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Nature Communications May 2024Growth rate maximization is an important fitness strategy for microbes. However, the wide distribution of slow-growing oligotrophic microbes in ecosystems suggests that... (Review)
Review
Growth rate maximization is an important fitness strategy for microbes. However, the wide distribution of slow-growing oligotrophic microbes in ecosystems suggests that rapid growth is often not favored across ecological environments. In many circumstances, there exist trade-offs between growth and other important traits (e.g., adaptability and survival) due to physiological and proteome constraints. Investments on alternative traits could compromise growth rate and microbes need to adopt bet-hedging strategies to improve fitness in fluctuating environments. Here we review the mechanistic role of trade-offs in controlling bacterial growth and further highlight its ecological implications in driving the emergences of many important ecological phenomena such as co-existence, population heterogeneity and oligotrophic/copiotrophic lifestyles.
Topics: Phenotype; Bacteria; Ecosystem; Bacterial Physiological Phenomena; Adaptation, Physiological
PubMed: 38762599
DOI: 10.1038/s41467-024-48591-9 -
Blood Cancer Journal Aug 2023T-lymphocytes are prevalent in the tumor microenvironment of follicular lymphoma (FL). However, the phenotype of T-cells may vary, and the prevalence of certain T-cell...
T-lymphocytes are prevalent in the tumor microenvironment of follicular lymphoma (FL). However, the phenotype of T-cells may vary, and the prevalence of certain T-cell subsets may influence tumor biology and patient survival. We therefore analyzed a cohort of 82 FL patients using CyTOF to determine whether specific T-cell phenotypes were associated with distinct tumor microenvironments and patient outcome. We identified four immune subgroups with differing T-cell phenotypes and the prevalence of certain T-cell subsets was associated with patient survival. Patients with increased T cells with early differentiation stage tended to have a significantly better survival than patients with increased T-cells of late differentiation stage. Specifically, CD57 T cells, with a late-stage differentiation phenotype, were significantly more abundant in FL patients who had early disease progression and therefore correlated with an inferior survival. Single cell analysis (CITE-seq) revealed that CD57 T cells exhibited a substantially different transcriptome from CD57 T cells with upregulation of inflammatory pathways, evidence of immune exhaustion and susceptibility to apoptosis. Taken together, our results show that different tumor microenvironments among FL patients are associated with variable T-cell phenotypes and an increased prevalence of CD57 T cells is associated with poor patient survival.
Topics: Humans; T Follicular Helper Cells; Tumor Microenvironment; Lymphoma, Follicular; Cell Differentiation; Phenotype
PubMed: 37591873
DOI: 10.1038/s41408-023-00899-3 -
Journal of Biomedical Semantics Aug 2023Phenotypes are observable characteristics of an organism and they can be highly variable. Information about phenotypes is collected in a clinical context to characterize...
MOTIVATION
Phenotypes are observable characteristics of an organism and they can be highly variable. Information about phenotypes is collected in a clinical context to characterize disease, and is also collected in model organisms and stored in model organism databases where they are used to understand gene functions. Phenotype data is also used in computational data analysis and machine learning methods to provide novel insights into disease mechanisms and support personalized diagnosis of disease. For mammalian organisms and in a clinical context, ontologies such as the Human Phenotype Ontology and the Mammalian Phenotype Ontology are widely used to formally and precisely describe phenotypes. We specifically analyze axioms pertaining to phenotypes of collections of entities within a body, and we find that some of the axioms in phenotype ontologies lead to inferences that may not accurately reflect the underlying biological phenomena.
RESULTS
We reformulate the phenotypes of collections of entities using an ontological theory of collections. By reformulating phenotypes of collections in phenotypes ontologies, we avoid potentially incorrect inferences pertaining to the cardinality of these collections. We apply our method to two phenotype ontologies and show that the reformulation not only removes some problematic inferences but also quantitatively improves biological data analysis.
