46 research outputs found
p57Kip2 Phosphorylation Modulates Its Localization, Stability, and Interactions
No full textp57Kip2 is a member of the cyclin-dependent kinase (CDK) Interacting Protein/Kinase Inhibitory Protein (CIP/Kip) family that also includes p21Cip1/WAF1 and p27Kip1. Different from its siblings, few data are available about the p57Kip2 protein, especially in humans. Structurally, p57Kip2 is an intrinsically unstructured protein, a characteristic that confers functional flexibility with multiple transient interactions influencing the metabolism and roles of the protein. Being an IUP, its localization, stability, and binding to functional partners might be strongly modulated by post-translational modifications, especially phosphorylation. In this work, we investigated by two-dimensional analysis the phosphorylation pattern of p57Kip2 in different cellular models, revealing how the human protein appears to be extensively phosphorylated, compared to p21Cip1/WAF1 and p27Kip1. We further observed clear differences in the phosphoisoforms distributed in the cytosolic and nuclear compartments in asynchronous and synchronized cells. Particularly, the unmodified form is detectable only in the nucleus, while the more acidic forms are present in the cytoplasm. Most importantly, we found that the phosphorylation state of p57Kip2 influences the binding with some p57Kip2 partners, such as CDKs, LIMK1 and CRM1. Thus, it is necessary to completely identify the phosphorylated residues of the protein to fully unravel the roles of this CIP/Kip protein, which are still partially identified
Serendipity Virtual Elements for General Elliptic Equations in Three Dimensions
No full textWe study the use of the Virtual Element Method (VEM) of order k for general second order elliptic problems with variable coefficients in three space dimensions. Moreover, we investigate numerically also the Serendipity version of the VEM and the associated computational gain in terms of degrees of freedom
abCDEuropa: guida al wiki dei CDE italiani
No full textIl wiki dei CDE italiani è uno strumento pensato e creato specificamente per l’uso online poiché ha una struttura reticolare di rimandi incrociati invece di un’esposizione lineare.Questa breve guida non intende quindi riproporre il wiki dei CDE, che è uno strumento dinamico in continua evoluzione e aggiornamento, bensì fornire in una pluralità di supporti oltre al web - carta, libro elettronico - indicazioni generali e sintetiche sui principali contenuti del wiki
An Anisoptropic Surface Remeshing Strategy Combining Higher Dimensional Embedding with Radial Basis Functions
Get PDFAbstractMany applications heavily rely on piecewise triangular meshes to describe complex surface geometries. High-quality meshes significantly improve numerical simulations. In practice, however, one often has to deal with several challenges. Some regions in the initial mesh may be overrefined, others too coarse. Additionally, the triangles may be too thin or not properly oriented. We present a novel mesh adaptation procedure which greatly improves the problematic input mesh and overcomes all of these drawbacks. By coupling surface reconstruction via radial basis functions with the higher dimensional embedding surface remeshing technique, we can automatically generate anisotropic meshes. Moreover, we are not only able to fill or coarsen certain mesh regions but also align the triangles according to the curvature of the reconstructed surface. This yields an acceptable trade-off between computational complexity and accuracy
Tetrahedral Mesh Improvement Using Moving Mesh Smoothing and Lazy Searching Flips
Get PDFAbstractWe combine the new moving mesh smoothing, based on the integration of an ordinary differential equation coming from a given functional, with the new lazy flip technique, a reversible edge removal algorithm for local mesh quality improvement. These strategies already provide good mesh improvement on themselves, but their combination achieves astonishing results not reported so far. Provided numerical comparison with some publicly available mesh improving software show that we can obtain final tetrahedral meshes with dihedral angles between 40° and 123°
Prune-1 drives polarization of tumor-associated macrophages (TAMs) within the lung metastatic niche in triple-negative breast cancer
Get PDFM2-tumor-associated macrophages (M2-TAMs) in the tumor microenvironment represent a prognostic indicator for poor outcome in triple-negative breast cancer (TNBC).
Here we show that Prune-1 overexpression in human TNBC patients has positive correlation to lung metastasis and infiltrating M2-TAMs. Thus, we demonstrate that Prune-1 promotes lung metastasis in a genetically engineered mouse model of metastatic TNBC augmenting M2-polarization of TAMs within the tumor microenvironment. Thus, this occurs through TGF-beta enhancement, IL-17F secretion, and extracellular vesicle protein content modulation.
