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Molecular Biology and Evolution Sep 2020Understanding the genetic basis of similar phenotypes shared between lineages is a long-lasting research interest. Even though animal evolution offers many examples of...
Understanding the genetic basis of similar phenotypes shared between lineages is a long-lasting research interest. Even though animal evolution offers many examples of parallelism, for many phenotypes little is known about the underlying genes and mutations. We here use a combination of whole-genome sequencing, expression analyses, and comparative genomics to study the parallel genetic origin of ptilopody (Pti) in chicken. Ptilopody (or foot feathering) is a polygenic trait that can be observed in domesticated and wild avian species and is characterized by the partial or complete development of feathers on the ankle and feet. In domesticated birds, ptilopody is easily selected to fixation, though extensive variation in the type and level of feather development is often observed. By means of a genome-wide association analysis, we identified two genomic regions associated with ptilopody. At one of the loci, we identified a 17-kb deletion affecting PITX1 expression, a gene known to encode a transcription regulator of hindlimb identity and development. Similarly to pigeon, at the second loci, we observed ectopic expression of TBX5, a gene involved in forelimb identity and a key determinant of foot feather development. We also observed that the trait evolved only once as foot-feathered birds share the same haplotype upstream TBX5. Our findings indicate that in chicken and pigeon ptilopody is determined by the same set of genes that affect similar molecular pathways. Our study confirms that ptilopody has evolved through parallel evolution in chicken and pigeon.
Topics: Animals; Biological Evolution; Chickens; Columbidae; Feathers; Foot; Haplotypes; Multifactorial Inheritance; Paired Box Transcription Factors; T-Box Domain Proteins; Whole Genome Sequencing
PubMed: 32344429
DOI: 10.1093/molbev/msaa092 -
The Science of the Total Environment Jan 2023Contaminated groundwater resources threaten human health and destroy ecosystems in many areas worldwide. Groundwater remediation is crucial for environmental recovery;...
Contaminated groundwater resources threaten human health and destroy ecosystems in many areas worldwide. Groundwater remediation is crucial for environmental recovery; however, it can be cost prohibitive. Planning a cost-effective remediation design can take a long time, as it may involve the evaluation of many management decisions, and the corresponding simulation models are computationally demanding. Parallel optimization can facilitate much faster management decisions for cost-effective groundwater remediation design using complex pollutant transport models. However, the efficiency of different parallel optimization algorithms varies depending on both the search strategy and parallelism. In this paper, we show the performance of a parallel surrogate-based optimization algorithm called parallel stochastic radial basis function (p-SRBF), which has not been previously used on contaminant remediation problems. The two case problems involve two superfund sites (i.e., the Umatilla Aquifer and Blaine Aquifer), and one objective evaluation takes 5 and 30 min for the two problems, respectively. Exceptional speedup (superlinear) is achieved with 4 to 16 cores, and excellent speedup is achieved using up to 64 cores, obtaining a good solution at 80 % efficiency. We compare our p-SRBF with three different parallel derivative-free optimization algorithms, including genetic algorithm, mesh adaptive direct search, and asynchronous parallel pattern search optimization, in terms of objective quality, computational reduction and robust behavior across multiple trials. p-SRBF outperforms the other algorithms, as it finds the best solution in both the Umatilla and Blaine cases and reduces the computational budget by at least 50 % in both problems. Additionally, statistical comparisons show that the p-SRBF results are better than those of the alternative algorithms at the 5 % significant level. This study enriches theoretical real-world groundwater remediation methods. The results demonstrate that p-SRBF is promising for environmental management problems that involve computationally expensive models.
Topics: Humans; Ecosystem; Water Pollutants, Chemical; Groundwater; Algorithms; Computer Simulation; Environmental Restoration and Remediation
PubMed: 36270371
DOI: 10.1016/j.scitotenv.2022.159544 -
Journal of Virology Sep 2019Congenital human cytomegalovirus (HCMV) infection causes a broad spectrum of central and peripheral nervous system disorders, ranging from microcephaly to hearing loss....