Topics: Animals; Humans; Phenotype; Databases, Factual; Machine Learning; Biological Ontologies; Mammals
PubMed: 37550716
DOI: 10.1186/s13326-023-00290-y -
Biomedicine & Pharmacotherapy =... Oct 2023The CREB3 family of proteins, encompassing CREB3 and its four homologs (CREB3L1, CREB3L2, CREB3L3, and CREB3L4), exerts pivotal control over cellular protein metabolism... (Review)
Review
The CREB3 family of proteins, encompassing CREB3 and its four homologs (CREB3L1, CREB3L2, CREB3L3, and CREB3L4), exerts pivotal control over cellular protein metabolism in response to unfolded protein reactions. Under conditions of endoplasmic reticulum stress, activation of the CREB3 family occurs through regulated intramembrane proteolysis within the endoplasmic reticulum membrane. Perturbations in the function and expression of the CREB3 family have been closely associated with the development of diverse diseases, with a particular emphasis on cancer. Recent investigations have shed light on the indispensable role played by CREB3 family members in modulating the onset and progression of various human cancers. This comprehensive review endeavors to provide an in-depth examination of the involvement of CREB3 family members in distinct human cancer types, accentuating their significance in the pathogenesis of cancer and the manifestation of malignant phenotypes.
Topics: Humans; Neoplasms; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Phenotype; Cyclic AMP Response Element-Binding Protein
PubMed: 37595431
DOI: 10.1016/j.biopha.2023.115335 -
EBioMedicine May 2024Atopic dermatitis (AD) is the most common form of chronic skin inflammation with diverse clinical variants. Historically, various AD phenotypes have been grouped... (Review)
Review
Atopic dermatitis (AD) is the most common form of chronic skin inflammation with diverse clinical variants. Historically, various AD phenotypes have been grouped together without considering their heterogeneity. This approach has resulted in a lack of phenotype- and endotype-adapted therapeutic strategies. Comprehensive insights into AD pathogenesis have enabled precise medicinal approach for AD. These efforts aimed to redefine the endophenotype of AD and develop various biomarkers for diverse purposes. Among these endeavours, efforts are underway to elucidate the mechanisms (and related biomarkers) that lead to the emergence and progression of atopic diseases originating from AD (e.g., atopic march). This review focuses on diverse AD phenotypes and calls for a definition of endophenotypes. While awaiting scientific validation, these biomarkers ensure predicting disease onset and trajectory and tailoring therapeutic strategies for the future.
Topics: Dermatitis, Atopic; Humans; Biomarkers; Phenotype; Endophenotypes; Animals
PubMed: 38614010
DOI: 10.1016/j.ebiom.2024.105121 -
Human Genetics Oct 2023Congenital hearing loss affects one in 500 newborns. Sequence variations in OTOF, which encodes the calcium-binding protein otoferlin, are responsible for 1-8% of... (Review)
Review
Congenital hearing loss affects one in 500 newborns. Sequence variations in OTOF, which encodes the calcium-binding protein otoferlin, are responsible for 1-8% of congenital, nonsyndromic hearing loss and are the leading cause of auditory neuropathy spectrum disorders. The natural history of otoferlin-related hearing loss, the relationship between OTOF genotype and hearing loss phenotype, and the outcomes of clinical practices in patients with this genetic disorder are incompletely understood because most analyses have reported on small numbers of cases with homogeneous OTOF genotypes. Here, we present the first systematic, quantitative literature review of otoferlin-related hearing loss, which analyzes patient-specific data from 422 individuals across 61 publications. While most patients display a typical phenotype of severe-to-profound hearing loss with prelingual onset, 10-15% of patients display atypical phenotypes, including mild-to-moderate, progressive, and temperature-sensitive hearing loss. Patients' phenotypic presentations appear to depend on their specific genotypes. For example, non-truncating variants located in and immediately downstream of the CE calcium-binding domain are more likely to produce atypical phenotypes. Additionally, the prevalence of certain sequence variants and their associated phenotypes varies between populations due to evolutionary founder effects. Our analyses also suggest otoacoustic emissions are less common in older patients and those with two truncating OTOF variants. Critically, our review has implications for the application and limitations of clinical practices, including newborn hearing screenings, hearing aid trials, cochlear implants, and upcoming gene therapy clinical trials. We conclude by discussing the limitations of available research and recommendations for future studies on this genetic cause of hearing loss.
