Conservation of the Restricted Expression of Brassicaceae Bsister-Like Genes in Seeds Requires a Transposable Element in Arabidopsis thaliana.

Changes in transcription factor binding sites (TFBSs) can alter the spatiotemporal expression pattern and transcript abundance of genes. Loss and gain of TFBSs were shown to cause shifts in expression patterns in numerous cases. However, we know little about the evolution of extended regulatory sequences incorporating many TFBSs. We compare, across the crucifers (Brassicaceae, cabbage family), the sequences between the translated regions of Arabidopsis Bsister (ABS)-like MADS-box genes (including paralogous GOA-like genes) and the next gene upstream, as an example of family-wide evolution of putative upstream regulatory regions (PURRs). ABS-like genes are essential for integument development of ovules and endothelium formation in seeds of Arabidopsis thaliana. A combination of motif-based gene ontology enrichment and reporter gene analysis using A. thaliana as common trans-regulatory environment allows analysis of selected Brassicaceae Bsister gene PURRs. Comparison of TFBS of transcriptionally active ABS-like genes with those of transcriptionally largely inactive GOA-like genes shows that the number of in silico predicted TFBS) is similar between paralogs, emphasizing the importance of experimental verification for in silico characterization of TFBS activity and analysis of their evolution. Further, our data show highly conserved expression of Brassicaceae ABS-like genes almost exclusively in the chalazal region of ovules. The Arabidopsis-specific insertion of a transposable element (TE) into the ABS PURRs is required for stabilizing this spatially restricted expression, while other Brassicaceae achieve chalaza-specific expression without TE insertion. We hypothesize that the chalaza-specific expression of ABS is regulated by cis-regulatory elements provided by the TE.

A land plant phylogenetic framework for GLABROUS INFLORESCENCE STEMS (GIS), SUPERMAN, JAGGED and allies plus their TOPLESS co-repressor.

Members of the plant specific family of C1-1i zincfinger transcriptionfactors (ZF-TFs), such as SUPERMAN, JAGGED, KNUCKLES or GIS,regulatediversedevelopmental processes including sexual reproduction. C1-1is consist of one zinc-finger and one to two EAR domains, connected by large intrinsically disordered regions (IDR). While the role of C1-i1 ZF-TFs in development processes is well known for some genes in Arabidopsis, rice or tomatoa comprehensive and broadphylogenetic background is lacking, yet knowledge of orthology is a requirement for a better understanding of C1-1i-Zf-TFs diverse roles in plants. Here, we provide a fine-grained and land plant wide classification of C1-1i sub-families and their known co-repressors TOPLESS and TOPLESS RELATED. Our work combines the identification of orthologous groups with Maximum-Likelihood phylogeny reconstructions and digital gene expression analyses mining high quality land plant genomes and transcriptomes to generate a comprehensive framework of C1-1i ZF-TF evolution. We show that C1-1i's are low to moderate copy genesand that orthologous genesonly partiallyhaveconserved sub-family and life cycle stage dependent expression pattern across land plants while others are highly diverged. Our workprovides the phylogenetic framework for C1-1i ZF-TFs, s and strengthen C1-1 ZF-TFs as a potential model for IDR-research in plants.

A cornucopia of diversity-Ranunculales as a model lineage.

The Ranunculales are a hyperdiverse lineage in many aspects of their phenotype, including growth habit, floral and leaf morphology, reproductive mode, and specialized metabolism. Many Ranunculales species, such as opium poppy and goldenseal, have a high medicinal value. In addition, the order includes a large number of commercially important ornamental plants, such as columbines and larkspurs. The phylogenetic position of the order with respect to monocots and core eudicots and the diversity within this lineage make the Ranunculales an excellent group for studying evolutionary processes by comparative studies. Lately, the phylogeny of Ranunculales was revised, and genetic and genomic resources were developed for many species, allowing comparative analyses at the molecular scale. Here, we review the literature on the resources for genetic manipulation and genome sequencing, the recent phylogeny reconstruction of this order, and its fossil record. Further, we explain their habitat range and delve into the diversity in their floral morphology, focusing on perianth organ identity, floral symmetry, occurrences of spurs and nectaries, sexual and pollination systems, and fruit and dehiscence types. The Ranunculales order offers a wealth of opportunities for scientific exploration across various disciplines and scales, to gain novel insights into plant biology for researchers and plant enthusiasts alike.

