Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity.

The sensor RIG-I detects double-stranded RNA derived from RNA viruses. Although RIG-I is also known to have a role in the antiviral response to DNA viruses, physiological RNA species recognized by RIG-I during infection with a DNA virus are largely unknown. Using next-generation RNA sequencing (RNAseq), we found that host-derived RNAs, most prominently 5S ribosomal RNA pseudogene 141 (RNA5SP141), bound to RIG-I during infection with herpes simplex virus 1 (HSV-1). Infection with HSV-1 induced relocalization of RNA5SP141 from the nucleus to the cytoplasm, and virus-induced shutoff of host protein synthesis downregulated the abundance of RNA5SP141-interacting proteins, which allowed RNA5SP141 to bind RIG-I and induce the expression of type I interferons. Silencing of RNA5SP141 strongly dampened the antiviral response to HSV-1 and the related virus Epstein-Barr virus (EBV), as well as influenza A virus (IAV). Our findings reveal that antiviral immunity can be triggered by host RNAs that are unshielded following depletion of their respective binding proteins by the virus.

Rapid detection of viable microbes with 5-cyano-2,3-di-(p-tolyl)tetrazolium chloride and 5(6)-carboxyfluorescein diacetate using a fibre fluorescence spectroscopy system.

AIMS: To assess the efficacy of two commercially available viability dyes, 5-cyano-2,3-di-(p-tolyl)tetrazolium chloride (CTC) and 5(6)-carboxyfluorescein diacetate (CFDA), in reporting on viable cell concentration and species using an all-fibre fluorometer. METHODS AND RESULTS: Four bacterial species (two Gram-positive and two Gram-negative) commonly associated with food poisoning or food spoilage (Escherichia coli, Salmonella enterica, Staphylococcus aureus, and Bacillus cereus) were stained with CTC or CFDA and the fibre fluorometer was used to collect full fluorescence emission spectra. A good correlation between concentration and fluorescence intensity was found for Gram-negative bacteria between 107 and 108 colony-forming units (CFU) ml-1. There was no correlation with concentration for Gram-positive bacteria; however, the information in the CTC and CFDA spectra shows the potential to distinguish Gram-negative cells from Gram-positive cells, although it may simply reflect the overall bacterial metabolic activity under staining conditions from this study. CONCLUSIONS: The limit of detection (LoD) is too high in the dip-probe approach for analysis; however, the development of an approach measuring the fluorescence of single cells may improve this limitation. The development of new bacteria-specific fluorogenic dyes may also address this limitation. The ability to differentiate bacteria using these dyes may add value to measurements made to enumerate bacteria using CTC and CFDA.

The US3 Kinase of Herpes Simplex Virus Phosphorylates the RNA Sensor RIG-I To Suppress Innate Immunity.

Recent studies have demonstrated that the signaling activity of the cytosolic pathogen sensor retinoic acid-inducible gene-I (RIG-I) is modulated by a variety of posttranslational modifications (PTMs) to fine-tune the antiviral type I interferon (IFN) response. Whereas K63-linked ubiquitination of the RIG-I caspase activation and recruitment domains (CARDs) catalyzed by TRIM25 or other E3 ligases activates RIG-I, phosphorylation of RIG-I at S8 and T170 represses RIG-I signal transduction by preventing the TRIM25-RIG-I interaction and subsequent RIG-I ubiquitination. While strategies to suppress RIG-I signaling by interfering with its K63-polyubiquitin-dependent activation have been identified for several viruses, evasion mechanisms that directly promote RIG-I phosphorylation to escape antiviral immunity are unknown. Here, we show that the serine/threonine (Ser/Thr) kinase US3 of herpes simplex virus 1 (HSV-1) binds to RIG-I and phosphorylates RIG-I specifically at S8. US3-mediated phosphorylation suppressed TRIM25-mediated RIG-I ubiquitination, RIG-I-MAVS binding, and type I IFN induction. We constructed a mutant HSV-1 encoding a catalytically-inactive US3 protein (K220A) and found that, in contrast to the parental virus, the US3 mutant HSV-1 was unable to phosphorylate RIG-I at S8 and elicited higher levels of type I IFNs, IFN-stimulated genes (ISGs), and proinflammatory cytokines in a RIG-I-dependent manner. Finally, we show that this RIG-I evasion mechanism is conserved among the alphaherpesvirus US3 kinase family. Collectively, our study reveals a novel immune evasion mechanism of herpesviruses in which their US3 kinases phosphorylate the sensor RIG-I to keep it in the signaling-repressed state. IMPORTANCE Herpes simplex virus 1 (HSV-1) establishes lifelong latency in the majority of the human population worldwide. HSV-1 occasionally reactivates to produce infectious virus and to facilitate dissemination. While often remaining subclinical, both primary infection and reactivation occasionally cause debilitating eye diseases, which can lead to blindness, as well as life-threatening encephalitis and newborn infections. To identify new therapeutic targets for HSV-1-induced diseases, it is important to understand the HSV-1-host interactions that may influence infection outcome and disease. Our work uncovered direct phosphorylation of the pathogen sensor RIG-I by alphaherpesvirus-encoded kinases as a novel viral immune escape strategy and also underscores the importance of RNA sensors in surveilling DNA virus infection.

