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Some introduced passerine species can cause considerable damage to arable crops in New Zealand. These crops are usually surrounded by hedgerows and, in Canterbury, these are commonly Monterey pine (Pinus radiata) and macrocarpa (Cupressus macrocarpa). The present study aimed to determine whether bird abundance and species composition differed among field margins bordered either by hedgerows of common species (pine and macrocarpa), mixed hedgerows (a variety of native and introduced plant species) or bare fence lines (no hedgerow). The numbers and species of birds along line transects traversing field margins were recorded on three different farms during spring and summer 2012. Generally, the same 12 introduced bird species were found along the different margins. However, a greater number of chaffinch (Fringilla coelebs), European goldfinch (Carduelis carduelis), European greenfinch (Carduelis chloris) and, to a lesser extent, house sparrow (Passer domesticus) were recorded in common hedgerows than in mixed species hedgerows and bare fence lines. This study indicates that composition of vegetation at field margins may influence the relative abundance of introduced birds. [ABSTRACT FROM PUBLISHER]

The movement of managed alfalfa leafcutting bees (Megachile rotundata (F.)) in and around carrot flowers is compared with that of the honey bee (Apis mellifera L.) in a field trial to assess their relative efficacy as pollinators of hybrid carrot seed crops. Seed set is measured on carrot flowers inside cages with and without alfalfa leafcutting bees and compared with seed set in open field conditions in the presence of honey bees. Non-caged alfalfa leafcutting bees spend a similar amount of time on umbels and visit a similar number of umblets per umble as honey bees. Seed yield (number and weight of seeds) for flowers pollinated by caged alfalfa leafcutting bees is similar to that of flowers pollinated mainly by honey bees. However, it is not known how effective alfalfa leafcutting bees are compared with honey bees when not confined in cages (i.e. open pollination) under a range of commercial field conditions, particularly in the absence of plant species preferred by alfalfa leafcutting bees. [ABSTRACT FROM AUTHOR]

Techniques to recruit and retain college fraternity and sorority members who reported past 30-day smoking into a cessation trial are described. Recruitment efforts included relationship-building, raffles, and screening survey administration during existing meetings. Surveys were administered to 76% (n = 3,276) of members in 30 chapters, 79% of eligible members agreed to participate, and 76% of those completed assessments and were enrolled in the trial (n = 452). The retention rate was 73%. Retention efforts included cash incentives, flexible scheduling, multiple reminders, chapter incentives, and use of chapter members as study personnel. Retention was not related to demographic, behavioral, or group characteristics. The strategies of partnership, convenience, and flexibility appear effective and may prove useful to investigators recruiting similar samples. © 2010 Wiley Periodicals, Inc. Res Nurs Health 33:144-155, 2010 [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this research note was to examine the sample representation, feasibility and completion, and data quality when using an unmoderated remote study (i.e., conducted without direct contact with a researcher) for a listening comprehension task with 4- to 11-year-old children., Method: Thirty-five participants met inclusionary criteria for this study. Sample representation was examined descriptively. Feasibility and completion (i.e., submission of parent questionnaires and more than 50% of task with no missing data) were examined descriptively and compared with differences of proportions tests. Data quality (i.e., missing data for items with interference or not codable) was examined descriptively with multilevel logistic regression models, as well as one-sample proportions tests by listening comprehension task and participant characteristics., Results: Our sample skewed toward predominantly White and toward families with highly educated parents. Overall, most participants completed the task and had quality data (i.e., audibly clear responses that could be coded, few missing responses, and task completion) in this unmoderated format. There were not any statistically significant effects across participant characteristics in terms of rates of completion. Data quality only significantly differed by response type with mouse selection having the least amount of missing data followed by prompted audio-recorded questions and then open-ended audio-recorded questions., Conclusions: The unmoderated remote study approach seems feasible for a listening comprehension task for most children ages 4-11 years old. Future work is needed to determine if these results apply to samples with broader representation. Overall, we found good data quality despite the less controlled environment in remote studies., Supplemental Material: https://doi.org/10.23641/asha.23114924.

Visual, as compared to verbal, tasks are often assumed to be easier for individuals with autism spectrum disorder (ASD), but is this true for story comprehension? This study evaluated story comprehension monitoring across visual, listening, and written modalities and assessed predictors in two closely matched groups (age, socioeconomic status, language, nonverbal cognition, and word reading) of children and adolescents (8-14 years) with ASD (n = 20) and typical development (typically developing [TD]; n = 20). The results of mixed-effects models indicated that story comprehension monitoring was low overall, and performance was comparable across visual, listening, and written modalities for participants with ASD. Age, vocabulary, nonverbal working memory, response and distractor inhibition, and social communication significantly predicted comprehension monitoring., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The purposes of this study were to (a) examine children's access to services for their speech and language disorders during their lifetimes; (b) identify any child, disorder, and family characteristics associated with access to services; and (c) describe the speech and language service providers among children who received care., Study Design: Data from the 2012 National Health Interview Survey were used for this retrospective cohort study. Our sample included 491 children (ages 3;0-17;11 [years;months]) with speech disorders and 333 children with language disorders. We measured the receipt of services for speech or language difficulties (main outcome) and the type of professional providing services (secondary outcome). We examined associations between services and child, disorder, and family characteristics., Results: Approximately 75% of children with speech and language disorders had ever received services for their difficulties. Privately insured children and children with co-occurring conditions were more likely to receive services than their peers who were uninsured (speech: 6.1 [1.7,21.3]; language: 6.6 [1.3,32.9]) and had no co-occurring conditions (speech: 2.1 [1.2,3.9]; language: 2.9 [1.5,5.5]). Speech-language pathologists (SLPs) were the most commonly reported provider of services (speech: 68%, language: 60%) followed by early interventionists., Conclusions: Most children with speech and language disorders received services. However, disparities existed by race/ethnicity, health insurance type, co-occurring diagnoses, and disorder duration (speech only). Most children who received services were being provided with care by the experts of speech and language: SLPs. Updated population-based data and implementation studies are needed to document speech and language screening, referral, and access to services., Supplemental Material: https://doi.org/10.23641/asha.19799389.

In this epilogue for the Clinicians and Researchers Navigating Implementation Science in CSD forum, we begin by summarizing the eight articles in this forum that describe where the field is in terms of published implementation science (IS) articles in communication sciences and disorders (CSD) and how numerous teams have begun incorporating IS into their research programs. We then situate these articles across three themes: (1) levels of analysis and support; (2) research methods, frameworks, and models; and (3) underserved populations. Next, we consider the challenges and opportunities for conducting IS in CSD. Finally, we conclude by offering tangible steps for researchers, department heads, clinicians, patients, organizations/administrators, and funders in doing and supporting IS research in CSD.

In this prologue, we introduce readers to the Forum: Clinicians and Researchers Navigating Implementation Science in CSD. Implementation science (IS), or the study of the adoption of evidence-based practice in real-world settings, is a key area of development in communication sciences and disorders (CSD). The goal of this forum was to show by example how researchers and clinicians are collaborating to begin to apply IS in CSD. This goal culminated in a scoping review of IS in CSD, a tutorial on incorporating IS into clinical practice research, three articles on stakeholder engagement, and three examples of IS studies in CSD included in this forum. We hope this forum helps clinicians and researchers to begin wherever they are in their knowledge and understanding of IS in CSD.

