Colloidal stabilization of hydrophobic InSe 2D nanosheets in a model environmental aqueous solution and their impact on Shewanella oneidensis MR-1.

Semiconductor InSe 2D nanomaterials have emerged as potential photoresponsive materials for broadly distributed photodetectors and wearable electronics technologies due to their high photoresponsivity and thermal stability. This paper addresses an environmental concern about the fate of InSe 2D nanosheets when disposed and released into the environment after use. Semiconducting materials are potentially reactive and often form environmentally damaging species, for example reactive oxygen and nitrogen species, when degraded. InSe nanosheets are prepared using a semi bottom-up approach which involves a reaction between indium and selenium precursors at elevated temperature in an oxygen-free environment to prevent oxidation. InSe nanosheets are formed as a stable intermediate with micrometer-sized lateral dimensions and a few monolayer thickness. The InSe 2D nanosheets are obtained when the reaction is stopped after 30 minutes by cooling. Keeping the reaction at elevated temperature for a longer period, for example 60 minutes leads to the formation of InSe 3D nanoparticles of about 5 nm in diameter, a thermodynamically more stable form of InSe. The paper focuses on the colloidal stabilization of InSe nanosheets in an aqueous solution that contains epigallocatechin gallate (EGCG), a natural organic matter (NOM) simulant. We show that EGCG coats the surface of the hydrophobic, water-insoluble InSe nanosheets via physisorption. The formed EGCG-coated InSe nanosheets are colloidally stable in aqueous solution. While unmodified semiconducting InSe nanosheets could produce reactive oxygen species (ROS) when illuminated, our study shows low levels of ROS generation by EGCG-coated InSe nanosheets under ambient light, which might be attributed to ROS quenching by EGCG. Growth-based viability (GBV) assays show that the colloidally stable EGCG-coated InSe nanosheets adversely impact the bacterial growth of Shewanella oneidensis MR-1, an environmentally relevant Gram-negative bacterium in aqueous media. The impact on bacterial growth is driven by the EGCG coating of the nanosheets. In addition, live/dead assays show insignificant membrane damage of the Shewanella oneidensis MR-1 cells by InSe nanosheets, suggesting a weak association of EGCG-coated nanosheets with the cells. It is likely that the adverse impact of EGCG-coated nanosheets on bacterial growth is the result of increasing local concentration of EGCG either when adsorbed on the nanosheets when the nanosheets interact with the cells, or when desorbed from the EGCG-coated nanosheets to interact with the bacterial cells.

Behavioural responses of a large, heat-sensitive mammal to climatic variation at multiple spatial scales.

Climate warming creates energetic challenges for endothermic species by increasing metabolic and hydric costs of thermoregulation. Although endotherms can invoke an array of behavioural and physiological strategies for maintaining homeostasis, the relative effectiveness of those strategies in a climate that is becoming both warmer and drier is not well understood. In accordance with the heat dissipation limit theory which suggests that allocation of energy to growth and reproduction by endotherms is constrained by the ability to dissipate heat, we expected that patterns of habitat use by large, heat-sensitive mammals across multiple scales are critical for behavioural thermoregulation during periods of potential heat stress and that they must invest a large portion of time to maintain heat balance. To test our predictions, we evaluated mechanisms underpinning the effectiveness of bed sites for ameliorating daytime heat loads and potential heat stress across the landscape while accounting for other factors known to affect behaviour. We integrated detailed data on microclimate and animal attributes of moose Alces alces, into a biophysical model to quantify costs of thermoregulation at fine and coarse spatial scales. During summer, moose spent an average of 67.8% of daylight hours bedded, and selected bed sites and home ranges that reduced risk of experiencing heat stress. For most of the day, shade could effectively mitigate the risk of experiencing heat stress up to 10°C, but at warmer temperatures (up to 20°C) wet soil was necessary to maintain homeostasis via conductive heat loss. Consistent selection across spatial scales for locations that reduced heat load underscores the importance of the thermal environment as a driver of behaviour in this heat-sensitive mammal. Moose in North America have long been characterized as riparian-obligate species because of their dependence on woody plant species for food. Nevertheless, the importance of dissipating endogenous heat loads conductively through wet soil suggests riparian habitats also are critical thermal refuges for moose. Such refuges may be especially important in the face of a warming climate in which both high environmental temperatures and drier conditions will likely exacerbate limits to heat dissipation, especially for large, heat-sensitive animals.

