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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 -
Analytical Chemistry Sep 2022Proteomic analysis on the scale that captures population and biological heterogeneity over hundreds to thousands of samples requires rapid mass spectrometry methods,...
Proteomic analysis on the scale that captures population and biological heterogeneity over hundreds to thousands of samples requires rapid mass spectrometry methods, which maximize instrument utilization (IU) and proteome coverage while maintaining precise and reproducible quantification. To achieve this, a short liquid chromatography gradient paired to rapid mass spectrometry data acquisition can be used to reproducibly quantify a moderate set of analytes. High-throughput profiling at a limited depth is becoming an increasingly utilized strategy for tackling large sample sets but the time spent on loading the sample, flushing the column(s), and re-equilibrating the system reduces the ratio of meaningful data acquired to total operation time and IU. The dual-trap single-column configuration (DTSC) presented here maximizes IU in rapid analysis (15 min per sample) of blood and cell lysates by parallelizing trap column cleaning and sample loading and desalting with the analysis of the previous sample. We achieved 90% IU in low microflow (9.5 μL/min) analysis of blood while reproducibly quantifying 300-400 proteins and over 6000 precursor ions. The same IU was achieved for cell lysates and over 4000 proteins (3000 at CV below 20%) and 40,000 precursor ions were quantified at a rate of 15 min/sample. Thus, DTSC enables high-throughput epidemiological blood-based biomarker cohort studies and cell-based perturbation screening.
Topics: Biomarkers; Chromatography, Liquid; Humans; Mass Spectrometry; Proteome; Proteomics
PubMed: 36044770
DOI: 10.1021/acs.analchem.2c02609 -
Science Advances Nov 2021Understanding the dynamics of speciation is a central topic in evolutionary biology. Here, we investigated how morphological and genomic differentiation accumulated...
Understanding the dynamics of speciation is a central topic in evolutionary biology. Here, we investigated how morphological and genomic differentiation accumulated along the speciation continuum in the African cichlid fish . While morphological differentiation was continuously distributed across different lake-stream population pairs, we found that there were two categories with respect to genomic differentiation, suggesting a “gray zone” of speciation at ~0.1% net nucleotide divergence. Genomic differentiation was increased in the presence of divergent selection and drift compared to drift alone. The quantification of phenotypic and genetic parallelism in four cichlid species occurring along a lake-stream environmental contrast revealed parallel and antiparallel components in rapid adaptive divergence, and morphological convergence in species replicates inhabiting the same environments. Furthermore, we show that the extent of parallelism was higher when ancestral populations were more similar. Our study highlights the complementary roles of divergent selection and drift on speciation and parallel evolution.
PubMed: 34731007
DOI: 10.1126/sciadv.abg5391 -
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 -
Molecular and Cellular Endocrinology Jul 2013Rodents are clearly valuable models for assessing disruption of fertility. The effects of different steroid treatments at different stages of reproductive life through... (Review)
Review
Rodents are clearly valuable models for assessing disruption of fertility. The effects of different steroid treatments at different stages of reproductive life through from fetal to adult have been assessed for effects on fertility, ovarian morphology, hypothalamic-pituitary function or metabolic consequences. The results show that steroid treatments do disrupt fertility in many cases, but the underlying mechanisms are complicated by the effects of the different treatments at multiple sites. As models for PCOS at the ovarian level however, there are a number of problems particularly related to the fact that rodents are multi-ovular species. Apart from an absence of ovulation and corpora lutea, many of the different steroid regimes result in an increase in large atretic, or cystic follicles that do not parallel PCOS in women. Indeed a number of treatments are given at times when they will cause disruption of the positive feedback effects of estradiol, thus blocking ovulation in adult life. The resulting ovarian morphology thus appears to be like that of PCOS but is in fact not a clear mimic. This review of the various studies highlights parallels and problems with the use of rodents to study the mechanisms underlying the development of PCOS in women.
Topics: Animals; Disease Models, Animal; Female; Gonadal Steroid Hormones; Humans; Ovary; Pituitary Gland; Polycystic Ovary Syndrome; Rodentia
PubMed: 23098676
DOI: 10.1016/j.mce.2012.10.007 -
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 -
Genes Nov 2019Genomic biomarkers such as DNA methylation (DNAm) are employed for age prediction. In recent years, several studies have suggested the association between changes in...
Genomic biomarkers such as DNA methylation (DNAm) are employed for age prediction. In recent years, several studies have suggested the association between changes in DNAm and its effect on human age. The high dimensional nature of this type of data significantly increases the execution time of modeling algorithms. To mitigate this problem, we propose a two-stage parallel algorithm for selection of age related CpG-sites. The algorithm first attempts to cluster the data into similar age ranges. In the next stage, a parallel genetic algorithm (PGA), based on the MapReduce paradigm (MR-based PGA), is used for selecting age-related features of each individual age range. In the proposed method, the execution of the algorithm for each age range (data parallel), the evaluation of chromosomes (task parallel) and the calculation of the fitness function (data parallel) are performed using a novel parallel framework. In this paper, we consider 16 different healthy DNAm datasets that are related to the human blood tissue and that contain the relevant age information. These datasets are combined into a single unioned set, which is in turn randomly divided into two sets of train and test data with a ratio of 7:3, respectively. We build a Gradient Boosting Regressor (GBR) model on the selected CpG-sites from the train set. To evaluate the model accuracy, we compared our results with state-of-the-art approaches that used these datasets, and observed that our method performs better on the unseen test dataset with a Mean Absolute Deviation (MAD) of 3.62 years, and a correlation (R) of 95.96% between age and DNAm. In the train data, the MAD and R are 1.27 years and 99.27%, respectively. Finally, we evaluate our method in terms of the effect of parallelization in computation time. The algorithm without parallelization requires 4123 min to complete, whereas the parallelized execution on 3 computing machines having 32 processing cores each, only takes a total of 58 min. This shows that our proposed algorithm is both efficient and scalable.
