[Associations between Personality Structure, Psychodynamic Conflicts and Defense Styles in Adolescents with Mental Health Problems]. / Die Zusammenhänge von psychischer Struktur, psychodynamischen Konflikten und Abwehrstilen bei Adoleszenten mit psychischen Beschwerden.

OBJECTIVES: An exploration of the interrelationships between central psychodynamic constructs in adolescents with mental health problems was conducted. METHODS: 230 adolescents (Mage=18.0±1.9) were assessed using the Structure and the Conflict Questionnaire of the Operationalized Psychodynamic Diagnosis System in Childhood and Adolescence and the Defense Style Questionnaire for Adolescents. RESULTS: Controlling for the influence of gender, age, and socioeconomic status, low to moderate associations were revealed between increased psychodynamic conflict levels and immature defense styles (r=0.20 to 0.39, p<0.05 to 0.001) as wells as deficits in the personality structure and increased psychodynamic conflict levels (r=0.15 to 0.55, p<0.05 to p<0.001) or immature defense styles (r=0.30 to 0.69, p<0.001). Psychodynamic conflicts as well as defense styles could be predicted by the structural dimensions as well as age and sex (R2=0 .04 to 0.49, p<0.05 to 0.001). CONCLUSIONS: Theory-compliant correlations were demonstrated. The findings are particularly relevant against the background of the revision of the classification of personality functioning (ICD-11) in childhood and adolescence.

Key Challenges for In Vitro Testing of Tobacco Products for Regulatory Applications: Recommendations for the In Vitro Mouse Lymphoma Assay.

The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to develop recommendations for optimal scientific and technical approaches for conducting in vitro assays to assess potential toxicity within and across traditional tobacco and various tobacco and nicotine next-generation products (NGPs), including Heated Tobacco Products (HTPs) and Electronic Nicotine Delivery Systems (ENDS). This report was developed by a working group composed of attendees of the seventh IIVS workshop, 'Approaches and recommendations for conducting the mouse lymphoma gene mutation assay (MLA) and introduction to in vitro disease models', which was held virtually on 21-23 June 2022. This publication provides a background overview of the MLA, and includes the description of assay conduct and data interpretation, key challenges and recommended best practices for evaluating tobacco and nicotine products, with a focus on the evaluation of NGPs, and a summary of how the assay has been used to evaluate and compare tobacco and nicotine products.

Association of part-time clinical work with well-being and mental health in General Internal Medicine: A survey among Swiss hospitalists.

INTRODUCTION: Burnout and low job satisfaction are increasing among the General Internal Medicine (GIM) workforce. Whether part-time compared to full-time clinical employment is associated with better wellbeing, job satisfaction and health among hospitalists remains unclear. MATERIALS AND METHODS: We conducted an anonymized cross-sectional survey among board-certified general internists (i.e. hospitalists) from GIM departments in 14 Swiss hospitals. Part-time clinical work was defined as employment of <100% as a clinician. The primary outcome was well-being, as measured by the extended Physician Well-Being Index (ePWBI), an ePWBI ≥3 indicating poor wellbeing. Secondary outcomes included depressive symptoms, mental and physical health, and job satisfaction. We compared outcomes in part-time and full time workers using propensity score-adjusted multivariate regression models. RESULTS: Of 199 hospitalists invited, 137 (69%) responded to the survey, and 124 were eligible for analysis (57 full-time and 67 part-time clinicians). Full-time clinicians were more likely to have poor wellbeing compared to part-time clinicians (ePWBI ≥3 54% vs. 31%, p = 0.012). Part-time compared to full-time clinical work was associated with a lower risk of poor well-being in adjusted analyses (odds ratio 0.20, 95% confidence interval 0.07-0.59, p = 0.004). Compared to full-time clinicians, there were fewer depressive symptoms (3% vs. 18%, p = 0.006), and mental health was better (mean SF-8 Mental Component Summary score 47.2 vs. 43.2, p = 0.028) in part-time clinicians, without significant differences in physical health and job satisfaction. CONCLUSIONS: Full-time clinical hospitalists in GIM have a high risk of poor well-being. Part-time compared to full-time clinical work is associated with better well-being and mental health, and fewer depressive symptoms.