Characterization of profunda femoris vein thrombosis.

OBJECTIVE: The incidence of and risk factors for profunda femoris vein (PFV) thrombosis are poorly characterized. We prospectively identified patients with PFV deep venous thrombosis (DVT) to characterize the demographics and anatomic distribution of proximal DVT in patients with PFV DVT. METHODS: A prospective study was conducted of patients at a tertiary care university hospital with DVT diagnosed by venous duplex ultrasound scanning between June 2014 and June 2015. DVT patients were categorized as having PFV involvement (yes or no), and the anatomic distribution of other sites of ipsilateral venous thrombi was further stratified to determine whether there was external iliac vein (EIV), common femoral vein (CFV), or femoropopliteal vein (FPV) DVT. Demographic characteristics of the patients were compared between groups, PFV DVT vs proximal DVT without PFV DVT. RESULTS: Of 4584 lower extremity venous duplex ultrasound studies performed, 398 (8.7%) scans were positive for proximal DVT from 260 patients; 23.1% of patients with DVT (60/260) had DVT involving the PFV. Of 112 patients who had CFV DVT, 55 (49.1%) also had ipsilateral involvement of the PFV. Of 60 patients with PFV DVT, 55 (91.7%) had involvement of the ipsilateral CFV. Patients in the PFV DVT group were more likely to have a history of a hypercoagulable disorder (26.7% vs 14.5%; P = .029) and a history of immobility (58.3% vs 42%; P = .026) compared with those with proximal DVT without PFV DVT. There were no differences in smoking, recent surgery, personal or family history of DVT, other medical comorbidities, inpatient status, or survival. There was no difference in laterality of DVT between the PFV DVT and proximal DVT without PFV DVT groups (35% vs 41.5% left, 35% vs 33.5% right, 30% vs 25% bilateral; P = .619). There was a higher proportion of PFV DVT with EIV involvement (21.7% vs 2.5%; P < .00001) and a higher proportion of PFV DVT with CFV + FPV involvement (65.0% vs 19%; P < .00001) compared with proximal DVT without PFV DVT. There was no difference in survival between the PFV DVT and proximal DVT without PFV DVT groups. CONCLUSIONS: Patients with PFV thrombosis tend to have more thrombus burden with more frequent concurrent DVT in the EIV and FPV. Patients with PFV DVT are also more likely to have a history of hypercoagulable disorder and immobility. Ultrasound protocols for assessment of DVT should include routine examination of the PFV as a potential marker of a more virulent prothrombotic state.

Healthcare providers' experiences screening for intimate partner violence among migrant and seasonal farmworking women: A phenomenological study.

BACKGROUND: Migrant and seasonal farmworking (MSFW) women patients experience substantially more intimate partner violence (IPV) than the general population, but few health-care providers screen patients for IPV. While researchers have examined screening practices in health-care settings, none have exclusively focused on MSFW women. OBJECTIVE: The aim of this phenomenological study was to explore the experiences of health-care providers who have screened for and/or addressed IPV with MSFW women patients. DESIGN: Researchers utilized descriptive phenomenology to capture the lived experiences of these health-care providers. Data were analysed using Colaizzi's seven-stage framework. SETTING AND PARTICIPANTS: Interviews were conducted with nine female participants - all of whom: (i) were clinically active health-care providers within the MSFW community, (ii) were bilingual in English and Spanish or had access to a translator, (iii) had treated MSFW patients who had experienced IPV and (iv) were at least 18 years of age. RESULTS: Participants' experiences were reflected in four emergent themes: (i) provider-centered factors, (ii) patient-centered factors, (iii) clinic-centered factors and (iv) community-centered factors. Participants described barriers to establish routine IPV assessment, decrease patient ambivalence and increase on-site support and community resources. DISCUSSION AND CONCLUSIONS: This study aimed to generate a greater understanding of the experiences of health-care providers with screening for and addressing IPV with MSFW patients. Implications and recommendations for research, clinical practice and policy are provided.

