The master antioxidant defense is activated during EBV latent infection.

IMPORTANCE: To our knowledge, this is the first report delineating the activation of the master antioxidant defense during EBV latency. We show that EBV-triggered reactive oxygen species production activates the Keap1-NRF2 pathway in EBV-transformed cells, and LMP1 plays a major role in this event, and the stress-related kinase TBK1 is required for NRF2 activation. Moreover, we show that the Keap1-NRF2 pathway is important for cell proliferation and EBV latency maintenance. Our findings disclose how EBV controls the balance between oxidative stress and antioxidant defense, which greatly improve our understanding of EBV latency and pathogenesis and may be leveraged to opportunities toward the improvement of therapeutic outcomes in EBV-associated diseases.

Social functioning mediates the relationship between psychiatric symptoms and recovery among veteran and community service users with serious mental illness.

OBJECTIVE: Previous research has established the impact of psychiatric symptoms on social functioning, while there is a paucity of research examining how social functioning relates to personal recovery, an individual's self-assessment of their mental health recovery. This study examined the mediating effect of social engagement, interpersonal communication, and satisfaction with support in the relationship between distinct psychiatric symptom clusters and perceived mental health recovery. METHODS: In a cross-sectional study, both patient self-report and provider assessment data were collected for 250 patients with serious mental illness (SMI) across four mental health service sites. Parallel mediation analytic models were used. RESULTS: Interpersonal communication partially mediated the relationship between positive and negative symptom clusters and personal recovery. Satisfaction with social supports partially mediated the relationship between excited symptoms and personal recovery. Both interpersonal communication and satisfaction with social supports partially mediated the relationship between general psychological distress and depressive symptoms and personal recovery. Collectively, social functioning mediators explained nearly half of the relationship between general psychological distress and excited symptoms and personal recovery and nearly all of the relationship between positive symptoms and personal recovery. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Clinical providers working with persons with SMI should regularly assess social functioning in addition to assessing psychiatric symptoms and personal recovery factors and should incorporate social skills education into SMI group and individual treatments. Social functioning as a target of treatment may be especially beneficial for patients who are dissatisfied with other interventions or feel they have experienced the maximum benefit from treatment and are seeking additional methods to support personal recovery. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Self-Stigma and PTSD: Conceptualization and Implications for Research and Treatment.

Preliminary empirical evidence suggests that self-stigma may be a significant problem for those with posttraumatic stress disorder (PTSD). Although research on self-stigma for persons with PTSD is limited, some PTSD symptoms, such as negative thoughts about oneself, feelings of shame, and avoidance-particularly of social interactions-may be conceptually related to self-stigma, potentially explaining the co-occurrence and relevance of self-stigma in PTSD. This Open Forum reviews how the social cognitive model may explain the co-occurrence of self-stigma and PTSD, considers how this model may inform treatment approaches for self-stigma in PTSD, and identifies next steps to empirically test the proposed theory.

Gynogenetic Production of Embryos in Xenopus tropicalis Using a Cold Shock Procedure: Rapid Screening Method for Gene Editing Phenotypes.

Gynogenesis is a form of parthenogenesis in which eggs require sperm for fertilization but develop to adulthood without the contribution of paternal genome information, which happens naturally in some species. In Xenopus, gynogenetic diploid animals can be made experimentally. In mutagenesis strategies that only generate one allele of a recessive mutation, as might occur during gene editing, gynogenesis can be used to quickly reveal a recessive phenotype in eggs carrying a recessive mutation, thereby skipping one generation normally required to screen by conventional genetics. Xenopus oocytes do not complete meiosis until shortly after fertilization, and the second polar body is retained in fertilized eggs. Using ultraviolet (UV)-irradiated sperm, fertilization can be triggered without a genetic paternal contribution. Upon applying cold shock at the proper time to such embryos, ejection of the second polar body can be suppressed and both maternal sister chromatids are retained, leading to the development of gynogenetic diploid embryos. Because the genome of the resultant animals consists of recombined sister chromatids because of crossover events during meiosis, it is not completely homozygous throughout the whole genome. Nevertheless, the genome is homozygous at some loci proximal to the centromere that are unlikely to undergo recombination during meiosis and homozygous at reduced frequency if mutations are farther from the centromere, but still generally at a scorable level. Therefore, this technique is useful for rapid screening phenotypes of recessive mutations in such regions. We describe here a step-by-step protocol to achieve cold shock-mediated gynogenesis in Xenopus tropicalis.

