117 research outputs found
Respuesta de la respiración del suelo a la temperatura y humedad del suelo en sistemas forestales mediterráneos
La respiración del suelo es uno de los mayores flujos en el ciclo global de carbono y supone unas 80-98 Pg C año-1, por lo que cambios en las condiciones de los suelos pueden tener grandes efectos en las emisiones globales de carbono a la atmósfera. Esto hace que sea importante conocer y entender los mecanismos que influyen en la respiración de los suelos. La temperatura del suelo se ha reconocido como uno de los factores principales que influyen en la respiración del suelo aunque la humedad del suelo no es menos importante, sobre todo en climas como el mediterráneo donde es uno de los factores ecológicos más importantes. El objetivo del trabajo es determinar la relación que tienen la temperatura y la humedad del suelo con la respiración del mismo, y valorar si la gestión forestal influye en dicha relación
Fear recognition for women using a reduced set of physiological signals
This article belongs to the Section Biomedical Sensors.Emotion recognition is benefitting from the latest research into physiological monitoring and wireless communications, among other remarkable achievements. These technologies can indeed provide solutions to protect vulnerable people in scenarios such as personal assaults, the abuse of children or the elderly, gender violence or sexual aggression. Cyberphysical systems using smart sensors, artificial intelligence and wearable and inconspicuous devices can serve as bodyguards to detect these risky situations (through fear-related emotion detection) and automatically trigger a protection protocol. As expected, these systems should be trained and customized for each user to ensure the best possible performance, which undoubtedly requires a gender perspective. This paper presents a specialized fear recognition system for women based on a reduced set of physiological signals. The architecture proposed is characterized by the usage of three physiological sensors, lightweight binary classification and the conjunction of linear (temporal and frequency) and non-linear features. Moreover, a binary fear mapping strategy between dimensional and discrete emotional information based on emotional self-report data is implemented to avoid emotional bias. The architecture is evaluated using a public multi-modal physiological dataset with two approaches (subject-dependent and subject-independent models) focusing on the female participants. As a result, the proposal outperforms the state-of-the-art in fear recognition, achieving a recognition rate of up to 96.33% for the subject-dependent model.This activity is partially supported by Community of Madrid in the pluri-annual agreement with Universidad Carlos III de Madrid, in the line of action "Excelence with the University Faculty", V Regional Plan of Scientific Research and Technology Innovation 2016-2020, and by the Community of Madrid Region Government under the Synergic Program: EMPATIA-CM, Y2018/TCS-5046
Comparative studies on lectin–carbohydrate interactions in low and high density homo- and heteroglycoclusters
12 páginas, 5 figuras, 3 tablas, 3 esquemas.A versatile synthetic procedure to construct series of high- and low-density homo- and heteroglycoclusters is reported. The binding properties of these synthetic multivalent glycoconjugates to concanavalin A (Con A), a model lectin, have been assessed by using a range of competitive and non-competitive binding assays including enzyme-linked lectin assays (ELLA), isothermal titration microcalorimetry (ITC) and surface plasmon resonance (SPR). In all cases, highly dense glycoclusters showed a substantial amplification of the lectin-binding strength in comparison with low-density counterparts. Interestingly, highly-dense glycoligand presentations, regardless of their homo- or heteroglycoligand pattern, furnished similar Con A binding properties, supporting the existence of a synergic effect (heterocluster effect) due to secondary interactions of “non-active” structural motifs in the presence of a certain density of “active” glycoligands.We thank the Spanish Ministerio de Educación y Ciencia (contracts number CTQ2006-15515-C02-01/BQUand CTQ2007-61180/PPQ) and the Junta de Andalucía for financial support.Peer reviewe
Fatal respiratory failure in a term newborn due to non-previously described compound heterozygous ABCA3 mutations
