Endocrinology of protochordates

2005 ◽  
Vol 83 (1) ◽  
pp. 225-255 ◽  
Author(s):  
Nancy M Sherwood ◽  
Bruce A Adams ◽  
Javier A Tello
Keyword(s):  
Sex Steroids ◽  
Large Scale ◽  
Steroid Receptors ◽  
Endocrine System ◽  
Egf Receptors ◽  
Vertebrate Lineage ◽  
Surface Receptors ◽  
Functional Studies ◽  
Full Complement ◽  
X Receptors

Large-scale gene duplications occurred early in the vertebrate lineage after the split with protochordates. Thus, protochordate hormones and their receptors, transcription factors, and signaling pathways may be the foundation for the endocrine system in vertebrates. A number of hormones have been identified including cionin, a likely ancestor of cholecytokinin (CCK) and gastrin. Both insulin and insulin-like growth hormone (IGF) have been identified in separate cDNAs in a tunicate, whereas only a single insulin-like peptide was found in amphioxus. In tunicates, nine distinct forms of gonadotropin-releasing hormone (GnRH) are shown to induce gamete release, even though a pituitary gland and sex steroids are lacking. In both tunicates and amphioxus, there is evidence of some components of a thyroid system, but the lack of a sequenced genome for amphioxus has slowed progress in the structural identification of its hormones. Immunocytochemistry has been used to tentatively identify a number of hormones in protochordates, but structural and functional studies are needed. For receptors, protochordates have many vertebrate homologs of nuclear receptors, such as the thyroid, retinoic acid, and retinoid X receptors. Also, tunicates have cell surface receptors including the G-protein-coupled type, such as β-adrenergic, putative endocannabinoid, cionin (CCK-like), and two GnRH receptors. Several tyrosine kinase receptors include two epidermal growth factor (EGF) receptors (tunicates) and an insulin/IGF receptor (amphioxus). Interestingly, neither steroid receptors nor a full complement of enzymes for synthesis of sex steroids are encoded in the Ciona genome. Tunicates appear to have some but not all of the necessary molecules to develop a vertebrate-like pituitary or complete thyroid system.

scholarly journals Large scale genome-wide association and LDLA mapping study identifies QTLs for boar taint and related sex steroids

BMC Genomics ◽  
2011 ◽  
Vol 12 (1) ◽  
Author(s):  
Eli Grindflek ◽  
Sigbjørn Lien ◽  
Hanne Hamland ◽  
Marianne HS Hansen ◽  
Matthew Kent ◽  
...  
Keyword(s):  
Sex Steroids ◽  
Large Scale ◽  
Boar Taint ◽  
Genome Wide Association ◽  
Mapping Study ◽  
Genome Wide

scholarly journals Toward Targeting Antiapoptotic MCL-1 for Cancer Therapy

2020 ◽  
Vol 4 (1) ◽  
pp. 299-313
Author(s):  
Gemma L. Kelly ◽  
Andreas Strasser
Keyword(s):  
Cell Death ◽  
Structural Analysis ◽  
Cancer Therapy ◽  
Tumor Cells ◽  
Large Scale ◽  
Tissue Homeostasis ◽  
Clinical Testing ◽  
Malignant Cells ◽  
Functional Studies ◽  
Genome Analyses

Apoptosis is critical for embryonic development, tissue homeostasis, and the removal of infected or otherwise dangerous cells. It is controlled by three subgroups of the BCL-2 protein family—the BH3-only proteins that initiate cell death; the effectors of cell killing, BAX and BAK; and the antiapoptotic guardians, including MCL-1 and BCL-2. Defects in apoptosis can promote tumorigenesis and render malignant cells refractory to anticancer therapeutics. Activation of cell death by inhibiting antiapoptotic BCL-2 family members has emerged as an attractive strategy for cancer therapy, with the BCL-2 inhibitor venetoclax leading the way. Large-scale cancer genome analyses have revealed frequent amplification of the locus encoding antiapoptotic MCL-1 in human cancers, and functional studies have shown that MCL-1 is essential for the sustained survival and expansion of many types of tumor cells. Structural analysis and medicinal chemistry have led to the development of three distinct small-molecule inhibitors of MCL-1 that are currently undergoing clinical testing.