Bioinformatics-Driven Identification of p62 as A Crucial Oncogene in Liver Cancer.

Liver hepatocellular carcinoma (LIHC) is the major form of liver cancer that is the fourth most common cause of cancer death worldwide. It has been reported that the multifunctional protein p62 (also known as SQSTM1) plays a cancer-promoting role in LIHC, but the detailed mechanisms underlying p62 interaction with LIHC remains unclear. To gain a comprehensive understanding of p62 interaction with LIHC in clinical settings, we performed bioinformatic analyses using various online algorithms derived from high throughput profiling. Our results indicate that p62 expression is significantly upregulated, partially due to its promoter demethylation, rather than p62 gene mutation, in LIHC. Mutation of TP53, CTNNB1, or ALB significantly correlates with, and mutation of AXIN1 reversely correlates with, the p62 expression level. Its upregulation occurs as early as liver cirrhosis, and go through all stages of the carcinogenesis. HCV infection makes a significant contribution to p62 upregulation in LIHC. We further identified p62-associated molecular signatures in LIHC, including many genes that are involved in antioxidant stress and metabolism, such as SRX1 and TXNRD1. Regarding to the clinical outcome, p62 expression level reversely correlates with the survival of LIHC patients (p<0.01). Importantly, we experimentally validated that p62 depletion in liver cancer cell lines downregulates the expression of SRX1 and TXNRD1 at both transcriptional and translational levels, and reduces cell proliferation. As the potential mechanisms underlying the tumor-promoting role of p62, we show that p62 upregulation is remarkably associated with reprogramming of pathways mediated by p53, Wnt/ß-catenin, and Keap1-NRF2, which are crucial for oncogenesis in many contexts. Our findings provide a comprehensive insight into the interaction between p62 and LIHC, offering valuable information for understanding of LIHC pathogenesis.

Body mass index and age are associated with ventricular end-diastolic pressure in adults with a Fontan circulation.

INTRODUCTION: Systemic ventricular end-diastolic pressure is an important haemodynamic variable in adult patients with Fontan circulation. Risk factors associated with elevated end-diastolic pressure have not been clearly identified in this population. METHODS: All patients > 18 years with Fontan circulation who underwent cardiac catheterisation at our centre between 1/08 and 3/19 were included. Relevant patient variables were extracted. Univariate and multivariate general linear models were analysed to identify variables associated with end-diastolic pressure. RESULTS: Forty-two patients were included. Median age was 24.0 years (20.9-29.0) with a body mass index of 23.7 kg/m2 (21.5-29.7). 10 (23.8%) patients had a systemic right ventricle. The median (Interquartile range) and mean pulmonary artery pressure were 11.0 mmHg (9.0-12.0) and 16.0 mmHg (13.0-18.0), respectively. On univariate analysis, end-diastolic pressure was positively associated with body mass index (p < 0.01), age > 25 years (p = 0.04), symptoms of heart failure (p < 0.01), systemic ventricular systolic pressure (p = 0.03), pulmonary artery mean pressure (p < 0.01), and taking diuretics (p < 0.01) or sildenafil (p < 0.01). End-diastolic pressure was negatively associated with aortic saturation (p < 0.01). On multivariate analysis, end-diastolic pressure was positively associated with age ≥ 25 years (p < 0.01), and body mass index (p = 0.04). CONCLUSIONS: In a cohort of adult patients with Fontan circulation undergoing catheterisation, end-diastolic pressure was positively associated with age ≥ 25 years and body mass index on multivariate analysis. Maintaining a healthy body mass index may offer haemodynamic benefit in adults with Fontan physiology.

Blocking the orexin system following therapeutic exposure promoted between session habituation, but not PTSD symptom reduction.

