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Journal of Cellular Physiology Apr 2024Vascular smooth muscle cells (VSMCs) play a critical role in regulating vasotone, and their phenotypic plasticity is a key contributor to the pathogenesis of various... (Review)
Review
Vascular smooth muscle cells (VSMCs) play a critical role in regulating vasotone, and their phenotypic plasticity is a key contributor to the pathogenesis of various vascular diseases. Two main VSMC phenotypes have been well described: contractile and synthetic. Contractile VSMCs are typically found in the tunica media of the vessel wall, and are responsible for regulating vascular tone and diameter. Synthetic VSMCs, on the other hand, are typically found in the tunica intima and adventitia, and are involved in vascular repair and remodeling. Switching between contractile and synthetic phenotypes occurs in response to various insults and stimuli, such as injury or inflammation, and this allows VSMCs to adapt to changing environmental cues and regulate vascular tone, growth, and repair. Furthermore, VSMCs can also switch to osteoblast-like and chondrocyte-like cell phenotypes, which may contribute to vascular calcification and other pathological processes like the formation of atherosclerotic plaques. This provides discusses the mechanisms that regulate VSMC phenotypic switching and its role in the development of vascular diseases. A better understanding of these processes is essential for the development of effective diagnostic and therapeutic strategies.
Topics: Humans; Aortic Dissection; Atherosclerosis; Cell Proliferation; Cells, Cultured; Hypertension; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Phenotype
PubMed: 38291732
DOI: 10.1002/jcp.31200 -
The ISME Journal Sep 2023Experimental evolution in a laboratory helps researchers to understand the genetic and phenotypic background of adaptation under a particular condition. Simultaneously,...
Experimental evolution in a laboratory helps researchers to understand the genetic and phenotypic background of adaptation under a particular condition. Simultaneously, the simplified environment that represents certain aspects of a complex natural niche permits the dissection of relevant parameters behind the selection, including temperature, oxygen availability, nutrients, and biotic factors. The presence of other microorganisms or a host has a major influence on microbial evolution that often differs from the adaptation paths observed in response to abiotic conditions. In the current issue of the ISME Journal, Cosetta and colleagues reveal how cross-kingdom interaction representing the cheese microbiome succession promotes distinct evolution of the food- and animal-associated bacterium, . The authors also identified a global regulator-dependent adaption that leads to evolved derivatives exhibiting reduced pigment production and colony morphologies in addition to altered differentiation phenotypes that potentially contribute to increased fitness.
Topics: Staphylococcus; Biological Evolution; Phenotype
PubMed: 37524911
DOI: 10.1038/s41396-023-01479-w -
Clinical Therapeutics Nov 2023Despite an increase in treatment options, and substantial reductions in cardiovascular mortality over the past half-century, atherosclerosis remains the most prevalent... (Review)
Review
PURPOSE
Despite an increase in treatment options, and substantial reductions in cardiovascular mortality over the past half-century, atherosclerosis remains the most prevalent cause of premature mortality worldwide. The development of innovative new therapies is crucial to further minimize atherosclerosis-related deaths. The diverse array of cell phenotypes derived from vascular smooth muscle cells (SMCs) and macrophages within atherosclerotic plaques are increasingly becoming recognized for their beneficial and detrimental roles in plaque stability and disease burden. This review explores how contemporary transcriptomics and fate-mapping studies have revealed vascular cell plasticity as a relatively unexplored target for therapeutic intervention.
METHODS
Recent literature for this narrative review was obtained by searching electronic databases (ie, Google Scholar, PubMed). Additional studies were sourced from reference lists and the authors' personal databases.
FINDINGS
The lipid-rich and inflammatory plaque milieu induces SMC phenotypic switching to both beneficial and detrimental phenotypes. Likewise, macrophage heterogeneity increases with disease burden to a variety of pro-inflammatory and anti-inflammatory activation states. These vascular cell phenotypes are determinants of plaque structure stability, and it is therefore highly likely that they influence clinical outcomes. Development of clinical treatments targeting deleterious phenotypes or promoting pro-healing phenotypes remains in its infancy. However, existing treatments (statins) have shown beneficial effects toward macrophage polarization, providing a rationale for more targeted approaches. In contrast, beneficial SMC phenotypic modulation with these pharmacologic agents has yet to be achieved. The range of modulated vascular cell phenotypes provides a multitude of novel targets and the potential to reduce future adverse events.
IMPLICATIONS
Vascular cell phenotypic heterogeneity must continue to be explored to lower cardiovascular events in the future. The rapidly increasing weight of evidence surrounding the role of SMC plasticity and macrophage polarity in plaque vulnerability provides a strong foundation upon which development of new therapeutics must follow. This approach may prove to be crucial in reducing cardiovascular events and improving patient benefit in the future.
