Overexpression of mitochondrial if1 prevents metastatic disease of colorectal cancer by enhancing anoikis and tumor infiltration of NK cells

Increasing evidences show that the ATPase Inhibitory Factor 1 (IF1), the physiological inhibitor of the ATP synthase, is overexpressed in a large number of carcinomas contributing to metabolic reprogramming and cancer progression. Herein, we show that in contrast to the findings in other carcinomas, the overexpression of IF1 in a cohort of colorectal carcinomas (CRC) predicts less chances of disease recurrence, IF1 being an independent predictor of survival. Bioinformatic and gene expression analyses of the transcriptome of colon cancer cells with differential expression of IF1 indicate that cells overexpressing IF1 display a less aggressive behavior than IF1 silenced (shIF1) cells. Proteomic and functional in vitro migration and invasion assays confirmed the higher tumorigenic potential of shIF1 cells. Moreover, shIF1 cells have increased in vivo metastatic potential. The higher metastatic potential of shIF1 cells relies on increased cFLIP-mediated resistance to undergo anoikis after cell detachment. Furthermore, tumor spheroids of shIF1 cells have an increased ability to escape from immune surveillance by NK cells. Altogether, the results reveal that the overexpression of IF1 acts as a tumor suppressor in CRC with an important anti-metastatic role, thus supporting IF1 as a potential therapeutic target in CRCThis research was funded by grants from Ministerio de Ciencia, Innovación y Universidades (SAF2013-41945-R, SAF2016-75916-R and SAF2016-75452-R), CIBERER-ISCIII (CB06/07/0017) and Fundación Ramón Areces, Spai

Allele specific expression analysis identifies regulatory variation associated with stress-related genes in the Mexican highland maize landrace Palomero Toluqueño.

BackgroundGene regulatory variation has been proposed to play an important role in the adaptation of plants to environmental stress. In the central highlands of Mexico, farmer selection has generated a unique group of maize landraces adapted to the challenges of the highland niche. In this study, gene expression in Mexican highland maize and a reference maize breeding line were compared to identify evidence of regulatory variation in stress-related genes. It was hypothesised that local adaptation in Mexican highland maize would be associated with a transcriptional signature observable even under benign conditions.MethodsAllele specific expression analysis was performed using the seedling-leaf transcriptome of an F1 individual generated from the cross between the highland adapted Mexican landrace Palomero Toluqueño and the reference line B73, grown under benign conditions. Results were compared with a published dataset describing the transcriptional response of B73 seedlings to cold, heat, salt and UV treatments.ResultsA total of 2,386 genes were identified to show allele specific expression. Of these, 277 showed an expression difference between Palomero Toluqueño and B73 alleles under benign conditions that anticipated the response of B73 cold, heat, salt and/or UV treatments, and, as such, were considered to display a prior stress response. Prior stress response candidates included genes associated with plant hormone signaling and a number of transcription factors. Construction of a gene co-expression network revealed further signaling and stress-related genes to be among the potential targets of the transcription factors candidates.DiscussionPrior activation of responses may represent the best strategy when stresses are severe but predictable. Expression differences observed here between Palomero Toluqueño and B73 alleles indicate the presence of cis-acting regulatory variation linked to stress-related genes in Palomero Toluqueño. Considered alongside gene annotation and population data, allele specific expression analysis of plants grown under benign conditions provides an attractive strategy to identify functional variation potentially linked to local adaptation

Microfilament-coordinated adhesion dynamics drives single cell migration and shapes whole tissues [version 1; Referees:4:approved]