Lessons learned from implementing a digital rehabilitation care planning platform to improve care access for patients with work disability: qualitative process evaluation of the RehaPro-SERVE study.

BACKGROUND: Inpatient rehabilitation therapies can be applied for in Germany by patients of working age to support their return to work. However, there are some problems that impede an easy and uncomplicated application process. An interdisciplinary case management approach for rehabilitation care planning was developed to facilitate the access to rehabilitation. Case conferences (CCs) were held with relevant stakeholders and took place on a digital communication platform. We conducted a qualitative process evaluation to understand the implementation of the intervention and to identify contextual factors as well as mechanisms for a successful implementation in the context of primary care. METHODS: The process evaluation included interviews with primary care physicians (PCPs), patients and stakeholders involved in the intervention process. Reflexive thematic analysis was used to analyse the data. Emerging themes were structured according to the Donabedian framework of structure, process and outcomes. RESULTS: A total of 18 interviews were conducted. Important results included the desire for more patient involvement and case management. Patients especially valued the opportunity to receive support from a social worker. Limitations of the platform related to usability and limited opportunities for stakeholder communication. Despite training for PCPs, several problems arose regarding the clarity of the intervention process. Patients were satisfied with their application process and the treatments offered, while PCPs reported an increase in workload. CONCLUSIONS: A digitalisation of the application procedure for rehabilitation and further treatment options is acceptable to patients and personal support of a social worker is particularly valued. However, patients should be included in the CC in terms of a shared decision-making process. The digital platform requires sufficient training and adjustments have to be made to enhance usability and to improve the efficiency of the process for PCPs. Overall, the exchange between the various stakeholders in the CC is considered particularly useful in more complex cases. TRIAL REGISTRATION: DRKS German Clinical Trials Register, DRKS0 00242 07. Registered on 22 March 2021.

Transcriptome analysis of gynoecium morphogenesis uncovers the chronology of gene regulatory network activity.

The gynoecium is the most complex organ formed by the flowering plants. It encloses the ovules, provides a surface for pollen contact and self-incompatibility reactions, allows pollen tube growth, and, post fertilization, develops into the fruit. Consequently, the regulation of gynoecium morphogenesis is complex and appropriate timing of this process in part determines reproductive success. However, little is known about the global control of gynoecium development, even though many regulatory genes have been characterized. Here, we characterized dynamic gene expression changes using laser-microdissected gynoecium tissue from four developmental stages in Arabidopsis. We provide a high-resolution map of global expression dynamics during gynoecium morphogenesis and link these to the gynoecium interactome. We reveal groups of genes acting together early and others acting late in morphogenesis. Clustering of co-expressed genes enables comparisons between the leaf, shoot apex, and gynoecium transcriptomes, allowing the dissection of common and distinct regulators. Furthermore, our results lead to the discovery of genes with putative transcription factor activity (B3LF1, -2, DOFLF1), which, when mutated, lead to impaired gynoecium expansion, illustrating that global transcriptome analyses reveal yet unknown developmental regulators. Our data show that genes encoding highly interacting proteins, such as SEPALLATA3, AGAMOUS, and TOPLESS, are expressed evenly during development but switch interactors over time, whereas stage-specific proteins tend to have fewer interactors. Our analysis connects specific transcriptional regulator activities, protein interactions, and underlying metabolic processes, contributing toward a dynamic network model for gynoecium development.

Transcriptome analysis reveals major transcriptional changes during regrowth after mowing of red clover (Trifolium pratense).

BACKGROUND: Red clover (Trifolium pratense) is globally used as a fodder plant due its high nutritional value and soil improving qualities. In response to mowing, red clover exhibits specific morphological traits to compensate the loss of biomass. The morphological reaction is well described, but the underlying molecular mechanisms and its role for plants grown in the field are unclear. RESULTS: Here, we characterize the global transcriptional response to mowing of red clover by comparing plants grown under greenhouse conditions with plants growing on agriculturally used fields. Unexpectedly, we found that biotic and abiotic stress related changes of plants grown in the field overlay their regrowth related transcriptional changes and characterized transcription related protein families involved in these processes. Further, we can show that gibberellins, among other phytohormones, also contribute to the developmental processes related to regrowth after biomass-loss. CONCLUSIONS: Our findings show that massive biomass loss triggers less transcriptional changes in field grown plants than their struggle with biotic and abiotic stresses and that gibberellins also play a role in the developmental program related to regrowth after mowing in red clover. Our results provide first insights into the physiological and developmental processes of mowing on red clover and may serve as a base for red clover yield improvement.

