The evolutionary history of the catenin gene family during metazoan evolution

<p>Abstract</p> <p>Background</p> <p>Catenin is a gene family composed of three subfamilies; p120, beta and alpha. Beta and p120 are homologous subfamilies based on sequence and structural comparisons, and are members of the armadillo repeat protein superfamily. Alpha does not appear to be homologous to either beta or p120 based on the lack of sequence and structural similarity, and the alpha subfamily belongs to the vinculin superfamily. Catenins link the transmembrane protein cadherin to the cytoskeleton and thus function in cell-cell adhesion. To date, only the beta subfamily has been evolutionarily analyzed and experimentally studied for its functions in signaling pathways, development and human diseases such as cancer. We present a detailed evolutionary study of the whole catenin family to provide a better understanding of how this family has evolved in metazoans, and by extension, the evolution of cell-cell adhesion.</p> <p>Results</p> <p>All three catenin subfamilies have been detected in metazoans used in the present study by searching public databases and applying species-specific BLAST searches. Two monophyletic clades are formed between beta and p120 subfamilies using Bayesian phylogenetic inference. Phylogenetic analyses also reveal an array of duplication events throughout metazoan history. Furthermore, numerous annotation issues for the catenin family have been detected by our computational analyses.</p> <p>Conclusions</p> <p>Delta2/ARVCF catenin in the p120 subfamily, beta catenin in the beta subfamily, and alpha2 catenin in the alpha subfamily are present in all metazoans analyzed. This implies that the last common ancestor of metazoans had these three catenin subfamilies. However, not all members within each subfamily were detected in all metazoan species. Each subfamily has undergone duplications at different levels (species-specific, subphylum-specific or phylum-specific) and to different extents (in the case of the number of homologs). Extensive annotation problems have been resolved in each of the three catenin subfamilies. This resolution provides a more coherent description of catenin evolution.</p

The sulfur pathway and diagnosis of sulfate depletion in grapevine

Sulfur is an essential nutrient to all plant species. Plants assimilate sulfur in a well-described pathway, which has been taken up by roots. Regulatory mech- anism has been the subject of many research papers. However, recent studies highlighted differences between crop plants and the model plant Arabidopsis thaliana. Our work focuses on the identification of genes involved in the sulfur metabolism in the Vitis vinifera genome, and their response to sulfur deficiency and other abiotic stress endured by grapevine in the field, namely water stress. Here, we describe the identification and brief characterization of the first assimilation enzymes involved in the sulfur pathway, the enzyme responsible for sulfur activa- tion, ATP sulfurylase (ATPS), and the two enzymes that reduce sulfate to sulfide, Adenosine 50-phosphosulate reductase (APR) and Sulfite reductase (SiR). A reduc- tion was observed in the number of ATPS and APR isoforms identified in V. vinifera genome when compared to A. thaliana or Glycine max genomes. Two ATPS isoforms were present in the Vitis genome, of which only ATPS1 transcript was detected in the tested tissues, and one APR isoform, suggesting an absence of redundancy in the role of both enzymes. ATPS1, APR and SiR transcript level was up-regulated in response to 2 days exposure to sulfur deficiency in V. vinifera cell cultures, which was completely reversed by the addition of GSH to the culture medium. Apparently, oxidative stress triggered GSH has a pivotal role in the regulation of ATPS1, APR and SiR transcription level, since their up-regulation was observed in mRNA from field grapevine berries under water stress, which is known to induce oxidative stress.info:eu-repo/semantics/publishedVersio