We also find murine inactivating gene variants in human TNBC patient cohorts that are involved in activation of the innate immune response, cell adhesion, apoptotic pathways, and DNA repair. Altogether, we indicate that the overexpression of Prune-1, IL-10, COL4A1, ILR1, and PDGFB, together with inactivating mutations of PDE9A, CD244, Sirpblb, SV140, lqcal, and PIP5K1B genes, might represent a route of metastatic lung dissemination that need future prognostic validations
Detection of Human Papillomaviruses in the Nasopharynx of Breastfed Infants: New Findings and Meta-Analysis
No full textVertical transmission of human papillomaviruses (HPVs) from mother to infant is known to occur during labor, delivery or breastfeeding. Infection with mucosal HPV 6 and 11 may cause recurrent respiratory papillomatosis in children, which is a rare and severe respiratory disease. The cutaneous HPV genotypes have also been described to be transmitted from mother to newborn through skin-to-skin contacts and during breastfeeding. To investigate the perinatal transmission of alpha and beta HPVs we collected nasopharyngeal specimens from 0–12-months-old infants born by vaginal delivery and breastfed at the time of sample collection. The mucosal and cutaneous HPVs were searched by nested PCR using the MY09/11-MGPs and CP65/70-CP66/69 primer sets, respectively, and genotypes identified by direct sequencing analysis. Fourteen out of 113 (12.4%) samples tested positive for HPV and sequence analysis allowed us to identify eight beta genotypes (HPV 5b, 20, 25, 100, 107, 124, 152 and RTRX7). Moreover, we performed a comprehensive review of published studies on the prevalence of mucosal and cutaneous HPVs among 5126 newborns and observed that 10% and 53% were positive for alpha and beta HPVs, respectively. In all studies there was an inverse correlation between the rate of alpha HPV positivity and age, while a significant positive trend was observed in beta HPV detection and age with the highest rate among children older than 12 months (Χ2 test for trend of 10.6, p < 0.001). Further studies are needed to confirm the hypothesis that beta HPVs are transmitted to breastfeeding infants through shedding of viruses in the breast milk or on the external breast epithelium
abCDEuropa: guida al wiki dei CDE italiani
No full textIl wiki dei CDE italiani è uno strumento pensato e creato specificamente per l’uso online poiché ha una struttura reticolare di rimandi incrociati invece di un’esposizione lineare.
Questa breve guida non intende quindi riproporre il wiki dei CDE, che è uno strumento dinamico in continua evoluzione e aggiornamento, bensì fornire in una pluralità di supporti oltre al web - carta, libro elettronico - indicazioni generali e sintetiche sui principali contenuti del wiki
CAG repeat expansion in the Huntington's disease gene shapes linear and circular RNAs biogenesis.
No full textAlternative splicing (AS) appears to be altered in Huntington's disease (HD), but its significance for early, pre-symptomatic disease stages has not been inspected. Here, taking advantage of Htt CAG knock-in mouse in vitro and in vivo models, we demonstrate a correlation between Htt CAG repeat length and increased aberrant linear AS, specifically affecting neural progenitors and, in vivo, the striatum prior to overt behavioral phenotypes stages. Remarkably, a significant proportion (36%) of the aberrantly spliced isoforms are not-functional and meant to non-sense mediated decay (NMD). The expanded Htt CAG repeats further reflect on a previously neglected, global impairment of back-splicing, leading to decreased circular RNAs production in neural progenitors. Integrative transcriptomic analyses unveil a network of transcriptionally altered micro-RNAs and RNA-binding proteins (Celf, hnRNPs, Ptbp, Srsf, Upf1, Ythd2) which might influence the AS machinery, primarily in neural cells. We suggest that this unbalanced expression of linear and circular RNAs might alter neural fitness, contributing to HD pathogenesis
O lado negro do preto: o fardo da farda narrativas de integrantes do BOPE-SC sobre mandato policial de grupos especiais de polícia
Get PDFDissertação (mestrado) - Unversidade Federal de Santa Catarina, Centro de Filosofia e Ciências Humanas, Programa de Pós-Graduação em Antropologia Social, Florianópolis, 2010Aborda-se o conceito de mandato policial de grupos especiais de polícia a partir de observação participante e entrevistas junto a integrantes do BOPE-SC, tendo como método a análise de narrativas. Apresenta-se a carência de estudos que tratem explicitamente do mandato policial e algumas possíveis compreensíveis do que o seja a partir de uma análise da produção bibliográfica encontrada. Abordam-se, especificamente, as menções ao mandato policial de grupos especiais de polícia, ressaltando-se que só foram encontradas em manuais/monografias/sites de autoria de instituições de Segurança Pública ou representantes delas, nas quais o discurso não é analítico, mas apenas prescritivo/normativo. O fato de apenas nativos haverem falado, até o momento, sobre grupos especiais de polícia articula-se com as considerações feitas a propósito da posição do pesquisador em Antropologia, haja vista a condição da própria autora de compor o quadro de uma força policial ter sido uma via de entrada em campo. A entrada em campo também é descrita, a partir