Nuclear actin-related proteins at the core of epigenetic control

Nuclear Actin-Related Proteins (ARPs) and actin combine as heterodimers to bind a large helicase subunit and form a core complex essential to the assembly and function of most chromatin remodeling and modifying machines. They are the most common shared subunits of these large and diverse assemblies in eukaryotes. We recently argued that most nuclear ARPs evolved directly from actin prior to the divergence of the eukaryotic kingdoms and did not evolve from pre-existing ARPs.2 Arabidopsis plants defective in nuclear ARP4, ARP5, ARP6 or ARP7 have extreme developmental phenotypes. Our recent publication demonstrates that ARP5-defective plants are not only dwarfed and have aberrant cell sizes, but are also hypersensitive to mutagenic agents that cause double strand DNA breaks.5 In Smith et al.6 we show that ARP6-defective plants, in addition to their extreme developmental phenotypes like small organs and early flowering, present an apparent Phosphate Starvation Response with strong morphological and molecular phenotypes. Herein, we interpret our latest data in the light of a hypothesis stating that in addition to their roles in overcoming DNA compaction that affects basal gene expression and silencing, nuclear ARP-containing chromatin complexes exert primary epigenetic control over high-level regulatory factors. © 2010 Landes Bioscience

Hijacking membrane transporters for arsenic phytoextraction

Arsenic is a toxic metalloid and recognized carcinogen. Arsenate and arsenite are the most common arsenic species available for uptake by plants. As an inorganic phosphate (Pi) analog, arsenate is acquired by plant roots through endogenous Pi transport systems. Inside the cell, arsenate is reduced to the thiol-reactive form arsenite. Glutathione (GSH)-conjugates of arsenite may be extruded from the cell or sequestered in vacuoles by members of the ATP-binding cassette (ABC) family of transporters. In the present study we sought to enhance both plant arsenic uptake through Pi transporter overexpression, and plant arsenic tolerance through ABC transporter overexpression. We demonstrate that Arabidopsis thaliana plants overexpressing the high-affinity Pi transporter family members, AtPht1;1 or AtPht1;7, are hypersensitive to arsenate due to increased arsenate uptake. These plants do not exhibit increased sensitivity to arsenite. Co-overexpression of the yeast ABC transporter YCF1 in combination with AtPht1;1 or AtPht1;7 suppresses the arsenate-sensitive phenotype while further enhancing arsenic uptake. Taken together, our results support an arsenic transport mechanism in which arsenate uptake is increased through Pi transporter overexpression, and arsenic tolerance is enhanced through YCF1-mediated vacuolar sequestration. This work substantiates the viability of coupling enhanced uptake and vacuolar sequestration as a means for developing a prototypical engineered arsenic hyperaccumulator. © 2012 Elsevier B.V

Arabidopsis actin-related protein ARP5 in multicellular development and DNA repair

Actin-related protein 5 (ARP5) is a conserved subunit of the INO80 chromatin-remodeling complex in yeast and mammals. We have characterized the expression and subcellular distribution of Arabidopsis thaliana ARP5 and explored its role in the epigenetic control of multicellular development and DNA repair. ARP5-specific monoclonal antibodies localized ARP5 protein to the nucleoplasm of interphase cells in Arabidopsis and Nicotiana tabacum. ARP5 promoter-reporter fusions and the ARP5 protein are ubiquitously expressed. A null mutant and a severe knockdown allele produced moderately dwarfed plants with all organs smaller than the wild type. The small and slightly deformed organs such as leaves and hypocotyls were composed of small-sized cells. The ratio of leaf stomata to epidermal cells was high in the mutant, which also exhibited a delayed stomatal development compared with the wild type. Mutant plants were hypersensitive to DNA-damaging reagents including hydroxyurea, methylmethane sulfonate, and bleocin, demonstrating a role for ARP5 in DNA repair. Interestingly, the hypersensitivity phenotype of ARP5 null allele arp5-1 is stronger than the severe knockdown allele arp5-2. Moreover, a wild-type transgene fully complemented all developmental and DNA repair mutant phenotypes. Despite the common participation of both ARP4 and ARP5 in the INO80 complex, ARP4- and ARP5-deficient plants displayed only a small subset of common phenotypes and each displayed novel phenotypes, suggesting that in Arabidopsis they have both shared and unique functions. © 2009 Elsevier Inc. All rights reserved

