85 research outputs found
Endosymbiotic calcifying bacteria across sponge species and oceans
Este artĂculo contiene 14 páginas, 7 figuras, 1 tabla.From an evolutionary point of view, sponges are ideal targets to study marine symbioses as they are the
most ancient living metazoans and harbour highly diverse microbial communities. A recently discovered
association between the sponge Hemimycale columella and an intracellular bacterium that generates
large amounts of calcite spherules has prompted speculation on the possible role of intracellular
bacteria in the evolution of the skeleton in early animals. To gain insight into this purportedly ancestral
symbiosis, we investigated the presence of symbiotic bacteria in Mediterranean and Caribbean
sponges. We found four new calcibacteria OTUs belonging to the SAR116 in two orders (Poecilosclerida
and Clionaida) and three families of Demospongiae, two additional OTUs in cnidarians and one more
in seawater (at 98.5% similarity). Using a calcibacteria targeted probe and CARD-FISH, we also found
calcibacteria in Spirophorida and Suberitida and proved that the calcifying bacteria accumulated at
the sponge periphery, forming a skeletal cortex, analogous to that of siliceous microscleres in other
demosponges. Bacteria-mediated skeletonization is spread in a range of phylogenetically distant
species and thus the purported implication of bacteria in skeleton formation and evolution of early
animals gains relevance.The research has been funded by MARSYMBIOMICS
project (Spanish MINECO, CTM2013-43287-P) BluePharmTrain (FP7 People-INT, Ref. 2013- 667786), and
Grup Consolidat SGR-120, to MJU. LG benefited from a fellowship within the Benthomics project (Spanish
MICINN, CTM-2010-22218-C02-01).Peer reviewe
Molecular phylogenies confirm the presence of two cryptic Hemimycale species in the Mediterranean and reveal the polyphyly of the genera Crella and Hemimycale (Demospongiae: Poecilosclerida)
Este artĂculo contiene 24 páginas, 4 figuras, 3 tablas.Background: Sponges are particularly prone to hiding cryptic species as their
paradigmatic plasticity often favors species phenotypic convergence as a result of
adaptation to similar habitat conditions. Hemimycale is a sponge genus (Family
Hymedesmiidae, Order Poecilosclerida) with four formally described species, from
which only Hemimycale columella has been recorded in the Atlanto-Mediterranean
basin, on shallow to 80 m deep bottoms. Contrasting biological features between
shallow and deep individuals of Hemimycale columella suggested larger genetic
differences than those expected between sponge populations. To assess whether
shallow and deep populations indeed belong to different species, we performed a
phylogenetic study of Hemimycale columella across the Mediterranean. We
also included other Hemimycale and Crella species from the Red Sea, with the
additional aim of clarifying the relationships of the genus Hemimycale.
Methods: Hemimycale columella was sampled across the Mediterranean, and
Adriatic Seas. Hemimycale arabica and Crella cyathophora were collected from
the Red Sea and Pacific. From two to three specimens per species and locality
were extracted, amplified for Cytochrome C Oxidase I (COI) (M1–M6 partition),
18S rRNA, and 28S (D3–D5 partition) and sequenced. Sequences were aligned using
Clustal W v.1.81. Phylogenetic trees were constructed under neighbor joining (NJ),
Bayesian inference (BI), and maximum likelihood (ML) criteria as implemented in
Geneious software 9.01. Moreover, spicules of the target species were observed
through a Scanning Electron microscope.
Results: The several phylogenetic reconstructions retrieved both Crella and
Hemimycale polyphyletic. Strong differences in COI sequences indicated that
C. cyathophora from the Red Sea might belong in a different genus, closer to
Hemimycale arabica than to the Atlanto-Mediterranean Crella spp. Molecular and
external morphological differences between Hemimycale arabica and the Atlanto-
Mediterranean Hemimycale also suggest that Hemimycale arabica fit in a separate
genus. On the other hand, the Atlanto-Mediterranean Crellidae appeared in 18S
and 28S phylogenies as a sister group of the Atlanto-Mediterranean Hemimycale.