Implementation of Multimodal Pain Protocol Associated With Opioid Use Reduction in Trauma Patients.

INTRODUCTION: Many trauma centers have adopted multimodal pain protocols (MMPPs) to provide safe and effective pain control. The objective was to evaluate the association of a protocol on opioid use in trauma patients and patient-reported pain scores. METHODS: This was a retrospective review of adult trauma patients admitted from 7/1-9/30/2018 to 7/1-9/30/2019 at an urban academic level 1 trauma center. The MMPP consisted of scheduled nonopioid medications implemented on July 1, 2019. Patients were stratified by level of care upon admission, intensive care unit (ICU) or floor, and by injury severity score (ISS) (ISS < 16 or ISS ≥ 16). Pain scores, opioid, and nonopioid analgesic medication use were compared for the hospital stay or first 30 d. RESULTS: Seven hundred ninety eight patients were included with a mean age of 54 ± 22 y and 511 (64.0%) were men. Demographic and clinical characteristics between those in the pre-MMP (n = 404) and post-MMPP (n = 394) groups were not different. The average pain scores were not different between the two groups (3.7 versus 3.8, P = 0.44), but patients in the post-MMPP group received 36% less morphine milliequivalents (109.6 versus 70; P < 0.0001). The MMPP had the largest effect on patients admitted to the ICU regardless of injury severity. ICU patients with ISS ≥ 16 had the greatest reduction in morphine milliequivalents (174.6 versus 84.4; P < 0.0001). The use of nonopioid analgesics was significantly increased in all groups. CONCLUSIONS: A MMPP is associated with a reduction of opioids and increase in nonopioid analgesics with no difference in patient-reported pain scores.

Do all roads lead to Rome? A retrospective analysis on surgical technique in sleeve gastrectomy.

BACKGROUND: New York University Langone Health has three accredited bariatric centers, with 10 different bariatric surgeons. This retrospective analysis compares surgeon techniques in laparoscopic or robotic sleeve gastrectomy (SG) to identify associations with perioperative morbidity and mortality. METHODS: All adults who underwent SG between 2017 and 2021 at NYU Langone Health were evaluated via EMR and MBSAQIP 30-day data. We also surveyed all 10 bariatric surgeons and compared their techniques and total adverse outcomes. Bleeding, SSI, mortality, readmission, and reoperation were specifically sub-analyzed via logistic regression. RESULTS: 86 (2.77%) out of 3,104 patients who underwent SG encountered an adverse event. Lower adverse outcomes were observed with a laparoscopic approach, 40-Fr bougie, buttressing, not oversewing the staple line, using hemostatic agents, stapling 3-cm from pylorus, and no routine UGI series. Lower bleeding rates were observed in a laparoscopic approach, 40-Fr bougie, buttressing, not oversewing the staple line, using hemostatic agents, stapling 3-cm from pylorus, no routine UGI series, and not proceeding with SG if hiatal hernia is present. Lower SSI rates were observed with ViSiGi™ bougie, no hemostatic agents, and routine EGD. Lower readmission rates were observed with 40-Fr bougie, buttressing, not oversewing, and stapling 3-cm from pylorus. Hemostatic agents had higher reoperation rates. It was not feasible to test for mortality given the low incidence. CONCLUSION: Certain surgical techniques in SG among our bariatric surgeons had a significant effect on the rates of adverse outcomes, bleeding, readmission, reoperation, and SSI. Our findings warrant further investigation into these techniques via multivariate regression or prospective design. LIMITATIONS: This study was limited by its retrospective and univariate design. We did not account for interaction. The sample size was small, and follow-up of 30 days was relatively short. We did not include patient characteristics in the model or control for surgeon skill.

