Data Descriptor: A genome-scale RNAi screen for genetic interactors of the dynein co-factor nud-2 in Caenorhabditis elegans

Cytoplasmic dynein 1 (dynein) is the predominant microtubule minus end-directed motor in animals and participates in a wide range of cellular processes, including membrane trafficking, nuclear migration, and cell division. Dynein's functional diversity depends on co-factors that regulate its subcellular localization, interaction with cargo, and motor activity. The ubiquitous co-factor nuclear distribution gene E (NudE) is implicated in many of dynein's functions, and mutations in NudE cause the brain developmental disease microcephaly. To identify genetic interactors of the Caenorhabditis elegans NudE homolog nud-2, we performed a genome-wide RNAi screen with the null allele nud-2(ok949), which compromises dynein function but leaves animals viable and fertile. Using bacterial feeding to deliver dsRNAs in a 96-well liquid format and a semi-automated fluorescence microscopy approach for counting parents and progeny, we screened 19762 bacterial clones and identified 38 genes whose inhibition caused enhanced lethality in nud-2(ok949) relative to the nud-2(+) control. Further study of these genes, many of which participate in cell division, promises to provide insight into the function and regulation of dynein.The authors acknowledge the support of the BioSciences Screening i3S Scientific Platform. Funding for this project was provided by the European Research Council under the European Union's Seventh Framework Programme (ERC grant agreement n o ERC-2013-StG-338410-DYNEINOME to R.G.), by the European Molecular Biology Organization (EMBO Installation Grant 2545 to R.G.), by the Fundacao para a Ciencia e a Tecnologia (IF/01015/2013/CP1157/CT0006 to R.G. and SFRH/BD/103495/2014 to H. R.), and by 'Norte-01-0145-FEDER-000029-Advancing cancer research: from basic knowledge to application', supported by the Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement through the European Regional Development Fund (FEDER

SEASONAL VARIATIONS, METAL DISTRIBUTION AND WATER QUALITY IN THE TODOS OS SANTOS RIVER, SOUTHEASTERN BRAZIL: A MULTIVARIATE ANALYSIS

In aquatic habitats, metal contamination from natural and anthropogenic sources continues to pose a concern for human and environmental health. Thus, it is important to complete monitoring studies to assess patterns and the extent of metal contamination in these ecosystems. The objective of this study was to determine the concentrations of 31 chemical elements and water quality parameters of the Todos os Santos River located in the Mucuri Valley, Minas Gerais, Brazil and use multivariate statistical analyses to determine any seasonal and spatial patterns in the data. Results demonstrated that metals including Al, Fe, and Ni exceeded Brazilian and international guidelines for these elements with nutrients such as P also exceeding water quality standards. Principal components analysis indicated distinct geographical and seasonal patterns for multiple elements with hierarchical cluster analysis confirming the observed spatial patterns of contamination in the Todos os Santos River

Psychosocial correlates of physical activity in school children aged 8-10 years

Background: Understanding correlates of physical activity (PA) among children in different populations may contribute to fostering active lifestyles. This study considered gender differences in relationships between biologic (body mass index, BMI), demographic (socioeconomic sport status, SES) and psychosocial correlates of PA and level of PA in Portuguese primary school children. Methods: 683 children, aged 8–10 years, from 20 different elementary schools in northern Portugal were surveyed. Weight status was classified using International Obesity Task Force (IOTF) criteria for the BMI. Family SES was estimated from school records. PA level and psychosocial correlates (attraction to PA, perceived physical competence and parental socialization) were obtained with interview and standardized questionnaires, respectively. Sex-specific hierarchical multiple regression analyses (SPSS 18.0) were conducted and included two blocks of predictor variables (biologic and demographic, and psychosocial). Results: Level of PA was significantly higher in boys than girls. Enjoyment of participation in vigorous PA was positively associated with level of PA. Perceived acceptance by peers in games and sports and parental encouragement were positively and significantly related to PA in girls. Perceived physical competence was positively and significantly related to PA in boys. Weight status and SES were not associated with PA. Conclusions: Boys and girls differed in perceived attractiveness of PA and perceived physical competence, both of which influenced level of PA. Differences in perceptions may be important aspects of motivation for PA in school children

