A fern AINTEGUMENTA gene mirrors BABY BOOM in promoting apogamy in Ceratopteris richardii.

Asexual reproduction is widespread in land plants, including ferns where 10% of all species are obligate asexuals. In these ferns, apogamous sporophytes are generated directly from gametophytes, bypassing fertilization. In the model fern Ceratopteris richardii, a sexual species, apogamy can be induced by culture on high sugar media. BABY BOOM (BBM) genes in angiosperms are known to promote somatic embryogenesis, which like apogamy produce sporophytes without fertilization. Here, a Brassica napus BBM (BnBBM) was used to investigate genetic similarity between apogamy in ferns and somatic embryogenesis in angiosperms. A C. richardii transcriptome was constructed from which one AINTEGUMENTA-LIKE unigene, CrANT, was identified. Whole mount in situ hybridization showed that CrANT is expressed in sperm and fertilized eggs. Phylogenetic analysis grouped CrANT with other non-seed-plant ANT genes to the euANT clade but in a branch separate from BBM genes. Overexpression of CrANT or BnBBM promotes apogamy in C. richardii without sugar supplement. CrANT knockdown gametophytes responded weakly to sugar for apogamy promotion. Theses results suggest some genetic conservation between apogamy and somatic embryogenesis and that such asexual reproduction may be ancient.

Convergence of genes and cellular pathways dysregulated in autism spectrum disorders.

Rare copy-number variation (CNV) is an important source of risk for autism spectrum disorders (ASDs). We analyzed 2,446 ASD-affected families and confirmed an excess of genic deletions and duplications in affected versus control groups (1.41-fold, p = 1.0 × 10(-5)) and an increase in affected subjects carrying exonic pathogenic CNVs overlapping known loci associated with dominant or X-linked ASD and intellectual disability (odds ratio = 12.62, p = 2.7 × 10(-15), ∼3% of ASD subjects). Pathogenic CNVs, often showing variable expressivity, included rare de novo and inherited events at 36 loci, implicating ASD-associated genes (CHD2, HDAC4, and GDI1) previously linked to other neurodevelopmental disorders, as well as other genes such as SETD5, MIR137, and HDAC9. Consistent with hypothesized gender-specific modulators, females with ASD were more likely to have highly penetrant CNVs (p = 0.017) and were also overrepresented among subjects with fragile X syndrome protein targets (p = 0.02). Genes affected by de novo CNVs and/or loss-of-function single-nucleotide variants converged on networks related to neuronal signaling and development, synapse function, and chromatin regulation.

Evolutionary origins of pectin methylesterase genes associated with novel aspects of angiosperm pollen tube walls.

The early evolution of angiosperms was marked by a number of innovations of the reproductive cycle including an accelerated fertilization process involving faster transport of sperm to the egg via a pollen tube. Fast pollen tube growth rates in angiosperms are accompanied by a hard shank-soft tip pollen tube morphology. A critical actor in that morphology is the wall-embedded enzyme pectin methylesterase (PME), which in type II PMEs is accompanied by a co-transcribed inhibitor, PMEI. PMEs convert the esterified pectic tip wall to a stiffer state in the subapical flank by pectin de-esterification. It is hypothesized that rapid and precise targeting of PME activity was gained with the origin of type II genes, which are derived and have only expanded since the origin of vascular plants. Pollen-active PMEs have yet to be reported in early-divergent angiosperms or gymnosperms. Gene expression studies in Nymphaea odorata found transcripts from four type II VGD1-like and 16 type I AtPPME1-like homologs that were more abundant in pollen and pollen tubes than in vegetative tissues. The near full-length coding sequence of one type II PME (NoPMEII-1) included at least one PMEI domain. The identification of possible VGD1 homologs in an early-diverging angiosperm suggests that the refined control of PMEs that mediate de-esterification of pectins near pollen tube tips is a conserved feature across angiosperms. The recruitment of type II PMEs into a pollen tube elongation role in angiosperms may represent a key evolutionary step in the development of faster growing pollen tubes.

Conservation of Male Sterility 2 function during spore and pollen wall development supports an evolutionarily early recruitment of a core component in the sporopollenin biosynthetic pathway.

The early evolution of plants required the acquisition of a number of key adaptations to overcome physiological difficulties associated with survival on land. One of these was a tough sporopollenin wall that enclosed reproductive propagules and provided protection from desiccation and UV-B radiation. All land plants possess such walled spores (or their derived homologue, pollen). We took a reverse genetics approach, consisting of knock-out and complementation experiments to test the functional conservation of the sporopollenin-associated gene MALE STERILTY 2 (which is essential for pollen wall development in Arabidopsis thaliana) in the bryophyte Physcomitrella patens. Knock-outs of a putative moss homologue of the A. thaliana MS2 gene, which is highly expressed in the moss sporophyte, led to spores with highly defective walls comparable to that observed in the A. thaliana ms2 mutant, and extremely compromised germination. Conversely, the moss MS2 gene could not rescue the A. thaliana ms2 phenotype. The results presented here suggest that a core component of the biochemical and developmental pathway required for angiosperm pollen wall development was recruited early in land plant evolution but the continued increase in pollen wall complexity observed in angiosperms has been accompanied by divergence in MS2 gene function.

Genome-wide transcriptomic analysis of the sporophyte of the moss Physcomitrella patens.

Bryophytes, the most basal of the extant land plants, diverged at least 450 million years ago. A major feature of these plants is the biphasic alternation of generations between a dominant haploid gametophyte and a minor diploid sporophyte phase. These dramatic differences in form and function occur in a constant genetic background, raising the question of whether the switch from gametophyte-to-sporophyte development reflects major changes in the spectrum of genes being expressed or alternatively whether only limited changes in gene expression occur and the differences in plant form are due to differences in how the gene products are put together. This study performed replicated microarray analyses of RNA from several thousand dissected and developmentally staged sporophytes of the moss Physcomitrella patens, allowing analysis of the transcriptomes of the sporophyte and early gametophyte, as well as the early stages of moss sporophyte development. The data indicate that more significant changes in transcript profile occur during the switch from gametophyte to sporophyte than recently reported, with over 12% of the entire transcriptome of P. patens being altered during this major developmental transition. Analysis of the types of genes contributing to these differences supports the view of the early sporophyte being energetically and nutritionally dependent on the gametophyte, provides a profile of homologues to genes involved in angiosperm stomatal development and physiology which suggests a deeply conserved mechanism of stomatal control, and identifies a novel series of transcription factors associated with moss sporophyte development.

Palliative care in the older adult Veteran.

The United States military Veteran population is aging, thus leading to a group of Veterans who have functional disabilities, sensory impairments, and geriatric syndromes such as frailty and dementia. As they age, Veterans are also at risk of being diagnosed with a variety of serious illnesses, such as neurologic conditions and cancers, some of which are a consequence of prior military service or toxic exposures. In addition to frailty and multicomplexity, Veterans have higher rates of mental health disorders than civilians. All of these factors lead to a population of older Veterans who can benefit from palliative care involvement. Major tenets of palliative care focus on enhancing quality of life and provision of goal-concordant care, which are also aims of the services provided by the Veterans Health Administration (VHA) to all enrolled Veterans. Palliative care involvement in the holistic care of Veterans can deliver expert pain and symptom management, promote Veteran-centric plans of care, and provide crucial support of complex medical decision making often required for those Veterans with serious illness. In this review article, we discuss the unique palliative care needs of Veterans as they age, while also sharing information about relevant resources and services provided by the VHA.

Affective-motivational brain responses to direct gaze in children with autism spectrum disorder.

BACKGROUND: It is unclear why children with autism spectrum disorders (ASD) tend to be inattentive to, or even avoid eye contact. The goal of this study was to investigate affective-motivational brain responses to direct gaze in children with ASD. To this end, we combined two measurements: skin conductance responses (SCR), a robust arousal measure, and asymmetry in frontal electroencephalography (EEG) activity which is associated with motivational approach and avoidance tendencies. We also explored whether degree of eye openness and face familiarity modulated these responses. METHODS: Skin conductance responses and frontal EEG activity were recorded from 14 children with ASD and 15 typically developing children whilst they looked at familiar and unfamiliar faces with eyes shut, normally open or wide-open. Stimuli were presented in such a way that they appeared to be looming towards the children. RESULTS: In typically developing children, there were no significant differences in SCRs between the different eye conditions, whereas in the ASD group the SCRs were attenuated to faces with closed eyes and increased as a function of the degree of eye openness. In both groups, familiar faces elicited marginally greater SCRs than unfamiliar faces. In typically developing children, normally open eyes elicited greater relative left-sided frontal EEG activity (associated with motivational approach) than shut eyes and wide-open eyes. In the ASD group, there were no significant differences between the gaze conditions in frontal EEG activity. CONCLUSIONS: Collectively, the results replicate previous finding in showing atypical modulation of arousal in response to direct gaze in children with ASD but do not support the assumption that this response is associated with an avoidant motivational tendency. Instead, children with ASD may lack normative approach-related motivational response to eye contact.

