The Secret Life of Translation Initiation in Prostate Cancer

Prostate cancer (PCa) is the second most prevalent cancer in men worldwide. Despite the advances understanding the molecular processes driving the onset and progression of this disease, as well as the continued implementation of screening programs, PCa still remains a significant cause of morbidity and mortality, in particular in low-income countries. It is only recently that defects of the translation process, i.e., the synthesis of proteins by the ribosome using a messenger (m)RNA as a template, have begun to gain attention as an important cause of cancer development in different human tissues, including prostate. In particular, the initiation step of translation has been established to play a key role in tumorigenesis. In this review, we discuss the state-of-the-art of three key aspects of protein synthesis in PCa, namely, misexpression of translation initiation factors, dysregulation of the major signaling cascades regulating translation, and the therapeutic strategies based on pharmacological compounds targeting translation as a novel alternative to those based on hormones controlling the androgen receptor pathway

Pyrophosphate-Dependent ATP Formation from Acetyl Coenzyme A in Syntrophus aciditrophicus, a New Twist on ATP Formation.

UnlabelledSyntrophus aciditrophicus is a model syntrophic bacterium that degrades key intermediates in anaerobic decomposition, such as benzoate, cyclohexane-1-carboxylate, and certain fatty acids, to acetate when grown with hydrogen-/formate-consuming microorganisms. ATP formation coupled to acetate production is the main source for energy conservation by S. aciditrophicus However, the absence of homologs for phosphate acetyltransferase and acetate kinase in the genome of S. aciditrophicus leaves it unclear as to how ATP is formed, as most fermentative bacteria rely on these two enzymes to synthesize ATP from acetyl coenzyme A (CoA) and phosphate. Here, we combine transcriptomic, proteomic, metabolite, and enzymatic approaches to show that S. aciditrophicus uses AMP-forming, acetyl-CoA synthetase (Acs1) for ATP synthesis from acetyl-CoA. acs1 mRNA and Acs1 were abundant in transcriptomes and proteomes, respectively, of S. aciditrophicus grown in pure culture and coculture. Cell extracts of S. aciditrophicus had low or undetectable acetate kinase and phosphate acetyltransferase activities but had high acetyl-CoA synthetase activity under all growth conditions tested. Both Acs1 purified from S. aciditrophicus and recombinantly produced Acs1 catalyzed ATP and acetate formation from acetyl-CoA, AMP, and pyrophosphate. High pyrophosphate levels and a high AMP-to-ATP ratio (5.9 ± 1.4) in S. aciditrophicus cells support the operation of Acs1 in the acetate-forming direction. Thus, S. aciditrophicus has a unique approach to conserve energy involving pyrophosphate, AMP, acetyl-CoA, and an AMP-forming, acetyl-CoA synthetase.ImportanceBacteria use two enzymes, phosphate acetyltransferase and acetate kinase, to make ATP from acetyl-CoA, while acetate-forming archaea use a single enzyme, an ADP-forming, acetyl-CoA synthetase, to synthesize ATP and acetate from acetyl-CoA. Syntrophus aciditrophicus apparently relies on a different approach to conserve energy during acetyl-CoA metabolism, as its genome does not have homologs to the genes for phosphate acetyltransferase and acetate kinase. Here, we show that S. aciditrophicus uses an alternative approach, an AMP-forming, acetyl-CoA synthetase, to make ATP from acetyl-CoA. AMP-forming, acetyl-CoA synthetases were previously thought to function only in the activation of acetate to acetyl-CoA

Virulence Genes among Enterococcus faecalis

Most Enterococcus faecalis and E. faecium are harmless to humans; however, strains harboring virulence genes, including esp, gelE, cylA, asa1, and hyl, have been associated with human infections. E. faecalis and E. faecium are present in beach waters worldwide, yet little is known about their virulence potential. Here, multiplex PCR was used to compare the distribution of virulence genes among E. faecalis and E. faecium isolated from beaches in Southern California and Puerto Rico to isolates from potential sources including humans, animals, birds, and plants. All five virulence genes were found in E. faecalis and E. faecium from beach water, mostly among E. faecalis. gelE was the most common among isolates from all source types. There was a lower incidence of asa1, esp, cylA, and hyl genes among isolates from beach water, sewage, septage, urban runoff, sea wrack, and eelgrass as compared to human isolates, indicating that virulent strains of E. faecalis and E. faecium may not be widely disseminated at beaches. A higher frequency of asa1 and esp among E. faecalis from dogs and of asa1 among birds (mostly seagull) suggests that further studies on the distribution and virulence potential of strains carrying these genes may be warranted

