-
Gastroenterology Report 2024Inflammatory bowel disease (IBD) research often relies on animal models to study the etiology, pathophysiology, and management of IBD. Among these models, rats and mice... (Review)
Review
Inflammatory bowel disease (IBD) research often relies on animal models to study the etiology, pathophysiology, and management of IBD. Among these models, rats and mice are frequently employed due to their practicality and genetic manipulability. However, for studies aiming to closely mimic human pathology, non-human primates such as monkeys and dogs offer valuable physiological parallels. Guinea pigs, while less commonly used, present unique advantages for investigating the intricate interplay between neurological and immunological factors in IBD. Additionally, New Zealand rabbits excel in endoscopic biopsy techniques, providing insights into mucosal inflammation and healing processes. Pigs, with their physiological similarities to humans, serve as ideal models for exploring the complex relationships between nutrition, metabolism, and immunity in IBD. Beyond mammals, non-mammalian organisms including zebrafish, , and nematodes offer specialized insights into specific aspects of IBD pathology, highlighting the diverse array of model systems available for advancing our understanding of this multifaceted disease. In this review, we conduct a thorough analysis of various animal models employed in IBD research, detailing their applications and essential experimental parameters. These include clinical observation, Disease Activity Index score, pathological assessment, intestinal barrier integrity, fibrosis, inflammatory markers, intestinal microbiome, and other critical parameters that are crucial for evaluating modeling success and drug efficacy in experimental mammalian studies. Overall, this review will serve as a valuable resource for researchers in the field of IBD, offering insights into the diverse array of animal models available and their respective applications in studying IBD.
PubMed: 38634007
DOI: 10.1093/gastro/goae021 -
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 -
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 -
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 -
Advanced Science (Weinheim,... Apr 2018A platform compatible with microtiter plates to parallelize environmental treatments to test the complex impacts of multiple stressors, including parameters relevant to...
A platform compatible with microtiter plates to parallelize environmental treatments to test the complex impacts of multiple stressors, including parameters relevant to climate change and point source pollutants is developed. This platform leverages (1) the high rate of purely diffusive gas transport in aerogels to produce well-defined centimeter-scale gas concentration gradients, (2) spatial light control, and (3) established automated liquid handling. The parallel gaseous, aqueous, and light control provided by the platform is compatible with multiparameter experiments across the life sciences. The platform is applied to measure biological effects in over 700 treatments in a five-parameter full factorial study with the microalgae . Further, the CO response of multicellular organisms, and under surfactant and nanomaterial stress are tested with the platform.
PubMed: 29721416
DOI: 10.1002/advs.201700677 -
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 -
Journal of the Belgian Society of... Sep 2018Thirty years ago, we reported that parallel aspect of the L5-S1 disc on a lateral view of the spine might be considered to be an initial stage of disk degeneration. The...
PURPOSE
Thirty years ago, we reported that parallel aspect of the L5-S1 disc on a lateral view of the spine might be considered to be an initial stage of disk degeneration. The current study represents an attempt to increase the validity of parallel sign on conventional radiograph using MR real T1 mapping.
METHODS
Forty-four young asymptomatic volunteers (mean age 21.6 ± 2.3) underwent lumbar spine MRI, twice the same day, morning and afternoon. Dedicated sequences using the inversion-recovery technique were used to calculate the T1 relaxation time. A region of interest (ROI) representing the nucleus pulposus was defined in each disk. The volunteers were stratified according to the presence or absence of a parallel morphology of L5-S1. Correlation between endplates angles, sacral slopes and T1 values were then evaluated.
RESULTS
L5-S1 space looks parallel for angles <10° (mean value 6.9° ± 1.4°). Sacral slope was lower in parallel disks (31.7 ± 4.9° vs. 40.1 ± 5.6°), showing a significant difference of 8.4° (p < 0.05). The T1 relaxation values show a significant difference between the two groups (p < 0.05) with a difference of 96 ms for the morning (1090.9 ± 33.3 ms for the parallel group and 1186.9 ± 41.2 ms for the non-parallel) and 121.9 ms for the afternoon (respectively 1004.7 ± 22.2 ms and 1126.6 ± 12.9 ms).
CONCLUSION
The difference between the two groups suggests that parallel morphology of the L5-S1 disk is associated with lower water content.
PubMed: 30320297
DOI: 10.5334/jbsr.1501 -
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