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1.
Development ; 149(11)2022 06 01.
Article in English | MEDLINE | ID: mdl-35575098

ABSTRACT

Boundary domains delimit and organize organ growth throughout plant development almost relentlessly, building plant architecture and morphogenesis. Boundary domains display reduced growth and orchestrate development of adjacent tissues in a non-cell-autonomous manner. How these two functions are achieved remains elusive despite the identification of several boundary-specific genes. Here, we show using morphometrics at the organ and cellular levels that leaf boundary domain development requires SPINDLY (SPY), an O-fucosyltransferase, to act as cell growth repressor. Furthermore, we show that SPY acts redundantly with the CUP-SHAPED COTYLEDON transcription factors (CUC2 and CUC3), which are major determinants of boundaries development. Accordingly, at the molecular level CUC2 and SPY repress a common set of genes involved in cell wall loosening, providing a molecular framework for the growth repression associated with boundary domains. Atomic force microscopy confirmed that young leaf boundary domain cells have stiffer cell walls than marginal outgrowth. This differential cell wall stiffness was reduced in spy mutant plants. Taken together, our data reveal a concealed CUC2 cell wall-associated gene network linking tissue patterning with cell growth and mechanics.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Cell Wall/metabolism , Gene Expression Regulation, Plant/genetics , Gene Regulatory Networks , Mutation , Plant Leaves/genetics , Plant Leaves/metabolism
2.
J Med Internet Res ; 26: e54478, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38656779

ABSTRACT

BACKGROUND: Mental health (MH) problems in youth are prevalent, burdening, and frequently persistent. Despite the existence of effective treatment, the uptake of professional help is low, particularly due to attitudinal barriers. OBJECTIVE: This study evaluated the effectiveness and acceptability of 2 video-based microinterventions aimed at reducing barriers to MH treatment and increasing the likelihood of seeking professional help in young people. METHODS: This study was entirely web based and open access. The interventions addressed 5 MH problems: generalized anxiety disorder, depression, bulimia, nonsuicidal self-injury, and problematic alcohol use. Intervention 1 aimed to destigmatize and improve MH literacy, whereas intervention 2 aimed to induce positive outcome expectancies regarding professional help seeking. Of the 2435 participants who commenced the study, a final sample of 1394 (57.25%) participants aged 14 to 29 years with complete data and sufficient durations of stay on the video pages were randomized in a fully automated manner to 1 of the 5 MH problems and 1 of 3 conditions (control, intervention 1, and intervention 2) in a permuted block design. After the presentation of a video vignette, no further videos were shown to the control group, whereas a second, short intervention video was presented to the intervention 1 and 2 groups. Intervention effects on self-reported potential professional help seeking (primary outcome), stigma, and attitudes toward help seeking were examined using analyses of covariance across and within the 5 MH problems. Furthermore, we assessed video acceptability. RESULTS: No significant group effects on potential professional help seeking were found in the total sample (F2,1385=0.99; P=.37). However, the groups differed significantly with regard to stigma outcomes and the likelihood of seeking informal help (F2,1385=3.75; P=.02). Furthermore, separate analyses indicated substantial differences in intervention effects among the 5 MH problems. CONCLUSIONS: Interventions to promote help seeking for MH problems may require disorder-specific approaches. The study results can inform future research and public health campaigns addressing adolescents and young adults. TRIAL REGISTRATION: German Clinical Trials Register DRKS00023110; https://drks.de/search/de/trial/DRKS00023110.


Subject(s)
Internet , Adolescent , Adult , Female , Humans , Male , Young Adult , Help-Seeking Behavior , Mental Disorders/psychology , Mental Disorders/therapy , Mental Health , Patient Acceptance of Health Care/psychology , Patient Acceptance of Health Care/statistics & numerical data , Video Recording
3.
Eur Child Adolesc Psychiatry ; 33(2): 451-465, 2024 Feb.
Article in English | MEDLINE | ID: mdl-36853515

