Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders.

The complexity of the traumatic brain injury (TBI) pathology, particularly concussive injury, is a serious obstacle for diagnosis, treatment, and long-term prognosis. Here we utilize modern systems biology in a rodent model of concussive injury to gain a thorough view of the impact of TBI on fundamental aspects of gene regulation, which have the potential to drive or alter the course of the TBI pathology. TBI perturbed epigenomic programming, transcriptional activities (expression level and alternative splicing), and the organization of genes in networks centered around genes such as Anax2, Ogn, and Fmod. Transcriptomic signatures in the hippocampus are involved in neuronal signaling, metabolism, inflammation, and blood function, and they overlap with those in leukocytes from peripheral blood. The homology between genomic signatures from blood and brain elicited by TBI provides proof of concept information for development of biomarkers of TBI based on composite genomic patterns. By intersecting with human genome-wide association studies, many TBI signature genes and network regulators identified in our rodent model were causally associated with brain disorders with relevant link to TBI. The overall results show that concussive brain injury reprograms genes which could lead to predisposition to neurological and psychiatric disorders, and that genomic information from peripheral leukocytes has the potential to predict TBI pathogenesis in the brain

Simultaneous evolutionary expansion and constraint of genomic heterogeneity in multifocal lung cancer.

Recent genomic analyses have revealed substantial tumor heterogeneity across various cancers. However, it remains unclear whether and how genomic heterogeneity is constrained during tumor evolution. Here, we sequence a unique cohort of multiple synchronous lung cancers (MSLCs) to determine the relative diversity and uniformity of genetic drivers upon identical germline and environmental background. We find that each multicentric primary tumor harbors distinct oncogenic alterations, including novel mutations that are experimentally demonstrated to be functional and therapeutically targetable. However, functional studies show a strikingly constrained tumorigenic pathway underlying heterogeneous genetic variants. These results suggest that although the mutation-specific routes that cells take during oncogenesis are stochastic, genetic trajectories may be constrained by selection for functional convergence on key signaling pathways. Our findings highlight the robust evolutionary pressures that simultaneously shape the expansion and constraint of genomic diversity, a principle that holds important implications for understanding tumor evolution and optimizing therapeutic strategies.Across cancer types tumor heterogeneity has been observed, but how this relates to tumor evolution is unclear. Here, the authors sequence multiple synchronous lung cancers, highlighting the evolutionary pressures that simultaneously shape the expansion and constraint of genomic heterogeneity

Effects of diet and/or exercise in enhancing spinal cord sensorimotor learning.

Given that the spinal cord is capable of learning sensorimotor tasks and that dietary interventions can influence learning involving supraspinal centers, we asked whether the presence of omega-3 fatty acid docosahexaenoic acid (DHA) and the curry spice curcumin (Cur) by themselves or in combination with voluntary exercise could affect spinal cord learning in adult spinal mice. Using an instrumental learning paradigm to assess spinal learning we observed that mice fed a diet containing DHA/Cur performed better in the spinal learning paradigm than mice fed a diet deficient in DHA/Cur. The enhanced performance was accompanied by increases in the mRNA levels of molecular markers of learning, i.e., BDNF, CREB, CaMKII, and syntaxin 3. Concurrent exposure to exercise was complementary to the dietary treatment effects on spinal learning. The diet containing DHA/Cur resulted in higher levels of DHA and lower levels of omega-6 fatty acid arachidonic acid (AA) in the spinal cord than the diet deficient in DHA/Cur. The level of spinal learning was inversely related to the ratio of AA:DHA. These results emphasize the capacity of select dietary factors and exercise to foster spinal cord learning. Given the non-invasiveness and safety of the modulation of diet and exercise, these interventions should be considered in light of their potential to enhance relearning of sensorimotor tasks during rehabilitative training paradigms after a spinal cord injury

Risk-based Prioritization among Air Pollution Control Strategies in the Yangtze River Delta, China

