S194-P-FADD as a marker of aggressiveness and poor prognosis in human T-cell lymphoblastic lymphoma

T-cell lymphoblastic lymphoma is a haematological disease with an urgent need for reliable prognostic biomarkers that allow therapeutic stratification and dose adjustment. The scarcity of human samples is responsible for the delayed progress in the study and the clinical management of this disease, especially compared with T-cell acute lymphoblastic leukaemia, its leukemic counterpart. In the present work, we have determined by immunohistochemistry that S194-P-FADD protein is significantly reduced in a cohort of 22 samples from human T-cell lymphoblastic lymphoma. Notably, the extent of such reduction varies significantly among samples and has revealed determinant for the outcome of the tumour. We demonstrate that Fas-associated protein with death domain (FADD) phosphorylation status affects protein stability, subcellular localization and non-apoptotic functions, specifically cell proliferation. Phosphorylated FADD would be more stable and preferentially localized to the cell nucleus; there, it would favour cell proliferation. We show that patients with higher levels of S194-P-FADD exhibit more proliferative tumours and that they present worse clinical characteristics and a significant enrichment to an oncogenic signature. This supports that FADD phosphorylation may serve as a predictor for T-cell lymphoblastic lymphoma aggressiveness and clinical status. In summary, we propose FADD phosphorylation as a new biomarker with prognostic value in T-cell lymphoblastic lymphoma

An alternative differential method of femtosecond pump-probe examination of materials

We describe an alternative method for femtosecond pumpprobe beam examination of energy transport properties of materials. All already reported techniques have several drawbacks which limit precise measurements of reflection coefficient as function of time. A typical problem is present when rough samples are being studied. In this case the pump-beam polarization changes randomly which may produce a spurious signal, drastically reducing the signal to noise ratio. Some proposals to alleviate such problema have been reported, however, they have not been totally satisfactory. The method presented here consists on measuring the difference between the two delays’ signals of the probe-beam. As will be explained, our proposal is free of typical drawbacks. We also propose a numerical method to recover the DR(t)/R curve from the measured data. Numerical simulations show that our proposal is a viable alternative

A tritrophic interaction model for an olive tree pest, the olive moth - Prays oleae (Bernard)

The olive tree (Olea europaea L.) is among the oldest and most widespread crops in the Mediterranean basin. Portugal is the third olive producer in the European Union, and Trás-os-Montes region, located in northeastern Portugal, is the second Portuguese producing olive region. The olive moth, Prays oleae (Bernard) (Lepidoptera: Praydidae) is a key olive pest in Trás-os-Montes. This pest is a natural host/prey of several organisms which include larvae of generalist and specialist parasitoids as well as generalist predators and entomopathogens. Its most abundant parasitoid is the specialist Ageniaspis fuscicollis (Dalman) (Hymenoptera: Encyrtidae) and this, in Trás-os-Montes region, is commonly followed by the facultative hyperparasitoid Elasmus flabellatus (Fonscolombe) (Hymenoptera: Eulophidae). Spiders represent a relevant group of generalist predators in olive agroecosystems and encompass an important predatory action in agroecosystems as well as an ability to reduce the populations of various insect pests. In this context, a mathematical model, considering the population of the olive moth, the two parasitoids populations and the spider population as the variables in our system, was constructed. The ecosystem steady states for feasibility and stability were assessed. The possible pesticide effects, that represent essentially extra mortality rates for each one of the insect populations, and potential abundance variations on their populations under a climate change scenario were included. Results indicate that the most important natural control agent is A. fuscicollis but in certain conditions E. flabellatus or spiders may be relevant contributors for the pest reduction. This approach may provide a useful tool to assist the field researchers on this pest system and its managementinfo:eu-repo/semantics/publishedVersio

Exploiting the passenger ACO1-deficiency arising from 9p21 deletions to kill T-cell lymphoblastic neoplasia cells

