In vivo robotics: the automation of neuroscience and other intact-system biological fields

Robotic and automation technologies have played a huge role in in vitro biological science, having proved critical for scientific endeavors such as genome sequencing and high-throughput screening. Robotic and automation strategies are beginning to play a greater role in in vivo and in situ sciences, especially when it comes to the difficult in vivo experiments required for understanding the neural mechanisms of behavior and disease. In this perspective, we discuss the prospects for robotics and automation to influence neuroscientific and intact-system biology fields. We discuss how robotic innovations might be created to open up new frontiers in basic and applied neuroscience and present a concrete example with our recent automation of in vivo whole-cell patch clamp electrophysiology of neurons in the living mouse brain.National Institutes of Health (U.S.) (Single Cell Grant 1 R01 EY023173)Human Frontier Science Program (Strasbourg, France)McGovern Institute for Brain Research at MIT. Neurotechnology (MINT) ProgramMIT Media Lab ConsortiumNew York Stem Cell Foundation (Robertson Investigator Award)National Institutes of Health (U.S.) (Director's New Innovator Award 1DP2OD002002)National Institutes of Health (U.S.) (EUREKA Award 1R01GM104948)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Science Foundation (U.S.) (CAREER Award CBET 1053233)National Science Foundation (U.S.) (DMS1042134)Paul G. Allen Family Foundation (Distinguished Investigator in Neuroscience Award)Skolkovo Institute of Science and Technolog

Initial Leakage Under Pit and Fissure Sealants Assessed by Neutron Activation

An improved neutron activation method and a model system were used to study microleakage associated with three pit and fissure sealants. Both the sealant and the etching procedure were evaluated on enamel surfaces as well as in prepared model pits. Leakage was reduced to 3 to 4 μg for all three materials, and the etching process was relatively ineffective in forming an initial seal.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66699/2/10.1177_00220345740530062501.pd

Arp2/3 Complex Is Required for Macrophage Integrin Functions but Is Dispensable for FcR Phagocytosis and In Vivo Motility

The Arp2/3 complex nucleates branched actin, forming networks involved in lamellipodial protrusion, phagocytosis, and cell adhesion. We derived primary bone marrow macrophages lacking Arp2/3 complex (Arpc2−/−) and directly tested its role in macrophage functions. Despite protrusion and actin assembly defects, Arpc2−/− macrophages competently phagocytose via FcR and chemotax toward CSF and CX3CL1. However, CR3 phagocytosis and fibronectin haptotaxis, both integrin-dependent processes, are disrupted. Integrin-responsive actin assembly and αM/β2 integrin localization are compromised in Arpc2−/− cells. Using an in vivo system to observe endogenous monocytes migrating toward full-thickness ear wounds we found that Arpc2−/− monocytes maintain cell speeds and directionality similar to control. Our work reveals that the Arp2/3 complex is not a general requirement for phagocytosis or chemotaxis but is a critical driver of integrin-dependent processes. We demonstrate further that cells lacking Arp2/3 complex function in vivo remain capable of executing important physiological responses that require rapid directional motility. Using a combination of cell culture-based and in vivo mouse experiments, Rotty et al. demonstrate that the actin-nucleating Arp2/3 complex is not absolutely required for macrophage FcR phagocytosis, chemotaxis, or in vivo monocyte directional motility. Rather, the complex has a critical role in regulating integrin-dependent macrophage processes

Periodic solutions for a class of nonlinear partial differential equations in higher dimension

We prove the existence of periodic solutions in a class of nonlinear partial differential equations, including the nonlinear Schroedinger equation, the nonlinear wave equation, and the nonlinear beam equation, in higher dimension. Our result covers cases where the bifurcation equation is infinite-dimensional, such as the nonlinear Schroedinger equation with zero mass, for which solutions which at leading order are wave packets are shown to exist.Comment: 34 page

Transitions of cardio-metabolic risk factors in the Americas between 1980 and 2014

Describing the prevalence and trends of cardiometabolic risk factors that are associated with non-communicable diseases (NCDs) is crucial for monitoring progress, planning prevention, and providing evidence to support policy efforts. We aimed to analyse the transition in body-mass index (BMI), obesity, blood pressure, raised blood pressure, and diabetes in the Americas, between 1980 and 2014

Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved