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Nongovernmental migrant shelters in Mexico play a key role in documenting the factors that shape forced migration from Central America. Existing intake protocols in shelters are largely oriented to humanitarian legal frameworks that determine eligibility for international protection based on interpersonal violence and political persecution. This qualitative study calls attention to how existing humanitarian logics may obscure climate- and health-related disruptions as drivers of forced migration from Central America in the context of everyday humanitarian practice. In May 2022 we compared migrant's responses (n = 40) to a standardized intake protocol at a nongovernmental humanitarian migrant shelter in Mexico with responses to semi-structured interviews that focused on migrants' perceptions of climate change and health as drivers of forced displacement. We found that slow- and rapid-onset climatic disruptions; illness and disease; and various forms of violence and repression are often interrelated drivers of forced displacement. Comparing intake protocols and in-depth interview responses, we found that climate- and health-related drivers of forced displacement are rarely documented. These findings speak to the importance of critically examining everyday humanitarian practices in the context of ongoing advocacy that calls for climate-related disruptions to be integrated into existing humanitarian protection frameworks. • Climate-health risks contribute to forced displacement from Central America • Central Americans often access humanitarian migrant shelters while crossing Mexico. • Climate-health risks as migration drivers are rarely documented in shelters. • Shelters mediate how climate-health risks are made known, obscured, and governed. [ABSTRACT FROM AUTHOR]

Spain suffered a Civil War between 1936 and 1939 that ended with the victory of the National Forces led by General Franco. Once the Spanish Civil War ended, 2238 subjects were executed and buried in several mass graves in the Cemetery of Paterna, one of Spain's largest mass grave sites. Efforts to locate and identify all the victims of the mass graves of the Paterna cemetery are ongoing, but the actual data of the percentage of DNA identifications remains uncertain. Following this, we conducted a meta-research study including 15 mass graves and 933 subjects to determine the DNA identification rates in the mass graves of the Paterna cemetery. We found that the total proportion of identified subjects in the mass graves was 15.9 % (95 % CI: 10.0–22.9). Moreover, we found that the model between the identification success rate (ISR) and the number of relatives that donated DNA (NRTDD) in the mass graves of the cemetery of Paterna was ISR = NRTDD−0.424. Results obtained about the proportion of identified subjects and the model between the ISR and the NRTDD imply the need for a scientific reflection between all the research groups involved in the identification tasks to modify deficiencies and update identification protocols to obtain better future results. • More than 2200 subjects lay in mass graves in the Cemetery of Paterna. • Fifteen mass graves with 933 subjects were analyzed. • The proportion of identified subjects was 15.9 % (95 % CI: 10.0–22.9). • The model between the ISR and the NRTDD was: ISR = NRTDD-0.424. [ABSTRACT FROM AUTHOR]

L'originalité de notre travail porte sur le destin des affects chez des femmes adultes ayant subi des agressions sexuelles répétées de la part de leur père durant leur enfance et/ou leur adolescence. Nous nous intéresserons plus particulièrement aux effets du trauma sur leur vie affective. Une méthodologie qualitative a été choisie, combinant entretiens cliniques de recherche et épreuve projective du Rorschach pour trois femmes suivies dans une association d'aide aux victimes. Après qu'elles eurent donné leur accord, nous nous sommes assurés qu'elles étaient suivies par un thérapeute car la recherche pouvait réactiver des souvenirs dramatiques et provoquer chez elles du mal-être. À partir du Rorschach, nous pouvons repérer le manque de liaison entre affect et représentation chez nos patientes. Pour deux patientes, l'affect est volatil, pouvant être de nature plaisante puis basculer rapidement dans le déplaisir ou générer de l'angoisse. Chez la troisième patiente, il est réprimé. Cette répression empêche l'expression des affects qui échoueraient à être pris en charge par le psychisme du fait de leur caractère désorganisant. Chez des femmes ayant vécu une expérience traumatique telle que l'inceste, la vie affective semble touchée, atteinte. À l'issue de cette recherche, le terme de distorsion est discuté, renvoyant d'une part à la déformation et d'autre part, au mouvement imposé. Il cumule donc l'idée de contrainte par l'autre et de discontinuité (touchant au mode de la qualité). Nous pouvons émettre l'hypothèse que l'affect serait distordu, en raison d'une impossibilité précoce de l'environnement à donner du sens aux éprouvés du jeune enfant. Ce dernier a été pris précocement dans le désir du parent incestueux, l'amenant à se soumettre aux attentes de l'agresseur et à s'oublier. En plus de la distorsion, une autre voie peut être possible, celle de la répression où l'affect est réprimé, le sujet se retirant de sa vie psychique et émotionnelle afin de ne plus ressentir. Distorsion affective et répression semblent associées au clivage du moi car le sujet se coupe d'une partie de lui-même en refusant de reconnaître des pans de sa vie émotionnelle (répression), ou d'identifier des affects comme s'il avait perdu sa capacité de discrimination (le plaisant/le mauvais). Ne peut-on pas y voir un effet de l'identification à l'agresseur ? Reconnaître les destins de l'affect (distorsion et répression) chez des femmes ayant subi un inceste nous encourage à interroger les modalités d'accompagnement thérapeutique classique basées sur la libre association. Dans un premier temps, cet appel à l'associativité pourrait s'apparenter à une menace à laquelle le sujet répondrait soit par un repli, une mise en retrait (anesthésie affective), soit par un sentiment de dilution des limites. Afin d'aménager le cadre thérapeutique, le clinicien, en s'appuyant sur le transfert et le contre-transfert, pourrait offrir des mots pour qualifier l'expérience affective malmenée par l'inceste. En effet, ce dernier a pu redoubler la difficulté à identifier et à reconnaître ce qui est bien, mal, plaisant ou au contraire déplaisant en lien avec des expériences primaires, ayant entravé la fonction réflexive. The originality of our work lies in the fate of affects in adult women who have been repeatedly sexually abused by their fathers during their childhood and/or adolescence. We are particularly interested in the effects of their emotional life trauma. A qualitative methodology was chosen, combining clinical research interviews and a projective Rorschach test for three women followed in a victim support association. After they had given their consent, we made sure they were followed by a therapist because the research could reactivate dramatic memories and cause them to feel unwell. From the Rorschach, we can identify the lack of connection between affect and representation in our patients. For two patients, the affect is volatile, which can be of a pleasant nature and then quickly switch to displeasure or generate anxiety. In the third patient, it is repressed. This repression prevents the expression of affects, which would fail to be taken care of by the psyche because of their disorganizing character. Women who have lived through a traumatic experience such as incest, seem to have their emotional life affected. At the end of this research, the term distortion is discussed, referring on the one hand to deformation and on the other hand to imposed movement. It thus cumulates the idea of constraint by the other and discontinuity (touching on the mode of quality). We can put forward the hypothesis that the affect would be distorted, due to an early impossibility of the environment to give meaning to the experiences of the young child. The latter was caught early in the desire of the incestuous parent, leading him to submit to the expectations of the aggressor and to forget himself. In addition to distortion, another way may be possible, that of repression where the affect is repressed, the subject withdrawing from his psychic and emotional life in order to no longer feel. Emotional distortion and repression seem to be associated with the self clivage as the subject cuts himself off from a part of himself by refusing to recognize parts of his emotional life (repression), or to identify affects as if he had lost his ability to discriminate (the good/bad). Can't this be seen as an effect of identification with the aggressor? Recognizing the fates of affect (distortion and repression) in women who have suffered from incest encourages us to question the classic therapeutic accompaniment modalities based on free association. Initially, this call for associativity could resemble a threat to which the subject would respond either by withdrawing or withdrawing (affective anaesthesia), or by a feeling of dilution of limits. In order to arrange the therapeutic framework, the clinician, relying on transference and counter-transference, could offer words to qualify the incest emotional experience abused by incest. Indeed, the latter could redouble the difficulty in identifying and recognizing what is good, bad, pleasant, or on the contrary unpleasant in relation to primary experiences, which have hindered the reflexive function. [ABSTRACT FROM AUTHOR]