The adenosine triphosphate binding cassette member A3 (ABCA3) is a lipid transporter involved in pulmonary surfactant biogenesis. ABCA3 deficiency is increasingly being recognized as a cause of respiratory distress syndrome in term neonates. The clinical spectrum and severity of lung disease caused by
ABCA3 mutations vary widely. We present a term newborn who presented respiratory distress short afterbirth. Despite treatment and supportive care, she developed a refractory progressive hypoxic respiratory failure and she died. She received repeated surfactant doses always with transient improvement. She was found to be a compound heterozygote for 2 non-previously described ABCA3 gene mutations, one inherited from each parent
Mango ergonómico y sistema para instrumento de cirugía endoscópica o laparoscópica
Mango para una herramienta distal de cirugía endoscópica o laparoscópica, que comprende una empuñadura, una rueda de orientación y una palanca de accionamiento, de tal forma que la palma de la mano y los dedos corazón, anular y meñique rodean y sujetan firmemente la empuñadura, mientras que el dedo pulgar se apoya sobre la palanca de accionamiento, y el dedo índice se apoya sobre la rueda de orientación, tal que la palanca de accionamiento comprende una parte visible, y una parte no visible, donde la parte visible de la palanca de accionamiento está situada en la zona superior de la empuñadura, y su movimiento está comprendido a lo largo del eje longitudinal de la herramienta, presentando diferentes posiciones que conllevan diferentes grados de apertura de la herramienta distal, y tal que una de las direcciones de accionamiento requiere fuerza por parte del portador para conseguir el movimiento de la herramienta distal, mientras que la dirección opuesta no requiere fuerza, y donde la parte no visible de la palanca de accionamiento presenta dos aberturas enfrentadas y configuradas para situar un pivote que sirve a la palanca de accionamiento de sostén en el movimiento, de tal forma que el eje longitudinal del pivote es perpendicular al movimiento de la palanca de accionamiento, y donde además dicha parte no visible de la palanca de accionamiento comprende en su interior un elemento de accionamiento cuyo eje longitudinal es paralelo al eje longitudinal del pivote.Solicitud: 201500530 (15.07.2015)Nº Pub. de Solicitud: ES2562350A1 (03.03.2016)Nº de Patente: ES2562350B2 (28.09.2016
Therapy-Induced Senescence Enhances the Efficacy of HER2-Targeted Antibody–Drug Conjugates in Breast Cancer
Eficàcia; Conjugats de fàrmacs; Càncer de mamaEficacia; Conjugados de medicamentos; Cáncer de mamaEfficacy; Drug conjugates; Breast cancerAntibody–drug conjugates (ADC) are antineoplastic agents recently introduced into the antitumor arsenal. T-DM1, a trastuzumab-based ADC that relies on lysosomal processing to release the payload, is approved for HER2-positive breast cancer. Next-generation ADCs targeting HER2, such as [vic-]trastuzumab duocarmazine (SYD985), bear linkers cleavable by lysosomal proteases and membrane-permeable drugs, mediating a bystander effect by which neighboring antigen-negative cells are eliminated. Many antitumor therapies, like DNA-damaging agents or CDK4/6 inhibitors, can induce senescence, a cellular state characterized by stable cell-cycle arrest. Another hallmark of cellular senescence is the enlargement of the lysosomal compartment. Given the relevance of the lysosome to the mechanism of action of ADCs, we hypothesized that therapies that induce senescence would potentiate the efficacy of HER2-targeting ADCs. Treatment with the DNA-damaging agent doxorubicin and CDK4/6 inhibitor induced lysosomal enlargement and senescence in several breast cancer cell lines. While senescence-inducing drugs did not increase the cytotoxic effect of ADCs on target cells, the bystander effect was enhanced when HER2-negative cells were cocultured with HER2-low cells. Knockdown experiments demonstrated the importance of cathepsin B in the enhanced bystander effect, suggesting that cathepsin B mediates linker cleavage. In breast cancer patient-derived xenografts, a combination treatment of CDK4/6 inhibitor and SYD985 showed improved antitumor effects over either treatment alone. These data support the strategy of combining next-generation ADCs targeting HER2 with senescence-inducing therapies for tumors with heterogenous and low HER2 expression.