ABSTRACT

Adolescence is a critical phase for the development of substance use disorders (SUDs). For Europe and Germany, there are limited data on problematic substance use from representative youth samples. Trait mindfulness is relevant in buffering against substance use-related problems and associated deficits in self-regulatory control. The objective of this study is to estimate 12-month prevalence rates for SUDs in a representative sample of adolescents in Germany and to examine associations with mindfulness and related factors such as stress, impulsivity, sensation seeking and symptoms of psychopathology. A sample of 4001 adolescents aged 12-18 years from Germany was surveyed based on DSM-IV diagnostic criteria for SUDs. Logistic regression analyses were used to examine associations with mindfulness-related variables. Criteria of at least one of the assessed SUDs were endorsed by 11.2% of the adolescents. Alcohol use disorders had the highest prevalence rate (10.1%) followed by cannabis use disorders (2.6%). For both substances, the criteria for abuse were met about twice as often as those for dependence. The prevalence of cigarette dependence was 1.7%, while the prevalence for e-cigarette dependence was only 0.1%. Prevalence rates were higher for male youth and increasing with age. SUD prevalence was also related to mindfulness, impulsivity and sensation seeking and externalizing symptoms of psychopathology. The statistically significant associations varied across different SUDs. SUDs appear highly prevalent among German adolescents. The results have public health implications with regard to treatment needs and prevention measures in the youth population in Germany.


Subject(s)
Alcoholism , Electronic Nicotine Delivery Systems , Mindfulness , Substance-Related Disorders , Humans , Male , Adolescent , Alcoholism/epidemiology , Prevalence , Substance-Related Disorders/epidemiology , Substance-Related Disorders/diagnosis , Impulsive Behavior , Germany/epidemiology , Personality
4.
Article in English | MEDLINE | ID: mdl-38748240

ABSTRACT

Cannabis use disorder (CUD) is the most frequent reason for psychiatric inpatient substance use disorder (SUD) treatment among 15-19-year-olds in Germany. Despite effective treatment programs, relapse rates remain high. Thus, existing multi-component programs (TAU) need to be enhanced with SUD-specific elements. Mindfulness-based interventions (MBI) seem promising as they can positively influence SUD-related behaviors (e. g. craving). Given limited research in adolescents, this randomized controlled trial investigated the extent to which MBI-based group therapy (Mind it!) as an add-on treatment to TAU led to fewer cannabis use days after 6 months in 84 adolescent inpatients with CUD. Additionally, craving, severity of CUD, and changes in mindfulness were monitored (pre-, post-, and follow-up (FU) assessments). The results revealed a significant reduction in cannabis use days in both groups at 6-month FU (d = - 0.72 and = - 0.75). Although minor additional benefits of Mind it! were evident post-treatment, specifically reduction of craving and SUD severity, by the 6-month mark, TAU exhibited a more substantial decrease in SUD severity (d = 0.78), and reward craving (d = 0.28) compared to Mind it!. Regarding self-regulation skills (mindfulness), Mind it! demonstrated superiority over TAU after 6-month FU (d = 0.27). Therapists judged the MBI as feasible. (Serious) adverse events were unrelated to Mind it!. There was a systematic dropout among Mind it! participants. Primarily, the results emphasize the effectiveness of TAU in reducing cannabis use. MBI also seem feasible for youth, but results remain inconsistent and unstable over time. Importantly, enhanced adherence to reduce dropouts is needed.Trial registration: German Clinical Trials Register, DRKS00014041. Registered on 17 April 2018.

5.
Article in German | MEDLINE | ID: mdl-38526678

ABSTRACT

BACKGROUND: The aim of the current study was to assess the prevalence of the (problematic) consumption of alcohol, tobacco, and cannabis as well as the (problematic) use of social media, e­products, computer games, and gambling among apprentices. METHOD: Cross-sectional survey of 4591 apprentices at 17 vocational schools from Bavaria, Schleswig-Holstein, and Hamburg. Data was collected using questionnaires between March 2021 and April 2022. The primary endpoints were the 30-day prevalence and the problematic consumption and usage behavior of the mentioned substances/behaviors using screening instruments. RESULTS: Among the assessed substances/behaviors, social media were used most frequently by the apprentices with a 30-day prevalence of 97.7%, followed by alcohol (64.3%) and computer games (55.8%). Cigarettes were consumed by 35.1%, e­products by 17.9%, and cannabis by 15.4% of the apprentices. Of the apprentices, 12.2% reported having gambled in the past 30 days. Rates of problematic use were 47.4% for alcohol, 18.0% for tobacco, 6.2% for e­products, and 1.6% for cannabis. Problematic use of social media was indicated by 45.0% of the apprentices, of gambling by 2.2%, and of computer games by 0.7%. DISCUSSION: These results suggest that apprentices constitute a risk group for problematic substance use, indicating increased need for intervention. In particular, secondary prevention efforts in the areas of alcohol and social media should be taken into consideration due to their widespread prevalence in the vocational school setting.