scholarly journals Heterelogous Expression of Plant Genes

2009 ◽  
Vol 2009 ◽  
pp. 1-16 ◽  
Author(s):  
Filiz Yesilirmak ◽  
Zehra Sayers
Keyword(s):  
Large Scale ◽  
Protein Production ◽  
Insect Cells ◽  
Protein Characterization ◽  
Model Organisms ◽  
Plant Proteins ◽  
Production Methods ◽  
Functional Studies ◽  
Recombinant Plant ◽  
Plant Genes

Heterologous expression allows the production of plant proteins in an organism which is simpler than the natural source. This technology is widely used for large-scale purification of plant proteins from microorganisms for biochemical and biophysical analyses. Additionally expression in well-defined model organisms provides insights into the functions of proteins in complex pathways. The present review gives an overview of recombinant plant protein production methods using bacteria, yeast, insect cells, and Xenopus laevis oocytes and discusses the advantages of each system for functional studies and protein characterization.

A Cell-based Model of Hemostasis

2001 ◽  
Vol 85 (06) ◽  
pp. 958-965 ◽  
Author(s):  
Dougald Monroe ◽  
Maureane Hoffman
Keyword(s):  
Large Scale ◽  
Coagulation Factors ◽  
Cellular Receptors ◽  
Platelet Surface ◽  
Surface Receptors ◽  
Coagulation Proteins ◽  
A Cell ◽  
And Control ◽  
Prevailing View

SummaryBased on our work and that of many other workers, we have developed a model of coagulation in vivo. Many workers have demonstrated mechanisms by which cells can influence the coagulation process. Nonetheless, the prevailing view of hemostasis remains that the protein coagulation factors direct and control the process with cells serving primarily to provide a phosphatidylserine containing surface on which the procoagulant complexes are assembled. By contrast, we propose a model in which coagulation is regulated by properties of cell surfaces. This model emphasizes the importance of specific cellular receptors for the coagulation proteins. Thus, cells with similar phosphatidylserine content can play very different roles in hemostasis depending on their complement of surface receptors. We propose that coagulation occurs not as a “cascade”, but in three overlapping stages: 1) initiation, which occurs on a tissue factor bearing cell; 2) amplification, in which platelets and cofactors are activated to set the stage for large scale thrombin generation; and 3) propagation, in which large amounts of thrombin are generated on the platelet surface. This cell based model explains some aspects of hemostasis that a protein-centric model does not.

scholarly journals Polymyositis, Topological Proteomics Technology and Paradigm for Cell Invasion Dynamics

2002 ◽  
Vol 4 (1) ◽  
pp. 75-84 ◽  
Author(s):  
Walter Schubert
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Surface ◽  
Cell Invasion ◽  
Large Scale ◽  
Expression Patterns ◽  
Inflammatory Myopathy ◽  
Protein Profiling ◽  
Cell Surface Receptors ◽  
Surface Receptors

Polymyositis is an inflammatory myopathy characterized by muscle invasion of T-cells penetrating the basal lamina and displacing the plasma membrane of normal muscle fibers. This investigation presents a technology for the direct mapping of protein networks involved in T-cell invasionin situ. Simultaneous localization of 17 adhesive cell surface receptors reveals 18 different combinatorial expression patterns (CEP), which are unique for the T-cell invasion process in muscle tissue. Each invasion step can be assigned to specific CEP on the surface of individual T-cells. This indicates, that the T-cell invasion is enciphered combinatorially in the T-cells' adhesive cell surface proteome fraction. Given 217possible combinations, the T-cell appears to have at its disposal a highly non-random restricted repertoire to specify migratory pathways at the cell surface. These higher-level order functions in the cellular proteome cannot be detected by large-scale protein profiling techniques from tissue homogenates. High-throughput whole cell mapping machines working on structurally intact tissues, as shown here, will allow to measure how cells of different origin (immune cells, tumor cells) combine cell surface receptors to encipher specificity and selectivity for interactions.