State organized psychological repression in the German Democratic Republic (GDR; 1949 – 1990) included "quiet" measures, such as wiretapping, spreading of rumours, or provoking failures in professional and social domains. Goal of these measures was to systematically undermine the psychosocial integrity of a political opponent, and induce anxiety, social isolation and confusion. These experiences of severe chronic stress have been shown to have a negative health impact on those affected, even many years later. The present study aims to unfold the physiological and emotional mechanisms potentially causing these psychological and physiological long-term consequences. Specifically, we focus on physiological stress reactivity and interpersonal abilities of victims of political repression. 60 participants (30 with repression experiences, 30 control, age range 50-80) participate in a modified version of the Trier Social Stress Test (TSST). We measure salivary cortisol and subjective stress at nine time points throughout the testing session. Additionally, we assess participants' interpersonal abilities using a standardized questionnaire. Results are currently pending. Understanding how severe stress experiences influence body and mind in the long term is relevant not only for the rehabilitation of past victims, but is essential for the care of current and future victims of political repression in authoritarian regimes. [ABSTRACT FROM AUTHOR]

Exploring sexual dimorphisms in the brain morphology is important for their impact and therapeutic implications for several neurological diseases. The hypothesis that sex could influence the transcriptome of brain cells could be the basis regarding the different response to cognitive decline identified in men and women. In this paper, we analyzed several prefrontal cortices (PFC) microarrays datasets of young/middle-aged healthy subjects and then Alzheimer's disease (AD) patients, according to the sex. The significant transcriptomes were overlapped with the main genes characterizing cells of the central nervous system (CNS) in order to determine the respective weighted percentages of significantly expression gene modulation (WPSEG). We identified differences in brain transcriptional activity between young and middle-aged. In middle-aged women, the WPSEG were higher for the Astrocytes, the Endotheliocytes, and the Microglia. In addition, the sex-matched analysis of transcriptome identified a convergent molecular signature in men and women AD patients. Furthermore, the WPSEG belonging to CNS cells in PFC of healthy middle-aged subjects was correlated to AD profiles according to the sex. Since our results, it is possible to conclude that during the aging the PFC' cells adopt transcriptional strategies sex-dependent that could potentially control the development of neurodegenerative diseases. Unlabelled Image • There is a difference proportion of gray matter in human men and women. • Online microarray datasets could be used to identify the brain cells transcriptome difference between men and women. • There are substantial differences in brain transcriptional activity between young and middle-aged men and women. • The transcriptome sex-matched analysis identified a convergent molecular signature in AD men and women patients. [ABSTRACT FROM AUTHOR]

Highlights • A mindfulness meditation practice was associated with increased eudaimonic well-being in a sample of breast cancer survivors. • Increases in eudaimonic well-being correlated with decreases in the Conserved Transcriptional Response to Adversity (CTRA). • Eudaimonia-related CTRA reductions were driven primarily by increased expression of anti-viral and antibody-related genes. • The intervention was associated with reduced pro-inflammatory gene expression. • Changes in CTRA gene expression were not related to changes in distress or hedonic well-being. Abstract Background The conserved transcriptional response to adversity (CTRA), characterized by increased expression of proinflammatory genes and decreased expression of antiviral and antibody-related genes, is upregulated in the context of chronic adversity and distress and has been linked to cancer progression. Several studies suggest that the CTRA may also be down-regulated in association with some positive psychological states, particularly eudaimonic well-being. However, it is not clear if the link between inter-individual differences in the CTRA and eudaimonic well-being can be extended to intra-individual change. Using a standardized mindfulness-based intervention, the current study tested whether mindfulness-related increases in eudaimonic well-being related to intra-individual reduction in the CTRA in a sample of younger breast cancer survivors. Methods Participants were 22 women who had been diagnosed and treated for early-stage breast cancer at or before age 50 (M age = 46.6 years) and had no evidence of active disease. Women completed self-report questionnaires and provided peripheral blood samples before and after a 6-week mindfulness meditation intervention. Regression analyses were used to quantify associations between the magnitude of change in eudaimonic well-being and the magnitude of change in the global CTRA score. Results Women reported significant increases in eudaimonic well–being and showed decreased expression of the pro-inflammatory subcomponent of the CTRA from pre- to post-intervention. The magnitude of increase in eudaimonic well-being was associated with the magnitude of decrease in the composite CTRA score, and this relationship was driven primarily by increased expression of the antiviral/antibody-related CTRA subcomponent. While the intervention was also associated with reduced depressive symptoms, there was no association between change in depressive symptoms and change in the overall CTRA composite score or either of its subcomponents. Conclusions Results are consistent with the hypothesis that eudaimonic well-being may be an important mechanism in interventions aimed at enhancing health in vulnerable groups, and contribute to our understanding of how psychological well-being may influence physical health in cancer patients. [ABSTRACT FROM AUTHOR]

Highlights • Repressors have lower cortisol reactivity to group psychosocial stress. • Repressors self-report less subjective stress compared to other coping styles. • Repressor psychophysiological dissociation differs for HPA axis and ANS reactivity. • Blunted cortisol reactivity may be an adverse health trajectory for repressors. Abstract Repressors are well-known to monitor potential psychosocial threats to their self-esteem and self-concept. In research, repressors are traditionally categorised as those scoring low on trait anxiety and high on defensiveness (as measured by social desirability scales). Examining repressors' cortisol reactivity to a group socio-evaluative laboratory stressor could be an important way to extend work on the classic 'repressor dissociation', which proposes that this group experience higher levels of physiological stress, but lower levels of subjective affect, during stressful situations. Research however has focused mainly on repressors' higher, more risk-prone levels of autonomic, rather than hypothalamic-pituitary-adrenal (HPA), reactivity to stressful stimuli. We assessed cortisol reactivity using a group-based acute psychosocial stressor, the Trier Social Stress Test for groups (TSST-G), which required participants to individually perform public speaking and mental arithmetic tasks in front of up to six other group members, as well as an evaluative panel of judges. Seventy-seven healthy young females (mean age ± SD: 20.2 ± 3.2 years) took part, of which 64 met the conventional criterion for a response to the TSST-G (<15.5% increase from baseline sample). The Stress-Arousal Checklist was completed pre- and post-TSST-G. Participants also completed the Perceived Stress Scale, the Trait Anxiety Inventory and the Marlow-Crowne Social Desirability Scale. The latter two measures were used to provide a categorisation of repressive coping style. Participants identified as repressive copers exhibited significantly lower cortisol reactivity during the TSST-G. Repressors also self-reported less subjective stress. These findings provide some evidence against the notion of the repressor dissociation and are discussed in terms of how cortisol hyporeactivity may be a pathway through which repressive coping adversely affects health. [ABSTRACT FROM AUTHOR]

Highlights • COUP-TFI transcriptional action depends on cellular context and co-factor accessibility. • COUP‐TFI imparts sensory identity during neocortical area map formation. • Temporal competence in neural progenitors depends on COUP-TF expression levels. • COUP‐TFI-mediated control of cortical development impacts on complex animal behaviors. • NR2F1 haploinsufficiency leads to syndromic visual and cognitive deficits in humans. Abstract Transcription factors are expressed in a dynamic fashion both in time and space during brain development, and exert their roles by activating a cascade of multiple target genes. This implies that understanding the precise function of a transcription factor becomes a challenging task. In this review, we will focus on COUP-TFI (or NR2F1), a nuclear receptor belonging to the superfamily of the steroid/thyroid hormone receptors, and considered to be one of the major transcriptional regulators orchestrating cortical arealization, cell-type specification and maturation. Recent data have unraveled the multi-faceted functions of COUP-TFI in the development of several mouse brain structures, including the neocortex, hippocampus and ganglionic eminences. Despite NR2F1 mutations and deletions in humans have been linked to a complex neurodevelopmental disease mainly associated to optic atrophy and intellectual disability, its role during the formation of the retina and optic nerve remains unclear. In light of its major influence in cortical development, we predict that its haploinsufficiency might be the cause of other cognitive diseases, not identified so far. Mouse models offer a unique opportunity of dissecting COUP-TFI function in different regions during brain assembly; hence, the importance of comparing and discussing common points linking mouse models to human patients' symptoms. [ABSTRACT FROM AUTHOR]