Subject(s)
Gambling , Social Media , Substance-Related Disorders , Video Games , Humans , Cross-Sectional Studies , Gambling/epidemiology , Germany/epidemiology , Substance-Related Disorders/epidemiology
6.
PLoS Genet ; 15(1): e1007913, 2019 01.
Article in English | MEDLINE | ID: mdl-30677017

ABSTRACT

Boundary domains play important roles during morphogenesis in plants and animals, but how they contribute to patterning and growth coordination in plants is not understood. The CUC genes determine the boundary domains in the aerial part of the plants and, in particular, they have a conserved role in regulating leaf complexity across Angiosperms. Here, we used tooth formation at the Arabidopsis leaf margin controlled by the CUC2 transcription factor to untangle intertwined events during boundary-controlled morphogenesis in plants. Combining conditional restoration of CUC2 function with morphometrics as well as quantification of gene expression and hormone signaling, we first established that tooth morphogenesis involves a patterning phase and a growth phase. These phases can be separated, as patterning requires CUC2 while growth can occur independently of CUC2. Next, we show that CUC2 acts as a trigger to promote growth through the activation of three functional relays. In particular, we show that KLUH acts downstream of CUC2 to modulate auxin response and that expressing KLUH can compensate for deficient CUC2 expression during tooth growth. Together, we reveal a genetic and molecular network that allows coordination of patterning and growth by CUC2-defined boundaries during morphogenesis at the leaf margin.


Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/genetics , Cytochrome P-450 Enzyme System/genetics , Morphogenesis/genetics , Arabidopsis/growth & development , Flowers/genetics , Gene Expression Regulation, Developmental/genetics , Gene Expression Regulation, Plant/genetics , Indoleacetic Acids/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/growth & development , Seeds/genetics , Seeds/growth & development
7.
Nervenarzt ; 93(4): 341-350, 2022 Apr.
Article in German | MEDLINE | ID: mdl-35267052

ABSTRACT

BACKGROUND: Addictive disorders are typically manifested during adolescence and have a high transmission rate into adulthood. When adulthood is reached the responsibility by the child and adolescent psychiatric care system ends and patients transition to adult psychiatry. A lack of supportive concepts and approaches to this transition can have detrimental effects on the long-term health of affected individuals. OBJECTIVE: Addiction treatment requirements of young adults transitioning between the systems of care are presented. Developmental psychopathological concepts are presented and treatment recommendations are provided. MATERIAL AND METHODS: The scientific literature on development-related approaches to addiction treatment was evaluated. Care conditions relevant to transitional psychiatry are discussed and a description of needs is carried out. RESULTS: Adolescents and young adults are very frequently affected by addictive disorders. The need for disorder-specific and age-specific transition-related concepts and services for these patients is high. During the transition from child and adolescent psychiatry to the psychiatric care system for adults, patients with substance-related disorders require treatment-related educational and age-appropriate psychosocial support services that address the high comorbidity and developmental delays. CONCLUSION: Age-specific and disorder-specific treatment services should be broadly expanded and the interfaces to youth welfare, addiction counseling and adult psychiatry should be better coordinated.


