Transcriptomic profiling reveals extraordinary diversity of venom peptides in unexplored predatory gastropods of the genus Clavus

Predatory gastropods of the superfamily Conoidea number over 12,000 living species. The evolutionary success of this lineage can be explained by the ability of conoideans to produce complex venoms for hunting, defense and competitive interactions. Whereas venoms of cone snails (family Conidae) have become increasingly well studied, the venoms of most other conoidean lineages remain largely uncharacterized. In the present study we present the venom gland transcriptomes of two species of the genus Clavus that belong to the family Drilliidae. Venom gland transcriptomes of two specimens of Clavus canalicularis, and two specimens of Cv. davidgilmouri were analyzed, leading to the identification of a total of 1,176 putative venom peptide toxins ( drillipeptides ). Based on the combined evidence of secretion signal sequence identity, entire precursor similarity search (BLAST), and the orthology inference, putative Clavus toxins were assigned to 158 different gene families. The majority of identified transcripts comprise signal, pro-, mature peptide, and post- regions, with a typically short ( \u3c 50 amino acids) and cysteine-rich mature peptide region. Thus drillipeptides are structurally similar to conotoxins. However, convincing homology with known groups of Conus toxins was only detected for very few toxin families. Among these are Clavus counterparts of Conus venom insulins (drillinsulins), porins (drilliporins), highly diversified lectins (drillilectins). The short size of most drillipeptpides and structural similarity to conotoxins was unexpected, given that most related conoidean gastropod families (Terebridae and Turridae) possess longer mature peptide regions. Our findings indicate that, similar to conotoxins, drillipeptides may represent a valuable resource for future pharmacological exploration

230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Costa, K. M., Hayes, C. T., Anderson, R. F., Pavia, F. J., Bausch, A., Deng, F., Dutay, J., Geibert, W., Heinze, C., Henderson, G., Hillaire-Marcel, C., Hoffmann, S., Jaccard, S. L., Jacobel, A. W., Kienast, S. S., Kipp, L., Lerner, P., Lippold, J., Lund, D., Marcantonio, F., McGee, D., McManus, J. F., Mekik, F., Middleton, J. L., Missiaen, L., Not, C., Pichat, S., Robinson, L. F., Rowland, G. H., Roy-Barman, M., Alessandro, Torfstein, A., Winckler, G., & Zhou, Y. 230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean. Paleoceanography and Paleoclimatology, 35(2), (2020): e2019PA003820, doi:10.1029/2019PA003820.230Th normalization is a valuable paleoceanographic tool for reconstructing high‐resolution sediment fluxes during the late Pleistocene (last ~500,000 years). As its application has expanded to ever more diverse marine environments, the nuances of 230Th systematics, with regard to particle type, particle size, lateral advective/diffusive redistribution, and other processes, have emerged. We synthesized over 1000 sedimentary records of 230Th from across the global ocean at two time slices, the late Holocene (0–5,000 years ago, or 0–5 ka) and the Last Glacial Maximum (18.5–23.5 ka), and investigated the spatial structure of 230Th‐normalized mass fluxes. On a global scale, sedimentary mass fluxes were significantly higher during the Last Glacial Maximum (1.79–2.17 g/cm2kyr, 95% confidence) relative to the Holocene (1.48–1.68 g/cm2kyr, 95% confidence). We then examined the potential confounding influences of boundary scavenging, nepheloid layers, hydrothermal scavenging, size‐dependent sediment fractionation, and carbonate dissolution on the efficacy of 230Th as a constant flux proxy. Anomalous 230Th behavior is sometimes observed proximal to hydrothermal ridges and in continental margins where high particle fluxes and steep continental slopes can lead to the combined effects of boundary scavenging and nepheloid interference. Notwithstanding these limitations, we found that 230Th normalization is a robust tool for determining sediment mass accumulation rates in the majority of pelagic marine settings (>1,000 m water depth).We thank Zanna Chase and one anonymous reviewer for valuable feedback. K. M. C. was supported by a Postdoctoral Scholarship at WHOI. L. M. acknowledges funding from the Australian Research Council grant DP180100048. The contribution of C. T. H., J. F. M., and R. F. A. were supported in part by the U.S. National Science Foundation (US‐NSF). G. H. R. was supported by the Natural Environment Research Council (grant NE/L002434/1). S. L. J. acknowledges support from the Swiss National Science Foundation (grants PP002P2_144811 and PP00P2_172915). This study was supported by the Past Global Changes (PAGES) project, which in turn received support from the Swiss Academy of Sciences and the US‐NSF. This work grew out of a 2018 workshop in Aix‐Marseille, France, funded by PAGES, GEOTRACES, SCOR, US‐NSF, Aix‐Marseille Université, and John Cantle Scientific. All data are publicly available as supporting information to this document and on the National Center for Environmental Information (NCEI) at https://www.ncdc.noaa.gov/paleo/study/28791

