An -omics Perspective on Marine Invertebrate Larvae

2018 ◽  
Keyword(s):  
Large Scale ◽  
Natural Variation ◽  
Molecular Mechanisms ◽  
Marine Invertebrate ◽  
Life History Evolution ◽  
Molecular Approaches ◽  
Fine Detail ◽  
Technological Advances ◽  
Gene Environment ◽  
Invertebrate Larvae

The diverse phenotypes exhibited by marine invertebrate larvae are the result of complex gene-environment interactions. Recently, technological advances in molecular biology have enabled large-scale -omics approaches, which can provide a global overview of the molecular mechanisms that shape the larval genotype-phenotype landscape. -omics approaches are facilitating our understanding of larval development and life history evolution, larval response to environmental stress, the larval microbiome, larval physiology and feeding, and larval behavior. These large-scale molecular approaches are even more effective when combined with large-scale environmental monitoring and phenotypic measurements. Current -omics approaches to studying larvae can be improved by the addition of functional genetic analyses and the reporting of natural variation in gene expression between individuals and populations. Systems-level approaches that combine multiple -omics techniques will allow us to explore in fine detail the interactions of environmental and genotypic influences on larval phenotype.

Gene-Environment Interaction in the Determination of Levels of Plasma Fibrinogen

1999 ◽  
Vol 82 (08) ◽  
pp. 818-825 ◽  
Author(s):  
Le-Anh Luong ◽  
Hugh Montgomery ◽  
Ian Day ◽  
Vidya Mohamed-Ali ◽  
John Yudkin ◽  
...  
Keyword(s):  
Risk Factors ◽  
Healthy Subjects ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Smoking Habit ◽  
Plasma Fibrinogen ◽  
Environment Interaction ◽  
Gene Environment ◽  
Genotype Information

IntroductionThis review will focus on the inflammatory risk factors that may influence changes in plasma fibrinogen levels and that may influence an individual’s risk of ischemic heart disease (IHD). These inflammatory risk factors occur to a different extent in individuals as their environment changes. Although a specific genotype may be associated, in healthy subjects, with modest differences in levels of a risk factor for thrombosis, this effect may be larger or smaller in subgroups of subjects. Documenting such gene-environment interactions is important if genotype information is ever to be used in a clinical or diagnostic setting. Understanding the molecular mechanisms of such interactions is vital to the development of novel therapeutic approaches to reduce risk of myocardial infarction (MI).We review some of the gene-environment interactions detected to date for the G-455A β-fibrinogen gene promoter polymorphism. Carriers of the A allele, representing roughly 20% of the population, consistently have, on average, 7% to 10% higher fibrinogen levels than those with the genotype GG. Data will be presented to demonstrate interaction between situations of inflammatory stimulation (e.g., smoking habit, presence of ischemic disease, and level of physical exercise) in the determination of the magnitude of the effect of the A allele on plasma fibrinogen levels.The cytokine interleukin-6 (IL-6) is the likely link between inflammatory processes and IHD. Recently we have identified a functional G/C polymorphism at -174bp in the IL-6 promoter, with the G allele being a 2 to 4 times stronger promoter upon stimulation with interleukin-1 (IL-1) or lipopolysaccharide (LPS). In a small study of healthy subjects, the C allele was associated with significantly lower mean plasma levels of IL-6, an effect which may be protect against the development of IHD. Finally, we describe a rapid throughput genotyping method that is useful for large-scale genetic epidemiology studies.

Gene–environment interaction in autoimmune disease

2014 ◽  
Vol 16 ◽  
Author(s):  
Justine A Ellis ◽  
Andrew S Kemp ◽  
Anne-Louise Ponsonby
Keyword(s):  
Autoimmune Disease ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Disease Risk ◽  
Personalised Medicine ◽  
Current Evidence ◽  
Environment Interaction ◽  
Gene Environment ◽  
Genes And Environment ◽  
Genetic And Environmental Factors

Autoimmune disease manifests in numerous forms, but as a disease group is relatively common in the population. It is complex in aetiology, with genetic and environmental determinants. The involvement of gene variants in autoimmune disease is well established, and evidence for significant involvement of the environment in various disease forms is growing. These factors may act independently, or they may interact, with the effect of one factor influenced by the presence of another. Identifying combinations of genetic and environmental factors that interact in autoimmune disease has the capacity to more fully explain disease risk profile, and to uncover underlying molecular mechanisms contributing to disease pathogenesis. In turn, such knowledge is likely to contribute significantly to the development of personalised medicine, and targeted preventative approaches. In this review, we consider the current evidence for gene–environment (G–E) interaction in autoimmune disease. Large-scale G–E interaction research efforts, while well-justified, face significant practical and methodological challenges. However, it is clear from the evidence that has already been generated that knowledge on how genes and environment interact at a biological level will be crucial in fully understanding the processes that manifest as autoimmunity.