Subject(s)
Behavior, Addictive , Psychiatry , Substance-Related Disorders , Adolescent , Adolescent Psychiatry , Adult , Child , Comorbidity , Humans , Substance-Related Disorders/diagnosis , Substance-Related Disorders/epidemiology , Substance-Related Disorders/therapy , Young Adult
8.
New Phytol ; 232(5): 1909-1916, 2021 12.
Article in English | MEDLINE | ID: mdl-34498760

ABSTRACT

The timing of leaf emergence at the shoot apical meristem, or plastochron, is highly regulated in plants. Among the genes known to regulate the plastochron in Arabidopsis (Arabidopsis thaliana), KLUH (KLU), orthologous to the rice (Oryza sativa) PLASTOCHRON1, encodes the cytochrome P450 CYP78A5, and is thought to act through generation of a still unknown mobile signal. As klu mutants display not only a short plastochron but also a branching phenotype reminiscent of strigolactone (SL) mutants, we investigated whether KLU/CYP78A5 is involved in SL biosynthesis. We combined a genetic approach, a parasitic plant seed germination bioassay to test klu root exudates, and analysis of transcript abundances of SL-biosynthesis genes in the Arabidopsis klu mutants. We demonstrate that KLU is not involved in the SL-biosynthesis pathway. Moreover, this work allowed us to uncover a new role for SL during Arabidopsis development in modulating plastochron via a KLU-dependent pathway. Globally our data reveal that KLU is required for plastochron-specific SL responses, a first indication of crosstalk between SL and the KLU-derived signal.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Plant , Heterocyclic Compounds, 3-Ring , Lactones
9.
Z Kinder Jugendpsychiatr Psychother ; 49(6): 486-493, 2021 Nov.
Article in German | MEDLINE | ID: mdl-32795136

ABSTRACT

Disorders due to substance use or addictive behaviours in the ICD-11 Abstract. This paper concerns the revised classification of Substance-Related and Addictive Disorders in the 11th edition of the International Classification of Diseases (ICD-11) of the World Health Organization. The revision of the ICD serves to reflect changes in the understanding and diagnosis of addictive disorders and the need to improve clinical applicability. Regarding substance-related and non-substance-related addictive disorders, considerable innovations were introduced compared to the previous version. Major innovations include an expanded range of substance classes, significant adjustments (i. e., simplifications) in the conceptual and diagnostic guidelines of substance-related disorders, particularly "substance dependence", the introduction of the category of "addictive behaviour," and, associated with this, the assignment of "gambling disorder" to the addictive disorders, and the inclusion of the new (screen-related) "gaming disorder." In addition, for the first time the ICD catalogue includes an expansion of diagnostic options for early, preclinical phenotypes of addiction disorders ("Episodic Harmful Use"). This article summarizes the changes in the field of addiction disorders and discusses them from a child and adolescent psychiatric perspective.


Subject(s)
Behavior, Addictive , Gambling , Substance-Related Disorders , Adolescent , Behavior, Addictive/diagnosis , Diagnostic and Statistical Manual of Mental Disorders , Humans , International Classification of Diseases , Substance-Related Disorders/diagnosis
10.
Z Kinder Jugendpsychiatr Psychother ; 50(2): 121-132, 2021 Mar.
Article in German | MEDLINE | ID: mdl-34668740

ABSTRACT

Use of Electronic Cigarettes (e-cigs) and e-Shishas by Children and Adolescents: Evidence Paper of the Joint Addiction Commission of the German Societies and Professional Associations of Child and Adolescent Psychiatry and Psychotherapy Abstract. The particular risks associated with the consumption of electronic cigarettes (e-cigs) in children and adolescents are not sufficiently considered in the health policy discourse. The present article evaluates the current dissemination and consumption patterns of e-cigarettes as well as the health risks attached to children and adolescents. Based on data from current national and international studies, there has been a clear increase in the consumption of e-cigarettes over the past years. This stands in sharp contrast to the overall decline in tobacco consumption among both children and adolescents in Germany. Young people without tobacco experience are now consuming more frequently e-cigarettes than those who occasionally or regularly use tobacco. They also are experimenting more frequently with conventional cigarettes if they have previously consumed e-cigarettes. The largely unregulated availability of e-cigarette products to the newest generation, such as JUUL, led to a dramatic increase in their prevalence among high-school students in the USA. Products with high nicotine content and multiple flavors are being marketed intensively as trendy lifestyle products to young user groups via advertising and social media campaigns. These products are also becoming increasingly relevant in Germany. The success of tobacco prevention in recent years is presently jeopardized by the ongoing effective advertising for e-cigarettes. The Addiction Commission of the German Child and Youth Psychiatric Federations and Scientific Societies therefore call for an immediate, strict, and comprehensive ban of e-cigarette advertising.


