Diagnosticand pronostic utility of serum microrna-21 in colorectal cancer

Los microRNAs son estructuras moleculares de 20-22 nucleótidos con actividad post-transcripional que están implicados en la carcinogénesis mediante una regulación genética post-transcripcional. Presentamos un estudio prospectivo donde se determina la expresión sérica de microRNA-21 en pacientes con diagnóstico de adenocarcinoma de colon. MATERIAL Y MÉTODOS. Estudio de cohorte prospectivo de al menos 100 pacientes con diagnóstico de adenocarcinoma de colon, y de al menos 60 pacientes con apendicitis aguda como grupo control. Se realizó el análisis de microRNA-21 sérico mediante PCR de las muestras sanguíneas de los pacientes obtenidas de forma preoperatoria. RESULTADOS. La comparación de la expresión del microRNA-21 sérico fue mayor en los pacientes con cáncer colorrectal que en los pacientes del grupo control, siendo el área bajo la curva de 0,603. En el análisis univariante, la expresión del miR- 21 se relaciona de forma estadísticamente significativa con la recidiva local (p=0,025) y con la mortalidad (p=0,029). En el análisis multivariante también se puso de manifiesto que las expresiones mayores (sobreexpresiones) de miR-21 se relacionaban con una reducción del riesgo derecidiva del 51%, mientras que dicha sobreexpresión se relacionaba con una reducción de mortalidad del 50%. CONCLUSIONES. La expresión del microRNA-21 sérico podría ser considerado como un potencial marcador diagnóstico para el cáncer colorrectal. La expresión sérica del microRNA-21 se correlaciona con la recidiva y mortalidad en el cáncer colorrectal. Nuestros resultados sugieren que el miR-21 sérico es un prometedor marcador diagnóstico y pronóstico, y pone de manifiesto su potencial utilidad clínica en el cáncer colorrectalMicroRNAs (miRNAs) are small, noncoding RNAs that are involved in carcinogenesis through postranscriptional gene regulatory activity. Few studies have focused on the detection of miR-21 in serum rather than in tissue. The current study aimed to measure serum miR-21 expression levels and to evaluate their association with the outcome of colorectal cancer (CRC). METHODS. Blood samples were collected from almost 100 CRC patients undergoing surgery with curative intent, and almost 60 control patients. The expression levels of miR-21 were measured using a quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS. Serum microRNA-21 expression was higher in colorectal cancer patients than in control patients, with a ROC curve of 0.603. A univariate analysis revealed that lower expression levels of serum miR-21 were associated with higher local recurrence (p=0.025) and mortality (p=0.029). A logistic regression analysis demonstrated that the relative overexpression of miR-21 (expression >1) was associated with a 51% reduction in the risk of recurrence. A Cox regression analysis identified that a relative increase in miR-21 expression (>1) was associated with a 50% reduction in the risk of mortality CONCLUSIONS. Serum microRNA-21 expression could be considered as a potential diagnostic marker for colorectal cancer. The expression level of serum miR-21 correlates with the recurrence and mortality of CRC patients. Our results suggest that circulating serum miR-21 is a promising diagnostic and prognostic tumour marker, and they highlight the potential clinical utility of miR-21 in colorectal cancerEl presente estudio ha sido financiado con la ayuda otorgada por la Fundación para la Investigación Sanitaria en Castilla La Mancha (FISCAM) y por la Fundación Mutua Madrileña Investigación Médic

TransverseDiff gravity is to scalar-tensor as unimodular gravity is to General Relativity

Transverse Diffeomorphism (TDiff) theories are well-motivated theories of gravity from the quantum perspective, which are based upon a gauge symmetry principle. The main contribution of this work is to firmly establish a correspondence between TransverseDiff and the better-known scalar-tensor gravity --- in its more general form ---, a relation which is completely analogous to that between unimodular gravity and General Relativity. We then comment on observational aspects of TDiff. In connection with this proof, we derive a very general rule that determines under what conditions the procedure of fixing a gauge symmetry can be equivalently applied before the variational principle leading to the equations of motion, as opposed to the standard procedure, which takes place afterwards; this rule applies to gauge-fixing terms without derivatives.Comment: 10 pages; amsart style; v3: version as appeared in JCAP, redaction improve

