Updated Systematic Review and Quantitative Synthesis of Physical Activity Levels in Multiple Sclerosis.

OBJECTIVE: This article provided an updated quantitative synthesis of physical activity levels in persons with multiple sclerosis compared with controls and other clinical populations. DESIGN: A systematic search through PubMed, Scopus, and PsycINFO was conducted for articles published between August 2016 and July 2022. Articles that included a group comparison of at least one measurement of physical activity between adults with multiple sclerosis and controls or other clinical populations were included in the meta-analysis. RESULTS: Twenty-four studies met the inclusion criteria and yielded a total of 119 comparisons. There was a moderate difference in physical activity levels between persons with multiple sclerosis and controls (effect size = -0.56, P < 0.01), but no significant difference between persons with multiple sclerosis and other clinical populations (effect size = 0.01, P = 0.90). The pooled effect sizes comparing multiple sclerosis with controls ( Q104 = 457.9, P < 0.01) as well as with clinical populations ( Q13 = 108.4, P < 0.01) were heterogeneous. Moderating variables included sex, disability status, measurement method, outcome, intensity, and application of a multiple sclerosis-specific cut-point. CONCLUSIONS: Physical activity levels remain significantly lower in persons with multiple sclerosis compared with controls, but the magnitude of difference has become smaller over the past decade. There is a need for continued development of effective physical activity programs that can reach the greater community with multiple sclerosis.

EnsembleSplice: ensemble deep learning model for splice site prediction.

BACKGROUND: Identifying splice site regions is an important step in the genomic DNA sequencing pipelines of biomedical and pharmaceutical research. Within this research purview, efficient and accurate splice site detection is highly desirable, and a variety of computational models have been developed toward this end. Neural network architectures have recently been shown to outperform classical machine learning approaches for the task of splice site prediction. Despite these advances, there is still considerable potential for improvement, especially regarding model prediction accuracy, and error rate. RESULTS: Given these deficits, we propose EnsembleSplice, an ensemble learning architecture made up of four (4) distinct convolutional neural networks (CNN) model architecture combination that outperform existing splice site detection methods in the experimental evaluation metrics considered including the accuracies and error rates. We trained and tested a variety of ensembles made up of CNNs and DNNs using the five-fold cross-validation method to identify the model that performed the best across the evaluation and diversity metrics. As a result, we developed our diverse and highly effective splice site (SS) detection model, which we evaluated using two (2) genomic Homo sapiens datasets and the Arabidopsis thaliana dataset. The results showed that for of the Homo sapiens EnsembleSplice achieved accuracies of 94.16% for one of the acceptor splice sites and 95.97% for donor splice sites, with an error rate for the same Homo sapiens dataset, 4.03% for the donor splice sites and 5.84% for the acceptor splice sites datasets. CONCLUSIONS: Our five-fold cross validation ensured the prediction accuracy of our models are consistent. For reproducibility, all the datasets used, models generated, and results in our work are publicly available in our GitHub repository here: https://github.com/OluwadareLab/EnsembleSplice.

Comparative expression profiling reveals widespread coordinated evolution of gene expression across eukaryotes.

Comparative studies of gene expression across species have revealed many important insights, but have also been limited by the number of species represented. Here we develop an approach to identify orthologs between highly diverged transcriptome assemblies, and apply this to 657 RNA-seq gene expression profiles from 309 diverse unicellular eukaryotes. We analyzed the resulting data for coevolutionary patterns, and identify several hundred protein complexes and pathways whose expression levels have evolved in a coordinated fashion across the trillions of generations separating these species, including many gene sets with little or no within-species co-expression across environmental or genetic perturbations. We also detect examples of adaptive evolution, for example of tRNA ligase levels to match genome-wide codon usage. In sum, we find that comparative studies from extremely diverse organisms can reveal new insights into the evolution of gene expression, including coordinated evolution of some of the most conserved protein complexes in eukaryotes.

Synthesis of Ligand-free CdS Nanoparticles within a Sulfur Copolymer Matrix.