Transcriptomes of parents identify parenting strategies and sexual conflict in a subsocial beetle

This work was funded by UK NERC grants to M.G.R. and A.J.M. an NERC studentship to D.J.P. the University of Georgia and a US NSF grant to A.J.M. and M.G.R.Parenting in the burying beetle Nicrophorus vespilloides is complex and, unusually, the sex and number of parents that can be present is flexible. Such flexibility is expected to involve specialized behaviour by the two sexes under biparental conditions. Here, we show that offspring fare equally well regardless of the sex or number of parents present. Comparing transcriptomes, we find a largely overlapping set of differentially expressed genes in both uniparental and biparental females and in uniparental males including vitellogenin, associated with reproduction, and takeout, influencing sex-specific mating and feeding behaviour. Gene expression in biparental males is similar to that in non-caring states. Thus, being ‘biparental’ in N. vespilloides describes the family social organization rather than the number of directly parenting individuals. There was no specialization; instead, in biparental families, direct male parental care appears to be limited with female behaviour unchanged. This should lead to strong sexual conflict.Publisher PDFPeer reviewe

Intensivist-based deep sedation using propofol for pediatric outpatient flexible bronchoscopy

AIM To evaluate the safety and efficacy of sedating pediatric patients for outpatient flexible bronchoscopy. METHODS A retrospective chart review was conducted for all children, age 17 years or under who underwent flexible bronchoscopy under deep sedation in an outpatient hospital-based setting. Two sedation regimens were used; propofol only or ketamine prior to propofol. Patients were divided into three age groups; infants (less than 12 mo), toddlers (1-3 years) and children (4-17 years). Demographics, indication for bronchoscopy, sedative dosing, sedation and recovery time and adverse events were reviewed. RESULTS Of the total 458 bronchoscopies performed, propofol only regimen was used in 337 (74%) while propofol and ketamine was used in 121 (26%). About 99% of the procedures were successfully completed. Children in the propofol + ketamine group tend to be younger and have lower weight compared to the propofol only group. Adverse events including transient hypoxemia and hypotension occurred in 8% and 24% respectively. Median procedure time was 10 min while the median discharge time was 35 min. There were no differences in the indication of the procedure, propofol dose, procedure or recovery time in either sedative regimen. When compared to other age groups, infants had a higher incidence of hypoxemia. CONCLUSION Children can be effectively sedated for outpatient flexible bronchoscopy with high rate of success. This procedure should be performed under vigilance of highly trained providers

Language processing skills linked to FMR1 variation: A study of gaze-language coordination during rapid automatized naming among women with the FMR1 premutation

This work is licensed under a Creative Commons Attribution 4.0 International License.The FMR1 premutation (PM) is relatively common in the general population. Evidence suggests that PM carriers may exhibit subtle differences in specific cognitive and language abilities. This study examined potential mechanisms underlying such differences through the study of gaze and language coordination during a language processing task (rapid automatized naming; RAN) among female carriers of the FMR1 PM. RAN taps a complex set of underlying neuropsychological mechanisms, with breakdowns implicating processing disruptions in fundamental skills that support higher order language and executive functions, making RAN (and analysis of gaze/language coordination during RAN) a potentially powerful paradigm for revealing the phenotypic expression of the FMR1 PM. Forty-eight PM carriers and 56 controls completed RAN on an eye tracker, where they serially named arrays of numbers, letters, colors, and objects. Findings revealed a pattern of inefficient language processing in the PM group, including a greater number of eye fixations (namely, visual regressions) and reduced eye-voice span (i.e., the eyes’ lead over the voice) relative to controls. Differences were driven by performance in the latter half of the RAN arrays, when working memory and processing load are the greatest, implicating executive skills. RAN deficits were associated with broader social-communicative difficulties among PM carriers, and with FMR1-related molecular genetic variation (higher CGG repeat length, lower activation ratio, and increased levels of the fragile X mental retardation protein; FMRP). Findings contribute to an understanding of the neurocognitive profile of PM carriers and indicate specific gene-behavior associations that implicate the role of the FMR1 gene in language-related processes.NIH R01DC010191NIH R01MH091131NIH P30 HD0311

