Accumulation of non-numerical evidence during nonsymbolic number processing in the brain: An fMRI study

Behavioral evidence has shown that when performing a nonsymbolic number comparison task (e.g., deciding which of two dot arrays contains more dots), participants\u27 responses are sensitive to affected by both numerical (e.g., number of items) and non-numerical magnitudes (i.e., area, density, etc.). Thus far it is unclear what brain circuits support this process of accumulating non-numerical variables during nonsymbolic number processing. To investigate this, 21 adult participants were asked to engage in a dot comparison task. To measure the neural correlates of accumulating numerical and non-numerical variables, we manipulated the number of the non-numerical magnitudes that were congruent (correlated with number) or incongruent (anticorrelated with number). In a control task, participants were asked to choose the darker of two gray rectangles (brightness task). The tasks were matched in terms of their difficulty. The results of a whole brain analysis for regions sensitive to the congruity of numerical and non-numerical magnitudes revealed a region in the right inferior frontal gyrus (rIFG). Activation in this region was found to be correlated with the relative congruency of numerical and non-numerical magnitudes. In contrast, this region was not modulated by difficulty of the brightness control task. Accordingly in view of these findings, we suggest that the rIFG supports the accumulation of non-numerical magnitudes that are positively correlated with number. Therefore taken together, this study reveals a brain region whose pattern of activity is influenced by the congruency between numerical and non-numerical variables during nonsymbolic number judgments. Hum Brain Mapp 38:4908-4921, 2017. © 2017 Wiley Periodicals, Inc

Temperature influence on phytoplankton community growth rates

A large database of field estimates of phytoplankton community growth rates in natural populations was compiled and analyzed to determine the apparent temperature effect on phytoplankton community growth rate. We conducted an ordinary least squares regression to optimize the parameters in two commonly used growth-temperature relations (Arrhenius and Q10 models). Both equations fit the observational data equally with the optimized parameter values. The optimum apparent Q10 value was 1.47 ± 0.08 (95% confidence interval, CI). Microzooplankton grazing rates closely matched the temperature trends for phytoplankton growth. This likely reflects a dynamic adjustment of biomass and grazing rates by the microzooplankton to match their available food source, illustrating tight coupling of phytoplankton growth and microzooplankton grazing rates. The field-measured temperature effect and growth rates were compared with estimates from the satellite Carbon-based Productivity Model (CbPM) and three Earth System Models (ESMs), with model output extracted at the same month and sampling locations as the observations. The optimized, apparent Q10 value calculated for the CbPM was 1.51, with overestimation of growth rates. The apparent Q10 value in the Community Earth System Model (V1.0) was 1.65, with modest underestimation of growth rates. The GFDL-ESM2M and GFDL-ESM2G models produced apparent Q10 values of 1.52 and 1.39, respectively. Models with an apparent Q10 that is significantly greater than ~1.5 will overestimate the phytoplankton community growth response to the ongoing climate warming and will have spatial biases in estimated growth rates for the current era

Replicating the Networking, Mentoring and Venture Creation Benefits of Entrepreneurship Centres on a Shoestring: A Student-centred Approach to Entrepreneurship Education and Venture Creation

As support for both university-level entrepreneurial education and the use of experiential learning methods to foster student entrepreneurs increases, so too have the number of university-established or affiliated entrepreneurship centers. The activity at the center of this study aimed to combine experiential learning methods with assets associated with entrepreneurship centers, including venture creation, networking, and mentoring. Students were invited to participate in a competition wherein they were guided through the business creation process and pitched their ideas to investor judges who chose the winner and provided capital start-up funding and consulting. This research puts forth that university faculty at institutions without entrepreneurship centers can organize experiences to provide the benefits of entrepreneurship centers. The study used interviews to find that many of the benefits of entrepreneurship centers were able to be replicated using this method. The project is outlined, outcomes are analyzed, and the results and lessons learned are discussed

Heterologous Gln/Asn-Rich Proteins Impede the Propagation of Yeast Prions by Altering Chaperone Availability

Prions are self-propagating conformations of proteins that can cause heritable phenotypic traits. Most yeast prions contain glutamine (Q)/asparagine (N)-rich domains that facilitate the accumulation of the protein into amyloid-like aggregates. Efficient transmission of these infectious aggregates to daughter cells requires that chaperones, including Hsp104 and Sis1, continually sever the aggregates into smaller “seeds.” We previously identified 11 proteins with Q/N-rich domains that, when overproduced, facilitate the de novo aggregation of the Sup35 protein into the [PSI +] prion state. Here, we show that overexpression of many of the same 11 Q/N-rich proteins can also destabilize pre-existing [PSI+] or [URE3] prions. We explore in detail the events leading to the loss (curing) of [PSI+] by the overexpression of one of these proteins, the Q/N-rich domain of Pin4, which causes Sup35 aggregates to increase in size and decrease in transmissibility to daughter cells. We show that the Pin4 Q/N-rich domain sequesters Hsp104 and Sis1 chaperones away from the diffuse cytoplasmic pool. Thus, a mechanism by which heterologous Q/N-rich proteins impair prion propagation appears to be the loss of cytoplasmic Hsp104 and Sis1 available to sever [PSI+]

