An anaphase surveillance mechanism prevents micronuclei formation from frequent chromosome segregation errors

Micronuclei are a hallmark of cancer and several other human disorders. Recently, micronuclei were implicated in chromothripsis, a series of massive genomic rearrangements that may drive tumor evolution and progression. Here, we show that Aurora B kinase mediates a surveillance mechanism that integrates error correction during anaphase with spatial control of nuclear envelope reassembly to prevent micronuclei formation. Using high-resolution live-cell imaging of human cancer and non-cancer cells, we uncover that anaphase lagging chromosomes are more frequent than previously anticipated, yet they rarely form micronuclei. Micronuclei formation from anaphase lagging chromosomes is prevented by a midzone-based Aurora B phosphorylation gradient that stabilizes kinetochore-microtubule attachments and assists spindle forces required for anaphase error correction while delaying nuclear envelope reassembly on lagging chromosomes, independently of microtubule density. We propose that a midzone-based Aurora B phosphorylation gradient actively monitors and corrects frequent chromosome segregation errors to prevent micronuclei formation during human cell division.We thank António Pereira and Ana Almeida for assistance with CH-STED, Ariana Jacome for the generation of lentiviral vectors, Cristina Ferrás and Marco Novais-Cruz for drawing attention to the effects of nocodazole treatment and washout on the Aurora B phosphorylation gradient, current and former lab members for suggestions, and Jonathan Higgins and Andrew McAinsh for discussing results prior to publication. This work was funded by the European Research Council (ERC) consolidator grant CODECHECK , under the European Union’s Horizon 2020 research and innovation programme (grant agreement 681443 ), and Fundação para a Ciência e a Tecnologia of Portugal ( PTDC/MED-ONC/3479/2020 )

Spatiotemporal control of mitotic exit during anaphase by an aurora B-Cdk1 crosstalk

According to the prevailing ‘clock’ model, chromosome decondensation and nuclear envelope reformation when cells exit mitosis are byproducts of Cdk1 inactivation at the metaphase-anaphase transition, controlled by the spindle assembly checkpoint. However, mitotic exit was recently shown to be a function of chromosome separation during anaphase, assisted by a midzone Aurora B phosphorylation gradient-the ‘ruler’ model. Here we found that Cdk1 remains active during anaphase due to ongoing APC/CCdc20- and APC/CCdh1-mediated degradation of B-type Cyclins in Drosophila and human cells. Failure to degrade B-type Cyclins during anaphase prevented mitotic exit in a Cdk1-dependent manner. Cyclin B1-Cdk1 localized at the spindle midzone in an Aurora B-dependent manner, with incompletely separated chromosomes showing the highest Cdk1 activity. Slowing down anaphase chromosome motion delayed Cyclin B1 degradation and mitotic exit in an Aurora B-dependent manner. Thus, a crosstalk between molecular ‘rulers’ and ‘clocks’ licenses mitotic exit only after proper chromosome separation.We thank Eric Griffis, Jean-René Huynh, Claudio Sunkel, Jonathon Pines, Melina Schuh and Christian Lehner for the kind gift of reagents, and Marco Gonzalez-Gaitán for supporting OA during the final stages of this work. LPC is the recipient of a Marie Skłodowska-Curie Action fellowship (grant agreement 746515). EMS holds an FCT Investigator position and his work is supported by Fundac¸ ão para a Ciência e a Tecnologia (PTDC/BEX-BCM/0432/2014). This work was supported by R01GM107026 grant to TJM and a Commonwealth Honors College grant to CMC Confocal and FLIM microscopy data collection was performed in the Light Microscopy Facility and Nikon Center of Excellence at the Institute for Applied Life Sciences, University of Massachusetts Amherst with support from the Massachusetts Life Science Center. Work in the HM lab is supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 681443) and FLAD Life Science 2020

Geo-environmental mapping using physiographic analysis: constraints on the evaluation of land instability and groundwater pollution hazards in the Metropolitan District of Campinas, Brazil

Geo-environmental terrain assessments and territorial zoning are useful tools for the formulation and implementation of environmental management instruments (including policy-making, planning, and enforcement of statutory regulations). They usually involve a set of procedures and techniques for delimitation, characterisation and classification of terrain units. However, terrain assessments and zoning exercises are often costly and time-consuming, particularly when encompassing large areas, which in many cases prevent local agencies in developing countries from properly benefiting from such assessments. In the present paper, a low-cost technique based on the analysis of texture of satellite imagery was used for delimitation of terrain units. The delimited units were further analysed in two test areas situated in Southeast Brazil to provide estimates of land instability and the vulnerability of groundwater to pollution hazards. The implementation incorporated procedures for inferring the influences and potential implications of tectonic fractures and other discontinuities on ground behaviour and local groundwater flow. Terrain attributes such as degree of fracturing, bedrock lithology and weathered materials were explored as indicators of ground properties. The paper also discusses constraints on- and limitations of- the approaches taken