Key Challenges and Recommendations for In Vitro Testing of Tobacco Products for Regulatory Applications: Consideration of Test Materials and Exposure Parameters.

The Institute for In Vitro Sciences (IIVS) is sponsoring a series of workshops to identify, discuss and develop recommendations for optimal scientific and technical approaches for conducting in vitro assays, to assess potential toxicity within and across tobacco and various next generation nicotine and tobacco products (NGPs), including heated tobacco products (HTPs) and electronic nicotine delivery systems (ENDS). The third workshop (24-26 February 2020) summarised the key challenges and made recommendations concerning appropriate methods of test article generation and cell exposure from combustible cigarettes, HTPs and ENDS. Expert speakers provided their research, perspectives and recommendations for the three basic types of tobacco-related test articles: i) pad-collected material (PCM); ii) gas vapour phase (GVP); and iii) whole smoke/aerosol. These three types of samples can be tested individually, or the PCM and GVP can be combined. Whole smoke/aerosol can be bubbled through media or applied directly to cells at the air-liquid interface. Summaries of the speaker presentations and the recommendations developed by the workgroup are presented. Following discussion, the workshop concluded the following: that there needs to be greater standardisation in aerosol generation and collection processes; that methods for testing the NGPs need to be developed and/or optimised, since simply mirroring cigarette smoke testing approaches may be insufficient; that understanding and quantitating the applied dose is fundamental to the interpretation of data and conclusions from each study; and that whole smoke/aerosol approaches must be contextualised with regard to key information, including appropriate experimental controls, environmental conditioning, analytical monitoring, verification and performance criteria.

Bis-choline tetrathiomolybdate prevents copper-induced blood-brain barrier damage.

In Wilson disease, excessive copper accumulates in patients' livers and may, upon serum leakage, severely affect the brain according to current viewpoints. Present remedies aim at avoiding copper toxicity by chelation, for example, by D-penicillamine (DPA) or bis-choline tetrathiomolybdate (ALXN1840), the latter with a very high copper affinity. Hence, ALXN1840 may potentially avoid neurological deterioration that frequently occurs upon DPA treatment. As the etiology of such worsening is unclear, we reasoned that copper loosely bound to albumin, that is, mimicking a potential liver copper leakage into blood, may damage cells that constitute the blood-brain barrier, which was found to be the case in an in vitro model using primary porcine brain capillary endothelial cells. Such blood-brain barrier damage was avoided by ALXN1840, plausibly due to firm protein embedding of the chelator bound copper, but not by DPA. Mitochondrial protection was observed, a prerequisite for blood-brain barrier integrity. Thus, high-affinity copper chelators may minimize such deterioration in the treatment of neurologic Wilson disease.

Studying OTUD6B-OTUB1 Protein-Protein Interaction by Low-Throughput GFP-Trap Assays and High-Throughput AlphaScreen Assays.

Protein-protein interactions (PPI) are involved in a myriad of cellular processes, and their deregulation can lead to many diseases. One such process is protein ubiquitination that requires an orchestrated action of three key enzymes to add ubiquitin moieties to substrate proteins. Importantly, this process is reversible through deubiquitinating enzymes. Both ubiquitination and deubiquitination require many PPIs that once classified can be utilized to identify small molecule inhibitors counteracting these reactions. Here, we study the protein-protein interaction between the two deubiquitinating enzymes OTUB1 and OTUD6B and report for the first time that both proteins directly interact with each other. We describe the GFP-Trap immunoprecipitation as a cell-based method to analyze the OTUD6B-OTUB1 interaction in the cellular context and the AlphaScreen (amplified luminescent proximity homogeneous assay) assay as a tool to detect direct interactions and to search for PPI inhibitors.