Highlights • GR represses BDNF expression in BZ neuron-like cells. • Bdnf exon IV is sensitive to neuroexcitatory signals. • GR represses exon IV binding on EGR1 response element. • GR and EGR1 interact on Bdnf exon IV promoter. • New crosstalk between GR, EGR1 and BDNF in neurons. Abstract The brain-derived neurotrophic factor (BDNF) is a key player in brain functions such as synaptic plasticity, stress, and behavior. Its gene structure in rodents contains 8 untranslated exons (I to VIII) whose expression is finely regulated and which spliced onto a common and unique translated exon IX. Altered Bdnf expression is associated with many pathologies such as depression, Alzheimer's disease and addiction. Through binding to glucocorticoid receptor (GR), glucocorticoids play a pivotal role for stress responses, mood and neuronal plasticity. We recently showed in neuronal primary culture and in the immortalized neuronal-like BZ cells that GR repressed Bdnf expression, notably the bdnf exon IV containing mRNA isoform (Bdnf4) via GR binding to a short 275-bp sequence of Bdnf promoter. Herein, we demonstrate by transient transfection experiments and mutagenesis in BZ cells that GR interacts with an early growth response protein 1 (EGR1) response element (EGR-RE) located in the transcription start site of Bdnf exon IV promoter. Using Chromatin Immunoprecipitation, we find that both GR and EGR1 bind to this promoter sequence in a glucocorticoid-dependent manner and demonstrate by co-immunoprecipitation that GR and EGR1 are interacting physically. Interestingly, EGR1 has been widely characterized as a regulator of brain plasticity. In conclusion, we deciphered a mechanism by which GR downregulates Bdnf expression, identifying a novel functional crosstalk between glucocorticoid pathways, immediate early growth response proteins and Bdnf. As all these factors are well-recognized germane for brain pathophysiology, these findings may have significant implications in neurosciences as well as in therapeutics. [ABSTRACT FROM AUTHOR]

The governance of sleep sex (or sexsomnia) in the criminal law is a nightmare. Press reports of sleeping, often drunk, men acquitted as automatons of raping adults and children suggest cases are rising. The use of automatism, rather than insanity, in these cases is strong evidence of the immemorial struggle faced by legal psychiatry in appropriately construing unconscious defendants. This paper responds by drawing on well-established psychoanalytic conceptions of unconsciousness to present sexsomnia as dispositional to the defendant. Taking the Freudian concepts of eros and death instinct, it asserts that sexsomniacs are acting on repressed sadistic desires. Accordingly, those on notice of their sexsomnia, who fail to mitigate the risk of further attacks, should be guilty of rape. Reliance on (a reformed) insanity defence - being a denial of responsibility at the time of the offence - undermines the scope of the criminal law to self-responsibilise sexsomniacs against perpetrating unwanted sex. [ABSTRACT FROM AUTHOR]

Abstract Psychological wellbeing of residential staff has substantial impact on the therapeutic milieu. These staff members are regularly confronted with aggression and other stressors, leading to low work satisfaction, burn-out and high staff turnover. The aim of this study is to evaluate the efficacy of Non-violent Resistance (NVR), a method for professionals to cope with aggressive behaviour of children and adolescents in residential care, with respect to work climate, living group climate, and aggression. NVR was implemented using a quasi-experimental stepped wedge design at three sites providing child and adolescent residential care in the Netherlands. Work and living group climate was assessed seven times, every three months. In addition, the average number of aggressive incidents before and after NVR implementation were described. A total of 519 work climate assessments by 186 staff members and 260 living group climate assessments by 124 children were collected. Multilevel analysis showed significant positive effects on the following elements of work climate: team functioning, satisfaction, task-significance, having a shared vision and on commitment at one of the three participating sites. Living group climate changed, but not in the expected direction. At two sites the living group climate was more repressive after NVR implementation. Aggressive episodes were low before and remained low after NVR implementation. These findings provide limited evidence that the implementation of NVR has a positive influence on work climate in residential settings. This study is a first step in investigating the relationship between NVR and improving work climate, living climate and aggression in the turbulent practice of residential youth care. The manner that NVR is implemented seems to have a substantial effect on the efficacy of NVR. Optimising the implementation along with assessing and improving readiness for change and more research on the possible influence of contextual factors is needed to fully evaluate the efficacy of NVR in residential setting. Highlights • Examines the influence of Non-violent Resistance on work climate, group climate and aggression in residential youth care. • Provides limited evidence that the implementation of Non-violent Resistance has a positive influence on work climate. • Contextual factors seem to influence intervention success, living group climate, work climate and thus quality of care. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that high-level executive control can occur unconsciously. In this study, we tested whether unconscious executive control extends to memory retrieval and forgetting. In a first experiment, participants learned word-word associations and were trained to either actively recall or forget theses associations in response to conscious visual cues (Think/No-Think paradigm). Then, the very same cues were subliminally presented while participants were performing a grammatical gender categorization task on distinct word pairs. Memory retrieval tested a few minutes later was significantly influenced by conscious and masked cues, suggesting that memory recall could be manipulated unbeknownst to the participants. In a second experiment, we replicated these findings and added a baseline condition in which some words were not preceded by masked cues. Memory recall was significantly reduced both when words were preceded by an unconscious instruction to forget compared to the baseline condition (i.e. no cue), and to the unconscious instructions to recall. Overall, our results suggest that executive control can occur unconsciously and suppress a specific memory outside of one's awareness. [ABSTRACT FROM AUTHOR]

Long-Non-Coding RNAs (LncRNAs) are a class of non-coding endogenous RNAs contributing to numerous biological processes. LeERF1 is a tomato ethylene response factor (ERF) near the end of the ethylene signal transduction pathway. To identify lncRNAs in tomato and elucidate their roles in ethylene signaling, deep sequencing was deployed in over-expression and repression LeERF1 transgenic and control tomato fruits. A total of 397 lncRNAs were identified, including 169 tomato lncRNAs that had not previously been identified. Among these, 12 were differentially expressed between the transgenic and control tomato fruits. Numerous lncRNA target genes were identified including many associated with ethylene signaling including auxin response factors and auxin-induced proteins, F-box proteins, ERFs and MADS-box proteins. In addition, two lncRNAs were found to be the precursor of three miRNAs and four lncRNAs could be targeted by five miRNAs. We propose a regulatory model highlighting the relationships between lncRNAs and their targets involved in ethylene signal transduction which establishes a foundation for addressing the role of LncRNAs in ethylene response. [ABSTRACT FROM AUTHOR]

Highlights • We tested how the availability of avoidance impacts the conditioned response. • Availability of avoidance reduced differential skin conductance responses. • Removing the availability of avoidance sustained differential skin conductance responses. • Greater avoidance predicted stronger return of differential skin conductance responses. Abstract Pervasive avoidance behaviour is a core feature of anxiety disorders. However, little is known about how the availability of avoidance modulates learned threat responding. To assess this question, we recorded avoidance behaviour, electrodermal activity and expectancy ratings in 53 healthy participants during an associative learning paradigm with embedded unavoidable and avoidable trials. When avoidance was available, we observed greater avoidance behaviour for threat versus safety cues, as well as reduced differential skin conductance responses for unavoidable threat versus safety cues. When avoidance was unavailable, as during the extinction phase, we observed sustained differential skin conductance responses for threat versus safety cues. For all phases, we found greater expectancy ratings for threat versus safe cues. Furthermore, greater avoidance behaviour predicted larger differential skin conductance responses to threat versus safety cues during extinction. Overall, the results show that the conditioned response is attenuated during situations where avoidance is available, but it recovers when avoidance is unavailable, subsequently prolonging threat extinction. [ABSTRACT FROM AUTHOR]

