Nematode chromosomes Carlton, Peter M; Davis, Richard E; Ahmed, Shawn
Genetics (Austin),
05/2022, Letnik:
221, Številka:
1
Journal Article
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Abstract
The nematode Caenorhabditis elegans has shed light on many aspects of eukaryotic biology, including genetics, development, cell biology, and genomics. A major factor in the success of C. ...elegans as a model organism has been the availability, since the late 1990s, of an essentially gap-free and well-annotated nuclear genome sequence, divided among 6 chromosomes. In this review, we discuss the structure, function, and biology of C. elegans chromosomes and then provide a general perspective on chromosome biology in other diverse nematode species. We highlight malleable chromosome features including centromeres, telomeres, and repetitive elements, as well as the remarkable process of programmed DNA elimination (historically described as chromatin diminution) that induces loss of portions of the genome in somatic cells of a handful of nematode species. An exciting future prospect is that nematode species may enable experimental approaches to study chromosome features and to test models of chromosome evolution. In the long term, fundamental insights regarding how speciation is integrated with chromosome biology may be revealed.
Clustering multivariate time series using energy distance Davis, Richard A.; Fernandes, Leon; Fokianos, Konstantinos
Journal of time series analysis,
September‐November 2023, 2023-09-00, 20230901, Letnik:
44, Številka:
5-6
Journal Article
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A novel methodology is proposed for clustering multivariate time series data using energy distance defined in Székely and Rizzo (2013). Specifically, a dissimilarity matrix is formed using the energy ...distance statistic to measure the separation between the finite‐dimensional distributions for the component time series. Once the pairwise dissimilarity matrix is calculated, a hierarchical clustering method is then applied to obtain the dendrogram. This procedure is completely nonparametric as the dissimilarities between stationary distributions are directly calculated without making any model assumptions. In order to justify this procedure, asymptotic properties of the energy distance estimates are derived for general stationary and ergodic time series. The method is illustrated in a simulation study for various component time series that are either linear or nonlinear. Finally, the methodology is applied to two examples; one involves the GDP of selected countries and the other is the population size of various states in the U.S.A. in the years 1900–1999.
Brain fog is one symptom that has been underexplored in traumatic brain injury (TBI). We explored the cognitive and affective correlates of brain fog in people with symptomatic mild TBI (n = 15), ...moderate‐to‐severe TBI (n = 15), and a healthy control group (n = 16). Measures across the studies assessed “brain fog” (Mental Clutter Scale), objective cognition (Useful Field of View® and Cogstate Brief Battery®), post‐concussive symptoms (Post‐Concussion Symptom Scale), and depressive symptoms (Profile of Moods Scale). Brain fog was higher in symptomatic mild TBI and moderate‐to‐severe TBI compared with healthy controls. Greater brain fog corresponded to greater depressive symptoms in symptomatic mild TBI. Greater brain fog corresponded to poorer episodic memory and working memory in moderate‐to‐severe TBI. Brain fog appears to reflect challenges in recovery, including depressive symptoms and worse cognitive function. Screening for brain fog might be worthwhile in people with brain injuries.
Schistosomes, blood flukes, are an important global public health concern. Paired adult female schistosomes produce large numbers of eggs that are primarily responsible for the disease pathology and ...critical for dissemination. Consequently, understanding schistosome sexual maturation and egg production may open novel perspectives for intervening with these processes to prevent clinical symptoms and to interrupt the life-cycle of these blood-flukes. microRNAs (miRNAs) are key regulators of many biological processes including development, cell proliferation, metabolism, and signal transduction. Here, we report on the identification of Schistosoma japonicum miRNAs using small RNA deep sequencing in the key stages of male-female pairing, gametogenesis, and egg production. We identified 38 miRNAs, including 10 previously unknown miRNAs. Eighteen of the miRNAs were differentially expressed between male and female schistosomes and during different stages of sexual maturation. We identified 30 potential target genes for 16 of the S. japonicum miRNAs using antibody-based pull-down assays and bioinformatic analyses. We further validated some of these target genes using either in vitro luciferase assays or in vivo miRNA suppression experiments. Notably, suppression of the female enriched miRNAs bantam and miR-31 led to morphological alteration of ovaries in female schistosomes. These findings uncover key roles for specific miRNAs in schistosome sexual maturation and egg production.