Attitudes of medical students to general practice: a multinational cross-sectional survey.

BACKGROUND: A shortage of general practitioners (GPs) is common to many European countries. To counteract this, it is essential to understand the factors that encourage or discourage medical students from choosing to become a GP. OBJECTIVE: To evaluate medical students' attitudes towards general practice and to identify factors that discourage them from considering a career as a GP. METHODS: In this multinational cross-sectional online survey, 29 284 students from nine German, four Austrian and two Slovenian universities were invited to answer a questionnaire consisting of 146 closed and 13 open-ended items. RESULTS: Of the 4486 students that responded (response rate: 15.3%), 3.6% wanted to become a GP, 48.1% were undecided and 34.6% did not want to be a GP. Significant predictors for interest in becoming a GP were higher age [odds ratio (OR) = 1.06; 95% confidence interval (CI) = 1.02-1.10], positive evaluation of the content of a GP's work (OR = 4.44; 95% CI = 3.26-6.06), organizational aspects (OR = 1.42; 95% CI = 1.13-1.78), practical experience of general practice (OR = 1.66; 95% CI = 1.08-2.56) and the country of the survey [Slovenian versus German students (Reference): OR = 2.19; 95% CI = 1.10-4.38; Austrian versus German students (Reference): OR = 0.50; 95% CI = 0.32-0.79]. CONCLUSION: Strategies to convince undecided students to opt for a career as a GP should include a positive representation of a GP's work and early and repeated experience of working in a general practice during medical school.

Coughing children in family practice and primary care: a systematic review of prevalence, aetiology and prognosis.

BACKGROUND: For evidence-based decision making, primary care physicians need to have specific and reliable information on the pre-test probabilities of underlying diseases and a symptom's course. We performed a systematic review of symptom-evaluating studies in primary care, following three research questions: (1) What is the prevalence of the symptom cough in children consulting primary care physicians? (2) What are the underlying aetiologies of cough and the respective frequencies? (3) What is the prognosis of children with cough? METHODS: Following a pre-defined algorithm and independent double reviewer ratings we searched MEDLINE and EMBASE. All quantitative original research articles in English, French or German were included if they focused on unselected study populations of children consulting a primary care physician for cough. We used the random effects model for meta-analysis in subgroups, if justifiable in terms of heterogeneity. RESULTS: We identified 14 eligible studies on prevalence, five on aetiology and one on prognosis. Prevalence estimates varied between 4.7 and 23.3% of all reasons for an encounter, or up to estimates of 60% when related to patients or consultations. Cough in children is more frequent than in adults, with lowest prevalences in adolescents and in summer. Acute cough is mostly caused by upper respiratory tract infections (62.4%) and bronchitis (33.3%); subacute or chronic cough by recurrent respiratory tract infection (27.7%), asthma (up to 50.4% in cough persisting more than 3 weeks), and pertussis (37.2%). Potentially serious diseases like croup, pneumonia or tuberculosis are scarce. In children with subacute and chronic cough the total duration of cough ranged from 24 to 192 days. About 62.3% of children suffering from prolonged cough are still coughing two months after the beginning of symptoms. CONCLUSION: Cough is one of the most frequent reasons for an encounter in primary care. Our findings fit in with current guideline recommendations supporting a thoughtful wait-and-see approach in acute cough and a special awareness in chronic cough of the possibility of asthma and pertussis. Further evidence of aetiological pre-test probabilities is needed to assess the diagnostic gain based on patient history and clinical signs for differential diagnoses of cough in children.

Prevalence, aetiologies and prognosis of the symptom cough in primary care: a systematic review and meta-analysis.