In this study, based on the 2 × 2 achievement goal framework (Elliot & McGregor, 2001), a four-dimensional classroom goal structure model (4CGS model) containing mastery-approach, mastery-avoidance, performance-approach, and performance-avoidance goal structures was proposed and tested using the data of 941 7th-grade Taiwanese students. The results of exploratory factor analysis, confirmatory factor analysis and a discriminant validity test supported the independence of the four CGS constructs and revealed that the 4CGS model provided a far better fit than the other alternative models. Latent variable regression analysis disclosed differential associations between the 4CGS model and several important consequences (i.e., personal achievement goals, approach behaviors, and avoidance behaviors). Taken together, this study showed that CGS could indeed be divided into four distinct constructs that had differential predictive effects on these consequences. [ABSTRACT FROM AUTHOR]

There is an important theoretical distinction between biological and sociolegal incest offenders, but this is not always recognized in clinical or empirical work. The purpose of the current meta-analysis was to examine the extent to which biological and sociolegal incest offenders differ on a number of theoretically or clinically relevant domains. We compared a total of 4192 biological incest offenders to 2322 sociolegal incest offenders across 27 samples that were disseminated between 1984 and 2012 ( Mdn = 1993). Sociolegal incest offenders exhibited more antisocial tendencies (general self-regulation problems, impulsivity, drug and alcohol problems) compared to biological incest offenders. Biological incest offenders exhibited more psychopathology (repression, mental health difficulties) compared to sociolegal incest offenders. Differences were generally small to moderate in magnitude. Contrary to expectations, there were no meaningful differences between groups on atypical sexual interests ( d s ranged from − 0.09 to 0.11), though sociolegal incest offenders were more likely to have sexual self-regulation problems. One meaningful moderator emerged: whether the biological incest offender group was composed only of biological fathers or of both biological fathers and other biological relatives (e.g., uncles and grandfathers). The theoretical implications of these results are discussed, and areas of future research are highlighted. [ABSTRACT FROM AUTHOR]

HacA is a conserved basic leucine zipper transcription factor that serves as the master transcriptional regulator in the unfolded protein response (UPR). To comprehensively evaluate the role of HacA in Aspergillus oryzae , a homokaryotic hacA disruption mutant (HacA-DE) and a strain that expressed a constitutively active form of HacA (HacA-CA) were successfully generated, and transcriptome analyses of these mutants were performed. Growth and phenotypic profiles demonstrated that hyphal growth and sporulation were impaired in the HacA-DE and HacA-CA strains that were grown on complete and minimal media, and the growth impairment was more pronounced for the HacA-CA strain. Compared with a wild-type (WT) strain, the transcriptome results indicated that differentially expressed genes in these mutants mainly fell into four categories: the protein secretory pathway, amino acid metabolism, lipid metabolism, and carbohydrate metabolism. Furthermore, we identified 80 and 36 genes of the secretory pathway whose expression significantly differed in the HacA-CA strain (compared with the WT and HacA-DE strains) and HacA-DE strain (compared with the WT strain), respectively, which mostly belonged to protein folding/UPR, glycosylation, and vesicle transport processes. Both the HacA-CA and HacA-DE strains exhibited reduced expression of extracellular enzymes, especially amylolytic enzymes, which resulted from the activation of the repression under secretion stress mechanism in response to endoplasmic reticulum stress. Collectively, our results suggest that the function of HacA is important not only for UPR induction, but also for growth and fungal physiology, as it serves to reduce secretion stress in A. oryzae . [ABSTRACT FROM AUTHOR]

Repressive coping has been associated with elevated risk of disease and negative health outcomes in past studies. Although a prior study of healthy men found that repression was associated with lower body mass index (BMI), no study has examined repressive coping among obese individuals. This study examined the relationship of repressive coping with BMI and obesity-relevant psychosocial factors among 104 overweight and obese participants in a behavioral weight management program. Participants completed questionnaires assessing repressive coping, stigmatization, psychological distress, and quality of life. BMI was objectively measured. Repressors reported lower stigmatization, anxiety, and depression as well as higher emotional and weight-related quality of life. Repressors and non-repressors had equivalent BMI and reported similar impairment in physical quality of life, but stigmatization moderated the relationship between repressive coping and physical quality of life (b=0.31, p=0.039), reflecting better physical quality of life among non-repressors with lower stigmatization. Obese individuals who engage in repressive coping may tend to underreport psychological symptoms, social difficulties, and impairments in quality of life. Higher physical quality of life among non-repressors with lower stigmatization may reflect a combined influence of coping and social processes in physical quality of life among obese individuals. [ABSTRACT FROM AUTHOR]

Dickeya dadantii is a pathogen infecting a wide range of plant species. Soft rot, the visible symptom, is mainly due to production of pectate lyases (Pels) that can destroy plant cell walls. Previously, we found that nucleoid-associated protein (NAP) H-NS is a key regulator of pel gene expression. The primary binding sites of this NAP have been determined here by footprinting experiments on the pelD gene, encoding an essential virulence factor. Quantitative analysis of DNAse I footprints and surface plasmon resonance imagery experiments further revealed that high-affinity binding sites initiate cooperative binding to establish the nucleoprotein structure required for gene expression silencing. Mutations in the primary binding sites resulted in reduction or loss of repression by H-NS. Overall, these data suggest that H-NS represses pelD , and by inference, other pel genes, by a cooperative binding mechanism, through oligomerization of H-NS molecules. [ABSTRACT FROM AUTHOR]

Previously, we evaluated the effects of lactational exposure to a representative mixture of the six indicator non-dioxin-like polychlorinated biphenyls (∑6 NDL-PCBs) at low levels on the neurobiological changes and developmental/behavioral performances in mice. In this study, we analyzed the global gene expression profile in cerebellar neurons isolated from male mice presenting the most significant induction of anxiety-like behavior in our previous study (10 ng/kg ∑6 NDL-PCBs). Our results revealed changes in the expression of 16658 genes in the neurons of the exposed mice. Among these, 693 upregulated [fold change (FC) > 2; p < 0.05] and 665 downregulated (FC < 2; p < 0.05) genes were statistically linked to gene ontology terms (GO). Overexpressed genes belonged to GO terms involved with the cell cycle, DNA replication, cell cycle checkpoint, response to DNA damage stimulus, regulation of RNA biosynthetic processes, and microtubule cytoskeleton organization. Downregulated genes belonged to terms involved with the transmission of nerve impulses, projection neurons, synapse hands, cell junctions, and regulation of RNA biosynthetic processes. Using qPCR, we quantified gene expression related to DNA damage and validated the transcriptomic study, as a significant overexpression of Atm-Atr Bard1, Brca2, Fancd2, Figf, Mycn, p53 and Rad51 was observed between groups ( p < 0.001). Finally, using immunoblots we determined the expression level of six selected proteins. We found that changes in the protein expression of Atm Brca1, p53, Kcnma1, Npy4r and Scn1a was significant between exposed and control groups ( p < 0.05), indicating that the expression pattern of these proteins agreed with the expression pattern of their genes by qPCR, further validating our transcriptomic findings. In conclusion, our study showed that early life exposure of male mice to a low level of ∑6 NDL-PCBs induced p53-dependent responses to cellular stress and a decrease in the expression of proteins involved in the generation, conduction, and transmission of electrical signals in neurons. [ABSTRACT FROM AUTHOR]

