The BH4 domain of Bcl-2 orthologues from different classes of vertebrates can act as an evolutionary conserved inhibitor of IP3 receptor channels

Heterogeneity of erythrocyte glucose-6-phosphate dehydrogenase (G6PD, E.C. 1.1.1.49) activity and electrophoretic patterns among representatives of different classes of vertebrates

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In the last decades, the use and misuse of pesticides in the agriculture have increased, having a severe impact on ecosystems and their fauna. Although the various effects of pesticides on biodiversity have been already documented in several studies, to our knowledge no consistent overview of the impact of pesticides in vertebrates, both terrestrial and aquatic, is available. In this review, we try to present a concise compilation of the teratogenic effects of pesticides on the different classes of vertebrates – mammals, birds, reptiles, amphibians and fish.

Background. Glycoproteins (including mucin) of vertebrate’s intestine play an important role in its protection against chemical and mechanical damage and bacterial attacks. Their diversity was described by many authors, but understanding of their chemical structure remains far from complete. These data can be extended by methods of lectin histochemistry. Objective. To investigate the rearrangement of intestinal carbohydrate determinants in the context of vertebrate evolution. Methods. Distal and proximal segments of small and large intestines of humans (Homo sapiens), laboratory (Wistar) rat (Rattus norvegicus f. Domesticus), rock pigeon (Columba livia), smooth snake (Coronella austriaca), common frog (Rana temporaria), common carp (Cyprinus carpio) that belong to different classes of vertebrates were taken for the experiment. Nine lectins with different carbohydrate specificities: wheat germ (WGA), potato (STA), elderberry bark (SNA), golden rain bark (LABA), locust bark (RPBA), roe carp (CCRA), Phaseolus vulgaris erytroagglutinin (PHA-E), peanut (PNA) and jack fruit (AIA) – were included into the panel. Results. Differences in lectin staining between small and large intestine were more pronounced in higher (human, rat) than in lower (frog, carp) vertebrates. Lectin receptors were more diverse in frog intestine in comparison with carp. Lectin interaction with mucin secretory granules of smooth snake revealed lack of N-acetyl-D-glucosamine residues and abundance of N-acetyl-D-galactosamine determinants. Conclusion. Intestines of all studied vertebrate species demonstrate high content of secretory mucins that exposed terminal acidic carbohydrates including sialic acid. The diversity and differences in the structure of glycans of the digestive tract of vertebrates is apparently determined by several factors – diet, environmental and living conditions, intestinal microbiota interactions etc.

The reactions of the mature erythrocytes of seventeen species of fishes to the vital dyes neutral red, Janus green B, and brilliant cresyl blue, have been studied. In most teleosts the primary vital granules are readily demonstrated by neutral red and consist of one or two small granules eccentrically placed near one pole of the nucleus, but in the menhaden, alewife, and mackerel the primary granules are most numerous and are either arranged in a single definite line about the nucleus or scattered irregularly throughout the cytoplasm. In the elasmobranchs the granules are large, numerous, and scattered. In a majority of the teleosts the primary granules may be demonstrated as basophilic bodies in dry films stained by Wright's method and are also frequently seen in fresh unstained preparations.Secondary or induced granules may also appear in the cytoplasm of cells exposed for long periods to the dye. The degree of induction of new bodies does not appear to depend entirely on external factors but is determined to a large extent by factors inherent in the cytoplasm of the given species. In general the mitochondria are filamentous, reduced in number, and lie in chose contact with the surface of the nucleus.The reticular substance in all mature erythrocytes of the fishes is greatly reduced and appears either as short irregular filaments or as minute granular remnants. It is best demonstrated with brilliant cresyl blue.An attempt is made to compare the relative degree of differentiation attained by the mature erythrocytes of the several classes of vertebrates. The following criteria have been considered: changes in nuclear-cytoplasmic ratio; chromatin distribution in the nucleus; involution of the nucleoli; loss of basophilia; changes in the form, distribution, and volume of mitochondrial substance; reduction of reticular substance; amount of primary granules; and degree of induction of secondary granules. Of these criteria the degree of persistence of reticulation has been found to be the most consistent, and on this basis the several classes of vertebrates are arranged in the following ascending order of relative differentiation attained by their erythrocytes at maturity: amphibians, reptiles, fishes, birds, and mammals. This arrangement is also supported by the behavior of the nucleoli, which persist in the erythrocytes f amphibians and reptiles but are not usually demonstrated in the mature cells of fishes and birds.The history of the primary and secondary granules is less regular and consequently less useful for measuring the relative differentiation attained by the cells of different classes of vertebrates. However, within a given class of vertebrates it is concluded that the presence of a large number of primary granules or the rapid induction of new granules in mature cells may be regarded as supplementary evidence of a lesser degree of differentiation. The presence of primary granules or the degree of induction of new granules, however, cannot always be correlated with the degree of persistence of reticulation.It is also concluded on the basis of this survey of the vertebrate erythrocyte that primary granules, secondary granules, and patterns of reticulation as revealed by vital dyes, must be regarded as three separate entities which are not genetically related.