Congenital human cytomegalovirus (HCMV) infection causes a broad spectrum of central and peripheral nervous system disorders, ranging from microcephaly to hearing loss. These ramifications mandate the study of virus-host interactions in neural cells. Neural progenitor cells are permissive for lytic infection. We infected two induced pluripotent stem cell (iPSC) lines and found these more primitive cells to be susceptible to infection but not permissive. Differentiation of infected iPSCs induced expression of viral antigens. iPSCs can be cultured in three dimensions to generate cerebral organoids, closely mimicking development. Mock- or HCMV-infected iPSCs were subjected to a cerebral organoid generation protocol. HCMV IE1 protein was detected in virus-infected organoids at 52 days postinfection. Absent a significant effect on organoid size, infection induced regions of necrosis and the presence of large vacuoles and cysts. Perhaps more in parallel with the subtler manifestations of HCMV-induced birth defects, infection dramatically altered neurological development of organoids, decreasing the number of developing and fully formed cortical structure sites, with associated changes in the architectural organization and depth of lamination within these structures, and manifesting aberrant expression of the neural marker β-tubulin III. Our observations parallel published descriptions of infected clinical samples, which often contain only sparse antigen-positive foci yet display areas of focal necrosis and cellular loss, delayed maturation, and abnormal cortical lamination. The parallels between pathologies present in clinical specimens and the highly tractable three-dimensional (3D) organoid system demonstrate the utility of this system in modeling host-virus interactions and HCMV-induced birth defects. Human cytomegalovirus (HCMV) is a leading cause of central nervous system birth defects, ranging from microcephaly to hearing impairment. Recent literature has provided descriptions of delayed and abnormal maturation of developing cortical tissue in infected clinical specimens. We have found that infected induced pluripotent stem cells can be differentiated into three-dimensional, viral protein-expressing cerebral organoids. Virus-infected organoids displayed dramatic alterations in development compared to those of mock-infected controls. Development in these organoids closely paralleled observations in HCMV-infected clinical samples. Infection induced regions of necrosis, the presence of larger vacuoles and cysts, changes in the architectural organization of cortical structures, aberrant expression of the neural marker β-tubulin III, and an overall reduction in numbers of cortical structure sites. We found clear parallels between the pathologies of clinical specimens and virus-infected organoids, demonstrating the utility of this highly tractable system for future investigations of HCMV-induced birth defects.
Topics: Cell Differentiation; Cell Line; Coculture Techniques; Cytomegalovirus; Cytomegalovirus Infections; Humans; Immediate-Early Proteins; Induced Pluripotent Stem Cells; Models, Biological; Neural Stem Cells; Organ Culture Techniques; Organoids; Tubulin
PubMed: 31217239
DOI: 10.1128/JVI.00957-19 -
Journal of Computational Biology : a... Aug 2018The comparison and assessment of similarity across metagenomes are still an open problem. Uncultivated samples suffer from high variability, thus making it difficult for... (Comparative Study)
Comparative Study
The comparison and assessment of similarity across metagenomes are still an open problem. Uncultivated samples suffer from high variability, thus making it difficult for heuristic sequence comparison methods to find precise matches in reference databases. Finer methods are required to provide higher accuracy and certainty, although these come at the expense of larger computation times. Therefore, in this work, we present our software for the highly parallel, fine-grained pairwise alignment of metagenomes. First, an analysis of the computational limitations of performing coarse-grained global alignments in parallel manner is described, and a solution is discussed and employed by our proposal. Second, we show that our development is competitive with state-of-the-art software in terms of speed and consumption of resources, while achieving more accurate results. In addition, the parallel scheme adopted is tested, depicting a performance of up to 98% efficiency while using up to 64 cores. Sequential optimizations are also tested and show a speedup of 9× over our previous proposal.
Topics: Algorithms; Computational Biology; Humans; Metagenome; Metagenomics; Sequence Alignment; Software
PubMed: 30084692
DOI: 10.1089/cmb.2018.0081 -
Frontiers in Network Physiology 2022Whole brain network models are now an established tool in scientific and clinical research, however their use in a larger workflow still adds significant informatics...
Whole brain network models are now an established tool in scientific and clinical research, however their use in a larger workflow still adds significant informatics complexity. We propose a tool, RateML, that enables users to generate such models from a succinct declarative description, in which the mathematics of the model are described without specifying how their simulation should be implemented. RateML builds on NeuroML's Low Entropy Model Specification (LEMS), an XML based language for specifying models of dynamical systems, allowing descriptions of neural mass and discretized neural field models, as implemented by the Virtual Brain (TVB) simulator: the end user describes their model's mathematics once and generates and runs code for different languages, targeting both CPUs for fast single simulations and GPUs for parallel ensemble simulations. High performance parallel simulations are crucial for tuning many parameters of a model to empirical data such as functional magnetic resonance imaging (fMRI), with reasonable execution times on small or modest hardware resources. Specifically, while RateML can generate Python model code, it enables generation of Compute Unified Device Architecture C++ code for NVIDIA GPUs. When a CUDA implementation of a model is generated, a tailored model driver class is produced, enabling the user to tweak the driver by hand and perform the parameter sweep. The model and driver can be executed on any compute capable NVIDIA GPU with a high degree of parallelization, either locally or in a compute cluster environment. The results reported in this manuscript show that with the CUDA code generated by RateML, it is possible to explore thousands of parameter combinations with a single Graphics Processing Unit for different models, substantially reducing parameter exploration times and resource usage for the brain network models, in turn accelerating the research workflow itself. This provides a new tool to create efficient and broader parameter fitting workflows, support studies on larger cohorts, and derive more robust and statistically relevant conclusions about brain dynamics.