Subject(s)
Behavior, Addictive , Electronic Nicotine Delivery Systems , Smoking Water Pipes , Adolescent , Adolescent Psychiatry , Child , Humans , Psychotherapy
11.
Z Kinder Jugendpsychiatr Psychother ; 48(5): 381-392, 2020 Sep.
Article in German | MEDLINE | ID: mdl-30453823

ABSTRACT

Prevention of substance use disorders Abstract. Introduction: Adolescence is a vulnerable period for the development of Substance Use Disorders and preventive intervention is a public health priority. In this article, we summarize the available evidence for behavioral preventive action for Substance Use Disorders and related dysregulated behaviors during adolescence in various settings. Results: Current meta-analytic evidence is available mainly for the school and family settings and increasingly also for internet-based prevention. The literature is dominated by US-studies that focus on universal school-based approaches for legal substances in middle adolescence. Only few German studies are published. Taken together the results indicate that developmentally sensitive substance use prevention is effective across different settings with consistent small-to-middle sized effects. Differential effectiveness analyses for schoolbased prevention suggest that younger adolescents benefit most from universal prevention, while for older adolescents targeted approaches are more effective. Conclusions: Across the relevant settings, effective preventive measures are available. However, the results could be improved. There is a need for translational research on effective and more individualized approaches to prevention and differential effects of intervention modules. Moreover, there is a need for research on the implementation of evidence-based programs and especially in Germany, coordinated approaches on community levels are lacking.


Subject(s)
Substance-Related Disorders/prevention & control , Adolescent , Germany , Humans , Substance-Related Disorders/psychology
12.
Z Kinder Jugendpsychiatr Psychother ; 48(6): 448-452, 2020 Nov.
Article in German | MEDLINE | ID: mdl-32208050

ABSTRACT

Substance-related disorders in adolescence and young adulthood Abstract. Adolescence is a critical period for the onset of addiction and comorbid psychological disorders. Although substance use disorders (SUD) are among the most prevalent psychiatric conditions and a leading cause for hospitalization in the young population, young people with SUD can be considered an underserved population. Existing capacities for the provision of specific health services including withdrawal treatment for young SUD patients are inadequate, and medical rehabilitation facilities are lacking almost completely. Because SUD often becomes a chronic condition with high degree of relapse, from a life-course perspective this demands a highly connected healthcare structure at the intersection of child and adolescent and adult psychiatry as well as other health services. These interconnected services must be sensitive to the developmental needs and aspects of adolescent SUD, such as motivational, social, and educational factors. Moreover, there is a need for ongoing and often multidisciplinary support during the transition from child and adolescent to adult psychiatry with a transparent medical documentation and clear allocation of costs. The establishment and formative evaluation of (specific) medical rehabilitation facilities for children, adolescents, and young adults is highly recommended to improve the current healthcare situation for young SUD patients.


Subject(s)
Substance-Related Disorders , Adolescent , Chronic Disease , Hospitalization/statistics & numerical data , Humans , Prevalence , Substance-Related Disorders/diagnosis , Substance-Related Disorders/epidemiology , Substance-Related Disorders/psychology , Young Adult
13.
Prax Kinderpsychol Kinderpsychiatr ; 69(4): 353-374, 2020 Jul.
Article in German | MEDLINE | ID: mdl-32615894

