Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features

Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy. Through genome-wide DNA methylation screening of > 25,000 tumors, we discovered a molecularly distinct class comprising 30 tumors, mostly diagnosed histologically as DLGNTs. Copy-number profiles derived from the methylation arrays revealed unifying characteristics, including loss of chromosomal arm 1p in all cases. Furthermore, this molecular DLGNT class can be subdivided into two subgroups [DLGNT methylation class (MC)-1 and DLGNT methylation class (MC)-2], with all DLGNT-MC-2 additionally displaying a gain of chromosomal arm 1q. Co-deletion of 1p/19q, commonly seen in IDH-mutant oligodendroglioma, was frequently observed in DLGNT, especially in DLGNT-MC-1 cases. Both subgroups also had recurrent genetic alterations leading to an aberrant MAPK/ERK pathway, with KIAA1549:BRAF fusion being the most frequent event. Other alterations included fusions of NTRK1/2/3 and TRIM33:RAF1, adding up to an MAPK/ERK pathway activation identified in 80% of cases. In the DLGNT-MC-1 group, age at diagnosis was significantly lower (median 5 vs 14 years, p < 0.01) and clinical course less aggressive (5-year OS 100, vs 43% in DLGNT-MC-2). Our study proposes an additional molecular layer to the current histopathological classification of DLGNT, of particular use for cases without typical morphological or radiological characteristics, such as diffuse growth and radiologic leptomeningeal dissemination. Recurrent 1p deletion and MAPK/ERK pathway activation represent diagnostic biomarkers and therapeutic targets, respectively—laying the foundation for future clinical trials with, e.g., MEK inhibitors that may improve the clinical outcome of patients with DLGNT

INFLUENCIA DEL PROGRAMA PRESUPUESTAL 091 EN LA GESTIÓN INSTITUCIONAL DE LAS INSTITUCIONES EDUCATIVAS DE INICIAL, UGEL N° 04 TRUJILLO SUR ESTE – 2018

El presente estudio de investigación tuvo como objetivo determinar la Influencia del Programa Presupuestal 091 en la Gestión Institucional de las Instituciones Educativas de Inicial, UGEL N° 04 Trujillo Sur Este – 2018. Investigación tuvo un enfoque cuantitativo, diseño correlacional causal transversal, la población lo conforman los directivos y docentes de las instituciones educativas que ascienden a un total de 113, la muestra fue de 88 docentes y directivos; para la recolección de datos se empleó dos cuestionarios tipo escala Likert, que fueron validados con el coeficiente de V de Aiken, y se realizó la confiabilidad con el coeficiente de Alfa de Cronbach, en donde se obtuvo para el Programa Presupuestal 091 el resultado de 0,967 y para gestión institucional fue 0,943 (excelente fiabilidad). Los resultados fueron analizados con del software estadístico SPSS V. 23, en donde se determinó que el Programa Presupuestal 091 influye significativamente en la gestión institucional de las Instituciones Educativas de Inicial, UGEL N° 04 Trujillo Sur Este, 2018, con un valor de significancia de prueba Tau-b de Kendall de 0.016, el coeficiente Rho de Spearman = 0.257 (positiva baja), determinándose aceptar la hipótesis de investigación y rechazar hipótesis nula. Por otro lado, se determinó que el nivel de desempeño del Programa Presupuestal 091 fue de nivel eficiente con 51.1% a diferencia del nivel de gestión institucional fue de nivel regular con 78.4%. Palabras clave: programa presupuestal, gestión institucional, planificación estratégica

Discovery and characterisation of detached M-dwarf eclipsing binaries in the WFCAM Transit Survey

We report the discovery of 16 detached M-dwarf eclipsing binaries with J<16 mag and provide a detailed characterisation of three of them, using high-precision infrared light curves from the WFCAM Transit Survey (WTS). Such systems provide the most accurate and model-independent method for measuring the fundamental parameters of these poorly understood yet numerous stars, which currently lack sufficient observations to precisely calibrate stellar evolution models. We fully solve for the masses and radii of three of the systems, finding orbital periods in the range 1.5<P<4.9 days, with masses spanning 0.35-0.50 Msun and radii between 0.38-0.50 Rsun, with uncertainties of ~3.5-6.4% in mass and ~2.7-5.5% in radius. Close-companions in short-period binaries are expected to be tidally-locked into fast rotational velocities, resulting in high levels of magnetic activity. This is predicted to inflate their radii by inhibiting convective flow and increasing star spot coverage. The radii of the WTS systems are inflated above model predictions by ~3-12%, in agreement with the observed trend, despite an expected lower systematic contribution from star spots signals at infrared wavelengths. We searched for correlation between the orbital period and radius inflation by combining our results with all existing M-dwarf radius measurements of comparable precision, but we found no statistically significant evidence for a decrease in radius inflation for longer period, less active systems. Radius inflation continues to exists in non-synchronised systems indicating that the problem remains even for very low activity M-dwarfs. Resolving this issue is vital not only for understanding the most populous stars in the Universe, but also for characterising their planetary companions, which hold the best prospects for finding Earth-like planets in the traditional habitable zone.Comment: 30 pages, 14 figures, 16 tables, Accepted for publication in MNRA

