Novel image analysis tool for rapid screening of cell morphology in preclinical animal models of disease.

The field of cell biology has seen major advances in both cellular imaging modalities and the development of automated image analysis platforms that increase rigor, reproducibility, and throughput for large imaging data sets. However, there remains a need for tools that provide accurate morphometric analysis of single cells with complex, dynamic cytoarchitecture in a high-throughput and unbiased manner. We developed a fully automated image-analysis algorithm to rapidly detect and quantify changes in cellular morphology using microglia cells, an innate immune cell within the central nervous system, as representative of cells that exhibit dynamic and complex cytoarchitectural changes.

Analog Nanoscale Electro-Optical Synapses for Neuromorphic Computing Applications.

The typically nonlinear and asymmetric response of synaptic memristors to positive and negative electrical pulses makes the realization of accurate deep neural networks very challenging. Here, we integrate a two-terminal valence change memory (VCM) into a photonic/plasmonic circuit and show that the switching properties of this memristor become more gradual and symmetric under light irradiation. The added optical input acts on the VCM as a third, independent modulation channel.

Robust high-dimensional memory-augmented neural networks.

Traditional neural networks require enormous amounts of data to build their complex mappings during a slow training procedure that hinders their abilities for relearning and adapting to new data. Memory-augmented neural networks enhance neural networks with an explicit memory to overcome these issues. Access to this explicit memory, however, occurs via soft read and write operations involving every individual memory entry, resulting in a bottleneck when implemented using the conventional von Neumann computer architecture.

Testing a gamified Spider App to reduce spider fear and avoidance.

Mobile applications are increasingly part of mental health programs and various apps have been developed for treating anxiety disorders. Typically, they aim to improve anxiety symptoms via established CBT techniques, such as exposure principles, which are considered extremely unpleasant for fearful individuals. We combined in a mobile application exposure principles with gamification elements (e.

Interaction between magnesium and methylglyoxal in diabetic polyneuropathy and neuronal models.

Objective: The lack of effective treatments against diabetic sensorimotor polyneuropathy demands the search for new strategies to combat or prevent the condition. Because reduced magnesium and increased methylglyoxal levels have been implicated in the development of both type 2 diabetes and neuropathic pain, we aimed to assess the putative interplay of both molecules with diabetic sensorimotor polyneuropathy.

Methods: In a cross-sectional study, serum magnesium and plasma methylglyoxal levels were measured in recently diagnosed type 2 diabetes patients with (n = 51) and without (n = 184) diabetic sensorimotor polyneuropathy from the German Diabetes Study baseline cohort.

The relationship between regional medical campus enrollment and rates of matching to family medicine residency.

Background: The Michael G. DeGroote School of Medicine expanded its medical education across three campus sites (Hamilton, Niagara Regional and Waterloo Regional) in 2007. Ensuring the efficacy and equivalency of the quality of training are important accreditation considerations in distributed medical education.

Verticillium Wilt in Oilseed Rape-the Microbiome is Crucial for Disease Outbreaks as Well as for Efficient Suppression.

Microbiome management is a promising way to suppress verticillium wilt, a severe disease in caused by . In order to improve current biocontrol strategies, we compared bacterial antagonists in different assays using a hierarchical selection and evaluation scheme, and we integrated outcomes of our previous studies. The result was strongly dependent on the assessment method chosen (in vitro, in vivo, in situ), on the growth conditions of the plants and their genotype.

Automated high content image analysis of dendritic arborization in primary mouse hippocampal and rat cortical neurons in culture.

Background: Primary neuronal cell cultures are useful for studying mechanisms that influence dendritic morphology during normal development and in response to various stressors. However, analyzing dendritic morphology is challenging, particularly in cultures with high cell density, and manual methods of selecting neurons and tracing dendritic arbors can introduce significant bias, and are labor-intensive. To overcome these challenges, semi-automated and automated methods are being developed, with most software solutions requiring computer-assisted dendrite tracing with subsequent quantification of various parameters of dendritic morphology, such as Sholl analysis.