Relationships between intra-individual variability and subclinical psychosis.

Extensive research indicates that elevated intra-individual variability (IIV) of reaction time is associated with subclinical psychosis, as well as clinically diagnosed psychotic disorder. However, findings regarding the details of this relationship are equivocal. In particular, it is unknown whether associations between elevated IIV and subclinical psychosis are specific to certain psychotic symptoms or to complex reaction time tasks. Data from 492 undergraduates from the University of Otago were used to address this issue. Schizotypy and psychotic-like experiences (PLE) were assessed via interview and questionnaire, and participants completed both a simple reaction time (SRT) task and a continuous performance task-identical pairs version (CPT-IP). The individual standard deviation and coefficient of variation (ICV) were used as measures of IIV. Participants reporting PLE were more likely to have elevated ICV on the CPT-IP. These associations were specific to paranoid psychotic experiences, and to the suspiciousness subscale of the Schizotypal Personality Questionnaire. There were also weak associations between SRT ICV and PLE. The inclusion of a battery of reaction time tasks assessing different aspects of cognitive control is suggested for future research, and the findings are discussed in relation to theoretical approaches to paranoia and delusions.

Intra-individual variability and psychotic-like experiences in adolescents: Findings from the ALSPAC cohort.

Clinical and epidemiological studies have demonstrated associations between elevated intra-individual variability (IIV) of reaction time and psychotic disorders. However, little attention has been paid to the relationship between performance stability and psychotic-like experiences (PLE) in adolescence, before psychotic disorder onset. Data from 6702 children from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used to address this issue. Children took part in a semi-structured clinical interview regarding psychotic symptoms at age 12 and 18, and reaction time variability was assessed at age 13 and 15. Children who had elevated IIV at age 15 were more likely to report suspected or definite PLE at age 18, with larger associations being found for more frequent or bizarre symptoms. Elevated IIV at age 15 was also associated with persistent PLE between age 12 and 18. These findings tentatively suggest that elevated IIV in early adolescence may be predictive of later PLE, and offer some support for the notion of a psychosis continuum.

Embodied cognition: Is activation of the motor cortex essential for understanding action verbs?

In 8 experiments using language processing tasks ranging from lexical decision to sensibility judgment, participants made hand or foot responses after reading hand- or foot-associated words such as action verbs. In general, response time (RT) tended to be faster when the hand- versus foot-associated word was compatible with the limb that was required to respond (e.g., hand response to a hand-associated word) than when it was incompatible (e.g., foot response to a hand-associated word). To see whether this compatibility effect reflects differential hand- versus foot-specific motor activation produced by the words, as suggested by some embodied theories of language understanding, we monitored 2 event-related potential (ERP) measures previously found to be sensitive to the activation of these limbs. As expected, the ERP results replicated previous findings that the monitored ERPs differ for hand versus foot movements. More importantly, the ERPs provided no evidence of any difference for hand- versus foot-associated words. Thus, the results weaken previous claims that the understanding of action verbs requires activation of the motor areas used to carry out the named action. Instead, they support claims that language-related compatibility effects on RT may arise prior to motor processes, which implies that such effects are not decisive evidence for embodied language understanding. (PsycINFO Database Record

Autism spectrum disorder: Consensus guidelines on assessment, treatment and research from the British Association for Psychopharmacology.

