CARACTERIZACIÓN FISICOQUÍMICA Y SENSORIAL DE Vanilla planifolia Jacks. ex Andrews CON DIFERENTES ESQUEMAS DE BENEFICIADO

Vanilla is an important and valuable aromatic species worldwide; it is native from Mexico, currently the fifth most important producer in the international market. The vanilla fruits (siliques) develop unique physicochemical and sensory traits through a mostly traditional fermentative process (curing) and from these a vainillin-rich extract is obtained, which is the principal aromatic agent. Although a Mexican Norm (NMX) regulates pod quality characteristics, various criteria are not very precise and lacks a description of sensory attributes. Cured fruits were sampled from different locations in Puebla and Veracruz and physicochemically characterized to correlate them to the NMX; besides a sensory profile was developed based on their geographic origin and curing scheme. None of these variables could clearly explain variations on physicochemical parameters and sensory profiles obtained. Thus, a more controlled study is suggested to obtain more consistent conclusions.La vainilla es una especie aromática importante y valuada a nivel global; es originaria de México, quien es el quinto productor en el mercado internacional. Los frutos (silicuas) de vainilla desarrollan características fisicoquímicas y sensoriales únicas a través de un proceso fermentativo mayoritariamente tradicional (beneficiado), y a partir de ellos se obtiene un extracto rico en vainillina, que es el principal agente aromático. Aunque existe una Norma Mexicana (NMX) que regula aspectos de calidad de las vainas, diversos criterios son poco precisos y carece de una descripción de los atributos sensoriales. Se muestrearon frutos beneficiados de diferentes locaciones de Puebla y Veracruz, México, para caracterizarlos fisicoquímicante y correlacionarlas con la NMX; además se desarrolló un perfil sensorial de acuerdo a su origen geográfico y esquema de beneficiado. Ninguna de estas variables pudo explicar claramente las variaciones en parámetros fisicoquímicos y en los perfiles sensoriales obtenidos, por lo que se sugiere un estudio más controlado para obtener conclusiones más consistentes

Homozygous R136S mutation in PRNP gene causes inherited early onset prion disease

Altres ajuts: Fundació la Marató de TV3/201821-31Background: More than 40 pathogenic heterozygous PRNP mutations causing inherited prion diseases have been identified to date. Recessive inherited prion disease has not been described to date. Methods: We describe the clinical and neuropathological data of inherited early-onset prion disease caused by the rare PRNP homozygous mutation R136S. In vitro PrP propagation studies were performed using recombinant-adapted protein misfolding cyclic amplification technique. Brain material from two R136S homozygous patients was intracranially inoculated in TgMet129 and TgVal129 transgenic mice to assess the transmissibility of this rare inherited form of prion disease. Results: The index case presented symptoms of early-onset dementia beginning at the age of 49 and died at the age of 53. Neuropathological evaluation of the proband revealed abundant multicentric PrP plaques and Western blotting revealed a ~ 8 kDa protease-resistant, unglycosylated PrP fragment, consistent with a Gerstmann-Sträussler-Scheinker phenotype. Her youngest sibling suffered from progressive cognitive decline, motor impairment, and myoclonus with onset in her late 30s and died at the age of 48. Genetic analysis revealed the presence of the R136S mutation in homozygosis in the two affected subjects linked to homozygous methionine at codon 129. One sibling carrying the heterozygous R136S mutation, linked to homozygous methionine at codon 129, is still asymptomatic at the age of 74. The inoculation of human brain homogenates from our index case and an independent case from a Portuguese family with the same mutation in transgenic mice expressing human PrP and in vitro propagation of PrP studies failed to show disease transmissibility. Conclusion: In conclusion, biallelic R136S substitution is a rare variant that produces inherited early-onset human prion disease with a Gerstmann-Sträussler-Scheinker neuropathological and molecular signature. Even if the R136S variant is predicted to be "probably damaging", heterozygous carriers are protected, at least from an early onset providing evidence for a potentially recessive pattern of inheritance in human prion diseases

Infrared-Emitting Multimodal Nanostructures for Controlled In Vivo Magnetic Hyperthermia