Characterization and application of electrically active neuronal networks established from human induced pluripotent stem cell-derived neural progenitor cells for neurotoxicity evaluation.

Neurotoxicity is mediated by a variety of modes-of-actions leading to disturbance of neuronal function. In order to screen larger numbers of compounds for their neurotoxic potential, in vitro functional neuronal networks (NN) might be helpful tools. We established and characterized human NN (hNN) from hiPSC-derived neural progenitor cells by comparing hNN formation with two different differentiation media: in presence (CINDA) and absence (neural differentiation medium (NDM)) of maturation-supporting factors.

Isoform-selective as opposed to complete depletion of fibroblast growth factor 2 (FGF-2) has no major impact on survival and gene expression in SOD1 amyotrophic lateral sclerosis mice.

We have previously shown that total knockout of fibroblast growth factor-2 (FGF-2) results in prolonged survival and improved motor performance in superoxide dismutase 1 (SOD1 ) mutant mice, the most widely used animal model of the fatal adult onset motor neuron disease amyotrophic lateral sclerosis (ALS). Moreover, we found differential expression of growth factors in SOD1 mice, with distinct regulation patterns of FGF-2 in spinal cord and muscle tissue. Within the present study we aimed to characterize FGF-2-isoform specific effects on survival, motor performance as well as gene expression patterns predominantly in muscle tissue by generating double mutant SOD1 FGF-2 high molecular weight- and SOD1 FGF-2 low molecular weight-knockout mice.

Enriching Beneficial Microbial Diversity of Indoor Plants and Their Surrounding Built Environment With Biostimulants.

Microbial diversity is suggested as the key for plant and human health. However, how microbial diversity can be enriched is largely unknown but of great interest for health issues. Biostimulants offer the way to directly augment our main living areas by the healthy microbiome of indoor plants.

Characterizing the multiple roles of FGF-2 in SOD1 ALS mice in vivo and in vitro.

We have previously shown that knockout of fibroblast growth factor-2 (FGF-2) and potential compensatory effects of other growth factors result in amelioration of disease symptoms in a transgenic mouse model of amyotrophic lateral sclerosis (ALS). ALS is a rapidly progressive neurological disorder leading to degeneration of cortical, brain stem, and spinal motor neurons followed by subsequent denervation and muscle wasting. Mutations in the superoxide dismutase 1 (SOD1) gene are responsible for approximately 20% of familial ALS cases and SOD1 mutant mice still are among the models best mimicking clinical and neuropathological characteristics of ALS.

Teratological and Behavioral Screening of the National Toxicology Program 91-Compound Library in Zebrafish (Danio rerio).

To screen the tens of thousands of chemicals for which no toxicity data currently exists, it is necessary to move from in vivo rodent models to alternative models, such as zebrafish. Here, we used dechorionated Tropical 5D wild-type zebrafish embryos to screen a 91-compound library provided by the National Toxicology Program (NTP) for developmental toxicity. This library contained 86 unique chemicals that included negative controls, flame retardants, polycyclic aromatic hydrocarbons (PAHs), drugs, industrial chemicals, and pesticides.

Deficiency of the clock gene Bmal1 affects neural progenitor cell migration.

We demonstrate the impact of a disrupted molecular clock in Bmal1-deficient (Bmal1) mice on migration of neural progenitor cells (NPCs). Proliferation of NPCs in rostral migratory stream (RMS) was reduced in Bmal1 mice, consistent with our earlier studies on adult neurogenesis in hippocampus. However, a significantly higher number of NPCs from Bmal1 mice reached the olfactory bulb as compared to wild-type littermates (Bmal1 mice), indicating a higher migration velocity in Bmal1 mice.

PCB 95 promotes dendritic growth in primary rat hippocampal neurons via mTOR-dependent mechanisms.