Genome-wide RNAi screen for synthetic lethal interactions with the C. elegans kinesin-5 homolog BMK-1

Kinesins are a superfamily of microtubule-based molecular motors that perform various transport needs and have essential roles in cell division. Among these, the kinesin-5 family has been shown to play a major role in the formation and maintenance of the bipolar mitotic spindle. Moreover, recent work suggests that kinesin-5 motors may have additional roles. In contrast to most model organisms, the sole kinesin-5 gene in Caenorhabditis elegans, bmk-1, is not required for successful mitosis and animals lacking bmk-1 are viable and fertile. To gain insight into factors that may act redundantly with BMK-1 in spindle assembly and to identify possible additional cellular pathways involving BMK-1, we performed a synthetic lethal screen using the bmk-1 deletion allele ok391. We successfully knocked down 82% of the C. elegans genome using RNAi and assayed viability in bmk-1(ok391) and wild type strains using an automated high-throughput approach based on fluorescence microscopy. The dataset includes a final list of 37 synthetic lethal interactions whose further study is likely to provide insight into kinesin-5 function.We thank the members of the Medema, Kops, Lens, Boxem, The, van den Heuvel, Carvalho and Gassmann laboratories for helpful discussion. To Belen Fernandez-Garcia for helping on hit picking from the genome-wide library. To Oliver Pelz for help with web cellHTS2 application during data analysis. A.F. Maia is a FCT-Fundacao para a Ciencia e a Tecnologia postdoctoral fellow (SFRH/BPD/71364/2010). The R.H. Medema laboratory was supported by the Netherlands Organization for Scientific Research (ZonMw 918.46.616) and the Netherlands Genomics Initiative. S. van den Heuvel received funding from the Netherlands Organisation for Scientific Research (NWO), Chemical Sciences (CW ECHO project 711.011.010). Work on C.E. Sunkel laboratory was funded by FEDER funds through the Operational Competitiveness Programme-COMPETE and by National Funds through FCT-Fundacao para a Ciencia e a Tecnologia under the project FCOMP-01-0124-FEDER-019740 (PTDC/BIA-BCM/120366/2010). R. Gassmann laboratory is supported by an ERC Starting Grant (338410), an EMBO Installation Grant, and funding from the Fundacao para a Ciencia e a Tecnologia (IF/01015/2013/CP1157/CT0006). R.H. Medema had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis

Concomitant sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman Disease) and diffuse large B-cell lymphoma: a case report

IntroductionSinus histiocytosis with massive lymphadenopathy, also known as Rosai-Dorfman Disease, is a rare and benign source of lymphadenopathy first described in 1969, which mimics neoplastic processes. This disease commonly presents in children and young adults with supra-diaphragmatic lymphadenopathy or extranodal lesions consisting of tissue infiltrates composed of a polyclonal population of histiocytes. Since its description greater than 400 cases have been described, sometimes in patients with a variety of treated and untreated neoplastic diseases. However, the literature contains reports of only 19 cases of Rosai-Dorfman Disease in association with lymphomas, Hodgkin's or non-Hodgkin's. The majority of these cases have the two diagnoses, malignant lymphoma and Rosai-Dorfman Disease, separated in time. Interestingly, infradiaphragmatic lymphadenopathy was a feature in the majority of previously reported cases of Rosai-Dorfman Disease and non-Hodgkin's lymphoma.Case presentationThis report provides details of a case with co-existing sinus histiocytosis with massive lymphadenopathy and diffuse large B cell non-Hodgkin's lymphoma. This case is the fifth described case of simultaneous Rosai-Dorfman Disease and concurrent non-Hodgkin's lymphoma. Unfortunately, the diagnosis of a clinically aggressive diffuse large B cell lymphoma was made at autopsy. The aggressive biological behavior of the diffuse large B cell lymphoma in this patient may have been related to the underlying immune dysregulation believed to be part of the pathophysiology of Rosai-Dorfman Disease.ConclusionTaken together this report and the preceding reports of Rosai-Dorfman Disease and non-Hodgkin's lymphoma suggests that in cases with a diagnosis of Rosai-Dorfman Disease in the setting of prominent infradiaphragmatic lymphadenopathy, clinicians should maintain a high index of suspicion for the presence of occult non-Hodgkin's lymphoma especially if the clinical course is atypical for classic Rosai-Dorfman Disease