There is a need to identify strategies to increase the effectiveness of treatments for posttraumatic stress disorder (PTSD). Sleep is often disturbed in PTSD and has been implicated in learning processes that underlie recovery from PTSD, including extinction of conditioned fear. Our prior study suggested that diminished arousal during sleep may enhance benefits of therapeutic exposure for PTSD. The orexin system regulates arousal, and blocking the system diminishes arousal and promotes sleep. We, therefore, examined whether a dual orexin receptor antagonist, suvorexant, administered following evening exposure sessions, would enhance their therapeutic effectiveness for PTSD. In this randomized double-blind placebo-controlled trial, adults with PTSD completed four written narrative exposure (WNE) sessions, two of which took place in the evening, and two the next morning. Participants received either suvorexant or placebo after each evening WNE. We found that suvorexant increased N3 sleep and decreased N2 sleep and rapid-eye-movement latency measured by polysomnography. Between session habituation indexed by subjective distress ratings was greater with suvorexant, but there was no group difference in the reduction of PTSD severity from baseline to 1-week follow-up. No safety concerns emerged. The present findings provide preliminary support for enhancement of an effect of therapeutic exposure for PTSD by suvorexant. Further studies with larger samples are needed to translate the present findings into clinical applications, including studies to develop optimal suvorexant administration and exposure session schedules to achieve persistent benefits to sleep and possibly greater treatment augmentation.

The Ubiquitin Sensor and Adaptor Protein p62 Mediates Signal Transduction of a Viral Oncogenic Pathway.

The Epstein-Barr virus (EBV) protein LMP1 serves as a paradigm that engages complicated ubiquitination-mediated mechanisms to activate multiple transcription factors. p62 is a ubiquitin sensor and a signal-transducing adaptor that has multiple functions in diverse contexts. However, the interaction between p62 and oncogenic viruses is poorly understood. We recently reported a crucial role for p62 in oncovirus-mediated oxidative stress by acting as a selective autophagy receptor. In this following pursuit, we further discovered that p62 is upregulated in EBV type 3 compared to type 1 latency, with a significant contribution from NF-κB and AP1 activities downstream of LMP1 signaling. In turn, p62 participates in LMP1 signal transduction through its interaction with TRAF6, promoting TRAF6 ubiquitination and activation. As expected, short hairpin RNA (shRNA)-mediated knockdown (KD) of p62 transcripts reduces LMP1-TRAF6 interaction and TRAF6 ubiquitination, as well as p65 nuclear translocation, which was assessed by Amnis imaging flow cytometry. Strikingly, LMP1-stimulated NF-κB, AP1, and Akt activities are all markedly reduced in p62-/- mouse embryo fibroblasts (MEFs) and in EBV-negative Burkitt's lymphoma (BL) cell lines with CRISPR-mediated knockout (KO) of the p62-encoding gene. However, EBV-positive BL cell lines (type 3 latency) with CRISPR-mediated KO of the p62-encoding gene failed to survive. In consequence, shRNA-mediated p62 KD impairs the ability of LMP1 to regulate its target gene expression, promotes etoposide-induced apoptosis, and reduces the proliferation of lymphoblastic cell lines (LCLs). These important findings have revealed a previously unrecognized novel role for p62 in EBV latency and oncogenesis, which advances our understanding of the mechanism underlying virus-mediated oncogenesis. IMPORTANCE As a ubiquitin sensor and a signal-transducing adaptor, p62 is crucial for NF-κB activation, which involves the ubiquitin machinery, in diverse contexts. However, whether p62 is required for EBV LMP1 activation of NF-κB is an open question. In this study, we provide evidence that p62 is upregulated in EBV type 3 latency and, in turn, p62 mediates LMP1 signal transduction to NF-κB, AP1, and Akt by promoting TRAF6 ubiquitination and activation. In consequence, p62 deficiency negatively regulates LMP1-mediated gene expression, promotes etoposide-induced apoptosis, and reduces the proliferation of LCLs. These important findings identified p62 as a novel signaling component of the key viral oncogenic signaling pathway.

Algorithm-Based Meta-Analysis Reveals the Mechanistic Interaction of the Tumor Suppressor LIMD1 With Non-Small-Cell Lung Carcinoma.