An insect's fitness varies on different host plant species, and can be affected by previous host feeding experience. In New Zealand, Bactericera cockerelli (the tomato potato psyllid (TPP)) overwinter on various host species, and later migrate to annually grown crop host plants. How changing host plant species affects the insect's fitness is unknown. This study evaluated if transferring adult TPP from non-crop to crop host species impacts the development and survival of their progeny. TPP were reared on non-crop host species, boxthorn, poroporo, and crop host species, potato and tomato. Adults were transferred from non-crop to the crop host species and allowed to oviposit for 48 hours before being removed. The eggs and nymphs were monitored every 24 hours for the development and survival of each life stage. The incubation period of eggs from adults transferred from poroporo to tomato was 6.9 days, and for boxthorn to tomato was 7.2 days, and was less than for eggs of adults moved from tomato to tomato (9.0 days) and potato to potato (9.2 days) (P < 0.05). Nymph developmental time was similar for all treatments. Total development time (egg to adult) was shorter for the progeny of adults from poroporo transferred to tomato (20.5 days) than those from tomato to tomato (23.2). The survival of eggs did not differ across treatments. Fewer nymphs survived when adults were transferred from tomato to tomato (50.4%) than those from poroporo to tomato (92.1%) (P < 0.05). Total survival (egg to adult) was higher for progeny of adults transferred from poroporo to tomato (80.0%) compared to boxthorn to potato (35.3%), boxthorn to boxthorn (40.7%), poroporo to potato (33.9%) and tomato to tomato (37.6%) (P < 0.05). The implications of this shift in fitness are discussed in relation to TPP management., Competing Interests: The authors have declared that no competing interests exist.

Purpose Reading comprehension is consistently poor in many school-age children with autism spectrum disorder (ASD). The purpose of this tutorial is to provide an overview from a multicomponent view on the many predictors that may contribute to reading comprehension difficulties in ASD. Method This tutorial reviews current literature on profiles and predictors of reading comprehension in ASD. The review is situated from a multicomponent theoretical view based on the "direct and indirect effects of reading" model that builds on the familiar "simple view of reading." Each component, including word reading, listening comprehension, morphosyntax, vocabulary, working memory, comprehension monitoring, inferencing, and theory of mind, is separately reviewed, with consideration of the current evidence for their contribution to reading comprehension in ASD. At the end of each section, key takeaways are provided. To conclude, a summary with general clinical implications, case examples, and recommendations for future research across all components is offered. Conclusions Reading comprehension in ASD may be affected by any one or several components in any given individual. Speech-language pathologists have expertise and play a critical role in assessing and intervening on these components. The age and language status (language impaired or not) of a child are emerging as important factors for what to assess and consider for intervention. However, more research is needed that intentionally examines language status, evaluates reading comprehension at targeted ages or narrower age ranges, and/or examines language and reading development longitudinally.

'Lure-and-infect' is an insect pest management strategy with high potential but so far there are few examples of its application. Using traps as surrogates for auto-dissemination devices, we tested the attractiveness to naturally occurring thrips (Thysanoptera: Thripidae) of three trap types differing in colour and structure, with and without the thrips lure methyl isonicotinate (MI), and sticky plate traps as a control. The aim was to find more effective traps that could be further developed into devices for auto-dissemination and lure-and-infect of thrips. The number of thrips captured varied substantially with trap type and the presence of the MI lure. We found a high visual response to a sticky 'white ruffle' trap (i.e., a 30-cm-long cylindrical outline of folded fabric), compared to a commonly used blue sticky plate trap (Bug-scan) as the control. This effect was seen both in a greenhouse with roses ( Rosa spp.), where we encountered western flower thrips, Frankliniella occidentalis (Pergande), and in a grass field, where we encountered onion thrips, Thrips tabaci Lindeman, and New Zealand flower thrips, Thrips obscuratus (Crawford). In the absence of MI, the white ruffle trap caught 7-22× more thrips than the control Bug-scan trap. A similarly designed blue ruffle trap and a modified Lynfield trap caught lower thrips numbers than the white ruffle and the control Bug-scan traps. Presence of MI substantially increased the captures of T. tabaci in all three trap types in the field (2.5-18×). In the greenhouse, without MI the white ruffle trap caught 3.5-14× more thrips than the Bug-scan, blue ruffle, or modified Lynfield traps. Presence of MI increased the captures of F. occidentalis males and females in the Lynfield and blue ruffle traps (1.4-2.8×), but not in the white ruffle trap in the greenhouse (ca. 1.1×). The importance of visual and olfactory factors for the design of effective auto-dissemination and lure-and-infect strategies for thrips management is discussed., (© 2020 The Authors. Entomologia Experimentalis et Applicata published by John Wiley & Sons Ltd on behalf of Netherlands Entomological Society.)

Sirtuin 3 (SIRT3) is a deacetylase that modulates proteins that control metabolism and protects against oxidative stress. Modulation of SIRT3 activity has been proposed as a promising therapeutic target for ameliorating metabolic diseases and associated cardiac disturbances. In this study, we investigated the role of SIRT3 in inflammation and fibrosis in the heart using male mice with constitutive and systemic deletion of SIRT3 and human cardiac AC16 cells. SIRT3 knockout mice showed cardiac fibrosis and inflammation that was characterized by augmented transcriptional activity of AP-1. Consistent with this, SIRT3 overexpression in human and neonatal rat cardiomyocytes partially prevented the inflammatory and profibrotic response induced by TNF-α. Notably, these effects were associated with a decrease in the mRNA and protein levels of FOS and the DNA-binding activity of AP-1. Finally, we demonstrated that SIRT3 inhibits FOS transcription through specific histone H3 lysine K27 deacetylation at its promoter. These findings highlight an important function of SIRT3 in mediating the often intricate profibrotic and proinflammatory responses of cardiac cells through the modulation of the FOS/AP-1 pathway. Since fibrosis and inflammation are crucial in the progression of cardiac hypertrophy, heart failure, and diabetic cardiomyopathy, our results point to SIRT3 as a potential target for treating these diseases.

Background: Management of tomato potato psyllid (TPP; Bactericera cockerelli (Šulc)) predominantly relies on insecticides. However, biological control agents (BCAs) could provide viable alternatives to suppress TPP populations. In this laboratory experiment, we assessed the predatory mite Amblydromalus limonicus (Garman & McGregor) as a BCA of TPP on whole plants of two tomato and two pepper cultivars over a 5-week period., Results: Plant species and cultivar had a significant effect on the ability of A. limonicus to suppress populations of TPP. Numbers of TPP were suppressed by A. limonicus on four pepper treatments, but on only one tomato treatment. Amblydromalus limonicus could survive and reproduce on pepper and tomato, but more were found on pepper at the end of the 5-week period., Conclusion: Amblydromalus limonicus has the potential to suppress TPP populations on pepper but not tomato cultivars, based on the present study. Possible reasons for these results include the difference in leaf morphology between species, and higher predator:prey ratios on pepper than tomato because of the longer TPP generation time on pepper. © 2018 Society of Chemical Industry., (© 2018 Society of Chemical Industry.)

Word reading and oral language predict reading comprehension, which is generally poor, in individuals with autism spectrum disorder (ASD). However, working memory (WM), despite documented weaknesses, has not been thoroughly investigated as a predictor of reading comprehension in ASD. This study examined the role of three parallel WM N-back tasks using abstract shapes, familiar objects, and written words in children (8-14 years) with ASD (n = 19) and their typically developing peers (n = 24). All three types of WM were significant predictors of reading comprehension when considered alone. However, these relationships were rendered non-significant with the addition of age, word reading, vocabulary, and group entered into the models. Oral vocabulary emerged as the strongest predictor of reading comprehension.

