Free Will & Empirical Arguments for Epiphenomenalism

While philosophers have worried about mental causation for centuries, worries about the causal relevance of conscious phenomena are also increasingly featuring in neuroscientific literature. Neuroscientists have regarded the threat of epiphenomenalism as interesting primarily because they have supposed that it entails free will scepticism. However, the steps that get us from a premise about the causal irrelevance of conscious phenomena to a conclusion about free will are not entirely clear. In fact, if we examine popular philosophical accounts of free will, we find, for the most part, nothing to suggest that free will is inconsistent with the presence of unconscious neural precursors to choices. It is only if we adopt highly non-naturalistic assumptions about the mind (e.g. if we embrace Cartesian dualism and locate free choice in the non-physical realm) that it seems plausible to suppose that the neuroscientific data generates a threat to free will

Sex Reversal in Zebrafish fancl Mutants Is Caused by Tp53-Mediated Germ Cell Apoptosis

The molecular genetic mechanisms of sex determination are not known for most vertebrates, including zebrafish. We identified a mutation in the zebrafish fancl gene that causes homozygous mutants to develop as fertile males due to female-to-male sex reversal. Fancl is a member of the Fanconi Anemia/BRCA DNA repair pathway. Experiments showed that zebrafish fancl was expressed in developing germ cells in bipotential gonads at the critical time of sexual fate determination. Caspase-3 immunoassays revealed increased germ cell apoptosis in fancl mutants that compromised oocyte survival. In the absence of oocytes surviving through meiosis, somatic cells of mutant gonads did not maintain expression of the ovary gene cyp19a1a and did not down-regulate expression of the early testis gene amh; consequently, gonads masculinized and became testes. Remarkably, results showed that the introduction of a tp53 (p53) mutation into fancl mutants rescued the sex-reversal phenotype by reducing germ cell apoptosis and, thus, allowed fancl mutants to become fertile females. Our results show that Fancl function is not essential for spermatogonia and oogonia to become sperm or mature oocytes, but instead suggest that Fancl function is involved in the survival of developing oocytes through meiosis. This work reveals that Tp53-mediated germ cell apoptosis induces sex reversal after the mutation of a DNA–repair pathway gene by compromising the survival of oocytes and suggests the existence of an oocyte-derived signal that biases gonad fate towards the female developmental pathway and thereby controls zebrafish sex determination

The planetary system around HD 190622 (TOI-1054): Measuring the gas content of low-mass planets orbiting F-stars

Context. Giant planets are known to dominate the long-term stability of planetary systems due to their prevailing gravitational interactions, but they are also thought to play an important role in planet formation. Observational constraints improve our understanding of planetary formation processes such as the delivery of volatile-rich planetesimals from beyond the ice line into the inner planetary system. Additional constraints may come from studies of the atmosphere, but almost all such studies of the atmosphere investigate the detection of certain species, and abundances are not routinely quantitatively measured. Aims. Accurate measurements of planetary bulk parameters-that is, mass and density-provide constraints on the inner structure and chemical composition of transiting planets. This information provides insight into properties such as the amounts of volatile species, which in turn can be related to formation and evolution processes. Methods. The Transiting Exoplanet Survey Satellite (TESS) reported a planetary candidate around HD 190622 (TOI-1054), which was subsequently validated and found to merit further characterization with photometric and spectroscopic facilities. The KESPRINT collaboration used data from the High Accuracy Radial Velocity Planet Searcher (HARPS) to independently confirm the planetary candidate, securing its mass, and revealing the presence of an outer giant planet in the system. The CHEOPS consortium invested telescope time in the transiting target in order to reduce the uncertainty on the radius, improving the characterization of the planet. Results. We present the discovery and characterization of the planetary system around HD 190622 (TOI-1054). This system hosts one transiting planet, which is smaller than Neptune (3.087-0.053+0.058REarth, 7.7 ± 1.0 MEarth) but has a similar bulk density (1.43 ± 0.21 g cm-3) and an orbital period of 16 days; and a giant planet, not known to be transiting, with a minimum mass of 227.0 ± 6.7 MEarth in an orbit with a period of 315 days. Conclusions. Our measurements constrain the structure and composition of the transiting planet. HD 190622b has singular properties among the known population of transiting planets, which we discuss in detail. Among the sub-Neptune-sized planets known today, this planet stands out because of its large gas content

Using C. elegans to decipher the cellular and molecular mechanisms underlying neurodevelopmental disorders

Prova tipográfica (uncorrected proof)Neurodevelopmental disorders such as epilepsy, intellectual disability (ID), and autism spectrum disorders (ASDs) occur in over 2 % of the population, as the result of genetic mutations, environmental factors, or combination of both. In the last years, use of large-scale genomic techniques allowed important advances in the identification of genes/loci associated with these disorders. Nevertheless, following association of novel genes with a given disease, interpretation of findings is often difficult due to lack of information on gene function and effect of a given mutation in the corresponding protein. This brings the need to validate genetic associations from a functional perspective in model systems in a relatively fast but effective manner. In this context, the small nematode, Caenorhabditis elegans, presents a good compromise between the simplicity of cell models and the complexity of rodent nervous systems. In this article, we review the features that make C. elegans a good model for the study of neurodevelopmental diseases. We discuss its nervous system architecture and function as well as the molecular basis of behaviors that seem important in the context of different neurodevelopmental disorders. We review methodologies used to assess memory, learning, and social behavior as well as susceptibility to seizures in this organism. We will also discuss technological progresses applied in C. elegans neurobiology research, such as use of microfluidics and optogenetic tools. Finally, we will present some interesting examples of the functional analysis of genes associated with human neurodevelopmental disorders and how we can move from genes to therapies using this simple model organism.The authors would like to acknowledge Fundação para a Ciência e Tecnologia (FCT) (PTDC/SAU-GMG/112577/2009). AJR and CB are recipients of FCT fellowships: SFRH/BPD/33611/2009 and SFRH/BPD/74452/2010, respectively