Background: The Yangtze River Delta (YRD) in China is a densely populated region with recent dramatic increases in energy consumption and atmospheric emissions. Objectives: We studied how different emission sectors influence population exposures and the corresponding health risks, to inform air pollution control strategy design. Methods: We applied the Community Multiscale Air Quality (CMAQ) Modeling System to model the marginal contribution to baseline concentrations from different sectors. We focused on nitrogen oxide (NOx) control while considering other pollutants that affect fine particulate matter [aerodynamic diameter $\leq 2.5 \mu m (PM_{2.5})$] and ozone concentrations. We developed concentration–response (C-R) functions for $PM_{2.5}$ and ozone mortality for China to evaluate the anticipated health benefits. Results: In the YRD, health benefits per ton of emission reductions varied significantly across pollutants, with reductions of primary $PM_{2.5}$ from the industry sector and mobile sources showing the greatest benefits of 0.1 fewer deaths per year per ton of emission reduction. Combining estimates of health benefits per ton with potential emission reductions, the greatest mortality reduction of 12,000 fewer deaths per year [95% confidence interval (CI), 1,200–24,000] was associated with controlling primary $PM_{2.5}$ emissions from the industry sector and reducing sulfur dioxide $(SO_2)$ from the power sector, respectively. Benefits were lower for reducing $NO_x$ emissions given lower consequent reductions in the formation of secondary $PM_{2.5}$ (compared with $SO_2$) and increases in ozone concentrations that would result in the YRD. Conclusions: Although uncertainties related to C-R functions are significant, the estimated health benefits of emission reductions in the YRD are substantial, especially for sectors and pollutants with both higher health benefits per unit emission reductions and large potential for emission reductions

Statistical Analysis of the Price Jumps of Financial Assets Based on LOB Data

The price process in electronic markets is one prototypical example of a stochastic process, and it has historically be fitted and analyzed using different stochastic models such as Levy processes, diffusions, and SDEs (stochastic differential equations). In this thesis, we analyze Microsoft stock data in 2014-11-03 with the goal of studying the presence of jumps based on Limit Order Book (LOB) data. To this end, we divide the whole day’s data into many consecutive intervals and proceed to apply a jump detection method to identify the intervals that could potentially have jumps. After obtaining the intervals with potential jumps, we zoom in these intervals and compare them in order to characterize their features. More specifically, we analyze the price LOB data from both the traditional side and the statistical side, and our aim is that try to identify statistical differences between the intervals with jumps and without any jump, and then give evidence to support this jump detection method and conjecture reasons for the appearance of sharp price changes in small intervals

Malaria incidence from 2005–2013 and its associations with meteorological factors in Guangdong, China

Background: The temporal variation of malaria incidence has been linked to meteorological factors in many studies, but key factors observed and corresponding effect estimates were not consistent. Furthermore, the potential effect modification by individual characteristics is not well documented. This study intends to examine the delayed effects of meteorological factors and the sub-population's susceptibility in Guangdong, China. Methods: The Granger causality Wald test and Spearman correlation analysis were employed to select climatic variables influencing malaria. The distributed lag non-linear model (DLNM) was used to estimate the non-linear and delayed effects of weekly temperature, duration of sunshine, and precipitation on the weekly number of malaria cases after controlling for other confounders. Stratified analyses were conducted to identify the sub-population's susceptibility to meteorological effects by malaria type, gender, and age group. Results: An incidence rate of 1.1 cases per 1,000,000 people was detected in Guangdong from 2005-2013. High temperature was associated with an observed increase in malaria incidence, with the effect lasting for four weeks and a maximum relative risk (RR) of 1.57 (95% confidence interval (CI): 1.06-2.33) by comparing 30°C to the median temperature. The effect of sunshine duration peaked at lag five and the maximum RR was 1.36 (95% CI: 1.08-1.72) by comparing 24 hours/week to 0 hours/week. A J-shaped relationship was found between malaria incidence and precipitation with a threshold of 150 mm/week. Over the threshold, precipitation increased malaria incidence after four weeks with the effect lasting for 15 weeks, and the maximum RR of 1.55 (95% CI: 1.18-2.03) occurring at lag eight by comparing 225 mm/week to 0 mm/week. Plasmodium falciparum was more sensitive to temperature and precipitation than Plasmodium vivax. Females had a higher susceptibility to the effects of sunshine and precipitation, and children and the elderly were more sensitive to the change of temperature, sunshine duration, and precipitation. Conclusion: Temperature, duration of sunshine and precipitation played important roles in malaria incidence with effects delayed and varied across lags. Climatic effects were distinct among sub-groups. This study provided helpful information for predicting malaria incidence and developing the future warning system.School of Nursin

Fully Band Resolved Scattering Rate in MgB2 Revealed by Nonlinear Hall Effect and Magnetoresistance Measurements

We have measured the normal state temperature dependence of the Hall effect and magnetoresistance in epitaxial MgB2 thin films with variable disorders characterized by the residual resistance ratio RRR ranging from 4.0 to 33.3. A strong nonlinearity of the Hall effect and magnetoresistance have been found in clean samples, and they decrease gradually with the increase of disorders or temperature. By fitting the data to the theoretical model based on the Boltzmann equation and ab initio calculations for a four-band system, for the first time, we derived the scattering rates of these four bands at different temperatures and magnitude of disorders. Our method provides a unique way to derive these important parameters in multiband systems.Comment: 4 pages, 4 figure