Genetic and Genomic Strategies in Learning and Memory

Abstract: Learning and memory is a property of central importance in the nervous system, yet many of the molecular mechanisms for this behavior remain enshrouded in mystery. Despite the daunting nature of the problem, a number of complementary strategies have been employed to unravel the complexities of learning and memory, ranging from genetics to biochemistry. One of the most recent tools brought to bear in this area is genomics. Here, we review some of the most significant insights that have been so far obtained in learning and memory, and we suggest possible areas of future progress

Circulation first – the time has come to question the sequencing of care in the ABCs of trauma; an American Association for the Surgery of Trauma multicenter trial

Background The traditional sequence of trauma care: Airway, Breathing, Circulation (ABC) has been practiced for many years. It became the standard of care despite the lack of scientific evidence. We hypothesized that patients in hypovolemic shock would have comparable outcomes with initiation of bleeding treatment (transfusion) prior to intubation (CAB), compared to those patients treated with the traditional ABC sequence. Methods This study was sponsored by the American Association for the Surgery of Trauma multicenter trials committee. We performed a retrospective analysis of all patients that presented to trauma centers with presumptive hypovolemic shock indicated by pre-hospital or emergency department hypotension and need for intubation from January 1, 2014 to July 1, 2016. Data collected included demographics, timing of intubation, vital signs before and after intubation, timing of the blood transfusion initiation related to intubation, and outcomes. Results From 440 patients that met inclusion criteria, 245 (55.7%) received intravenous blood product resuscitation first (CAB), and 195 (44.3%) were intubated before any resuscitation was started (ABC). There was no difference in ISS, mechanism, or comorbidities. Those intubated prior to receiving transfusion had a lower GCS than those with transfusion initiation prior to intubation (ABC: 4, CAB:9, p = 0.005). Although mortality was high in both groups, there was no statistically significant difference (CAB 47% and ABC 50%). In multivariate analysis, initial SBP and initial GCS were the only independent predictors of death. Conclusion The current study highlights that many trauma centers are already initiating circulation first prior to intubation when treating hypovolemic shock (CAB), even in patients with a low GCS. This practice was not associated with an increased mortality. Further prospective investigation is warranted. Trial registration IRB approval number: HM20006627. Retrospective trial not registered

Effects of increased body mass index on employment status:a Mendelian randomisation study

Background: The obesity epidemic may have substantial implications for the global workforce, including causal effects on employment, but clear evidence is lacking. Obesity may prevent people from being in paid work through poor health or through social discrimination. We studied genetic variants robustly associated with body mass index (BMI) to investigate its causal effects on employment. Dataset/methods: White UK ethnicity participants of working age (men 40–64 years, women 40–59 years), with suitable genetic data were selected in the UK Biobank study (N = 230,791). Employment status was categorised in two ways: first, contrasting being in paid employment with any other status; and second, contrasting being in paid employment with sickness/disability, unemployment, early retirement and caring for home/family. Socioeconomic indicators also investigated were hours worked, household income, educational attainment and Townsend deprivation index (TDI). We conducted observational and two-sample Mendelian randomisation (MR) analyses to investigate the effect of increased BMI on employment-related outcomes. Results: Regressions showed BMI associated with all the employment-related outcomes investigated. MR analyses provided evidence for higher BMI causing increased risk of sickness/disability (OR 1.08, 95% CI 1.04, 1.11, per 1 Kg/m2 BMI increase) and decreased caring for home/family (OR 0.96, 95% CI 0.93, 0.99), higher TDI (Beta 0.038, 95% CI 0.018, 0.059), and lower household income (OR 0.98, 95% CI 0.96, 0.99). In contrast, MR provided evidence for no causal effect of BMI on unemployment, early retirement, non-employment, hours worked or educational attainment. There was little evidence for causal effects differing by sex or age. Robustness tests yielded consistent results. Discussion: BMI appears to exert a causal effect on employment status, largely by affecting an individual’s health rather than through increased unemployment arising from social discrimination. The obesity epidemic may be contributing to increased worklessness and therefore could impose a substantial societal burden

Forest disturbance and vector transmitted diseases in thelowland tropical rainforest of central Panama