Moreover, what was known up to now as Hemimycale columella, is formed by two cryptic species with contrasting bathymetric distributions. Some small
but consistent morphological differences allow species distinction.
Conclusions: A new family (Hemimycalidae) including the genus Hemimycale and
the two purported new genera receiving C. cyathophora and Hemimycale arabica
might be proposed according to our phylogenetic results. However, the inclusion
of additional Operational Taxonomic Unit (OTUs) appears convenient before taking
definite taxonomical decisions. A new cryptic species (Hemimycale mediterranea
sp. nov.) is described. Morphologically undifferentiated species with contrasting
biological traits, as those here reported, confirm that unidentified cryptic species
may confound ecological studies.The research has been funded by MARSYMBIOMICS project (Spanish MINECO,
CTM2013-43287-P), BluePharmTrain (FP7 People-INT, Ref. 2013-667786), and Grup
Consolidat SGR-120, to Maria J. Uriz. Leire Garate benefited from a fellowship within
the Benthomics project (Spanish MICINN, CTM-2010-22218-C02-01).Peer reviewe
MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations
The development of Imatinib Mesylate (IM), the first specific inhibitor of BCR-ABL1, has had a major impact in patients with Chronic Myeloid Leukemia (CML), establishing IM as the standard therapy for CML. Despite the clinical success obtained with the use of IM, primary resistance to IM and molecular evidence of persistent disease has been observed in 20-25% of IM treated patients. The existence of second generation TK inhibitors, which are effective in patients with IM resistance, makes identification of predictors of resistance to IM an important goal in CML. In this study, we have identified a group of 19 miRNAs that may predict clinical resistance to IM in patients with newly diagnosed CML
In-silico gene essentiality analysis of polyamine biosynthesis reveals APRT as a potential target in cancer
Constraint-based modeling for genome-scale metabolic networks has emerged in the last years as a promising approach to elucidate drug targets in cancer. Beyond the canonical biosynthetic routes to produce biomass, it is of key importance to focus on metabolic routes that sustain the proliferative capacity through the regulation of other biological means in order to improve in-silico gene essentiality analyses. Polyamines are polycations with central roles in cancer cell proliferation, through the regulation of transcription and translation among other things, but are typically neglected in in silico cancer metabolic models. In this study, we analysed essential genes for the biosynthesis of polyamines. Our analysis corroborates the importance of previously known regulators of the pathway, such as Adenosylmethionine Decarboxylase 1 (AMD1) and uncovers novel enzymes predicted to be relevant for polyamine homeostasis. We focused on Adenine phosphoribosyltransferase (APRT) and demonstrated the detrimental consequence of APRT gene silencing on diferent leukaemia cell lines. Our results highlight the importance of revisiting the metabolic models used for in-silico gene essentiality analyses in order to maximize the potential for drug target identifcation in cance
MicroRNA expression profiling in Imatinib-resistant Chronic Myeloid Leukemia patients without clinically significant ABL1-mutations
The development of Imatinib Mesylate (IM), the first specific inhibitor of BCR-ABL1, has had a major impact in patients with Chronic Myeloid Leukemia (CML), establishing IM as the standard therapy for CML. Despite the clinical success obtained with the use of IM, primary resistance to IM and molecular evidence of persistent disease has been observed in 20-25% of IM treated patients. The existence of second generation TK inhibitors, which are effective in patients with IM resistance, makes identification of predictors of resistance to IM an important goal in CML. In this study, we have identified a group of 19 miRNAs that may predict clinical resistance to IM in patients with newly diagnosed CML
Frequent and simultaneous epigenetic inactivation of TP53 pathway genes in acute lymphoblastic leukemia
