfulness to Manage Moral Injury (MMMI) program. Methods: Aim 1: To develop and then adapt the MMCP program based on feedback from experts and veterans who took part in Study 1. Aim 2: To develop an equally intensive facilitator-led online Educational Support (ES) program to serve as a comparison intervention and conduct a run-through of each program with 20 veterans (10 MMMI; 10 ES). Aim 3: To conduct a small-scale randomized controlled trial (N = 42 veterans; 21 MMMI; 21 ES) in which we will collect pre-post-test and weekly benchmark data for both refined intervention arms. Results: Study 1 and 2 are completed. Data collection for Study 3 will be completed in 2022. Conclusion: MMMI is designed to provide a live facilitated mindfulness program to address symptoms of moral injury. If Study 3 demonstrates good benchmarks, with additional large-scale testing, MMMI may be a promising treatment that can reach veterans who may not seek traditional VAMC care and/or who prefer a web-based program.

A combined helium atom scattering and density-functional theory study of the Nb(100) surface oxide reconstruction: Phonon band structures and vibrational dynamics.

Helium atom scattering and density-functional theory (DFT) are used to characterize the phonon band structure of the (3 × 1)-O surface reconstruction of Nb(100). Innovative DFT calculations comparing surface phonons of bare Nb(100) to those of the oxide surface show increased resonances for the oxide, especially at higher energies. Calculated dispersion curves align well with experimental results and yield atomic displacements to characterize polarizations. Inelastic helium time-of-flight measurements show phonons with mixed longitudinal and shear-vertical displacements along both the ⟨1̄00⟩, Γ̄X̄ and ⟨11̄0⟩, Γ̄M̄ symmetry axes over the entire first surface Brillouin zone. Force constants calculated for bulk Nb, Nb(100), and the (3 × 1)-O Nb(100) reconstruction indicate much stronger responses from the oxide surface, particularly for the top few layers of niobium and oxygen atoms. Many of the strengthened bonds at the surface create the characteristic ladder structure, which passivates and stabilizes the surface. These results represent, to our knowledge, the first phonon dispersion data for the oxide surface and the first ab initio calculation of the oxide's surface phonons. This study supplies critical information for the further development of advanced materials for superconducting radiofrequency cavities.

A dyadic examination of alcohol use and intimate partner aggression among women in same-sex relationships.

Despite considerable evidence linking alcohol use and intimate partner aggression among mixed-sex couples, scant research has examined this association in same-sex couples using a dyadic framework. The aim of the present study was to examine associations between one's own and their partner's alcohol use (i.e., drinks per week, hazardous alcohol use) and intimate partner aggression (physical, psychological) perpetration while accounting for the interdependence among partners in alcohol use. Participants were 326 women (Mage = 27.57, SD = 3.65) from 163 female-female couples who independently completed measures of drinks per week, hazardous alcohol use, psychological intimate partner aggression victimization and perpetration, and physical intimate partner aggression victimization and perpetration. Actor-partner interdependence structural equation models found that (1) actor drinks per week were positively associated with one's own physical assault perpetration (2) actor hazardous alcohol use was positively associated with one's own physical assault and psychological aggression perpetration and (3) partner drinks per week and hazardous alcohol use were positively associated with actor's psychological aggression perpetration. No other significant effects were detected. Collectively, findings highlight the nuanced relationship between alcohol use and intimate partner aggression among same-sex female couples and suggest that one's own alcohol use is associated with intimate partner psychological and physical aggression perpetration. In contrast, the only partner effect was partner's alcohol use in association with actor's psychological aggression perpetration. These findings differ from prior research with heterosexual couples and underscore the need for future research with same-sex couples rather than attempts to generalize findings across populations.

Hookups Among U.S. College Students: Examining the Association Between Hookup Motives and Personal Affect.

"Hooking up" is prevalent on college campuses and is related to both positive and negative outcomes for students. The current study was an exploratory examination of hookup motives, and positive and negative affect, related to the most recent hookup experience. Participants were 256 U.S. college students who reported hooking up in the last 12 months. Students completed a 30-min anonymous online survey assessing behaviors and cognitions during their most recent hookup, including alcohol use at the time of the hookup, motives for hooking up, and post-hookup affect. The model demonstrated that gender, conformity motives, and social-relationship motives significantly and positively predicted negative affect, whereas enhancement motives negatively predicted negative affect. Coping and enhancement motives significantly and positively predicted positive affect, whereas alcohol use negatively predicted positive affect. This study was a unique examination of hookup motives, with important findings that explained large portions of variance in post-hookup affect. The overall model explained approximately 23% of the variance in negative affect and 49% of the variance in positive affect. Findings highlight that, depending on the hookup motive, hooking up can be associated with positive outcomes, such as positive affect.