La gestión del proyecto de vinculación en la formación de capacidades para la transformación ciudadana

Los procesos sustantivos: docencia, vinculación e investigación en la Educación Superior de Ecuador constituyen objetivos a desarrollar por las diferentes instituciones educativas del país Tales procesos inciden en la preparación de los profesionales, logrando en estos un pensamiento crítico y un desarrollo de la conciencia social, estimula habilidades investigativas para asimilar los cambios tecnológicos. Al aplicar el trabajo académico en los sectores de la sociedad se logra un beneficio que repercute en bienestar de la población. El trabajo se realiza en la Universidad Metropolitana de Ecuador y tiene como objetivo analizar la gestión del proyecto de vinculación formación de capacidades para la transformación ciudadana. Para ello se han aplicados métodos empíricos de investigación asumiendo una metodología cualitativa, usando técnicas cuantitativas

Submillimeter Array Observations of the RX J1633.9-2442 Transition Disk: Evidence for Multiple Planets in the Making

We present continuum high resolution Submillimeter Array (SMA) observations of the transition disk object RX J1633.9-2442, which is located in the Ophiuchus molecular cloud and has recently been identified as a likely site of ongoing giant planet formation. The observations were taken at 340 GHz (880 micron) with the SMA in its most extended configuration, resulting in an angular resolution of 0.3" (35 AU at the distance of the target). We find that the disk is highly inclined (i ~50 deg) and has an inner cavity ~25 AU in radius, which is clearly resolved by our observations. We simultaneously model the entire optical to millimeter wavelength spectral energy distribution (SED) and SMA visibilities of RX J1633.9-2442 in order to constrain the structure of its disk. We find that an empty cavity ~25 AU in radius is inconsistent with the excess emission observed at 12, 22, and 24 micron. Instead, the mid-IR excess can be modeled by either a narrow, optically thick ring at ~10 AU or an optically thin region extending from ~7 AU to ~25 AU. The inner disk (r < 5 AU) is mostly depleted of small dust grains as attested by the lack of detectable near-IR excess. We also present deep Keck aperture masking observations in the near-IR, which rule out the presence of a companion up to 500 times fainter than the primary star (in K-band) for projected separations in the 5-20 AU range. We argue that the complex structure of the RX J1633.9-2442 disk is best explained by multiple planets embedded within the disk. We also suggest that the properties and incidence of objects such as RX J1633.9-2442, T Cha, and LkCa 15 (and those of the companions recently identified to these two latter objects) are most consistent with the runaway gas accretion phase of the core accretion model, when giant planets gain their envelopes and suddenly become massive enough to open wide gaps in the disk.Comment: Accepted for publication in Ap