Background & Aims: Anecdotal evidence suggests that individuals with autism spectrum disorder (ASD) prefer non-fiction books over fiction books. The current study was the first to investigate parent-reports of children with ASD's fiction and non-fiction book preferences and whether these relate to individual differences in social communication, oral language, and/or reading abilities., Method: Children (ages 8-14 years, M = 10.89, SD = 1.17) with ASD diagnoses ( n = 19) and typically developing (TD) peers ( n = 21) participated. Children completed standardized measures of social communication, oral language, and reading abilities. Parents reported children's current favorite book, and from these responses, we coded children's fiction versus non-fiction book preferences., Main Contribution: Contrary to anecdotal evidence, children with ASD preferred fiction similar to their TD peers. Fiction versus non-fiction book preference was significantly related to social communication abilities across both groups. Children's oral language and reading abilities were related, as expected, but the evidence for a relationship between social communication and reading comprehension was mixed., Conclusions: This study provides preliminary evidence supporting the association of social communication in fiction versus non-fiction book preference, which may be related to children's comprehension and support the theoretical role of social communication knowledge in narrative/fiction., Implications: It should not be assumed that all children with ASD prefer expository/non-fiction or do not read narrative/fiction. Children who prefer non-fiction may need additional social communication knowledge support to improve their understanding of narrative fiction., Competing Interests: The data collected for this study was originally part of MMD’s doctoral dissertation at the University of Wisconsin-Madison. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The effect of ionizing irradiation on cytoplasmic organelles is often underestimated because the general dogma considers direct DNA damage in the nuclei to be the primary cause of radiation induced toxicity. Using a precision microbeam irradiator, we examined the changes in mitochondrial dynamics and functions triggered by targeted cytoplasmic irradiation with α-particles. Mitochondrial dysfunction induced by targeted cytoplasmic irradiation led to activation of autophagy, which degraded dysfunctional mitochondria in order to maintain cellular energy homeostasis. The activation of autophagy was cytoplasmic irradiation-specific and was not detected in nuclear irradiated cells. This autophagic process was oxyradical-dependent and required the activity of the mitochondrial fission protein dynamin related protein 1 (DRP1). The resultant mitochondrial fission induced phosphorylation of AMP activated protein kinase (AMPK) which leads to further activation of the extracellular signal-related kinase (ERK) 1/2 with concomitant inhibition of the mammalian target of rapamycin (mTOR) to initiate autophagy. Inhibition of autophagy resulted in delayed DNA damage repair and decreased cell viability, which supports the cytoprotective function of autophagy. Our results reveal a novel mechanism in which dysfunctional mitochondria are degraded by autophagy in an attempt to protect cells from toxic effects of targeted cytoplasmic radiation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Weak central coherence (processing details over gist), poor oral language abilities, poor suppression, semantic interference, and poor comprehension monitoring have all been implicated to affect reading comprehension in individuals with autism spectrum disorder (ASD). This study viewed the contributions of different supporting skills as a collective set of skills necessary for context integration-a multi-component view-to examine individual differences in reading comprehension in school-age children (8-14 years) with ASD (n = 23) and typically developing control peers (n = 23). Participants completed a written ambiguous sentence comprehension task in which participants had to integrate context to determine the correct homonym meaning via picture selection. Both comprehension products (i.e., offline representations after reading) and processes (i.e., online processing during reading) were evaluated. Results indicated that children with ASD, similar to their TD peers, integrated the context to access the correct homonym meanings while reading. However, after reading the sentences, when participants were asked to select the meanings, both groups experienced semantic interference between the two meanings. This semantic interference hindered the children with ASD's sentence representation to a greater degree than their peers. Individual differences in age/development, word recognition, vocabulary breadth (i.e., number of words in the lexicon), and vocabulary depth (i.e., knowledge of the homonym meanings) contributed to sentence comprehension in both children with ASD and their peers. Together, this evidence supports a multi-component view, and that helping children with ASD develop vocabulary depth may have cascading effects on their reading comprehension. Autism Res 2017, 10: 2002-2022. © 2017 International Society for Autism Research, Wiley Periodicals, Inc., Lay Summary: Like their peers, children with ASD were able to integrate context, or link words while reading sentences with ambiguous words (words with two meanings). After reading the sentences, both groups found it hard to pick the correct meaning of the ambiguous sentence and this decision was more difficult for the participants with ASD. Older children, children with better word reading abilities, and children with higher vocabularies were better at understanding ambiguous sentences. Helping children with ASD to develop richer vocabularies could be important for improving their reading comprehension., (© 2017 International Society for Autism Research, Wiley Periodicals, Inc.)

The purpose of this study was to examine intimate partner abuse (IPA), parental attachment, and romantic attachment among college women. More specifically, IPA was examined such that women who had experienced abuse and those who had not were compared with respect to parental and romantic attachment using the lens of attachment theory. Undergraduate women (N = 502) completed an online survey assessing their experiences of IPA as well as their parental and romantic attachment styles. Bivariate correlations demonstrated that IPA was significantly associated with all study variables (i.e., love withdrawal, care, and overprotection from both mother and father; romantic anxiety) in the hypothesized directions with the exception of romantic avoidance not being associated with abuse. Regarding the comparison of women who had experienced abuse (n = 367) to women who had not experienced abuse (n = 135), one-way analyses of variance (ANOVAs) revealed significant group mean differences in the hypothesized directions between abused and nonabused women with respect to love withdrawal and overprotection from both mothers and fathers, and romantic anxiety. In addition, psychological IPA and physical IPA were examined separately, yielding additional group differences regarding care from father and care from both mother and father, respectively. This work begins to examine attachment and IPA in new ways because it examines both parental attachment and romantic attachment in relation to IPA.

Background: Both children with autism spectrum disorders (ASD) and children with specific language impairment (SLI) have been shown to have difficulties with grammatical processing. A comparison of these two populations with neurodevelopmental disorders was undertaken to examine similarities and differences in the mechanisms that may underlie grammatical processing. Research has shown that working memory (WM) is recruited during grammatical processing. The goal of this study was to examine morphosyntactic processing on a grammatical judgment task in children who varied in clinical diagnosis and language abilities and to assess the extent to which performance is predicted by nonverbal working memory (WM). Two theoretical perspectives were evaluated relative to performance on the grammatical judgment task-the "working memory" account and the "wrap-up" account. These accounts make contrasting predictions about the detection of grammatical errors occurring early versus late in the sentence., Methods: Participants were 84 school-age children with SLI ( n  = 21), ASD ( n  = 27), and typical development (TD, n  = 36). Performance was analyzed based on diagnostic group as well as language status (normal language, NL, n  = 54, and language impairment, LI, n  = 30). A grammatical judgment task was used in which the position of the error in the sentence (early versus late) was manipulated. A visual WM task (N-back) was administered and the ability of WM to predict morphosyntactic processing was assessed., Results: Groups differed significantly in their sensitivity to grammatical errors (TD > SLI and NL > LI) but did not differ in nonverbal WM. Overall, children in all groups were more sensitive and quicker at detecting errors occurring late in the sentence than early in the sentence. Nonverbal WM predicted morphosyntactic processing across groups, but the specific profile of association between WM and early versus late error detection was reversed for children with and without language impairment., Conclusions: Findings primarily support a "wrap up" account whereby the accumulating sentence context for errors positioned late in the sentence (rather than early) appeared to facilitate morphosyntactic processing. Although none of the groups displayed deficits in visual WM, individual differences in these nonverbal WM resources predicted proficiency in morphosyntactic processing.