PubMed: 36926112
DOI: 10.3389/fnetp.2022.826345 -
Journal of Applied Statistics 2021The logit binomial logistic dose response model is commonly used in applied research to model binary outcomes as a function of the dose or concentration of a substance....
The logit binomial logistic dose response model is commonly used in applied research to model binary outcomes as a function of the dose or concentration of a substance. This model is easily tailored to assess the relative potency of two substances. Consequently, in instances where two such dose response curves are parallel so one substance can be viewed as a dilution of the other, the degree of that dilution is captured in the relative potency model parameter. It is incumbent that experimental researchers working in fields including biomedicine, environmental science, toxicology and applied sciences choose efficient experimental designs to run their studies to both fit their dose response curves and to garner important information regarding drug or substance potency. This article provides far-reaching practical design strategies for dose response model fitting and estimation of relative potency using key illustrations. These results are subsequently extended here to handle situations where the assessment of parallelism and the proper dose-scale are also of interest. Conclusions and recommended strategies are supported by both theoretical and simulation results.
PubMed: 35707079
DOI: 10.1080/02664763.2021.1880556 -
Journal of Evolutionary Biology Nov 2022Examples of parallel evolution have been crucial for our understanding of adaptation via natural selection. However, strong parallelism is not always observed even in... (Review)
Review
Examples of parallel evolution have been crucial for our understanding of adaptation via natural selection. However, strong parallelism is not always observed even in seemingly similar environments where natural selection is expected to favour similar phenotypes. Leveraging this variation in parallelism within well-researched study systems can provide insight into the factors that contribute to variation in adaptive responses. Here we analyse the results of 36 studies reporting 446 average trait values in Trinidadian guppies, Poecilia reticulata, from different predation regimes. We examine how the extent of predator-driven phenotypic parallelism is influenced by six factors: sex, trait type, rearing environment, ecological complexity, evolutionary history, and time since colonization. Analyses show that parallel evolution in guppies is highly variable and weak on average, with only 24.7% of the variation among populations being explained by predation regime. Levels of parallelism appeared to be especially weak for colour traits, and parallelism decreased with increasing complexity of evolutionary history (i.e., when estimates of parallelism from populations within a single drainage were compared to estimates of parallelism from populations pooled between two major drainages). Suggestive - but not significant - trends that warrant further research include interactions between the sexes and different trait categories. Quantifying and accounting for these and other sources of variation among evolutionary 'replicates' can be leveraged to better understand the extent to which seemingly similar environments drive parallel and nonparallel aspects of phenotypic divergence.
Topics: Animals; Poecilia; Biological Evolution; Predatory Behavior; Adaptation, Physiological; Selection, Genetic
PubMed: 36098479
DOI: 10.1111/jeb.14086 -
The Journal of Chemical Physics Jul 2023Exploring the structures and spectral features of proteins with advanced quantum chemical methods is an uphill task. In this work, a fragment-based molecular tailoring...
Exploring the structures and spectral features of proteins with advanced quantum chemical methods is an uphill task. In this work, a fragment-based molecular tailoring approach (MTA) is appraised for the CAM-B3LYP/aug-cc-pVDZ-level geometry optimization and vibrational infrared (IR) spectra calculation of ten real proteins containing up to 407 atoms and 6617 basis functions. The use of MTA and the inherently parallel nature of the fragment calculations enables a rapid and accurate calculation of the IR spectrum. The applicability of MTA to optimize the protein geometry and evaluate its IR spectrum employing a polarizable continuum model with water as a solvent is also showcased. The typical errors in the total energy and IR frequencies computed by MTA vis-à-vis their full calculation (FC) counterparts for the studied protein are 5-10 millihartrees and 5 cm-1, respectively. Moreover, due to the independent execution of the fragments, large-scale parallelization can also be achieved. With increasing size and level of theory, MTA shows an appreciable advantage in computer time as well as memory and disk space requirement over the corresponding FCs. The present study suggests that the geometry optimization and IR computations on the biomolecules containing ∼1000 atoms and/or ∼15 000 basis functions using MTA and HPC facility can be clearly envisioned in the near future.