Colorectal cancer carcinogenesis

El cáncer colorrectal representó en el año 2008 el tercer tumor más diagnosticado en España, siendo la segunda neoplasia que causó más fallecimientos. El conocimiento del proceso carcinogenético de este tipo de enfermedad permitirá el descubrimiento de nuevas terapéuticas que conlleven menores tasas de incidencia y mortalidad. El continuo avance en la enfermedad tumoral hace que esta revisión sea una puesta al día en el conocimiento de la carcinogénesis del cáncer colorrectalIn 2008, colorectal cancer represented the third most commonly diagnosed tumor in Spain, and the second tumor that caused more deaths. Knowledge of the carcinogenetic process of this disease will allow the discovery of new therapies involving lower rates of incidence and mortality. The continuous progress in tumor disease makes this review an update on the knowledge of colorectal cancer carcinogenesi

Mediating the Presence of Others: Reconceptualising Co-Presence as Mediated Intimacy

Drawing insight from queer and media studies, this article analyses data from the UK study Adults’ Media Lives. The authors claim that this study reveals the significance of people’s intimate relationships to their media practices, highlighting in particular how people’s media practices mediate the ‘presence’ of others. The authors put forward the concept of mediated intimacy to capture both the cultural intimacy people have with media and the mediation of intimacy by media practices. Mediating intimacy has implications for normative conceptions of intimate life, including the significance of ‘time’ to the values of ‘home’ and ‘work’

Texture-Based Analysis of 18F-Labeled Amyloid PET Brain Images

Amyloid positron emission tomography (PET) brain imaging with radiotracers like [18F]florbetapir (FBP) or [18F]flutemetamol (FMM) is frequently used for the diagnosis of Alzheimer’s disease. Quantitative analysis is usually performed with standardized uptake value ratios (SUVR), which are calculated by normalizing to a reference region. However, the reference region could present high variability in longitudinal studies. Texture features based on the grey-level co-occurrence matrix, also called Haralick features (HF), are evaluated in this study to discriminate between amyloid-positive and negative cases. A retrospective study cohort of 66 patients with amyloid PET images (30 [18F]FBP and 36 [18F]FMM) was selected and SUVRs and 6 HFs were extracted from 13 cortical volumes of interest. Mann–Whitney U-tests were performed to analyze differences of the features between amyloid positive and negative cases. Receiver operating characteristic (ROC) curves were computed and their area under the curve (AUC) was calculated to study the discriminatory capability of the features. SUVR proved to be the most significant feature among all tests with AUCs between 0.692 and 0.989. All HFs except correlation also showed good performance. AUCs of up to 0.949 were obtained with the HFs. These results suggest the potential use of texture features for the classification of amyloid PET image

Importance of Post-Translational Modifications for Functionality of a Chloroplast-Localized Carbonic Anhydrase (CAH1) in Arabidopsis thaliana

Background: The Arabidopsis CAH1 alpha-type carbonic anhydrase is one of the few plant proteins known to be targeted to the chloroplast through the secretory pathway. CAH1 is post-translationally modified at several residues by the attachment of N-glycans, resulting in a mature protein harbouring complex-type glycans. The reason of why trafficking through this non-canonical pathway is beneficial for certain chloroplast resident proteins is not yet known. Therefore, to elucidate the significance of glycosylation in trafficking and the effect of glycosylation on the stability and function of the protein, epitope-labelled wild type and mutated versions of CAH1 were expressed in plant cells. Methodology/Principal Findings: Transient expression of mutant CAH1 with disrupted glycosylation sites showed that the protein harbours four, or in certain cases five, N-glycans. While the wild type protein trafficked through the secretory pathway to the chloroplast, the non-glycosylated protein formed aggregates and associated with the ER chaperone BiP, indicating that glycosylation of CAH1 facilitates folding and ER-export. Using cysteine mutants we also assessed the role of disulphide bridge formation in the folding and stability of CAH1. We found that a disulphide bridge between cysteines at positions 27 and 191 in the mature protein was required for correct folding of the protein. Using a mass spectrometric approach we were able to measure the enzymatic activity of CAH1 protein. Under circumstances where protein N-glycosylation is blocked in vivo, the activity of CAH1 is completely inhibited. Conclusions/Significance: We show for the first time the importance of post-translational modifications such as N-glycosylation and intramolecular disulphide bridge formation in folding and trafficking of a protein from the secretory pathway to the chloroplast in higher plants. Requirements for these post-translational modifications for a fully functional native protein explain the need for an alternative route to the chloroplast.This work was supported by the Swedish Research Council (VR), the Kempe Foundations and Carl Tryggers Foundation to GS, and grant numbers BIO2006-08946 and BIO2009-11340 from the Spanish Ministerio de Ciencia e Innovación (MICINN) to A