[Associations Between Personality Structure, Unconscious Conflicts, and Defense Styles in Adolescence]. / Psychische Struktur, intrapsychische Konflikte und Abwehrstile in der Adoleszenz.

Associations Between Personality Structure, Unconscious Conflicts, and Defense Styles in Adolescence According to the Operationalized Psychodynamic Diagnosis in Childhood and Adolescence, associations between personality structure, unconscious conflicts, and defense styles are postulated. So far, an empirical investigation of these associations in mentally healthy adolescents is missing. The present study aims to contribute to the understanding of unconscious conflicts as well as the unconscious defense of conflicts by elucidating intrapersonal factors within a normative sample. Furthermore, the aim of this study is to analyse the extent to which sex, age, and socioeconomic status are related to personality structure, unconscious conflicts, and defense styles. A total of 175 adolescents (Mage = 16.98 ± 1.83) participated in the study. Measurement instruments were the Structure and the Conflict Questionnaire of the Operationalized Psychodynamic Diagnosis in Childhood and Adolescence as well as the Defense Style Questionnaire for Adolescents and Young Adults. Sex-specific differences were found for the passive identity conflict. Regarding the personality structure, unconscious conflicts or defense styles, associations with age or socioeconomic status of adolescents were not found. The associations between personality structure, unconscious conflicts, and defense styles as postulated by OPD-CA-2 were empirically proven regarding the passive self-worth, guilt, and identity conflict as well as the active guilt conflict. Overall, this study indicates the low presence of unconscious conflicts in mentally healthy adolescents and the possibility of elucidating these conflicts by means of personality structure and defense styles.

Viral DNA Binding Protein SUMOylation Promotes PML Nuclear Body Localization Next to Viral Replication Centers.

Human adenoviruses (HAdVs) have developed mechanisms to manipulate cellular antiviral measures to ensure proper DNA replication, with detailed processes far from being understood. Host cells repress incoming viral genomes through a network of transcriptional regulators that normally control cellular homeostasis. The nuclear domains involved are promyelocytic leukemia protein nuclear bodies (PML-NBs), interferon-inducible, dot-like nuclear structures and hot spots of SUMO posttranslational modification (PTM). In HAdV-infected cells, such SUMO factories are found in close proximity to newly established viral replication centers (RCs) marked by the adenoviral DNA binding protein (DBP) E2A. Here, we show that E2A is a novel target of host SUMOylation, leading to PTMs supporting E2A function in promoting productive infection. Our data show that SUMOylated E2A interacts with PML. Decreasing SUMO-E2A protein levels by generating HAdV variants mutated in the three main SUMO conjugation motifs (SCMs) led to lower numbers of viral RCs and PML-NBs, and these two structures were no longer next to each other. Our data further indicate that SUMOylated E2A binds the host transcription factor Sp100A, promoting HAdV gene expression, and represents the molecular bridge between PML tracks and adjacent viral RCs. Consequently, E2A SCM mutations repressed late viral gene expression and progeny production. These data highlight a novel mechanism used by the virus to benefit from host antiviral responses by exploiting the cellular SUMO conjugation machinery.IMPORTANCE PML nuclear bodies (PML-NBs) are implicated in general antiviral defense based on recruiting host restriction factors; however, it is not understood so far why viruses would establish viral replication centers (RCs) juxtaposed to such "antiviral" compartments. To understand this enigma, we investigate the cross talk between PML-NB components and viral RCs to find the missing link connecting both compartments to promote efficient viral replication and gene expression. Taken together, the current concept is more intricate than originally believed, since viruses apparently take advantage of several specific PML-NB-associated proteins to promote productive infection. Simultaneously, they efficiently inhibit antiviral measures to maintain the viral infectious program. Our data provide evidence that SUMOylation of the viral RC marker protein E2A represents the basis of this virus-host interface and regulates various downstream events to support HAdV productive infection. These results are the basis of our current attempts to generate and screen for specific E2A SUMOylation inhibitors to constitute novel therapeutic approaches to limit and prevent HAdV-mediated diseases and mortality of immunosuppressed patients.