An expert review of the aetiology, assessment, and treatment of autism spectrum disorder, and recommendations for diagnosis, management and service provision was coordinated by the British Association for Psychopharmacology, and evidence graded. The aetiology of autism spectrum disorder involves genetic and environmental contributions, and implicates a number of brain systems, in particular the gamma-aminobutyric acid, serotonergic and glutamatergic systems. The presentation of autism spectrum disorder varies widely and co-occurring health problems (in particular epilepsy, sleep disorders, anxiety, depression, attention deficit/hyperactivity disorder and irritability) are common. We did not recommend the routine use of any pharmacological treatment for the core symptoms of autism spectrum disorder. In children, melatonin may be useful to treat sleep problems, dopamine blockers for irritability, and methylphenidate, atomoxetine and guanfacine for attention deficit/hyperactivity disorder. The evidence for use of medication in adults is limited and recommendations are largely based on extrapolations from studies in children and patients without autism spectrum disorder. We discuss the conditions for considering and evaluating a trial of medication treatment, when non-pharmacological interventions should be considered, and make recommendations on service delivery. Finally, we identify key gaps and limitations in the current evidence base and make recommendations for future research and the design of clinical trials.

Improvement of tissue culture, genetic transformation, and applications of biotechnology to Brassica.

Development of in vitro plant regeneration method from Brassica explants via organogenesis and somatic embryogenesis is influenced by many factors such as culture environment, culture medium composition, explant sources, and genotypes which are reviewed in this study. An efficient in vitro regeneration system to allow genetic transformation of Brassica is a crucial tool for improving its economical value. Methods to optimize transformation protocols for the efficient introduction of desirable traits, and a comparative analysis of these methods are also reviewed. Hence, binary vectors, selectable marker genes, minimum inhibitory concentration of selection agents, reporter marker genes, preculture media, Agrobacterium concentration and regeneration ability of putative transformants for improvement of Agrobacterium-mediated transformation of Brassica are discussed.

Origin and function of stomata in the moss Physcomitrella patens.

Stomata are microscopic valves on plant surfaces that originated over 400 million years (Myr) ago and facilitated the greening of Earth's continents by permitting efficient shoot-atmosphere gas exchange and plant hydration1. However, the core genetic machinery regulating stomatal development in non-vascular land plants is poorly understood2-4 and their function has remained a matter of debate for a century5. Here, we show that genes encoding the two basic helix-loop-helix proteins PpSMF1 (SPEECH, MUTE and FAMA-like) and PpSCREAM1 (SCRM1) in the moss Physcomitrella patens are orthologous to transcriptional regulators of stomatal development in the flowering plant Arabidopsis thaliana and essential for stomata formation in moss. Targeted P. patens knockout mutants lacking either PpSMF1 or PpSCRM1 develop gametophytes indistinguishable from wild-type plants but mutant sporophytes lack stomata. Protein-protein interaction assays reveal heterodimerization between PpSMF1 and PpSCRM1, which, together with moss-angiosperm gene complementations6, suggests deep functional conservation of the heterodimeric SMF1 and SCRM1 unit is required to activate transcription for moss stomatal development, as in A. thaliana7. Moreover, stomata-less sporophytes of ΔPpSMF1 and ΔPpSCRM1 mutants exhibited delayed dehiscence, implying stomata might have promoted dehiscence in the first complex land-plant sporophytes.

New interview and observation measures of the broader autism phenotype: group differentiation.

To identify the broader autism phenotype (BAP), the Family History Interview subject and informant versions and an observational tool (Impression of Interviewee), were developed. This study investigated whether the instruments differentiated between parents of children with autism, and parents of children with Down syndrome (DS). The BAP scores of parents of 28 multiplex autism families were compared with parents from, 32 DS families. The BAP measures provided good group differentiation but when considered together, the subject interview did not improve group differentiation. The differentiation was better for fathers than mothers. The measures do carry an important degree of validity; whether they can differentiate the BAP from other social disorders should be tested.

New Interview and Observation Measures of the Broader Autism Phenotype: Description of Strategy and Reliability Findings for the Interview Measures.