Polychlorinated biphenyls (PCBs), and in particular non-dioxin-like (NDL) congeners, continue to pose a significant risk to the developing nervous system. PCB 95, a prevalent NDL congener in the human chemosphere, promotes dendritic growth in rodent primary neurons by activating calcium-dependent transcriptional mechanisms that normally function to link activity to dendritic growth. Activity-dependent dendritic growth is also mediated by calcium-dependent translational mechanisms involving mechanistic target of rapamycin (mTOR), suggesting that the dendrite-promoting activity of PCB 95 may also involve mTOR signaling.

Current Availability of Stem Cell-Based In Vitro Methods for Developmental Neurotoxicity (DNT) Testing.

There is evidence that chemical exposure during development can cause irreversible impairments of the human developing nervous system. Therefore, testing compounds for their developmentally neurotoxic potential has high priority for different stakeholders: academia, industry, and regulatory bodies. Due to the resource-intensity of current developmental neurotoxicity (DNT) in vivo guidelines, alternative methods that are scientifically valid and have a high predictivity for humans are especially desired by regulators.

Development of the Concept for Stem Cell-Based Developmental Neurotoxicity Evaluation.

Human brain development consists of a series of complex spatiotemporal processes that if disturbed by chemical exposure causes irreversible impairments of the nervous system. To evaluate a chemical disturbance in an alternative assay, the concept evolved that the complex procedure of brain development can be disassembled into several neurodevelopmental endpoints which can be represented by a combination of different alternative assays. In this review article, we provide a scientific rationale for the neurodevelopmental endpoints that are currently chosen to establish assays with human stem/and progenitor cells.

Comparative performance analysis of human iPSC-derived and primary neural progenitor cells (NPC) grown as neurospheres in vitro.

Developmental neurotoxicity (DNT) testing performed in rats is resource-intensive (costs, time, animals) and bears the issue of species extrapolation. Thus, reliable alternative human-based approaches are needed for predicting neurodevelopmental toxicity. Human induced pluripotent stem cells (hiPSCs) represent a basis for an alternative method possibly being part of an alternative DNT testing strategy.

Aerial Warfare: A Volatile Dialogue between the Plant Pathogen and Its Antagonist .

Verticillium wilt caused by spp. results in severe yield losses in a broad range of crops. outbreaks are challenging to control, and exacerbated by increases in soil temperatures and drought associated with global warming.

Omnisphero: a high-content image analysis (HCA) approach for phenotypic developmental neurotoxicity (DNT) screenings of organoid neurosphere cultures in vitro.

Current developmental neurotoxicity (DNT) testing in animals faces major limitations, such as high cost and time demands as well as uncertainties in their methodology, evaluation and regulation. Therefore, the use of human-based 3D in vitro systems in combination with high-content image analysis (HCA) might contribute to DNT testing with lower costs, increased throughput and enhanced predictivity for human hazard identification. Human neural progenitor cells (hNPCs) grown as 3D neurospheres mimic basic processes of brain development including hNPC migration and differentiation and are therefore useful for DNT hazard identification.

A phase II study of the HSP90 inhibitor AUY922 in chemotherapy refractory advanced pancreatic cancer.

Objectives: AUY922 is a novel heat shock protein inhibitor with preclinical activity in pancreatic cancer. This phase II study evaluated the efficacy of AUY922 in patients with advanced pancreatic cancer previously treated with chemotherapy.

Methods: In this single-arm, Simon two-stage phase II trial, patients with metastatic or locally advanced pancreatic ductal adenocarcinoma who had progressed on at least one line of chemotherapy and were of good performances status (ECOG 0 or 1) were treated with AUY922 at a dose of 70 mg/m(2) IV weekly.

Epigallocatechin gallate (EGCG) inhibits adhesion and migration of neural progenitor cells in vitro.

Food supplements based on herbal products are widely used during pregnancy as part of a self-care approach. The idea that such supplements are safe and healthy is deeply seated in the general population, although they do not underlie the same strict safety regulations than medical drugs. We aimed to characterize the neurodevelopmental effects of the green tea catechin epigallocatechin gallate (EGCG), which is now commercialized as high-dose food supplement.