Moral Injury as a Mediator of the Associations Between Sexual Harassment and Mental Health Symptoms and Substance Use Among Women Veterans.

Moral injury is an array of symptoms theorized to develop in response to morally injurious events, defined as events that challenge one's core moral beliefs and expectations about the self, others, and world. Recent measures of moral injury have distinguished self-directed moral injury (e.g., moral injury symptoms that emerge following the perpetration of morally injurious events) from other-directed moral injury, the symptoms of which are believed to stem from one's response to actions that others have committed (e.g., within-rank violence, failures of leadership, and acts of betrayal committed by trusted others or institutions). Using a convenience sample of 154 primarily former military women, the present study examined if other-directed moral injury symptoms (e.g., anger, betrayal, and mistrust) associated with military experience would mediate the association between military sexual harassment and mental health and substance abuse symptoms. Results demonstrated that 85.8% (n = 127) of the of this sample of women veterans reported experiencing sexual harassment during their military service. Using a single mediation model, we further demonstrated that other-directed moral injury mediated the association between sexual harassment experience and mental health symptoms. Given the percentage of women veterans who reported sexual harassment, these results suggest that additional training for military members, and particularly, military leaders, is necessary to begin to reduce sexual harassment. In addition, mental health providers who work with current and former military members should consider how other-directed moral injury may be associated with mental health symptoms among women veterans who have experienced sexual harassment while in the military.

Examining the added value of harm reduction strategies to emailed boosters to extend the effects of online interventions for college drinkers.

Objective: Brief computer-delivered interventions (CDIs) reduce college student drinking and related problems but can be less efficacious and enduring than in-person interventions. The present study examined: (a) the utility of emailed personalized boosters after an evidence-based online CDI for alcohol (i.e., eCHECKUP TO GO), and (b) the added value of including protective behavioral strategies (PBS) in boosters containing personalized normative feedback (PNF) versus PNF alone. Method: 528 young adult (ages 18-24) college drinkers (71.6% female; 52.5% Black, 40.3% White) with a mean age of 19.9 years (SD = 1.65) were randomized to receive: CDI-only; CDI plus a PNF-only booster; or CDI plus a booster containing both PNF and PBS feedback. Booster emails were sent 2 weeks post-intervention. Online surveys completed pre-intervention and at 1 and 3 months assessed alcohol consumption, problems, descriptive normative perceptions, and PBS use. Results: The CDI led to significant reductions in alcohol consumption across all conditions, with no effect of boosters on drinking. Controlling for quantity, no reductions in problems were observed. Descriptive norms reduced significantly, with no condition differences. Only PBS use showed condition effects, such that the CDI-only and PNF-only booster groups reported reduced PBS use at 1 month, but the norms-plus-PBS booster group did not. Conclusions: The CDI was sufficient to change alcohol consumption and perceived norms without boosters, although the inclusion of boosters with PBS feedback may mitigate against PBS use reductions. Longer follow-ups may detect delayed booster benefits, or a larger dose through repeated exposure over time may be needed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The role of alcohol demand on daily microaggressions and alcohol use among emerging adult bisexual+ women.

