Plan de negocio : "Evaluaci?n e implementaci?n del servicio de mensajer?a in house, en el Instituto Nacional de Defensa de la Competencia y de la Protecci?n de la Propiedad Intelectual (Indecopi)"

Habiendo tomado conocimiento que en el Indecopi se realiza el servicio de mensajer?a a trav?s de una empresa contratada, servicio que tiene como caracter?stica principal la ineficiencia en la entrega de los documentos y la devoluci?n de los cargos, lo que conlleva al incumplimiento de los plazos de ley, insatisfacci?n de los clientes internos (?reas usuarias del servicio) y lo clientes externos (administrados), que esperan recibir sus documentos de forma predecible, oportuna y confiable por parte del Indecopi, se identific? una oportunidad de mejora del servicio de mensajer?a, a trav?s de la implementaci?n del servicio de mensajer?a in house, o una mensajer?a mixta in-house y a trav?s de una empresa contratada

Macroevolution of the plant–hummingbird pollination system

ABSTRACTPlant–hummingbird interactions are considered a classic example of coevolution, a process in which mutually dependent species influence each other's evolution. Plants depend on hummingbirds for pollination, whereas hummingbirds rely on nectar for food. As a step towards understanding coevolution, this review focuses on the macroevolutionary consequences of plant–hummingbird interactions, a relatively underexplored area in the current literature. We synthesize prior studies, illustrating the origins and dynamics of hummingbird pollination across different angiosperm clades previously pollinated by insects (mostly bees), bats, and passerine birds. In some cases, the crown age of hummingbirds pre‐dates the plants they pollinate. In other cases, plant groups transitioned to hummingbird pollination early in the establishment of this bird group in the Americas, with the build‐up of both diversities coinciding temporally, and hence suggesting co‐diversification. Determining what triggers shifts to and away from hummingbird pollination remains a major open challenge. The impact of hummingbirds on plant diversification is complex, with many tropical plant lineages experiencing increased diversification after acquiring flowers that attract hummingbirds, and others experiencing no change or even a decrease in diversification rates. This mixed evidence suggests that other extrinsic or intrinsic factors, such as local climate and isolation, are important covariables driving the diversification of plants adapted to hummingbird pollination. To guide future studies, we discuss the mechanisms and contexts under which hummingbirds, as a clade and as individual species (e.g. traits, foraging behaviour, degree of specialization), could influence plant evolution. We conclude by commenting on how macroevolutionary signals of the mutualism could relate to coevolution, highlighting the unbalanced focus on the plant side of the interaction, and advocating for the use of species‐level interaction data in macroevolutionary studies

ERK5/BMK1 is a novel target of the tumor suppressor VHL: implication in clear cell renal carcinoma

Hi ha quatre pàgines de material suplementari sense numeracióExtracellular signal-regulated kinase 5 (ERK5), also known as big mitogen-activated protein kinase (MAPK) 1, is implicated in a wide range of biologic processes, which include proliferation or vascularization. Here, we show that ERK5 is degraded through the ubiquitin-proteasome system, in a process mediated by the tumor suppressor von Hippel-Lindau (VHL) gene, through a prolyl hydroxylation-dependent mechanism. Our conclusions derive from transient transfection assays in Cos7 cells, as well as the study of endogenous ERK5 in different experimental systems such as MCF7, HMEC, or Caki-2 cell lines. In fact, the specific knockdown of ERK5 in pVHL-negative cell lines promotes a decrease in proliferation and migration, supporting the role of this MAPK in cellular transformation. Furthermore, in a short series of fresh samples from human clear cell renal cell carcinoma, high levels of ERK5 correlate with more aggressive and metastatic stages of the disease. Therefore, our results provide new biochemical data suggesting that ERK5 is a novel target of the tumor suppressor VHL, opening a new field of research on the role of ERK5 in renal carcinomas

Adipose Co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes

BACKGROUND: High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation. METHODS: Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA). Overlap between TG-associated networks from each of the three study samples were calculated using a Fisher’s Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network. RESULTS: We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG) were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1) reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals. CONCLUSIONS: This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations

Human genetic and metabolite variation reveals that methylthioadenosine is a prognostic biomarker and an inflammatory regulator in sepsis.