do uso que os participantes fizeram das categorias de mulher, psicóloga e policial civil, como já tendo sinalizado uma categoria fundamental para o entendimento do mandato policial de grupos especiais de polícia: a de masculinidade, identificada pelos policiais a atributos de virilidade como o uso da força e como condição na qual o sujeito se iniciaria. Fundamenta-se, no capítulo seguinte, como a representação que os policiais em questão fazem dos suspeitos/autores de crimes tem por função a estruturação, por oposição, da identidade do grupo especial de polícia. Em seguida, discute-se que o mandato de grupos especiais de grupo de polícia coloca em suspensão as categorias de Justiça e Direito, sendo que os policiais definem em seu trabalho sempre tendo por referência (tanto para se aproximar, como para se distanciar) o ordenamento jurídico e para, a partir dele, definirem o que consideram o princípio fundamental de sua atuação: a justiça. Entende-se que a suspensão de tais categorias deve ser pensada a partir das concepções destes policiais sobre o que os particulariza (que é, a propósito, o mesmo que entendem que os diferencia da polícia convencional): uma certa moral. Moral esta desenvolvida e visibilizada pelos treinamentos/cursos de formação e #mística# própria ao batalhão, e que atenderia a anseios inclusive da própria sociedade. Sobre a última, cabe mencionar a particular função da farda do batalhão: a de distintivo. Como uma síntese das discussões realizadas até o momento, compreende-se o mandato policial de grupos especiais de polícia como fundado em um ethos guerreiro, a partir do quê os policiais compreendem as relações estabelecidas entre as praças e os oficiais, entre o Comando do BOPE-SC e seus subordinados, entre o Comando do BOPE-SC e o Comando Geral. Este ethos guerreiro é exemplarmente manifesto no uso que fazem de metáforas animas e da categoria #rusticidade# para falarem de todas estas relações; principalmente, para falarem do trânsito entre diferentes posições hierárquicas realizado por todos os envolvidos nestas relações.The concept of police mandate of special police units is approached through communicating observation and interviews with police officers of BOPE-SC, using as a method the narrative analyses. The literature about police mandate shows a lack of studies that address explicitly the police mandate, as well as several possible understandings of what it is, originating from the overview of a bibliographic production found. References to the mandate of police special units have been specially approached, emphasizing that they had been found in manuals/monographs/websites authored by institutions of Public Safety or their representatives, in which the speech is not analytical, but only prescriptive/normative. The fact that only native people have spoken about special police units so far is articulated with the considerations made about the position of the anthropology researcher, considering that even the author belongs to the ranks of a police force was a way of entry in field. The ingress into the field is also described through the use made by the participants of the categories of woman, psychologist and civil police officer, as pointing a fundamental category for the understanding of the police mandate of special police units: the one of masculinity, identified by the police officers as attributes of virility as the use of strength and as a condition in which people would begin. It is for this structure role that masculinity, thus understood, has for the group, who identify himself as opposed to feminine. It is based, still, as a representation that the police officers do about suspects/offenders have as their function the structuring, also for opposition, of the police special unit#s identity. Then, it is brought about that the mandate of special police units puts in suspension the categories of Law and Justice, once the policemen agree in their work always having as reference (for both approaches, and to distance themselves from) the legal methodology, in order to, according to it, determine what they consider the fundamental principle of its activities: the justice. It#s of common understanding that the suspension of these categories must be thought from the conceptions of these police officers about what particularize them (which is, moreover, the same understanding that differ them from the conventional police): a certain moral. This moral developed and visualized by practice/training courses and "mystical" of the own battalion, that would respond to the concerns even of the society itself. About this mystical, it#s important to mention the particular function of the uniform of the battalion: as the distinguishing. As a summary of the discussions held so far, the police mandate of special police units is understood as founded in a warrior ethos, from what the police officers understand the relations set between the non-commissioned officers and the officers, between the BOPE's command and its subordinates, and between the BOPE's command and the General Command of the Military Police. This warrior ethos is exemplary manifested in their use of animal metaphors and in the category of "rusticity" to talk about all these relations, mainly to talk about the traffic between different hierarchical positions made by all the people involved in these relationships