Non-small-cell lung carcinoma (NSCLC) is the major type of lung cancer, which is among the leading causes of cancer-related deaths worldwide. LIMD1 was previously identified as a tumor suppressor in lung cancer, but their detailed interaction in this setting remains unclear. In this study, we have carried out multiple genome-wide bioinformatic analyses for a comprehensive understanding of LIMD1 in NSCLC, using various online algorithm platforms that have been built for mega databases derived from both clinical and cell line samples. Our results indicate that LIMD1 expression level is significantly downregulated at both mRNA and protein levels in both lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), with a considerable contribution from its promoter methylation rather than its gene mutations. The Limd1 gene undergoes mutation only at a low rate in NSCLC (0.712%). We have further identified LIMD1-associated molecular signatures in NSCLC, including its natural antisense long non-coding RNA LIMD1-AS1 and a pool of membrane trafficking regulators. We have also identified a subgroup of tumor-infiltrating lymphocytes, especially neutrophils, whose tumor infiltration levels significantly correlate with LIMD1 level in both LUAD and LUSC. However, a significant correlation of LIMD1 with a subset of immune regulatory molecules, such as IL6R and TAP1, was only found in LUAD. Regarding the clinical outcomes, LIMD1 expression level only significantly correlates with the survival of LUAD (p<0.01) but not with that of LUSC (p>0.1) patients. These findings indicate that LIMD1 plays a survival role in LUAD patients at least by acting as an immune regulatory protein. To further understand the mechanisms underlying the tumor-suppressing function of LIMD1 in NSCLC, we show that LIMD1 downregulation remarkably correlates with the deregulation of multiple pathways that play decisive roles in the oncogenesis of NSCLC, especially those mediated by EGFR, KRAS, PIK3CA, Keap1, and p63, in both LUAD and LUSC, and those mediated by p53 and CDKN2A only in LUAD. This study has disclosed that LIMD1 can serve as a survival prognostic marker for LUAD patients and provides mechanistic insights into the interaction of LIMD1 with NSCLC, which provide valuable information for clinical applications.

Rapid resolution of colitis related to immunosuppressive medication after infliximab administration.

Immunosuppression is necessary after solid organ transplantation. The non-infectious side effects associated with many of these agents are not well understood. We report a case of colitis, most resembling inflammatory bowel disease, that persisted despite withdrawal of tacrolimus and mycophenolate mofetil and transition to alternative agents. The patient was treated for clostridium difficile without improvement. Endoscopic biopsies demonstrated non-specific inflammation without evidence of active infection. An extensive immunologic and oncologic workup was negative. Ultimately, we trialed the administration of infliximab, a monoclonal antibody that inhibits TNF-alpha receptors that is commonly used in the treatment of inflammatory bowel disease. With infliximab treatment, the patient experienced rapid resolution of his disease and has remained in remission.

p62-mediated Selective autophagy endows virus-transformed cells with insusceptibility to DNA damage under oxidative stress.

DNA damage response (DDR) and selective autophagy both can be activated by reactive oxygen/nitrogen species (ROS/RNS), and both are of paramount importance in cancer development. The selective autophagy receptor and ubiquitin (Ub) sensor p62 plays a key role in their crosstalk. ROS production has been well documented in latent infection of oncogenic viruses including Epstein-Barr Virus (EBV). However, p62-mediated selective autophagy and its interplay with DDR have not been investigated in these settings. In this study, we provide evidence that considerable levels of p62-mediated selective autophagy are spontaneously induced, and correlate with ROS-Keap1-NRF2 pathway activity, in virus-transformed cells. Inhibition of autophagy results in p62 accumulation in the nucleus, and promotes ROS-induced DNA damage and cell death, as well as downregulates the DNA repair proteins CHK1 and RAD51. In contrast, MG132-mediated proteasome inhibition, which induces rigorous autophagy, promotes p62 degradation but accumulation of the DNA repair proteins CHK1 and RAD51. However, pretreatment with an autophagy inhibitor offsets the effects of MG132 on CHK1 and RAD51 levels. These findings imply that p62 accumulation in the nucleus in response to autophagy inhibition promotes proteasome-mediated CHK1 and RAD51 protein instability. This claim is further supported by the findings that transient expression of a p62 mutant, which is constitutively localized in the nucleus, in B cell lines with low endogenous p62 levels recaptures the effects of autophagy inhibition on CHK1 and RAD51 protein stability. These results indicate that proteasomal degradation of RAD51 and CHK1 is dependent on p62 accumulation in the nucleus. However, small hairpin RNA (shRNA)-mediated p62 depletion in EBV-transformed lymphoblastic cell lines (LCLs) had no apparent effects on the protein levels of CHK1 and RAD51, likely due to the constitutive localization of p62 in the cytoplasm and incomplete knockdown is insufficient to manifest its nuclear effects on these proteins. Rather, shRNA-mediated p62 depletion in EBV-transformed LCLs results in significant increases of endogenous RNF168-γH2AX damage foci and chromatin ubiquitination, indicative of activation of RNF168-mediated DNA repair mechanisms. Our results have unveiled a pivotal role for p62-mediated selective autophagy that governs DDR in the setting of oncogenic virus latent infection, and provide a novel insight into virus-mediated oncogenesis.