Deliberate and local increase of the temperature within solid tumors represents an effective therapeutic approach. Thermal therapies embrace this concept leveraging the capability of some species to convert the absorbed energy into heat. To that end, magnetic hyperthermia (MHT) uses magnetic nanoparticles (MNPs) that can effectively dissipate the energy absorbed under alternating magnetic fields. However, MNPs fail to provide real-time thermal feedback with the risk of unwanted overheating and impeding on-the-fly adjustment of the therapeutic parameters. Localization of MNPs within a tissue in an accurate, rapid, and cost-effective way represents another challenge for increasing the efficacy of MHT. In this work, MNPs are combined with state-of-the-art infrared luminescent nanothermometers (LNTh; Ag2S nanoparticles) in a nanocapsule that simultaneously overcomes these limitations. The novel optomagnetic nanocapsule acts as multimodal contrast agents for different imaging techniques (magnetic resonance, photoacoustic and near-infrared fluorescence imaging, optical and X-ray computed tomography). Most crucially, these nanocapsules provide accurate (0.2 degrees C resolution) and real-time subcutaneous thermal feedback during in vivo MHT, also enabling the attainment of thermal maps of the area of interest. These findings are a milestone on the road toward controlled magnetothermal therapies with minimal side effects.E.X. and R.M. contributed equally to this work. Work partially supported by the Ministerio de Ciencia, Innovación y Universidades (PID2019-106301RB-I00 and PID2019-105195RA-I00), by the Spanish Ministry of Economy and Competitiveness (MAT2017-85617-R, SEV-2016-0686), by the Comunidad de Madrid (RENIM-CM, B2017/BMD-3867, co-financed by the European Structural and Investment Fund; NANOMAGCOST-CM P2018/NMT-4321), by the European COST Actions CA17115 (MyWave) and CA17140 (Nano2Clinic), by the Spanish Scientific Network HiperNano (RED2018-102626-T) and by the European Commission Horizon 2020 project NanoTBTech (Grant Number: 801305). D.G.-C. acknowledges CAM for funding PEJ-2018-AI/IND-11245. A.B. acknowledges funding from Comunidad de Madrid through TALENTO grant ref. 2019-T1/IND-14014. E.X. is grateful for a Juan de la Cierva Formación scholarship (FJC2018-036734-I). R.M. acknowledges the support of the European Commission through the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant agreement N 797945 (LANTERNS). A. E. acknowledges the support from Comunidad de Madrid (Talento project 2018-T1/IND-1005) and from AECC (Ideas Semilla 2019 project). P.R.S. is grateful for a Juan de la Cierva Incorporación scholarship (IJC2019-041915-I). Procedures involving animal experiments were approved by the regional authority for animal experimentation of the Comunidad de Madrid and were conducted in agreement with the Universidad Autónoma de Madrid Ethics Committee, in compliance with the European Union directives 63/2010UE and Spanish regulation RD 53/2013

TESLA Technical Design Report Part III: Physics at an e+e- Linear Collider

The TESLA Technical Design Report Part III: Physics at an e+e- Linear ColliderComment: 192 pages, 131 figures. Some figures have reduced quality. Full quality figures can be obtained from http://tesla.desy.de/tdr. Editors - R.-D. Heuer, D.J. Miller, F. Richard, P.M. Zerwa

Inhibition of Specific NF-κB Activity Contributes to the Tumor Suppressor Function of 14-3-3σ in Breast Cancer

14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting

Short Day–Mediated Cessation of Growth Requires the Downregulation of AINTEGUMENTALIKE1 Transcription Factor in Hybrid Aspen

Day length is a key environmental cue regulating the timing of major developmental transitions in plants. For example, in perennial plants such as the long-lived trees of the boreal forest, exposure to short days (SD) leads to the termination of meristem activity and bud set (referred to as growth cessation). The mechanism underlying SD–mediated induction of growth cessation is poorly understood. Here we show that the AIL1-AIL4 (AINTEGUMENTALIKE) transcription factors of the AP2 family are the downstream targets of the SD signal in the regulation of growth cessation response in hybrid aspen trees. AIL1 is expressed in the shoot apical meristem and leaf primordia, and exposure to SD signal downregulates AIL1 expression. Downregulation of AIL gene expression by SDs is altered in transgenic hybrid aspen plants that are defective in SD perception and/or response, e.g. PHYA or FT overexpressors. Importantly, SD–mediated regulation of growth cessation response is also affected by overexpression or downregulation of AIL gene expression. AIL1 protein can interact with the promoter of the key cell cycle genes, e.g. CYCD3.2, and downregulation of the expression of D-type cyclins after SD treatment is prevented by AIL1 overexpression. These data reveal that execution of SD–mediated growth cessation response requires the downregulation of AIL gene expression. Thus, while early acting components like PHYA and the CO/FT regulon are conserved in day-length regulation of flowering time and growth cessation between annual and perennial plants, signaling pathways downstream of SD perception diverge, with AIL transcription factors being novel targets of the CO/FT regulon connecting the perception of SD signal to the regulation of meristem activity