objective To explore possible changes in the community attributes of haematophagous insects as afunction of forest disturbance. We compare the patterns of diversity and abundance, plus thebehavioural responses of three epidemiologically distinct vector assemblages across sites depictingvarious levels of forest cover.methods Over a 3-year period, we sampled mosquitoes, sandflies and biting-midges in forestedhabitats of central Panama. We placed CDC light traps in the forest canopy and in the understorey togather blood-seeking females.results We collected 168 405 adult haematophagous dipterans in total, including 26 genera and 86species. Pristine forest settings were always more taxonomically diverse than the disturbed forest sites,confirming that disturbance has a negative impact on species richness. Species of Phlebotominae andCulicoides were mainly classified as climax (i.e. forest specialist) or disturbance-generalist, which tendto decrease in abundance along with rising levels of disturbance. In contrast, a significant portion ofmosquito species, including primary and secondary disease vectors, was classified as colonists (i.e.disturbed-areas specialists), which tend to increase in numbers towards more disturbed forest habitats.At pristine forest, the most prevalent species of Phlebotominae and Culicoides partitioned the verticalniche by being active at the forest canopy or in the understorey; yet this pattern was less clear indisturbed habitats. Most mosquito species were not vertically stratified in their habitat preference.conclusion We posit that entomological risk and related pathogen exposure to humans is higher inpristine forest scenarios for Culicoides and Phlebotominae transmitted diseases, whereas forestdisturbance poses a higher entomological risk for mosquito-borne infections. This suggests that theDilution Effect Hypothesis (DEH) does not apply in tropical rainforests where highly abundant, yetunrecognised insect vectors and neglected zoonotic diseases occur. Comprehensive, community levelentomological surveillance is, therefore, the key for predicting potential disease spill over in scenariosof pristine forest intermixed with anthropogenic habitats. We suggest that changes in forest qualityshould also be considered when assessing arthropod-borne disease transmission risk.objective To explore possible changes in the community attributes of haematophagous insects as afunction of forest disturbance. We compare the patterns of diversity and abundance, plus thebehavioural responses of three epidemiologically distinct vector assemblages across sites depictingvarious levels of forest cover.methods Over a 3-year period, we sampled mosquitoes, sandflies and biting-midges in forestedhabitats of central Panama. We placed CDC light traps in the forest canopy and in the understorey togather blood-seeking females.results We collected 168 405 adult haematophagous dipterans in total, including 26 genera and 86species. Pristine forest settings were always more taxonomically diverse than the disturbed forest sites,confirming that disturbance has a negative impact on species richness. Species of Phlebotominae andCulicoides were mainly classified as climax (i.e. forest specialist) or disturbance-generalist, which tendto decrease in abundance along with rising levels of disturbance. In contrast, a significant portion ofmosquito species, including primary and secondary disease vectors, was classified as colonists (i.e.disturbed-areas specialists), which tend to increase in numbers towards more disturbed forest habitats.At pristine forest, the most prevalent species of Phlebotominae and Culicoides partitioned the verticalniche by being active at the forest canopy or in the understorey; yet this pattern was less clear indisturbed habitats. Most mosquito species were not vertically stratified in their habitat preference.conclusion We posit that entomological risk and related pathogen exposure to humans is higher inpristine forest scenarios for Culicoides and Phlebotominae transmitted diseases, whereas forestdisturbance poses a higher entomological risk for mosquito-borne infections. This suggests that theDilution Effect Hypothesis (DEH) does not apply in tropical rainforests where highly abundant, yetunrecognised insect vectors and neglected zoonotic diseases occur. Comprehensive, community levelentomological surveillance is, therefore, the key for predicting potential disease spill over in scenariosof pristine forest intermixed with anthropogenic habitats. We suggest that changes in forest qualityshould also be considered when assessing arthropod-borne disease transmission risk

The Hybrid Mouse Diversity Panel: a resource for systems genetics analyses of metabolic and cardiovascular traits

The Hybrid Mouse Diversity Panel (HMDP) is a collection of approximately 100 well-characterized inbred strains of mice that can be used to analyze the genetic and environmental factors underlying complex traits. While not nearly as powerful for mapping genetic loci contributing to the traits as human genome-wide association studies, it has some important advantages. First, environmental factors can be controlled. Second, relevant tissues are accessible for global molecular phenotyping. Finally, because inbred strains are renewable, results from separate studies can be integrated. Thus far, the HMDP has been studied for traits relevant to obesity, diabetes, atherosclerosis, osteoporosis, heart failure, immune regulation, fatty liver disease, and host-gut microbiota interactions. High-throughput technologies have been used to examine the genomes, epigenomes, transcriptomes, proteomes, metabolomes, and microbiomes of the mice under various environmental conditions. All of the published data are available and can be readily used to formulate hypotheses about genes, pathways and interactions

Statistical Analysis of Multiplex Brain Gene Expression Images

Analysis of variance (ANOVA) was employed to investigate 9,000 gene expression patterns from brains of both normal mice and mice with a pharmacological model of Parkinson's disease (PD). The data set was obtained using voxelation, a method that allows high-throughput acquisition of 3D gene expression patterns through analysis of spatially registered voxels (cubes). This method produces multiple volumetric maps of gene expression analogous to the images reconstructed in biomedical imaging systems. The ANOVA model was compared to the results from singular value decomposition (SVD) by using the first 42 singular vectors of the data matrix, a number equal to the rank of the ANOVA model. The ANOVA was also compared to the results from non-parametric statistics. Lastly, images were obtained for a subset of genes that emerged from the ANOVA as significant. The results suggest that ANOVA will be a valuable framework for insights into the large number of gene expression patterns obtained from voxelation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45422/1/11064_2004_Article_454311.pd