Perillyl alcohol (PA) is a monoterpene found in essential oils of mints, cherries, citreous fruits and lemon grass, reported to have antioxidant and anti-inflammatory properties. However, the role of PA in stroke is still illusive. Since oxidative stress and inflammation play a pivotal role in ischemia–reperfusion (I–R) injury, this study was designed to elucidate the potential effects of PA against I–R induced pathology in rat׳s brain. Middle cerebral artery occlusion (MCAO) for 2 h followed by 22 h reperfusion in Wistar male rats (250–280 g, 14–16 weeks old) induced the behavioral and histological alterations along with exhausted antioxidant status and enhanced inflammatory mediators. However, PA administration (25, 50 and 100 mg/kg b.wt orally once daily for 7 days) prior to MCAO significantly attenuated neurological deficits related to flexion test and spontaneous motor activity, improved grip strength and motor coordination in a dose dependent manner. PA treatment also inhibited oxidative stress in MCAO rats as evident from decreased lipid peroxidation and augmented level of reduced glutathione and restored activities of catalase, glutathione peroxidase, and glutathione reductase and thus, reduced infarct volume and protected the brain histology after I–R injury. Furthermore, PA markedly suppressed the level of proinflammatory cytokines (IL-1β, TNF α and IL-6) and down regulated expressions of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (NOS-2) and nuclear factor κB (NF-κB) in MCAO group. In conclusion, PA mediates neuroprotection against I–R injury via mitigation of oxidative stress and inflammation and thus, may be a good therapeutic approach in stroke prone patient. [ABSTRACT FROM AUTHOR]

Abstract: We introduce a simple compartmental model for the dynamics of a revolution in dictatorial regimes that employ censorship and police repression. A defining property of the model is the use of visibility and policing terms that feature rapid transitions as a function of the size of the revolution, for which we provide conceptual and network-based mathematical justifications. The complete mathematical classification of the dynamical behaviour of the model leads to a division in parameter space that is interpreted naturally in terms of stability of the regime (stable police state, meta-stable police state, unstable police state, and failed state). We show that these dynamical properties of the model are generic for a broad class of visibility and policing functions that feature rapid transitions. We investigate how the model can be applied to the peaceful revolutions of the Arab Spring in Tunisia and Egypt, taking into account the influence of the Internet and new media on the visibility of the revolution and the ensuing reduced effectivity of censorship. Within the model this leads to significant, discontinuous changes in regime stability, which greatly increase the probability of realized revolutions. These properties of the model inform possible answers to questions on causes and timing of the Arab Spring revolutions, and the role of the Internet and new media. The broader relevance of the model classification is also investigated by applying it to the current political situation in some other countries with regimes that employ censorship and police repression. [Copyright &y& Elsevier]

Actin cytoskeleton is critical for cell motility and division, both of which are important for angiogenesis. MicroRNAs (miRNA/miR) are emerging as pivotal modulators of vascular development and disease. How miRNAs regulate actin cytoskeleton dynamics in endothelial cells (EC) and neovascularization is still unclear. Here, we report that miR-24 regulates actin dynamics in ECs through targeting multiple members downstream of Rho signaling, including Pak4, Limk2, and Diaph1 proteins. Overexpression of miR-24 in ECs blocks stress fiber and lamellipodia formation, represses EC migration, proliferation, and tube formation in vitro, as well as angiogenesis in an ex vivo aortic ring assay. Moreover, subretinal delivery of miR-24 mimics represses laser-induced choroidal neovascularization (CNV) in vivo. Mechanistically, knockdown of miR-24 target protein LIMK2 or PAK4 inhibits stress fiber formation and tube formation in vitro, mimicking miR-24 overexpression phenotype in angiogenesis, while overexpression of LIMK2 and PAK4 by adenoviruses partially rescued the tube formation defects in miR-24 overexpressing ECs. Taken together, these findings suggest that miR-24 represses angiogenesis by simultaneously regulating multiple components in the actin cytoskeleton pathways. Manipulation of actin cytoskeleton pathways by miR-24 may represent an attractive therapeutic solution for the treatment of wet age-related macular degeneration (AMD) and other vascular diseases. [ABSTRACT FROM AUTHOR]

Highlights: [•] Nuclear receptors inhibit inflammatory gene transcription via distinct mechanisms. [•] GR colocalizes with other regulators and represses their targets genome-wide. [•] GR utilizes cofactors as context-specific coactivators or corepressors. [ABSTRACT FROM AUTHOR]

Abstract: Mitoxantrone has been approved by the FDA for the treatment of multiple sclerosis (MS). However, the mechanisms by which mitoxantrone modulates MS are largely unknown. Activated astrocytes produce nitric oxide (NO), TNF-α, and IL-1β, molecules which can be toxic to central nervous system (CNS) cells including oligodendrocytes, thus potentially contributing to the pathology associated with MS. MCP-1 is a chemokine believed to modulate the migration of monocytes to inflammatory lesions present in the CNS of MS patients. IL-12 and IL-23 have been demonstrated to play critical roles in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, by contributing to the development of CD4+ T cell lineages termed Th1 and Th17, respectively. The current study demonstrates that mitoxantrone inhibits lipopolysachharide (LPS) induction of NO, TNF-α, IL-1β, and MCP-1 production by primary astrocytes. Mitoxantrone also inhibited IL-12 and IL-23 production by these cells. Furthermore, mitoxantrone suppressed the expression of C-reactive protein (CRP). Finally, we demonstrate that mitoxantrone suppressed LPS induction of NF-κB DNA-binding activity, suggesting a novel mechanism by which mitoxantrone suppresses the expression of proinflammatory molecules. Collectively, these studies demonstrate that mitoxantrone represses astrocyte production of potentially cytotoxic molecules, as well as molecules capable of altering T-cell phenotype. These in vitro studies suggest mechanisms by which mitoxantrone may modulate inflammatory diseases including MS. [Copyright &y& Elsevier]

Abstract: Objective: In this paper, we try to demonstrate how pubertal fantasies work on the adolescent and mostly foster the crossing of the adolescent experience when they are repressed. Repression reveals at the same time instincts strength and power of ego''s defense mechanisms standing against it. Psychic conflict guarantees this instinctual activity''s elaboration. But when these fantasies invade these teenagers’ psychic life, when they overflow it for lack of being repressed enough, they can in this way contribute to wandering moments, or even to the appearance of serious development disorders. Methods: Reflection spreads in this paper from a clinical case presentation retracing some moments of the psychotherapy of a teenager battling against powerful incestuous fantasies. The case methodology permits clinic presentation and comments, which enlighten some of its aspects. The long-term therapeutic follow-up of this teenager permits to bring out some fundamental points regarding his ways of psychic functioning. Results: The adolescence process dynamic appears from the angle of the instinctual violence acting like a trauma, which could lead to an acting out, a collapse or a perverse development, as it is the case for the teenager presented here and as it is seen more generally in the more fragile subjects. But the adolescence process, when the ego defenses are sufficiently well formed, when the latency has been able to find its place, generally also permits an elaboration of this same pubertal violence, transformed then into a creativity source. Perspective: The parental narcissistic support role turns out decisive when the adolescent''s psychological containing ability reveals itself insufficient to treat the influx of the somatic and psychological excitations caused by the entry in the puberty. When the adolescent''s mechanisms of defense were not enough able to constitute during childhood and that the parental narcissistic support is failing, the therapist role consists in supporting the teenager in his ability to face his pubertal feelings, to reconstruct his defenses before any attempt of analysis of his psychic life. We suggest thinking of the entry in the therapeutic work with the fragile adolescents on a narcissistic plan as a time of construction of the ego defenses. [Copyright &y& Elsevier]