Objective: Bisexual women drink more and have more alcohol consequences than heterosexual and lesbian women. This higher risk may in part be attributable to sexual orientation microaggressions. Drinking to cope motivations and alcohol demand may influence the association between microaggressions and alcohol use. The present study used a daily diary design to examine the association between microaggressions and same-day alcohol use (yes/no, quantity) and consequences, and if drinking to cope and alcohol demand moderate this association among bisexual+ (i.e., bi+) women. Method: Participants were 103 emerging adult bi+ women who completed a baseline assessment, including an alcohol purchase task to measure alcohol demand. Subsequently, participants reported their experiences of microaggressions, alcohol use, and alcohol consequences for 28 days. Multilevel model analyses were conducted. Results: Microaggressions were associated with a higher likelihood to drink and greater same-day alcohol use and consequences. The association between microaggressions and alcohol quantity was stronger for those who had a lower price associated with the highest expenditure (lower P max). For those who would stop drinking at lower price values (lower breakpoint), reported spending less overall on alcohol (lower O max), and had lower P max values, microaggressions were associated with more consequences. For those with higher breakpoint, O max, and P max microaggressions were not associated with consequences. Conclusions: Microaggressions may have a deleterious impact on alcohol use and consequences for bi+ women, particularly for those with lower alcohol demand. Clinicians should encourage bi+ clients to consider how microaggressions influence their drinking and support clients to engage in positive coping skills. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Own soul's warning: Moral injury, suicidal ideation, and meaning in life.

OBJECTIVE: Moral injury (an inner conflict [or cognitive dissonance] used to describe psychological, ethical, and/or spiritual conflict experienced when an individual's basic sense of humanity is violated) has been associated with suicidal ideation among military populations. However, mechanisms linking moral injury to suicidal ideation, particularly variables that may protect against suicidal ideation, have received limited attention. This study examined whether two domains of meaning in life (presence of meaning in life and searching for meaning in life) mediated the links between self- and other-directed moral injury and suicidal ideation. METHOD: Participants were a community sample of 269 predominantly recent-era former service members who completed an online, anonymous voluntary survey. RESULTS: When examined in separate models, self-directed moral injury and other-directed moral injury were found to associate with higher suicidal ideation via a lower presence of meaning in life (no significant associations with searching for meaning in life). When examined in an exploratory combined model (i.e., both self-directed and other-directed moral injury entered in the same model), only the association between self-directed moral injury and suicidal ideation via the presence of meaning in life remained statistically significant. CONCLUSIONS: Our findings suggest that the presence of meaning in life may serve as a protective factor for veterans experiencing moral injury (particularly self-directed moral injury) that is associated with suicidal ideation. It is possible that guiding veterans with moral injury symptoms to develop more meaning or purpose in their lives may reduce suicidal ideation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Remote exposure to traumatic events and PTSD symptoms among U.S. Air Force intelligence personnel: Moderating effects of morally injurious experiences.

OBJECTIVES: U.S. Air Force (USAF) intelligence, surveillance, and reconnaissance (ISR) personnel continuously view high-resolution, real-time imagery and video feeds that include intermittent exposure to graphic events. This brief report examined whether cumulative exposure (still imagery, video, and audio) to graphic events was associated with posttraumatic stress disorder (PTSD) symptoms among USAF ISR personnel. We also examined whether morally injurious experiences (MIEs)-as well as three MIE subtypes: (a) personal moral transgressions, (b) transgressions by others, and (c) feelings of betrayal by others-moderated the association between ISR work-related traumatic exposure and PTSD symptoms. METHOD: Participants were 277 USAF ISR personnel assigned to intelligence units. RESULTS: We found two significant moderation effects. First, we found that the association between ISR remote graphic media exposure and PTSD symptoms was strongest for participants with higher levels of MIE exposure. Second, we found that the ISR remote graphic media exposure-PTSD symptoms association was strongest among participants who reported higher levels of MIEs that were self-directed; that is, they reported being troubled with believing they had violated their own morals, values, or principles. CONCLUSIONS: Findings emphasize the importance of moral injury in understanding PTSD symptoms in ISR personnel. Specifically, because MIEs and PTSD are possible in remote combat agents, prevention and intervention efforts for ISR actors should directly target this special population with recognition that (a) remote combat exposure can be traumatic and (b) perceived violations of moral beliefs or values may be central to any posttraumatic psychopathology. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Sex differences in predictors of recurrent major depression among current-era military veterans.