Aberrant DNA methylation is one of the most frequent alterations in patients with Acute Lymphoblastic Leukemia (ALL). Using methylation bead arrays we analyzed the methylation status of 807 genes implicated in cancer in a group of ALL samples at diagnosis (n = 48). We found that 154 genes were methylated in more than 10% of ALL samples. Interestingly, the expression of 13 genes implicated in the TP53 pathway was downregulated by hypermethylation. Direct or indirect activation of TP53 pathway with 5-aza-2'-deoxycitidine, Curcumin or Nutlin-3 induced an increase in apoptosis of ALL cells. The results obtained with the initial group of 48 patients was validated retrospectively in a second cohort of 200 newly diagnosed ALL patients. Methylation of at least 1 of the 13 genes implicated in the TP53 pathway was observed in 78% of the patients, which significantly correlated with a higher relapse (p = 0.001) and mortality (p<0.001) rate being an independent prognostic factor for disease-free survival (DFS) (p = 0.006) and overall survival (OS) (p = 0.005) in the multivariate analysis. All these findings indicate that TP53 pathway is altered by epigenetic mechanisms in the majority of ALL patients and correlates with prognosis. Treatments with compounds that may reverse the epigenetic abnormalities or activate directly the p53 pathway represent a new therapeutic alternative for patients with ALL
Methylation status of Wnt signaling pathway genes affects the clinical outcome of Philadelphia-positive acute lymphoblastic leukemia
The clinical significance of aberrant promoter methylation of the
canonical Wnt pathway antagonist genes (sFRP1, sFRP2, sFRP4,
sFRP5, Wif1, Dkk3, and Hdpr1) and also putative tumor-suppressor
gene Wnt5a, belonging to the non-canonical Wnt signaling pathway,
was investigated in a large series of 75 patients with Philadelphia
chromosome-positive acute lymphoblastic leukemia by methylationspecific
polymerase chain reaction. At least one methylated gene
was observed in cells from 66% (49/75) of patients (methylated
group). Disease-free survival and overall survival at 9 years were 51
and 40%, respectively, for the unmethylated group and 3 and 2%,
respectively, for the methylated group (both P < 0.0001). Multivariate
analysis demonstrated that the Wnt methylation profile was an
independent prognostic factor predicting disease-free survival
(P = 0.007) and overall survival (P = 0.039). Abnormal DNA methylation
of promoter-associated CpG islands in the Wnt signaling pathway is
very common in Philadelphia chromosome-positive acute lymphoblastic
leukemia and potentially defines subgroups with distinct
clinical characteristics
Epigenetic regulation of human cancer/testis antigen gene, HAGE, in chronic myeloid leukemia
Cancer testis antigens (CTA) provide attractive targets for cancer-specific immunotherapy.
Although CTA genes are expressed in some normal tissues, such as the testis,
this immunologically protected site lacks MHC I expression and as such, does not
present self antigens to T cells. To date, CTA genes have been shown to be expressed
in a range of solid tumors via demethylation of their promoter CpG islands, but rarely
in chronic myeloid leukemia (CML) or other hematologic malignancies
Promoter hypomethylation of the LINE-1 retrotransposable elements activates sense/antisense transcription and marks the progression of chronic myeloid leukemia
Aberrant genome-wide hypomethylation is thought to be
related to tumorigenesis by promoting genomic instability.
Since DNA methylation is considered an important mechanism
for the silencingof retroelements, hypomethylation
in human tumors may lead to their reactivation. However,
the role of DNA hypomethylation in chronic myeloid
leukemia (CML) remains to be elucidated. In this study,
the methylation status of the LINE-1 (L1) retrotransposon
promoter was analysed in CML samples from the chronicphase
(CP, nÂĽ140) and the blast crisis (BC, nÂĽ47). L1
hypomethylation was significantly more frequent in BC
(74.5%) than in CP (38%) (Po0.0001). Furthermore,
L1 hypomethylation led to activation of both ORF1 sense
transcription (Po0.0001) and c-MET gene antisense
transcription (Po0.0001), and was significantly associated
with high levels of BCR–ABL (P¼0.02) and
DNMT3b4 (PÂĽ0.001) transcripts. Interestingly, in
CP-CML, extensive L1 hypomethylation was associated
with poorer prognosis in terms of cytogenetic response
to interferon (PÂĽ0.004) or imatinib (PÂĽ0.034) and
progression-free survival (PÂĽ0.005). The above results
strongly suggest that activation of both sense and
antisense transcriptions by aberrant promoter hypomethylation
of the L1 elements plays a role in the progression
and clinical behavior of the CML
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