Impact of Traumatic Stress on Sleep and Management Options in Women.

After exposure to traumatic stress, women are at greater risk than men for developing symptoms of some psychiatric disorders, including insomnia and nightmares. Sleep disturbance is one of the most refractory symptoms of posttraumatic stress disorder. Women were included in a few studies that examined efficacy of psychological or pharmacologic interventions for trauma-related sleep disturbances. Studies demonstrated preliminary evidence for efficacy of cognitive behavioral therapy for insomnia, imagery rehearsal therapy, and combinations of these techniques in treating insomnia and nightmares in trauma-exposed women. Prazosin as an adjunct to ongoing treatment is a potentially efficacious strategy for treating trauma-related nightmares in women.

Neuromuscular Adaptations Following Training and Protein Supplementation in a Group of Trained Weightlifters.

The purpose of this study was to examine the effects of a recovery supplement compared with a placebo on muscle morphology in trained weightlifters. Vastus lateralis and muscle fiber cross sectional area of type I and type II fibers were compared between groups using a series of 2 × 2 (group × time) repeated measure ANOVAs. Both groups on average improved cross-sectional area of the vastus lateralis, type I and type II muscle fibers from pre-to-post but individual response varied within both groups. Greater magnitude of changes in type I and type II muscle fibers were observed for the placebo group but not for vastus lateralis cross sectional area. Additionally, subjects were divided into large and small fiber groups based on combined fiber size at the start of the investigation. These findings indicate that the recovery supplement utilized provided no greater effect compared with a placebo in a 12-week block periodization protocol in trained weightlifters. The primary determinate of fiber size changes in the study was determined to be the initial fiber size of muscle fibers with larger practical changes observed in the small fiber group compared with the large fiber group in type I, II, and ultrasound cross-sectional area (CSA).

LIMD1 is induced by and required for LMP1 signaling, and protects EBV-transformed cells from DNA damage-induced cell death.

LIMD1 (LIM domain-containing protein 1) is considered as a tumor suppressor, being deregulated in many cancers to include hematological malignancies; however, very little is known about the underlying mechanisms of its deregulation and its roles in carcinogenesis. Epstein-Barr Virus (EBV) is associated with a panel of malignancies of lymphocytic and epithelial origin. Using high throughput expression profiling, we have previously identified LIMD1 as a common marker associated with the oncogenic transcription factor IRF4 in EBV-related lymphomas and other hematological malignancies. In this study, we have identified potential conserved IRF4- and NFκB-binding motifs in the LIMD1 gene promoter, and both are demonstrated functional by promoter-reporter assays. We further show that LIMD1 is partially upregulated by EBV latent membrane protein 1 (LMP1) via IRF4 and NFκB in EBV latency. As to its role in the setting of EBV latent infection, we show that LIMD1 interacts with TRAF6, a crucial mediator of LMP1 signal transduction. Importantly, LIMD1 depletion impairs LMP1 signaling and functions, potentiates ionomycin-induced DNA damage and apoptosis, and inhibits p62-mediated selective autophagy. Taken together, these results show that LIMD1 is upregulated in EBV latency and plays an oncogenic role rather than that of a tumor suppressor. Our findings have identified LIMD1 as a novel player in EBV latency and oncogenesis, and open a novel research avenue, in which LIMD1 and p62 play crucial roles in linking DNA damage response (DDR), apoptosis, and autophagy and their potential interplay during viral oncogenesis.

Standardization and Scaling of a Community-Based Palliative Care Model.