A computational psychiatry approach identifies how alpha-2A noradrenergic agonist Guanfacine affects feature-based reinforcement learning in the macaque

[EN] Noradrenaline is believed to support cognitive flexibility through the alpha 2A noradrenergic receptor (a2A-NAR) acting in prefrontal cortex. Enhanced flexibility has been inferred from improved working memory with the a2A-NA agonist Guanfacine. But it has been unclear whether Guanfacine improves specific attention and learning mechanisms beyond working memory, and whether the drug effects can be formalized computationally to allow single subject predictions. We tested and confirmed these suggestions in a case study with a healthy nonhuman primate performing a feature-based reversal learning task evaluating performance using Bayesian and Reinforcement learning models. In an initial dose-testing phase we found a Guanfacine dose that increased performance accuracy, decreased distractibility and improved learning. In a second experimental phase using only that dose we examined the faster feature-based reversal learning with Guanfacine with single-subject computational modeling. Parameter estimation suggested that improved learning is not accounted for by varying a single reinforcement learning mechanism, but by changing the set of parameter values to higher learning rates and stronger suppression of non-chosen over chosen feature information. These findings provide an important starting point for developing nonhuman primate models to discern the synaptic mechanisms of attention and learning functions within the context of a computational neuropsychiatry framework.This research was supported by grants from the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Ontario Ministry of Economic Development and Innovation (MEDI). We thank Dr. Hongying Wang for invaluable help with drug administration and animal careHassani, SA.; Oemisch, M.; Balcarras, M.; Westendorff, S.; Ardid-Ramírez, JS.; Van Der Meer, MA.; Tiesinga, P.... (2017). 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Neuregulin1/ErbB system: importance in the control of cardiovascular function

The family of Neuregulins (NRG), growth factors like epidermal growth factor, is known to induce growth and differentiation of epithelial, glial, neuronal, and skeletal muscle cells. This family comprises four members, being NRG1 the most largely studied, particularly at the cardiovascular level. The biological effects of NRG1 in the adult heart are mediated by the tyrosine kinase receptors ErbB. In the adult heart, NRG1 is expressed by cells of the endocardial endothelium and the cardiac microvascular endothelium, and the receptors ErbB2/ErbB4 are expressed by ventricular cardiomyocytes and are located in T-tubule system and intercalated disks in close proximity to the system components of excitation-contraction coupling. The importance of the NRG/ErbB signaling axis at the cardiovascular level became evident after discovering that patients treated with trastuzumab (inhibitory antibody against ErbB2, used in the treatment of breast cancer) can develop ventricular dysfunction and have higher risk of cardiomyopathy when co-administered with anthracyclines. Subsequent studies in vitro and in vivo have clarified the effects and the respective signaling pathways associated with the NRG/ErbB system in the adult heart. Some cardiovascular functions of the NRG1/ErbB system have been described at the vascular (stimulation of angiogenesis and ateroprotector effect) and myocardium level (negative inotropic effect) as well as effect on the survival, cell growth and organization of the cardiomyocytes (myofibrillar organization and cell-to-cell contact between cardiomyocytes). Furthermore, the interaction of this system with other neurohumoral mediators has been studied. Thus, there seems to be a physiological role in modulating the sympathovagal balance and an interaction with endothelin-1 signaling. All these effects result from the activation of different intracellular signaling cascades, as a consequence of the binding of NRG1 to ErbB receptors. Some cardiac signaling pathways identified until now include molecules such as MEK / Erk 1/2, phosphatidylinositol 3-kinase/ Akt, focal adhesion kinase, Gab (Grb-2-associated binder) family, vascular endothelial growth factor and NO production by endothelial nitric oxide synthase. Thus, the aim of this paper was to make an up-to-date review of existing information on NRG1/ErbB signaling axis, with particular focus on its cardiovascular effects