[Practical Evaluation of Patients with Syncopal Events]. / Synkope ­ Eine praktische Abklärungsstrategie.

Syncope is defined as a transient, self-limited loss of consciousness due to insufficient cerebral blood perfusion. In a clinical setting, syncopal events usually present a diagnostic dilemma due to its broad differential diagnosis ranging from banal to potentially harmful causes. In the absence of a working hypothesis, multiple tests are ordered that result in high costs but are of questionable diagnostic and therapeutic value. This article provides a practical overview and, based on international guidelines and selected studies, proposes a standardized approach to patients with syncope. Initial evaluation of these patients includes taking a careful medical history, physical examination and ECG. These tests result in an individual risk assessment that supports decision-making whether further analysis should be performed in an outpatient or inpatient setting. Additional tests including echocardiography, laboratory analysis, cardiac monitoring, CT-scans, are ordered according to prior evaluation. This article reviews the most common diagnostic tests, their indications and the clinical relevance for the evaluation of patients with syncopal events. Therapeutic options are not within the focus of this article.

A Calculation Tool and Process to Pre-Position Pharmaceuticals for Anthrax Post-Exposure Prophylaxis.

Anthrax, caused by Bacillus anthracis, is considered a severe bioterrorism threat because of its high mortality rate. The Chicago Healthcare System Coalition for Preparedness and Response (CHSCPR) aims to pre-position antibiotic medical countermeasures (MCMs) at healthcare facilities in order to provide on-site anthrax post-exposure prophylaxis. Pharmacists proposed moving toward a new process that involved the development of a standardized calculation methodology for acquiring supply drugs. This was an interventional quality improvement project aimed at optimizing inventory, acquisition, and distribution of antibiotic MCMs for anthrax post-exposure prophylaxis at Chicago hospitals for hospital personnel, associated first responders, and their families. The primary goal of the project was to pre-position a sufficient quantity of pharmaceuticals to allow Chicago hospitals to function as closed points of dispensing (PODs) for 72 hours; a secondary goal was to provide a 96-hour supply of anthrax post-exposure prophylaxis. A total of 35 Chicago hospitals were invited to participate in this intervention study, and 30 hospitals agreed to participate. Based on our calculation tool, we initially identified 6 (20%) hospitals with adequate oral doxycycline and ciprofloxacin inventory to last 72 hours and 3 (10%) hospitals with inventory to last 96 hours as a closed POD for anthrax post-exposure prophylaxis. The necessary quantities of medication needed to establish 72 and 96 hours of anthrax post-exposure prophylaxis were calculated by the CHSCPR and negotiated with a drug wholesaler to obtain product with maximum shelf-life and discounted pricing. Acting as a group purchaser, the CHSCPR organized drop shipment of medication directly to facilities from a wholesaler. This systematically calculated, pre-deployed pharmaceutical cache enhanced availability of antibiotic MCMs for anthrax post-exposure prophylaxis in 30 Chicago hospitals, allowing them to function as closed PODs for 96 hours during an incident.

A High-Throughput Screening Strategy for Development of RNF8-Ubc13 Protein-Protein Interaction Inhibitors.