Perceptions of Same-Sex Relationships and Marriage as Gender Role Violations: An Examination of Gendered Expectations (Sexism).

The current study sought to add to the literature that has demonstrated a link between sexism and sexual prejudice. The study evaluated whether a community sample with an age range of 19-64 (n = 122), including 32% sexual minority participants, believe that dating, sex, and marriage with same-sex partners are perceived to be gender role violations. Results varied by participant sexual/gender identity (LGBTQ or heterosexual) and political ideology. Liberal LGBTQ persons do not see same-sex relationships as gender role violations; LGBTQ non-liberals and heterosexual liberals rated same-sex relationships as mild violations; and non-liberal heterosexuals perceive same-sex relationships as "moderate" violations. Our results suggest both positive movement in attitudes toward same-sex relationships, including same-sex marriage, and broader recognition that gender identity, gender role expression, and sexual orientation are separate and distinct components of one's overall sexual identity.

Maternal Depression History Moderates Parenting Responses to Compliant and Noncompliant Behaviors of Children with ADHD.

Maternal depression and parenting are robust predictors of developmental outcomes for children with attention-deficit/hyperactivity disorder (ADHD). However, methods commonly used to examine parent-child interactions in these families do not account for temporal associations between child and parent behavior that have been theorized to maintain negative child behavior. Moreover, studies examining associations between maternal depression and parenting in families of children with ADHD have not compared mothers who were currently depressed, remitted, and never clinically depressed. This study utilized sequential analysis to examine how maternal reinforcement of compliant and noncompliant child behavior differs as a function of maternal depression history. Within the 82 participating mother-child dyads, 21 mothers were currently depressed, 29 mothers had a lifetime history of depression but were in remission for at least 1 month, and 32 mothers had never been clinically depressed. 24 girls (29.6 %) and 57 boys (70.4 %) between the ages of 6-12 years old (M = 8.7, SD = 2.0) and were diagnosed with ADHD. Results indicated that all mothers were less likely to respond optimally than non-optimally to child compliant and noncompliant behaviors during observed parent-child interactions; however, currently depressed mothers were least likely to reinforce child compliance and responded most coercively to child noncompliance relative to the other groups. Remitted mothers in this sample were more coercive than never clinically depressed mothers, but were more likely to follow through with commands than never clinically depressed mothers. Implications for behavioral parent training programs aimed at skill development for depressed mothers of children with ADHD are discussed.

Cardiomyocyte-specific BMAL1 plays critical roles in metabolism, signaling, and maintenance of contractile function of the heart.

Circadian clocks are cell autonomous, transcriptionally based, molecular mechanisms that confer the selective advantage of anticipation, enabling cells/organs to respond to environmental factors in a temporally appropriate manner. Critical to circadian clock function are 2 transcription factors, CLOCK and BMAL1. The purpose of the present study was to reveal novel physiologic functions of BMAL1 in the heart, as well as to determine the pathologic consequences of chronic disruption of this circadian clock component. To address this goal, we generated cardiomyocyte-specific Bmal1 knockout (CBK) mice. Following validation of the CBK model, combined microarray and in silico analyses were performed, identifying 19 putative direct BMAL1 target genes, which included a number of metabolic (e.g., ß-hydroxybutyrate dehydrogenase 1 [Bdh1]) and signaling (e.g., the p85α regulatory subunit of phosphatidylinositol 3-kinase [Pik3r1]) genes. Results from subsequent validation studies were consistent with regulation of Bdh1 and Pik3r1 by BMAL1, with predicted impairments in ketone body metabolism and signaling observed in CBK hearts. Furthermore, CBK hearts exhibited depressed glucose utilization, as well as a differential response to a physiologic metabolic stress (i.e., fasting). Consistent with BMAL1 influencing critical functions in the heart, echocardiographic, gravimetric, histologic, and molecular analyses revealed age-onset development of dilated cardiomyopathy in CBK mice, which was associated with a severe reduction in life span. Collectively, our studies reveal that BMAL1 influences metabolism, signaling, and contractile function of the heart.

Understanding circadian gene function: animal models of tissue-specific circadian disruption.