Induction and Dorsoventral Patterning of the Telencephalon

Glucosensing and glucose homeostasis: From fish to mammals

The B cell lymphoma-2 (Bcl-2) homologs myeloid cell leukemia-1 (Mcl-1) and A1 are prosurvival factors that selectively bind a subset of proapoptotic Bcl homology (BH) 3-only proteins. To investigate the molecular basis of the selectivity, we determined the solution structure of the C-terminal Bcl-2-like domain of Mcl-1. This domain shares features expected of a prosurvival Bcl-2 protein, having a helical fold centered on a core hydrophobic helix and a surface-exposed hydrophobic groove for binding its cognate partners. A number of residues in the binding groove differentiate Mcl-1 from its homologs, and in contrast to other Bcl-2 homologs, Mcl-1 has a binding groove in a conformation intermediate between the open structures characterized by peptide complexes and the closed state observed in unliganded structures. Mutagenesis of potential binding site residues was used to probe the contributions of groove residues to the binding properties of Mcl-1. Although mutations in Mcl-1 had little impact on binding, a single mutation in the BH3-only ligand Bad enabled it to bind both Mcl-1 and A1 while retaining its binding to Bcl-2, Bcl-xL, and Bcl-w. Elucidating the selective action of certain BH3-only ligands is required for delineating their mode of action and will aid the search for effective BH3-mimetic drugs.

Comparison of nucleotide sequences from different classes of vertebrates that diverged more than 300 million years ago, revealed the existence of highly conserved regions (HCRs) with more than 70% similarity over 100 to 1450 nt in non-coding parts of genes. Such a conservation is unexpected because it is much longer and stronger than what is necessary for specifying the binding of a regulatory protein. HCRs are relatively frequent, particularly in genes that are essential to cell life. In multigene families, conserved regions are specific of each isotype and are probably involved in the control of their specific pattern of expression. Studying HCRs distribution within genes showed that functional constraints are generally much stronger in 3'-non-coding regions than in promoters or introns. The 3'-HCRs are particularly A + T-rich and are always located in the transcribed untranslated regions of genes, which suggests that they are involved in post-transcriptional processes. However, current knowledge of mechanisms that regulate mRNA export, localisation, translation, or degradation is not sufficient to explain the strong functional constraints that we have characterised.

Neurodegenerative diseases afflict a significant percentage of the world's population. The human nervous system is unable to regenerate after an insult, or due to senility, while low vertebrates still exhibit this ability. Comparative neurobiology can increase knowledge about neuronal degeneration and regeneration. Anamni vertebrates retain the ability to regenerate up to large areas of the nervous system. The regenerative ability of central nervous system components depends on the phylogenetic distance between classes of vertebrates. It decreases during evolution. Teleosts can skilfully regenerate brain, spinal cord and retina. Amphibians and reptiles can only regenerate certain areas; spinal cord regeneration in reptiles is limited to axonal regrowth. Retina regeneration is possible in bird embryo but not in the adult. In this review, we analyse how the regeneration of neurons occurs in different classes of vertebrates, and how the study of these mechanisms could be applied to the search for new therapies for neurodegenerative disorders.

Stimulating neuronal regeneration is a potential strategy to treat sight-threatening diseases of the retina. In some classes of vertebrates, retinal regeneration occurs spontaneously to effectively replace neurons lost to acute damage in order to restore visual function. There are different mechanisms and cellular sources of retinal regeneration in different species, include the retinal pigmented epithelium, progenitors seeded across the retina, and the Müller glia. This review briefly summarizes the different mechanisms of retinal regeneration in frogs, fish, chicks, and rodents. The bulk of this review summarizes and discusses recent findings regarding regeneration from Müller glia-derived progenitors, with emphasis on findings in the chick retina. The Müller glia are a promising source of regeneration-supporting cells that are intrinsic to the retina and significant evidence indicated these glias can be stimulated to produce neurons in different classes of vertebrates. The key to harnessing the neurogenic potential of Müller glia is to identify the secreted factors, signaling pathways, and transcription factors that enable de-differentiation, proliferation, and neurogenesis. We review findings regarding the roles of mitogen-activated protein kinase and notch signaling in the proliferation and generation of Müller glia-derived retinal progenitors.