The ubiquitin-proteasome system plays an essential role in a broad range of cellular signaling pathways. Ubiquitination is a posttranslational protein modification that involves the action of an enzymatic cascade (E1, E2, and E3 enzymes) for the covalent attachment of ubiquitin to target proteins. The emerging knowledge of the molecular mechanisms and correlation of deregulation of the ubiquitin system in human diseases is uncovering new opportunities for therapeutics development. The E3 ligase RNF8 acts in cooperation with the heterodimeric E2 enzyme Ubc13/Uev1a to generate ubiquitin conjugates at the sides of DNA double-strand breaks, and recent findings suggest RNF8 as a potential therapeutic target for the treatment of breast cancer. Here, we present a novel high-throughput screening (HTS)-compatible assay based on the AlphaScreen technology to identify inhibitors of the RNF8-Ubc13 protein-protein interaction, along with a follow-up strategy for subsequent validation. We have adapted the AlphaScreen assay to a 384-well format and demonstrate its reliability, reproducibility, and suitability for automated HTS campaigns. In addition, we have established a biochemical orthogonal homogeneous time-resolved fluorescence (HTRF) assay in HTS format and a cellular microscopy-based assay allowing verification of the primary hits. This strategy will be useful for drug screening programs aimed at RNF8-Ubc13 modulation.

The Y2 receptor agonist PYY(3-36) increases the behavioural response to novelty and acute dopaminergic drug challenge in mice.

The gastrointestinal hormone PYY(3-36) is a preferential Y2 neuropeptide Y (NPY) receptor agonist. Recent evidence indicates that PYY(3-36) acts on central dopaminergic pathways, but its influence on dopamine-dependent behaviours remains largely unknown. We therefore explored the effects of peripheral PYY(3-36) treatment on the behavioural responses to novelty and to dopamine-activating drugs in mice. In addition, we examined whether PYY(3-36) administration may activate distinct dopamine and γ-aminobutyric acid (GABA) cell populations in the mesoaccumbal and nigrostriatal pathways. We found that i.p. PYY(3-36) injection led to a dose-dependent increase in novel object exploration. The effective dose of PYY(3-36) (1 µg/100 g body weight) also potentiated the locomotor reaction to the indirect dopamine receptor agonist amphetamine and increased stereotyped climbing/leaning responses following administration of the direct dopamine receptor agonist apomorphine. PYY(3-36) administration did not affect activity of midbrain dopaminergic cells as evaluated by double immuno-enzyme staining of the neuronal early gene product c-Fos with tyrosine hydroxylase. PYY(3-36) did, however, lead to a marked increase in the number of cells co-expressing c-Fos with glutamic acid decarboxylase in the nucleus accumbens and caudate putamen, indicating activation of GABAergic cells in dorsal and ventral striatal areas. Our results support the hypothesis that acute administration of the preferential Y2 receptor agonist PYY(3-36) modulates dopamine-dependent behaviours. These effects do not seem to involve direct activation of midbrain dopamine cells but instead are associated with neuronal activation in the major input areas of the mesoaccumbal and nigrostriatal pathways.

Possible mechanisms of circulating PYY-induced satiation in male rats.

Peptide tyrosine-tyrosine (PYY) is implicated in eating control, but the site(s) and mechanism(s) of its action remain uncertain. We tested acute effects of intrameal hepatic portal vein (HPV) PYY(3-36) infusions on eating in adult, male rats and measured HPV and jugular vein (JV) plasma levels of PYY in response to a solid, mixed-nutrient meal. We also examined the effects of HPV PYY(3-36) infusions on JV plasma levels, flavor acceptance, and neuronal activation. Intrameal HPV PYY(3-36) infusions [1 and 3 nmol/kg body weight (BW)] selectively reduced (P < 0.05) ongoing meal size. HPV PYY levels increased (P < 0.05) during a chow (12.5 kcal) or an isocaloric high-fat meal. JV PYY levels were generally lower than HPV levels but also increased in response to the chow meal. HPV PYY(3-36) infusion (1 nmol/kg BW) caused a greater increase in JV PYY than a meal, but neither 1 nor 3 nmol/kg BW PYY(3-36) caused conditioned flavor avoidance. HPV PYY(3-36) (1 nmol/kg BW) increased the number of c-Fos-expressing cells in the nucleus tractus solitarii, the hypothalamic arcuate and paraventricular nuclei, the central area of the amygdala, and the nucleus accumbens but not in the area postrema and parabrachial nucleus. These data show that HPV infusions of PYY(3-36) inhibit eating in rats without causing avoidance, and they identify some brain areas that might be involved. Endogenous PYY may induce satiation by acting directly in the brain, but further studies should examine whether PYY(3-36) administrations that mimic the meal-induced increase in plasma PYY are sufficient to inhibit eating.