Do all roads lead to Rome?: A retrospective analysis on surgical technique in Roux-en-Y gastric bypass.

BACKGROUND: New York University Langone Health has three accredited bariatric centers, with altogether ten different bariatric surgeons. This retrospective analysis compares individual surgeon techniques in laparoscopic or robotic Roux-en-Y gastric bypass (RYGB) to identify potential associations with perioperative morbidity and mortality. METHODS: All adult patients who underwent RYGB between 2017 and 2021 at NYU Langone Health campuses were evaluated via electronic medical records and MBSAQIP 30-day follow-up data. We surveyed all ten practicing bariatric surgeons to analyze the relationship between their techniques and total adverse outcomes. Bleeding, SSI, mortality, readmission, and reoperation were specifically sub-analyzed via logistic regression. RESULTS: 54 (7.59%) out of 711 patients who underwent laparoscopic or robotic RYGB encountered an adverse outcome. Lower adverse outcomes were observed with laparoscopic approach, creating the JJ anastomosis first, flat positioning, division of the mesentery, Covidien™ laparoscopic staplers, gold staples, unidirectional JJ anastomosis, hand-sewn common enterotomy, 100-cm Roux limb, 50-cm biliopancreatic limb, and routine EGD. Lower bleeding rates were observed with flat positioning, gold staples, hand-sewn common enterotomy, 50-cm biliopancreatic limb, and routine EGD. Lower readmission rates were observed in laparoscopic, flat positioning, Covidien™ staplers, unidirectional JJ anastomosis, and hand-sewn common enterotomy. Gold staples had lower reoperation rates. Otherwise, there was no statistically significant difference in SSI. CONCLUSION: Certain surgical techniques in RYGB within our bariatric surgery group had significant effects on the rates of total adverse outcomes, bleeding, readmission, and reoperation. Our findings warrant further investigation into the aforementioned techniques via multivariate regression models or prospective study design. LIMITATIONS: This study was limited by the inherent nature of its retrospective and univariate statistical design. We did not account for the interaction between techniques. The sample size of surgeons was small, and follow-up of 30 days was relatively short. We did not include patient characteristics in the model or control for surgeon skill.

Low subjective social status is associated with daily selection of fewer healthy foods and more high-fat/high sugar foods.

Socioeconomic status has been related to poorer eating behaviors, potentially due to feeling of lower status relative to peers. Despite experimental evidence that temporarily feeling of lower status can contribute to greater caloric intake, it remains unclear how feeling of lower social status relate to eating behavior in daily life. This study aimed to test whether lower subjective social status (SSS)-the feeling of having relatively lower social status-in American society and relative to college peers were related to daily food selection. A sample of 131 young adults (Mage = 20.3, SD = 0.8; 60% female; 46% Latinos; 34% European American; 15% Asian American; 5% of other ethnicities) reported their SSS in society and in college and completed 15 daily reports regarding the number of daily servings they had of fruits, vegetables, fried foods, fast foods, desserts, and sugary drinks. Multilevel models with days nested within individuals were used to test whether low SSS in society or college related to daily food intake. Next, we examined whether associations were driven by young adults' perceived stress and daily stressors. Analyses controlled for age, gender, ethnicity, family and personal income, and parents' education to test the unique associations between subjective status and food intake. Whereas SSS in society was not related to food intake, young adults with lower SSS in their college consumed fewer daily servings of healthy foods and more daily servings of high-fat/high-sugar foods. Although lower college SSS was related to greater perceived stress, perceived stress and daily stressors were consistently unrelated to daily food intake. Findings suggested that lower SSS in local environments (e.g., college) may impact young adults' daily food choices through processes beyond heightened stress.

The Relationship Between Family Socioeconomic Status and Adolescent Sleep and Diurnal Cortisol.

OBJECTIVE: This study aimed to investigate the associations between indices of family socioeconomic status and sleep during adolescence and to examine whether measures of hypothalamic-pituitary-adrenal (HPA) axis functioning mediate the observed associations. METHODS: A total of 350 ethnically diverse adolescents (57% female; mean [standard deviation] age wave 1 = 16.4 [0.7] years) completed a three-wave longitudinal study in which sleep and cortisol data were collected at 2-year time intervals. Sleep duration, latency, and variability were assessed via actigraphy during a period of 8 days per study wave. Salivary cortisol was collected across 3 days per study wave to assess cortisol diurnal slope, area under the curve, and the cortisol awakening response. Adolescents' caregivers reported their education levels, family income, and economic hardship. RESULTS: A greater family income-to-needs ratio was associated with longer adolescent sleep duration ( b = 2.90, p = .023), whereas greater parental education was associated with shorter sleep duration ( b = -3.70, p = .030), less sleep latency ( b = -0.74, p = .016), and less variability across days ( b = -2.06, p = .010). Diurnal cortisol slope statistically mediated the association of parental education with sleep duration ( b = -0.48, 95% confidence interval = -1.099 to -0.042), but not the association of income-to-needs ratio with sleep duration. CONCLUSIONS: Findings suggest that parental education and family resources may have unique impacts upon sleep and HPA axis functioning during the period of adolescence. Future research is needed to examine family and behavioral factors that may underlie socioeconomic status associations with adolescent sleep and HPA axis functioning.

AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges.

Long-term in vivo expression of a broad and potent entry inhibitor could circumvent the need for a conventional vaccine for HIV-1. Adeno-associated virus (AAV) vectors can stably express HIV-1 broadly neutralizing antibodies (bNAbs). However, even the best bNAbs neutralize 10-50% of HIV-1 isolates inefficiently (80% inhibitory concentration (IC80) > 5 µg ml(-1)), suggesting that high concentrations of these antibodies would be necessary to achieve general protection. Here we show that eCD4-Ig, a fusion of CD4-Ig with a small CCR5-mimetic sulfopeptide, binds avidly and cooperatively to the HIV-1 envelope glycoprotein (Env) and is more potent than the best bNAbs (geometric mean half-maximum inhibitory concentration (IC50) < 0.05 µg ml(-1)). Because eCD4-Ig binds only conserved regions of Env, it is also much broader than any bNAb. For example, eCD4-Ig efficiently neutralized 100% of a diverse panel of neutralization-resistant HIV-1, HIV-2 and simian immunodeficiency virus isolates, including a comprehensive set of isolates resistant to the CD4-binding site bNAbs VRC01, NIH45-46 and 3BNC117. Rhesus macaques inoculated with an AAV vector stably expressed 17-77 µg ml(-1) of fully functional rhesus eCD4-Ig for more than 40 weeks, and these macaques were protected from several infectious challenges with SHIV-AD8. Rhesus eCD4-Ig was also markedly less immunogenic than rhesus forms of four well-characterized bNAbs. Our data suggest that AAV-delivered eCD4-Ig can function like an effective HIV-1 vaccine.

Subcortical structural variations associated with low socioeconomic status in adolescents.

Low socioeconomic status (SES) is associated with a higher probability of multiple exposures (e.g., neighborhood violence, poor nutrition, housing instability, air pollution, and insensitive caregiving) known to affect structural development of subcortical brain regions that subserve threat and reward processing, however, few studies have examined the relationship between SES and such subcortical structures in adolescents. We examined SES variations in volume and surface morphometry of subcortical regions. The sample comprised 256 youth in eighth grade (mean age = 13.9 years), in whom high dimensional deformation mapping of structural 3T magnetic resonance imaging scans was performed. Vertex-wise linear regression analyses examined associations between income to poverty ratio and surfaces of the hippocampus, amygdala, thalamus, caudate, putamen, nucleus accumbens and pallidum, with the covariates age, pubertal status, and intracranial volume. Given sex differences in pubertal development and subcortical maturation at this age, the analyses were stratified by sex. Among males, who at this age average an earlier pubertal stage than females, the relationship between SES and local shape variation in subcortical regions was almost entirely positive. For females, the relationship between SES and local shape variation was negative. Racial identity was associated with SES in our sample, however supplementary analyses indicated that most of the associations between SES and subcortical structure were independent of it. Although these cross-sectional results are not definitive, they are consistent with a scenario where low SES delays structural maturation of subcortical regions involved with threat and reward processing. Future longitudinal studies are needed to test this hypothesis.