ABSTRACT

Mindfulness in Development-oriented Approaches to Substance Use Prevention and Therapy: Rationale, Design and Objectives of the Research Consortium IMAC-Mind Substance use disorders (SUD) are a major contributor to morbidity and mortality. They are typically initiated during adolescence and can have fatal implications for healthy development. Despite substantial scientific advances, there remains a need to prioritize research directed at reducing risks for SUD, particularly in vulnerable periods and populations from a developmental perspective. Research indicates that reward sensitivity, impulsivity, deficient self-regulation, and stress reactivity develop markedly in childhood and adolescence and play an important role in the initiation and maintenance of SUD. A growing number of research results suggest that these factors can be favorably influenced by mindfulness-based interventions and that mindfulness-based exercises can be successfully integrated into established prevention and treatment programs. In this paper we summarize the conceptual relationships between the development and maintenance of addiction disorders and mindfulness, discuss existing empirical findings with regard to childhood and adolescence, and present the aims, study designs and intervention models of the subprojects from the ongoing research network "IMAC-Mind: Improving Mental Health and Reducing Addiction in Childhood and Adolescence through Mindfulness: Mechanisms, Prevention and Treatment".


Subject(s)
Mental Health , Mindfulness , Substance-Related Disorders/prevention & control , Substance-Related Disorders/therapy , Adolescent , Behavior, Addictive/prevention & control , Behavior, Addictive/therapy , Child , Humans , Imidazoles
14.
Prax Kinderpsychol Kinderpsychiatr ; 68(5): 376-401, 2019 Jun.
Article in German | MEDLINE | ID: mdl-31250722

ABSTRACT

Current State of Family-Based Prevention and Therapy of Substance-Use Disorders in Children and Adolescents: A Review Adolescence is a vulnerable period for substance use disorders (SUD) as indicated by epidemiological studies. Research demonstrates the family's role for the etiology of SUD and provides a rationale for interventions based on family-associated risk and resilience factors. In this article, we summarize published results for family-based interventions from 2008-2018. Taken together, prevention programs can be effective when they focus on the promotion of broader developmental competencies and familial resources, rather than narrowly addressing substance use. Moreover, programs could benefit from targeting youth and parents as done in the "Strengthening Families Program 10-14"; most existing programs however target parents and do not include the adolescents. Family-based treatment programs with an evidence base are Multisystemic Therapy, Functional Family Therapy, Multidimensional Family Therapy and Brief Strategic Family Therapy. Overall, the effects of family-based interventions are small-to-middle sized but vary significantly across populations. Across the field of family-based interventions, there is a need for more knowledge on effective components and differential effects. The results could be improved by translational research such as on the emerging concept of mindfulness. Moreover, there is a need for implementation research and the effectiveness of service delivery programs on the community level in Germany.


Subject(s)
Family Therapy , Psychotherapy , Substance-Related Disorders/prevention & control , Substance-Related Disorders/therapy , Adolescent , Child , Germany , Humans , Parents/psychology
15.
Genes Dev ; 24(19): 2127-32, 2010 Oct 01.
Article in English | MEDLINE | ID: mdl-20889713

ABSTRACT

The Arabidopsis basic helix-loop-helix (bHLH) proteins INDEHISCENT (IND) and ALCATRAZ (ALC) specify tissues required for fruit opening that have major roles in seed dispersal and plant domestication. Here, we show that synthesis of the phytohormone gibberellin is a direct and necessary target of IND, and that ALC interacts directly with DELLA repressors, which antagonize ALC function but are destabilized by gibberellin. Thus, the gibberellin/DELLA pathway has a key role in patterning the Arabidopsis fruit, and the interaction between DELLA and bHLH proteins, previously shown to connect gibberellin and light responses, is a versatile regulatory module also used in tissue patterning.


Subject(s)
Arabidopsis/growth & development , Arabidopsis/metabolism , Fruit/growth & development , Gibberellins/metabolism , Arabidopsis/cytology , Arabidopsis/genetics , Arabidopsis Proteins/metabolism , Basic Helix-Loop-Helix Transcription Factors/metabolism , Fruit/cytology , Fruit/metabolism , Gene Expression Regulation, Plant , Gibberellins/biosynthesis
16.
J Exp Bot ; 68(21-22): 5801-5811, 2017 12 16.
Article in English | MEDLINE | ID: mdl-29186469

