McGill University

About: McGill University is a education organization based out in Montreal, Quebec, Canada. It is known for research contribution in the topics: Population & Poison control. The organization has 72688 authors who have published 162565 publications receiving 6966523 citations. The organization is also known as: Royal institution of advanced learning & University of McGill College.

Using MicrobiomeAnalyst for comprehensive statistical, functional, and meta-analysis of microbiome data.

Abstract: MicrobiomeAnalyst is an easy-to-use, web-based platform for comprehensive analysis of common data outputs generated from current microbiome studies. It enables researchers and clinicians with little or no bioinformatics training to explore a wide variety of well-established methods for microbiome data processing, statistical analysis, functional profiling and comparison with public datasets or known microbial signatures. MicrobiomeAnalyst currently contains four modules: Marker-gene Data Profiling (MDP), Shotgun Data Profiling (SDP), Projection with Public Data (PPD), and Taxon Set Enrichment Analysis (TSEA). This protocol will first introduce the MDP module by providing a step-wise description of how to prepare, process and normalize data; perform community profiling; identify important features; and conduct correlation and classification analysis. We will then demonstrate how to perform predictive functional profiling and introduce several unique features of the SDP module for functional analysis. The last two sections will describe the key steps involved in using the PPD and TSEA modules for meta-analysis and visual exploration of the results. In summary, MicrobiomeAnalyst offers a one-stop shop that enables microbiome researchers to thoroughly explore their preprocessed microbiome data via intuitive web interfaces. The complete protocol can be executed in ~70 min. This protocol details MicrobiomeAnalyst, a user-friendly, web-based platform for comprehensive statistical, functional, and meta-analysis of microbiome data.

Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus.

Abstract: Interferons are circulating factors that bind to cell surface receptors, activating a signaling cascade, ultimately leading to both an antiviral response and an induction of growth inhibitory and/or apoptotic signals in normal and tumor cells. Attempts to exploit the ability of interferons to limit the growth of tumors in patients has met with limited results because of cancer-specific mutations of gene products in the interferon pathway. Although interferon-non-responsive cancer cells may have acquired a growth/survival advantage over their normal counterparts, they may have simultaneously compromised their antiviral response. To test this, we used vesicular stomatitis virus (VSV), an enveloped, negative-sense RNA virus exquisitely sensitive to treatment with interferon. VSV rapidly replicated in and selectively killed a variety of human tumor cell lines even in the presence of doses of interferon that completely protected normal human primary cell cultures. A single intratumoral injection of VSV was effective in reducing the tumor burden of nude mice bearing subcutaneous human melanoma xenografts. Our results support the use of VSV as a replication-competent oncolytic virus and demonstrate a new strategy for the treatment of interferon non-responsive tumors.

The cholinergic system in the pathophysiology and treatment of Alzheimer's disease.

Abstract: Cholinergic synapses are ubiquitous in the human central nervous system. Their high density in the thalamus, striatum, limbic system, and neocortex suggest that cholinergic transmission is likely to be critically important for memory, learning, attention and other higher brain functions. Several lines of research suggest additional roles for cholinergic systems in overall brain homeostasis and plasticity. As such, the brain's cholinergic system occupies a central role in ongoing research related to normal cognition and age-related cognitive decline, including dementias such as Alzheimer's disease. The cholinergic hypothesis of Alzheimer's disease centres on the progressive loss of limbic and neocortical cholinergic innervation. Neurofibrillary degeneration in the basal forebrain is believed to be the primary cause for the dysfunction and death of forebrain cholinergic neurons, giving rise to a widespread presynaptic cholinergic denervation. Cholinesterase inhibitors increase the availability of acetylcholine at synapses in the brain and are one of the few drug therapies that have been proven clinically useful in the treatment of Alzheimer's disease dementia, thus validating the cholinergic system as an important therapeutic target in the disease. This review includes an overview of the role of the cholinergic system in cognition and an updated understanding of how cholinergic deficits in Alzheimer's disease interact with other aspects of disease pathophysiology, including plaques composed of amyloid-β proteins. This review also documents the benefits of cholinergic therapies at various stages of Alzheimer's disease and during long-term follow-up as visualized in novel imaging studies. The weight of the evidence supports the continued value of cholinergic drugs as a standard, cornerstone pharmacological approach in Alzheimer's disease, particularly as we look ahead to future combination therapies that address symptoms as well as disease progression.

Mental rotation of the neuronal population vector.

Abstract: A rhesus monkey was trained to move its arm in a direction that was perpendicular to and counterclockwise from the direction of a target light that changed in position from trial to trial. Solution of this problem was hypothesized to involve the creation and mental rotation of an imagined movement vector from the direction of the light to the direction of the movement. This hypothesis was tested directly by recording the activity of cells in the motor cortex during performance of the task and computing the neuronal population vector in successive time intervals during the reaction time. The population vector rotated gradually counterclockwise from the direction of the light to the direction of the movement at an average rate of 732 degrees per second. These results provide direct, neural evidence for the mental rotation hypothesis and indicate that the neuronal population vector is a useful tool for "reading out" and identifying cognitive operations of neuronal ensembles.