Good Relationships With Parents During Childhood as Buffers of the Association Between Childhood Disadvantage and Adult Susceptibility to the Common Cold.

OBJECTIVE: Children reared by parents of low socioeconomic status (SES) go on to have elevated rates of physical health problems and premature mortality. However, many children reared in low-SES families remain healthy throughout the life-span. Here, secondary analyses of archival data tested the hypothesis that a positive relationship with parents during childhood acts as a buffer of the increased risk of adult susceptibility to infectious illness associated with low childhood SES. METHODS: One hundred seventy-six healthy adults reported their childhood SES and the quality of their relationships with their parents during childhood. Relationship quality was defined as parental care, love and support, lack of conflict with parents, and family cohesiveness. Afterward, participants were exposed to a respiratory virus and monitored in quarantine for 5 days for the development of a "common cold" as indicated by infection and objective markers of illness. RESULTS: The increased risk of developing a cold associated with being reared in a low SES household was attenuated by a positive relationship with parents during childhood (b(SE) = 0.08 (0.03), p = .010). This buffering of disease risk held up across the four components of relationship quality (p values < .05). The association was independent of adult SES, demographics, prechallenge immunity to the virus, current levels of neuroticism and stress, parental divorce during childhood, and number of siblings (p values < .05). CONCLUSIONS: Individuals with positive relationships with their parents during childhood are buffered from the increased risk of adult susceptibility to an infectious disease associated with low childhood SES.

Early life adversity exposure and circulating markers of inflammation in children and adolescents: A systematic review and meta-analysis.

This study provides a comprehensive review of the published research on the association between early life adversity and markers of inflammation in children and adolescents. We conducted a systematic review of the published literature on the association between early life adversity and markers of inflammation in pediatric populations. To date, 27 studies have been published in this area representing a wide range of global populations and diverse methods of which nearly half were prospective, longitudinal studies. Of these 27, only 12 studies shared an inflammatory outcome with 4 or more other studies; 9 for CRP, and 6 for IL-6. The association between early life adversity and both CRP, z = .07 [.04, .10], and IL-6, z = .17 [-.07, .42], were small and only significant for CRP although comparable in magnitude to the effects observed in adult samples. Descriptively, the association between early life adversity and CRP appeared to be stronger in studies conducted in infants and adolescents compared with middle childhood. There was minimal evidence of publication bias for studies measuring CRP, but evidence of publication bias for studies using IL-6. Eight studies have looked at the association between early life adversity and stimulated inflammatory cytokines in vitro, and both the methods and results of these studies were mixed; the majority observed exaggerated production of inflammatory cytokines despite mixed methodological approaches that make comparisons across studies difficult. In summary, the evidence supporting an association between early life adversity and inflammation in pediatric samples is limited so far by the number of studies and their heterogeneous methodological approaches. More research that is grounded in a developmental framework and informed by the complexity of the innate immune system is needed in this area.

Subjective social status and stress responsivity in late adolescence.