The desmosome and pemphigus

Desmosomes are patch-like intercellular adhering junctions (“maculae adherentes”), which, in concert with the related adherens junctions, provide the mechanical strength to intercellular adhesion. Therefore, it is not surprising that desmosomes are abundant in tissues subjected to significant mechanical stress such as stratified epithelia and myocardium. Desmosomal adhesion is based on the Ca2+-dependent, homo- and heterophilic transinteraction of cadherin-type adhesion molecules. Desmosomal cadherins are anchored to the intermediate filament cytoskeleton by adaptor proteins of the armadillo and plakin families. Desmosomes are dynamic structures subjected to regulation and are therefore targets of signalling pathways, which control their molecular composition and adhesive properties. Moreover, evidence is emerging that desmosomal components themselves take part in outside-in signalling under physiologic and pathologic conditions. Disturbed desmosomal adhesion contributes to the pathogenesis of a number of diseases such as pemphigus, which is caused by autoantibodies against desmosomal cadherins. Beside pemphigus, desmosome-associated diseases are caused by other mechanisms such as genetic defects or bacterial toxins. Because most of these diseases affect the skin, desmosomes are interesting not only for cell biologists who are inspired by their complex structure and molecular composition, but also for clinical physicians who are confronted with patients suffering from severe blistering skin diseases such as pemphigus. To develop disease-specific therapeutic approaches, more insights into the molecular composition and regulation of desmosomes are required

Seismic site characterization of the Kastelli (Kissamos) Basin in northwest Crete (Greece): Assessments using ambient noise recordings

Crete is actively seismic and site response studies are needed for estimating local site conditions subjected to seismic activity. In order to collect basic data, we performed ambient noise recordings to estimate the site response of the surface and near subsurface structure of the small-scale Kastelli Basin in northwest Crete. The spatial horizontal to vertical spectral ratios (HVSR) resonance pattern of the investigated sites in the centre of the Basin consists of either one or two peaks divided into low to high frequency range in different sites as follows: (a) in some sites only one amplified peak at low frequencies (0.6–1.2 Hz), (b) in other sites only one amplified peak at medium frequencies (2.9–8.5 Hz) and (c) in yet other sites two amplified peaks in the low to high frequency range (0.6–15.5 Hz). The investigated sites are amplified in the frequency range 0.6–15.5 Hz, while the amplitude reaches to a factor of 4 in the spectral ratios. The one HVSR amplified peak at low frequencies is related to locally soft or thick Quaternary deposits. Microtremors were measured in the coastal northwest part of the Basin in a well—lithified Cretaceous limestone site characterized by fractures and faults striking predominantly in a sector NNE to NNW. Sites of one amplified peak at medium frequencies are extended from coastal northwest to southwest delineating a structure striking to NNW. The two amplified peaks are attributed to shallow subsurface heterogeneities/irregularities, locally induced by fault zones and to the overlying Quaternary deposits. Spatial HVSR variations in the frequency and HVSR shape delineate four structures striking NNE, NNW and in a sector NW to WNW, crosscutting the dense populated Basin suggesting that microtremors could be a valuable tool for providing a first approximation of fault zone delineation at least for the Kastelli-Kissamos Basin. The Basin is classified into the X soil category of the Greek Seismic Code 2000.This work was implemented through the project entitled “Interdisciplinary Multi-Scale Research of Earth-quake Physics and Seismotectonics at the Front of the Hellenic Arc (IMPACT-ARC)” in the framework of action “ARCHIMEDES III—Support of Research Teams at TEI of Crete” (MIS380353) of the Operational Program “Education and Lifelong Learning” and is co-financed by the European Union (European Social Fund) and Greek national fund

The monoclonal antibody EPR1614Y against the stem cell biomarker keratin K15 lacks specificity and reacts with other keratins

Keratin 15 (K15), a type I keratin, which pairs with K5 in epidermis, has been used extensively as a biomarker for stem cells. Two commercial antibodies, LHK15, a mouse monoclonal and EPR1614Y, a rabbit monoclonal, have been widely employed to study K15 expression. Here we report differential reactivity of these antibodies on epithelial cells and tissue sections. Although the two antibodies specifically recognised K15 on western blot, they reacted differently on skin sections and cell lines. LHK15 reacted in patches, whereas EPR1614Y reacted homogenously with the basal keratinocytes in skin sections. In cultured cells, LHK15 did not react with K15 deficient NEB-1, KEB-11, MCF-7 and SW13 cells expressing only exogenous K8 and K18 but reacted when these cells were transduced with K15. On the other hand, EPR1614Y reacted with these cells even though they were devoid of K15. Taken together these results suggest that EPR1614Y recognises a conformational epitope on keratin filaments which can be reconstituted by other keratins as well as by K15. In conclusion, this report highlights that all commercially available antibodies may not be equally specific in identifying the K15 positive stem cell