BACKGROUND: Although limited, the descriptions of Community-Based Palliative Care (CBPC) demonstrates variability in team structures, eligibility, and standardization across care settings. OBJECTIVE: In 2014, Four Seasons Compassion for Life, a nonprofit hospice and palliative care (PC) organization in Western North Carolina (WNC), was awarded a Centers for Medicare and Medicaid Services Health Care Innovation (CMMI) Award to expand upon their existing innovative model to implement, evaluate, and demonstrate CBPC in the United States. The objective of this article is to describe the processes and challenges of scaling and standardizing the CBPC model. DESIGN: Four Season's CBPC model serves patients in both inpatient and outpatient settings using an interdisciplinary team to address symptom management, psychosocial/spiritual care, advance care planning, and patient/family education. Medicare beneficiaries who are ≥65 years of age with a life-limiting illness were eligible for the CMMI project. RESULTS: The CBPC model was scaled across numerous counties in WNC and Upstate South Carolina. Over the first two years of the project, scaling occurred into 21 counties with the addition of 2 large hospitals, 52 nursing facilities, and 2 new clinics. To improve efficiency and effectiveness, a PC screening referral guide and a risk stratification approach were developed and implemented. Care processes, including patient referral and initial visit, were mapped. CONCLUSION: This article describes an interdisciplinary CBPC model in all care settings to individuals with life-limiting illness and offers guidance for risk stratification assessments and mapping care processes that may help PC programs as they develop and work to improve efficiencies.

Muscle hypertrophy in prediabetic men after 16 wk of resistance training.

Resistance training of healthy young men typically results in muscle hypertrophy and a shift in vastus lateralis composition away from type IIx fibers to an increase in IIa fiber content. Our previous studies of 8 wk of resistance training found that many metabolic syndrome men and women paradoxically increased IIx fibers with a decrease in IIa fibers. To confirm the hypothesis that obese subjects might have muscle remodeling after resistance training very different from healthy lean subjects, we subjected a group of nine obese male volunteers to progressive resistance training for a total of 16 wk. In these studies, weight loss was discouraged so that muscle changes would be attributed to the training alone. Detailed assessments included comparisons of histological examinations of needle biopsies of vastus lateralis muscle pretraining and at 8 and 16 wk. Prolonging the training from 8 to 16 wk resulted in increased strength, improved body composition, and more muscle fiber hypertrophy, but euglycemic clamp-quantified insulin responsiveness did not improve. Similar to prior studies, muscle fiber composition shifted toward more fast-twitch type IIx fibers (23 to 42%). Eight weeks of resistance training increased the muscle expression of phosphorylated Akt2 and mTOR. Muscle GLUT4 expression increased, although insulin receptor and IRS-1 expression did not change. We conclude that resistance training of prediabetic obese subjects is effective at changing muscle, resulting in fiber hypertrophy and increased type IIx fiber content, and these changes continue up to 16 wk of training.NEW & NOTEWORTHY Obese, insulin-resistant men responded to 16 wk of progressive resistance training with muscle hypertrophy and increased strength and a shift in muscle fiber composition toward fast-twitch, type IIx fibers. Activation of muscle mTOR was increased by 8 wk but did not increase further at 16 wk despite continued augmentation of peak power and rate of force generation.

Pre-Training Muscle Characteristics of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness.

Stuart, CA, Lee, ML, South, MA, Howell, MEA, Cartwright, BM, Ramsey, MW, and Stone, MH. Pre-training muscle characteristics of subjects who are obese determine how well exercise training will improve their insulin responsiveness. J Strength Cond Res 31(3): 798-808, 2017-Only half of prediabetic subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pretraining characteristics favoring a positive response to exercise training. Thirty nondiabetic subjects who were obese volunteered for 8 weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition, and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow-twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and glucose transporter type 4 (GLUT4) expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole-body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not increase beyond their pretraining baseline.

no privacy, a Xenopus tropicalis mutant, is a model of human Hermansky-Pudlak Syndrome and allows visualization of internal organogenesis during tadpole development.

