Concept: Cosmological argument
The Zika virus has spread rapidly in the Americas since its first identification in Brazil in early 2015. Prenatal Zika virus infection has been linked to adverse pregnancy and birth outcomes, most notably microcephaly and other serious brain anomalies. To determine whether Zika virus infection during pregnancy causes these adverse outcomes, we evaluated available data using criteria that have been proposed for the assessment of potential teratogens. On the basis of this review, we conclude that a causal relationship exists between prenatal Zika virus infection and microcephaly and other serious brain anomalies. Evidence that was used to support this . . .
There are ever more compelling tools available for neuroscience research, ranging from selective genetic targeting to optogenetic circuit control to mapping whole connectomes. These approaches are coupled with a deep-seated, often tacit, belief in the reductionist program for understanding the link between the brain and behavior. The aim of this program is causal explanation through neural manipulations that allow testing of necessity and sufficiency claims. We argue, however, that another equally important approach seeks an alternative form of understanding through careful theoretical and experimental decomposition of behavior. Specifically, the detailed analysis of tasks and of the behavior they elicit is best suited for discovering component processes and their underlying algorithms. In most cases, we argue that study of the neural implementation of behavior is best investigated after such behavioral work. Thus, we advocate a more pluralistic notion of neuroscience when it comes to the brain-behavior relationship: behavioral work provides understanding, whereas neural interventions test causality.
Previous research highlights how adept people are at emotional recovery after rejection, but less research has examined factors that can prevent full recovery. In five studies, we investigate how changing one’s self-definition in response to rejection causes more lasting damage. We demonstrate that people who endorse an entity theory of personality (i.e., personality cannot be changed) report alterations in their self-definitions when reflecting on past rejections (Studies 1, 2, and 3) or imagining novel rejection experiences (Studies 4 and 5). Further, these changes in self-definition hinder post-rejection recovery, causing individuals to feel haunted by their past, that is, to fear the recurrence of rejection and to experience lingering negative affect from the rejection. Thus, beliefs that prompt people to tie experiences of rejection to self-definition cause rejection’s impact to linger.
White-nose syndrome (WNS) has caused recent catastrophic declines among multiple species of bats in eastern North America. The disease’s name derives from a visually apparent white growth of the newly discovered fungus Geomyces destructans on the skin (including the muzzle) of hibernating bats. Colonization of skin by this fungus is associated with characteristic cutaneous lesions that are the only consistent pathological finding related to WNS. However, the role of G. destructans in WNS remains controversial because evidence to implicate the fungus as the primary cause of this disease is lacking. The debate is fuelled, in part, by the assumption that fungal infections in mammals are most commonly associated with immune system dysfunction. Additionally, the recent discovery that G. destructans commonly colonizes the skin of bats of Europe, where no unusual bat mortality events have been reported, has generated further speculation that the fungus is an opportunistic pathogen and that other unidentified factors are the primary cause of WNS. Here we demonstrate that exposure of healthy little brown bats (Myotis lucifugus) to pure cultures of G. destructans causes WNS. Live G. destructans was subsequently cultured from diseased bats, successfully fulfilling established criteria for the determination of G. destructans as a primary pathogen. We also confirmed that WNS can be transmitted from infected bats to healthy bats through direct contact. Our results provide the first direct evidence that G. destructans is the causal agent of WNS and that the recent emergence of WNS in North America may represent translocation of the fungus to a region with a naive population of animals. Demonstration of causality is an instrumental step in elucidating the pathogenesis and epidemiology of WNS and in guiding management actions to preserve bat populations against the novel threat posed by this devastating infectious disease.
Interest in the relationship between cannabis use and psychosis has increased dramatically in recent years, in part because of concerns related to the growing availability of cannabis and potential risks to health and human functioning. There now exists a plethora of scientific articles addressing this issue, but few provide a clear verdict about the causal nature of the cannabis-psychosis association. Here, we review recent research reports on cannabis and psychosis, giving particular attention to how each report provides evidence relating to two hypotheses: (1) cannabis as a contributing cause and (2) shared vulnerability. Two primary kinds of data are brought to bear on this issue: studies done with schizophrenic patients and studies of first-episode psychosis. Evidence reviewed here suggests that cannabis does not in itself cause a psychosis disorder. Rather, the evidence leads us to conclude that both early use and heavy use of cannabis are more likely in individuals with a vulnerability to psychosis. The role of early and heavy cannabis use as a prodromal sign merits further examination, along with a variety of other problem behaviors (e.g., early or heavy use of cigarettes or alcohol and poor school performance). Future research studies that focus exclusively on the cannabis-psychosis association will therefore be of little value in our quest to better understand psychosis and how and why it occurs.
Monitoring progress with disease and injury reduction in many populations will require widespread use of verbal autopsy (VA). Multiple methods have been developed for assigning cause of death from a VA but their application is restricted by uncertainty about their reliability.