Circadian rhythms are the daily patterns that occur within an organism, from gene expression to behavior. These rhythms are governed not only externally by environmental cues but also internally, with cell-autonomous molecular clock mechanisms present nearly ubiquitously throughout the cells of organisms. In more complex organisms, it has been suggested that the clock mechanisms serve varied functions depending on the tissue in which they are found. By disrupting core circadian gene function in specific tissues of animal models, the various roles of the circadian clock in differing tissues can begin to be defined. This review provides an overview of the model organisms used to elucidate tissue-specific functions of the molecular circadian clock.

Intimate partner violence screening among migrant/seasonal farmworker women and healthcare: a policy brief.

Migrant and seasonal farm working (MSFW) women report higher rates of intimate partner violence (IPV) as compared to the national average (Hazen and Soriano in Violence Against Women 13:562-582, 2007). Although prior researchers have indicated that implementing IPV screenings in healthcare settings significantly increases rates of identifying IPV (Nelson et al. in Ann Intern Med 156:1-17, 2012; Ramsay et al. in Br Med J 325:314-318, 2002); many providers opt not to screen (Jonassen and Mazor in Acad Med 78(10):S20-S23, 2003; Smith et al. in Fam Community Health 20:1-18, 1998). The purpose of this policy brief is to review previous research related to IPV among MSFW women and, based on the findings, recommend policies that may help to improve the detection, intervention, resources, and available science with respect to this underserved population.

Determinants of pH-dependent modulation of translocation in dermonecrotic G-protein-deamidating toxins.

Cytotoxic necrotizing factors from E. coli (CNF1, CNF2) and Yersinia (CNFy)share N-terminal sequence similarity with Pasteurella multocida toxin (PMT). This common N-terminal region harbors the receptor-binding and translocation domains that mediate uptake and delivery of the C-terminal catalytic cargo domains into the host cytosol. Subtle variations in the N-terminal ~500 amino acids of CNFs and PMT could allow for selective recognition of cellular receptors and thus, selective target cell specificity. Through studies with cellular inhibitors, we have identified an additional novel function for this region in modulating responses of these toxin proteins to changes in pH during intoxication and delivery of the catalytic cargo domain into the cytosol.

Development and preliminary evaluation of an integrated treatment targeting parenting and depressive symptoms in mothers of children with attention-deficit/hyperactivity disorder.

OBJECTIVE: More than 50% of mothers of children with attention-deficit/hyperactivity disorder (ADHD) have a lifetime history of major depressive disorder (MDD). Maternal depressive symptoms are associated with impaired parenting and predict adverse developmental and treatment outcomes for children with ADHD. For these reasons, we developed and examined the preliminary efficacy of an integrated treatment targeting parenting and depressive symptoms for mothers of children with ADHD. This integrated intervention incorporated elements of 2 evidence-based treatments: behavioral parent training (BPT) and cognitive behavioral depression treatment. METHOD: Ninety-eight mothers with at least mild depressive symptoms were randomized to receive either standard BPT (n = 51) or the integrated parenting intervention for ADHD (IPI-A; n = 47). Participants were assessed at baseline, posttreatment, and 3- to 6-month follow-up on measures of (a) self-reported maternal depressive symptoms, (b) observed positive and negative parenting, and (c) observed and mother-reported child disruptive behavior and mother-reported child and family impairment. RESULTS: The IPI-A produced effects of small to moderate magnitude relative to BPT on maternal depressive symptoms, observed negative parenting, observed child deviance, and child impairment at posttreatment and on maternal depressive symptoms, child disruptive behavior, child impairment and family functioning at follow-up. Contrary to expectations, the BPT group demonstrated moderate to large effects relative to IPI-A on observed positive parenting at follow-up. CONCLUSIONS: This treatment development study provides encouraging preliminary support for the integrated intervention targeting parenting and depressive symptoms in mothers of children with ADHD. Future studies should examine whether this integrated intervention improves long-term developmental outcomes for children with ADHD. (PsycINFO Database Record (c) 2013 APA, all rights reserved).

Arf6-dependent intracellular trafficking of Pasteurella multocida toxin and pH-dependent translocation from late endosomes.