Although major depressive disorder (MDD) is a frequent diagnosis among women seeking care in the Veterans Health Administration, little is known about its course. For example, recurrence of MDD and its predictors have been investigated in civilians, but not among female veterans. Because female veterans differ from their civilian counterparts and from male veterans on demographic variables, including race, ethnicity, marital status, and educational level, it is important to identify factors affecting MDD course within this population. We investigated frequency and correlates of recurrent MDD among female veterans and their male counterparts. From a postdeployment research registry of 3,247 participants (660 women and 2,587 men), we selected those with a current episode of MDD (141 women and 462 men). For each sex, we compared those diagnosed with recurrent MDD with those experiencing a single episode on demographics, comorbid diagnoses, family history of mental illness, traumatic experiences, combat exposure, and social support. In contrast to findings in most civilian samples, recurrent MDD was significantly more frequent in female (70.2%) than in male (45.2%) depressed veterans, χ²(1) = 26.96, p < .001. In multivariable analyses, recurrence among women was associated with greater experiences of childhood abuse and more trauma during military service and with lower rates of posttraumatic stress disorder. Among men, recurrence was associated with older age, family history of psychiatric hospitalization, more postmilitary trauma, and lifetime anxiety disorder and with lower likelihood of war zone deployment. Trauma was associated with recurrence in both sexes, but the features of traumatic events differed in women and men. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Weekly Drinking and Binge Drinking Mediate the Association Between Drinking Location and Sexual Coercion.

It has been well documented that alcohol use is a risk factor for sexual assault. However, few studies have examined how alcohol use is associated with sexual coercion experiences. Furthermore, off-campus parties and bars are drinking locations where alcohol use is high among college students. It is important to determine other risk factors, such as the drinking location, that may affect alcohol use and sexual coercion. The current study examined whether alcohol use (drinks per week and binge drinking) mediated the association between drinking location frequency (off-campus party and bar/restaurant) and experiencing sexual coercion in the past 30 days. Participants were N = 295 young adult (Mage = 21.17 years, SD = 2.70) undergraduate women who reported drinking at least once in the past 30 days and completed an online survey. Results revealed that 88 (29.8%) participants experienced sexual coercion in the past 30 days. Participants who experienced sexual coercion in the past 30 days reported greater drinks per week, were more likely to binge drink, and reported drinking more frequently at off-campus parties than those who had not experienced sexual coercion. Drinks per week significantly mediated the relationship between drinking location frequency (off-campus party and bar/restaurant) and sexual coercion. Specifically, more frequent drinking at off-campus parties and bars/restaurants was associated with greater drinks per week, which in turn was related to experiencing sexual coercion in the past 30 days. Binge drinking significantly mediated the association between frequency of drinking at a bar/restaurant and sexual coercion, but not off-campus drinking frequency. Findings suggest that college student alcohol interventions that target harm reduction should consider including information about how the drinking location may intersect with alcohol use to increase risk for sexual coercion.

Rumination as a Mediator of the Associations Between Moral Injury and Mental Health Problems in Combat-Wounded Veterans.

Moral injury is hypothesized to develop from witnessing or engaging in events that violate one's beliefs about themselves and has been shown to be associated with negative mental health symptoms. Although there has been an increase in research examining moral injury among military veterans, mechanisms that link moral injury to mental health outcomes are not well understood. The present study examined rumination subcomponents (problem-focused thoughts, counterfactual thinking, repetitive thoughts, and anticipatory thoughts) as possible mediators of the associations between moral injury (both self-directed and other-directed symptoms) and negative mental health symptoms (i.e., depression, anxiety, suicidality, sleep disturbance, memory problems, and posttraumatic stress disorder symptoms). Participants were 189 combat wounded veterans (180 men; Mean age = 43.14 years) who had experienced one or more deployments (defined as 90 days or more). Nearly all participants reported a service-connected disability (n = 176, 93.1%), with the average participant reporting a 90% total VA disability ranking, and most participants had received a purple heart (n = 163, 86.2%). Within our comprehensive mediation model, we found eight significant mediation effects with the most consistent mediator being problem-focused thoughts. Specifically, both self-directed and other- directed moral injury were associated with increased problem-focused thoughts, which in turn was associated with higher reported symptoms of depression, anxiety, and posttraumatic stress disorder. Taken together, rumination, and in particular, problem-focused thoughts, is relevant to understand the increased vulnerability of military veterans to exhibit poor mental health outcomes when experiencing moral injury.

A brief history of spaceflight from 1961 to 2020: An analysis of missions and astronaut demographics.