Self-Affirmation Improves Problem-Solving under Stress

High levels of acute and chronic stress are known to impair problem-solving and creativity on a broad range of tasks. Despite this evidence, we know little about protective factors for mitigating the deleterious effects of stress on problem-solving. Building on previous research showing that self-affirmation can buffer stress, we tested whether an experimental manipulation of self-affirmation improves problem-solving performance in chronically stressed participants. Eighty undergraduates indicated their perceived chronic stress over the previous month and were randomly assigned to either a self-affirmation or control condition. They then completed 30 difficult remote associate problem-solving items under time pressure in front of an evaluator. Results showed that self-affirmation improved problem-solving performance in underperforming chronically stressed individuals. This research suggests a novel means for boosting problem-solving under stress and may have important implications for understanding how self-affirmation boosts academic achievement in school settings. © 2013 Creswell et al

Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat

Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

The yeast P5 type ATPase, Spf1, regulates manganese transport into the endoplasmic reticulum

The endoplasmic reticulum (ER) is a large, multifunctional and essential organelle. Despite intense research, the function of more than a third of ER proteins remains unknown even in the well-studied model organism Saccharomyces cerevisiae. One such protein is Spf1, which is a highly conserved, ER localized, putative P-type ATPase. Deletion of SPF1 causes a wide variety of phenotypes including severe ER stress suggesting that this protein is essential for the normal function of the ER. The closest homologue of Spf1 is the vacuolar P-type ATPase Ypk9 that influences Mn2+ homeostasis. However in vitro reconstitution assays with Spf1 have not yielded insight into its transport specificity. Here we took an in vivo approach to detect the direct and indirect effects of deleting SPF1. We found a specific reduction in the luminal concentration of Mn2+ in ∆spf1 cells and an increase following it’s overexpression. In agreement with the observed loss of luminal Mn2+ we could observe concurrent reduction in many Mn2+-related process in the ER lumen. Conversely, cytosolic Mn2+-dependent processes were increased. Together, these data support a role for Spf1p in Mn2+ transport in the cell. We also demonstrate that the human sequence homologue, ATP13A1, is a functionally conserved orthologue. Since ATP13A1 is highly expressed in developing neuronal tissues and in the brain, this should help in the study of Mn2+-dependent neurological disorders

Use of placebo interventions among Swiss primary care providers

Background: Placebo interventions can have meaningful effects for patients. However, little is known about the circumstances of their use in clinical practice. We aimed to investigate to what extent and in which way Swiss primary care providers use placebo interventions. Furthermore we explored their ideas about the ethical and legal issues involved. Methods: 599 questionnaires were sent to general practitioners (GPs) and paediatricians in private practice in the Canton of Zurich in Switzerland. To allow for subgroup analysis GPs in urban, suburban, and rural areas as well as paediatricians were selected in an even ratio. Results: 233 questionnaires were completed (response rate 47%). 28% of participants reported that they never used placebo interventions. More participants used impure placebos therapeutically than pure placebos (57% versus 17%, McNemar's chi2 = 78, p<0.001). There is not one clear main reason for placebo prescription. Placebo use was communicated to patients mostly as being "a drug or a therapy" (64%). The most frequently chosen ethical premise was that they "can be used as long as the physician and the patient work together in partnership" (60% for pure and 75% for impure placebos, McNemar's chi2 = 12, p<0.001). A considerable number of participants (11-38%) were indecisive about statements regarding the ethical and legal legitimacy of using placebos. Conclusions: The data obtained from Swiss primary care providers reflect a broad variety of views about placebo interventions as well as a widespread uncertainty regarding their legitimacy. Primary care providers seem to preferentially use impure as compared to pure placebos in their daily practice. An intense debate is required on appropriate standards regarding the clinical use of placebo interventions among medical professionals

Primary brain T-cell lymphoma of the lymphoblastic type presenting as altered mental status

The authors present a case of a 56-year-old man with altered mental status. Magnetic resonance imaging (MRI) of the brain revealed non-enhancing abnormalities on T2 and FLAIR imaging in the brainstem, cerebellum, and cerebrum. Immunohistochemisty demonstrated precursor T-cell lymphoblastic lymphoma. After treatment with methotrexate, he improved clinically without focal sensorimotor deficits and with improving orientation. MRI showed almost complete resolution of brainstem and cerebral lesions. To the authors’ knowledge, there are only five previous reports of primary central nervous system T-cell lymphoblastic lymphoma. Since treatable, it deserves consideration in patients with altered mental status and imaging abnormalities that include diffuse, non-enhancing changes with increased signal on T2-weighted images