Topics: Proteins; Water; Solvents; Quantum Theory; Spectrum Analysis, Raman; Spectroscopy, Fourier Transform Infrared
PubMed: 37522406
DOI: 10.1063/5.0149572 -
Frontiers in Integrative Neuroscience 2015Area V5 of the visual brain, first identified anatomically in 1969 as a separate visual area, is critical for the perception of visual motion. As one of the most... (Review)
Review
Area V5 of the visual brain, first identified anatomically in 1969 as a separate visual area, is critical for the perception of visual motion. As one of the most intensively studied parts of the visual brain, it has yielded many insights into how the visual brain operates. Among these are: the diversity of signals that determine the functional capacities of a visual area; the relationship between single cell activity in a specialized visual area and perception of, and preference for, attributes of a visual stimulus; the multiple asynchronous inputs into, and outputs from, an area as well as the multiple operations that it undertakes asynchronously; the relationship between activity at given, specialized, areas of the visual brain and conscious awareness; and the mechanisms used to "bind" signals from one area with those from another, with a different specialization, to give us our unitary perception of the visual world. Hence V5 is, in a sense, a microcosm of the visual world and its study gives important insights into how the whole visual brain is organized-anatomically, functionally and perceptually.
PubMed: 25883556
DOI: 10.3389/fnint.2015.00021 -
American Journal of Physiology.... Mar 2017WNT-5A is a secreted growth factor that belongs to the noncanonical members of the Wingless-related MMTV-integration family. Previous studies pointed to a connection...
WNT-5A is a secreted growth factor that belongs to the noncanonical members of the Wingless-related MMTV-integration family. Previous studies pointed to a connection between WNT-5A and the fibrogenic factor TGF-β warranting further studies into the functional role of WNT-5A in liver fibrosis. Therefore, we studied WNT-5A expressions in mouse and human fibrotic livers and examined the relation between WNT-5A and various fibrosis-associated growth factors, cytokines, and extracellular matrix proteins. WNT-5A gene and protein expressions were significantly increased in fibrotic mouse and human livers compared with healthy livers. Regression or therapeutic intervention in mice resulted in decreased hepatic WNT-5A levels paralleled by lower collagen levels. Immunohistochemical analysis showed WNT-5A staining in fibrotic septa colocalizing with desmin staining indicating WNT-5A expression in myofibroblasts. In vitro studies confirmed WNT-5A expression in this cell type and showed that TGF-β significantly enhanced WNT-5A expression in contrast to PDGF-BB and proinflammatory cytokines IL-1β and TNF-α. Additionally, TGF-β induces the expression of the WNT receptors FZD2 and FZD8. After silencing of WNT-5A, reduced levels of collagen type I, vimentin, and fibronectin in TGF-β-stimulated myofibroblasts were measured compared with nonsilencing siRNA-treated controls. Interestingly, the antifibrotic cytokine IFNγ suppressed WNT-5A in vitro and in vivo. IFNγ-treated fibrotic mice showed significantly less WNT-5A expression compared with untreated fibrotic mice. In conclusion, WNT-5A paralleled collagen I levels in fibrotic mouse and human livers. WNT-5A expression in myofibroblasts is induced by the profibrotic factor TGF-β and plays an important role in TGF-β-induced regulation of fibrotic matrix proteins, whereas its expression can be reversed upon treatment, both in vitro and in vivo. This study describes the localization and functional role of WNT-5A in human and mouse fibrotic livers. Hepatic WNT-5A expression parallels collagen type I expression. In vivo and in vitro, the myofibroblasts were identified as the key hepatic cells producing WNT-5A. WNT-5A is under control of TGF-β and its activities are primarily profibrotic.
Topics: Animals; Cell Line; Collagen; Desmin; Gene Silencing; Humans; Interferon-gamma; Interleukin-1beta; Liver; Liver Cirrhosis; Mice; Myofibroblasts; Signal Transduction; Transforming Growth Factor beta; Wnt-5a Protein
PubMed: 28057611
DOI: 10.1152/ajpgi.00160.2016