Organization of multiprotein complexes at cell–cell junctions

The formation of stable cell–cell contacts is required for the generation of barrier-forming sheets of epithelial and endothelial cells. During various physiological processes like tissue development, wound healing or tumorigenesis, cellular junctions are reorganized to allow the release or the incorporation of individual cells. Cell–cell contact formation is regulated by multiprotein complexes which are localized at specific structures along the lateral cell junctions like the tight junctions and adherens junctions and which are targeted to these site through their association with cell adhesion molecules. Recent evidence indicates that several major protein complexes exist which have distinct functions during junction formation. However, this evidence also indicates that their composition is dynamic and subject to changes depending on the state of junction maturation. Thus, cell–cell contact formation and integrity is regulated by a complex network of protein complexes. Imbalancing this network by oncogenic proteins or pathogens results in barrier breakdown and eventually in cancer. Here, I will review the molecular organization of the major multiprotein complexes at junctions of epithelial cells and discuss their function in cell–cell contact formation and maintenance

Predicación y ortodoxia en el Persiles

Cervantes was not exempt from the influence exercised in society by the preachers of his time, especially in view of the social and ideological repercussions inherent in the genre of sacred oratory. In this article I study its presence in Cervantes, concretely in the Persiles. By means of an analysis of the examples of preaching registered in the novel, I demonstrate the author’s orthodoxy, as opposed to some recent critical studies that question it.Cervantes no fue ajeno a la influencia que los predicadores ejercían en la sociedad de su tiempo, dada la gran repercusión social, e ideológica, de la que gozó el género oratorio. En este artículo se estudia su presencia en la obra de Cervantes, singularmente en el Persiles, donde a través del análisis de los ejemplos de predicación que se registran en la novela se demuestra su ortodoxia, en contra de aportaciones críticas recientes que la cuestionan

Cancer Biomarker Discovery: The Entropic Hallmark

Background: It is a commonly accepted belief that cancer cells modify their transcriptional state during the progression of the disease. We propose that the progression of cancer cells towards malignant phenotypes can be efficiently tracked using high-throughput technologies that follow the gradual changes observed in the gene expression profiles by employing Shannon's mathematical theory of communication. Methods based on Information Theory can then quantify the divergence of cancer cells' transcriptional profiles from those of normally appearing cells of the originating tissues. The relevance of the proposed methods can be evaluated using microarray datasets available in the public domain but the method is in principle applicable to other high-throughput methods. Methodology/Principal Findings: Using melanoma and prostate cancer datasets we illustrate how it is possible to employ Shannon Entropy and the Jensen-Shannon divergence to trace the transcriptional changes progression of the disease. We establish how the variations of these two measures correlate with established biomarkers of cancer progression. The Information Theory measures allow us to identify novel biomarkers for both progressive and relatively more sudden transcriptional changes leading to malignant phenotypes. At the same time, the methodology was able to validate a large number of genes and processes that seem to be implicated in the progression of melanoma and prostate cancer. Conclusions/Significance: We thus present a quantitative guiding rule, a new unifying hallmark of cancer: the cancer cell's transcriptome changes lead to measurable observed transitions of Normalized Shannon Entropy values (as measured by high-throughput technologies). At the same time, tumor cells increment their divergence from the normal tissue profile increasing their disorder via creation of states that we might not directly measure. This unifying hallmark allows, via the the Jensen-Shannon divergence, to identify the arrow of time of the processes from the gene expression profiles, and helps to map the phenotypical and molecular hallmarks of specific cancer subtypes. The deep mathematical basis of the approach allows us to suggest that this principle is, hopefully, of general applicability for other diseases