Phenotypic Analysis of BAT versus WAT Differentiation.

The Western world is in the midst of an epidemic of obesity, which is the cause of severe clinical complications such as type 2 diabetes, hypertension, and cardiovascular disease. Obesity develops when energy intake chronically exceeds energy expenditure; thus, either reducing the energy intake and/or increasing the energy expenditure has been used in the treatment and prevention of obesity. On a cellular level, energy storage is mediated by white adipocyte tissue (WAT). In contrast, brown adipose tissue (BAT) contributes to body temperature and metabolic homeostasis by metabolizing lipids and glucose. Adipose tissue is a notoriously difficult tissue to work with, due to the high content of triglycerides and the fragility of the cells. In this unit, several approaches to analysis of BAT and WAT are described that overcome these limitations. Curr. Protoc. Mouse Biol. 3:205-216 © 2013 by John Wiley & Sons, Inc.

Primate early life stress leads to long-term mild hippocampal decreases in corticosteroid receptor expression.

BACKGROUND: Expression of mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) genes are moderately reduced in several brain regions in depression. These reductions could be partly due to early life stress (ELS), which predicts emotional disorders. Controlled primate studies are important to test whether ELS sufficient to induce long-term emotional changes also induces long-term altered MR and/or GR brain expression. METHODS: In the common marmoset, ELS of daily 30-120-min social isolation across month-1 resulted in some long-term changes in homeostasis and emotional behavior. In some of these same subjects, the aim of this study was to use marmoset-specific riboprobes to determine whether ELS produced long-term effects on brain MR and GR gene expression. RESULTS: At adolescence, relative to control subjects, ELS marmosets exhibited mildly reduced messenger RNA signal for both MR (-15%, p = .05) and GR (-13%, p = .02) in hippocampus-primarily CA1-2-but not in prefrontal cortex, other cortical regions, or hypothalamus. CONCLUSIONS: In adolescent marmoset monkey brains, reduced hippocampal expression of MR and GR are consistent chronic-indicators of ELS. It is unlikely that these chronic, mild, specific reductions were acute-mediators of the observed long-term emotional effects of ELS. However, they do suggest involvement of hippocampal MR/GR in the neurodevelopmental effects of ELS.

DNA microarrays provide new options for allergen testing.

Microarray studies are increasingly used for toxicological research and even for the development of new toxicological test methods. Since gene-expression changes in cultured cells can be conveniently measured with microarrays, this method might be of use for in vitro toxicity testing, for example, in the field of contact sensitization. Allergic contact dermatitis, the clinical manifestation of contact sensitization, may occur when sensitizing chemicals enter the skin and get in contact with epidermal and dermal antigen-presenting cells. The resulting maturation process in these cells can be measured by employing gene-expression analysis. Biomarkers currently known seem to be insufficient to identify all kinds of contact sensitizers, which may partly activate different signaling pathways (e.g., metal or organic sensitizers). Therefore, genome-wide screenings using whole-genome DNA microarrays and extensive data analysis can be performed in order to identify additional genes. Ultimately, marker genes detected in whole-genome experiments can be included in small-scale-targeted microarrays in order to establish the final test method.

Overweight and obesity in children starting school in Augsburg: prevalence and influencing factors.