The potent mitogenic toxin from Pasteurella multocida (PMT) is the major virulence factor associated with a number of epizootic and zoonotic diseases caused by infection with this respiratory pathogen. PMT is a glutamine-specific protein deamidase that acts on its intracellular G-protein targets to increase intracellular calcium, cytoskeletal, and mitogenic signaling. PMT enters cells through receptor-mediated endocytosis and then translocates into the cytosol through a pH-dependent process that is inhibited by NH(4)Cl or bafilomycin A1. However, the detailed mechanisms that govern cellular entry, trafficking, and translocation of PMT remain unclear. Co-localization studies described herein revealed that while PMT shares an initial entry pathway with transferrin (Tfn) and cholera toxin (CT), the trafficking pathways of Tfn, CT, and PMT subsequently diverge, as Tfn is trafficked to recycling endosomes, CT is trafficked retrograde to the ER, and PMT is trafficked to late endosomes. Our studies implicate the small regulatory GTPase Arf6 in the endocytic trafficking of PMT. Translocation of PMT from the endocytic vesicle occurs through a pH-dependent process that is also dependent on both microtubule and actin dynamics, as evidenced by inhibition of PMT activity in our SRE-based reporter assay, with nocodazole and cytochalasin D, respectively, suggesting that membrane translocation and cytotoxicity of PMT is dependent on its transfer to late endosomal compartments. In contrast, disruption of Golgi-ER trafficking with brefeldin A increased PMT activity, suggesting that inhibiting PMT trafficking to non-productive compartments that do not lead to translocation, while promoting formation of an acidic tubulovesicle system more conducive to translocation, enhances PMT translocation and activity.

Clinical verification of the performance of the pathwork tissue of origin test: utility and limitations.

Gene expression-based assays have been introduced into the clinical arena to assist in the diagnosis of poorly differentiated or undifferentiated tumors. The US Food and Drug Administration has cleared the microarray-based Pathwork Tissue of Origin (TOO) Test (Pathwork Diagnostics, Sunnyvale, CA) for the molecular characterization of such challenging specimens. We aimed at verifying the analytic and clinical performance of this test on 43 poorly differentiated and undifferentiated tumor samples, including 6 off-panel cases and 7 cancers of unknown primary (CUP). Our results showed 97% (95% confidence interval, 80.4%-99.8%) agreement between the Pathwork TOO Test result and the complete diagnosis, which included clinical correlations and immunohistochemical staining, after the original diagnosis. We concluded that for off-panel and CUP samples, the tissue type and the cell type may be confounded by the Pathwork TOO Test and that careful clinicopathologic assessment is needed when interpreting results from this helpful ancillary tool for pathologists.

The relation between maternal ADHD symptoms & improvement in child behavior following brief behavioral parent training is mediated by change in negative parenting.

This study examined the extent to which maternal attention-deficit/hyperactivity disorder (ADHD) symptoms predict improvement in child behavior following brief behavioral parent training. Change in parenting was examined as a potential mediator of the negative relationship between maternal ADHD symptoms and improvement in child behavior. Seventy mothers of 6-10 year old children with ADHD underwent a comprehensive assessment of adult ADHD prior to participating in an abbreviated parent training program. Before and after treatment, parenting was assessed via maternal reports and observations and child disruptive behavior was measured via maternal report. Controlling for pre-treatment levels, maternal ADHD symptomatology predicted post-treatment child disruptive behavior problems. The relation between maternal ADHD symptomatology and improvement in child behavior was mediated by change in observed maternal negative parenting. This study replicated findings linking maternal ADHD symptoms with attenuated child improvement following parent training, and is the first to demonstrate that negative parenting at least partially explains this relationship. Innovative approaches combining evidence-based treatment for adult ADHD with parent training may therefore be necessary for families in which both the mother and child have ADHD. Larger-scale studies using a full evidence-based parent training program are needed to replicate these findings.

Implications of high level pseudogene transcription in Mycobacterium leprae.