Four ultra-short period eclipsing M-dwarf binaries in the WFCAM Transit Survey

We report on the discovery of four ultra-short period (P<0.18 days) eclipsing M-dwarf binaries in the WFCAM Transit Survey. Their orbital periods are significantly shorter than of any other known main-sequence binary system, and are all significantly below the sharp period cut-off at P~0.22 days as seen in binaries of earlier type stars. The shortest-period binary consists of two M4 type stars in a P=0.112 day orbit. The binaries are discovered as part of an extensive search for short-period eclipsing systems in over 260,000 stellar lightcurves, including over 10,000 M-dwarfs down to J=18 mag, yielding 25 binaries with P<0.23 days. In a popular paradigm, the evolution of short period binaries of cool main-sequence stars is driven by loss of angular momentum through magnetised winds. In this scheme, the observed P~0.22 day period cut-off is explained as being due to timescales that are too long for lower-mass binaries to decay into tighter orbits. Our discovery of low-mass binaries with significantly shorter orbits implies that either these timescales have been overestimated for M-dwarfs, e.g. due to a higher effective magnetic activity, or that the mechanism for forming these tight M-dwarf binaries is different from that of earlier type main-sequence stars.Comment: 22 pages, 17 figures, 3 tables Accepted for publication in MNRA

ACE and CXCL10 as predictive biomarkers in the LEA study

Background: LEA Study (GEICAM/2006-11/GBG51), is a randomized clinical trial comparing bevacizumab in combination with endocrine therapy (ET + B) with endocrine therapy (ET) in postmenopausal women with advanced or metastatic HR-positive/HER2-negative breast cancer (BC) with indication of hormonotherapy as first-line treatment. Patients with secondary hypertension had better progression-free survival (PFS) and overall survival (OS). We have evaluated the role of two hypertension-related biomarkers, Angiotensin-Converting Enzyme (ACE) and Small-Inducible Cytokine B10 (CXCL10) as prognostic and/or predictive biomarkers of benefit to bevacizumab in the first line metastatic disease. Methods: From 380 patients, 266 were included in 33 Spanish sites. Median age was 64 years, 63.5% had measurable disease, 97.4% were metastatic at randomization, 51.5% had visceral disease and 52.6% received previous chemotherapy. PFS was 14.3 months (range 0.8-61.1), OS was 34 months (range 0.8-71.6) and 93 patients had Objective Response (OR). We analyzed 124 plasma samples collected before treatment (52 from ET and 72 from ET + B arms). Circulating levels of ACE and CXCL10 were determined by ELISA. ACE levels of 115ng/ml and 135ng/ml were pre-defined as cutoff values. CXCL10 was explored as a quantitative variable. Results: PFS was 15.1 months (range 1.4-61.1), OS was 31.1 months (range 2.8-61.1) and 40.3% had OR. OR was significantly different between treatment arms (p < 0.001) but not PFS or OS. Median ACE concentration was 130.9ng/ml (range 35.3-315.4). Low ACE (<135ng/ml) had better PFS in the whole population (p = 0.048) and in the ET + B arm (p = 0.041). ACE cutoff of 115 ng/ml was not able to identify any subgroup with better prognosis. Median CXCL10 concentration was 230.3pg/ml (range 15.1-4129.6). A higher expression of CXCL10 was significantly associated with worse OS in the whole population (p < 0.0001) and each treatment arm (p = 0.002 and p = 0.001 in ET and ET + B, respectively). No association with OR were identified neither for ACE nor for CXCL10. Conclusions: ACE levels could be considered a prognostic and a bevacizumab predictive biomarker of PFS. CXCL10 could be prognostic of OS. Confirmatory studies are warranted

Spectroscopy of new brown dwarf members of rho Ophiuchi and an updated initial mass function