Subjective social status (SSS) reflects one's perception of one's standing within society. SSS has been linked with health outcomes, over and above socioeconomic status, and is thought to influence health in part by shaping stress responsivity. To test this, the present study examined the links between SSS and psychological, hypothalamic-pituitary-adrenal (HPA) axis, and cardiovascular responsivity in a sample of 87 ethnically diverse late adolescents (Mage = 18.39 years). Participants rated their family's SSS while either in high school (n = 50) or 1 year afterward (n = 37). Participants completed the Trier Social Stress Task (TSST) and reported their fear during baseline and after task completion, provided six saliva samples throughout the task, and had their heart rate monitored continuously throughout the task. Multilevel models, with time points nested within participants, were conducted to assess reactivity and recovery for each outcome. Results indicated that lower SSS was associated with greater fear reactivity and faster rates of HPA axis reactivity and recovery to baseline. Regarding cardiovascular responses, no differences were observed with respect to heart rate. Lower SSS predicted increased respiratory sinus arrhythmia during the stress task only among participants who rated their SSS while in high school; no association was observed for those who rated SSS after high school. Results suggest that perceptions of one's family's standing in society can shape responses to stress and potentially broader health.HighlightsSubjective social status (SSS) was linked with differences in stress responsivity. Specifically, lower SSS was associated with greater increases in fear following an acute stressor and faster rates of cortisol reactivity and recovery. Adolescents with lower SSS in high school showed less cardiovascular reactivity and recovery with respect to respiratory sinus arrhythmia, a marker of parasympathetic nervous system activity.

Commentary: Ecology momentary assessment as a tool for understanding dynamic patterns in child and adolescent health and development - reflections on Russell and Gajos (2020).

Ecological momentary assessment (EMA) has served as a methodological tool across subdisciplines in psychology, shedding light on family, personality, and affective processes, and physical and mental health. In their review, Russell and Gajos demonstrate how EMA can overcome several limitations of traditional methods in developmental psychopathology to answer questions about mental and behavioral health in youth. They also provide thoughtful future directions on integrating sensor technology, advancing modeling techniques for temporally dense data, and employing EMA for delivering interventions. This commentary similarly advocates for the use of EMA but extends Russell and Gajos's review by emphasizing EMA's utility for understanding and revealing dynamic changes and processes along micro timescales that have relevance for youth's health and development. We discuss how EMA can be especially fruitful for advancing theory and practice when administered in bursts and when combined with traditional assessments and longer-term longitudinal designs. Because such studies are resource-intensive, we also consider how extant EMA studies can be leveraged and subjected to meta- and mega-analytic techniques to inform theories and future EMA designs. We conclude that EMA is a promising tool for elucidating dynamic fluctuations in experiences and intra- and interpersonal processes that contribute to child and adolescent development and risk.

Sleep problems in adolescence are prospectively linked to later depressive symptoms via the cortisol awakening response.

Sleep disturbance is a symptom of and a well-known risk factor for depression. Further, atypical functioning of the HPA axis has been linked to the pathogenesis of depression. The purpose of this study was to examine the role of adolescent HPA axis functioning in the link between adolescent sleep problems and later depressive symptoms. Methods: A sample of 157 17-18 year old adolescents (61.8% female) completed the Pittsburgh Sleep Quality Inventory (PSQI) and provided salivary cortisol samples throughout the day for three consecutive days. Two years later, adolescents reported their depressive symptoms via the Center for Epidemiological Studies Depression Scale (CES-D). Results: Individuals (age 17-18) with greater sleep disturbance reported greater depressive symptoms two years later (age 19-20). This association occurred through the indirect effect of sleep disturbance on the cortisol awakening response (CAR) (indirect effect = 0.14, 95%CI [.02 -.39]). Conclusions: One pathway through which sleep problems may lead to depressive symptoms is by up-regulating components of the body's physiological stress response system that can be measured through the cortisol awakening response. Behavioral interventions that target sleep disturbance in adolescents may mitigate this neurobiological pathway to depression during this high-risk developmental phase.

Depressive symptoms and immune transcriptional profiles in late adolescents.

BACKGROUND: Rates of depression increase and peak during late adolescence and alterations in immune processes are thought to be both a risk factor and outcome of depression. However, few studies have examined depression-immune dynamics among adolescents. Using a functional genomics approach, the current study examined whether depressive symptoms were associated with activation of a gene expression profile, characterized by upregulated expression of pro-inflammatory-related genes and downregulated expression of antiviral-related genes in a sample of older adolescents (Mage = 18.37, SD = 0.51). METHOD: Participants (n = 87) reported on their depressive symptoms during the past week using the CES-D, and provided blood samples for genome-wide transcriptional profiling of mRNA. RESULTS: Adolescents with clinically-significant levels of depressive symptoms (CES-D ≥ 16) exhibited upregulated expression of inflammation-related genes and downregulated expression of antiviral-related genes compared to their peers with lower levels of depressive symptoms (CES-D < 16). Bioinformatics analyses suggested that this pattern of differential gene expression was mediated by greater activity of the pro-inflammatory transcription factor, nuclear factor-kappa B (NF-κB), and reduced activity of glucocorticoid receptors (GRs) and interferon response factors (IRFs). Additional analyses implicated monocytes, B cells, and dendritic cells as primary cellular sources of the observed gene expression patterns associated with depressive symptoms. CONCLUSION: Results are consistent with past work demonstrating links between depression and altered immunity. They provide a molecular basis for these associations and suggest that the underlying molecular signature may emerge as early as late adolescence when rates of depression tend to increase.