A genome-wide association study follow-up suggests a possible role for PPARG in systemic sclerosis susceptibility

Introduction: A recent genome-wide association study (GWAS) comprising a French cohort of systemic sclerosis (SSc) reported several non-HLA single-nucleotide polymorphisms (SNPs) showing a nominal association in the discovery phase. We aimed to identify previously overlooked susceptibility variants by using a follow-up strategy.<p></p> Methods: Sixty-six non-HLA SNPs showing a P value <10-4 in the discovery phase of the French SSc GWAS were analyzed in the first step of this study, performing a meta-analysis that combined data from the two published SSc GWASs. A total of 2,921 SSc patients and 6,963 healthy controls were included in this first phase. Two SNPs, PPARG rs310746 and CHRNA9 rs6832151, were selected for genotyping in the replication cohort (1,068 SSc patients and 6,762 healthy controls) based on the results of the first step. Genotyping was performed by using TaqMan SNP genotyping assays. Results: We observed nominal associations for both PPARG rs310746 (PMH = 1.90 × 10-6, OR, 1.28) and CHRNA9 rs6832151 (PMH = 4.30 × 10-6, OR, 1.17) genetic variants with SSc in the first step of our study. In the replication phase, we observed a trend of association for PPARG rs310746 (P value = 0.066; OR, 1.17). The combined overall Mantel-Haenszel meta-analysis of all the cohorts included in the present study revealed that PPARG rs310746 remained associated with SSc with a nominal non-genome-wide significant P value (PMH = 5.00 × 10-7; OR, 1.25). No evidence of association was observed for CHRNA9 rs6832151 either in the replication phase or in the overall pooled analysis.<p></p> Conclusion: Our results suggest a role of PPARG gene in the development of SSc

FICARAM-15 Cruise Report 20th March – 22nd May 2013 on board BIO Hespérides by the Group FICARAM

54 páginas, 19 figuras, 3 anexosThe FICARAM-15 is the fifteenth repetition of a section conducted in 1994. This section is part of the international program GOSHIP (http://www.go-ship.org/CruisePlans.html) to develop a globally coordinated network of sustained hydrographic sections as part of the global ocean/climate observing system. The objective of the FICARAM-15 cruise is to investigate the temporal evolution of the anthropogenic carbon and evaluate the CO2 absorption capacity of the South Atlantic region, the Equatorial zone, and the subtropical region of Azores-Gibraltar in the North Atlantic. This cruise is supported by the CATARINA project funded by the Ministry of Economy and Competitiveness (CTM2010-17141) and is part of the European Union FP7 project CARBOCHANGE (http://carbochange.b.uib.no/). The objective of FICARAM-15 cruise is framed in the CATARINA project conducted by the tasks I.2.1 (air-sea CO2 exchange) I.3 (ventilation of water masses), I.4.1 (zonal variability of N2O and CH4), I.4.2 (anthropogenic carbon storage), I.4.4 (saturation horizon of calcium carbonate along the section) and I.5.4 (evolution of the acidification rates). Another component of the FICARAM-15 cruise aims to examine the biological and biogeochemical mechanisms that hinder total dissolved organic carbon (DOC) remineralisation in marine systems, taking a multidisciplinary perspective and applying many different approaches. This is the global objective of the Spanish project DOREMI (CTM2012-34294) that joins this FICARAM-15 cruise.During the FICARAM cruise the physical oceanography group was responsible for collecting the following data sets: CTD and XBT data; vessel-mounted ADCP and lowered ADCP; continuous thermosalinograph. Physical oceanographers participated in the cruise financed through Project “Tipping Corners in the Meridional Overturning Circulation” (TIC-MOC), CTM2011-28867. The FICARAM-15 cruise was organized in two phases with a common sampling. LEG 1: From Punta Arenas (Chile) to Recife (Brazil): 62 stations. Chief Scientist: Aida F. Ríos, PI of CATARINA project LEG 2: From Recife (Brazil) to Cartagena (Spain): 46 stations Chief Scientist: Celia Marrasé, PI of DOREMI project This report contains the sampling of all the variables at each station along the FICARAM section, as well as the analysis of the biogeochemical variables and the preliminary results. The principal investigator of the DOREMI project produced another report with the common sampling section, showing the analysis and results of the experiments on dissolved organic matter carried out on board.This cruise is supported by the CATARINA project funded by the Ministry of Economy and Competitiveness (CTM2010-17141) and is part of the European Union FP7 project CARBOCHANGE (http://carbochange.b.uib.no/)Peer reviewe