Modelo pedagógico para la autopreparación en la disciplina Filosofía y Sociedad

A study was carried out at the University of Medical Sciences of Guantanamo during the period 2009-2011, with the objective of developing a computer system of teaching activities , through self - management of knowledge, allows the highest preparation of first year students in The discipline Philosophy and Society. The results of the research carried out by the group of research professors fulfilling the task "Computerization of the discipline Philosophy and Society" within the "Galenomedia Research Project". Its use is widespread in all the headquarters of the medical university. It is verified that with the elaboration of computer products applied to the teaching of Philosophy, it is possible to raise the quality and the efficiency in the educational-academic and political-ideological formation in our students of Medical Sciences.Se realiza un estudio en la Universidad de Ciencias Médicas de Guantánamo durante el período 2009 - 2011, con el objetivo de elaborar un sistema informático de actividades docentes que permitan, mediante la autogestión de conocimientos, la más elevada  preparación de los estudiantes de primer año en la disciplina Filosofía y Sociedad. Se presentan los resultados de la investigación realizada por el colectivo de profesores investigadores cumpliendo la tarea “Informatización de la disciplina Filosofía y Sociedad” dentro del “Proyecto de Investigación Galenomedia”. Está generalizado su uso en todas las sedes de la universidad médica. Se comprueba que con la elaboración de productos informáticos aplicados a la enseñanza de la Filosofía, se puede elevar la calidad y la eficiencia en la formación docente-académica y político-ideológica en nuestros estudiantes de Ciencias Médicas

Study of the common genetic background for rheumatoid arthritis and systemic lupus erythematosus

BACKGROUND: Evidence is beginning to emerge that there may be susceptibility loci for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) that are common to both diseases. OBJECTIVE: To investigate single nucleotide polymorphisms that have been reported to be associated with SLE in a UK cohort of patients with RA and controls. METHODS: 3962 patients with RA and 9275 controls were included in the study. Eleven SNPs mapping to confirmed SLE loci were investigated. These mapped to the TNFSF4, BANK1, TNIP1, PTTG1, UHRF1BP1, ATG5, JAZF1, BLK, KIAA1542, ITGAM and UBE2L3 loci. Genotype frequencies were compared between patients with RA and controls using the trend test. RESULTS: The SNPs mapping to the BLK and UBE2L3 loci showed significant evidence for association with RA. Two other SNPs, mapping to ATG5 and KIAA1542, showed nominal evidence for association with RA (p=0.02 and p=0.02, respectively) but these were not significant after applying a Bonferroni correction. Additionally, a significant global enrichment in carriage of SLE alleles in patients with RA compared with controls (p=9.1×10(-7)) was found. Meta-analysis of this and previous studies confirmed the association of the BLK and UBE2L3 gene with RA at genome-wide significance levels (p<5×10(-8)). Together, the authors estimate that the SLE and RA overlapping loci, excluding HLA-DRB1 alleles, identified so far explain ∼5.8% of the genetic susceptibility to RA as a whole. CONCLUSION: The findings confirm the association of the BLK and UBE2L3 loci with RA, thus adding to the list of loci showing overlap between RA and SLE

ATEROGENESIS

La aterosclerosis humana es un proceso patológico complejo, de causa multifactorial, compuesto de dos fenómenos estrechamente relacionados: la aterosis, que se caracteriza por la acumulación de lípidos tanto intra como extracelularmente y que incluye la formación de las llamadas células espumosas y reacción inflamatoria; y la esclerosis, que es el endurecimiento cicatrizal de la pared arterial, caracterizado por el incremento de miocitos, distrofia de la matriz extracelular, calcificación, necrobiosis y mayor reacción inflamatoria. El endotelio es quizá el órgano más grande del cuerpo con funciones endócrinas, autócrinas y parácrinas. Realiza varias funciones, entre las que se hallan, la regulación del intercambio de moléculas entre la sangre y la pared vascular; controla el tono vascular a través del óxido nítrico y la prostaglandina I2, causando relajación del músculo liso vascular, así como también, desarrolla funciones antitrombóticas-fibrinolíticas entre otras. Un factor fundamental en la aterosclerosis es la disfunción endotelial, cuyo aspecto clave es la disminución del óxido nítrico, la cual pudiera deberse a un aumento en su degradación metabólica ó bien, a una reducción en su síntesis. De igual importancia es la participación de las lipoproteínas de baja densidad (LDL), que en condiciones de disfunción endotelial, permanecen un tiempo mayor en el espacio subendotelial, donde son oxidadas (modificadas),originando las LDL mínimamente modificadas (MM-LDL).Las células que participan directamente en la formación de la placa ateromatosa son los monocitos, que al madurar en el espacio subendotelial se convierten en macrófagos. Por otro lado, las MM-LDL se exponen a un mayor grado de oxidación y son capaces de estimular ó activar al macrófago, el cual, al no contar con un mecanismo que limite la entrada de colesterol, degrada pobremente a las LDL oxidadas. A consecuencia de la incorporación no controlada de colesterol, el macrófago se ceba y se convierte en una célula espumosa, la cual al morir, los lípidos restantes formarán el núcleo ateromatoso junto con sustancias tóxicas, las que lesionarán al endotelio, que pasa de presentar una disfunción sin anomalías morfológicas hasta ser un endotelio dañado, que en algunas zonas puede inclusive, ser destruido y desaparecer. La exposición de este endotelio no funcional a la sangre del colágeno subyacente, estimula la adhesión plaquetaria, las que en conjunto con los macrófagos secretan factores de crecimiento, que terminan por estimular la proliferación y migración de células musculares lisas de la capa media.Palabras claves: aterogenesis, ateroma, aterosclerosis humanaatherogenesis, atheroma, human atherosclerosi