An ethnographic study of Latino preschool children's oral health in rural California: Intersections among family, community, provider and regulatory sectors

<p>Abstract</p> <p>Background</p> <p>Latino children experience a higher prevalence of caries than do children in any other racial/ethnic group in the US. This paper examines the intersections among four societal sectors or contexts of care which contribute to oral health disparities for low-income, preschool Latino¹children in rural California.</p> <p>Methods</p> <p>Findings are reported from an ethnographic investigation, conducted in 2005–2006, of family, community, professional/dental and policy/regulatory sectors or contexts of care that play central roles in creating or sustaining low income, rural children's poor oral health status. The study community of around 9,000 people, predominantly of Mexican-American origin, was located in California's agricultural Central Valley. Observations in homes, community facilities, and dental offices within the region were supplemented by in-depth interviews with 30 key informants (such as dental professionals, health educators, child welfare agents, clinic administrators and regulatory agents) and 47 primary caregivers (mothers) of children at least one of whom was under 6 years of age.</p> <p>Results</p> <p>Caregivers did not always recognize visible signs of caries among their children, nor respond quickly unless children also complained of pain. Fluctuating seasonal eligibility for public health insurance intersected with limited community infrastructure and civic amenities, including lack of public transportation, to create difficulties in access to care. The non-fluoridated municipal water supply is not widely consumed because of fears about pesticide pollution. If the dentist brought children into the clinic for multiple visits, this caused the accompanying parent hardship and occasionally resulted in the loss of his or her job. Few general dentists had received specific training in how to handle young patients. Children's dental fear and poor provider-parent communication were exacerbated by a scarcity of dentists willing to serve rural low-income populations. Stringent state fiscal reimbursement policies further complicated the situation.</p> <p>Conclusion</p> <p>Several societal sectors or contexts of care significantly intersected to produce or sustain poor oral health care for children. Parental beliefs and practices, leading for example to delay in seeking care, were compounded by lack of key community or economic resources, and the organization and delivery of professional dental services. In the context of state-mandated policies and procedures, these all worked to militate against children receiving timely care that would considerably reduce oral health disparities among this highly disadvantaged population.</p

Efficient Matrix-Element Matching with Sector Showers

A Markovian shower algorithm based on "sector antennae" is presented and its main properties illustrated. Tree-level full-color matrix elements can be automatically incorporated in the algorithm and are re-interpreted as process-dependent 2 -> n antenna functions. In hard parts of phase-space, these functions generate tree-level matrix-element corrections to the shower. In soft parts, they should improve the logarithmic accuracy of it. The number of matrix-element evaluations required per order of matching is 1, with an unweighting efficiency that remains very high for arbitrary numbers of legs. Total rates can be augmented to NLO precision in a straightforward way. As a proof of concept, we present an implementation in the publicly available VINCIA plug-in to the PYTHIA 8 event generator, for hadronic $Z^0$ decays including tree-level matrix elements through ${\cal O}(\alpha_s^4)$.Comment: 35 pages, 24 figure

TRIB1 regulates tumor growth via controlling tumor-associated macrophage phenotypes and is associated with breast cancer survival and treatment response

Methods: Bioinformatic analysis was used to investigate the link between TRIB1 expression in breast cancer and therapeutic response to chemotherapy. In vivo models of breast cancer included immune-competent mice to characterize the consequences of altered (reduced or elevated) myeloid Trib1 expression on tumor growth and composition of stromal immune cell populations. Results: TRIB1 was highly expressed by TAMs in breast cancer and high TRIB1 expression correlated with response to chemotherapy and patient survival. Both overexpression and knockout of myeloid Trib1 promote mouse breast tumor growth, albeit through different molecular mechanisms. Myeloid Trib1 deficiency led to an early acceleration of tumor growth, paired with a selective reduction in perivascular macrophage numbers in vivo and enhanced oncogenic cytokine expression in vitro. In contrast, elevated levels of Trib1 in myeloid cells led to an increased late-stage mammary tumor volume, coupled with a reduction of NOS2 expressing macrophages and an overall reduction of macrophages in hypoxic tumor regions. In addition, we show that myeloid Trib1 is a previously unknown, negative regulator of the anti-tumor cytokine IL-15, and that increased myeloid Trib1 expression leads to reduced IL-15 levels in mammary tumors, with a consequent reduction in the number of T-cells that are key to anti-tumor immune responses. Conclusions: Together, these results define a key role for TRIB1 in chemotherapy responses for human breast cancer and provide a mechanistic understanding for the importance of the control of myeloid TRIB1 expression in the development of this disease