BACKGROUND: The Mycobacterium leprae genome has less than 50% coding capacity and 1,133 pseudogenes. Preliminary evidence suggests that some pseudogenes are expressed. Therefore, defining pseudogene transcriptional and translational potentials of this genome should increase our understanding of their impact on M. leprae physiology. RESULTS: Gene expression analysis identified transcripts from 49% of all M. leprae genes including 57% of all ORFs and 43% of all pseudogenes in the genome. Transcribed pseudogenes were randomly distributed throughout the chromosome. Factors resulting in pseudogene transcription included: 1) co-orientation of transcribed pseudogenes with transcribed ORFs within or exclusive of operon-like structures; 2) the paucity of intrinsic stem-loop transcriptional terminators between transcribed ORFs and downstream pseudogenes; and 3) predicted pseudogene promoters. Mechanisms for translational "silencing" of pseudogene transcripts included the lack of both translational start codons and strong Shine-Dalgarno (SD) sequences. Transcribed pseudogenes also contained multiple "in-frame" stop codons and high Ka/Ks ratios, compared to that of homologs in M. tuberculosis and ORFs in M. leprae. A pseudogene transcript containing an active promoter, strong SD site, a start codon, but containing two in frame stop codons yielded a protein product when expressed in E. coli. CONCLUSION: Approximately half of M. leprae's transcriptome consists of inactive gene products consuming energy and resources without potential benefit to M. leprae. Presently it is unclear what additional detrimental affect(s) this large number of inactive mRNAs has on the functional capability of this organism. Translation of these pseudogenes may play an important role in overall energy consumption and resultant pathophysiological characteristics of M. leprae. However, this study also demonstrated that multiple translational "silencing" mechanisms are present, reducing additional energy and resource expenditure required for protein production from the vast majority of these transcripts.

Molecular determination of Mycobacterium leprae viability by use of real-time PCR.

Mycobacterium leprae, the etiological agent of leprosy, is noncultivable on axenic media. Therefore, the viability of M. leprae for clinical or experimental applications is often unknown. To provide new tools for M. leprae viability determination, two quantitative reverse transcriptase PCR (RT-PCR) assays were developed and characterized. M. leprae sodA mRNA and 16S rRNA were used as RNA targets, and M. leprae repetitive element (RLEP) DNA was used to determine relative bacterial numbers in the same purified bacterial preparations or from crude biological specimens. Results demonstrated that both assays were good predictors of M. leprae viability during short-term experiments (48 h) involving rifampin (rifampicin) treatment in axenic medium, within rifampin-treated murine macrophages (MPhi), or within immune-activated MPhi. Moreover, these results strongly correlated those of other M. leprae viability assays, including radiorespirometry-based and Live/Dead BacLight viability assays. The 16S rRNA/RLEP assay consistently identified the presence of M. leprae in eight multibacillary leprosy patient biopsy specimens prior to multidrug therapy (MDT) and demonstrated a decline in viability during the course of MDT. In contrast, the sodA/RLEP assay was able to detect the presence of M. leprae in only 25% of pretreatment biopsy specimens. In conclusion, new tools for M. leprae viability determination were developed. The 16S rRNA/RLEP RT-PCR M. leprae viability assay should be useful both for short-term experimental purposes and for predicting M. leprae viability in biopsy specimens to monitor treatment efficacy, whereas the sodA/RLEP RT-PCR M. leprae viability assay should be limited to short-term experimental research purposes.

Associations between maternal attention-deficit/hyperactivity disorder symptoms and parenting.

Mothers of children with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for an ADHD diagnosis themselves, which is likely associated with impairments in parenting. The present study utilized a multi-method assessment of maternal ADHD and parenting to examine the extent to which maternal ADHD symptoms are associated with maladaptive parenting. Participants included 70 6-10 year old children with DSM-IV ADHD and their biological mothers. Results suggested that mothers with higher levels of ADHD symptoms reported lower levels of involvement and positive parenting and higher levels of inconsistent discipline. During observed parent-child interactions, maternal ADHD symptoms were negatively associated with positive parenting, and positively associated with negative parenting and repeated commands before giving the child an opportunity to comply. Given prior research suggesting that maladaptive parenting behaviors are risk factors for the later development of conduct problems among children with ADHD, these findings have important clinical implications for family-based assessment and treatment of ADHD.