Willingness towards cognitive engagement: a preliminary study based on a behavioural entropy approach

Faced with a novel task some people enthusiastically embark in it and work with determination, while others soon lose interest and progressively reduce their efforts. Although cognitive neuroscience has explored the behavioural and neural features of apathy, the why’s and how’s of positive engagement are only starting to be understood. Stemming from the observation that the left hemisphere is commonly associated to a proactive (‘do something’) disposition, we run a preliminary study exploring the possibility that individual variability in eagerness to engage in cognitive tasks could reflect a preferred left- or right-hemisphere functioning mode. We adapted a task based on response-independent reinforcement and used entropy to characterize the degree of involvement, diversification, and predictability of responses. Entropy was higher in women, who were overall more active, less dependent on instructions, and never reduced their engagement during the task. Conversely, men showed lower entropy, took longer pauses, and became significantly less active by the end of the allotted time, renewing their efforts mainly in response to negative incentives. These findings are discussed in the light of neurobiological data on gender differences in behaviour

Willingness towards cognitive engagement: a preliminary study based on a behavioural entropy approach

Faced with a novel task some people enthusiastically embark in it and work with determination, while others soon lose interest and progressively reduce their efforts. Although cognitive neuroscience has explored the behavioural and neural features of apathy, the why’s and how’s of positive engagement are only starting to be understood. Stemming from the observation that the left hemisphere is commonly associated to a proactive (‘do something’) disposition, we run a preliminary study exploring the possibility that individual variability in eagerness to engage in cognitive tasks could reflect a preferred left- or right-hemisphere functioning mode. We adapted a task based on response-independent reinforcement and used entropy to characterize the degree of involvement, diversification, and predictability of responses. Entropy was higher in women, who were overall more active, less dependent on instructions, and never reduced their engagement during the task. Conversely, men showed lower entropy, took longer pauses, and became significantly less active by the end of the allotted time, renewing their efforts mainly in response to negative incentives. These findings are discussed in the light of neurobiological data on gender differences in behaviour

Dead regions in the cochlea at high frequencies: implications for the adaptation to hearing aids

In patients with moderate to severe high-frequency hearing loss, cochlear damage may include dead regions where there are no functional inner hair cells and/or associated neurons. AIM: This study examines speech recognition in sensorineural impaired hearing patients with and without cochlear dead regions at high frequencies. METHODS: a clinical and experimental study was made of thirty patients with sensorineural hearing loss that were classified into two groups: group 1 - included 15 subjects with hearing loss and no dead regions; and group 2 - included 15 subjects with dead regions in the cochlea at high frequencies. Patients undertook word recognition score and speech reception threshold tests, with and without background noise. The speech tests were done with and without hearing aids in two situations: program 1 - broadband amplification (bandwidth 8000 Hz); and program 2 - amplification up to 2560 Hz, without high frequency gain. RESULTS: For subjects with no dead regions in the cochlea (group 1) performance improved with program 1. For subjects with dead regions in the cochlea (group 2) performance improved with program 2. CONCLUSIONS: Subjects with no dead regions in the cochlea benefited from high-frequency information. Subjects with dead regions in the cochlea benefited from reduced gain at high frequencies.Em perdas auditivas de grau moderado a severo nas freqüências altas, a lesão coclear pode estar relacionada a zonas mortas, regiões onde as células ciliadas internas e/ou neurônios adjacentes não são funcionais. OBJETIVO: Avaliar o reconhecimento de fala em pacientes com e sem zonas mortas na cóclea em freqüências altas. MATERIAL e MÉTODO: Estudo clínico e experimental de 30 indivíduos adultos, distribuídos em dois grupos: grupo 1 - 15 indivíduos sem zonas mortas, e grupo 2 - 15 com zonas mortas na cóclea. Os pacientes foram submetidos à pesquisa do índice de reconhecimento de fala, limiar de reconhecimento de sentenças, sem e com ruído competitivo. Os testes de fala foram realizados sem prótese, com próteses auditivas amplificando a faixa de freqüências de 100 a 8000 Hz (programa 1) e com amplificação restrita, 100 a 2560 Hz (programa 2). RESULTADOS: O grupo 1 apresentou melhor desempenho utilizando as próteses auditivas no programa 1. Já o grupo 2 obteve melhor desempenho com o programa 2. CONCLUSÕES: Pacientes sem zonas mortas na cóclea obtêm maior benefício com a amplificação em freqüências altas. Na presença de zonas mortas em freqüências altas, o melhor desempenho é obtido com a amplificação restrita nestas freqüências.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade Federal de São Paulo (UNIFESP) EPMUNIFESP, EPMUNIFESP, EPMSciEL

GESTÃO DO CONHECIMENTO CIENTÍFICO EM UNIVERSIDADES: MAPEAMENTO DOS PROCESSOS DE DESENVOLVIMENTO DE PROJETOS

A gestão de projetos tem se constituído em um tema de extrema importância na atualidade, pois permite que as organizações possam atingir seus objetivos de forma mais eficiente, eficaz e efetiva, contudo, estudos relacionados à temática de gestão de projetos de ensino, pesquisa e extensão nas universidades ainda são pouco significativos. Destaca-se que a produção do conhecimento é um produto caro para a universidade, pois ao desenvolver um projeto de ensino, pesquisa ou extensão, há a necessidade de recursos de diversos tipos, por isso, espera-se que a produção científica gere resultados qualificados, que permitam à universidade cumprir com sua função social. Este trabalho, que integra um dos módulos do sistema de gestão para a sustentabilidade do conhecimento científico em universidades, foi desenvolvido com o intuito de mapear a gestão dos projetos na UFSM campus Palmeira das Missões. A coleta de dados foi realizada com coordenadores de projetos da referida instituição e a análise foi realizada através de estatística descritiva e análise de conteúdo. Os resultados do mapeamento revelaram alguns aspectos negativos relacionados às etapas de Elaboração, Registro, Execução e Avaliação dos projetos, bem como, desconhecimento de procedimentos e normativas institucionais de gestão de projetos