Marking vertebrates langerhans cells, from fish to mammals

BackgroundInterferon regulatory factors (IRFs), which can be identified based on a unique helix-turn-helix DNA-binding domain (DBD) are a large family of transcription factors involved in host immune response, haemotopoietic differentiation and immunomodulation. Despite the identification of ten IRF family members in mammals, and some recent effort to identify these members in fish, relatively little is known in the composition of these members in other classes of vertebrates, and the evolution and probably the origin of the IRF family have not been investigated in vertebrates.ResultsGenome data mining has been performed to identify any possible IRF family members in human, mouse, dog, chicken, anole lizard, frog, and some teleost fish, mainly zebrafish and stickleback, and also in non-vertebrate deuterostomes including the hemichordate, cephalochordate, urochordate and echinoderm. In vertebrates, all ten IRF family members, i.e. IRF-1 to IRF-10 were identified, with two genes of IRF-4 and IRF-6 identified in fish and frog, respectively, except that in zebrafish exist three IRF-4 genes. Surprisingly, an additional member in the IRF family, IRF-11 was found in teleost fish. A range of two to ten IRF-like genes were detected in the non-vertebrate deuterostomes, and they had little similarity to those IRF family members in vertebrates as revealed in genomic structure and in phylogenetic analysis. However, the ten IRF family members, IRF-1 to IRF-10 showed certain degrees of conservation in terms of genomic structure and gene synteny. In particular, IRF-1, IRF-2, IRF-6, IRF-8 are quite conserved in their genomic structure in all vertebrates, and to a less degree, some IRF family members, such as IRF-5 and IRF-9 are comparable in the structure. Synteny analysis revealed that the gene loci for the ten IRF family members in vertebrates were also quite conservative, but in zebrafish conserved genes were distributed in a much longer distance in chromosomes. Furthermore, all ten different members are clustered in respectively different clades; but the IRF-11 was clustered with one in sea urchin.ConclusionsIn vertebrates, the ten well-characterized IRF family members shared a relatively high degree of similarity in genomic structure and syntenic gene arrangement, implying that they might have been evolved in a similar pattern and with similar selective pressure in different classes of vertebrates. Genome and/or gene duplication, and probably gene shuffling or gene loss might have occurred during the evolution of these IRF family members, but arrangement of chromosome or its segment might have taken place in zebrafish. However, the ten IRF family members in vertebrates and those IRF-like genes in non-vertebrate deuterostomes were quite different in those analyzed characters, as they might have undergone different patterns of evolution.

Phylogenetic conservation of brain microtubule-associated proteins MAP2 and TAU

Anti-apoptotic Bcl-2-family members not only neutralize pro-apoptotic proteins but also directly regulate intracellular Ca(2+) signaling from the endoplasmic reticulum (ER), critically controlling cellular health, survival, and death initiation. Furthermore, distinct Bcl-2-family members may selectively regulate inositol 1,4,5-trisphosphate receptor (IP3R): Bcl-2 likely acts as an endogenous inhibitor of the IP3R, preventing pro-apoptotic Ca(2+) transients, while Bcl-XL likely acts as an endogenous IP3R-sensitizing protein promoting pro-survival Ca(2+) oscillations. Furthermore, distinct functional domains in Bcl-2 and Bcl-XL may underlie the divergence in IP3R regulation. The Bcl-2 homology (BH) 4 domain, which targets the central modulatory domain of the IP3R, is likely to be Bcl-2's determining factor. In contrast, the hydrophobic cleft targets the C-terminal Ca(2+)-channel tail and might be more crucial for Bcl-XL's function. Furthermore, one amino acid critically different in the sequence of Bcl-2's and Bcl-XL's BH4 domains underpins their selective effect on Ca(2+) signaling and distinct biological properties of Bcl-2 versus Bcl-XL. This difference is evolutionary conserved across five classes of vertebrates and may represent a fundamental divergence in their biological function. Moreover, these insights open novel avenues to selectively suppress malignant Bcl-2 function in cancer cells by targeting its BH4 domain, while maintaining essential Bcl-XL functions in normal cells. Thus, IP3R-derived molecules that mimic the BH4 domain's binding site on the IP3R may function synergistically with BH3-mimetic molecules selectivity suppressing Bcl-2's proto-oncogenic activity. Finally, a more general role for the BH4 domain on IP3Rs, rather than solely anti-apoptotic, may not be excluded as part of a complex network of molecular interactions.