Phenotypic Plasticity of Feeding Structures in Marine Invertebrate Larvae

2018 ◽  
Keyword(s):  
Phenotypic Plasticity ◽  
Molecular Mechanisms ◽  
Sea Urchins ◽  
Marine Invertebrate ◽  
Future Research ◽  
Trade Offs ◽  
Feeding Structure ◽  
Research Findings ◽  
Planktotrophic Larvae ◽  
Invertebrate Larvae

Nearly three decades ago, biologists discovered that planktotrophic larvae of sea urchins can alter the size of their ciliated feeding structures in response to the concentration of food (i.e., unicellular algae). In the years since, this response has become one of the best-studied examples of phenotypic plasticity in marine organisms. Researchers have found that this form of plasticity occurs widely among different types of feeding larvae in several phyla, and involves energetic trade-offs with a suite of correlated life history characters. Furthermore, investigators have recently started to unravel the genetic and molecular mechanisms underlying this plasticity. We review the literature on feeding-structure plasticity in marine invertebrate larvae. We highlight the diversity of species and variety of experimental designs and statistical methodologies, summarize research findings to draw more general conclusions, and target promising directions for future research.

Evolutionary Ecology of Marine Invertebrate Larvae

2018 ◽  
Keyword(s):  
Evolutionary Ecology ◽  
Marine Invertebrate ◽  
Ecological Factors ◽  
Larval Ecology ◽  
Larval Biology ◽  
Interdisciplinary Field ◽  
Technological Advances ◽  
Pelagic Environment ◽  
Fundamental Phenomenon ◽  
Invertebrate Larvae

For more than a century, evolutionary biologists, ecologists, and oceanographers alike have been intellectually stimulated by marine invertebrate larval forms. In 1995, Ecology of Marine Invertebrate Larvae, edited by the late Dr. Larry McEdward, captured the fundamental phenomenon and tremendous diversity of reproductive, biological, and oceanographic aspects of larval ecology. Now, more than twenty years later, this current edited volume provides an update to many of the original 13 chapters, while also reviewing several braches of larval ecology and evolution that have developed since. In Evolutionary Ecology of Marine Invertebrate Larvae, authors review the origins of marine invertebrate larvae and the developmental mechanisms and ecological factors that may generate this great diversity, and how these microscopic organisms feed, develop, and behave in the pelagic environment. Whether actively swimming in the coastal seas or the deep abyss, larvae are often in motion and must settle on the seafloor; however, if delayed, they are susceptible to a multitude of consequences later in life. Now, in an age of change, larvae face a warmer, more acidic, and more toxic ocean than ever before. Responses to these stressors plus many other facets of larval biology can be broadly profiled, thanks to current technological advances. This edited volume provides a major synthesis of an important interdisciplinary field. It aims to foster stimulating discussions centered on the evolution and ecology of marine invertebrate larvae.

scholarly journals A microbial perspective on the life-history evolution of marine invertebrate larvae: if, where, and when to feed

2017 ◽  
Author(s):  
Tyler J. Carrier ◽  
Jason Macrander ◽  
Adam M. Reitzel
Keyword(s):  
Life History ◽  
Marine Invertebrate ◽  
Life History Evolution ◽  
Trade Offs ◽  
Pelagic Environment ◽  
History Evolution ◽  
Planktotrophic Larvae ◽  
Invertebrate Larvae ◽  
Microbiome Data ◽  
Feeding Environments

AbstractThe feeding environment for planktotrophic larvae has a major impact on development and progression towards competency for metamorphosis. High phytoplankton environments that promote growth often have a greater microbial load and incidence of pathogenic microbes, while areas with lower food availability have a lower number of potential pathogens. Trade-offs between metabolic processes associated with growth and immune functionality have been described throughout the animal kingdom and may influence the life-history evolution of marine invertebrate planktotrophic larvae in these environments. Namely, to avoid potential incidences of microbial-mediated mortality and/or dysbiosis, larvae should regulate time spent between these two feeding environments. We describe here transcriptomic and microbiome data that supports this trade-off in larvae, where larvae in a well-fed environment upregulate genes associated with metabolism and may regularly enter a state of dysbiosis, resulting in mortality. To address the hypothesis that the environmental microbiota is a selective force on if, where, and when planktotrophic larvae should feed, we present a strategy for determining the specific interactions of larvae and microbes at a scale representative of their larger pelagic environment.

scholarly journals RETRACTION: Illuminating the dark road from schizophrenia genetic associations to disease mechanisms

2016 ◽  
Vol 4 (2) ◽  
pp. 240-251 ◽  
Author(s):  
Ming Li ◽  
Daniel R Weinberger
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Human Populations ◽  
Genome Wide Association Studies ◽  
Genetic Associations ◽  
Molecular Approaches ◽  
Disease Biology

Abstract Recent large-scale genome-wide association studies (GWAS) have enabled the discovery of common genetic variations contributing to risk architectures of schizophrenia in human populations; however, the majority of GWAS-identified variants are located in large genomic regions spanning multiple genes, and recognizing the precise targets and mechanisms of these clinical associations is now the major challenge. Here, we review recent progress in schizophrenia genetics, functional genomics and related neuroscience research, and propose a functional pipeline to translate schizophrenia GWAS risk loci into disease biology and information for drug discovery. The pipeline includes identification of underlying molecular mechanisms using transcriptomic data in human brain, prioritization of putative functional causative variants by the integration of genetic epidemiological and bioinformatics methods as well as molecular approaches, and in vitro and in vivo experimental characterizations of the identified targeted species and causative variants to dissect the relevant disease biology. These approaches will accelerate progress from schizophrenia genetic studies to biological mechanisms and ultimately guide the development of prognostic, preventive and therapeutic measures.