BACKGROUND: Cough is a relevant reason for encounter in primary care. For evidence-based decision making, general practitioners need setting-specific knowledge about prevalences, pre-test probabilities, and prognosis. Accordingly, we performed a systematic review of symptom-evaluating studies evaluating cough as reason for encounter in primary care. METHODS: We conducted a search in MEDLINE and EMBASE. Eligibility criteria and methodological quality were assessed independently by two reviewers. We extracted data on prevalence, aetiologies and prognosis, and estimated the variation across studies. If justifiable in terms of heterogeneity, we performed a meta-analysis. RESULTS: We identified 21 eligible studies on prevalence, 12 on aetiology, and four on prognosis. Prevalence/incidence estimates were 3.8-4.2%/12.5% (Western primary care) and 10.3-13.8%/6.3-6.5% in Africa, Asia and South America. In Western countries the underlying diagnoses for acute cough or cough of all durations were respiratory tract infections (73-91.9%), influenza (6-15.2%), asthma (3.2-15%), laryngitis/tracheitis (3.6-9%), pneumonia (4.0-4.2%), COPD (0.5-3.3%), heart failure (0.3%), and suspected malignancy (0.2-1.8%). Median time for recovery was 9 to 11 days. Complete recovery was reported by 40.2- 67% of patients after two weeks, and by 79% after four weeks. About 21.1-35% of patients re-consulted; 0-1.3% of acute cough patients were hospitalized, none died. Evidence is missing concerning subacute and chronic cough. CONCLUSION: Prevalences and incidences of cough are high and show regional variation. Acute cough, mainly caused by respiratory tract infections, is usually self-limiting (supporting a "wait-and-see" strategy). We have no setting-specific evidence to support current guideline recommendations concerning subacute or chronic cough in Western primary care. Our study presents epidemiological data under non non-pandemic conditions. It will be interesting to compare these data to future research results of the post-pandemic era.

Safety and target engagement profile of two oxaloacetate doses in Alzheimer's patients.

INTRODUCTION: Brain bioenergetics are defective in Alzheimer's disease (AD). Preclinical studies find oxaloacetate (OAA) enhances bioenergetics, but human safety and target engagement data are lacking. METHODS: We orally administered 500 or 1000 mg OAA, twice daily for 1 month, to AD participants (n = 15 each group) and monitored safety and tolerability. To assess brain metabolism engagement, we performed fluorodeoxyglucose positron emission tomography (FDG PET) and magnetic resonance spectroscopy before and after the intervention. We also assessed pharmacokinetics and cognitive performance. RESULTS: Both doses were safe and tolerated. Compared to the lower dose, the higher dose benefited FDG PET glucose uptake across multiple brain regions (P < .05), and the higher dose increased parietal and frontoparietal glutathione (P < .05). We did not demonstrate consistent blood level changes and cognitive scores did not improve. CONCLUSIONS: 1000 mg OAA, taken twice daily for 1 month, is safe in AD patients and engages brain energy metabolism.

The prevention of musculoskeletal complaints: long-term effect of a work-related psychosocial coaching intervention compared to physiotherapy alone-a randomized controlled trial.

PURPOSE: Research shows that psychosocial factors play a significant role in the emergence of musculoskeletal complaints (MSC). The aim of this study was to determine the long-term effects on unspecific MSC by a combined physiotherapy and coaching intervention compared to physiotherapy alone. The coaching intervention focussed on enabling better strategies for coping with work stressors. METHODS: The participants of a previous randomized controlled intervention were invited to participate again in a third follow-up survey 22 months after the end of the intervention. In 2014, 65 nurses completed a 10-week personalised physiotherapy. Additionally, the intervention group (n = 33) passed five individual coaching sessions, plus an opening and closing session. 44 nurses (IG: n = 24; CG: n = 20) passed again a physical examination as well as another questionnaire assessment in 2016. The primary outcome was MSC, secondary outcomes were work ability and work-related well-being. Due to missing data, multiple imputations were conducted using the mice package in R. Data were analysed by ANOVA with two-way repeated measures, t tests for independent samples and Chi-squared tests. RESULTS: In respect of MSC, stronger improvement of movement in the vertebral column was observed in the IG compared to the CG. No differences between the IG and CG regarding other long-term effects were observed. CONCLUSIONS: The results suggest that the combined intervention of work-related coaching and physiotherapy had only a marginally stronger long-term effect with respect to MSC than physiotherapy alone.