Sepsis is a deleterious inflammatory response to infection with high mortality. Reliable sepsis biomarkers could improve diagnosis, prognosis, and treatment. Integration of human genetics, patient metabolite and cytokine measurements, and testing in a mouse model demonstrate that the methionine salvage pathway is a regulator of sepsis that can accurately predict prognosis in patients. Pathway-based genome-wide association analysis of nontyphoidal Salmonella bacteremia showed a strong enrichment for single-nucleotide polymorphisms near the components of the methionine salvage pathway. Measurement of the pathway's substrate, methylthioadenosine (MTA), in two cohorts of sepsis patients demonstrated increased plasma MTA in nonsurvivors. Plasma MTA was correlated with levels of inflammatory cytokines, indicating that elevated MTA marks a subset of patients with excessive inflammation. A machine-learning model combining MTA and other variables yielded approximately 80% accuracy (area under the curve) in predicting death. Furthermore, mice infected with Salmonella had prolonged survival when MTA was administered before infection, suggesting that manipulating MTA levels could regulate the severity of the inflammatory response. Our results demonstrate how combining genetic data, biomolecule measurements, and animal models can shape our understanding of disease and lead to new biomarkers for patient stratification and potential therapeutic targeting

Detección precoz de cáncer de cérvix según los discursos de las matronas de atención primaria en Segovia, España

OBJETIVO: Analizar los discursos de las matronas de atención primaria sobre el acceso y la utilización del Programa Preventivo de Cáncer de Cérvix. PROCEDIMIENTOS METODOLÓGICOS: Se desarrolló un estudio cualitativo en un área de baja densidad poblacional, Segovia, España, que cuenta con un alto porcentaje de población rural, entre 2008 y 2009. Se utilizó como técnica la entrevista semi-estructurada. Se realizaron diez entrevistas a las matronas de atención primaria de las 16 Zonas Básicas de Salud. El análisis de la información se basó en las propuestas de la Teoría Fundamentada. ANÁLISIS DE RESULTADOS: El acceso y utilización del Programa Preventivo de Cáncer de Cérvix se relaciona con la utilización de la consulta de la matrona por las mujeres, sus vivencias de los exámenes de citología vaginal y su percepción de riesgo a padecer un cáncer de cuello uterino. La barrera percibida es la distancia para acceder a la consulta de la matrona, y para las mujeres inmigrantes, además son barreras la posibilidad de no disponer de tarjeta sanitaria y desconocer la existencia del Programa. La exclusión social es también considerada una barrera de acceso y utilización. Se identificó como el principal facilitador, la recomendación de los médicos de familia de participar en el Programa. CONCLUSIONES: Las matronas perciben desigualdades de acceso y utilización del Programa Preventivo de Cáncer de Cérvix que se relacionan tanto con características individuales de las mujeres, como con el medio geográfico donde viven y con la propia estructura del Programa. Hay situaciones de vulneración de la equidad en colectivos de mujeres poco representadas a nivel encuestal, como las mujeres inmigrantes y las que residen en zonas rurales

The MAVERIC Survey: A Red Straggler Binary with an Invisible Companion in the Galactic Globular Cluster M10