Precursor T-cell lymphoblastic neoplasms are aggressive malignancies in need for more effective and specific therapeutic treatments. A significant fraction of these neoplasms harbor deletions on the locus 9p21, targeting the tumor suppressor CDKN2A but also deleting the aconitase 1 (ACO1) gene, a neighboring housekeeping gene involved in cytoplasm and mitochondrial metabolism. Here we show that reducing the aconitase activity with fluorocitrate decreases the viability of T-cell lymphoblastic neoplasia cells in correlation to the differential aconitase expression. The consequences of the treatment were evidenced in vitro using T-cell lymphoblastic neoplasia cell lines exhibiting 9p21 deletions and variable levels of ACO1 expression or activity. Similar results were observed in melanoma cell lines, suggesting a true potential for fluorocitrate in different cancer types. Notably, ectopic expression of ACO1 alleviated the susceptibility of cell lines to fluorocitrate and, conversely, knockdown experiments increased susceptibility of resistant cell lines. These findings were confirmed in vivo on athymic nude mice by using tumor xenografts derived from two T-cell lines with different levels of ACO1. Taken together, our results indicate that the non-targeted ACO1 deficiency induced by common deletions exerts a collateral cellular lethality that can be used as a novel therapeutic strategy in the treatment of several types of cancerInstituto de Salud Carlos III (ACCI-CIBERER-17); Spanish Ministerio de Economía y Competitividad (SAF2015-70561 R;MINECO/FEDER, EU); Spanish Ministerio de Ciencia, Innovación y Universidades (RTI2018-093330-B-I00; MCIU/FEDER, EU); Universidad Autónoma de Madrid, Spain (B2017/BMD-3778; LINFOMAS-CM); Spanish Association Against Cancer (AECC, 2018; PROYE18054PIRI); Fundación Ramón Areces (CIVP19S7917); Institutional grants from Fundación Ramón Areces and Banco de Santander to Centro de Biología Molecular Severo Ochoa are also acknowledge

SOCS3 deregulation contributes to aberrant activation of the JAK/STAT pathway in precursor T-cell neoplasms

Despite the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway being frequently altered in T-ALL/LBL, no specific therapy has been approved for T-ALL/LBL patients with constitutive signalling by JAK/STAT, so there is an urgent need to identify pathway members that may be potential therapeutic targets. In the present study, we searched for JAK/STAT pathway members potentially modulated through aberrant methylation and identified SOCS3 hypermethylation as a recurrent event in T-ALL/LBL. Additionally, we explored the implications of SOCS3 deregulation in T-ALL/LBL and demonstrated that SOCS3 counteracts the constitutive activation of the JAK/STAT pathway through different molecular mechanisms. Therefore, SOCS3 emerges as a potential therapeutic target in T-ALL/LBLComunidad de Madrid, Grant/Award Number: B2017/BMD-3778; LINFOMAS-CM; Fundación Científica Asociación Española Contra el Cáncer, Grant/Award Number: PROYE18054PIRI; Fundación Ramón Areces, Grant/Award Number: CIVP19S7917; Instituto de Investigación Sanitaria Fundación Jiménez Díaz; Ministerio de Ciencia, Innovación y Universidades, Grant/ Award Number: RTI2018- 093330-B-I00 and MCIU/FEDER; Ministerio de Economía y Competitividad, Grant/Award Number: SAF2015-70561-R and MINECO/FEDE

Improved metal-graphene contacts for low-noise, high-density microtransistor arrays for neural sensing

Poor metal contact interfaces are one of the main limitations preventing unhampered access to the full potential of two-dimensional materials in electronics. Here we present graphene solution-gated field-effect-transistors (gSGFETs) with strongly improved linearity, homogeneity and sensitivity for small sensor sizes, resulting from ultraviolet ozone (UVO) contact treatment. The contribution of channel and contact region to the total device conductivity and flicker noise is explored experimentally and explained with a theoretical model. Finally, in-vitro recordings of flexible microelectrocorticography (μ-ECoG) probes were performed to validate the superior sensitivity of the UVO-treated gSGFET to brain-like activity. These results connote an important step towards the fabrication of high-density gSGFET μ-ECoG arrays with state-of-the-art sensitivity and homogeneity, thus demonstrating the potential of this technology as a versatile platform for the new generation of neural interfaces

Associations between Daily Movement Distribution, Bone Structure, Falls, and Fractures in Older Adults: A Compositional Data Analysis Study