Stress, Psychological Resources, and HPA and Inflammatory Reactivity During Late Adolescence.

Psychosocial stress during childhood and adolescence is associated with alterations in the hypothalamic-pituitary-adrenal (HPA) axis and with heightened inflammation, both of which are implicated in poor health; however, factors that may protect against these effects relatively early in life are not well understood. Thus, we examined whether psychosocial resources protect against stress-related alterations in the HPA axis and heightened inflammation in a sample of 91 late adolescents. Participants completed measures of various stressors (major life events, daily interpersonal stress, early adversity), and psychosocial resources (mastery, optimism, self-esteem, and positive reappraisal). They also completed the Trier Social Stress Test and provided saliva and blood samples for the assessment of cortisol and interleukin-6 reactivity. Each of the stressors was associated with lower cortisol reactivity. Additionally, associations with major life events and daily stress were moderated by psychological resources, such that more life events and daily stress were associated with decreased HPA reactivity among adolescents with lower levels of psychological resources, but not among those with higher levels of psychological resources. This pattern of findings was observed only for cortisol reactivity and not for interleukin-6 reactivity. Findings suggest that psychological resources may counteract the effects of certain adversity-related decreases in cortisol reactivity.

Identification of a second binding site on the TRIM25 B30.2 domain.

The retinoic acid-inducible gene-I (RIG-I) receptor recognizes short 5'-di- and triphosphate base-paired viral RNA and is a critical mediator of the innate immune response against viruses such as influenza A, Ebola, HIV and hepatitis C. This response is reported to require an orchestrated interaction with the tripartite motif 25 (TRIM25) B30.2 protein-interaction domain. Here, we present a novel second RIG-I-binding interface on the TRIM25 B30.2 domain that interacts with CARD1 and CARD2 (caspase activation and recruitment domains) of RIG-I and is revealed by the removal of an N-terminal α-helix that mimics dimerization of the full-length protein. Further characterization of the TRIM25 coiled-coil and B30.2 regions indicated that the B30.2 domains move freely on a flexible tether, facilitating RIG-I CARD recruitment. The identification of a dual binding mode for the TRIM25 B30.2 domain is a first for the SPRY/B30.2 domain family and may be a feature of other SPRY/B30.2 family members.

One size does not fit all: Links between shift-and-persist and asthma in youth are moderated by perceived social status and experience of unfair treatment.

The links between low socioeconomic status and poor health are well established, yet despite adversity, some individuals with low socioeconomic status appear to avoid these negative consequences through adaptive coping. Previous research found a set of strategies, called shift-and-persist (shifting the self to stressors while persisting by finding meaning), to be particularly adaptive for individuals with low socioeconomic status, who typically face more uncontrollable stressors. This study tested (a) whether perceived social status, similar to objective socioeconomic status, would moderate the link between shift-and-persist and health, and (b) whether a specific uncontrollable stressor, unfair treatment, would similarly moderate the health correlates of shift-and-persist. A sample of 308 youth (Meanage = 13.0, range 8-17), physician diagnosed with asthma, completed measures of shift-and-persist, unfair treatment, asthma control, and quality of life in the lab, and 2 weeks of daily diaries about their asthma symptoms. Parents reported on perceived family social status. Results indicated that shift-and-persist was associated with better asthma profiles, only among youth from families with lower (vs. higher) parent-reported perceived social status. Shift-and-persist was also associated with better asthma profiles, only among youth who experienced more (vs. less) unfair treatment. These findings suggest that the adaptive values of coping strategies for youth with asthma depend on the family's perceived social status and on the stressor experienced.