ABSTRACT

The CUP-SHAPED COTYLEDON (CUC) transcription factors control plant boundary formation, thus allowing the emergence of novel growth axes. While the developmental roles of the CUC genes in different organs and across species are well characterized, upstream and downstream events that contribute to their function are still poorly understood. To identify new players in this network, we performed a suppressor screen of CUC2g-m4, a line overexpressing CUC2 that has highly serrated leaves. We identified a mutation that simplifies leaf shape and affects MURUS1 (MUR1), which is responsible for GDP-L-fucose production. Using detailed morphometric analysis, we show that GDP-L-fucose has an essential role in leaf shape acquisition by sustaining differential growth at the leaf margins. Accordingly, reduced CUC2 expression levels are observed in mur1 leaves. Furthermore, genetic analyses reveal a conserved role for GDP-L-fucose in different developmental contexts where it contributes to organ separation in the same pathway as CUC2. Taken together, our results reveal that GDP-L-fucose is necessary for proper establishment of boundary domains in various developmental contexts.


Subject(s)
Arabidopsis/genetics , Gene Expression Regulation, Plant , Guanosine Diphosphate Fucose/metabolism , Plant Leaves/growth & development , Arabidopsis/growth & development , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Gene Expression Regulation, Developmental , Guanosine Diphosphate Fucose/genetics , Mutation , Plant Leaves/genetics , Plant Leaves/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
17.
Haematologica ; 102(5): 883-894, 2017 05.
Article in English | MEDLINE | ID: mdl-28232371

ABSTRACT

While c-Myc dysregulation is constantly associated with highly proliferating B-cell tumors, nuclear factor (NF)-κB addiction is found in indolent lymphomas as well as diffuse large B-cell lymphomas, either with an activated B-cell like phenotype or associated with the Epstein-Barr virus. We raised the question of the effect of c-Myc in B cells with NF-κB activated by three different inducers: Epstein-Barr virus-latency III program, TLR9 and CD40. Induction of c-Myc overexpression increased proliferation of Epstein-Barr virus-latency III immortalized B cells, an effect that was dependent on NF-κB. Results from transcriptomic signatures and functional studies showed that c-Myc overexpression increased Epstein-Barr virus-latency III-driven proliferation depending on NF-κB. In vitro, induction of c-Myc increased proliferation of B cells with TLR9-dependant activation of MyD88, with decreased apoptosis. In the transgenic λc-Myc mouse model with c-Myc overexpression in B cells, in vivo activation of MyD88 by TLR9 induced splenomegaly related to an increased synthesis phase (S-phase) entry of B cells. Transgenic mice with both continuous CD40 signaling in B cells and the λc-Myc transgene developed very aggressive lymphomas with characteristics of activated diffuse large B-cell lymphomas. The main characteristic gene expression profile signatures of these tumors were those of proliferation and energetic metabolism. These results suggest that c-Myc is an NF-κB co-transforming event in aggressive lymphomas with an activated phenotype, activated B-cell like diffuse large B-cell lymphomas. This would explain why NF-κB is associated with both indolent and aggressive lymphomas, and opens new perspectives on the possibility of combinatory therapies targeting both the c-Myc proliferating program and NF-κB activation pathways in diffuse large B-cell lymphomas.


Subject(s)
B-Lymphocytes/metabolism , Cell Transformation, Viral , NF-kappa B/metabolism , Proto-Oncogene Proteins c-myc/metabolism , Animals , Apoptosis/genetics , B-Lymphocytes/virology , CD40 Antigens/genetics , CD40 Antigens/metabolism , Cell Line, Transformed , Cell Proliferation/genetics , Gene Expression Profiling/methods , Herpesvirus 4, Human/physiology , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/metabolism , Mice, Transgenic , Proto-Oncogene Proteins c-myc/genetics , Signal Transduction/genetics
18.
Prev Sci ; 18(8): 932-942, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28643133