Targeting CDK6 and BCL2 Exploits the MYB Addiction of Ph+ Acute Lymphoblastic Leukemia

Philadelphia chromosome–positive acute lymphoblastic leukemia (Phþ ALL) is currently treated with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy. However, most patients develop resistance to TKI through BCR-ABL1–dependent and –independent mechanisms. Newly developed TKI can target Phþ ALL cells with BCR-ABL1–dependent resistance; however, overcoming BCR-ABL1–independent mechanisms of resistance remains challenging because transcription factors, which are difficult to inhibit, are often involved. We show here that (i) the growth of Phþ ALL cell lines and primary cells is highly dependent on MYB-mediated transcriptional upregulation of CDK6, cyclin D3, and BCL2, and (ii) restoring their expression in MYB-silenced Phþ ALL cells rescues their impaired proliferation and survival. Levels of MYB and CDK6 were highly correlated in adult Phþ ALL (P ¼ 0.00008). Moreover, Phþ ALL cells exhibited a specific requirement for CDK6 but not CDK4 expression, most likely because, in these cells, CDK6 was predominantly localized in the nucleus, whereas CDK4 was almost exclusively cytoplasmic. Consistent with their essential role in Phþ ALL, pharmacologic inhibition of CDK6 and BCL2 markedly suppressed proliferation, colony formation, and survival of Phþ ALL cells ex vivo and in mice. In summary, these findings provide a proof-of-principle, rational strategy to target the MYB addiction of Phþ ALL. © 2017 American Association for Cancer Research

Effect of Quercetin on ABCC6 Transporter: Implication in HepG2 Migration.

Quercetin is a member of the flavonoid group of compounds, which is abundantly present in various dietary sources. It has excellent antioxidant properties and anti-inflammatory activity and is very effective as an anti-cancer agent against various types of tumors, both in vivo and in vitro. Quercetin has been also reported to modulate the activity of some members of the multidrug-resistance transporters family, such as P-gp, ABCC1, ABCC2, and ABCG2, and the activity of ecto-5'-nucleotidase (NT5E/CD73), a key regulator in some tumor processes such as invasion, migration, and metastasis. In this study, we investigated the effect of Quercetin on ABCC6 expression in HepG2 cells. ABCC6 is a member of the superfamily of ATP-binding cassette (ABC) transporters, poorly involved in drug resistance, whose mutations cause pseudoxanthoma elasticum, an inherited disease characterized by ectopic calcification of soft connective tissues. Recently, it has been reported that ABCC6 contributes to cytoskeleton rearrangements and HepG2 cell motility through purinergic signaling. Gene and protein expression were evaluated by quantitative Reverse-Transcription PCR (RT-qPCR) and western blot, respectively. Actin cytoskeleton dynamics was evaluated by laser confocal microscopy using fluorophore-conjugated phalloidin. Cell motility was analyzed by an in vitro wound-healing migration assay. We propose that ABCC6 expression may be controlled by the AKT pathway as part of an adaptative response to oxidative stress, which can be mitigated by the use of Quercetin-like flavonoids

KIAA0319 influences cilia length, cell migration and mechanical cell-substrate interaction

Funding: This work was supported by Action Medical Research/ The Chief Scientist (CSO) Office, Scotland [GN 2614], Royal Society [RG160373], Carnegie Trust [50341], Wellcome Trust ISSF grant 105621/Z/14/Z, and RS Macdonald Charitable Trust grants to SP and Engineering and Physical Sciences Research Council [EP/P030017/1], Biotechnology and Biological Sciences Research Council [BB/P027148/1], and the European Research Council Starting Grant ABLASE [640012] grants to MCG. SP is a Royal Society University Research Fellow.Following its association with dyslexia in multiple genetic studies, the KIAA0319 gene has been extensively investigated in different animal models but its function in neurodevelopment remains poorly understood. We developed the first human cellular knockout model for KIAA0319 in RPE1 retinal pigment epithelia cells via CRISPR-Cas9n to investigate its role in processes suggested but not confirmed in previous studies, including cilia formation and cell migration. We observed in the KIAA0319 knockout increased cilia length and accelerated cell migration. Using Elastic Resonator Interference Stress Microscopy (ERISM), we detected an increase in cellular force for the knockout cells that was restored by a rescue experiment. Combining ERISM and immunostaining we show that RPE1 cells exert highly dynamic, piconewton vertical pushing forces through actin-rich protrusions that are surrounded by vinculin-rich pulling sites. This protein arrangement and force pattern has previously been associated to podosomes in other cells. KIAA0319 depletion reduces the fraction of cells forming these actin-rich protrusions. Our results suggest an involvement of KIAA0319 in cilia biology and cell–substrate force regulation.Publisher PDFPeer reviewe

O015. Evaluation of the genetic polymorphism of the α3 (CHRNA3) and α5 (CHRNA5) nicotinic receptor subunits, in patients with cluster headache

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