Phylodynamics of foot-and-mouth disease virus O/PanAsia in Vietnam 2010-2014

© 2017 The Author(s). Foot-and-mouth disease virus (FMDV) is endemic in Vietnam, a country that plays an important role in livestock trade within Southeast Asia. The large populations of FMDV-susceptible species in Vietnam are important components of food production and of the national livelihood. In this study, we investigated the phylogeny of FMDV O/PanAsia in Vietnam, reconstructing the virus' ancestral host species (pig, cattle or buffalo), clinical stage (subclinical carrier or clinically affected) and geographical location. Phylogenetic divergence time estimation and character state reconstruction analyses suggest that movement of viruses between species differ. While inferred transmissions from cattle to buffalo and pigs and from pigs to cattle are well supported, transmission from buffalo to other species, and from pigs to buffalo may be less frequent. Geographical movements of FMDV O/PanAsia virus appears to occur in all directions within the country, with the South Central Coast and the Northeast regions playing a more important role in FMDV O/PanAsia spread. Genetic selection of variants with changes at specific sites within FMDV VP1 coding region was different depending on host groups analyzed. The overall ratio of non-synonymous to synonymous nucleotide changes was greater in pigs compared to cattle and buffalo, whereas a higher number of individual amino acid sites under positive selection were detected in persistently infected, subclinical animals compared to viruses collected from clinically diseased animals. These results provide novel insights to understand FMDV evolution and its association with viral spread within endemic countries. These findings may support animal health organizations in their endeavor to design animal disease control strategies in response to outbreaks

Suunnitteluprosessiohje

Tämän opinnäytetyön aiheena oli suunnitteluprosessiohje. Opinnäytetyön tavoitteena oli tehdä Suomen Imurikeskus Oy:lle vakioidut toimintatavat laitteistojen suunnittelun kululle, ja selvittää mahdollinen kehitysvaihtoehto tiedonhallinnalle. Opinnäytetyössä käytiin lävitse Suomen Imurikeskus Oy:n laitteistojen valmistuksen eri vaiheita suunnittelijoiden osalta. Tämän perusteella kehitettiin vakioidut toimintatavat suunnitteluprosessiohjeeseen. Kehitysvaihtoehtona tiedonhallinnalle harkittiin Vertex Systems Oy:n Vertex Flow PDM/PLM -ohjelmistoa ja ohjelmistoon käytiin tutustumassa Vertex Systems Oy:n järjestämssä PLM-päivässä Tampereella. Lopputuloksena saatiin valmistettua Suomen Imurikeskus Oy:n käyttöön toimiva suunnitteluprosessiohje laitteistojen suunnitteluun. Suunnitteluprosessiohje sisältää ohjeistuksen laitteistojen suunnittelun eri vaiheille.The purpose of this thesis was to create engineering process manual for Suomen Imurikeskus Oy. The manual is meant to clarify the correct procedures for the process of appliance planning and alternative options for data management. In this thesis different phases of manufacturing were examined from Suomen Imurikeskus Oy’s designers point of view. Based on the thesis some standardized procedures were created for the engineering process manual. Vertex Systems' Vertex Flow PDM/PLM software was considered as an option for data management and the software was familiarized by visiting PLM-fair hosted by Vertex Systems Oy in Tampere. End result of the thesis was an engineering process manual for appliance planning to Suomen Imurikeskus Oy use. Engineering process manual includes instructions to different steps of appliance planning

Validation of the Chronic Pain Acceptance Questionnaire-8 in an Australian pain clinic sample

Background: Recently, an 8-item short-form version of the Chronic Pain Acceptance Questionnaire (CPAQ-8) was developed predominantly in an internet sample. Further investigation of the factor structure in a multidisciplinary pain clinic sample is required. Investigation of the concurrent validity of the CPAQ-8 after accounting for the effects of variables commonly measured in the pain clinic setting is also necessary. Purpose: This study examines the factor structure and concurrent validity of the CPAQ-8 in a sample of treatmentseeking patients who attended a multidisciplinary pain clinic. Methods: Participants were 334 patients who attended an Australian multidisciplinary pain service. Participants completed the CPAQ, a demographic questionnaire, and measures of patient adjustment and functioning. Results: Confirmatory factor analysis identified a two-factor 8-item model consisting of Activity Engagement and Pain Willingness factors (SRMR=0.039, RMSEA=0.063, CFI=0.973, TLI=0.960) was superior to both the CPAQ and CPAQ with an item removed. The CPAQ and CPAQ-8 total scores were highly correlated (r=0.93). After accounting for pain intensity, the CPAQ-8 was a significant predictor of depression, anxiety, stress, and disability. The subscales of the CPAQ-8 were both unique contributors to depression and disability in regression analyses, after accounting for pain intensity and kinesiophobia, and after accounting for pain intensity and catastrophizing. Conclusions: The CPAQ-8 has a sound factor structure and similar psychometric properties to the CPAQ; it may have clinical utility as a measure of pain acceptance in treatmentseeking, chronic pain patients