Topics: Humans; Muscle, Smooth, Vascular; Cell Plasticity; Atherosclerosis; Plaque, Atherosclerotic; Macrophages; Phenotype
PubMed: 37709601
DOI: 10.1016/j.clinthera.2023.08.015 -
Proceedings. Biological Sciences Aug 2023Analyses of morphological disparity can incorporate living and fossil taxa to facilitate the exploration of how phenotypic variation changes through time. However,...
Analyses of morphological disparity can incorporate living and fossil taxa to facilitate the exploration of how phenotypic variation changes through time. However, taphonomic processes introduce non-random patterns of data loss in fossil data and their impact on perceptions of disparity is unclear. To address this, we characterize how measures of disparity change when simulated and empirical data are degraded through random and structured data loss. We demonstrate that both types of data loss can distort the disparity of clades, and that the magnitude and direction of these changes varies between the most commonly employed distance metrics and disparity indices. The inclusion of extant taxa and exceptionally preserved fossils mitigates these distortions and clarifies the full extent of the data lost, most of which would otherwise go uncharacterized. This facilitates the use of ancestral state estimation and evolutionary simulations to further control for the effects of data loss. Where the addition of such reference taxa is not possible, we urge caution in the extrapolation of general patterns in disparity from datasets that characterize subsets of phenotype, which may represent no more than the traits that they sample.
Topics: Phylogeny; Biological Evolution; Fossils; Phenotype
PubMed: 37554036
DOI: 10.1098/rspb.2023.0522 -
Journal of Plant Physiology Nov 2023A plant's genome encodes enzymes, transporters and many other proteins which constitute metabolism. Interactions of plants with their environment shape their growth,... (Review)
Review
A plant's genome encodes enzymes, transporters and many other proteins which constitute metabolism. Interactions of plants with their environment shape their growth, development and resilience towards adverse conditions. Although genome sequencing technologies and applications have experienced triumphantly rapid development during the last decades, enabling nowadays a fast and cheap sequencing of full genomes, prediction of metabolic phenotypes from genotype × environment interactions remains, at best, very incomplete. The main reasons are a lack of understanding of how different levels of molecular organisation depend on each other, and how they are constituted and expressed within a setup of growth conditions. Phenotypic plasticity, e.g., of the genetic model plant Arabidopsis thaliana, has provided important insights into plant-environment interactions and the resulting genotype x phenotype relationships. Here, we summarize previous and current findings about plant development in a changing environment and how this might be shaped and reflected in metabolism and its regulation. We identify current challenges in the study of plant development and metabolic regulation and provide an outlook of how methodological workflows might support the application of findings made in model systems to crops and their cultivation.
Topics: Gene-Environment Interaction; Genotype; Phenotype; Crops, Agricultural; Arabidopsis
PubMed: 37839392
DOI: 10.1016/j.jplph.2023.154116 -
Nature Reviews. Neurology Jan 2024Understanding rare genetic brain disorders with overlapping neurological and psychiatric phenotypes is of increasing importance given the potential for developing... (Review)
Review
Understanding rare genetic brain disorders with overlapping neurological and psychiatric phenotypes is of increasing importance given the potential for developing disease models that could help to understand more common, polygenic disorders. However, the traditional clinical boundaries between neurology and psychiatry result in frequent segregation of these disorders into distinct silos, limiting cross-specialty understanding that could facilitate clinical and biological advances. In this Review, we highlight multiple genetic brain disorders in which neurological and psychiatric phenotypes are observed, but for which in-depth, cross-spectrum clinical phenotyping is rarely undertaken. We describe the combined phenotypes observed in association with genetic variants linked to epilepsy, dystonia, autism spectrum disorder and schizophrenia. We also consider common underlying mechanisms that centre on synaptic plasticity, including changes to synaptic and neuronal structure, calcium handling and the balance of excitatory and inhibitory neuronal activity. Further investigation is needed to better define and replicate these phenotypes in larger cohorts, which would help to gain greater understanding of the pathophysiological mechanisms and identify common therapeutic targets.