A Dead Gene Walking: Convergent Degeneration of a Clade of MADS-Box Genes in Crucifers.

Genes are "born," and eventually they "die." These processes shape the phenotypic evolution of organisms and are hence of great biological interest. If genes die in plants, they generally do so quite rapidly. Here, we describe the fate of GOA-like genes that evolve in a dramatically different manner. GOA-like genes belong to the subfamily of Bsister genes of MIKC-type MADS-box genes. Typical MIKC-type genes encode conserved transcription factors controlling plant development. We show that ABS-like genes, a clade of Bsister genes, are indeed highly conserved in crucifers (Brassicaceae) maintaining the ancestral function of Bsister genes in ovule and seed development. In contrast, their closest paralogs, the GOA-like genes, have been undergoing convergent gene death in Brassicaceae. Intriguingly, erosion of GOA-like genes occurred after millions of years of coexistence with ABS-like genes. We thus describe Delayed Convergent Asymmetric Degeneration, a so far neglected but possibly frequent pattern of duplicate gene evolution that does not fit classical scenarios. Delayed Convergent Asymmetric Degeneration of GOA-like genes may have been initiated by a reduction in the expression of an ancestral GOA-like gene in the stem group of Brassicaceae and driven by dosage subfunctionalization. Our findings have profound implications for gene annotations in genomics, interpreting patterns of gene evolution and using genes in phylogeny reconstructions of species.

Virus-induced gene silencing: empowering genetics in non-model organisms.

Virus-induced gene silencing (VIGS) is an RNA interference-based technology used to transiently knock down target gene expression by utilizing modified plant viral genomes. VIGS can be adapted to many angiosperm species that cover large phylogenetic distances, allowing the analysis of gene functions in species that are not amenable to stable genetic transformation. With a vast amount of sequence information already available and even more likely to become available in the future, VIGS provides a means to analyze the functions of candidate genes identified in large genomic or transcriptomic screens. Here, we provide a comprehensive overview of target species and VIGS vector systems, assess recent key publications in the field, and explain how plant viruses are modified to serve as VIGS vectors. As many reports on the VIGS technique are being published, we also propose minimal reporting guidelines for carrying out these experiments, with the aim of increasing comparability between experiments. Finally, we propose methods for the statistical evaluation of phenotypic results obtained with VIGS-treated plants, as analysis is challenging due to the predominantly transient nature of the silencing effect.

Seed Plant-Specific Gene Lineages Involved in Carpel Development.

Evolutionary innovations are important drivers of speciation and some are the defining characters of entire phyla. One such major innovation is the carpel, the unifying character and most complex plant organ, composed of many clearly distinct tissue types to ensure reproductive success. The origin of the carpel is unknown, but many components of the gene regulatory network (GRN) governing carpel development and their genetic interactions are known from the core eudicot Arabidopsis thaliana. To unravel the evolution of the carpel GRN and to discriminate between "early" and "late" steps in carpel evolution, we calculated thorough phylogeny reconstructions based on sequenced genomes. The A. thaliana carpel GRN members ALCATRAZ (ALC), CRABS CLAW (CRC), HALF FILLED (HAF), HECATE (HEC), INDEHISCENT (IND), NGATHA (NGA), and SPATULA (SPT) were analyzed in their phylogenetic context. We find that the carpel GRN components are of various ages, but interestingly, we identify especially high retention rates for carpel development genes in Brassicaceae. Our data suggest that genes whose A. thaliana homologs are involved in processes already present in the most recent common ancestor of seed plants, such as reproductive meristem termination or adaxial/abaxial polarity specification, are not retained in duplicates after whole genome duplications (WGD). In contrast, genes involved in processes associated with derived carpel characters in Arabidopsis, such as the transmitting tract or style development show a higher gene retention rate after WGD. This work provides a starting point for analyses of carpel genes in early diverging angiosperms which would be very informative for evolutionary studies.

An Evolutionary Framework for Carpel Developmental Control Genes.