Horizontal pleiotropy occurs when the variant has an effect on disease outside of its effect on the exposure in Mendelian randomization (MR). Violation of the ‘no horizontal pleiotropy’ assumption can cause severe bias in MR. We developed the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test to identify horizontal pleiotropic outliers in multi-instrument summary-level MR testing. We showed using simulations that the MR-PRESSO test is best suited when horizontal pleiotropy occurs in <50% of instruments. Next we applied the MR-PRESSO test, along with several other MR tests, to complex traits and diseases and found that horizontal pleiotropy (i) was detectable in over 48% of significant causal relationships in MR; (ii) introduced distortions in the causal estimates in MR that ranged on average from -131% to 201%; (iii) induced false-positive causal relationships in up to 10% of relationships; and (iv) could be corrected in some but not all instances.
There are discrepant findings between (A) observational follow-ups and (B) interventional studies that investigate possible causal association between high physical activity and low mortality. Participation in vigorous physical activity at a specific time-point is an indicator of good fitness and health, and is associated with a reduced risk of death. However, neither randomised controlled trials nor experimental animal studies have provided conclusive evidence to show that physical activity started during adulthood extends lifespan. Consequently, the undisputed health-related benefits of exercise have yet to translate into any proven causal relationship with longevity. Physical activity improves fitness and physical function, and confers other health-related effects. These outcomes have a greater basis in evidence-based data than any claims of a reduced risk of death, especially when recommending physical activity for previously physically inactive middle-aged and elderly adults.
DISNOR is a new resource that aims at exploiting the explosion of data on the identification of disease-associated genes to assemble inferred disease pathways. This may help dissecting the signaling events whose disruption causes the pathological phenotypes and may contribute to build a platform for precision medicine. To this end we combine the gene-disease association (GDA) data annotated in the DisGeNET resource with a new curation effort aimed at populating the SIGNOR database with causal interactions related to disease genes with the highest possible coverage. DISNOR can be freely accessed at http://DISNOR.uniroma2.it/ where >3700 disease-networks, linking ∼2600 disease genes, can be explored. For each disease curated in DisGeNET, DISNOR links disease genes by manually annotated causal relationships and offers an intuitive visualization of the inferred ‘patho-pathways’ at different complexity levels. User-defined gene lists are also accepted in the query pipeline. In addition, for each list of query genes-either annotated in DisGeNET or user-defined-DISNOR performs a gene set enrichment analysis on KEGG-defined pathways or on the lists of proteins associated with the inferred disease pathways. This function offers additional information on disease-associated cellular pathways and disease similarity.
Evidence implicates ventral parieto-premotor cortices in representing the goal of grasping independent of the movements or effectors involved [Umilta, M. A., Escola, L., Intskirveli, I., Grammont, F., Rochat, M., Caruana, F., et al. When pliers become fingers in the monkey motor system. Proceedings of the National Academy of Sciences, U.S.A., 105, 2209-2213, 2008; Tunik, E., Frey, S. H., & Grafton, S. T. Virtual lesions of the anterior intraparietal area disrupt goal-dependent on-line adjustments of grasp. Nature Neuroscience, 8, 505-511, 2005]. Modern technologies that enable arbitrary causal relationships between hand movements and tool actions provide a strong test of this hypothesis. We capitalized on this unique opportunity by recording activity with fMRI during tasks in which healthy adults performed goal-directed reach and grasp actions manually or by depressing buttons to initiate these same behaviors in a remotely located robotic arm (arbitrary causal relationship). As shown previously [Binkofski, F., Dohle, C., Posse, S., Stephan, K. M., Hefter, H., Seitz, R. J., et al. Human anterior intraparietal area subserves prehension: A combined lesion and functional MRI activation study. Neurology, 50, 1253-1259, 1998], we detected greater activity in the vicinity of the anterior intraparietal sulcus (aIPS) during manual grasp versus reach. In contrast to prior studies involving tools controlled by nonarbitrarily related hand movements [Gallivan, J. P., McLean, D. A., Valyear, K. F., & Culham, J. C. Decoding the neural mechanisms of human tool use. Elife, 2, e00425, 2013; Jacobs, S., Danielmeier, C., & Frey, S. H. Human anterior intraparietal and ventral premotor cortices support representations of grasping with the hand or a novel tool. Journal of Cognitive Neuroscience, 22, 2594-2608, 2010], however, responses within the aIPS and premotor cortex exhibited no evidence of selectivity for grasp when participants employed the robot. Instead, these regions showed comparable increases in activity during both the reach and grasp conditions. Despite equivalent sensorimotor demands, the right cerebellar hemisphere displayed greater activity when participants initiated the robot’s actions versus when they pressed a button known to be nonfunctional and watched the very same actions undertaken autonomously. This supports the hypothesis that the cerebellum predicts the forthcoming sensory consequences of volitional actions [Blakemore, S. J., Frith, C. D., & Wolpert, D. M. The cerebellum is involved in predicting the sensory consequences of action. NeuroReport, 12, 1879-1884, 2001]. We conclude that grasp-selective responses in the human aIPS and premotor cortex depend on the existence of nonarbitrary causal relationships between hand movements and end-effector actions.