ALBERT

Description: Dos géneros de algas rojas Alsidium y Gloiocladia se reportan por primera para Cuba. Las algas fueron recolectadas en la costa de la región centro-sur de la isla. Las muestras fueron identificadas en base a características morfológicas, pero debido a la ausencia de estructuras reproductivas, Alsidium no se definió en un nivel específico. Por otra parte, Gloiocladia iyoensis se identificó con los especímenes de la localidad tipo, descrita en detalle, y su distribución geográfica se amplió.

Description: Two red algal genera Alsidium and Gloiocladia are reported for the first time from Cuba. The algae were collected on the coast of the central- southern region of the island. The samples were identified based on morphological characteristics, but due to the absence of reproductive structures, Alsidium was n ot d efined at a specific level. O n the other hand, Gloiocladia iyoensis was identified with specimens of the type locality, described in detail, and its geographic distribution was enlarged.

Description: Published

Description: Basado en material de herbario de las colecciones de macroalgas depositadas en el Acuario Nacional, Instituto de Ecología y Sistemática y Centro de Investigaciones Marinas, se comunica el hallazgo de dos nuevos registros para la flora marina bentónica de Cuba: Un alga roja, Dichotomaria obtusata var. major (W. R. Taylor) Wynne y un alga parda Sporochnus pedunculatus ( Hudson) C. Agardh. Adicionalmente se añaden nuevos datos de las especies Chrysymenia enteromorpha Harvey y Cladophora sericea (Hudson) Kützing.

Description: Published

Description: Se adiciona a las clorofíceas cubanas la especie Rhipidosiphon floridensis dentro de la familia Udoteaceae (Bryopsidales), colectada específicamente en Bahía de Cochinos, costa sur de Cuba. Esta se caracteriza por un estípite monosifonal, no corticado, rizoides hialinos, láminas calcificadas en forma de abanico, monoestratosas, compuestas por sifones que se ramifican dicotómicamente y se constriñen igual por encima de la dicotomía, a diferencia de R. javensis, especie tipo del género, que tiene constricciones desiguales por encima de la dicotomía.

Description: The specie Rhipidosiphon floridensis is added to the Cuban chlorophytes within the family Udoteaceae (Bryopsidales), collected specifically in Cochinos Bay, southern coast of Cuba. This is characterized by an upright, monosiphonous, uncorticated stipe, fine hyaline rhizoids, and a fan-shaped, unistratose, calcified, terminal blade composed of dichotomously branched siphons, that are constricted just above the dichotomy, unlike R. javensis, which has unequal constraints above the dichotomy.

Description: Published

Description: La Doctora María Elena Ibarra Martin nació el 27 de diciembre de 1932, en Santiago de Cuba. En 1959 fue investigadora del Instituto Cubano de Cartografía y Catastro. De 1960 a 1963 Jefe del Laboratorio de Paleontología y Petrografía del Instituto Cubano del Petróleo y del 1963 a 1968 Jefe del Laboratorio de Paleontología y Petrografía, Instituto Cubano de Recursos Minerales, donde realizó investigaciones micropaleontológicas sobre foraminíferos planctónicos para establecer correlaciones estratigráficas en las perforaciones petroleras en Cuba.

