Large-scale single-cell RNA sequencing (scRNA-seq) data sets that are produced in different laboratories and at different times contain batch effects that may compromise the integration and ...interpretation of the data. Existing scRNA-seq analysis methods incorrectly assume that the composition of cell populations is either known or identical across batches. We present a strategy for batch correction based on the detection of mutual nearest neighbors (MNNs) in the high-dimensional expression space. Our approach does not rely on predefined or equal population compositions across batches; instead, it requires only that a subset of the population be shared between batches. We demonstrate the superiority of our approach compared with existing methods by using both simulated and real scRNA-seq data sets. Using multiple droplet-based scRNA-seq data sets, we demonstrate that our MNN batch-effect-correction method can be scaled to large numbers of cells.
•A new HPLC method for the determination of amygdalin in food has been developed and optimised.•The method has been applied to commercially-available foods.•Results show that amygdalin can be ...detected at levels that reflect the raw material content and processing procedures employed.•Levels of amygdalin as reported do not present a food safety issue, though periodic monitoring might be sensible.
Cyanogenic glycosides are a large group of secondary metabolites that are widely distributed in the plant kingdom, including many plants that are commonly consumed by humans. The diverse chemical nature of cyanogenic glycosides means that extraction and analysis of individual compounds can be difficult. In addition, degradation can be rapid under appropriate conditions. Amygdalin is one of the cyanogenic glycosides found, for example, in apples, apricots and almonds. We have developed and applied a high performance liquid chromatographic procedure for amygdalin quantification to investigate extraction efficiency and to determine levels in a range of commercially-available foods for the first time. Our results show that seed from Rosaceae species contained relatively high amounts (range 0.1–17.5mgg−1) of amygdalin compared to seed from non-Rosaceae species (range 0.01–0.2mgg−1). The amygdalin content of processed food products was very low.
•Translational research requires the use of relevant preclinical pain models and assessment tools.•Clinically relevant behavioral tests should focus on restoring function by reducing pathological ...pain in the absence of disruptive side effects.•Grimace, Operant Behavior, Wheel Running, Burrowing, Nesting, Home Cage Monitoring, Gait Analysis, CPP and CPA are described.•Analysis of the advantages and limitations of these tests will help researchers identify appropriate tests for their particular goal.
The primary objective of preclinical pain research is to improve the treatment of pain. Decades of research using pain-evoked tests has revealed much about mechanisms but failed to deliver new treatments. Evoked pain-tests are often limited because they ignore spontaneous pain and motor or disruptive side effects confound interpretation of results. New tests have been developed to focus more closely on clinical goals such as reducing pathological pain and restoring function. The objective of this review is to describe and discuss several of these tests. We focus on: Grimace Scale, Operant Behavior, Wheel Running, Burrowing, Nesting, Home Cage Monitoring, Gait Analysis and Conditioned Place Preference/ Aversion. A brief description of each method is presented along with an analysis of the advantages and limitations. The pros and cons of each test will help researchers identify the assessment tool most appropriate to meet their particular objective to assess pain in rodents. These tests provide another tool to unravel the mechanisms underlying chronic pain and help overcome the translational gap in drug development.
This book brings together established and emerging international scholars to provide systematic reviews and illustrative cases drawn from tourism, leisure, hospitality, sport and event contexts. It ...offers a useful framework for focusing the goals and methodologies of future research efforts and for implementing the results of these efforts.
Receptor-interacting protein kinase-3 (RIPK3, or RIP3) is an essential protein in the "programmed" and "regulated" cell death pathway called necroptosis. Necroptosis is activated by the death ...receptor ligands and pattern recognition receptors of the innate immune system, and the findings of many reports have suggested that necroptosis is highly significant in health and human disease. This significance is largely because necroptosis is distinguished from other modes of cell death, especially apoptosis, in that it is highly proinflammatory given that cell membrane integrity is lost, triggering the activation of the immune system and inflammation. Here, we discuss the roles of RIPK3 in cell signaling, along with its role in necroptosis and various pathways that trigger RIPK3 activation and cell death. Lastly, we consider pathological situations in which RIPK3/necroptosis may play a role.