Cell adhesion to the substratum and/or other cells is a crucial step of cell migration. While essential in the case of solitary migrating cells (for example, immune cells), it becomes particularly important in collective cell migration, in which cells maintain contact with their neighbors while moving directionally. Adhesive coordination is paramount in physiological contexts (for example, during organogenesis) but also in pathology (for example, tumor metastasis). In this review, we address the need for a coordinated regulation of cell-cell and cell-matrix adhesions during collective cell migration. We emphasize the role of the actin cytoskeleton as an intracellular integrator of cadherin- and integrin-based adhesions and the emerging role of mechanics in the maintenance, reinforcement, and turnover of adhesive contacts. Recent advances in understanding the mechanical regulation of several components of cadherin and integrin adhesions allow us to revisit the adhesive clutch hypothesis that controls the degree of adhesive engagement during protrusion. Finally, we provide a brief overview of the major impact of these discoveries when using more physiological three-dimensional models of single and collective cell migration

Estudio de la cristalización de ZrO2 en el sistema sol-gel: ZrO2-SiO2

Los polvos en el sistema ZrO2-SiO2, obtenidos por el método sol-gel, se produjeron utilizando alcóxido de silicio (TEOS) y propóxido de zirconio. Después de la gelación, se investigó la cristalización del ZrO2 por difracción de rayos X (DRX), análisis térmico (ATD/ATG), y microscopía electrónica de barrido (MEB). Los geles frescos eran amorfos. Se llevaron a cabo tratamientos térmicos de 100 hasta 1400°C, manteniéndolos por períodos de tiempo de hasta182h. La primera fase en cristalizar fue la zirconia tetragonal Z(t), entre 300 y 500°C. La temperatura de cristalización para las composiciones ricas en zirconia fue menor y aumentó a medida que el contenido de sílice aumentaba. El análisis térmico diferencial (ATD) mostró que la cristalización de Z(t) ocurría en dos pasos. La transformación de zirconia tetragonal a monoclínica ocurría a 1000°C y era claramente observada sólo en composiciones ricas en zirconia (>80%). La sílice permanecía amorfa hasta 1200°C, cuando se formaba la fase ZrSiO4. Se propuso un diagrama de fases sol-gel metaestable para mostrar el proceso de cristalización en el intervalo de temperatura de 100 a 1400°C

Monitoring of the morphologic reconstruction of deposited ablation products in laser irradiation of silicon

Using electron microscopy, atomic force microscopy, X-ray microanalysis, and IR spectroscopy, it was established that, in the regime of continuous laser irradiation of silicon at P = 170 W in different gaseous atmospheres with an oxygen impurity, SiOx composite films with a complex morphology form. The main components of ablation products are clusters that form during flight of ablation products and as a result of separation of SiOx-clusters from the zone of the irradiation channel. The roughness and density of the films depend on the heating temperature of the target surface and the type of deposited clusters

Interplay of Postprandial Triglyceride-Rich Lipoprotein Composition and Adipokines in Obese Adolescents

In the context of the alarming rise of infant obesity and its health implications, the present research aims to uncover disruptions in postprandial lipid metabolism and the composition of triglyceride-rich lipoproteins in obese adolescents. A double-blind, controlled clinical trial in the postprandial phase on 23 adolescents aged 12 to 16 years was carried out. Twelve participants were categorized as obese (BMI > 30 kg/m2 and percentile > 95) and 11 as normal-weight (BMI = 20–25 kg/m2, percentile 5–85). Blood samples were collected after a 12-h overnight fast and postprandially after consumption of a standardized breakfast containing olive oil, tomato, bread, orange juice, and skimmed milk. Obese adolescents exhibited elevated triglyceride concentrations in both fasting and postprandial states and higher TG/apo-B48 ratios, indicating larger postprandial triglyceride-rich lipoprotein (TRL) particle size, which suggests impaired clearance. Obese subjects also exhibited higher n-6 PUFA concentrations, potentially linked to increased TRL hydrolysis and the release of pro-inflammatory adipokines. In contrast, TRL from normal-weight individuals showed higher concentrations of oleic acid and DHA (n-3 PUFA), with possible anti-inflammatory effects. The results indicate an interplay involving postprandial TRL metabolism and adipokines within the context of adolescent obesity, pointing to potential cardiovascular implications in the future.Spanish Ministry of Economy and Competitiveness (Grant number AGL2011-23810)”“Next Generation EU” fundsEuropean Union Recovery, Transformation and Resilience PlanMinistry of Universities, in the framework of the Margarita Salas, Maria Zambrano grants for the Requalification of the Spanish University System 2021–2023, organized by the Pablo de Olavide University, Sevill