Topics: Infant, Newborn; Humans; Aged; Hearing Loss; Deafness; Hearing Loss, Central; Genotype; Phenotype
PubMed: 37679651
DOI: 10.1007/s00439-023-02595-5 -
Skeletal Radiology Nov 2023A joint contains many different tissues that can exhibit pathological changes, providing many potential targets for treatment. Researchers are increasingly suggesting... (Review)
Review
A joint contains many different tissues that can exhibit pathological changes, providing many potential targets for treatment. Researchers are increasingly suggesting that osteoarthritis (OA) comprises several phenotypes or subpopulations. Consequently, a treatment for OA that targets only one pathophysiologic abnormality is unlikely to be similarly efficacious in preventing or delaying the progression of all the different phenotypes of structural OA. Five structural phenotypes have been proposed, namely the inflammatory, meniscus-cartilage, subchondral bone, and atrophic and hypertrophic phenotypes. The inflammatory phenotype is characterized by marked synovitis and/or joint effusion, while the meniscus-cartilage phenotype exhibits severe meniscal and cartilage damage. Large bone marrow lesions characterize the subchondral bone phenotype. The hypertrophic and atrophic OA phenotype are defined based on the presence large osteophytes or absence of any osteophytes, respectively, in the presence of concomitant cartilage damage. Limitations of the concept of structural phenotyping are that they are not mutually exclusive and that more than one phenotype may be present. It must be acknowledged that a wide range of views exist on how best to operationalize the concept of structural OA phenotypes and that the concept of structural phenotypic characterization is still in its infancy. Structural phenotypic stratification, however, may result in more targeted trial populations with successful outcomes and practitioners need to be aware of the heterogeneity of the disease to personalize their treatment recommendations for an individual patient. Radiologists should be able to define a joint at risk for progression based on the predominant phenotype present at different disease stages.
Topics: Humans; Osteoarthritis, Knee; Knee Joint; Osteophyte; Magnetic Resonance Imaging; Cartilage, Articular; Hypertrophy; Cartilage Diseases; Bone Diseases; Phenotype
PubMed: 36161341
DOI: 10.1007/s00256-022-04191-6 -
FEMS Yeast Research Jan 2024Among molecular biologists, the group of fungi called Saccharomycotina is famous for its yeasts. These yeasts in turn are famous for what they have in common-genetic,... (Review)
Review
Among molecular biologists, the group of fungi called Saccharomycotina is famous for its yeasts. These yeasts in turn are famous for what they have in common-genetic, biochemical, and cell-biological characteristics that serve as models for plants and animals. But behind the apparent homogeneity of Saccharomycotina species lie a wealth of differences. In this review, we discuss traits that vary across the Saccharomycotina subphylum. We describe cases of bright pigmentation; a zoo of cell shapes; metabolic specialties; and species with unique rules of gene regulation. We discuss the genetics of this diversity and why it matters, including insights into basic evolutionary principles with relevance across Eukarya.
Topics: Ascomycota; Biological Evolution; Yeasts; Phenotype
PubMed: 38218591
DOI: 10.1093/femsyr/foae002 -
Molecular Psychiatry Dec 2023Genome-wide association studies (GWAS) provide biological insights into disease onset and progression and have potential to produce clinically useful biomarkers. A... (Review)
Review
Genome-wide association studies (GWAS) provide biological insights into disease onset and progression and have potential to produce clinically useful biomarkers. A growing body of GWAS focuses on quantitative and transdiagnostic phenotypic targets, such as symptom severity or biological markers, to enhance gene discovery and the translational utility of genetic findings. The current review discusses such phenotypic approaches in GWAS across major psychiatric disorders. We identify themes and recommendations that emerge from the literature to date, including issues of sample size, reliability, convergent validity, sources of phenotypic information, phenotypes based on biological and behavioral markers such as neuroimaging and chronotype, and longitudinal phenotypes. We also discuss insights from multi-trait methods such as genomic structural equation modelling. These provide insight into how hierarchical 'splitting' and 'lumping' approaches can be applied to both diagnostic and dimensional phenotypes to model clinical heterogeneity and comorbidity. Overall, dimensional and transdiagnostic phenotypes have enhanced gene discovery in many psychiatric conditions and promises to yield fruitful GWAS targets in the years to come.
Topics: Humans; Genome-Wide Association Study; Phenotype; Mental Disorders; Genetic Predisposition to Disease; Biomarkers; Reproducibility of Results; Polymorphism, Single Nucleotide
PubMed: 37402851
DOI: 10.1038/s41380-023-02142-8 -
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