•No previous systematic studies on the extraction of H. sabdariffa.•Time, temperature and solvent affect extraction.•Boiling water, extracting for 10min achieved maximal results in different ...assays.•Extracts are rich sources of anthocyanins, potentially responsible for bioactivity.
Hibiscus sabdariffa extracts have attracted attention because of potentially useful bioactivity. However, there have been no systematic studies of extraction efficiencies of H. sabdariffa. The nature of extracts used in different studies has varied considerably, making comparisons difficult. Therefore, a systematic study of extracts of H. sabdariffa made with different solvents was carried out using water, methanol, ethyl acetate and hexane in the presence/absence of formic acid, using different extraction times and temperatures. The extracts were analysed for total polyphenol content, antioxidant capacity using DPPH, FRAP and TEAC assays, and specific anthocyanins were determined using HPLC and LC–MS. The results showed the highest antioxidant capacities were obtained by extracting using water, with or without formic acid, for 10min at 100°C. These extracts provided the highest concentrations of cyanidin 3-sambubioside and delphinidin 3-sambubioside. It will be important to use extraction conditions giving optimal extraction efficiencies for subsequent bioactivity experiments.
NF-κB proteins are a family of transcription factors that are of central importance in inflammation and immunity. NF-κB also plays important roles in other processes, including development, cell ...growth and survival, and proliferation, and is involved in many pathological conditions. Reactive Oxygen Species (ROS) are created by a variety of cellular processes as part of cellular signaling events. While certain NF-κB-regulated genes play a major role in regulating the amount of ROS in the cell, ROS have various inhibitory or stimulatory roles in NF-κB signaling. Here we review the regulation of ROS levels by NF-κB targets and various ways in which ROS have been proposed to impact NF-κB signaling pathways.
•Germination increases crude protein and total phenolic content of rice bean.•Acid pretreatment and germination improve antioxidant activities of rice bean.•Germination strongly affects an increase ...in alanine, glutamic acid and serine.•Acid pretreatment leads to a significant decrease in intensity of the 76kDa band.•Ethanolic extract contains more phenolics and antioxidant than water extract.
This research evaluated effect of germination period and acid pretreatment on chemical composition and antioxidant activity of rice bean sprouts. Moisture, total phenolics, reducing sugar and B vitamins (thiamine, riboflavin, and niacin) content of steamed sprouts increased with increasing germination time (p⩽0.05). Pretreatment with 1% (w/v) citric acid for 6h significantly increased the total phenolic content. The 18-h-germinated rice beans showed the highest crude protein content, as determined using the Kjeldahl method. During germination, acid pretreatment led to a significant decrease in the intensity of the 76-kDa band. Germination caused a significant increase in radical scavenging activity and ferric reducing antioxidant power, especially in sprouts from citric acid-treated seeds. The antioxidant activities of the ethanolic extracts from both pretreated beans and the control were 1.3–1.6 times higher than those obtained from the water extracts. Major phenolics found in both 0-h and 18-h-germinated rice beans were catechin and rutin.
Current computational workflows for comparative analyses of single-cell datasets typically use discrete clusters as input when testing for differential abundance among experimental conditions. ...However, clusters do not always provide the appropriate resolution and cannot capture continuous trajectories. Here we present Milo, a scalable statistical framework that performs differential abundance testing by assigning cells to partially overlapping neighborhoods on a k-nearest neighbor graph. Using simulations and single-cell RNA sequencing (scRNA-seq) data, we show that Milo can identify perturbations that are obscured by discretizing cells into clusters, that it maintains false discovery rate control across batch effects and that it outperforms alternative differential abundance testing strategies. Milo identifies the decline of a fate-biased epithelial precursor in the aging mouse thymus and identifies perturbations to multiple lineages in human cirrhotic liver. As Milo is based on a cell-cell similarity structure, it might also be applicable to single-cell data other than scRNA-seq. Milo is provided as an open-source R software package at https://github.com/MarioniLab/miloR .
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