Hypothetical biomolecular probe based on a genetic switch with tunable symmetry and stability

Background: Genetic switches are ubiquitous in nature, frequently associated with the control of cellular functions and developmental programs. In the realm of synthetic biology, it is of great interest to engineer genetic circuits that can change their mode of operation from monostable to bistable, or even to multistable, based on the experimental fine-tuning of readily accessible parameters. In order to successfully design robust, bistable synthetic circuits to be used as biomolecular probes, or understand modes of operation of such naturally occurring circuits, we must identify parameters that are key in determining their characteristics. Results: Here, we analyze the bistability properties of a general, asymmetric genetic toggle switch based on a chemical-reaction kinetic description. By making appropriate approximations, we are able to reduce the system to two coupled differential equations. Their deterministic stability analysis and stochastic numerical simulations are in excellent agreement. Drawing upon this general framework, we develop a model of an experimentally realized asymmetric bistable genetic switch based on the LacI and TetR repressors. By varying the concentrations of two synthetic inducers, doxycycline and isopropyl ??-D-1-thiogalactopyranoside, we predict that it will be possible to repeatedly fine-tune the mode of operation of this genetic switch from monostable to bistable, as well as the switching rates over many orders of magnitude, in an experimental setting. Furthermore, we find that the shape and size of the bistability region is closely connected with plasmid copy number. Conclusions: Based on our numerical calculations of the LacI-TetR asymmetric bistable switch phase diagram, we propose a generic work-flow for developing and applying biomolecular probes: Their initial state of operation should be specified by controlling inducer concentrations, and dilution due to cellular division would turn the probes into memory devices in which information could be preserved over multiple generations. Additionally, insights from our analysis of the LacI-TetR system suggest that this particular system is readily available to be employed in this kind of probe.clos

Prevalence, associated factors and predictors of anxiety: a community survey in Selangor, Malaysia

Background: Anxiety is the most common mental health disorders in the general population. This study aimed to determine the prevalence of anxiety, its associated factors and the predictors of anxiety among adults in the community of Selangor, Malaysia. Methods: A cross sectional study was carried out in three districts in Selangor, Malaysia. The inclusion criteria of this study were Malaysian citizens, adults aged 18 years and above, and living in the selected living quarters based on the list provided by the Department of Statistics Malaysia (DOS). Participants completed a set of questionnaires, including the validated Malay version of Generalized Anxiety Disorder 7 (GAD 7) to detect anxiety. Results: Of the 2512 participants who were approached, 1556 of them participated in the study (61.90 %). Based on the cut-off point of 8 and above in the GAD-7, the prevalence of anxiety was 8.2 %. Based on the initial multiple logistic regression analysis, the predictors of anxiety were depression, serious problems at work, domestic violence and high perceived stress. When reanalyzed again after removing depression, low self-esteem and high perceived stress, six predictors that were identified are cancer, serious problems at work, domestic violence, unhappy relationship with family, non-organizational religious activity and intrinsic religiosity. Conclusion: This study reports the prevalence of anxiety among adults in the community of Selangor, Malaysia and also the magnitude of the associations between various factors and anxiety

The evaluation of a continuing professional development package for primary care dentists designed to reduce stress, build resilience and improve clinical decision-making

Introduction: Stress and burnout are widely accepted as a problem for primary care dental practitioners. Previous programmes to address this issue have met with some success. Burnout is associated with poor coping skills and emotion regulation, and increased rates of clinical errors. Anxiety is associated with poor decision-making and is thought to be associated with poor clinical decision-making. Attempts to improve decision-making use increasing meta-awareness and review of thinking processes. Bibliotherapy is an effective method of delivering cognitive behavioural therapy as self-help or guided self-help (with some therapist input) formats. Objective: To evaluate the efficacy of a specially designed CPD package which was designed to improve coping skills, build resilience and reduce the impact of anxiety on dentists’ clinical decision-making. Design: A multi-centred quasi-experiment Setting: Lincolnshire and Nottinghamshire (England) 2014 Materials and methods: Thirty-five volunteer primary care dentists used two versions (self-help [SH] and guided self-help [GSH], which included a 3 hour workshop) of a specially written cognitive-behavioural-therapy bibliotherapy programme designed to improve well-being and decision-making. Main Outcome Measures: The main outcome measures were dentists’ burnout, depression, anxiety, stress and decision-making style. Data were also collected on use and evaluation of the programme. Results: At 6 weeks there was a clinically and statistically significant reduction in depression, anxiety and stress levels, a statistically significant reduction in burnout (emotional exhaustion) and hypervigilant decision-making and an increase in personal achievement (burnout). The improvements in depression, stress, emotional exhaustion and hypervigilant decision-making were maintained at 6 months. Dentists were overwhelmingly positive in their evaluation of the project and used most of its contents. Conclusion: With the caveat of small numbers and the lack of a no-treatment control, this project demonstrated that a self-help package can be highly acceptable to dentists and, in the short-to-medium term, improve dentists’ well-being and decision-making with implications for patient safety