This study examined the extent to which a discrepant comprehension-production profile (i.e., relatively more delayed comprehension than production) is characteristic of the early language phenotype in autism spectrum disorders (ASD) and tracked the developmental progression of the profile. Our findings indicated that a discrepant comprehension-production profile distinguished toddlers (30 months) with ASD from late talkers without ASD (91% sensitivity, 100% specificity) in groups that were comparable on expressive language, age, and socioeconomic status. Longitudinal data for children with ASD revealed that the discrepant profile steadily decreased from 30 to 44 months until there was no significant comprehension-production difference at 66 months. In conclusion, results suggest that lower comprehension than production may be an age-specific marker of toddlers with ASD.

Purpose: We aimed to outline the latent variables approach for measuring nonverbal executive function (EF) skills in school-age children, and to examine the relationship between nonverbal EF skills and language performance in this age group., Method: Seventy-one typically developing children, ages 8 through 11, participated in the study. Three EF components, inhibition, updating, and task-shifting, were each indexed using 2 nonverbal tasks. A latent variables approach was used to extract latent scores that represented each EF construct. Children were also administered common standardized language measures. Multiple regression analyses were conducted to examine the relationship between EF and language skills., Results: Nonverbal updating was associated with the Receptive Language Index on the Clinical Evaluation of Language Fundamentals-Fourth Edition (CELF-4). When composites denoting lexical-semantic and syntactic abilities were derived, nonverbal inhibition (but not shifting or updating) was found to predict children's syntactic abilities. These relationships held when the effects of age, IQ, and socioeconomic status were controlled., Conclusions: The study makes a methodological contribution by explicating a method by which researchers can use the latent variables approach when measuring EF performance in school-age children. The study makes a theoretical and a clinical contribution by suggesting that language performance may be related to domain-general EFs.

Chronic increased workload of the human heart causes ventricular hypertrophy, re-expression of the atrial essential myosin light chain (hALC-1), and improved contractile function. Although hALC-1 is an important positive inotropic regulator of the human heart, little is known about its regulation. Therefore, we investigated the role of the sex hormone 17β-estradiol (E2) on hALC-1 gene expression, the underlying molecular mechanisms, and the impact of this regulatory process on cardiac contractile function. We showed that E2 attenuated hALC-1 expression in human atrial tissues of both sexes and in human ventricular AC16 cells. E2 induced the nuclear translocation of estrogen receptor alpha (ERα) and hALC-1 in AC16 cells, where they cooperatively regulate the transcriptional activity of hALC-1 gene promoter. E2-activated ERα required the estrogen response element (ERE) motif within the hALC-1 gene promoter to reduce its transcriptional activity (vehicle: 15.55 ± 4.80 vs. E2: 6.51 ± 3.69; ~2 fold). This inhibitory effect was potentiated in the presence of hALC-1 (vehicle: 11.13 ± 3.66 vs. E2: 2.18 ± 1.10; ~5 fold), and thus, hALC-1 acts as a co-repressor of ERα-mediated transcription. Yeast two-hybrid screening of a human heart cDNA library revealed that ERα interacts physically with hALC-1 in the presence of E2. This interaction was confirmed by Co-Immunoprecipitation and immunofluorescence in human atrium. As a further novel effect, we showed that chronic E2-treatment of adult mouse cardiomyocytes overexpressing hALC-1 resulted in reduced cell-shortening amplitude and twitching kinetics of these cells independent of Ca 2+ activation levels. Together, our data showed that the expression of hALC-1 gene is, at least partly, regulated by E2/ERα, while hALC-1 acts as a co-repressor. The inotropic effect of hALC-1 overexpression in cardiomyocytes can be significantly repressed by E2.

The current study examined the relationship between nonverbal working memory and morphosyntactic processing in monolingual native speakers of English and bilingual speakers of English and Spanish. We tested 42 monolingual children and 42 bilingual children between the ages of 8 and 10years matched on age and nonverbal IQ. Children were administered an auditory Grammaticality Judgment task in English to measure morphosyntactic processing and a visual N-Back task and Corsi Blocks task to measure nonverbal working memory capacity. Analyses revealed that monolinguals were more sensitive to English morphosyntactic information than bilinguals, but the groups did not differ in reaction times or response bias. Furthermore, higher nonverbal working memory capacity was associated with greater sensitivity to morphosyntactic violations in bilinguals but not in monolinguals. The findings suggest that nonverbal working memory skills link more tightly to syntactic processing in populations with lower levels of language knowledge., (Copyright © 2015 Elsevier Inc. All rights reserved.)

The purpose of the current investigation was to examine forgiveness and intimate partner violence (IPV) among college women. Undergraduate women (N = 502) participated in an online study in which overall experiences of IPV, as well as experiences of psychological and physical IPV, were investigated with respect to transgression-specific and dispositional forgiveness. Simultaneous multivariate regressions revealed that (a) the experience of IPV was associated with higher levels of avoidance and revenge, and lower levels of benevolence, forgiveness of self, forgiveness of others, and forgiveness of uncontrollable situations; (b) types of IPV demonstrated differing impacts on forgiveness; and (c) the mere experience of IPV is more salient than its frequency., (© The Author(s) 2014.)

miR-146a is a microRNA whose transcript levels are induced in the heart upon activation of NF-κB, a transcription factor induced by pro-inflammatory molecules (such as TNF-α) that is strongly related to the pathogenesis of cardiac disorders. The main goal of this study consisted of studying new roles of miR-146a in cardiac pathological processes caused by the pro-inflammatory cytokine TNF-α. Our results demonstrate that miR-146a transcript levels were sharply increased in cardiac ventricular tissue of transgenic mice with specific overexpression of TNF-α in the heart, and also in a cardiomyocyte cell line of human origin (AC16) exposed to TNF-α. Among all the in silico predicted miR-146a target genes, Fos mRNA and protein levels notably decreased after TNF-α treatment or miR-146a overexpression. These changes correlated with a diminution in the DNA-binding activity of AP-1, the Fos-containing transcription factor complex. Interestingly, AP-1 inhibition was accompanied by a reduction in matrix metalloproteinase (MMP)-9 mRNA levels in human cardiac cells. The specific regulation of this MMP by miR-146a was further confirmed at the secretion and enzymatic activity levels, as well as after anti-miR-mediated miR-146a inhibition. The results reported here demonstrate that Fos is a direct target of miR-146a activity and that downregulation of the Fos-AP-1 pathway by miR-146a has the capacity to inhibit MMP-9 activity. Given that MMP-9 is an AP-1 target gene involved in cardiac remodeling, myocardial dysfunction and progression of heart failure, these findings suggest that miR-146a might be a new and promising therapeutic tool for treating cardiac disorders associated with enhanced inflammation in the heart., (© 2015. Published by The Company of Biologists Ltd.)

