Metabolomics of cerebrospinal fluid reveals changes in the central nervous system metabolism in a rat model of multiple sclerosis

Experimental Autoimmune Encephalomyelitis (EAE) is the most commonly used animal model for Multiple Sclerosis (MScl). CSF metabolomics in an acute EAE rat model was investigated using targetted LC–MS and GC–MS. Acute EAE in Lewis rats was induced by co-injection of Myelin Basic Protein with Complete Freund’s Adjuvant. CSF samples were collected at two time points: 10 days after inoculation, which was during the onset of the disease, and 14 days after inoculation, which was during the peak of the disease. The obtained metabolite profiles from the two time points of EAE development show profound differences between onset and the peak of the disease, suggesting significant changes in CNS metabolism over the course of MBP-induced neuroinflammation. Around the onset of EAE the metabolome profile shows significant decreases in arginine, alanine and branched amino acid levels, relative to controls. At the peak of the disease, significant increases in concentrations of multiple metabolites are observed, including glutamine, O-phosphoethanolamine, branched-chain amino acids and putrescine. Observed changes in metabolite levels suggest profound changes in CNS metabolism over the course of EAE. Affected pathways include nitric oxide synthesis, altered energy metabolism, polyamine synthesis and levels of endogenous antioxidants

Incremental Medians via Online Bidding

In the k-median problem we are given sets of facilities and customers, and distances between them. For a given set F of facilities, the cost of serving a customer u is the minimum distance between u and a facility in F. The goal is to find a set F of k facilities that minimizes the sum, over all customers, of their service costs. Following Mettu and Plaxton, we study the incremental medians problem, where k is not known in advance, and the algorithm produces a nested sequence of facility sets where the kth set has size k. The algorithm is c-cost-competitive if the cost of each set is at most c times the cost of the optimum set of size k. We give improved incremental algorithms for the metric version: an 8-cost-competitive deterministic algorithm, a 2e ~ 5.44-cost-competitive randomized algorithm, a (24+epsilon)-cost-competitive, poly-time deterministic algorithm, and a (6e+epsilon ~ .31)-cost-competitive, poly-time randomized algorithm. The algorithm is s-size-competitive if the cost of the kth set is at most the minimum cost of any set of size k, and has size at most s k. The optimal size-competitive ratios for this problem are 4 (deterministic) and e (randomized). We present the first poly-time O(log m)-size-approximation algorithm for the offline problem and first poly-time O(log m)-size-competitive algorithm for the incremental problem. Our proofs reduce incremental medians to the following online bidding problem: faced with an unknown threshold T, an algorithm submits "bids" until it submits a bid that is at least the threshold. It pays the sum of all its bids. We prove that folklore algorithms for online bidding are optimally competitive.Comment: conference version appeared in LATIN 2006 as "Oblivious Medians via Online Bidding

Cosmic Ray Extremely Distributed Observatory: a global network of detectors to probe contemporary physics mysteries

In the past few years, cosmic-rays beyond the GZK cut-off ($E > 5 \times 10^{19}$ eV) have been detected by leading collaborations such as Pierre Auger Observatory. Such observations raise many questions as to how such energies can be reached and what source can possibly produce them. Although at lower energies, mechanisms such as Fermi acceleration in supernovae front shocks seem to be favored, top-down scenarios have been proposed to explain the existence of ultra-high energy cosmic-rays: the decay of super-massive long-lived particles produced in the early Universe may yield to a flux of ultra-high energy photons. Such photons might be presently generating so called super-preshowers, an extended cosmic-ray shower with a spatial distribution that can be as wide as the Earth diameter. The Cosmic Ray Extremely Distributed Observatory (CREDO) mission is to find such events by means of a network of detectors spread around the globe. CREDO's strategy is to connect existing detectors and create a worldwide network of cosmic-ray observatories. Moreover, citizen-science constitutes an important pillar of our approach. By helping our algorithms to recognize detection patterns and by using smartphones as individual cosmic-ray detectors, non-scientists can participate in scientific discoveries and help unravel some of the deepest mysteries in physics.Comment: excited QCD Conference, CREDO Collaboration, 7 pages, 3 figure

Novel cerebrospinal fluid biomarkers of glucose transporter type 1 deficiency syndrome: Implications beyond the brain's energy deficit

We used next-generation metabolic screening to identify new biomarkers for improved diagnosis and pathophysiological understanding of glucose transporter type 1 deficiency syndrome (GLUT1DS), comparing metabolic cerebrospinal fluid (CSF) profiles from 12 patients to those of 116 controls. This confirmed decreased CSF glucose and lactate levels in patients with GLUT1DS and increased glutamine at group level. We identified three novel biomarkers significantly decreased in patients, namely gluconic + galactonic acid, xylose-α1-3-glucose, and xylose-α1-3-xylose-α1-3-glucose, of which the latter two have not previously been identified in body fluids. CSF concentrations of gluconic + galactonic acid may be reduced as these metabolites could serve as alternative substrates for the pentose phosphate pathway. Xylose-α1-3-glucose and xylose-α1-3-xylose-α1-3-glucose may originate from glycosylated proteins; their decreased levels are hypothetically the consequence of insufficient glucose, one of two substrates for O-glucosylation. Since many proteins are O-glucosylated, this deficiency may affect cellular processes and thus contribute to GLUT1DS pathophysiology. The novel CSF biomarkers have the potential to improve the biochemical diagnosis of GLUT1DS. Our findings imply that brain glucose deficiency in GLUT1DS may cause disruptions at the cellular level that go beyond energy metabolism, underlining the importance of developing treatment strategies that directly target cerebral glucose uptake

The psychological science accelerator’s COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data

A global experiment on motivating social distancing during the COVID-19 pandemic

Finding communication strategies that effectively motivate social distancing continues to be a global public health priority during the COVID-19 pandemic. This cross-country, preregistered experiment (n = 25,718 from 89 countries) tested hypotheses concerning generalizable positive and negative outcomes of social distancing messages that promoted personal agency and reflective choices (i.e., an autonomy-supportive message) or were restrictive and shaming (i.e., a controlling message) compared with no message at all. Results partially supported experimental hypotheses in that the controlling message increased controlled motivation (a poorly internalized form of motivation relying on shame, guilt, and fear of social consequences) relative to no message. On the other hand, the autonomy-supportive message lowered feelings of defiance compared with the controlling message, but the controlling message did not differ from receiving no message at all. Unexpectedly, messages did not influence autonomous motivation (a highly internalized form of motivation relying on one’s core values) or behavioral intentions. Results supported hypothesized associations between people’s existing autonomous and controlled motivations and self-reported behavioral intentions to engage in social distancing. Controlled motivation was associated with more defiance and less long-term behavioral intention to engage in social distancing, whereas autonomous motivation was associated with less defiance and more short- and long-term intentions to social distance. Overall, this work highlights the potential harm of using shaming and pressuring language in public health communication, with implications for the current and future global health challenges

The Psychological Science Accelerator’s COVID-19 rapid-response dataset

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments. Data were provided by 73,223 participants with varying completion rates. Participants completed the survey from 111 geopolitical regions in 44 unique languages/dialects. The anonymized dataset described here is provided in both raw and processed formats to facilitate re-use and further analyses. The dataset offers secondary analytic opportunities to explore coping, framing, and self-determination across a diverse, global sample obtained at the onset of the COVID-19 pandemic, which can be merged with other time-sampled or geographic data