Abstract: A longstanding question in false memory research is whether children’s implanted false memories represent actual memory traces or merely result from compliance. The current study examined this question using a response latency based deception task. Forty-five 8-year-old children received narratives about a true (first day at school) and false event (hot air balloon ride). Across two interviews, 58/32% of the participants developed a partial/full false memory. Interestingly, these children also showed higher false recall on an unrelated DRM paradigm compared to children without a false memory. The crucial finding, however, was that the results of the deception task revealed that children with partial and full false memories were faster to confirm than to deny statements relating to the false event. This indicates that children’s implanted false memories reflect actual memory traces, and are unlikely to be explained by mere compliance. [Copyright &y& Elsevier]

Abstract: Thought experiments have a long tradition in science. The thought experiment proposed in this article designs a brain that is compatible with a conceptual framework that integrates neuroscience and psychoanalysis. A connectionist model with emergent collective computational abilities is modified progressively and gradually to retrieve concepts such as the following: life instinct, the death instinct, the conscious, the preconscious, the unconscious, the free-association method, parapraxis, repetitive compulsion, repression, self, other, and “I”. In this model, the process of memorisation is represented by a neural network with deep depressions, the bottoms of which correspond to learned configurations known as “attractors”. This thought experiment could be helpful in suggesting new formulations of traditional psychoanalytic and neuroscientific constructs. [Copyright &y& Elsevier]

Abstract: Our comment is based upon the Freudian hypothesis stating that repression is a defect in translation. Applying this statement to bilingual subjects using foreign languages, the second language, because it''s less burdened with emotional repressions than native language, can turn into source of language troubles by arousing defense mechanisms, or, for the best, through an avoidance of repression, can reveal the subjects individual potential that had been repressed into/by the native language. The very complex relationships that J. Green, V. Nabokov and S. Beckett had with their native language show how the avoidance of repression related to their native language could be liberating for their writings. In the intercultural clinical psychopathology, this operation of translation rather entails defense mechanisms, instead of being a real vector of creation. [Copyright &y& Elsevier]

Abstract: Using publicly available microarray data from the frontal cortex of 30 individuals, spanning the ages of 26–106 years old, we investigate the expression patterns of compositionally distinct genes during human brain aging. Our analyses revealed that at advance ages, GC-poor genes appear to be induced while GC-rich genes are repressed. Interestingly, investigations upon two different types of genes, named pivotal (permanently expressed genes) and non-pivotal (on-off regulated genes), revealed an induction of the GC-poor pivotal genes and a repression of the GC-richer non-pivotal genes at advanced ages. Summarizing, this study shows that genes with different compositional properties have opposite age-related expression patterns, suggesting an implication of different regulation mechanisms related to their localization in different chromatin structure, which correlates with the GC level. Finally, an innovative approach on investigating human aging process is suggested, which involves the base composition of genes. [Copyright &y& Elsevier]

Abstract: Post translational modification (PTM) and proteolytic processing of proteins contributes to regulation of their stability, intracellular localization and interactions with other proteins, and to direct enhancement or repression of their activity. Both PTM and proteolysis are dynamic; levels and rates change in response to changes in the cellular environment. Tissue excision, post mortem interval and subsequent methods of tissue processing for protein analysis unavoidably alter the cellular environment and therefore features of protein profiles. To aid in understanding the time frame and protein specificity of these changes and the biological and technical contributions to them, we have compared features of protein profiles in mouse hippocampus and cortex following three methods of tissue handling: immediate lysate preparation, and rapid heating to 95°C and standard snap freezing in liquid nitrogen, prior to lysate preparation. In spite of the very short time frames involved, we observe protein-specific differences in levels of phosphorylation, general differences in patterns of sumoylation, and specific differences in levels of proteolytic cleavage of calcineurin and the neurotrophin receptor, TRKA. These differences vary with brain region and with post excision time to processing, and highlight the challenges inherent in accurately profiling the in vivo proteome. [Copyright &y& Elsevier]

Abstract: Sevoflurane is an anesthetic for the general anesthesia. In this study, we showed that sevoflurane anesthesia affects the expression of mouse Per2 (mPer2), which is a clock gene in the brain which is considered the organ where the anesthetics act in. 64.5% of mPer2 circadian expression was repressed under anesthesia in the suprachiasmatic nucleus (SCN) of the brain. After recovering from the anesthesia, the repressed mPer2 expression was restored to the same level as in non anesthesia-treated mice. This repression pattern was also observed in the subsequent phases of diurnal mPer2 expression. However, obvious phase-shift in the mPer2 expression was not showed in this study. On the other hand, the behavior analysis in this experiment exhibited that the phases in the circadian behavioral rhythm were shifted backwards. We also measured the NAD+ level in the SCN, which was a mediator regulating the mPer2 expression. Then, significant increase of NAD+ was detected under the anesthesia. These results indicate that the anesthesia induces the increase of NAD+, and consequently leads to the repression of mPer2 expression and modifies the circadian expression pattern and diurnal behavioral rhythm of mice. Furthermore, the modification of mPer2 expression by the anesthesia is considered to affect various gene expressions. [Copyright &y& Elsevier]

Abstract: In this study of 49 undergraduate university women, those exhibiting a repressive coping style – characterized by defensiveness against negative emotions – were compared to women with low-anxious and high-anxious coping styles during neutral and negative versions of a computerized emotional Stroop task (EST). Using Weinberger, Schwartz, and Davidson''s (1979) approach, the present study implemented the Marlowe–Crowne Social Desirability and the Spielberger Trait Anxiety scales for selection. Participants viewed neutral or negative words during the EST but responded to the color of the word. Analysis of continuous EEG recordings for the negative vs. neutral words revealed that the repressor group differed significantly from the other two groups in many aspects but that low- vs. high-anxious groups differed in fewer aspects. Based upon Eysenck and Derakshan''s (1997) model, repressor women appear to differ from low- and high-anxious women by utilizing an inhibitory process to avoid perceiving low-intensity threatening stimuli. [Copyright &y& Elsevier]

Abstract: In a cognitive perspective, repression is defined as a coping strategy whose objective is to extinguish awareness of subjective emotional experience, leading to restriction of subjective experience. It is characterized by avoidance of threatening and distressing information, minimization of negative affects and low tendency to anxiety. Several measures of repressive coping style have been developed and the Weinberger Adjustment Inventory (WAI) appears to be the most psychometrically sound measure of repression. Objectives: The main aim of this study was to translate and validate a French version of the WAI in non-clinical individuals on general population. The secondary objectives were to investigate its relationship to independent measures of anxiety, depression and alexithymia. Materials and methods: Subjects (n =159) were asked to complete the WAI questionnaire. A principal component analysis was carried out. The internal consistency was measured by the Cronbach alpha coefficients, and discriminant validity was assessed by examining correlations between the scales of the WAI. Because there is no other French validated instrument assessing repression, convergent validity was studied with alexithymia (Bermond-Vorst Alexithymia Questionnaire), anxiety and depression (Hospital Anxiety Depression Scale). Results: Our factorial structure of the French WAI resembles the Weinberger''s one. The “Consideration for Others” subscale does not belong to the Self-Restraint dimension: this is consistent with literature findings. The others results show solid metrological properties. Cronbach alpha reliabilities for principal and secondary factors were ranged from 0.80 to 0.93 (from 0.65 to 0.85 for the subscales) and the intercorrelations were low. Correlations were found between the WAI, the HAD and the Bvaq-b. Anxiety and Depression (HAD) are positively correlated to Distress and negatively correlated to Restraint, Defensiveness and Composite score. The repressive style, characterized by high scores on Defensiveness and Composite score, is positively correlated to affective component of alexithymia and negatively correlated to the cognitive score of alexithymia. Conclusion: Globally, findings replicate earlier findings obtained in the Anglo-American context. The French version of the WAI thus appears to be valid and will help studying repression in France, especially in its complex relationships to alexithymia. [Copyright &y& Elsevier]