Carpels are the female reproductive organs of flowering plants (angiosperms), enclose the ovules, and develop into fruits. The presence of carpels unites angiosperms, and they are suggested to be the most important autapomorphy of the angiosperms, e.g., they prevent inbreeding and allow efficient seed dispersal. Many transcriptional regulators and coregulators essential for carpel development are encoded by diverse gene families and well characterized in Arabidopsis thaliana. Among these regulators are AGAMOUS (AG), ETTIN (ETT), LEUNIG (LUG), SEUSS (SEU), SHORT INTERNODE/STYLISH (SHI/STY), and SEPALLATA1, 2, 3, 4 (SEP1, 2, 3, 4). However, the timing of the origin and their subsequent molecular evolution of these carpel developmental regulators are largely unknown. Here, we have sampled homologs of these carpel developmental regulators from the sequenced genomes of a wide taxonomic sampling of the land plants, such as Physcomitrella patens, Selaginella moellendorfii, Picea abies, and several angiosperms. Careful phylogenetic analyses were carried out that provide a phylogenetic background for the different gene families and provide minimal estimates for the ages of these developmental regulators. Our analyses and published work show that LUG-, SEU-, and SHI/STY-like genes were already present in the Most Recent Common Ancestor (MRCA) of all land plants, AG- and SEP-like genes were present in the MRCA of seed plants and their origin may coincide with the ξ Whole Genome Duplication. Our work shows that the carpel development regulatory network was, in part, recruited from preexisting network components that were present in the MRCA of angiosperms and modified to regulate gynoecium development.

Evolutionary diversification of CYC/TB1-like TCP homologs and their recruitment for the control of branching and floral morphology in Papaveraceae (basal eudicots).

Angiosperms possess enormous morphological variation in plant architectures and floral forms. Previous studies in Pentapetalae and monocots have demonstrated the involvement of TCP domain CYCLOIDEA/TEOSINTE BRANCHED1-like (CYC/TB1) genes in the control of floral symmetry and shoot branching. However, how TCP/CYC-like (CYL) genes originated, evolved and functionally diversified remain unclear. We conducted a comparative functional study in Ranunculales, the sister lineage to all other eudicots, between Eschscholzia californica and Cysticapnos vesicaria, two species of Papaveraceae with actinomorphic and zygomorphic flowers, respectively. Phylogenetic analysis indicates that CYL genes in Papaveraceae form two paralogous lineages, PapaCYL1 and PapaCYL2. Papaveraceae CYL genes show highly diversified expression patterns as well as functions. Enhanced branching by silencing of EscaCYL1 suggests that the role of CYC/TB1-like genes in branching control is conserved in Papaveraceae. In contrast to the arrest of stamen development in Pentapetalae, PapaCYL genes promote stamen initiation and growth. In addition, we demonstrate that CyveCYLs are involved in perianth development, specifying sepal and petal identity in Cysticapnos by regulating the B-class floral organ identity genes. Our data also suggest the involvement of CyveCYL genes in the regulation of flower symmetry in Cysticapnos. Our work provides evidence of the importance of TCP/CYC-like genes in the promotion of morphological diversity across angiosperms.

Prevalence, aetiologies and prognosis of the symptom dizziness in primary care - a systematic review.

BACKGROUND: Dizziness is a common reason for consulting a general practitioner and there is a broad range of possible underlying aetiologies. There are few evidence-based data about prevalence, aetiology and prognosis in primary care. We aimed to conduct a systematic review of symptom-evaluating studies on prevalence, aetiology or prognosis of dizziness in primary care. METHODS: We systematically searched MEDLINE and EMBASE. Two independent researchers screened titles and abstracts according to predefined criteria. We included all studies evaluating the symptoms 'dizziness' or 'vertigo' as a reason for consultation in primary care. We extracted data about study population and methodology and prevalence, aetiology and prognosis. Two raters independently judged study quality and risk of bias. We investigated the variation across studies using forest plots, I2 and prediction intervals. Since we anticipated a great amount of clinical and unexplained statistical heterogeneity, we provided qualitative syntheses instead of pooled estimates. RESULTS: We identified 31 studies (22 on prevalence, 14 on aetiology and 8 on prognosis). Consultation prevalence differs between 1,0 and 15,5%. The most common aetiologies are vestibular/peripheral (5,4-42,1%), benign peripheral positional vertigo (4,3-39,5%), vestibular neuritis (0,6-24,0%), Menière's disease (1,4-2,7%), cardiovascular disease (3,8-56,8%), neurological disease (1,4-11,4%), psychogenic (1,8-21,6%), no clear diagnosis (0,0-80,2%). While studies based on subjective patient assessment reported improvement rates from 37 to 77%, these findings could not be confirmed when applying instruments that measure symptom severity or quality of life. CONCLUSION: There is a broad variety of possible underlying diseases for the symptom dizziness. There exist only few methodologically sound studies concerning aetiology and prognosis of dizziness.

