67 research outputs found
New perspectives on Latin America in Soledad \uc1lvarez's poems
The poetry of Soledad \uc1lvarez goes from \u2018Vuelo posible\u2019, in which reality is investigated through an erotic and sensual use of words to \u2018Las estaciones \uedntimas\u2019, in which erotism is shaped into softer words reflecting the eternal conflict between reason and emotion. The perspective of the female figure emerges in her texts as a means to achieve and redefine the dominican identity through a painful and hard course towards the disclosure of human soul. This article will investigate the new perception of words in relation to the new chance of building a Nation\u2019s identity through themes that are not only historical
Biomarcadores clínicos de Remisión en pacientes con Artritis Reumatoide tratados con Anti-TNFα
The way rheumatoid arthritis (RA) is treated has changed dramatically in the last decade, with the use of molecular targeted therapies. These durgs act in pathways associated with the inflammatory process, improving disease control with less development of adverse effects. However, there are a percentage of patients in whom these therapies are not effective. So far, no validated biomarkers that can be used as a predictor of response in clinical practice has ben detected. Being able to predict which patients will respond to a certain treatment will optimize treatment with these expensive drugs.
Objectives: To identify biomarkers for anti-TNF therapy remission in patients with rheumatoid arthritis in a large cohort of patients.
Materials and Methods: A total of 628 RA patients that have received theire first anti-TNFα therapy (n = 159 adalimumab, etanercept and infliximab n = 251 n = 218) were included in the present study. All patients were collected as part of the IMID consortium. A number of epidemiological variables (ie origin, toxic habits, physical activity, level of education, etc.) and a large number of variables related to the AR itself (ie age of onset, presence of autoantibodies, previous treatments, etc) were collected. Clinical remission was defined as a value of DAS28El estudio de la fisiopatología de la Artritis Reumatoide (AR) ha permitido el desarrollo de fármacos capaces de actuar de forma precisa en las vías relacionadas con el proceso inflamatorio, logrando un mejor control de la enfermedad con un menor desarrollo de efectos adversos. Sin embargo, existe un porcentaje de pacientes en los que estas terapias no son eficaces. Hasta el momento no existe ningún biomarcador validado que pueda ser utilizado como un predictor de respuesta en la práctica clínica y tampoco se conoce con exactitud el mecanismo biológico por el cual algunos pacientes no responden de forma adecuada a estos tratamientos. El poder predecir que pacientes responderán a un tratamiento determinado permitirá optimizar el tratamiento con estos agentes.
Objetivo: Identificar biomarcadores de remisión no genéticos al tratamiento con terapias anti-TNFα en pacientes con artritis reumatoide en una gran cohorte de pacientes.
Materiales y métodos: Se incluyó a los 628 pacientes con diagnóstico de AR del proyecto PSE IMID-Kit que iniciaban una terapia biológica (adalimumab n=159, etanercept n=251 e infliximab n=218). Se registraron una serie de variables epidemiológicas (i.e. procedencia, habitos tóxicos, actividad física, grado de estudios, etc) y un elevado número de variables relacionadas con la propia AR (i.e. edad de inicio, presencia de autoanticuerpos, tratamientos previos, etc). La remisión clínica fue definida como un valor del DAS2
Whole brain radiotherapy with adjuvant or concomitant boost in brain metastasis: dosimetric comparison between helical and volumetric IMRT technique
To compare and evaluate the possible advantages related to the use of VMAT and helical IMRT and two different modalities of boost delivering, adjuvant stereotactic boost (SRS) or simultaneous integrated boost (SIB), in the treatment of brain metastasis (BM) in RPA classes I-II patients
Zc3h10 regulates adipogenesis by controlling translation and F-actin/mitochondria interaction
The commitment of mesenchymal stem cells to preadipocytes is stimulated by hormonal induction. Preadipocytes induced to differentiate repress protein synthesis, remodel their cytoskeleton, and increase mitochondrial function to support anabolic pathways. These changes enable differentiation into mature adipocytes. Our understanding of the factors that coordinately regulate the early events of adipocyte differentiation remains incomplete. Here, by using multipronged approaches, we have identified zinc finger CCCH-type containing 10 (Zc3h10) as a critical regulator of the early stages of adipogenesis. Zc3h10 depletion in preadipocytes resulted in increased protein translation and impaired filamentous (F)-actin remodeling, with the latter detrimental effect leading to mitochondrial and metabolic dysfunction. These defects negatively affected differentiation to mature adipocytes. In contrast, Zc3h10 overexpression yielded mature adipocytes with remarkably increased lipid droplet size. Overall, our study establishes Zc3h10 as a fundamental proadipogenic transcription factor that represses protein synthesis and promotes F-actin/mitochondria dynamics to ensure proper energy metabolism and favor lipid accumulation
Author Correction: Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth
Reprogramming of amino acid metabolism, sustained by oncogenic signaling, is crucial for cancer cell survival under nutrient limitation. Here we discovered that missense mutant p53 oncoproteins stimulate de novo serine/glycine synthesis and essential amino acids intake, promoting breast cancer growth. Mechanistically, mutant p53, unlike the wild-type counterpart, induces the expression of serine-synthesis-pathway enzymes and L-type amino acid transporter 1 (LAT1)/CD98 heavy chain heterodimer. This effect is exacerbated by amino acid shortage, representing a mutant p53-dependent metabolic adaptive response. When cells suffer amino acids scarcity, mutant p53 protein is stabilized and induces metabolic alterations and an amino acid transcriptional program that sustain cancer cell proliferation. In patient-derived tumor organoids, pharmacological targeting of either serine-synthesis-pathway and LAT1-mediated transport synergizes with amino acid shortage in blunting mutant p53-dependent growth. These findings reveal vulnerabilities potentially exploitable for tackling breast tumors bearing missense TP53 mutation
Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth
Reprogramming of amino acid metabolism, sustained by oncogenic signaling, is crucial for cancer cell survival under nutrient limitation. Here we discovered that missense mutant p53 oncoproteins stimulate de novo serine/glycine synthesis and essential amino acids intake, promoting breast cancer growth. Mechanistically, mutant p53, unlike the wild-type counterpart, induces the expression of serine-synthesis-pathway enzymes and L-type amino acid transporter 1 (LAT1)/CD98 heavy chain heterodimer. This effect is exacerbated by amino acid shortage, representing a mutant p53-dependent metabolic adaptive response. When cells suffer amino acids scarcity, mutant p53 protein is stabilized and induces metabolic alterations and an amino acid transcriptional program that sustain cancer cell proliferation. In patient-derived tumor organoids, pharmacological targeting of either serine-synthesis-pathway and LAT1-mediated transport synergizes with amino acid shortage in blunting mutant p53-dependent growth. These findings reveal vulnerabilities potentially exploitable for tackling breast tumors bearing missense TP53 mutations.Mutant p53 induces serine/glycine synthesis and essential amino acids intake. Under amino acid restriction, mutant p53 is stabilized and activates a transcriptional program that sustains a metabolic adaptive response promoting breast cancer cells growt
High-throughput gene discovery in the rat
The rat is an important animal model for human diseases and is widely used in physiology. In this article we present a new strategy for gene discovery based on the production of ESTs from serially subtracted and normalized cDNA libraries, and we describe its application for the development of a comprehensive nonredundant collection of rat ESTs. Our new strategy appears to yield substantially more EST clusters per ESTs sequenced than do previous approaches that did not use serial subtraction. However, multiple rounds of library subtraction resulted in high frequencies of otherwise rare internally primed cDNAs, defining the limits of this powerful approach. To date, we have generated >200,000 3′ ESTs from >100 cDNA libraries representing a wide range of tissues and developmental stages of the laboratory rat. Most importantly, we have contributed to ∼50,000 rat UniGene clusters. We have identified, arrayed, and derived 5′ ESTs from >30,000 unique rat cDNA clones. Complete information, including radiation hybrid mapping data, is also maintained locally at http://genome.uiowa.edu/clcg.html. All of the sequences described in this article have been submitted to the dbEST division of the NCBI
The Effect of Pre-Event Instructions on Eyewitness Identification
Research on eyewitness identification often involves exposing participants to a simulated crime and later testing memory using a lineup. We conducted a systematic review showing that pre-event instructions, instructions given before event exposure, are rarely reported and those that are reported vary in the extent to which they warn participants about the nature of the event or tasks. At odds with the experience of actual witnesses, some studies use pre-event instructions explicitly warning participants of the upcoming crime and lineup task. Both the basic and applied literature provide reason to believe that pre-event instructions may affect eyewitness identification performance. In the current experiment, we tested the impact of pre-event instructions on lineup identification decisions and confidence. Participants received non-specific pre-event instructions (i.e., “watch this video”) or eyewitness pre-event instructions (i.e., “watch this crime video, you’ll complete a lineup later”) and completed a culprit-absent or -present lineup. We found no support for the hypothesis that participants who receive eyewitness pre-event instructions have higher discriminability than participants who receive non-specific pre-event instructions. Additionally, confidence-accuracy calibration was not significantly different between conditions. However, participants in the eyewitness condition were more likely to see the event as a crime and to make an identification than participants in the non-specific condition. Implications for conducting and interpreting eyewitness identification research and the basic research on instructions and attention are discussed
New perspectives on Latin America in Soledad Álvarez’s poems
Ilustración: "Joel's ́pix (Iceland etc) 169", EasyflicThe poetry of Soledad Álvarez goes from Vuelo posible, in which reality is investigated through an erotic and sensual use of words to Las estaciones íntimas, in which erotism is shaped into softer words reflecting the eternal conflict between reason and emotion. The perspective of the female figure emerges in her texts as a means to achieve and redefine the identity of Santo Domingo through a painful
and hard course towards the disclosure of human soul. This article will investigate the new perception of words in relation to the new chance of building a Nation’s identity through themes that are not only
historical
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