Abstract: In this research, the sensorial dimension in acting is seen as having a secondary effect on the psyche. The use of sensations in acting is not thought of as a failure of psychic elaboration and of the ability to fantasize. It is thought of as an extension of a psychic elaboration that rests on the libidinization of muscular activity and opens up an entire field of potential representations and remembrances. Acting can be a way to search for internal certainty and continuity that often calls for the use of implicit memory. This type of memorization does not involve the production of memories per se and does not call for unconscious repression but reminds us of primitive processes of learning through repetition and mirroring. This research suggests that the world of sensations is often a pathway toward psychic work. [Copyright &y& Elsevier]

Abstract: Sustained activation of Akt kinase acts as a focal regulator to increase cell growth and survival, which causes tumorigenesis including breast cancer. Statins, potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, display anticancer activity. The molecular mechanisms by which statins block cancer cell growth are poorly understood. We demonstrate that in the tumors derived from MDA-MB-231 human breast cancer cell xenografts, simvastatin significantly inhibited phosphorylation of Akt with concomitant attenuation of the expression of the anti-apoptotic protein BclXL. In many cancer cells, BclXL is a target of NFκB. Simvastatin inhibited the DNA binding and transcriptional activities of NFκB resulting in marked reduction in transcription of BclXL. Signals transmitted by anti-neoplastic mechanism implanted in the cancer cells serve to obstruct the initial outgrowth of tumors. One such mechanism represents the action of the tumor suppressor protein PTEN, which negatively regulates Akt kinase activity. We provide the first evidence for significantly increased levels of PTEN in the tumors of simvastatin-administered mice. Importantly, simvastatin markedly prevented binding of NFκB to the two canonical recognition elements, NFRE-1 and NFRE-2 present in the PTEN promoter. Contrary to the transcriptional suppression of BclXL, simvastatin significantly increased the transcription of PTEN. Furthermore, expression of NFκB p65 subunit inhibited transcription of PTEN, resulting in reduced protein expression, which leads to enhanced phosphorylation of Akt. Taken together, our data present a novel bifaceted mechanism where simvastatin acts on a nodal transcription factor NFκB, which attenuates the expression of anti-apoptotic BclXL and simultaneously derepresses the expression of anti-proliferative/proapoptotic tumor suppressor PTEN to prevent breast cancer cell growth. [Copyright &y& Elsevier]

Abstract: Cells form stress granules (SGs), in response to unfavorable environments, to avoid apoptosis, but it is unclear whether and how SG formation and cellular apoptosis are coordinately regulated. In this study we detected the small GTPase, Ras homolog gene family member A (RhoA), and its downstream kinase, Rho-associated, coiled-coil containing protein kinase 1 (ROCK1), in SG, and found that their stress-induced activities were important for SG formation and subsequent global translational repression. Importantly, only activated RhoA and ROCK1 were sequestered into SG. Sequestration of activated ROCK1 into SG prevented ROCK1 from interacting with JNK-interacting protein 3 (JIP-3) and its activation of c-Jun N-terminal kinase (JNK), a pathway triggering apoptosis, thereby protecting cells from apoptosis. This study identifies a specific signaling pathway, mediated by RhoA and ROCK1, which determines cell fate by promoting SG formation or initiating apoptosis during stress. [Copyright &y& Elsevier]

Parathyroid hormone (PTH) is a hormone regulating bone remodeling through its actions on both bone formation and bone resorption. Previously we reported that PTH induces matrix metalloproteinase-13 (MMP-13) transcription in osteoblastic cells. Here, we show that histone deacetylase 4 (HDAC4) interacts with Runx2, binds the MMP-13 promoter, and suppresses MMP-13 gene transcription in the rat osteoblastic cell line, UMR 106-01. PTH induces the rapid cAMP-dependent protein kinase-dependent release of HDAC4 from the MMP13 promoter and subsequent transcription of MMP-13. Knock-out of HDAC4 either by siRNA in vitro or by gene deletion in vivo leads to an increase in MMP-13 expression, and overexpression of HDAC4 decreases the PTH induction of MMP-13. All of these observations indicate that HDAC4 represses MMP-13 gene transcription in bone. Moreover, PTH stimulates HDAC4 gene expression and enzymatic activity at times corresponding to the reassociation of HDAC4 with the MMP-13 promoter and a decline in its transcription. Thus, HDAC4 is a basal repressor of MMP-13 transcription, and PTH regulates HDAC4 to control MMP-13 promoter activity. These data identify a novel and discrete mechanism of regulating HDAC4 levels and, subsequently, gene expression. [ABSTRACT FROM AUTHOR]

Abstract: Thinking of boredom as the other side of agitation led us to build the following hypothesis: the experience of boredom during the period of latency is connected to the ability of the child to be alone in the presence of the mother and to the emergence of repression. We have elaborated this hypothesis working with agitated children admitted in After School Intensive Care Unit (USIS). [Copyright &y& Elsevier]

Abstract: Host invasion by pathogens is frequently associated with the activation of nuclear factor kappaB (NF-κB), which modulates the expression of genes involved in the immunological response of the host. However, pathogens may also subvert these mechanisms to secure their survival. We describe the effect of Leishmania amazonensis infection on NF-κB transcriptional factor activation in macrophages and the subsequent reduction in inducible nitric oxide synthase (iNOS) expression. L. amazonensis promastigote infection activates the p50/p50 NF-κB complex, a classic transcriptional repressor. Interestingly, L. amazonensis promotes the change of the classical p65/p50 NF-κB dimer induced by LPS, leading to the p50/p50 NF-κB complex activation in macrophages stimulated with LPS. Moreover, this parasite promotes the reduction of p65 total levels in infected macrophages. All these effects contribute to the observation that this parasite is able to restrain the NF-κB-dependent transcriptional activity induced by LPS. Strikingly, L. amazonensis reduces the mRNA levels of the iNOS in addition to protein expression and the production of nitric oxide in LPS-stimulated macrophages. Accordingly, as revealed by reporter-gene assays, L. amazonensis-induced iNOS repression requires NF-κB sites in the iNOS promoter region. In summary, our results suggest that L. amazonensis has developed an adaptive strategy to escape from host defense by activating the NF-κB repressor complex p50/p50. The activation of this specific host transcriptional response negatively regulates the expression of iNOS, favoring the establishment and success of L. amazonensis infection. [Copyright &y& Elsevier]

Abstract: Chronic stress is known to affect brain areas involved in learning and emotional responses. These changes, thought to be related to the development of cognitive deficits are evident in major depressive disorder and other stress-related pathophysiologies. The serotonin-related transcription factors (Freud-1/CC2D1A; five prime repressor element under dual repression/coiled-coil C2 domain 1a, and NUDR/Deaf-1; nuclear-deformed epidermal autoregulatory factor) are two important regulators of the 5-HT1A receptor. Using Western blotting and quantitative real-time polymerase chain reaction (qPCR) we examined the expression of mRNA and proteins for Freud-1, NUDR, and the 5-HT1A receptor in the prefrontal cortex (PFC) of male rats exposed to chronic restraint stress (CRS; 6 h/day for 21 days). After 21 days of CRS, significant reductions in both Freud-1 mRNA and protein were observed in the PFC (36.8% and 32%, respectively; P<0.001), while the levels of both NUDR protein and mRNA did not change significantly. Consistent with reduced Freud-1 protein, 5-HT1A receptor mRNA levels were equally upregulated in the PFC, while protein levels actually declined, suggesting post-transcriptional receptor downregulation. The data suggest that CRS produces distinct alterations in the serotonin system specifically altering Freud-1 and the 5-HT1A receptor in the PFC of the male rat while having no effect on NUDR. These results point to the importance of understanding the mechanism for the differential regulation of Freud-1 and NUDR in the PFC as a basis for understanding the related effects of chronic stress on the serotonin system (serotonin-related transcription factors) and stress-related disorders like depression. [Copyright &y& Elsevier]