Description: Published

Description: Refereed

Description: Aromatase is an enzyme member of the cytochrome P450 superfamily coded by the CYP19A1 gene. Its main action is the conversion of androgens into estrogens, transforming androstenedione into estrone and testosterone into estradiol. This enzyme is present in several tissues and it has a key role in the maintenance of the balance of androgens and estrogens, and therefore in the regulation of the endocrine system. With regard to chemical safety and human health, azoles, which are used as agrochemicals and pharmaceuticals, are potential endocrine disruptors due to their agonist or antagonist interactions with the human aromatase enzyme. This theoretical study investigated the active agonist and antagonist properties of “chemical classes of azoles” to determine the relationships of azole interaction with CYP19A1, using stereochemical and electronic properties of the molecules through classification and multilinear regression (MLR) modeling. The antagonist activities for the same substituent on diazoles and triazoles vary with its chemical composition and its position and both heterocyclic systems require aromatic substituents. The triazoles require the spherical shape and diazoles have to be in proper proportion of the branching index and the number of ring systems for the inhibition. Considering the electronic aspects, triazole antagonist activity depends on the electrophilicity index that originates from interelectronic exchange interaction (ωHF) and the LUMO energy ( E LUMO PM 7 ), and the diazole antagonist activity originates from the penultimate orbital ( E HOMONL PM 7 ) of diazoles. The regression models for agonist activity show that it is opposed by the static charges but favored by the delocalized charges on the diazoles and thiazoles. This study proposes that the electron penetration of azoles toward heme group decides the binding behavior and stereochemistry requirement for antagonist activity against CYP19A1 enzyme.

Description: Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell (HSC) malignancies characterized by ineffective hematopoiesis. Genetic alterations do not fully explain the molecular pathogenesis of the disease, indicating that other types of lesions, such as transcriptional aberrations, may play a role in its development. Moreover, MDS prevalence is almost exclusive to older patients, suggesting that elderly-related alterations may predispose to the development of this clinical entity. Thus, study of the transcriptional lesions occurring in the aging-MDS axis could shed some light of the molecular bases of the disease. To characterize the transcriptional profile of HSCs in aging and MDS, we isolated CD34+, CD38-, CD90+, CD45RA- cells from 11 untreated MDS patients with unilineage and multilineage dysplasia (median of 75 y/o), as well as from 16 young and 8 elderly healthy donors (median of 21 and 70 y/o, respectively), and their expression profile was analyzed using MARS-seq. Unsupervised principal component analysis demonstrated that the three groups of HSCs clustered separately, indicating that different expression profiles characterize healthy young and elderly, and MDS-associated HSCs. To better understand the gene expression deregulation of HSCs, we analyzed the transcriptional dynamisms along the aging-MDS axis, detecting groups of genes following different patterns of expression. Some gene clusters showed exclusive alteration either in aging or in the progression from elderly HSCs to MDS-HSCs, other groups of genes presented a continuous alteration along the axis, and some displayed opposite regulation in aging and in the transition to MDS (Figure 1). Genes showing specific downregulation in aging were involved in DNA damage sensing and repair, and in cell cycle regulation, whereas genes overexpressed in this process were enriched in apoptosis regulators and in cancer-associated genes, including AML-related factors. These findings indicate that transcriptional changes in aging may predispose for MDS and AML, and potentially other malignancies. Interestingly, we detected a group of genes in which the age-mediated upregulation of gene expression was reversed to that of young HSCs in MDS, indicating a "rejuvenation" profile of malignant HSCs. These genes were involved in response to inflammation, to different types of stress conditions such as hypoxia or radiation, and to cytokines. Elderly HSCs may upregulate such genes in response to the known inflammatory microenvironment of elderly bone marrow. Intriguingly, the decrease in expression detected in MDS suggests that malignant HSCs lose the ability of reacting to such stimuli, possibly favoring their survival in a hostile microenvironment. Finally, the analyses performed allowed for the identification of genes showing MDS-specific deregulation. Genes specifically overexpressed in MDS compared to normal (both young and elderly) HSCs, we enriched in transcriptional and epigenetic regulators, and among them, we detected the presence of DDIT3/CHOP, a member of the CCAAT/enhancer-binding protein (C/EBP) family of transcription factors. To determine its potential effects on hematopoietic deregulation, DDIT3 was exogenously overexpressed in healthy HSCs. Notably, its upregulation produced an erythroid bias in an ex-vivo differentiation system, with an increase in the percentage of erythroblasts and a decrease in granulocytes and monocytes compared to HSCs transduced with the empty vector. Transcriptomic analysis of transduced HSCs not subjected to differentiation demonstrated how DDIT3 overexpression produced an erythroid-prone state of HSCs, suggesting it may act as a pioneer factor in MDS-HSCs. Furthermore, gene set enrichment analysis showed that DDIT3 overexpression produced an MDS-like transcriptional profile, suggesting this factor may be key in the acquisition of the disease. Altogether, our results demonstrate that HSCs undergo transcriptional changes in the aging-MDS axis that may alter their intrinsic functions as well as their response to the microenvironment, ultimately contributing to the acquisition of the disease. In particular, our data show that DDIT3 may be a potential driver of MDS transformation. Disclosures Paiva: Amgen, Bristol-Myers Squibb, Celgene, Janssen, Merck, Novartis, Roche, and Sanofi; unrestricted grants from Celgene, EngMab, Sanofi, and Takeda; and consultancy for Celgene, Janssen, and Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau. Díez-Campelo:Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: Background: Incidence of AML is highest among the elderly and the general outcome is poor as compared to young patients, even those who tolerate intensive induction chemotherapy and achieve morphological CR. However, the role of MRD in redefining CR in elderly AML remains poorly investigated due to the reluctance to treat them with intensive chemotherapy, the renewed interest in low-intensity therapy such as hypomethylating agents (HMA), and the lack of molecular MRD markers in most patients. Aim: To help defining the role of MRD assessment by multidimensional flow cytometry (MFC) and therapeutic decision making in older AML patients treated with semi-intensive chemotherapy vs HMA. Methods: A total of 285 AML patients (excluding APL) with a median age of 75 were included in the phase III PETHEMA-FLUGAZA clinical trial and were randomized to receive 3 induction cycles with fludarabine and cytarabine (FLUGA) followed by 6 consolidation cycles with reduced intensity FLUGA, vs 3 induction cycles with 5-azacitidine (AZA) followed by 6 consolidation cycles with AZA. After consolidation, patients continued with the same treatment if MRD ≥0.01% or stopped if MRD