Physiology of Larval Feeding

2018 ◽  
Keyword(s):  
Growth And Development ◽  
Marine Invertebrate ◽  
Larval Growth ◽  
Circulatory System ◽  
Future Research ◽  
Larval Feeding ◽  
Digestive Physiology ◽  
Larval Body ◽  
The Individual ◽  
Invertebrate Larvae

The functional properties of marine invertebrate larvae represent the sum of the physiological activities of the individual, the interdependence among cells making up the whole, and the correct positioning of cells within the larval body. This chapter examines physiological aspects of nutrient acquisition, digestion, assimilation, and distribution within invertebrate larvae from an organismic and comparative perspective. Growth and development of larvae obviously require the acquisition of “food.” Yet the mechanisms where particulate or dissolved organic materials are converted into biomass and promote development of larvae differ and are variably known among groups. Differences in the physiology of the digestive system (secreted enzymes, gut transit time, and assimilation) within and among feeding larvae suggest the possibility of an underappreciated plasticity of digestive physiology. How the ingestion of seawater by and the existence of a circulatory system within larvae contribute to larval growth and development represent important topics for future research.

scholarly journals EGCG binds intrinsically disordered N-terminal domain of p53 and disrupts p53-MDM2 interaction

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Zhao ◽  
Alan Blayney ◽  
Xiaorong Liu ◽  
Lauren Gandy ◽  
Weihua Jin ◽  
...  
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
Epigallocatechin Gallate ◽  
Cancer Drug ◽  
Dynamic Interactions ◽  
Cancer Drug Discovery ◽  
Intrinsically Disordered ◽  
Terminal Domain ◽  
Cancerous Cells

AbstractEpigallocatechin gallate (EGCG) from green tea can induce apoptosis in cancerous cells, but the underlying molecular mechanisms remain poorly understood. Using SPR and NMR, here we report a direct, μM interaction between EGCG and the tumor suppressor p53 (KD = 1.6 ± 1.4 μM), with the disordered N-terminal domain (NTD) identified as the major binding site (KD = 4 ± 2 μM). Large scale atomistic simulations (>100 μs), SAXS and AUC demonstrate that EGCG-NTD interaction is dynamic and EGCG causes the emergence of a subpopulation of compact bound conformations. The EGCG-p53 interaction disrupts p53 interaction with its regulatory E3 ligase MDM2 and inhibits ubiquitination of p53 by MDM2 in an in vitro ubiquitination assay, likely stabilizing p53 for anti-tumor activity. Our work provides insights into the mechanisms for EGCG’s anticancer activity and identifies p53 NTD as a target for cancer drug discovery through dynamic interactions with small molecules.

scholarly journals Integrative cBioPortal Analysis Revealed Molecular Mechanisms That Regulate EGFR-PI3K-AKT-mTOR Pathway in Diffuse Gliomas of the Brain

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3247
Author(s):  
Petar Brlek ◽  
Anja Kafka ◽  
Anja Bukovac ◽  
Nives Pećina-Šlaus
Keyword(s):  
Large Scale ◽  
Molecular Mechanisms ◽  
In Silico Analysis ◽  
Total Sample ◽  
Mtor Signaling ◽  
Biological Behavior ◽  
Mrna Transcription ◽  
Diffuse Gliomas ◽  
New Treatment ◽  
Using Data

Diffuse gliomas are a heterogeneous group of tumors with aggressive biological behavior and a lack of effective treatment methods. Despite new molecular findings, the differences between pathohistological types still require better understanding. In this in silico analysis, we investigated AKT1, AKT2, AKT3, CHUK, GSK3β, EGFR, PTEN, and PIK3AP1 as participants of EGFR-PI3K-AKT-mTOR signaling using data from the publicly available cBioPortal platform. Integrative large-scale analyses investigated changes in copy number aberrations (CNA), methylation, mRNA transcription and protein expression within 751 samples of diffuse astrocytomas, anaplastic astrocytomas and glioblastomas. The study showed a significant percentage of CNA in PTEN (76%), PIK3AP1 and CHUK (75% each), EGFR (74%), AKT2 (39%), AKT1 (32%), AKT3 (19%) and GSK3β (18%) in the total sample. Comprehensive statistical analyses show how genomics and epigenomics affect the expression of examined genes differently across various pathohistological types and grades, suggesting that genes AKT3, CHUK and PTEN behave like tumor suppressors, while AKT1, AKT2, EGFR, and PIK3AP1 show oncogenic behavior and are involved in enhanced activity of the EGFR-PI3K-AKT-mTOR signaling pathway. Our findings contribute to the knowledge of the molecular differences between pathohistological types and ultimately offer the possibility of new treatment targets and personalized therapies in patients with diffuse gliomas.

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