Topics: Aging; Algorithms; Computational Biology; CpG Islands; DNA Methylation; Epigenesis, Genetic; Genetic Fitness; Humans; Models, Genetic
PubMed: 31775313
DOI: 10.3390/genes10120969 -
Brain and Language Oct 2010Songbirds share a number of parallels with humans that make them an attractive model system for studying the behavioral and neurobiological mechanisms that underlie the... (Review)
Review
Songbirds share a number of parallels with humans that make them an attractive model system for studying the behavioral and neurobiological mechanisms that underlie the learning and processing of vocal communication signals. Here we review the perceptual and cognitive mechanisms of audition in birds, and emphasize the behavioral and neural basis of song recognition. Where appropriate, we point out a number of intersections with human vocal communication behavior that suggest common mechanisms amenable to further study, and limitations of birdsong as a model for human language.
Topics: Animals; Auditory Pathways; Auditory Perception; Brain; Discrimination, Psychological; Hearing; Humans; Language; Recognition, Psychology; Songbirds; Vocalization, Animal
PubMed: 20471673
DOI: 10.1016/j.bandl.2009.09.008 -
Cureus May 2022Introduction The purpose of this study was to evaluate which of the three positions on the tragus (superior, middle, and inferior), when connected to the inferior border...
An Evaluation of the Relation Between Variation in Arch Forms and Relative Parallelism of the Occlusal Plane to the Line Joining the Inferior Border of Ala of the Nose With Different Tragal Levels of the Ear in Dentulous Subjects: An In Vivo Study.
Introduction The purpose of this study was to evaluate which of the three positions on the tragus (superior, middle, and inferior), when connected to the inferior border of the ala of the nose, was the most parallel to the natural occlusal plane in dentate patients, to correlate the level of the naturally existing occlusal plane with the ala-tragal line when the tragus was divided into three portions (superior, middle, and inferior), and to determine which position in the tragus occlusal plane is the most parallel. The study also evaluated the correlation between the variation of arch forms and the relative parallelism of the occlusal plane to the ala-tragal line at different tragal levels. Methods This study included 1405 subjects between the ages of 18 and 35 years. A custom-made occlusal plane analyzer was used to check the relative parallelism between the existing occlusal plane and the ala-tragal line when the tragus was divided into the superior, middle, and inferior portions. The Fox plane of the occlusal plane analyzer was placed on the occlusal plane and the paralleling rod was adjusted till parallelism was obtained. The point on the tragus (superior, middle, or inferior) at which parallelism existed was recorded. The study also measured the inter-canine and intermolar distance to find the type of arch form and related it to the position (superior, middle, or inferior) at which the ala tragal line was parallel to the occlusal plane. The assessment was done on both the right and left sides of the subjects. Results Out of the 2810 tragi, the most common location at which parallelism was established was the inferior part of the tragus, which accounted for 47% of the total. Seventy-one percent (71%) of the subjects showed ovoid arch form. When the variation of arch forms was compared to the level of occlusal plane, 46.8% of the subjects with tapered arch form, 54.5% of subjects with square arch form, and 46.0% of subjects with ovoid arch form had the level of the occlusal plane at the inferior portion of the tragus. Conclusion The result of the study indicated that in the majority of the tragi studied, 47% of the subjects had the occlusal plane parallel to a line joining the inferior border of the ala of the nose to the inferior part of the tragus. Irrespective of the arch form, the occlusal plane was found parallel to a line joining the inferior border of the ala of the nose and the inferior part of the tragus. Thus the tragal position did not show any correlation to the variation of arch forms.
PubMed: 35706729
DOI: 10.7759/cureus.24925 -
Vision Research Nov 2021People can perceive 3D information from contour drawings and some types of configurations of contours in such drawings are important for 3D perception. We know that our...
People can perceive 3D information from contour drawings and some types of configurations of contours in such drawings are important for 3D perception. We know that our visual system is sensitive to these configurations. Koshmanova & Sawada (2019, Vision Research, 154, 97-104) showed that the sensitivity is higher to a parallel configuration of contours than to a perpendicular configuration of contours. In this study, two psychophysical experiments were conducted that compared the sensitivity to a parallel configuration to two different configurations. In Experiment 1, orientation thresholds were measured with parallel and converging configurations composed of three contours. In Experiment 2, orientation thresholds of configurations composed of two contours were measured with parallel, collinear, and perpendicular configurations. The results of Experiment 1 showed that the visual system is more sensitive to parallel configurations than to converging configurations. The results of Experiment 2 showed that the sensitivity to the parallel configuration is analogous to the sensitivity to the collinear configuration, and it is higher than the sensitivity to the perpendicular configuration. The role that the parallel configuration plays in the 3D perception of contour-drawings is discussed.
Topics: Form Perception; Humans; Orientation; Pattern Recognition, Visual; Psychophysics
PubMed: 34333200
DOI: 10.1016/j.visres.2021.07.006