Aliphatic ligands are typically used during the synthesis of nanoparticles to help mediate their growth in addition to operating as high-temperature solvents. These coordinating ligands help solubilize and stabilize the nanoparticles while in solution, and can influence the resulting size and reactivity of the nanoparticles during their formation. Despite the ubiquity of using ligands during synthesis, the presence of aliphatic ligands on the nanoparticle surface can result in a number of problems during the end use of the nanoparticles, necessitating further ligand stripping or ligand exchange procedures. We have developed a way to synthesize cadmium sulfide (CdS) nanoparticles using a unique sulfur copolymer. This sulfur copolymer is primarily composed of elemental sulfur, which is a cheap and abundant material. The sulfur copolymer has the advantages of operating both as a high temperature solvent and as a sulfur source, which can react with a cadmium precursor during nanoparticle synthesis, resulting in the generation of ligand free CdS. During the reaction, only some of the copolymer is consumed to produce CdS, while the rest remains in the polymeric state, thereby producing a nanocomposite material. Once the reaction is finished, the copolymer stabilizes the nanoparticles within a solid polymeric matrix. The copolymer can then be removed before the nanoparticles are used, which produces nanoparticles that do not have organic coordinating ligands. This nascent synthesis technique presents a method to produce metal-sulfide nanoparticles for a wide variety of applications where the presence of organic ligands is not desired.

Pooled ChIP-Seq Links Variation in Transcription Factor Binding to Complex Disease Risk.

Cis-regulatory elements such as transcription factor (TF) binding sites can be identified genome-wide, but it remains far more challenging to pinpoint genetic variants affecting TF binding. Here, we introduce a pooling-based approach to mapping quantitative trait loci (QTLs) for molecular-level traits. Applying this to five TFs and a histone modification, we mapped thousands of cis-acting QTLs, with over 25-fold lower cost compared to standard QTL mapping. We found that single genetic variants frequently affect binding of multiple TFs, and CTCF can recruit all five TFs to its binding sites. These QTLs often affect local chromatin and transcription but can also influence long-range chromosomal contacts, demonstrating a role for natural genetic variation in chromosomal architecture. Thousands of these QTLs have been implicated in genome-wide association studies, providing candidate molecular mechanisms for many disease risk loci and suggesting that TF binding variation may underlie a large fraction of human phenotypic variation.

A First Report of Anguina pacificae in Ireland.

Anguina pacificae is a significant pest of Poa annua golf course greens in northern California. This study presents the first confirmed case of an A. pacificae infestation outside of North America, where the nematode's distribution is further restricted to a relatively limited coastal region. Species confirmation was made by morphometric and molecular methods and comparisons to closely related species including the European species, Anguina agropyri. The A. pacificae population detected on an Irish golf course was monitored over a 2-yr period and the life cycle compared with Californian population dynamics. A. pacificae was assessed for the potential risk of spreading to the local agricultural sector, in addition, the biosecurity risks from A. pacificae and plant parasitic nematodes in general were reviewed for northwest Europe.

Sulfur copolymer for the direct synthesis of ligand-free CdS nanoparticles.

Organic coordinating ligands are ubiquitously used to solubilize, stabilize and functionalize colloidal nanoparticles. Aliphatic organic ligands are typically used to control size during the nanoparticle growth period and are used as a high boiling point solvent for solution-based synthesis procedures. However, these aliphatic ligands are typically not well suited for the end use of the nanoparticles, so additional ligand exchange or ligand stripping procedures must be implemented after the nanoparticle synthesis. Herein we present a ligand-free CdS nanoparticle synthesis procedure using a unique sulfur copolymer. The sulfur copolymer is derived from elemental sulfur, which is a cheap and abundant material. This copolymer is used as a sulfur source and high boiling point solvent, which produces stabilized metal-sulfide nanoparticles that are suspended within a sulfur copolymer matrix. The copolymer can then be removed, thereby yielding ligand-free metal-sulfide nanoparticles.

A new system for comparative functional genomics of Saccharomyces yeasts.