Groucho/TLE proteins are global corepressors that are recruited to target promoters by different families of DNA-binding repressors. As these corepressors are widely expressed, the long-standing view had been that Groucho/TLE-mediated repression is regulated solely by the spatial and temporal distribution of partner repressors. It has recently emerged, however, that Groucho/TLE repressor activity is itself regulated, in a signal induced, context-dependent manner. Here we review the essential roles played by Groucho/TLE factors in different cell-signalling processes that illustrate different modes for regulating Groucho/TLE-mediated repression: (i) via the expression of partner repressors; (ii) by competition with coactivators and (iii) through post-translational modifications of Groucho/TLE. We also discuss how the intrinsic properties of repressors can result in differential responses to Groucho/TLE regulation. [Copyright &y& Elsevier]

Cognitive-behavioral conceptualizations of obsessive compulsive disorder (OCD) have predominantly viewed compulsions as being motivated by harm avoidance. However, sensations of things being incomplete or not "just right" may also underlie compulsions in OCD. Preliminary research suggests that distinguishing between harm avoidance and incompleteness in OCD may have practical utility, but the research on this topic is very limited to date. The current study further addressed the role of incompleteness in OCD. A confirmatory factor analysis provided evidence for harm avoidance and incompleteness as separate constructs in a student sample. Supporting the benefits of considering incompleteness in addition to harm avoidance, self-reported levels of both constructs were significantly correlated with all domains of OCD symptoms and perfectionism assessed. Further, some evidence for unique relationships was found (e.g., incompleteness with ordering and personally prescribed perfectionism; harm avoidance with obsessing). The role of incompleteness in OCD warrants greater attention. [ABSTRACT FROM AUTHOR]

Abstract: Estradiol receptors (ER), ERα and ERβ, are ligand-dependent transcription factors that regulate gene expression. Human and murine genetics suggest that ERα is the key target for estradiol action on bone, uterus and breast. To date, the molecular mode of action of estradiol and selective estradiol receptor modulators (SERMs) on bone is not fully understood. This is exemplified by a lack of in vitro assays that reliably predict SERM agonist activities in vivo. We hypothesized that ligand-dependent ERα transrepression, via protein–protein interactions at AP1, may predict estrogenic effects on bone. We modeled this using the MMP1 promoter, which encodes an AP1 binding site. We show that ICI-182780, raloxifene, 4-hydroxytamoxifen and estradiol all exhibit differential agonistic activities on the MMP1 promoter by suppressing activity by 20–80%. Transrepression efficacy and potency correlated with both uterotrophic (R 2 =0.98) and osteoprotective (R 2 =0.80) potential in the ovariectomized rat. This identifies MMP1 promoter transrepression as an agonist activity commonly shared by AF2 agonists and “antagonists” alike. Mutation analysis showed that the repression by estradiol and SERMs required correct amino acid sequences in the AF-2 domain. For instance, L540Q AF2 mutation did not alter responses to raloxifene, although it greatly increased responses to ICI-182780 (threefold) and reduced estradiol''s effect by 20%. Furthermore, all tested ligands repressed the MMP1 promoter through the L540Q mutant with identical efficacy. Together, these data suggest that estradiol and SERMs share common agonist transcriptional activity via protein–protein interactions at AP1. [Copyright &y& Elsevier]

Abstract: We investigated the effect of Snf1 kinase and its regulatory subunit Snf4 on the regulation of glucose and galactose metabolism in the yeast Saccharomyces cerevisiae by physiologically characterizing Δsnf1, Δsnf4 and Δsnf1Δsnf4 in CEN.PK background in glucose and glucose–galactose-mixture batch cultivations. The main result of this study showed that delayed induction of galactose catabolism was SNF1 or SNF4 gene deletion specific. In comparison to the reference strain, growth delay on galactose was found to last 2.4 times (7h), 3.1 times (10.5h) and 9.6 times (43h) longer for the Δsnf4, Δsnf1 and Δsnf1Δsnf4 strains, respectively. The maximum specific growth rates on galactose were determined to be two to three times lower for the recombinant strains compared to the reference strain (0.13h−1) and were found to be 0.07, 0.08 and 0.04h−1 for the Δsnf1, Δsnf4 and Δsnf1Δsnf4 strains, respectively. The study showed that Snf1 kinase was not solely responsible for the derepression of galactose metabolism. [Copyright &y& Elsevier]

Abstract: Chronic inflammatory lung diseases are characterized by increased expression of multiple inflammatory genes following activation by proinflammatory transcription factors, such as nuclear factor κB (NF-κB) and AP-1. Gene expression is, at least in part, regulated by acetylation of core histones through the action of coactivators, such as CREB-binding protein (CBP), which have intrinsic histone acetyltransferase (HAT) activity. Conversely gene repression is mediated via a combination of histone deacetylases (HDAC) and other corepressors. In asthma, the level of HAT activity is elevated in bronchial biopsies, whereas HDAC activity levels are only partially reduced and inhaled corticosteroids are able to reduce the increased HAT activity back to those seen in normal subjects. In contrast, in chronic obstructive pulmonary disease (COPD), there is a greater reduction in HDAC activity and HDAC2 expression but no difference in HAT activity. HAT and HDAC are also reported to modify a large and expanding number of nonhistone proteins, including nuclear import proteins, chaperones, cytoskeletal proteins, and other transcriptional factors, such as NF-κB and signal transducer and activation of transcription (STAT). Acetylation regulates several aspects of protein function and stability leading to differing effects on inflammatory gene expression and cell recruitment involved in the pathogenesis of inflammatory diseases. This review will examine the impact of acetylation on the function of key proteins involved in airway inflammatory disease and the effects of current therapies on acetylation status of key proteins. Further appreciation of the role of these changes may lead to the development of novel therapeutic approaches to inflammatory lung diseases that are currently difficult to treat. [Copyright &y& Elsevier]

Abstract: NIPP1 is a ubiquitously expressed nuclear protein that represses the transcription of targeted genes. Here we show that the transcriptional repression by NIPP1 is alleviated by the RNAi-mediated knockdown of EED and EZH2, two core components of the Polycomb Repressive Complex 2 (PRC2), and by the overexpression of a catalytically dead mutant of the histone methyltransferase EZH2. NIPP1 is present in a complex with EED and EZH2 in vivo and has distinct binding sites for these proteins. These data disclose an essential role for the PRC2 complex in the transcriptional repression by NIPP1. [Copyright &y& Elsevier]

Tbox18 (Tbx18) and Tbox15 (Tbx15) encode a closely related pair of vertebrate-specific T-box (Tbx) transcription factors. Functional analyses in the mouse have proven the requirement of Tbx15 in skin and skeletal development and of Tbx18 in the formation of the vertebral column, the ureter, and the posterior pole of the heart. Despite the accumulation of genetic data concerning the embryological roles of these genes, it is currently unclear how Tbx18 and Tbx15 exert their function on the molecular level. Here, we have initiated a molecular analysis of Tbx18 and Tbx15 proteins and have characterized functional domains for nuclear localization, DNA binding, and transcriptional modulation. We show that both proteins homo- and heterodimerize, bind to various combinations of T half-sites, and repress transcription in a Groucho-dependent manner. Competition with activating T-box proteins may constitute one mode of action as we show that Tbx18 interacts with Gata4 and Nkx2-5 and competes Tbx5-mediated activation of the cardiac Natriuretic peptide precursor type a-promoter and that ectopic expression of Tbx18 down-regulates Tbx6-activated Delta-like 1 expression in the somitic mesoderm in vivo. [ABSTRACT FROM AUTHOR]