Although kidney is a target organ of arsenic cytotoxicity, the underlying mechanisms of arsenic-induced nephrotoxicity remain poorly understood. As tetramethylpyrazine (TMP) has recently been found to be a renal protectant in multiple kidney injuries, we hypothesize that TMP could suppress arsenic nephrotoxicity. In this study, human renal proximal tubular epithelial cell line HK-2 was used to elucidate the precise mechanisms of arsenic nephrotoxicity as well as the protective mechanism of TMP in these cells. Sodium arsenite exposure dramatically increased cellular reactive oxygen species (ROS) production, decreased levels of cellular glutathione (GSH), decreased cytochrome c oxidase activity and mitochondrial membrane potential, which indicated mitochondrial dysfunction. On the other hand, sodium arsenite activated pro-inflammatory signals, including β-catenin, nuclear factor-κB (NF-κB), p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor alpha and cyclooxygenase-2 (COX-2). Small molecule inhibitors of NF-κB and p38 MAPK blocked arsenic-induced COX-2 expression, suggesting arsenic-induced COX-2 up-regulation was NF-κB- and p38 MAPK-dependent. Finally, sodium arsenite induced autophagy in HK-2 cells at early phase (6 h) and the subsequent apoptosis at 24 h. Treatment by TMP or by the antioxidant N-acetylcysteine decreased arsenic-induced ROS production, enhanced GSH levels, prevented mitochondria dysfunction and suppressed the activation of pro-inflammatory signals and the development of autophagy and apoptosis. Our results suggested that TMP may be used as a new potential therapeutic agent to prevent arsenic-induced nephrotoxicity by suppressing these pathological processes.

Adaptive cardiac remodeling is characterized by enhanced signaling of mTORC2 downstream kinase Akt. In females, 17ß-estradiol (E2), as well as Akt contribute essentially to sex-related premenopausal cardioprotection. Pharmacologic mTOR targeting with rapamycin is increasingly used for various clinical indications, yet burdened with clinical heterogeneity in therapy responses. The drug inhibits mTORC1 and less-so mTORC2. In male rodents, rapamycin decreases maladaptive cardiac hypertrophy whereas it leads to detrimental dilative cardiomyopathy in females. We hypothesized that mTOR inhibition could interfere with 17β-estradiol (E2)-mediated sexual dimorphism and adaptive cell growth and tested responses in murine female hearts and cultured female cardiomyocytes. Under physiological in vivo conditions, rapamycin compromised mTORC2 function only in female, but not in male murine hearts. In cultured female cardiomyocytes, rapamycin impaired simultaneously IGF-1 induced activation of both mTOR signaling branches, mTORC1 and mTORC2 only in presence of E2. Use of specific estrogen receptor (ER)α- and ERβ-agonists indicated involvement of both estrogen receptors (ER) in rapamycin effects on mTORC1 and mTORC2. Classical feedback mechanisms common in tumour cells with upregulation of PI3K signaling were not involved. E2 effect on Akt-pS473 downregulation by rapamycin was independent of ERK as shown by sequential mTOR and MEK-inhibition. Furthermore, regulatory mTORC2 complex defining component rictor phosphorylation at Ser1235, known to interfere with Akt-substrate binding to mTORC2, was not altered. Functionally, rapamycin significantly reduced trophic effect of E2 on cell size. In addition, cardiomyocytes with reduced Akt-pS473 under rapamycin treatment displayed decreased SERCA2A mRNA and protein expression suggesting negative functional consequences on cardiomyocyte contractility. Rictor silencing confirmed regulation of SERCA2A expression by mTORC2 in E2-cultured female cardiomyocytes. These data highlight a novel modulatory function of E2 on rapamycin effect on mTORC2 in female cardiomyocytes and regulation of SERCA2A expression by mTORC2. Conceivably, rapamycin abrogates the premenopausal "female advantage".

The purpose of this research was to examine the effects of violence on body image variables for college women. Undergraduate women participated in an online study assessing sexual violence (SV), intimate partner violence (IPV), self-objectification, body surveillance, and body shame experiences. Findings suggest that both SV and IPV contribute to women's body shame. In addition, the associations between IPV and body shame appear to be explained through self-objectification processes, but not the associations between SV and body shame. Thus, important differences between IPV and SV regarding self-objectification processes emerged. Theoretical and practical implications, as well as directions for future research, are discussed., (© The Author(s) 2015.)

Purpose: The current study compared the spontaneous expressive language of children with autism spectrum disorder (ASD) across multiple language sampling contexts: the Autism Diagnostic Observation Schedule (ADOS; Lord, Rutter, DiLavore, & Risi, 1999) and play with an examiner or parent., Method: Participants were children with ASD (n = 63; 55 boys) with a mean age of 45 months (SD = 3.94, range = 37-53). The number of utterances produced; percentage of intelligible utterances; number of different words; mean length of utterance; and the number of requests, comments, and instances of turn-taking were calculated for the ADOS, examiner-child play, and parent-child play. Children were categorized into Tager-Flusberg et al.'s (2009) developmental language phases for each context., Results: Effects of sampling context were identified for all variables examined. The ADOS resulted in fewer utterances and lower structural and pragmatic language performance than examiner-child play and/or parent-child play. Categorization of children into language phases differed across contexts., Conclusions: Use of the ADOS as a language sampling context may lead to underestimating the abilities of young children with ASD relative to play with an examiner or parent. Researchers and clinicians should be aware of context effects, particularly for assessments designed to observe autism symptoms.

Introduction: Endoplasmic reticulum (ER) stress has been linked to several cardiovascular diseases, such as atherosclerosis, heart failure and cardiac hypertrophy. ER stress impairs insulin signalling, thus contributing to the development of insulin resistance and diabetes. Since several studies have reported that PPARα may inhibit ER stress, the main aim of this study consisted in investigating whether activation of this nuclear receptor is able to prevent lipid-induced ER stress in cardiac cells, as well as studying the mechanisms involved., Methods: A cardiomyocyte cell line of human origin, AC16, was treated with palmitate in the presence or absence of several AMPK and PPARα pharmacological agonists and antagonists. For the in vivo studies, wild-type male mice were fed a standard diet, or a high-fat diet (HFD), for two months. At the end of the experiments, several ER stress markers were assessed in cardiac cells or in the mice hearts, using real-time RT-PCR and Western-blot analyses., Results: The results demonstrate that both palmitate and the HFD induced ER stress in cardiac cells, since they upregulated the expression (ATF3, BiP/GRP78 and CHOP), splicing (sXBP1), and phosphorylation (IRE-1α and eIF2α) of several ER stress markers. Interestingly, treatment with the PPARα agonist Wy-14,643 prevented an increase in the majority of these ER stress markers in human cardiac cells by means of AMPK activation., Conclusion: These data indicate that PPARα activation by Wy-14,643 might be useful to prevent the harmful effects of ER stress and associated cardiovascular diseases in obese patients, and even during diabetic cardiomyopathy, by enhancing AMPK activity., (Copyright © 2013 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.)