Topics: Humans; Autism Spectrum Disorder; Schizophrenia; Epilepsy; Phenotype; Neurons
PubMed: 38001363
DOI: 10.1038/s41582-023-00896-x -
Nature Reviews. Cancer Feb 2024Molecular abnormalities that shape human neoplasms dissociate their phenotypic landscape from that of the healthy counterpart. Through the lens of a microscope, tumour... (Review)
Review
Molecular abnormalities that shape human neoplasms dissociate their phenotypic landscape from that of the healthy counterpart. Through the lens of a microscope, tumour pathology optically captures such aberrations projected onto a tissue slide and has categorized human epithelial neoplasms into distinct histological subtypes based on the diverse morphogenetic and molecular programmes that they manifest. Tumour histology often reflects tumour aggressiveness, patient prognosis and therapeutic vulnerability, and thus has been used as a de facto diagnostic tool and for making clinical decisions. However, it remains elusive how the diverse histological subtypes arise and translate into pleiotropic biological phenotypes. Molecular analysis of clinical tumour tissues and their culture, including patient-derived organoids, and add-back genetic reconstruction of tumorigenic pathways using gene engineering in culture models and rodents further elucidated molecular mechanisms that underlie morphological variations. Such mechanisms include genetic mutations and epigenetic alterations in cellular identity codes that erode hard-wired morphological programmes and histologically digress tumours from the native tissues. Interestingly, tumours acquire the ability to grow independently of the niche-driven stem cell ecosystem along with these morphological alterations, providing a biological rationale for histological diversification during tumorigenesis. This Review comprehensively summarizes our current understanding of such plasticity in the histological and lineage commitment fostered cooperatively by molecular alterations and the tumour environment, and describes basic and clinical implications for future cancer therapy.
Topics: Humans; Carcinogenesis; Mutation; Phenotype; Stem Cells
PubMed: 38135758
DOI: 10.1038/s41568-023-00648-5 -
The Behavioral and Brain Sciences Sep 2023In discussing the relationship between genetically influenced differences and educational attainment (EA), Burt employs the concept of downward causation. I note the...
In discussing the relationship between genetically influenced differences and educational attainment (EA), Burt employs the concept of downward causation. I note the similarities between Burt's concept of downward causation and the sociogenomics concept of vertical pleiotropy and argue that her discussion of downward causation introduces an unnecessary normative component. The core problem concerns not the appropriateness of phenotypes that influence EA but mistaken assumptions about which phenotypes are being predicted.
Topics: Humans; Genetic Pleiotropy; Phenotype; Educational Status
PubMed: 37694917
DOI: 10.1017/S0140525X22002308 -
American Journal of Medical Genetics.... Oct 2023The oculoauriculofrontonasal syndrome (OAFNS) is a rare condition, with unknown etiology, characterized by the association of frontonasal dysplasia (FND) and... (Review)
Review
The oculoauriculofrontonasal syndrome (OAFNS) is a rare condition, with unknown etiology, characterized by the association of frontonasal dysplasia (FND) and oculoauriculovertebral spectrum (OAVS). Main clinical findings include widely spaced eyes, epibulbar dermoid, broad nose, mandibular hypoplasia, and preauricular tags. Here, we describe a case series of 32 Brazilian individuals with OAFNS and review the literature ascertaining individuals presenting phenotypes compatible with the diagnosis of OAFNS, aiming to refine the phenotype. This series emphasizes the phenotypic variability of the OAFNS and highlights the occurrence of rare craniofacial clefts as a part of the phenotype. The ectopic nasal bone, a hallmark of OAFNS, was frequent in our series, reinforcing the clinical diagnosis. The absence of recurrence, consanguinity, chromosomal, and genetic abnormalities reinforces the hypothesis of a nontraditional inheritance model. The phenotypic refinement provided by this series contributes to an investigation regarding the etiology of OAFNS.
Topics: Humans; Ear, External; Eye Abnormalities; Spine; Goldenhar Syndrome; Phenotype
PubMed: 37282829
DOI: 10.1002/ajmg.a.63319 -
Current Opinion in Allergy and Clinical... Apr 2024This review explores the evolving landscape of pediatric asthma and rhinitis, focusing on identifying and characterizing different subtypes. (Review)
Review
PURPOSE OF REVIEW
This review explores the evolving landscape of pediatric asthma and rhinitis, focusing on identifying and characterizing different subtypes.
RECENT FINDINGS
Childhood asthma and rhinitis are prevalent respiratory conditions frequently occurring together. To address the need for a precise definition of these diseases, an unbiased and comprehensive phenotyping approach has been undertaken with hypothesis-free analysis of extensive datasets to uncover new relationships among clinical, environmental, and biological characteristics. On the other hand, the concept of endotype is elaborate and multifaceted, representing distinct pathophysiological mechanisms underlying the clinical presentation and requires the identification of reliable biomarkers. The recognition of multiple inflammatory endotypes underscores the need for in-depth characterization, which could revolutionize the treatment landscape.
SUMMARY
Comprehending phenotypes and endotypes is crucial for customizing effective and personalized management approaches for children with asthma and rhinitis. More precise and efficient care can be administered through recognition and detailed characterization, ultimately enhancing patients' quality of life.
Topics: Child; Humans; Quality of Life; Asthma; Rhinitis; Phenotype; Biomarkers
PubMed: 38295125
DOI: 10.1097/ACI.0000000000000970