With aging, bone density is reduced, increasing the risk of suffering osteoporosis and fractures. Increasing physical activity (PA) may have preventive effects. However, until now, no studies have considered movement behaviors with compositional data or its association to bone mass and structure measured by peripheral computed tomography (pQCT). Thus, the aim of our study was to investigate these associations and to describe movement behavior distribution in older adults with previous falls and fractures and other related risk parameters, taking into account many nutritional and metabolic confounders. In the current study, 70 participants above 65 years old (51 females) from the city of Zaragoza were evaluated for the EXERNET-Elder 3.0 project. Bone mass and structure were assessed with pQCT, and PA patterns were objectively measured by accelerometry. Prevalence of fear of falling, risk of falling, and history of falls and fractures were asked through the questionnaire. Analyses were performed using a compositional data approach. Whole-movement distribution patterns were associated with cortical thickness. In regard to other movement behaviors, moderate-to-vigorous PA (MVPA) showed positive association with cortical thickness and total true bone mineral density (BMD) at 38% (all p < 0.05). In addition, less light PA (LPA) and MVPA were observed in those participants with previous fractures and fear of falling, whereas those at risk suggest that different exercise interventions should be designed in these populations in order to improve bone and prevent the risk of osteoporosis and subsequent fractures of falling and those with previous falls showed higher levels of PA. Our results showed positive associations between higher levels of MVPA and volumetric bone. The different movement patterns observed in the groups with a history of having suffered falls or fractures and other risk outcome

Reconstructing the impact of human activities in a NW Iberian Roman mining landscape for the last 2500 years

This article was made available through the Brunel Open Access Publishing Fund.Little is known about the impact of human activities during Roman times on NW Iberian mining landscapes beyond the geomorphological transformations brought about by the use of hydraulic power for gold extraction. We present the high-resolution pollen record of La Molina mire, located in an area intensely used for gold mining (Asturias, NW Spain), combined with other proxy data from the same peat core to identify different human activities, evaluate the strategies followed for the management of the resources and describe the landscape response to human disturbances. We reconstructed the timing and synchronicity of landscape changes of varying intensity and form occurred before, during and after Roman times. An open landscape was prevalent during the local Late Iron Age, a period of relatively environmental stability. During the Early Roman Empire more significant vegetation shifts took place, reflected by changes in both forest (Corylus and Quercus) and heathland cover, as mining/metallurgy peaked and grazing and cultivation increased. In the Late Roman Empire, the influence of mining/metallurgy on landscape change started to disappear. This decoupling was further consolidated in the Germanic period (i.e., Visigothic and Sueve domination of the region), with a sharp decrease in mining/metallurgy but continued grazing. Although human impact was intense in some periods, mostly during the Early Roman Empire, forest regeneration occurred afterwards: clearances were local and short-lived. However, the Roman mining landscape turned into an agrarian one at the onset of the Middle Ages, characterized by a profound deforestation at a regional level due to a myriad of human activities that resulted in an irreversible openness of the landscape. © 2014 The Authors

Metodología experimental aplicada a la Inmunología Molecular

El objetivo general del proyecto es aplicar un modelo pedagógico en el que participen los alumnos de manera activa y apliquen el método científico en base a los conocimientos que han adquirido, resolviendo y realizando un caso práctico en el laboratorio. Integra una estrategia didáctica que va a fomentar la participación activa del alumnado provocando un aprendizaje significativo, ya que el alumno tiene que resolver mediante el razonamiento un caso práctico y luego integrarlo en el laboratorio con el uso de una técnica ampliamente utilizada en Inmunología, como es la citometría de flujo.Depto. de Arquitectura de Computadores y AutomáticaFac. de InformáticaFALSEInnovasubmitte

Miradas y voces de la investigación educativa I

Fil: Ferreyra, Horacio Ademar. Universidad Católica de Córdoba. Facultad de Educación; ArgentinaFil: Calneggia, María Isabel. Universidad Católica de Córdoba. Facultad de Educación; ArgentinaFil: Di Francesco, Adriana Carlota. Universidad Católica de Córdoba. Facultad de Educación; Argentin