Aims: Oestrogen receptor alpha (ERα) and beta (ERβ) are involved in the regulation of pathological myocardial hypertrophy (MH). We hypothesize that both ER are also involved in physiological MH. Therefore, we investigated the role of ER in exercise-induced physiological MH in loss-of-function models and studied potential mechanisms of action., Methods and Results: We performed 1 and 8 weeks of voluntary cage wheel running (VCR) with male and female C57BL/6J wild-type (WT), ERα- and ERβ-deleted mice. In line with other studies, female WT mice ran more than males (P ≤ 0.001). After 8 weeks of VCR, both sexes showed an increase in left ventricular mass (females: P ≤ 0.01 and males: P ≤ 0.05) with more pronounced MH in females (P < 0.05). As previously shown, female ERα-deleted mice run less than female WT mice (P ≤ 0.001). ERβ-deleted mice showed similar running performance as WT mice (females vs. male: P ≤ 0.001), but did not develop MH. Only female WT mice showed an increase in phosphorylation of serine/threonine kinase (AKT), ERK1/2, p38-mitogen-activated protein kinase (MAPK), and ribosomal protein s6, as well as an increase in the expression of key regulators of mitochondrial function and mitochondrial respiratory chain proteins (complexes I, III, and V) after VCR. However, ERβ deletion abolished all observed sex differences. Mitochondrial remodelling occurred in female WT-VCR mice, but not in female ERβ-deleted mice., Conclusion: The sex-specific response of the heart to exercise is modulated by ERβ. The greater increase in physiological MH in females is mediated by induction of AKT signalling, MAPK pathways, protein synthesis, and mitochondrial adaptation via ERβ., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Chronic endoplasmic reticulum (ER) stress contributes to the apoptotic cell death in the myocardium, thereby playing a critical role in the development of cardiomyopathy. ER stress has been reported to be induced after high-fat diet feeding in mice and also after saturated fatty acid treatment in vitro. Therefore, since several studies have shown that peroxisome proliferator-activated receptor (PPAR)β/δ inhibits ER stress, the main goal of this study consisted in investigating whether activation of this nuclear receptor was able to prevent lipid-induced ER stress in cardiac cells., Methods and Results: Wild-type and transgenic mice with reduced PPARβ/δ expression were fed a standard diet or a high-fat diet for two months. For in vitro studies, a cardiomyocyte cell line of human origin, AC16, was treated with palmitate and the PPARβ/δ agonist GW501516. Our results demonstrate that palmitate induced ER stress in AC16 cells, a fact which was prevented after PPARβ/δ activation with GW501516. Interestingly, the effect of GW501516 on ER stress occurred in an AMPK-independent manner. The most striking result of this study is that GW501516 treatment also upregulated the protein levels of beclin 1 and LC3II, two well-known markers of autophagy. In accordance with this, feeding on a high-fat diet or suppression of PPARβ/δ in knockout mice induced ER stress in the heart. Moreover, PPARβ/δ knockout mice also displayed a reduction in autophagic markers., Conclusion: Our data indicate that PPARβ/δ activation might be useful to prevent the harmful effects of ER stress induced by saturated fatty acids in the heart by inducing autophagy., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Many children with autism spectrum disorder (ASD) have reading profiles characterized by higher decoding skills and lower reading comprehension. This study assessed whether this profile was apparent in young children with ASD and examined concurrent and longitudinal predictors of early reading. A discrepant profile of reading (higher alphabet and lower meaning) was found in 62% of this sample. Concurrent analyses revealed that reading proficiency was associated with higher nonverbal cognition and expressive language, and that social ability was negatively related to alphabet knowledge. Nonverbal cognition and expressive language at mean age 2½ years predicted later reading performance at mean age 5½ years. These results support the importance of early language skills as a foundation for reading in children with ASD.

High linear energy transfer (LET) radiation including α particles and heavy ions is the major type of radiation find in space and is considered a potential health risk for astronauts. Even though the chance that these high LET particles traversing through the cytoplasm of cells is higher than that through the nuclei, the contribution of targeted cytoplasmic irradiation, to the induction of genomic instability and other chromosomal damages induced by high LET radiation is not known. In the present study, we investigated whether mitochondria are the potential cytoplasmic target of high LET radiation in mediating cellular damage using a mitochondrial DNA (mtDNA) depleted (ρ 0 ) human small airway epithelial (SAE) cell model and a precision charged particle microbeam with a beam width of merely one micron. Targeted cytoplasmic irradiation by high LET α particles induced DNA oxidative damage and double strand breaks in wild type ρ + SAE cells. Furthermore, there was a significant increase in autophagy, micronuclei, which is an indication of genomic instability, together with the activation of nuclear factor kappa-B (NF-κB) and mitochondrial inducible nitric oxide synthase (iNOS) signaling pathways in ρ + SAE cells. In contrast, ρ 0 SAE cells exhibited a significantly lower response to these same endpoints examined after cytoplasmic irradiation with high LET α particles. The results indicate that mitochondria are essential in mediating cytoplasmic radiation induced genotoxic damage in mammalian cells. Furthermore, the findings may shed some light in the design of countermeasures for space radiation.

Direct DNA damage is often considered the primary cause of cancer in patients exposed to ionizing radiation or environmental carcinogens. Although mitochondria are known to play an important role in radiation-induced cellular response, the mechanisms by which cytoplasmic stimuli modulate mitochondrial dynamics and functions are largely unknown. In the present study, we examined changes in mitochondrial dynamics and functions triggered by α particle damage to the mitochondria in human small airway epithelial cells, using a precision microbeam irradiator with a beam width of 1 μm. Targeted cytoplasmic irradiation using this device resulted in mitochondrial fragmentation and a reduction of cytochrome c oxidase and succinate dehydrogenase activity, when compared with nonirradiated controls, suggesting a reduction in respiratory chain function. In addition, mitochondrial fragmentation or fission was associated with increased expression of the dynamin-like protein DRP1, which promotes mitochondrial fission. DRP1 inhibition by the drug mdivi-1 prevented radiation-induced mitochondrial fission, but respiratory chain function in mitochondria inhibited by radiation persisted for 12 hours. Irradiated cells also showed an increase in mitochondria-derived superoxide that could be quenched by dimethyl sulfoxide. Taken together, our results provide a mechanistic explanation for the extranuclear, nontargeted effects of ionizing radiation., (©2013 AACR)

Background: Resveratrol is a grape polyphenol that prevents cardiac hypertrophy and protects the heart from ischemic injury, metabolic dysregulation, and inflammatory processes in several murine models., Methods and Results: The aim of this study was to investigate the effects of resveratrol on the inflammatory processes in human cardiac AC16 cells in order to gain a better understanding of its cardioprotective mechanisms in the human heart. Resveratrol induced the DNA-binding activity of the pro-inflammatory transcription factor NF-κB in AC16 cells, and exacerbated the increase caused by tumor necrosis factor-α (TNF-α). In accordance with this, resveratrol increased the expression of the pro-inflammatory genes ICAM-1 (intercellular adhesion molecule-1) and TNF-α. In contrast, resveratrol decreased the expression of pro-inflammatory genes IL-6 (interleukin-6) and MCP-1 (monocyte chemoattractant protein-1). Likewise, resveratrol also induced inflammation in rat neonatal cardiomyocytes, and in the heart of mice fed a standard chow diet supplemented with resveratrol (1g/kg diet) for four months. Western-blot analyses revealed that NF-κB p65 subunit levels were upregulated in an IκB-dependent manner in the nuclei of resveratrol-treated human cardiac cells. Finally, resveratrol activated the signal transducer and activator of transcription 3 (STAT3) signaling and induced the expression of its anti-apoptotic downstream effector Bcl-xL, both involved in the cardioprotective survival activating factor enhancement (SAFE) pathway., Conclusions: Resveratrol enhanced NF-κB activity in human and murine cardiac cells, in a process that coincided with the activation of STAT3 and anti-apoptotic downstream effectors. Therefore, activation of the SAFE pathway by resveratrol might be involved in the cardioprotective effects of this compound., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Whereas sexual objectification has most commonly been studied among women, recent calls by counseling psychologists have urged for an extension of objectification research to more fully include men (e.g., Heimerdinger-Edwards, Vogel, & Hammer, 2011). The present study examined the factor structure of the Interpersonal Sexual Objectification Scale (ISOS; Kozee, Tylka, Augustus-Horvath, & Denchik, 2007) with men. Specifically, analyses included exploratory factor analysis (EFA) with a sample of 287 college men and confirmatory factor analysis (CFA) with an independent sample of 221 college men. A correlated 3-factor structure was suggested by multiple criteria in EFA and was further confirmed by CFA with a bifactor model illustrating the most item variance associated with a general interpersonal sexual objectification dimension for men.