Human spaceflight and the characteristics of people who become astronauts have changed over time. Here we present an analysis of n=1,265 manned spaceflights by n=562 astronauts from 1961-2020 to investigate historical trends over time and between space agencies in terms of astronaut demographics and spaceflight duration. Generalized linear models and generalized linear mixed models were implemented with adjustments for all available demographic data as covariates. Women continue to be underrepresented as astronauts, and were younger, had fewer children, and were less likely to have a military background than their male counterparts. Astronaut age has increased over time, although this increase was significant only for first-time spaceflights. The proportion of astronauts from civilian backgrounds has generally increased over time, although there is evidence this trend may be reversing. Spaceflight duration has increased over time, and has been longest for ROSCOSMOS cosmonauts and shortest for Chinese taikonauts. There were also differences between space agencies in terms of astronaut demographics, particularly between NASA and ROSCOSMOS, with first-time NASA astronauts more likely to be women, civilian and older than first-time ROSCOSMOS cosmonauts. As humankind embarks on exploration-class missions back to the lunar surface and then onward to Mars, and with new nations and commercial entities entering the international space community, the nature of spaceflight, and the diversity of the astronauts, will continue to evolve.

Nitrogen Trapping as a Therapeutic Strategy in Tumors with Mitochondrial Dysfunction.

Under conditions of inherent or induced mitochondrial dysfunction, cancer cells manifest overlapping metabolic phenotypes, suggesting that they may be targeted via a common approach. Here, we use multiple oxidative phosphorylation (OXPHOS)-competent and incompetent cancer cell pairs to demonstrate that treatment with α-ketoglutarate (aKG) esters elicits rapid death of OXPHOS-deficient cancer cells by elevating intracellular aKG concentrations, thereby sequestering nitrogen from aspartate through glutamic-oxaloacetic transaminase 1 (GOT1). Exhaustion of aspartate in these cells resulted in immediate depletion of adenylates, which plays a central role in mediating mTOR inactivation and inhibition of glycolysis. aKG esters also conferred cytotoxicity in a variety of cancer types if their cell respiration was obstructed by hypoxia or by chemical inhibition of the electron transport chain (ETC), both of which are known to increase aspartate and GOT1 dependencies. Furthermore, preclinical mouse studies suggested that cell-permeable aKG displays a good biosafety profile, eliminates aspartate only in OXPHOS-incompetent tumors, and prevents their growth and metastasis. This study reveals a novel cytotoxic mechanism for the metabolite aKG and identifies cell-permeable aKG, either by itself or in combination with ETC inhibitors, as a potential anticancer approach. SIGNIFICANCE: These findings demonstrate that OXPHOS deficiency caused by either hypoxia or mutations, which can significantly increase cancer virulence, renders tumors sensitive to aKG esters by targeting their dependence upon GOT1 for aspartate synthesis. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/17/3492/F1.large.jpg.

Genetic deletion of gpr27 alters acylcarnitine metabolism, insulin sensitivity, and glucose homeostasis in zebrafish.

G protein-coupled receptors (GPCRs) comprise the largest group of membrane receptors in eukaryotic genomes and collectively they regulate nearly all cellular processes. Despite the widely recognized importance of this class of proteins, many GPCRs remain understudied. G protein-coupled receptor 27 (Gpr27) is an orphan GPCR that displays high conservation during vertebrate evolution. Although, GPR27 is known to be expressed in tissues that regulate metabolism including the pancreas, skeletal muscle, and adipose tissue, its functions are poorly characterized. Therefore, to investigate the potential roles of Gpr27 in energy metabolism, we generated a whole body gpr27 knockout zebrafish line. Loss of gpr27 potentiated the elevation in glucose levels induced by pharmacological or nutritional perturbations. We next leveraged a mass spectrometry metabolite profiling platform to identify other potential metabolic functions of Gpr27. Notably, genetic deletion of gpr27 elevated medium-chain acylcarnitines, in particular C6-hexanoylcarnitine, C8-octanoylcarnitine, C9-nonanoylcarnitine, and C10-decanoylcarnitine, lipid species known to be associated with insulin resistance in humans. Concordantly, gpr27 deletion in zebrafish abrogated insulin-dependent Akt phosphorylation and glucose utilization. Finally, loss of gpr27 increased the expression of key enzymes in carnitine shuttle complex, in particular the homolog to the brain-specific isoform of CPT1C which functions as a hypothalamic energy senor. In summary, our findings shed light on the biochemical functions of Gpr27 by illuminating its role in lipid metabolism, insulin signaling, and glucose homeostasis.