To investigate the universality hypothesis of the initial mass function in the substellar regime, the population of the rho Ophiuchi molecular cloud is analysed by including a new sample of low-mass spectroscopically confirmed members. To that end, we have conducted a large spectroscopic follow-up of young substellar candidates uncovered in our previous photometric survey. The spectral types and extinction were derived for a newly found population of substellar objects, and its masses estimated by comparison to evolutionary models. A thoroughly literature search was conducted to provide an up-to-date census of the cluster, which was then used to derive the luminosity and mass functions, as well as the ratio of brown dwarfs to stars in the cluster. These results were then compared to other young clusters. It is shown that the study of the substellar population of the rho Ophiuchi molecular cloud is hampered only by the high extinction in the cluster ruling out an apparent paucity of brown dwarfs. The discovery of 16 new members of rho Ophiuchi, 13 of them in the substellar regime, reveals the low-mass end of its population and shows the success of our photometric candidate selection with the WIRCam survey. The study of the brown dwarf population of the cluster reveals a high disk fraction of 76 (+5-8)%. Taking the characteristic peak mass of the derived mass function and the ratio of brown dwarfs to stars into account, we conclude that the mass function of rho Ophiuchi is similar to other nearby young clusters.Comment: Accepted to A&A (30 December 2011); v2 includes language editin

Chemoinformatic-guided engineering of polyketide synthases

Polyketide synthase (PKS) engineering is an attractive method to generate new molecules such as commodity, fine and specialty chemicals. A central challenge in PKS design is replacing a partially reductive module with a fully reductive module through a reductive loop exchange, thereby generating a saturated β-carbon. In this work, we sought to establish an engineering strategy for reductive loop exchanges based on chemoinformatics, a field traditionally used in drug discovery. We first introduced a set of donor reductive loops of diverse genetic origin and chemical substrate structures into the first extension module of the lipomycin PKS (LipPKS1). These results demonstrated that chemical similarity between the substrate of the donor loops and recipient LipPKS1 correlated with product titers. Consequently, we identified donor loops with substrates chemically similar to LipPKS1 for further reductive loop exchanges, and we observed a statistically significant correlation with production. Reductive loops with the highest chemical similarity resulted in production of branched, short-chain fatty acids reaching a titer of 165 mg/L in Streptomyces albus J1074. Collectively, our work formulizes a new chemoinformatic paradigm for de novo PKS biosynthesis which may accelerate the production of valuable bioproducts

La vid silvestre en México. Actualidades y potencial

En ocho capítulos se aborda el estado del arte de la vid silvestre en MéxicoEl estudio de las especies vegetales nativas de México representa un reto que cada día más investigadores mexicanos asumen. Durante muchos años, el apoyo a la investigación pública ha sido mínimo; desde el punto de vista agronómico es insuficiente para avanzar a la velocidad que requiere nuestro país para afrontar problemas de producción y distribución de alimentos. Por esa razón, entre otras, me es grato presentar esta obra que compila parte de los trabajos de la Red de Vid Silvestre patrocinada por el Sistema Nacional de Recursos Fitogenéticos (sinarefi) dependiente de la sagarpa; trabajos apuntalados por investigadores que sin pertenecer a la red han colaborado en el estudio de las plantas del género Vitis. En este libro se muestra el potencial del país para aprovechar el recurso vid, empleado desde antes de la conquista española por nativos mexicanos que conocían sus bondades. Es necesario continuar el avance en el conocimiento de este recurso, por ello el presente libro pretende invitar a toda persona interesada en contribuir con el rescate y conservación de las vides mexicanas. Los autores y editores, así como las instituciones en donde laboramos y aquellas que patrocinan estas investigaciones, esperamos se cumpla este objetivo y que el lector, alumno, profesor, investigador, público en general, disfrute esta lectura y, sobre todo, se interese en el recurso VitisSEP, SINAREFI, UAEME

Chemoinformatic-Guided Engineering of Polyketide Synthases.

Polyketide synthase (PKS) engineering is an attractive method to generate new molecules such as commodity, fine and specialty chemicals. A significant challenge is re-engineering a partially reductive PKS&nbsp;module to produce a saturated β-carbon through a reductive loop (RL) exchange. In this work, we sought to establish that chemoinformatics, a field traditionally used in drug discovery, offers a viable strategy for RL exchanges. We first introduced a set of donor RLs of diverse genetic origin and chemical substrates&nbsp; into the first extension module of the lipomycin PKS (LipPKS1). Product titers of these engineered unimodular PKSs correlated with chemical structure&nbsp;similarity between the substrate of the donor RLs and recipient LipPKS1, reaching a titer of 165 mg/L of short-chain fatty acids produced by&nbsp;the host&nbsp;Streptomyces albus J1074. Expanding this method to larger intermediates that require bimodular communication, we introduced RLs of divergent chemosimilarity into LipPKS2 and determined triketide lactone production. Collectively, we observed a statistically significant correlation between atom pair chemosimilarity and production, establishing a new chemoinformatic method that may aid in the engineering of PKSs to produce desired, unnatural products