Each year, thousands of female adolescents run away from home due to sexual abuse, yet they continue to be victims of sexual assault once on the street. To date, few studies have examined how various forms of victimization are related to different types of substance use. The purpose of this article is to investigate the relationship between street exposure, childhood abuse, and different forms of street victimization with alcohol and marijuana use among 137 homeless and runaway female adolescents. Results from path analysis revealed that child sexual abuse was positively linked to trading sex and sexual and physical victimization. In addition, those who have traded sex experienced greater physical victimization, and who have spent more time away from home, used alcohol more frequently. Moreover, trading sex and experiencing more types of sexual victimization were positively linked to more frequent marijuana usage. Age, age at first run, longest time away from home, sexual abuse, and trading sex had significant indirect effects on alcohol and/or marijuana use. Together, these factors accounted for 27% of the variance in alcohol use and 37% of the variance in marijuana use.

The purpose of this study was to examine forgiveness and sexual violence among college women. Undergraduate women (N = 503) completed an online survey assessing experiences of sexual violence and forgiveness. Simultaneous multivariate regressions revealed that experiencing more sexual violence was associated with more revenge and avoidance, and less benevolence. Furthermore, findings indicated that more experiences of sexual violence were negatively associated with forgiveness of self, forgiveness of others, and forgiveness of uncontrollable situations. This work begins to fill critical gaps in the extant literature because it is the only study to date that examines sexual violence and the positive psychological construct of forgiveness. Implications and directions for future research are discussed.

This study examined intimate partner violence (IPV) and objectification. Specifically, the associations between psychological and physical abuse and self-objectification, body surveillance, and body shame for college women were considered through the lens of objectification theory. Consistent with Hypothesis 1, bivariate correlations showed that more psychological abuse was associated with more self-objectification, more body surveillance, and more body shame. As well, more physical abuse was associated with more body surveillance and more body shame. However, when the unique effects of psychological and physical abuse were considered in a path model, the links between psychological abuse and objectification remained while the links between physical abuse and objectification became nonsignificant. In addition, consistent with Hypothesis 2 and the model proposed by objectification theory, body surveillance and the combined effect of self-objectification and body surveillance explained relations between psychological abuse and body shame. This work fills an important gap in the current literature because it is the only study to date that examines relations between both psychological and physical abuse and self-objectification, body surveillance, and body shame. Implications and future directions are discussed.

Youth violence represents a serious problem affecting individuals, communities, and the larger society. Greater efforts aimed at the eradication of youth violence are necessary, and work in this field could be enhanced by psychometrically strong measures. The present study examined the factor structure of the Attitudes Toward Violence Scale (ATV) using exploratory factor analysis (EFA) with a sample of 359 high school students. A three-factor structure was identified. The three factors were invariant across sex, however, males obtained significantly higher scores on the three ATV factors and on the ATV total score showing generally moderate effect sizes. Directions for future research with the ATV are discussed.

Aims: 17β-Oestradiol (E2) and its receptors (ERα and ERβ) are important regulators of physiological and pathological processes in the cardiovascular system. ER act in concert with other regulatory factors mediating oestrogenic effects. However, the underlying mechanisms modulating ER transcriptional activity are not fully elucidated. To gain better understanding of E2-induced ERα action in the human heart, we aimed to identify and functionally analyse interaction partners of ERα., Methods and Results: Using yeast two-hybrid assays with a human heart cDNA library, we identified atrial natriuretic peptide precursor A (NPPA), a well-known cardiac hypertrophy marker, as a novel ERα interaction partner interacting in an E2-dependent manner. Mutation analyses and immunofluorescence data indicated that the LXXLL motif within NPPA is necessary for its E2-induced interaction with ERα, its action as a co-repressor of ERα, and its translocation into the nucleus of human and rat cardiomyocytes. Expression analysis and chromatin immunoprecipitation assays in a human left ventricular cardiomyocyte cell line, AC16, showed that NPPA interacts with E2/ERα, suppressing the transcriptional activity of ERα on E2-target genes, such as NPPA, connexin43, αactinin-2, nuclear factor of activated T-cells, and collagens I and III., Conclusion: We characterize for the first time an E2-regulated interaction of NPPA with ERα in cardiomyocytes, that may be crucial in physiological and/or pathological cardiac processes, thereby representing a potential therapeutic target.

Background: Mitochondrial dysfunction is a key determinant in chagasic cardiomyopathy development in mice; however, its relevance in human Chagas disease is not known. We determined if defects in mitochondrial biogenesis and dysregulation of peroxisome proliferator-activated receptor gamma (PPARγ) coactivator-1 (PGC-1)-regulated transcriptional pathways constitute a mechanism or mechanisms underlying mitochondrial oxidative-phosphorylation (OXPHOS) deficiency in human Chagas disease., Methods and Results: We utilized human cardiomyocytes and left-ventricular tissue from chagasic and other cardiomyopathy patients and healthy donors (n>6/group). We noted no change in citrate synthase activity, yet mRNA and/or protein levels of subunits of the respiratory complexes were significantly decreased in Trypanosoma cruzi-infected cardiomyocytes (0 to 24 hours) and chagasic hearts. We observed increased mRNA and decreased nuclear localization of PGC-1-coactivated transcription factors, yet the expression of genes for PPARγ-regulated fatty acid oxidation and nuclear respiratory factor (NRF1/2)-regulated mtDNA replication and transcription machinery was enhanced in infected cardiomyocytes and chagasic hearts. The D-loop formation was normal or higher, but mtDNA replication and mtDNA content were decreased by 83% and 40% to 65%, respectively. Subsequently, we noted that reactive oxygen species (ROS), oxidative stress, and mtDNA oxidation were significantly increased, yet NRF1/2-regulated antioxidant gene expression remained compromised in infected cardiomyocytes and chagasic hearts., Conclusions: The replication of mtDNA was severely compromised, resulting in a significant loss of mtDNA and expression of OXPHOS genes in T cruzi-infected cardiomyocytes and chagasic hearts. Our data suggest increased ROS generation and selective functional incapacity of NRF2-mediated antioxidant gene expression played a role in the defects in mtDNA replication and unfitness of mtDNA for replication and gene expression in Chagas disease.

Background: The incidence of asbestos-induced human cancers is increasing worldwide, and considerable evidence suggests that reactive oxygen species (ROS) are important mediators of these diseases. Our previous studies suggested that mitochondria might be involved in the initiation of oxidative stress in asbestos-exposed mammalian cells., Objective: We investigated whether mitochondria are a potential cytoplasmic target of asbestos using a mitochondrial DNA-depleted (ρ(0)) human small airway epithelial (SAE) cell model: ρ(0) SAE cells lack the capacity to produce mitochondrial ROS., Methods: We examined nuclear DNA damage, micronuclei (MN), intracellular ROS production, and the expression of inflammation-related nuclear genes in both parental and ρ(0) SAE cells in response to asbestos treatment., Results: Asbestos induced a dose-dependent increase in nuclear DNA oxidative damage and MN in SAE cells. Furthermore, there was a significant increase in intracellular oxidant production and activation of genes involved in nuclear factor κB and proinflammatory signaling pathways in SAE cells. In contrast, the effects of asbestos were minimal in ρ(0) SAE cells., Conclusions: Mitochondria are a major cytoplasmic target of asbestos. Asbestos may initiate mitochondria-associated ROS, which mediate asbestos-induced nuclear mutagenic events and inflammatory signaling pathways in exposed cells. These data provide new insights into the molecular mechanisms of asbestos-induced genotoxicity.