ABSTRACT

While the effectiveness of substance use prevention programs such as the Strengthening Families Program 10-14 (SFP) has been demonstrated in the USA, European SFP adaptations have not replicated these sizable effects. Following the rationale of the risk moderation hypothesis positing that elevated risk groups may benefit more from a preventive intervention than lower-risk groups, we reanalyzed evaluation data from a randomized controlled trial testing the adapted German version of SFP (SFP-D). We hypothesized a differential impact of risk status on intervention results. The study employed a minimal control condition. Of the N = 292 participating children, 73.5% qualified as at-risk because they lived in a deprived urban district, and 26.5% qualified as high risk because they additionally scored as "difficult" in the German Strengths and Difficulty Questionnaire (parents' reports using gender- and age-specific German norms). Outcomes were children's self-reports on substance use, mental health, family functioning, and quality of life. Data were analyzed with repeated measures linear mixed models and relative risk analyses. The high-risk group in the SFP-D condition achieved the best results compared with all other groups, especially in mental health and quality of life. Relative risk analyses on tobacco [alcohol] abstinence showed that an additional percentage of 29.8% [16.0%] of high-risk children in nonabstinent controls would have remained abstinent if they had participated in SFP-D. We conclude that risk load influences the impact of substance use prevention programs and discuss to what extent differential analyses can add value to prevention research.


Subject(s)
Family/psychology , Preventive Medicine/organization & administration , Adolescent , Child , Germany , Humans , Mental Health , Quality of Life , Risk
19.
Plant J ; 83(4): 732-42, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26119568

ABSTRACT

The evolution of plant reproductive strategies has led to a remarkable diversity of structures, especially within the flower, a structure characteristic of the angiosperms. In flowering plants, sexual reproduction depends notably on the development of the gynoecium that produces and protects the ovules. In Arabidopsis thaliana, ovule initiation is promoted by the concerted action of auxin with CUC1 (CUP-SHAPED COTYLEDON1) and CUC2, two genes that encode transcription factors of the NAC family (NAM/ATAF1,2/CUC). Here we highlight an additional role for CUC2 and CUC3 in Arabidopsis thaliana ovule separation. While CUC1 and CUC2 are broadly expressed in the medial tissue of the gynoecium, CUC2 and CUC3 are expressed in the placental tissue between developing ovules. Consistent with the partial overlap between CUC1, CUC2 and CUC3 expression patterns, we show that CUC proteins can physically interact, both in yeast cells and in planta. We found that the cuc2;cuc3 double mutant specifically harbours defects in ovule separation, producing fused seeds that share the seed coat, and suggesting that CUC2 and CUC3 promote ovule separation in a partially redundant manner. Functional analyses show that CUC transcription factors are also involved in ovule development in Cardamine hirsuta. Additionally we show a conserved expression pattern of CUC orthologues between ovule primordia in other phylogenetically distant species with different gynoecium architectures. Taken together these results suggest an ancient role for CUC transcription factors in ovule separation, and shed light on the conservation of mechanisms involved in the development of innovative structures.


Subject(s)
Ovule/growth & development , Ovule/metabolism , Arabidopsis/growth & development , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Cardamine/growth & development , Cardamine/metabolism , Gene Expression Regulation, Plant , Magnoliopsida/growth & development , Magnoliopsida/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/growth & development , Plants, Genetically Modified/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism
20.
EMBO J ; 31(1): 175-86, 2012 Jan 04.
Article in English | MEDLINE | ID: mdl-21946558

ABSTRACT

A new regulatory pathway involved in plant response to oxidative stress was revealed using the iron-induced Arabidopsis ferritin AtFER1 as a model. Using pharmacological and genetic approaches, the DownSTream (DST) cis-acting element in the 3'-untranslated region of the AtFER1 mRNA was shown to be involved in the degradation of this transcript, and oxidative stress triggers this destabilization. In the two previously identified trans-acting mutants (dst1 and dst2), AtFER1 mRNA stability is indeed impaired. Other iron-regulated genes containing putative DST sequences also displayed altered expression. Further physiological characterization identified this oxidative stress-induced DST-dependent degradation pathway as an essential regulatory mechanism to modulate mRNA accumulation patterns. Alteration of this control dramatically impacts plant oxidative physiology and growth. In conclusion, the DST-dependent mRNA stability control appears to be an essential mechanism that allows plants to cope with adverse environmental conditions.


Subject(s)
Arabidopsis Proteins/genetics , Arabidopsis/genetics , Iron/metabolism , RNA Stability , RNA, Plant/metabolism , Reactive Oxygen Species/metabolism , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Ferritins/genetics , Ferritins/metabolism , Gene Expression Regulation, Plant , Oxidative Stress
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