Co-translational protein targeting facilitates centrosomal recruitment of PCNT during centrosome maturation in vertebrates.

As microtubule-organizing centers of animal cells, centrosomes guide the formation of the bipolar spindle that segregates chromosomes during mitosis. At mitosis onset, centrosomes maximize microtubule-organizing activity by rapidly expanding the pericentriolar material (PCM). This process is in part driven by the large PCM protein pericentrin (PCNT), as its level increases at the PCM and helps recruit additional PCM components. However, the mechanism underlying the timely centrosomal enrichment of PCNT remains unclear. Here, we show that PCNT is delivered co-translationally to centrosomes during early mitosis by cytoplasmic dynein, as evidenced by centrosomal enrichment of PCNT mRNA, its translation near centrosomes, and requirement of intact polysomes for PCNT mRNA localization. Additionally, the microtubule minus-end regulator, ASPM, is also targeted co-translationally to mitotic spindle poles. Together, these findings suggest that co-translational targeting of cytoplasmic proteins to specific subcellular destinations may be a generalized protein targeting mechanism

Blended wing body with boundary layer ingestion conceptual design in a multidisciplinary design analysis optimization environment

This paper introduces the GENUS multidisciplinary concept level aircraft design and analysis environment developed by Cranfield University in recent years and it has been applied to the conceptual design of blended wing body (BWB) aircraft. Analytical disciplines include a variety of low-to-medium fidelity, physics-based and empirical methods, and aerodynamic analysis of high-order panel method. Boundary layer ingestion (BLI), as a special module, has been incorporated into the aerodynamic and propulsion analysis. The results of the Cranfield BW-11 are presented. In the highly-constrained design space, a type of highly fuel- efficient BWB concept can be studied, and the advantages of the BLI concept can also be explored based on this framework

Lifestyle and Health among Spanish University Students: Differences by Gender and Academic Discipline

Today the need to analyze health behaviour from a gender perspective is as imminent as ever, particularly at university, where the number of women who register is on the rise and has exceeded the number of male students worldwide. We carried out a prevalence study aimed at analyzing Spanish university students’ lifestyles and identify differences according to gender and academic discipline. Of 3,646 eligible subjects doing university courses related to health (Group A), education (Group B) and other professions (Group C), 985 (27.0%) participated in the study. Information was elicited about their physical activity level, disturbed eating attitudes, consumption of alcohol, tobacco and illegal substances. Prevalence and Odds Ratios (OR) were calculated according to sex and kind of academic discipline. The obtained data confirmed that only 27.4% of the students were considered as sufficiently active, while 14.9% of them suffered from disturbed eating attitudes (DEA). Women were particularly less active (OR 0.46 (0.32–0.66); <em>p</em> < 0.0001), and more sedentary than men (OR 1.40 (1.00–1.97); <em>p</em> = 0.03). Binge drinking was more frequent in female than in male students (OR 1.79 (1.29–2.47); <em>p</em> = 0.0004). A third of the analyzed sample admitted that they had used illegal substances, while a lower consumption prevalence was found in women (OR 0.53 (0.40–0.71); <em>p</em> < 0.0001). The studied population was not very active (27.4%), especially women (OR = 0.45). Therefore, it seems that Spanish university students lead an unhealthy lifestyle, a situation which seems more conspicuous amongst females

Control adaptativo para optimizar una intersección semafórica basado en un sistema embebido

In order to optimize the traffic flow on a road intersection, an adaptive control algorithm and a data base were designed; both components were hosted on a Raspberry Pi B+ embedded system. The data base helps to debug the performance of the controller. The efficiency of the algorithm was assessed using a virtual instrument, which emulated a traffic light intersection in the city of Cucuta, i. e., the magnetorresistive sensors, the activation process of the traffic lights and the traffic flow. By processing and updating the times assigned to the traffic lights, the traffic flow was increased up to 5.5 % and the maximum time a vehicle has to wait before passing through the traffic light was decreased up to 28 seconds. Aditionally the length of line was diminished up to 18 %. Based on this case study, it can be inferred that is possible to integrate the adaptive control and the embedded systems as software and hardware tools to improve the operation of traffic control systems.Para optimizar el flujo vehicular en una intersección vial se diseñaron un algoritmo de control adaptativo y una base de datos que apoya la depuración del rendimiento del controlador, ambos alojados en el sistema embebido Raspberry Pi B+. El desempeño del algoritmo fue evaluado con un instrumento virtual, que emuló una intersección semafórica de la ciudad de Cúcuta, esto es, los sensores magnetorresistivos, el proceso de encendido en las luces de los semáforos y el flujo vehicular. La manipulación de los tiempos de encendido en las luces de los semáforos, aumentó el flujo vehicular hasta 5.5% y, disminuyó el tiempo máximo de espera del vehículo para avanzar hasta 28 segundos y el largo de fila hasta un 18%. Con base en el caso de estudio, se puede inferir que es posible integrar el control adaptativo y los sistemas embebidos como herramientas de software y hardware para mejorar el funcionamiento en los sistemas de regulación vial

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Influence of daily beer or ethanol consumption on physical fitness in response to a high-intensity interval training program. The BEER-HIIT study

The authors would like to thank all the participants that took part of the study for their time and effort. We are grateful to Ms. Ana Yara PostigoFuentes for her assistance with the English language. This study is part of Cristina Molina-Hidalgo’s Doctoral Thesis conducted in the Official Doctoral Programme in Psychology of the University of Granada, Spain.Background: High-intensity interval training (HIIT) is an effective approach to improve physical fitness, but consuming beer, which is a regular practice in many physically active individuals, may interfere with these effects. The purposes of this study were to investigate the effects of a 10-week (2 days/week) HIIT program on cardiorespiratory fitness, muscle strength and power parameters, and also to assess the possible influence on them of a moderate consumption of beer (at least from Monday to Friday) or its alcohol equivalent. Methods: Young (24 ± 6 years old) healthy adults (n = 73, 35 females) were allocated to five groups. Four groups participated in the HIIT intervention program while the fifth group was a control Non-Training group (n = 15). Participants in the training groups chose whether they preferred receiving alcohol or alcohol-free beverages. Those choosing alcohol were randomized to either beer or ethanol intake: (i) T-Beer group (alcohol beer, 5.4%; n = 13) or (ii) T-Ethanol (sparkling water with vodka, 5.4%; n = 14). Those choosing alcohol-free intake were randomized to (iii) T-Water group (sparkling water, 0.0%; n = 16), or (iv) T-0.0Beer group (alcohol-free beer, 0.0%; n = 15). Men ingested 330 ml of the beverage at lunch and 330 ml at dinner; women ingested 330 ml at dinner. Before and after the intervention, maximal oxygen uptake in absolute and relative terms (VO2max.), maximal heart rate, total test duration, hand grip strength and four types of vertical jumps were measured. Results: HIIT induced significant improvements in absolute and relative values of VO2max, and total test duration (all p < 0.05) in all the training groups; also, clinical improvements were found in hand grip strength. These positive effects were not influenced by the regular intake of beer or alcohol. No changes in the vertical jumps occurred in any of the groups. Conclusions: A moderate beer or alcohol intake does not mitigate the positive effect of a 10-week HIIT on physical fitness in young healthy adults. Trial registration: ClinicalTrials.gov ID: NCT03660579. Registered 20 September 2018. Retrospectively registered.Centro de Informacion Cerveza y Salud (CICS), Madrid, SpainSpanish Government FPU14/04172 FPU15/0396