Significance:
Combining ADCs against HER2-positive breast cancers with therapies that induce cellular senescence may improve their therapeutic efficacy by facilitating a bystander effect against antigen-negative tumor cells.This work was supported by Breast Cancer Research Foundation (BCRF-20-008), Instituto de Salud Carlos III (project reference numbers AC15/00062, CB16/12/00449 and PI19/01181), the EC under the framework of the ERA-NET TRANSCAN-2 initiative co-financed by FEDER, Fundación Mutua Madrileña and Asociación Española Contra el Cáncer. S. Duro-Sánchez is supported by the Spanish Ministerio de Universidades by the grant Formación de Profesorado Universitario (FPU20/05388). A. Esteve-Codina is funded by ISCIII /MINECO (PT17/0009/0019) and co-funded by FEDER. The authors acknowledge Alyson MacInnes for reviewing and editing the article
New approaches for the identification of KChIP2 ligands to study the KV4.3 channelosome in atrial fibrillati
Resumen del trabajo presentado en el VIII Congreso Red Española de Canales iónico, celebrado en Alicante (España) del 24 al 27 de mayo de 2022.Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3. Kv4.3 is expressed in smooth muscle, heart and brain. Within the heart, Kv4.3 channels generate the transient outward potassium current (ITO). However, ITO characteristics are only observed when Kv4.3 assemble with accessory subunits as KChIP2 and DPP6. KV4.3 channelosome play a key role in atrial fibrillation (AF),the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] KChIP2 (Potassium Channel Interacting Protein 2) belongs to the calcium binding protein superfamily. It is the KChIP member predominantly expressed in heart and a key regulator of cardiac action potential duration. The identification of novel KChIP2 ligands could be useful to understand the role of KV4.3 channelosome in AF and it could help to discover new treatments for AF. [3] In this regard, structure-based virtual screening could be an important tool to accelerate the identification of novel KChIP2 ligands. In this communication, we will describe a multidisciplinary approach that, starting with a structurebased virtual screening, followed by an iterative process of synthesis/biological evaluation/docking studies, has led to the identification of new KChIP2 ligands.PID2019-104366RB-C21, PID2019-104366RB-C22, PID2020-114256RB-I00 and PID2020-119805RB-I00 grants funded by MCIN/AEI/10.13039/501100011033; and PIE202180E073 and 2019AEP148 funded by CSIC. C.V.B. holds PRE2020-093542 FPI grant funded by MCIN/AEI/10.13039/501100011033. PGS was recipient of an FPU grant (FPU17/02731). AB-B holds BES-2017-080184 FPI grant and A.P-L.holds RYC2018-023837-I grant both funded by MCIN/ AEI/ 10.13039/501100011033 and by “ESF Investing in your future
New approaches for the identification of KChIP2 ligands to study the KV4.3 channelosome in atrial fibrillati
Resumen del trabajo presentado en el VIII Congreso Red Española de Canales iónico, celebrado en Alicante (España) del 24 al 27 de mayo de 2022.Ion channels are macromolecular complexes present in the plasma membrane and in intracellular organelles of the cells, where they play important functions. The dysfunction of these channels results in several disorders named channelopathies, which represent a challenge for study and treatment.[1] We are focused on voltage-gated potassium channels, specifically on KV4.3. Kv4.3 is expressed in smooth muscle, heart and brain. Within the heart, Kv4.3 channels generate the transient outward potassium current (ITO). However, ITO characteristics are only observed when Kv4.3 assemble with accessory subunits as KChIP2 and DPP6. KV4.3 channelosome play a key role in atrial fibrillation (AF),the most common cardiac arrhythmia, with an estimated prevalence in the general population of 1.5–2%. However, current antiarrhythmic drugs for AF prevention have limited efficacy and considerable potential for adverse effects.[2] KChIP2 (Potassium Channel Interacting Protein 2) belongs to the calcium binding protein superfamily. It is the KChIP member predominantly expressed in heart and a key regulator of cardiac action potential duration. The identification of novel KChIP2 ligands could be useful to understand the role of KV4.3 channelosome in AF and it could help to discover new treatments for AF. [3] In this regard, structure-based virtual screening could be an important tool to accelerate the identification of novel KChIP2 ligands. In this communication, we will describe a multidisciplinary approach that, starting with a structurebased virtual screening, followed by an iterative process of synthesis/biological evaluation/docking studies, has led to the identification of new KChIP2 ligands.PID2019-104366RB-C21, PID2019-104366RB-C22, PID2020-114256RB-I00 and PID2020-119805RB-I00 grants funded by MCIN/AEI/10.13039/501100011033; and PIE202180E073 and 2019AEP148 funded by CSIC. C.V.B. holds PRE2020-093542 FPI grant funded by MCIN/AEI/10.13039/501100011033. PGS was recipient of an FPU grant (FPU17/02731). AB-B holds BES-2017-080184 FPI grant and A.P-L.holds RYC2018-023837-I grant both funded by MCIN/ AEI/ 10.13039/501100011033 and by “ESF Investing in your future
Cannabinoid receptor CB2 drives HER2 pro-oncogenic signaling in breast cancer
Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different models of cancer. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen and Freiburg between 1997 and 2010. CB2 mRNA expression was also analyzed in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the HER2 rat ortholog (neu) and lacks CB2, and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by co-localization, coimmunoprecipitation and proximity ligation assays. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis. We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade, and that an increased CB2 expression activates the HER2 prooncogenic signaling machinery at the level of the tyrosine kinase c-SRC. Finally, HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and suggest that CB2 may be a biomarker with prognostic value in these tumors
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