We describe a novel recessive and nonlethal pigmentation mutant in Xenopus tropicalis. The mutant phenotype can be initially observed in tadpoles after stage 39/40, when mutant embryos display markedly reduced pigmentation in the retina and the trunk. By tadpole stage 50 almost all pigmented melanophores have disappeared. Most interestingly, those embryos fail entirely to make pigmented iridophores. The combined reduction/absence of both pigmented iridophores and melanophores renders these embryos virtually transparent, permitting one to easily observe both the developing internal organs and nervous system; accordingly, we named this mutant no privacy (nop). We identified the causative genetic lesion as occurring in the Xenopus homolog of the human Hermansky-Pudlak Syndrome 6 (HPS6) gene, combining several approaches that utilized conventional gene mapping and classical and modern genetic tools available in Xenopus (gynogenesis, BAC transgenesis and TALEN-mediated mutagenesis). The nop allele contains a 10-base deletion that results in truncation of the Hps6 protein. In humans, HPS6 is one of the genes responsible for the congenital disease HPS, pathological symptoms of which include oculocutaneous albinism caused by defects in lysosome-related organelles required for pigment formation. Markers for melanin-producing neural crest cells show that the cells that would give rise to melanocytes are present in nop, though unpigmented. Abnormalities develop at tadpole stages in the pigmented retina when overall pigmentation becomes reduced and large multi-melanosomes are first formed. Ear development is also affected in nop embryos when both zygotic and maternal hsp6 is mutated: otoliths are often reduced or abnormal in morphology, as seen in some mouse HPS mutations, but to our knowledge not described in the BLOC-2 subset of HPS mutations nor described in non-mammalian systems previously. The transparency of the nop line suggests that these animals will aid studies of early organogenesis during tadpole stages. In addition, because of advantages of the Xenopus system for assessing gene expression, cell biological mechanisms, and the ontogeny of melanosome and otolith formation, this should be a highly useful model for studying the molecular mechanisms underlying the acquisition of the HPS phenotype and the underlying biology of lysosome-related organelle function.

Resilience in Palestinian adolescents living in Gaza.

[Correction Notice: An Erratum for this article was reported in Vol 9(1) of Psychological Trauma: Theory, Research, Practice, and Policy (see record 2016-36102-001). There were grammatical errors to the Method section of the abstract and the Method subsection Participants. Corrected versions are provided.] Objective: The pathogenic impact of ongoing political conflict on children and adolescents has been well-documented in the literature. The present study, by contrast, examined the factors that support adolescent health and utilized a salutogenic model to examine prevalence of depression and anxiety and predictors of resilience in a group of adolescents attending secondary school in Gaza. METHOD: There were 335 Palestinian adolescents (n = 335) enrolled in 11th and 12th grades in secondary schools in Gaza refugee camps completed the Beck Depression Inventory, the Beck Anxiety Inventory, and self-report measures assessing coping skills, self-regulation, optimism, parenting style, family sense of coherence, national identity, ethnic identity, and other demographic variables. RESULTS: Participants with stronger national identity, stronger family sense of coherence, greater self-regulation, and more optimism reported less depressive and anxious symptoms. In a logistic regression analysis, significant predictors of resilience (minimal to no anxiety and depression, n = 135) were age, optimism, family sense of coherence, ethnic identity, self-regulation, and coping skills. CONCLUSION: These findings indicate that older age, optimism, perception of family seeing the world as comprehensible, manageable, and meaningful, stronger Arab ethnic identity, greater self-regulation and stronger coping skills promote adolescent adaptation and health. Salutogenesis frames information about how resilient youth living in high threat environments may respond to preventative community-based behavioral health interventions as well as treatment of depression, anxiety, and other psychological distress among adolescents living with ongoing violence. (PsycINFO Database Record

Sleep and Processing of Trauma Memories.

Sleep has been implicated in learning processes that appear to underlie recovery from posttraumatic stress disorder (PTSD). The importance of quality and timing of sleep following exposure-based therapies has been suggested. The present study evaluated relationships between sleep and adaptive emotional processing following written narrative exposure (WNE) to memories of traumatic events experienced by participants with clinically significant PTSD symptoms. Participants included 21 urban-residing nontreatment-seeking adults with full or subthreshold symptoms of PTSD who completed 4 sessions of 30-min WNE with the first session either in the evening or the morning. There was a significant reduction of PTSD symptom severity after WNE sessions (partial η = .65), but there was no interaction between group assignment based on the initial session's proximity to sleep and initial reduction of PTSD symptom severity (partial η = .01). Polysomnography following evening WNE revealed increased duration of total sleep and N2%, reduced N3%, and increased eye movement density during REM sleep compared with baseline recordings (dz = 0.65 to 1.15). Reduced N3% and increased REM density were associated with less improvement of PTSD symptoms (r = .58 & -.63). These findings suggest a relationship between preservation of diminished arousal during sleep and adaptive trauma memory processing.