Gram-negative facultative Aggregatibacter actinomycetemcomitans is an oral pathogen associated with periodontitis. The genetic heterogeneity among A. actinomycetemcomitans strains has been long ...recognized. This study provides a comprehensive genomic analysis of A. actinomycetemcomitans and the closely related nonpathogenic Aggregatibacter aphrophilus. Whole genome sequencing by Illumina MiSeq platform was performed for 31 A. actinomycetemcomitans and 2 A. aphrophilus strains. Sequence similarity analysis shows a total of 3,220 unique genes across the 2 species, where 1,550 are core genes present in all genomes and 1,670 are variable genes (accessory genes) missing in at least 1 genome. Phylogenetic analysis based on 397 concatenated core genes distinguished A. aphrophilus and A. actinomycetemcomitans. The latter was in turn divided into 5 clades: clade b (serotype b), clade c (serotype c), clade e/f (serotypes e and f), clade a/d (serotypes a and d), and clade e′ (serotype e strains). Accessory genes accounted for 14.1% to 23.2% of the A. actinomycetemcomitans genomes, with a majority belonging to the category of poorly characterized by Cluster of Orthologous Groups classification. These accessory genes were often organized into genomic islands (n = 387) with base composition biases, suggesting their acquisitions via horizontal gene transfer. There was a greater degree of similarity in gene content and genomic islands among strains within clades than between clades. Strains of clade e′ isolated from human were found to be missing the genomic island that carries genes encoding cytolethal distending toxins. Taken together, the results suggest a pattern of sequential divergence, starting from the separation of A. aphrophilus and A. actinomycetemcomitans through gain and loss of genes and ending with the divergence of the latter species into distinct clades and serotypes. With differing constellations of genes, the A. actinomycetemcomitans clades may have evolved distinct adaptation strategies to the human oral cavity.
Light Pollution and Cancer Walker, 2nd, William H; Bumgarner, Jacob R; Walton, James C ...
International journal of molecular sciences,
12/2020, Letnik:
21, Številka:
24
Journal Article
Recenzirano
Odprti dostop
For many individuals in industrialized nations, the widespread adoption of electric lighting has dramatically affected the circadian organization of physiology and behavior. Although initially ...assumed to be innocuous, exposure to artificial light at night (ALAN) is associated with several disorders, including increased incidence of cancer, metabolic disorders, and mood disorders. Within this review, we present a brief overview of the molecular circadian clock system and the importance of maintaining fidelity to bright days and dark nights. We describe the interrelation between core clock genes and the cell cycle, as well as the contribution of clock genes to oncogenesis. Next, we review the clinical implications of disrupted circadian rhythms on cancer, followed by a section on the foundational science literature on the effects of light at night and cancer. Finally, we provide some strategies for mitigation of disrupted circadian rhythms to improve health.
Changes to photoperiod (day length) occur in anticipation of seasonal environmental changes, altering physiology and behavior to maximize fitness. In order for photoperiod to be useful as a ...predictive factor of temperature or food availability, day and night must be distinct. The increasing prevalence of exposure to artificial light at night (ALAN) in both field and laboratory settings disrupts photoperiodic time measurement and may block development of appropriate seasonal adaptations. Here, we review the effects of ALAN as a disruptor of photoperiodic time measurement and season-specific adaptations, including reproduction, metabolism, immune function, and thermoregulation.
•Circadian disruption disrupts photoperiodic time measurement and seasonal adaptations.•Light at night disrupts reproduction, immune function and metabolism, a crucial proxy for fitness.
Pain behavior and the systems that mediate opioid analgesia and opioid reward processing display circadian rhythms. Moreover, the pain system and opioid processing systems, including the mesolimbic ...reward circuitry, reciprocally interact with the circadian system. Recent work has demonstrated the disruptive relationship among these three systems. Disruption of circadian rhythms can exacerbate pain behavior and modulate opioid processing, and pain and opioids can influence circadian rhythms. This review highlights evidence demonstrating the relationship among the circadian, pain, and opioid systems. Evidence of how disruption of one of these systems can lead to reciprocal disruptions of the other is then reviewed. Finally, we discuss the interconnected nature of these systems to emphasize the importance of their interactions in therapeutic contexts.