Segurança do paciente em Unidades de Terapia Intensiva: desenvolvimento de um projeto de pesquisa

RESUMO Objetivo Relatar a experiência sobre os diferentes processos envolvidos no desenvolvimento de um Projeto de Pesquisa em Segurança do Paciente em Unidades de Terapia Intensiva. Método Estudo com delineamento misto: coorte histórica para a coleta dos dados dos pacientes e eventos adversos/incidentes e transversal para a coleta dos dados da equipe de enfermagem. A coleta de dados ocorreu durante 90 dias, em 2012, no Instituto Central do Hospital das Clínicas da Universidade de São Paulo e o Hospital Universitário da Universidade de São Paulo. Processos desenvolvidos A pesquisa envolveu diversas etapas para sua efetivação: implantação doNursing Activities Score (NAS) no Instituto Central do Hospital das Clínicas da Universidade de São Paulo, desenvolvimento de sistema de banco de dados, digitalização de prontuários, treinamento de monitores, extração e carga de dados dos pacientes e coleta de dados durante a passagem de plantão, prontuários. Considerações finais Treinamentos, comprometimento dos pesquisadores e parceria com profissionais da tecnologia da informação foram fundamentais para a qualidade dos resultados obtidos e da produção científica alcançada. Espera-se que esse relato de experiência possa orientar e encorajar os pesquisadores a realizar pesquisas complexas que contribuam para a construção do conhecimento na enfermagem e saúde

Internet addiction, fatigue, and sleep problems among adolescent students: a large-scale study

Aim: The aim of the present study was to examine the association between Internet Addiction (IA), fatigue, and sleep problems among university students. Methods: A total of 3,000 Turkish students aged 18 to 25 years were approached and 2,350 students (78.3%) participated in this cross-sectional study from April 2017 to September 2017 in public and private universities in Istanbul. Data were collected via a structured questionnaire including socio-demographic details, lifestyle and dietary habits, Internet Addiction Test (IAT), Fatigue Scale, and Epworth Sleepiness Scale [ESS]. Descriptive statistics, multivariate and factorial analyses were performed. Results: The overall prevalence of IA among the studied population was 17.7%. There were significant differences between gender, family income, father’s occupation, school performance, frequency and duration of watching television, physical activity, internet use duration, and sleep duration (all p<0.001). Significant differences were also found between participants with IA and those without IA in having headaches, blurred vision, double vision, hurting eyes, hearing problems, and eating fast food frequently (all p<0.001). Using multivariate regression analysis, the duration of internet use, physical and mental symptoms, headache, hurting eyes, tired eyes, hearing problems and ESS scores were significantly associated with (and primary predictors of) IA. Conclusion: The present study demonstrated that IA was associated with poor dietary habits, sleep problems, and fatigue symptoms

Aging and health: Self-efficacy for Self-direction in Health Scale

ABSTRACT OBJECTIVE To validate the Escala de Autoeficácia para a Autodireção na Saúde (EAAS – Self-efficacy for Self-direction in Health Scale). METHODS Non-experimental quantitative study of EAAS validation, by confirmatory factorial analyses, evaluating a sample of 508 older adults from the north and the center of Portugal with mean age of 71.67 (from 51 to 96 years), to whom the Self-efficacy for Self-direction in Health Scale, the Rosenberg Self-esteem Scale, the Positive and Negative Affect Schedule, the Satisfaction with Life Scale, and the Instrumental Activities of Daily Living Scale were applied. The EAAS was developed from the theoretical constructs of self-efficacy and from self-directed learning within the PALADIN European project framework, aiming to develop an instrument able to assess the extent to which older adults take good care of their health. RESULTS The internal consistency was 0.87 (Cronbach’s alpha) and confirmatory factorial analyses enabled to find a model near the one theoretically proposed, indicating a structure consisting of four dimensions: physical exercise, healthy diet, engaging in health-related learning, and visits to health professionals. From the psychometric point of view, the model in four factors showed quite satisfactory fit indicators. CONCLUSIONS The Self-efficacy for Self-direction in Health Scale, with 16 items, is adequate to evaluate to what extent older adults have confidence in their ability to take care of their own health, with high degree of autonomy