Segundo Congreso Salesiano de Ciencia, Tecnología e Innovación para la Sociedad

La segunda edición del Congreso Salesiano de Ciencia, Tecnología e Innovación para la Sociedad, CITIS, realizado el 2 y 3 de diciembre de 2015 y organizado por la Universidad Politécnica Salesiana (sede Guayaquil), ofreció un espacio idóneo para la presentación, difusión e intercambio de importantes investigaciones (nacionales e internacionales) a los docentes investigadores y a la comunidad universitaria en general. Los trabajos recogidos en estas Memorias Académicas pertenecen a diferentes líneas de investigación del área de la Ingeniería: Telecomunicaciones, Automatización y Control, Procesos Industriales, Sistemas Eléctricos de Potencia, Telemática e Informática Aplicada, áreas de interés en esta segunda edición del CITIS. Cabe destacar que se evidencia la preocupación por la dimensión humana y social mediante el desarrollo responsable de la ciencia y la tecnología. La realización de este Congreso ha puesto en evidencia la importancia y pertinencia de la actividad investigativa que se genera en las universidades (en proyectos desarrollados por los docentes investigadores e, incluso, por los estudiantes de grado y posgrado), así como los altos niveles de compromiso académico y social

Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC)

© The Author(s) 2018.Here, we investigated for the first time the frequency and number of circulating tumor plasma cells (CTPC) in peripheral blood (PB) of newly diagnosed patients with localized and systemic plasma cell neoplasms (PCN) using next-generation flow cytometry (NGF) and correlated our findings with the distinct diagnostic and prognostic categories of the disease. Overall, 508 samples from 264 newly diagnosed PCN patients, were studied. CTPC were detected in PB of all active multiple myeloma (MM; 100%), and smoldering MM (SMM) patients (100%), and in more than half (59%) monoclonal gammopathy of undetermined significance (MGUS) cases (p <0.0001); in contrast, CTPC were present in a small fraction of solitary plasmacytoma patients (18%). Higher numbers of CTPC in PB were associated with higher levels of BM infiltration and more adverse prognostic features, together with shorter time to progression from MGUS to MM (p <0.0001) and a shorter survival in MM patients with active disease requiring treatment (p ≤ 0.03). In summary, the presence of CTPC in PB as assessed by NGF at diagnosis, emerges as a hallmark of disseminated PCN, higher numbers of PB CTPC being strongly associated with a malignant disease behavior and a poorer outcome of both MGUS and MM.This work has been supported by the International Myeloma Foundation-Black Swan Research Initiative and the EuroFlow Consortium; Centro de Investigación Biomédica en Red de Cáncer (CIBER-ONC; Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER), numbers: CB16/12/00400, CB16/12/00369, CB16/12/00489 and CB16/12/00233; grant SA079U14 from the Consejería de Educación, Junta de Castilla y León, Valladolid, Spain and; grant DTS15/00119 from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain. Acuerdo de colaboración con Fundación de Hemoterapia y Hemodonación de Castilla y León, Valladolid, Spain. This study was also supported by the Qatar National Research Fund (QNRF) Award No. 7-916-3-237, the AACR-Millennium Fellowship in Multiple Myeloma Research (15-40-38-PAIV), ERA-NET TRANSCAN-2 (iMMunocell), by a 2017 Leonardo Grant (BZG10931) for Researchers and Cultural Creators, BBVA Foundation, and the European Research Council (ERC) 2015 Starting Grant (MYELOMANEXT)