Whole-genome sequencing, particularly in fungi, has progressed at a tremendous rate. More difficult, however, is experimental testing of the inferences about gene function that can be drawn from comparative sequence analysis alone. We present a genome-wide functional characterization of a sequenced but experimentally understudied budding yeast, Saccharomyces bayanus var. uvarum (henceforth referred to as S. bayanus), allowing us to map changes over the 20 million years that separate this organism from S. cerevisiae. We first created a suite of genetic tools to facilitate work in S. bayanus. Next, we measured the gene-expression response of S. bayanus to a diverse set of perturbations optimized using a computational approach to cover a diverse array of functionally relevant biological responses. The resulting data set reveals that gene-expression patterns are largely conserved, but significant changes may exist in regulatory networks such as carbohydrate utilization and meiosis. In addition to regulatory changes, our approach identified gene functions that have diverged. The functions of genes in core pathways are highly conserved, but we observed many changes in which genes are involved in osmotic stress, peroxisome biogenesis, and autophagy. A surprising number of genes specific to S. bayanus respond to oxidative stress, suggesting the organism may have evolved under different selection pressures than S. cerevisiae. This work expands the scope of genome-scale evolutionary studies from sequence-based analysis to rapid experimental characterization and could be adopted for functional mapping in any lineage of interest. Furthermore, our detailed characterization of S. bayanus provides a valuable resource for comparative functional genomics studies in yeast.

Real-time PCR detection and identification of prohibited mammalian and avian material in animal feeds.

A method for the detection and identification of "prohibited" mammalian or avian material in animal feed was developed and assessed through the analysis of DNA. A generic real-time PCR assay was designed to detect the presence of mammalian and avian mitochondrial DNA 16S rRNA genes in animal feed samples. Samples positive with this screening method were further investigated using identification assays to detect the 16S rRNA gene from bovine, ovine, porcine, and avian species and to determine whether the DNA originated from species whose material is prohibited from inclusion in farmed animal feed. An internal positive control was coamplified in the 16S real-time PCR assays to monitor PCR amplification efficiency and avoid potential false-negative results. Using vegetable-based feed standards spiked with meat and bone meal generated with a commercial rendering process, 0.1% meat and bone meal could be detected using the general and species-specific 16S assays. The species-specific assays had 100% specificity for the homologous target species. The 16S real-time PCR assays were evaluated alongside existing tests based on protein evaluation or microscopic examination for a wide range of commercial animal feed samples. In total, 111 (0.76%) of 14,678 samples examined contained prohibited material based on the results from at least one of these tests. However, most positive results did not represent noncompliance because they were associated with samples of pet food, which can legitimately contain material prohibited for use in food for farmed animals. The species-specific 16S assays confirmed the presence of prohibited material in 75% of the 111 samples, whereas the existing protein and microscope tests confirmed the presence of this material in 25 and 54% of the samples, respectively.

Starvation affects vitellogenin production but not vitellogenin mRNA levels in the lubber grasshopper, Romalea microptera.

The interaction of juvenile hormone (JH) and nutrition was studied during the oviposition cycle of the Eastern Lubber grasshopper (Romalea microptera). Starvation of females early or in the middle of the cycle inhibited oocyte growth. Starvation for 4 days also reduced hemolymph levels of JH III and vitellogenesis (Vg) to 25% and 15%, respectively, of the levels in fed animals. Likewise, Vg production by fat body fragments incubated in vitro was reduced to 2% of the levels in fed animals and total protein synthesis was reduced to 25%, suggesting that starvation had a stronger effect on Vg synthesis than on protein synthesis. These effects were reversed when starved animals were fed again. However, fat body levels of Vg-mRNA were similar in fed and starved animals, indicating that starvation did not affect transcript levels. We tested whether the decline in JH levels mediated the other starvation effects by infusing animals with JH III or vehicle for 2 days at the onset of starvation. Infusion of JH elevated JH and Vg-mRNA levels 670% and 103%, respectively, above the levels in vehicle-infused animals. However, Vg production and hemolymph levels of Vg were similar to the levels in vehicle-infused animals. These data suggest that JH alone is insufficient to stimulate Vg production.