Motivation: Identifying patterns of co-expression in microarray data by cluster analysis has been a productive approach to uncovering molecular mechanisms underlying biological processes under ...investigation. Using experimental replicates can generally improve the precision of the cluster analysis by reducing the experimental variability of measurements. In such situations, Bayesian mixtures allow for an efficient use of information by precisely modeling between-replicates variability. Results: We developed different variants of Bayesian mixture based clustering procedures for clustering gene expression data with experimental replicates. In this approach, the statistical distribution of microarray data is described by a Bayesian mixture model. Clusters of co-expressed genes are created from the posterior distribution of clusterings, which is estimated by a Gibbs sampler. We define infinite and finite Bayesian mixture models with different between-replicates variance structures and investigate their utility by analyzing synthetic and the real-world datasets. Results of our analyses demonstrate that (1) improvements in precision achieved by performing only two experimental replicates can be dramatic when the between-replicates variability is high, (2) precise modeling of intra-gene variability is important for accurate identification of co-expressed genes and (3) the infinite mixture model with the ‘elliptical’ between-replicates variance structure performed overall better than any other method tested. We also introduce a heuristic modification to the Gibbs sampler based on the ‘reverse annealing’ principle. This modification effectively overcomes the tendency of the Gibbs sampler to converge to different modes of the posterior distribution when started from different initial positions. Finally, we demonstrate that the Bayesian infinite mixture model with ‘elliptical’ variance structure is capable of identifying the underlying structure of the data without knowing the ‘correct’ number of clusters. Availability: The MS Windows™ based program named Gaussian Infinite Mixture Modeling (GIMM) implementing the Gibbs sampler and corresponding C++ code are available at http://homepages.uc.edu/~medvedm/GIMM.htm Supplemental information: http://expression.microslu.washington.edu/expression/kayee/medvedovic2003/medvedovic_bioinf2003.html
Disrupted or atypical light-dark cycles disrupts synchronization of endogenous circadian clocks to the external environment; extensive circadian rhythm desynchrony promotes adverse health outcomes. ...Previous studies suggest that disrupted circadian rhythms promote neuroinflammation and neuronal damage post-ischemia in otherwise healthy mice, however, few studies to date have evaluated these health risks with aging. Because most strokes occur in aged individuals, we sought to identify whether, in addition to being a risk factor for poor ischemic outcome, circadian rhythm disruption can increase risk for vascular cognitive impairment and dementia (VCID). We hypothesized that repeated 6 h phase advances (chronic jet lag; CJL) for 8 weeks alters cerebrovascular architecture leading to increased cognitive impairments in aged mice. Female CJL mice displayed impaired spatial processing during a spontaneous alternation task and reduced acquisition during auditory-cued associative learning. Male CJL mice displayed impaired retention of the auditory-cued associative learning task 24 h following acquisition. CJL increased vascular tortuosity in the isocortex, associated with increased risk for vascular disease. These results demonstrate that CJL increased sex-specific cognitive impairments coinciding with structural changes to vasculature in the brain. We highlight that CJL may accelerate aged-related functional decline and could be a crucial target against disease progression.
Circadian rhythms are important for all aspects of biology; virtually every aspect of biological function varies according to time of day. Although this is well known, variation across the day is ...also often ignored in the design and reporting of research. For this review, we analyzed the top 50 cited papers across 10 major domains of the biological sciences in the calendar year 2015. We repeated this analysis for the year 2019, hypothesizing that the awarding of a Nobel Prize in 2017 for achievements in the field of circadian biology would highlight the importance of circadian rhythms for scientists across many disciplines, and improve time-of-day reporting.