Description: Introduction: Comorbidities have a significant impact on the prognosis and survival of patients with MDS (Naqvi et al, JCO. 2011). Separately, CHIP associated mutations (TET2, DNMT3A, JAK2 and ASXL1) have also been noted to be associated with comorbidities, particularly atherosclerotic heart disease (Ebert et al. NEJM. 2017). This association is however not well studied in patients in MDS. The objective of this study was to determine the association of these CHIP mutations including TP53 with comorbidities in patients with MDS. Patients and Methods: We conducted a retrospective analysis of 566 consecutive patients with MDS who presented to MD Anderson Cancer Center from August 2013 to December 2016. The Adult Comorbidity Evaluation-27 (ACE-27) scale was used to assess the severity of comorbid conditions. Data on the demographics and International Prognostic Scoring System Revised (IPSS-R) were collected. We used next-generation sequencing to detect the presence of CHIP mutations in bone marrow samples. Spearman's correlation coefficient was used to assess the association between CHIP associated gene mutations as binary variables by the presence of mutations, and continuous variables by variant allele frequency (VAF) and comorbidities. Kaplan-Meier methods and Cox regression were used to assess survival. A prognostic model incorporating the IPSS-R, comorbidities by ACE-27 and TP53 mutation status (I-RAT) was developed to predict survival. Results: Of the 566 patients included in this study, 66% were male, and 82% were white; median age at presentation was 69 years (range: 22-93). A total of 334 (58%) patients had an IPSS-R of Intermediate, low and very low; complex karyotype was noted in 128 (23%) patients. The ACE-27 comorbidity scores were as follows: none, 101 (17%); mild, 214 (38%); moderate, 146 (26%); and severe, 105 (19%). Mutations in DNMT3A, ASXL1, TET2, JAK2 and TP53 were noted in 9%, 18%, 20%, 2% and 21% patients respectively. Two hundred and fifty (44%) MDS patients had no CHIP-associated mutations. With respect to the cardiovascular system, patients harboring DNMT3A were noted to have a higher incidence of myocardial infarction than those without DNMT3A mutation (14% vs 6%; p= 0.03). As expected, patients with a JAK2 mutation had higher number of venous thromboembolic events (18% vs 4%; p= 0.013). TET2, ASXL1 and TP53 mutations however were not associated with increased cardiovascular events in our patients. TP53 mutations were highly associated with history of prior malignancy: solid tumors, 44% vs 21%; p=