Links between looking and speaking in autism and first-degree relatives: insights into the expression of genetic liability to autism

Abstract Background Rapid automatized naming (RAN; naming of familiar items presented in an array) is a task that taps fundamental neurocognitive processes that are affected in a number of complex psychiatric conditions. Deficits in RAN have been repeatedly observed in autism spectrum disorder (ASD), and also among first-degree relatives, suggesting that RAN may tap features that index genetic liability to ASD. This study used eye tracking to examine neurocognitive mechanisms related to RAN performance in ASD and first-degree relatives, and investigated links to broader language and clinical-behavioral features. Methods Fifty-one individuals with ASD, biological parents of individuals with ASD (n = 133), and respective control groups (n = 45 ASD controls; 58 parent controls) completed RAN on an eye tracker. Variables included naming time, frequency of errors, and measures of eye movement during RAN (eye-voice span, number of fixations and refixations). Results Both the ASD and parent-ASD groups showed slower naming times, more errors, and atypical eye-movement patterns (e.g., increased fixations and refixations), relative to controls, with differences persisting after accounting for spousal resemblance. RAN ability and associated eye movement patterns were correlated with increased social-communicative impairment and increased repetitive behaviors in ASD. Longer RAN times and greater refixations in the parent-ASD group were driven by the subgroup who showed clinical-behavioral features of the broad autism phenotype (BAP). Finally, parent-child dyad correlations revealed associations between naming time and refixations in parents with the BAP and increased repetitive behaviors in their child with ASD. Conclusions Differences in RAN performance and associated eye movement patterns detected in ASD and in parents, and links to broader social-communicative abilities, clinical features, and parent-child associations, suggest that RAN-related abilities might constitute genetically meaningful neurocognitive markers that can help bridge connections between underlying biology and ASD symptomatology

The effect of training in reduced energy density eating and food self-monitoring accuracy on weight loss maintenance

Background: Failure to maintain weight losses in lifestyle change programs continues to be a major problem and warrants investigation of innovative approaches to weight control.Objective: The goal of this study was to compare two novel group interventions, both aimed at improving weight loss maintenance, with a control group.Methods and Procedures: A total of 103 women lost weight on a meal replacement&ndash;supplemented diet and were then randomized to one of three conditions for the 14-week maintenance phase: cognitive-behavioral treatment (CBT); CBT with an enhanced food monitoring accuracy (EFMA) program; or these two interventions plus a reduced energy density eating (REDE) program. Assessments were conducted periodically through an 18-month postintervention. Outcome measures included weight and self-reported dietary intake. Data were analyzed using completers only as well as baseline-carried-forward imputation.Results: Participants lost an average of 7.6 plusminus 2.6 kg during the weight loss phase and 1.8 plusminus 2.3 kg during the maintenance phase. Results do not suggest that the EFMA intervention was successful in improving food monitoring accuracy. The REDE group decreased the energy density (ED) of their diets more so than the other two groups. However, neither the REDE nor the EFMA condition showed any advantage in weight loss maintenance. All groups regained weight between 6- and 18-month follow-ups.Discussion: Although no incremental weight maintenance benefit was observed in the EFMA or EFMA + REDE groups, the improvement in the ED of the REDE group\u27s diet, if shown to be sustainable in future studies, could have weight maintenance benefits.<br /