scholarly journals Cloning of mouse 17β-hydroxysteroid dehydrogenase type 2, and analysing expression of the mRNAs for types 1, 2, 3, 4 and 5 in mouse embryos and adult tissues

1997 ◽  
Vol 325 (1) ◽  
pp. 199-205 ◽  
Author(s):  
Mika V. J. MUSTONEN ◽  
Matti H. POUTANEN ◽  
Veli V. ISOMAA ◽  
Pirkko T. VIHKO ◽  
Reijo K. VIHKO
Keyword(s):  
Sex Steroids ◽  
Steroid Receptors ◽  
Mouse Embryos ◽  
Key Factors ◽  
Reading Frame ◽  
Mouse Tissues ◽  
Low Activity ◽  
Oestradiol Production

17β-Hydroxysteroid dehydrogenases (17HSDs) are responsible for the conversion of low-activity sex steroids to more potent forms, and vice versa. 17HSD activity is essential for the biosynthesis of sex steroids in the gonads, and it is also one of the key factors regulating the availability of active ligands for sex-steroid receptors in various extragonadal tissues. In this study, we have characterized mouse 17HSD type 2 cDNA, and analysed the relative expression of 17HSD types 1, 2, 3, 4 and 5 mRNAs in mouse embryos and adult male and female tissues. The cDNA characterized has a open reading frame of 1146 bp, and encodes a protein of 381 amino acids with a predicted molecular mass of 41837 kDa. Northern-blot analysis of adult mouse tissues revealed that, of the different 17HSDs, the type 2 enzyme is most abundantly expressed. High expression of the enzyme, which oxidizes both testosterone and oestradiol, in several large organs of both sexes indicates that it is the isoform having the most substantial role in the metabolism of sex steroids. Interestingly, four of the five 17HSD enzymes were also detected by Northern blots of whole mouse embryos, and each of the enzymes showed a unique pattern of expression. The oestradiol-synthesizing type 1 enzyme predominates in early days of development embryonic day 7, but after that the oxidative type 2 enzyme becomes the predominant form of all 17HSDs. The data therefore suggest that there is transient oestradiol production in the early days of embryonic development, after which inactivation of sex steroids predominates in the fetus and placenta.

scholarly journals The liver X receptor pathway is highly upregulated in rheumatoid arthritis synovial macrophages and potentiates TLR-driven cytokine release

2013 ◽  
Vol 72 (12) ◽  
pp. 2024-2031 ◽  
Author(s):  
Darren Lee Asquith ◽  
Lucy E Ballantine ◽  
Jagtar Singh Nijjar ◽  
Manhal Khuder Makdasy ◽  
Sabina Patel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cholesterol Metabolism ◽  
Liver X Receptors ◽  
Blood Monocytes ◽  
Functional Studies ◽  
Inflammatory Processes ◽  
X Receptors ◽  
Factor Α ◽  
Necrosis Factor ◽  
Tlr Signalling

ObjectivesMacrophages are central to the inflammatory processes driving rheumatoid arthritis (RA) synovitis. The molecular pathways that are induced in synovial macrophages and thereby promote RA disease pathology remain poorly understood.MethodsWe used microarray to characterise the transcriptome of synovial fluid (SF) macrophages compared with matched peripheral blood monocytes from patients with RA (n=8).ResultsUsing in silico pathway mapping, we found that pathways downstream of the cholesterol activated liver X receptors (LXRs) and those associated with Toll-like receptor (TLR) signalling were upregulated in SF macrophages. Macrophage differentiation and tumour necrosis factor α promoted the expression of LXRα. Furthermore, in functional studies we demonstrated that activation of LXRs significantly augmented TLR-driven cytokine and chemokine secretion.ConclusionsThe LXR pathway is the most upregulated pathway in RA synovial macrophages and activation of LXRs by ligands present within SF augments TLR-driven cytokine secretion. Since the natural agonists of LXRs arise from cholesterol metabolism, this provides a novel mechanism that can promote RA synovitis.