Description: The ABCB1 transporter also known as P-glycoprotein (P-gp) is a transmembrane protein belonging to the ATP binding cassette super-family of transporters; it is a xenobiotic efflux pump that limits intracellular drug accumulation by pumping the compounds out of cells. P-gp contributes to a decrease of toxicity and possesses broad substrate specificity. It is involved in the failure of numerous anticancer and antiviral chemotherapies due to the multidrug resistance (MDR) phenomenon, where it removes the chemotherapeutics out of the targeted cells. Understanding the details of the ligand–P-gp interaction is therefore crucial for the development of drugs that might overcome the MRD phenomenon and for obtaining a more effective prediction of the toxicity of certain compounds. In this work, an in silico modeling was performed using homology modeling and molecular docking methods with the aim of better understanding the ligand–P-gp interactions. Based on different mouse P-gp structural templates from the PDB repository, a 3D model of the human P-gp (hP-gp) was constructed by means of protein homology modeling. The homology model was then used to perform molecular docking calculations on a set of thirteen compounds, including some well-known compounds that interact with P-gp as substrates, inhibitors, or both. The sum of ranking differences (SRD) was employed for the comparison of the different scoring functions used in the docking calculations. A consensus-ranking scheme was employed for the selection of the top-ranked pose for each docked ligand. The docking results showed that a high number of π interactions, mainly π–sigma, π–alkyl, and π–π type of interactions, together with the simultaneous presence of hydrogen bond interactions contribute to the stability of the ligand–protein complex in the binding site. It was also observed that some interacting residues in hP-gp are the same when compared to those observed in a co-crystallized ligand (PBDE-100) with mouse P-gp (PDB ID: 4XWK). Our in silico approach is consistent with available experimental results regarding P-gp efflux transport assay; therefore it could be useful in the prediction of the role of new compounds in systemic toxicity.

Description: Myelodysplastic syndromes (MDS) are clinically heterogeneous hematological malignancies with a propensity to evolve to acute myeloid leukemia. Recent studies have suggested that the different MDS risk subgroups are characterized by distinct hematopoietic architectures [Will 2012; Pang 2013], but the contribution of the specific hematopoietic stem cell (HSC) compartments to the aberrant differentiation responsible for the MDS phenotype and their role in disease progression are not fully understood. Although it is known that the cells that maintain the disease in the low-risk (LR) subgroup reside in the primitive long-term (LT)-HSC subset [Pang 2013], little is known about the hierarchical organization of high-risk (HR) disease. A detailed understanding of the architecture and dynamics of the HSC populations during MDS evolution could precisely identify the HSC responsible for relapse, and molecular characterization of these cells may allow for effective disease monitoring and progression prevention. With this purpose, we have immunophenotypically characterized the stem and progenitor cell compartments in 75 BM samples isolated from 67 patients with low- and high-risk MDS at different stages of the disease and have analyzed the variant allelic frequency in the HSC compartment of 280 leukemia-relevant genes by targeted next-generation sequencing. Our analyses show that MDS can be classified into 2 biological entities based on the cellular architecture of the stem and progenitor compartments and independently of the risk stratification. Indeed, when compared to 8 healthy donor controls, 10 patients at baseline (38%; 3 LR, 7 HR) showed a "CMP pattern of differentiation" characterized by a decreased number of granulocytic-monocytic progenitors (GMP) (5.3-fold; p=0.002), with no significant changes in the number of the common myeloid progenitors (CMP) and megakaryocytic-erythroid progenitors (MEP). Decreased GMP counts resulted in a higher frequency of the CMP (2.7-fold; p