Clinical genetic studies confirm the broader autism phenotype (BAP) in some relatives of individuals with autism, but there are few standardized assessment measures. We developed three BAP measures (informant interview, self-report interview, and impression of interviewee observational scale) and describe the development strategy and findings from the interviews. International Molecular Genetic Study of Autism Consortium data were collected from families containing at least two individuals with autism. Comparison of the informant and self-report interviews was restricted to samples in which the interviews were undertaken by different researchers from that site (251 UK informants, 119 from the Netherlands). Researchers produced vignettes that were rated blind by others. Retest reliability was assessed in 45 participants. Agreement between live scoring and vignette ratings was very high. Retest stability for the interviews was high. Factor analysis indicated a first factor comprising social-communication items and rigidity (but not other repetitive domain items), and a second factor comprised mainly of reading and spelling impairments. Whole scale Cronbach's alphas were high for both interviews. The correlation between interviews for factor 1 was moderate (adult items 0.50; childhood items 0.43); Kappa values for between-interview agreement on individual items were mainly low. The correlations between individual items and total score were moderate. The inclusion of several factor 2 items lowered the overall Cronbach's alpha for the total set. Both interview measures showed good reliability and substantial stability over time, but the findings were better for factor 1 than factor 2. We recommend factor 1 scores be used for characterising the BAP.

Commentary--Bridging the research and practice gap in autism: the importance of creating research partnerships with schools.

While the last 10 years have seen a significant increase in research published on early intervention and autism, there is a persistent disconnect between educational research and practice. Governments have invested significant funds in autism education, and a range of approaches have been implemented in schools, but there is limited research exploring whether these educational strategies are effective and a lack of involvement of teaching professionals in the research. Given that the majority of children and young people with autism spend most of their time in school and not in early or specialised intervention programmes, there is a compelling need to conduct better educational research and implement educational interventions in schools. We argue that building collaborative partnerships between researchers and school practitioners is central to achieving improved understanding of, and outcomes for, pupils on the autism spectrum. This commentary offers perspectives from teachers about their experiences of, and priorities for, research, and also presents a model of collaboration between autism school practitioners and researchers, which could support a more integrated approach to research. We reflect on the strengths and challenges of this as well as outcomes achieved so far.

A global public health strategy for autism spectrum disorders.

In recent years, there has been increasing awareness about autism spectrum disorders (ASD) around the world, including in low and middle income countries. Unlike countries in Western Europe and North America where infrastructure and capacity are available to help meet some of the needs of individuals with ASD, little expertise or capacity exists in most of the developing world. In 2008 Autism Speaks launched the Global Autism Public Health (GAPH) Initiative to facilitate the development of systematic and sustainable solutions for enhancing global autism awareness, research, training and service delivery. In the last 3 years Autism Speaks has established collaboration with stakeholders from over 20 countries who are working alongside dedicated local and international stakeholders to effect change. In this article, the GAPH framework is described, along with a few brief case examples that illustrate how the framework for implementation of the model can occur. GAPH is still in its infancy but has the potential to have significant impact through inclusive collaboration with local and international stakeholders to develop effective and sustainable public health solutions for disseminating best practices and delivering tangible benefits to individuals with ASD and their families.

Evolutionary development of the plant and spore wall.

BACKGROUND AND AIMS: Many key innovations were required to enable plants to colonize terrestrial habitats successfully. One of these was the acquisition of a durable spore/pollen wall capable of withstanding the harsh desiccating and UV-B-rich environment encountered on land. The spores of 'lower' spore-bearing plants and the pollen of 'higher' seed plants are homologous. In recent years, researchers have begun to investigate the molecular genetics of pollen wall development in angiosperms (including the model organism Arabidopsis thaliana). However, research into the molecular genetics of spore wall development in more basal plants has thus far been extremely limited. This review summarizes the literature on spore/pollen wall development, including the molecular genetics associated with pollen wall development in angiosperms, in a preliminary attempt to identify possible candidate genes involved in spore wall development in more basal plants. PRESENCE IN MOSS OF GENES INVOLVED IN POLLEN WALL DEVELOPMENT: Bioinformatic studies have suggested that genes implicated in pollen wall development in angiosperms are also present in moss and lycopsids, and may therefore be involved in spore wall development in basal plants. This suggests that the molecular genetics of spore/pollen development are highly conserved, despite the large morphological and functional differences between spores and pollen. FUTURE WORK: The use of high-throughput sequencing strategies and/or microarray experiments at an appropriate stage of 'lower' land plant sporogenesis will allow the identification of candidate genes likely to be involved in the development of the spore wall by way of comparison with those genes known to be involved in pollen wall development. Additionally, by conducting gene knock-out and gene swap experiments between 'lower' land plant species, such as the moss model species Physcomitrella patens, and the angiosperm model species arabidopsis it will be possible to test the role of these candidate genes.