Co-prescription patterns of cardiovascular preventive treatments: A cross-sectional study in the Aragon worker' health study (Spain)

Objectives: To identify cardiovascular disease (CVD) preventive treatments combinations, among them and with other drugs, and to determine their prevalence in a cohort of Spanish workers. Design: Cross-sectional study. Setting Aragon Workers'' Health Study (AWHS) cohort in Spain. Participants 5577 workers belonging to AWHS cohort. From these subjects, we selected those that had, at least, three prescriptions of the same therapeutic subgroup in 2014 (n=4605). Primary and secondary outcome measures Drug consumption was obtained from the Aragon Pharmaceutical Consumption Registry (Farmasalud). In order to know treatment utilisation, prevalence analyses were conducted. Frequent item set mining techniques were applied to identify drugs co-prescription patterns. All the results were stratified by sex and age. Results: 42.3% of men and 18.8% of women in the cohort received, at least, three prescriptions of a CVD preventive treatment in 2014. The most prescribed CVD treatment were antihypertensives (men: 28.2%, women 9.2%). The most frequent association observed among CVD preventive treatment was agents acting on the renin-angiotensin system and lipid-lowering drugs (5.1% of treated subjects). Co-prescription increased with age, especially after 50 years old, both in frequency and number of associations, and was higher in men. Regarding the association between CVD preventive treatments and other drugs, the most frequent pattern observed was lipid-lowering drugs and drugs used for acid related disorders (4.2% of treated subjects). Conclusions: There is an important number of co-prescription patterns that involve CVD preventive treatments. These patterns increase with age and are more frequent in men. Mining techniques are a useful tool to identify pharmacological patterns that are not evident in the individual clinical practice, in order to improve drug prescription appropriateness

Agricultura y contaminación del agua

El libro trata un tema cuya importancia contrasta con su escaso estudio. Los efectos negativos de las actividades agrícolas en la calidad del agua han recibido mucha atención en otros países y muy poca en el nuestro. En México, 76% del agua se emplea en la agricultura y el conocimiento de su huella contaminante es escaso. Este libro es resultado de una investigación multidisciplinaria que muestra a la agricultura poco amigable con el agua; que los agricultores tienen una percepción sesgada de su actividad y no reconocen sus efectos en el ambiente; que el gobierno interviene con políticas erróneas estimulando el uso de insumos contaminantes, y que un grupo importante de agricultores realiza prácticas agrícolas poco sustentables. Ante tal panorama, el libro aporta información sobre este problema en una importante región agrícola; propone algunas medidas e instrumentos para minimizarlo; cubre un vacío en la investigación y la información y espera que motive estudios similares en otras regiones del país

Brenneria quercina and Serratia spp. isolated from Spanish oak trees: molecular characterization and PCR development

Brenneria quercina has been reported as one of the causal agents of oak decline in Spain. To investigate the bacterial variability of this pathogen from different Spanish oak forests, a collection of 38 bacterial isolates from seven geographic locations and from different oak species was analysed by sequencing 16S rDNA and rep-PCR fingerprinting. All Spanish isolates of B. quercina were grouped by rep-PCR into a homogenous cluster that differed significantly from B. quercina reference strains from California. 16S rDNA analysis revealed that 34 out of 38 isolates were Brenneria . However, four isolates belonged to the genus Serratia , suggesting that this bacterium could cause cankers in oak trees. The information obtained by rep-PCR fingerprint analysis was used to develop PCR primers for the sensitive and specific detection of B. quercina from infected plant tissues. Pathogenicity tests performed with Brenneria and Serratia isolates showed that both were able to grow and cause cankers in oak trees