The role of serine palmitoyltransferase (SPT) and de novo ceramide biosynthesis in cardiac ceramide and sphingomyelin metabolism is unclear. To determine whether the de novo synthetic pathways, rather than ceramide uptake from circulating lipoproteins, is important for heart ceramide levels, we created cardiomyocyte-specific deficiency of Sptlc2, a subunit of SPT. Heart-specific Sptlc2-deficient (hSptlc2 KO) mice had a >35% reduction in ceramide, which was limited to C18:0 and very long chain ceramides. Sphingomyelinase expression, and levels of sphingomyelin and diacylglycerol were unchanged. But surprisingly phospholipids and acyl CoAs contained increased saturated long chain fatty acids. hSptlc2 KO mice had decreased fractional shortening and thinning of the cardiac wall. While the genes regulating glucose and fatty acid metabolism were not changed, expression of cardiac failure markers and the genes involved in the formation of extracellular matrices were up-regulated in hSptlc2 KO hearts. In addition, ER-stress markers were up-regulated leading to increased apoptosis. These results suggest that Sptlc2-mediated de novo ceramide synthesis is an essential source of C18:0 and very long chain, but not of shorter chain, ceramides in the heart. Changes in heart lipids other than ceramide levels lead to cardiac toxicity.

The purpose of this research was to conduct a replication-based and extension study examining the effectiveness of a 5-week career group counseling intervention, Advancing Career Counseling and Employment Support for Survivors (ACCESS; Chronister, 2008). The present study was conducted in a markedly different geographic region within a larger community as compared with the original investigation conducted by Chronister and McWhirter (2006). Women survivors of intimate partner violence (N = 73) participated in ACCESS, with career-search self-efficacy, perceived career barriers, perceived career supports, anxiety, and depression assessed at preintervention, postintervention, and 8-week follow-up. Women survivors demonstrated significant improvements in career-search self-efficacy and perceived career barriers at postintervention. Moreover, these same improvements were maintained at the 8-week follow-up assessment with the addition of significant improvements in perceived future financial supports, anxiety, and depression compared with preintervention scores. This work replicates the initial findings regarding the effectiveness of ACCESS with respect to career-search self-efficacy (Chronister & McWhirter, 2006) as well as extends the initial research to include improvements in perceived career barriers and perceived career supports. Moreover, the present study extends the work to include the mental health outcomes of anxiety and depression; results demonstrated improvements in these areas at 8-week follow-up. This investigation begins to fill a critical need for evaluated career-focused interventions for the underserved population of women survivors of intimate partner violence.

Owing to its high fat content, the classical Western diet has a range of adverse effects on the heart, including enhanced inflammation, hypertrophy, and contractile dysfunction. Proinflammatory factors secreted by cardiac cells, which are under the transcriptional control of nuclear factor-κB (NF-κB), may contribute to heart failure and dilated cardiomyopathy. The underlying mechanisms are complex, since they are linked to systemic metabolic abnormalities and changes in cardiomyocyte phenotype. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate metabolism and are capable of limiting myocardial inflammation and hypertrophy via inhibition of NF-κB. Since PPARβ/δ is the most prevalent PPAR isoform in the heart, we analyzed the effects of the PPARβ/δ agonist GW501516 on inflammatory parameters. A high-fat diet induced the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin-6, and enhanced the activity of NF-κB in the heart of mice. GW501516 abrogated this enhanced proinflammatory profile. Similar results were obtained when human cardiac AC16 cells exposed to palmitate were coincubated with GW501516. PPARβ/δ activation by GW501516 enhanced the physical interaction between PPARβ/δ and p65, which suggests that this mechanism may also interfere NF-κB transactivation capacity in the heart. GW501516-induced PPARβ/δ activation can attenuate the inflammatory response induced in human cardiac AC16 cells exposed to the saturated fatty acid palmitate and in mice fed a high-fat diet. This is relevant, especially taking into account that PPARβ/δ has been postulated as a potential target in the treatment of obesity and the insulin resistance state., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Pyruvate dehydrogenase kinase 4 (PDK4) inhibition by nuclear factor-κB (NF-κB) is related to a shift towards increased glycolysis during cardiac pathological processes such as cardiac hypertrophy and heart failure. The transcription factors estrogen-related receptor-α (ERRα) and peroxisome proliferator-activated receptor (PPAR) regulate PDK4 expression through the potent transcriptional coactivator PPARγ coactivator-1α (PGC-1α). NF-κB activation in AC16 cardiac cells inhibit ERRα and PPARβ/δ transcriptional activity, resulting in reduced PGC-1α and PDK4 expression, and an enhanced glucose oxidation rate. However, addition of the NF-κB inhibitor parthenolide to these cells prevents the downregulation of PDK4 expression but not ERRα and PPARβ/δ DNA binding activity, thus suggesting that additional transcription factors are regulating PDK4. Interestingly, a recent study has demonstrated that the transcription factor E2F1, which is crucial for cell cycle control, may regulate PDK4 expression. Given that NF-κB may antagonize the transcriptional activity of E2F1 in cardiac myocytes, we sought to study whether inflammatory processes driven by NF-κB can downregulate PDK4 expression in human cardiac AC16 cells through E2F1 inhibition. Protein coimmunoprecipitation indicated that PDK4 downregulation entailed enhanced physical interaction between the p65 subunit of NF-κB and E2F1. Chromatin immunoprecipitation analyses demonstrated that p65 translocation into the nucleus prevented the recruitment of E2F1 to the PDK4 promoter and its subsequent E2F1-dependent gene transcription. Interestingly, the NF-κB inhibitor parthenolide prevented the inhibition of E2F1, while E2F1 overexpression reduced interleukin expression in stimulated cardiac cells. Based on these findings, we propose that NF-κB acts as a molecular switch that regulates E2F1-dependent PDK4 gene transcription.

The incidence of hospital-acquired infection with methicillin-resistant Staphylococcus aureus (MRSA) is rising worldwide. Rapid identification of MRSA carriers is an important step in reducing the risk of transmission to other patients. Molecular methods are increasingly popular but are technically demanding and expensive. This study assesses the modification of one of the commercially available latex agglutination tests (Mastalex-MRSA) for the identification of penicillin-binding protein 2' on known strains of MRSA as well as other organisms identified from chromogenic agar plates. A total of 3050 patients with unknown MRSA status were processed through the routine laboratory during the investigation period and 73 of these were presumptive positive following overnight incubation. Of 70 patients who could be evaluated, 32 (43.8%) specimens would be suitable for use with the kit directly from overnight incubation on chromogenic agar, and the other 38 (52.1%) would be suitable following four hours' incubation on blood agar. The cost of one positive MRSA test with the inclusion of this test is Euro 15.15 compared with published reports of Euro 35.00 for a commercial polymerase chain reaction (PCR) test. This protocol would allow the reporting of presumptive positive MRSA results approximately 24 hours earlier than currently achieved.