Common forms of atherosclerosis involve multiple genetic and environmental factors. While human genome-wide association studies have identified numerous loci contributing to coronary artery disease ...and its risk factors, these studies are unable to control environmental factors or examine detailed molecular traits in relevant tissues. We now report a study of natural variations contributing to atherosclerosis and related traits in over 100 inbred strains of mice from the Hybrid Mouse Diversity Panel (HMDP). The mice were made hyperlipidemic by transgenic expression of human apolipoprotein E-Leiden (APOE-Leiden) and human cholesteryl ester transfer protein (CETP). The mice were examined for lesion size and morphology as well as plasma lipid, insulin and glucose levels, and blood cell profiles. A subset of mice was studied for plasma levels of metabolites and cytokines. We also measured global transcript levels in aorta and liver. Finally, the uptake of acetylated LDL by macrophages from HMDP mice was quantitatively examined. Loci contributing to the traits were mapped using association analysis, and relationships among traits were examined using correlation and statistical modeling. A number of conclusions emerged. First, relationships among atherosclerosis and the risk factors in mice resemble those found in humans. Second, a number of trait-loci were identified, including some overlapping with previous human and mouse studies. Third, gene expression data enabled enrichment analysis of pathways contributing to atherosclerosis and prioritization of candidate genes at associated loci in both mice and humans. Fourth, the data provided a number of mechanistic inferences; for example, we detected no association between macrophage uptake of acetylated LDL and atherosclerosis. Fifth, broad sense heritability for atherosclerosis was much larger than narrow sense heritability, indicating an important role for gene-by-gene interactions. Sixth, stepwise linear regression showed that the combined variations in plasma metabolites, including LDL/VLDL-cholesterol, trimethylamine N-oxide (TMAO), arginine, glucose and insulin, account for approximately 30 to 40% of the variation in atherosclerotic lesion area. Overall, our data provide a rich resource for studies of complex interactions underlying atherosclerosis.
Maximizing baseline function of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is essential for their effective application in models of cardiac toxicity and disease. Here, we aimed to ...identify factors that would promote an adequate level of function to permit robust single-cell contractility measurements in a human induced pluripotent stem cell (hiPSC) model of hypertrophic cardiomyopathy (HCM). A simple screen revealed the collaborative effects of thyroid hormone, IGF-1 and the glucocorticoid analog dexamethasone on the electrophysiology, bioenergetics, and contractile force generation of hPSC-CMs. In this optimized condition, hiPSC-CMs with mutations in MYBPC3, a gene encoding myosin-binding protein C, which, when mutated, causes HCM, showed significantly lower contractile force generation than controls. This was recapitulated by direct knockdown of MYBPC3 in control hPSC-CMs, supporting a mechanism of haploinsufficiency. Modeling this disease in vitro using human cells is an important step toward identifying therapeutic interventions for HCM.
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•T3+IGF-1+ dexamethasone improves the electrophysiology of hPSC cardiomyocytes•These factors synergistically enhance bioenergetics and contractile force generation•Cardiomyocytes with HCM-causing mutations have a contractile defect
Birket et al. identify a combination of factors that cooperatively improve the function of human pluripotent stem cell (hiPSC)-derived cardiomyocytes. Optimizing the system facilitated the identification of a contraction force defect in a model of hypertrophic cardiomyopathy (HCM), a disease affecting ∼1:500 of the population.
Inference procedures for noncausal autoregressive (AR) models have been well studied and applied in a variety of applications from environmental to financial. For such processes, the observation at ...time t may depend on both past and future shocks in the system. In this paper, we consider extension of the univariate noncausal AR models to the vector AR (VAR) case. The extension presents several interesting challenges since even a first-order VAR can possess both causal and noncausal components. Assuming a non-Gaussian distribution for the noise, we show how to compute an approximation to the likelihood function. Under suitable conditions, it is shown that the maximum likelihood estimator (MLE) of the vector of AR parameters is asymptotically normal. The estimation procedure is illustrated with a simulation study for a VAR(1) process and with two real data examples.
The spatial and temporal patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases and COVID-19 deaths in the United States are poorly understood. We show that variations in the ...cumulative reported cases and deaths by county, state, and date exemplify Taylor's law of fluctuation scaling. Specifically, on day 1 of each month from April 2020 through June 2021, each state's variance (across its counties) of cases is nearly proportional to its squared mean of cases. COVID-19 deaths behave similarly. The lower 99% of counts of cases and deaths across all counties are approximately lognormally distributed. Unexpectedly, the largest 1% of counts are approximately Pareto distributed, with a tail index that implies a finite mean and an infinite variance. We explain why the counts across the entire distribution conform to Taylor's law with exponent two using models and mathematics. The finding of infinite variance has practical consequences. Local jurisdictions (counties, states, and countries) that are planning for prevention and care of largely unvaccinated populations should anticipate the rare but extremely high counts of cases and deaths that occur in distributions with infinite variance. Jurisdictions should prepare collaborative responses across boundaries, because extremely high local counts of cases and deaths may vary beyond the resources of any local jurisdiction.
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