We present the discovery and characterization of a radio-bright binary in the Galactic globular cluster M10. First identified in deep radio continuum data from the Karl G. Jansky Very Large Array, M10-VLA1 has a flux density of 27 ± 4 μJy at 7.4 GHz and a flat-to-inverted radio spectrum. Chandra imaging shows an X-ray source with L X ≈ 1031 erg s−1 matching the location of the radio source. This places M10-VLA1 within the scatter of the radio-X-ray luminosity correlation for quiescent stellar-mass black holes, and a black hole X-ray binary is a viable explanation for this system. The radio and X-ray properties of the source disfavor, but do not rule out, identification as an accreting neutron star or white dwarf system. Optical imaging from the Hubble Space Telescope and spectroscopy from the SOAR telescope show that the system has an orbital period of 3.339 days and an unusual "red straggler" component: an evolved star found redward of the M10 red giant branch. These data also show UV/optical variability and double-peaked Hα emission characteristic of an accretion disk. However, SOAR spectroscopic monitoring reveals that the velocity semi-amplitude of the red straggler is low. We conclude that M10-VLA1 is most likely either a quiescent black hole X-ray binary with a rather face-on (i < 4°) orientation or an unusual flaring RS Canum Venaticorum variable-type active binary, and discuss future observations that could distinguish between these possibilities

Revisiting the usefulness of the short acute octreotide test to predict treatment outcomes in acromegaly

Introduction: We previously described that a short version of the acute octreotide test (sAOT) can predict the response to first-generation somatostatin receptor ligands (SRLs) in patients with acromegaly. We have prospectively reassessed the sAOT in patients from the ACROFAST study using current ultra-sensitive GH assays. We also studied the correlation of sAOT with tumor expression of E-cadherin and somatostatin receptor 2 (SSTR2) .Methods: A total of 47 patients treated with SRLs for 6 months were evaluated with the sAOT at diagnosis and correlated with SRLs' response. Those patients whose IGF1 decreased to = 3SDS, were considered non-responders. The 2 hours GH value (GH2h) after s.c. administration of 100 mcg of octreotide was used to define predictive cutoffs. E-cadherin and SSTR2 immunostaining in somatotropinoma tissue were investigated in 24/47 and 18/47 patients, respectively.Results: In all, 30 patients were responders and 17 were non-responders. GH(2h) was 0.68 (0.25-1.98) ng/mL in responders vs 2.35 (1.59-9.37) ng/mL in non-responders (p<0.001). GH(2h) = 1.4ng/mL showed the highest ability to identify responders (accuracy of 81%, sensitivity of 73.3%, and specificity of 94.1%). GH(2h) = 4.3ng/mL was the best cutoff for non-response prediction (accuracy of 74%, sensitivity of 35.3%, and specificity of 96.7%). Patients with E-cadherin-positive tumors showed a lower GH(2h) than those with E-cadherin-negative tumors [0.9 (0.3-2.1) vs 3.3 (1.5-12.1) ng/mL; p<0.01], and patients with positive E-cadherin presented a higher score of SSTR2 (7.5 +/- 4.2 vs 3.3 +/- 2.1; p=0.01).Conclusion: The sAOT is a good predictor tool for assessing response to SRLs and correlates with tumor E-cadherin and SSTR2 expression. Thus, it can be useful in clinical practice for therapeutic decision-making in patients with acromegaly

CUP-1 Is a Novel Protein Involved in Dietary Cholesterol Uptake in Caenorhabditis elegans

Sterols transport and distribution are essential processes in all multicellular organisms. Survival of the nematode Caenorhabditis elegans depends on dietary absorption of sterols present in the environment. However the general mechanisms associated to sterol uptake in nematodes are poorly understood. In the present work we provide evidence showing that a previously uncharacterized transmembrane protein, designated Cholesterol Uptake Protein-1 (CUP-1), is involved in dietary cholesterol uptake in C. elegans. Animals lacking CUP-1 showed hypersensitivity to cholesterol limitation and were unable to uptake cholesterol. A CUP-1-GFP fusion protein colocalized with cholesterol-rich vesicles, endosomes and lysosomes as well as the plasma membrane. Additionally, by FRET imaging, a direct interaction was found between the cholesterol analog DHE and the transmembrane “cholesterol recognition/interaction amino acid consensus” (CRAC) motif present in C. elegans CUP-1. In-silico analysis identified two mammalian homologues of CUP-1. Most interestingly, CRAC motifs are conserved in mammalian CUP-1 homologous. Our results suggest a role of CUP-1 in cholesterol uptake in C. elegans and open up the possibility for the existence of a new class of proteins involved in sterol absorption in mammals