INTRODUCTION: A comprehensive approach to the prevention of overweight and obesity requires identifying the socioeconomic and cultural factors involved. This study set out to determine the prevalence of overweight and obesity among children starting school in Augsburg, Germany. Another aim was to examine influencing factors and any associations between the findings and the children's first language. METHODS: In the context of the school entry health examination for the 2006/2007 school year, the parents of 2306 children were surveyed by means of an anonymous questionnaire. The investigators documented each child's sex, age, body weight, height, and first language, as well as the preschool attended. The data were evaluated descriptively using SPSS 14.0. RESULTS: Overall, 13.1% (n = 302) of the children were overweight, including 4.9% (n = 113) who were obese. The prevalence of overweight and obesity was nearly twice as high among children whose first language was not German. Half of all children did not attend a sports or dance group. More than half of the overweight children watched television for one to three hours each day. DISCUSSION: The prevalence of overweight and obesity differs depending on ethnic origin. Children from immigrant families are a high-risk group. Targeted prevention strategies are necessary for children of elementary school age. Our data may serve as the basis for developing neighborhood or district-wide interventions.

DJ-1 and Parkin modulate dopamine-dependent behavior and inhibit MPTP-induced nigral dopamine neuron loss in mice.

Parkin-deficient animals exhibit mitochondrial degeneration and increased oxidative stress vulnerability, and both mice and flies lacking DJ-1 are hypersensitive to environmental toxins associated with Parkinson's disease (PD). We used recombinant adeno-associated virus (AAV) gene transfer to study the influence of DJ-1 and Parkin on the dopaminergic system of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, a model for sporadic PD. After MPTP lesioning, significantly more dopamine neurons survived in the virus-injected substantia nigra of the AAV-DJ-1 and AAV-Parkin mice when compared with AAV-enhanced green fluorescent protein injected controls. Protection at the neuronal level was supported by increased amphetamine-induced contralateral turning behavior. Normal mice expressing DJ-1 showed apomorphine-induced ipsilateral turning, suggesting a hyporesponsiveness of striatal dopamine D1 receptors in the DJ-1-expressing hemisphere. MPTP drastically reduced dopamine to 19% of normal levels and neither DJ-1 nor Parkin protected against MPTP-induced catecholamine loss under these conditions. Our results show that Parkin and DJ-1 inhibit dopamine neuron death and enhance amphetamine-induced dopaminergic function in a mouse model of idiopathic PD. However, DJ-1 overexpression also reduced postsynaptic dopamine receptor responses in normal mice. These results warrant further exploration of DJ-1 and Parkin gene therapy for PD, although a better understanding of their effects on behavior and dopamine neurotransmission is required before these proteins can be safely used.

Condensed lignins are synthesized in poplar leaves exposed to ozone.

Poplar (Populus tremula x alba) trees (clone INRA 717-1-B4) were cultivated for 1 month in phytotronic chambers with two different levels of ozone (60 and 120 nL L(-1)). Foliar activities of shikimate dehydrogenase (EC 1.1.1.25), phenylalanine ammonia lyase (EC 4.3.1.5), and cinnamyl alcohol dehydrogenase (CAD, EC 1.1.1.195) were compared with control levels. In addition, we examined lignin content and structure in control and ozone-fumigated leaves. Under ozone exposure, CAD activity and CAD RNA levels were found to be rapidly and strongly increased whatever the foliar developmental stage. In contrast, shikimate dehydrogenase and phenylalanine ammonia lyase activities were increased in old and midaged leaves but not in the youngest ones. The increased activities of these enzymes involved in the late or early steps of the metabolic pathway leading to lignins were associated with a higher Klason lignin content in extract-free leaves. In addition, stress lignins synthesized in response to ozone displayed a distinct structure, relative to constitutive lignins. They were found substantially enriched in carbon-carbon interunit bonds and in p-hydroxyphenylpropane units, which is reminiscent of lignins formed at early developmental stages, in compression wood, or in response to fungal elicitor. The highest changes in lignification and in enzyme activities were obtained with the highest ozone dose (120 nL L(-1)). These results suggest that ozone-induced lignins might contribute to the poplar tolerance to ozone because of their barrier or antioxidant effect toward reactive oxygen species.