Poly(ADP-ribosyl)ation of Methyl CpG Binding Domain Protein 2 Regulates Chromatin Structure.

The epigenetic information encoded in the genomic DNA methylation pattern is translated by methylcytosine binding proteins like MeCP2 into chromatin topology and structure and gene activity states. We have shown previously that the MeCP2 level increases during differentiation and that it causes large-scale chromatin reorganization, which is disturbed by MeCP2 Rett syndrome mutations. Phosphorylation and other posttranslational modifications of MeCP2 have been described recently to modulate its function. Here we show poly(ADP-ribosyl)ation of endogenous MeCP2 in mouse brain tissue. Consequently, we found that MeCP2 induced aggregation of pericentric heterochromatin and that its chromatin accumulation was enhanced in poly(ADP-ribose) polymerase (PARP) 1(-/-) compared with wild-type cells. We mapped the poly(ADP-ribosyl)ation domains and engineered MeCP2 mutation constructs to further analyze potential effects on DNA binding affinity and large-scale chromatin remodeling. Single or double deletion of the poly(ADP-ribosyl)ated regions and PARP inhibition increased the heterochromatin clustering ability of MeCP2. Increased chromatin clustering may reflect increased binding affinity. In agreement with this hypothesis, we found that PARP-1 deficiency significantly increased the chromatin binding affinity of MeCP2 in vivo. These data provide novel mechanistic insights into the regulation of MeCP2-mediated, higher-order chromatin architecture and suggest therapeutic opportunities to manipulate MeCP2 function.

Genetics of flower development in Ranunculales - a new, basal eudicot model order for studying flower evolution.

Contents 361 I. 361 II. 362 III. 363 IV. 364 V. 364 Acknowledgements 365 References 365 SUMMARY: Ranunculales, the sister group to all other eudicots, encompasses species with a remarkable floral diversity, which are currently emerging as new model organisms to address questions relating to the genetic architecture of flower morphology and its evolution. These questions concern either traits only found in members of the Ranunculales or traits that have convergently evolved in other large clades of flowering plants. We present recent results obtained on floral organ identity and number, symmetry evolution and spur formation in Ranunculales species. We discuss benefits and future prospects of evo-devo studies in Ranunculales, which can provide the opportunity to decipher the genetic architecture of novel floral traits and also to appraise the degree of conservation of genetic mechanisms involved in homoplasious traits.

N-Acyl-Homoserine Lactone Primes Plants for Cell Wall Reinforcement and Induces Resistance to Bacterial Pathogens via the Salicylic Acid/Oxylipin Pathway.

The ability of plants to monitor their surroundings, for instance the perception of bacteria, is of crucial importance. The perception of microorganism-derived molecules and their effector proteins is the best understood of these monitoring processes. In addition, plants perceive bacterial quorum sensing (QS) molecules used for cell-to-cell communication between bacteria. Here, we propose a mechanism for how N-acyl-homoserine lactones (AHLs), a group of QS molecules, influence host defense and fortify resistance in Arabidopsis thaliana against bacterial pathogens. N-3-oxo-tetradecanoyl-l-homoserine lactone (oxo-C14-HSL) primed plants for enhanced callose deposition, accumulation of phenolic compounds, and lignification of cell walls. Moreover, increased levels of oxylipins and salicylic acid favored closure of stomata in response to Pseudomonas syringae infection. The AHL-induced resistance seems to differ from the systemic acquired and the induced systemic resistances, providing new insight into inter-kingdom communication. Consistent with the observation that short-chain AHLs, unlike oxo-C14-HSL, promote plant growth, treatments with C6-HSL, oxo-C10-HSL, or oxo-C14-HSL resulted in different transcriptional profiles in Arabidopsis. Understanding the priming induced by bacterial QS molecules augments our knowledge of plant reactions to bacteria and suggests strategies for using beneficial bacteria in plant protection.