Our analyses of these 1000 empirical papers, however, revealed that most failed to include sufficient temporal details when describing experimental methods and that few systematic differences in time-of-day reporting existed between 2015 and 2019. Overall, only 6.1% of reports included time-of-day information about experimental measures and manipulations sufficient to permit replication.
Circadian rhythms are a defining feature of biological systems, and knowing when in the circadian day these systems are evaluated is fundamentally important information. Failing to account for time of day hampers reproducibility across laboratories, complicates interpretation of results, and reduces the value of data based predominantly on nocturnal animals when extrapolating to diurnal humans.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The automation of behavioral tracking and analysis in preclinical research can serve to advance the rate of research outcomes, increase experimental scalability, and challenge the scientific ...reproducibility crisis. Recent advances in the efficiency, accuracy, and accessibility of deep learning (DL) and machine learning (ML) frameworks are enabling this automation. As the ongoing opioid epidemic continues to worsen alongside increasing rates of chronic pain, there are ever-growing needs to understand opioid use disorders (OUDs) and identify non-opioid therapeutic options for pain. In this review, we examine how these related needs can be advanced by the development and validation of DL and ML resources for automated pain and withdrawal behavioral tracking. We aim to emphasize the utility of these tools for automated behavioral analysis, and we argue that currently developed models should be deployed to address novel questions in the fields of pain and OUD research.
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•We examined the impact of sole-source LED lighting on kale morphology and physiology.•Shorter duration of higher B/R LED light ratios increased biomass; decreased height.•Shorter ...duration of higher B/R LED light ratios decreased chlorophyll fluorescence.•All B/R LED treatments decreased shoot zeaxanthin over continuous white LED light.•Lowest B/R LED ratio decreased soluble fructose, but increased tissue potassium (K).
Solid-state light emitting diodes (LEDs) are emerging as an energy efficient alternative lighting source in controlled environments. The objective of this study was to examine the impact of sole-source LED lighting quality/duration on biomass, morphology, and nutritional quality of kale (Brassica oleracea var. acephala) in a controlled environment. ‘Premier’ kale seedlings were grown hydroponically using a 30 d production cycle. Experimental LED treatments included: 1) white LED for 37 d; 2) 5% B/95% R for 37 d; 3) 20%B/80%R for 30 d; 4) 20%B/80%R for 25 d; 5) 20%B/80%R for 20 d; and 6) 20%B/80%R for 15 d prior to harvest. Treatments were arranged in a randomized complete block design, and three complete experimental runs were conducted. Plant height (cm), leaf length and width (cm), shoot and root fresh mass (g) and dry mass (g) were collected at harvest. Kale shoot tissues were measured for nutritionally important pigments, glucosinolates, mineral elements, and soluble carbohydrates. All plants treated with 20%B/80%R lighting were shorter compared to the white (37 d) and 5%B/95%R (37 d) treatments, respectively. Chlorophyll fluorescence parameters were influenced by LED treatment, while maximum quantum yield (QYmax) was not. LED light treatment impacted kale zeaxanthin (P = 0.01), antheraxanthin (P = 0.01), fructose (P = 0.03), and potassium (P = 0.02). Data suggest that increasing blue light during production has limited impact on 37-d old hydroponic kale developmental and nutritional parameters over continuous white LED lighting.
We demonstrate an integrated approach to build, test, and refine a model of a cellular pathway, in which perturbations to critical pathway components are analyzed using DNA microarrays, quantitative ...proteomics, and databases of known physical interactions. Using this approach, we identify 997 messenger RNAs responding to 20 systematic perturbations of the yeast galactose-utilization pathway, provide evidence that approximately 15 of 289 detected proteins are regulated posttranscriptionally, and identify explicit physical interactions governing the cellular response to each perturbation. We refine the model through further iterations of perturbation and global measurements, suggesting hypotheses about the regulation of galactose utilization and physical interactions between this and a variety of other metabolic pathways.