scholarly journals Pan-vertebrate comparative genomics unmasks retrovirus macroevolution

2014 ◽  
Vol 112 (2) ◽  
pp. 464-469 ◽  
Author(s):  
Alexander Hayward ◽  
Charlie K. Cornwallis ◽  
Patric Jern
Keyword(s):  
Large Scale ◽  
Endogenous Retroviruses ◽  
Evolutionary Time ◽  
Vertebrate Lineage ◽  
Internal Fertilization ◽  
Technological Advances ◽  
Host Lineage ◽  
Cell Genome ◽  
Cohesive Framework ◽  
Retroviral Evolution

Although extensive research has demonstrated host-retrovirus microevolutionary dynamics, it has been difficult to gain a deeper understanding of the macroevolutionary patterns of host–retrovirus interactions. Here we use recent technological advances to infer broad patterns in retroviral diversity, evolution, and host–virus relationships by using a large-scale phylogenomic approach using endogenous retroviruses (ERVs). Retroviruses insert a proviral DNA copy into the host cell genome to produce new viruses. ERVs are provirus insertions in germline cells that are inherited down the host lineage and consequently present a record of past host–viral associations. By mining ERVs from 65 host genomes sampled across vertebrate diversity, we uncover a great diversity of ERVs, indicating that retroviral sequences are much more prevalent and widespread across vertebrates than previously appreciated. The majority of ERV clades that we recover do not contain known retroviruses, implying either that retroviral lineages are highly transient over evolutionary time or that a considerable number of retroviruses remain to be identified. By characterizing the distribution of ERVs, we show that no major vertebrate lineage has escaped retroviral activity and that retroviruses are extreme host generalists, having an unprecedented ability for rampant host switching among distantly related vertebrates. In addition, we examine whether the distribution of ERVs can be explained by host factors predicted to influence viral transmission and find that internal fertilization has a pronounced effect on retroviral colonization of host genomes. By capturing the mode and pattern of retroviral evolution and contrasting ERV diversity with known retroviral diversity, our study provides a cohesive framework to understand host–virus coevolution better.

scholarly journals Targeted capture of complete coding regions across divergent species

2017 ◽  
Author(s):  
Ryan K Schott ◽  
Bhawandeep Panesar ◽  
Daren C Card ◽  
Matthew Preston ◽  
Todd A Castoe ◽  
...  
Keyword(s):  
Molecular Evolution ◽  
Large Scale ◽  
Functional Studies ◽  
Coding Regions ◽  
Sequencing Technologies ◽  
Phylogenetic Studies ◽  
Large Numbers ◽  
Capture Method ◽  
Targeted Capture ◽  
And Function

AbstractDespite continued advances in sequencing technologies, there is a need for methods that can efficiently sequence large numbers of genes from diverse species. One approach to accomplish this is targeted capture (hybrid enrichment). While these methods are well established for genome resequencing projects, cross-species capture strategies are still being developed and generally focus on the capture of conserved regions, rather than complete coding regions from specific genes of interest. The resulting data is thus useful for phylogenetic studies, but the wealth of comparative data that could be used for evolutionary and functional studies is lost. Here we design and implement a targeted capture method that enables recovery of complete coding regions across broad taxonomic scales. Capture probes were designed from multiple reference species and extensively tiled in order to facilitate cross-species capture. Using novel bioinformatics pipelines we were able to recover nearly all of the targeted genes with high completeness from species that were up to 200 myr divergent. Increased probe diversity and tiling for a subset of genes had a large positive effect on both recovery and completeness. The resulting data produced an accurate species tree, but importantly this same data can also be applied to studies of molecular evolution and function that will allow researchers to ask larger questions in broader phylogenetic contexts. Our method demonstrates the utility of cross-species approaches for the capture of full length coding sequences, and will substantially improve the ability for researchers to conduct large-scale comparative studies of molecular evolution and function.

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