Myogenin Regulates Exercise Capacity and Skeletal Muscle Metabolism in the Adult Mouse

Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle

\u3csup\u3e230\u3c/sup\u3eTh Normalization: New Insights on an Essential Tool for Quantifying Sedimentary Fluxes in the Modern and Quaternary Ocean

230Th normalization is a valuable paleoceanographic tool for reconstructing high‐resolution sediment fluxes during the late Pleistocene (last ~500,000 years). As its application has expanded to ever more diverse marine environments, the nuances of 230Th systematics, with regard to particle type, particle size, lateral advective/diffusive redistribution, and other processes, have emerged. We synthesized over 1000 sedimentary records of 230Th from across the global ocean at two time slices, the late Holocene (0–5,000 years ago, or 0–5 ka) and the Last Glacial Maximum (18.5–23.5 ka), and investigated the spatial structure of 230Th‐normalized mass fluxes. On a global scale, sedimentary mass fluxes were significantly higher during the Last Glacial Maximum (1.79–2.17 g/cm2kyr, 95% confidence) relative to the Holocene (1.48–1.68 g/cm2kyr, 95% confidence). We then examined the potential confounding influences of boundary scavenging, nepheloid layers, hydrothermal scavenging, size‐dependent sediment fractionation, and carbonate dissolution on the efficacy of 230Th as a constant flux proxy. Anomalous 230Th behavior is sometimes observed proximal to hydrothermal ridges and in continental margins where high particle fluxes and steep continental slopes can lead to the combined effects of boundary scavenging and nepheloid interference. Notwithstanding these limitations, we found that 230Th normalization is a robust tool for determining sediment mass accumulation rates in the majority of pelagic marine settings (\u3e1,000 m water depth)

Development of an educational intervention for patients with Irritable Bowel Syndrome (IBS) – a pilot study

<p>Abstract</p> <p>Background</p> <p>Many IBS patients experience that they receive limited information and that the health care system does not take their complaints seriously. We aimed to develop a structured patient education, an 'IBS school', and investigate if the efficacy could be evaluated in terms of improved knowledge, symptom severity and health related quality of life (HRQOL).</p> <p>Methods</p> <p>The IBS school consisted of six weekly two hour sessions in a group setting. Five different health care professionals were responsible for one session each. Questionnaires covering patients' experience of the education, perceived knowledge about IBS, gastrointestinal symptoms, and HRQOL, were used for evaluation at baseline and at three, six, and twelve months after education.</p> <p>Results</p> <p>Twelve IBS patients were included. The patients were overall satisfied with the IBS school. In line with this, the gastrointestinal symptoms, HRQOL, and perceived knowledge about IBS improved significantly after the education.</p> <p>Conclusion</p> <p>An IBS school seems to be a proper method to meet the patients' need of information about IBS and also to improve the patients' gastrointestinal symptoms, HRQOL, and knowledge about IBS. Further controlled studies are now needed in larger numbers of patients to confirm these preliminary results in order to implement this intervention in clinical practice.</p