The connexin43 mimetic peptide Gap19 inhibits hemichannels without altering gap junctional communication in astrocytes

In the brain, astrocytes represent the cellular population that expresses the highest amount of connexins (Cxs). This family of membrane proteins is the molecular constituent of gap junction channels and hemichannels that provide pathways for direct cytoplasm-to-cytoplasm and inside-out exchange, respectively. Both types of Cx channels are permeable to ions and small signaling molecules allowing astrocytes to establish dynamic interactions with neurons. So far, most pharmacological approaches currently available do not distinguish between these two channel functions, stressing the need to develop new specific molecular tools. In astrocytes two major Cxs are expressed, Cx43 and Cx30, and there is now evidence indicating that at least Cx43 operates as a gap junction channel as well as a hemichannel in these cells. Based on studies in primary cultures as well as in acute hippocampal slices, we report here that Gap 19, a nonapeptide derived from the cytoplasmic loop of Cx43, inhibits astroglial Cx43 hemichannels in a dose-dependent manner, without affecting gap junction channels. This peptide, which not only selectively inhibits hemichannels but is also specific for Cx43, can be delivered in vivo in mice as TAT-Gap19, and displays penetration into the brain parenchyma. As a result, Gap 19 combined with other tools opens up new avenues to decipher the role of Cx43 hemichannels in interactions between astrocytes and neurons in physiological as well as pathological situations

Fundamentos necesarios para el uso efectivo de la fuerza en la función policial

Human rights defenders and specialists in the field often states that > means police action in line with international standards of human rights. Although this is, without doubt, true, it must be understood that international standards of human rights only offers a limited orientation for a daily police work. In fact, good police work can never be fully grasped in rules and regulations, no matter how numerous and detailed these are. The necessary discretion that the police needs in order to perform its functions, presents problems for human rights defenders because they prefer clear regulations to measure the police behavior. Many police officers consider that the arguments of the defenders of human rights are naive that reflects the lacks of comprehension of their reality and try to impose an unrealistic burden on the police work. On the other hand, human rights defenders argue that the police use this as an excuse to deflect criticism. Immersion in the differentiated use of force, allows police servers to understand the limits of their functions within the operation generated by a group of people who, under different laws and regulations stipulated in the rules of good living, generates instability to the society, that is why the applicability of the differentiated use of force by the police gets involved in events formed by these human behaviors that are not in accordance with the rules and regulations of the law.Los defensores de los derechos humanos y los especialistas en la materia suelen sostener que «acción policial buena» significa una acción policial acorde con las normas internacionales de derechos humanos. Aunque esto es sin duda cierto, debe entenderse que las normas internacionales de derechos humanos sólo ofrecen una orientación limitada para el trabajo policial diario. De hecho, el buen trabajo policial nunca puede captarse plenamente en las normas y los reglamentos, por muy numerosos y detallados que sean. La necesaria discrecionalidad que la policía precisa para desempeñar sus funciones plantea problemas a los defensores de los derechos humanos que prefieren tener normas claras para medir el comportamiento de la policía. Muchos policías consideran que los razonamientos de los defensores de los derechos humanos son ingenuos, en el mejor de los casos, y teóricos, por no decir más, que reflejan la falta de comprensión de su realidad e imponen una carga poco realista al trabajo policial. Los defensores de los derechos humanos, por su parte, sostienen que la policía utiliza esto como excusa para eludir las críticas. La inmersión en el uso diferenciado de la fuerza, permite a los servidores policiales entender los límites de sus funciones dentro de la operatividad generada por un grupo de personas que, en condiciones diferentes a las leyes y regulaciones que estipulan las normas del buen vivir, generan inestabilidad a la sociedad, es por ello que la aplicabilidad del uso diferenciado de la fuerza por parte de los efectivos policiales se enzarza a los eventos formados por estas conductas humanas que no son acorde a las normas y reglamentos de ley

Continuous Experimentation and the cyber-physical systems challenge: An overview of the literature and the industrial perspective.

Context: New software development patterns are emerging aiming at accelerating the process of delivering value. One is Continuous Experimentation, which allows to systematically deploy and run instrumented software variants during development phase in order to collect data from the field of application. While currently this practice is used on a daily basis on web-based systems, technical difficulties challenge its adoption in fields where computational resources are constrained, e.g., cyber-physical systems and the automotive industry. Objective: This paper aims at providing an overview of the engagement on the Continuous Experimentation practice in the context of cyber-physical systems.Method: A systematic literature review has been conducted to investigate the link between the practice and the field of application. Additionally, an industrial multiple case study is reported. Results: The study presents the current state-of-the-art regarding Continuous Experimentation in the field of cyber-physical systems. The current perspective of Continuous Experimentation in industry is also reported. Conclusions: The field has not reached maturity yet. More conceptual analyses are found than solution proposals and the state-of-practice is yet to be achieved. However it is expected that in time an increasing number of solutions will be proposed and validated

Dipeptide repeat proteins inhibit homology-directed DNA double strand break repair in C9ORF72 ALS/FTD

BACKGROUND: The C9ORF72 hexanucleotide repeat expansion is the most common known genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two fatal age-related neurodegenerative diseases. The C9ORF72 expansion encodes five dipeptide repeat proteins (DPRs) that are produced through a non-canonical translation mechanism. Among the DPRs, proline-arginine (PR), glycine-arginine (GR), and glycine-alanine (GA) are the most neurotoxic and increase the frequency of DNA double strand breaks (DSBs). While the accumulation of these genotoxic lesions is increasingly recognized as a feature of disease, the mechanism(s) of DPR-mediated DNA damage are ill-defined and the effect of DPRs on the efficiency of each DNA DSB repair pathways has not been previously evaluated. METHODS AND RESULTS: Using DNA DSB repair assays, we evaluated the efficiency of specific repair pathways, and found that PR, GR and GA decrease the efficiency of non-homologous end joining (NHEJ), single strand annealing (SSA), and microhomology-mediated end joining (MMEJ), but not homologous recombination (HR). We found that PR inhibits DNA DSB repair, in part, by binding to the nucleolar protein nucleophosmin (NPM1). Depletion of NPM1 inhibited NHEJ and SSA, suggesting that NPM1 loss-of-function in PR expressing cells leads to impediments of both non-homologous and homology-directed DNA DSB repair pathways. By deleting NPM1 sub-cellular localization signals, we found that PR binds NPM1 regardless of the cellular compartment to which NPM1 was directed. Deletion of the NPM1 acidic loop motif, known to engage other arginine-rich proteins, abrogated PR and NPM1 binding. Using confocal and super-resolution immunofluorescence microscopy, we found that levels of RAD52, a component of the SSA repair machinery, were significantly increased iPSC neurons relative to isogenic controls in which the C9ORF72 expansion had been deleted using CRISPR/Cas9 genome editing. Western analysis of post-mortem brain tissues confirmed that RAD52 immunoreactivity is significantly increased in C9ALS/FTD samples as compared to controls. CONCLUSIONS: Collectively, we characterized the inhibitory effects of DPRs on key DNA DSB repair pathways, identified NPM1 as a facilitator of DNA repair that is inhibited by PR, and revealed deficits in homology-directed DNA DSB repair pathways as a novel feature of C9ORF72-related disease

Herpetofauna of the Bilsa Biological Station, province of Esmeraldas, Ecuador

The Bilsa Biological Station is located on the Mache-Chindul mountains and protects some of the last rainforest remnants in the province of Esmeraldas, northwestern Ecuador. Since 2004, we have been inventorying the amphibians and reptiles of Bilsa. We found 109 species of herpetofauna (37 amphibians and 72 reptiles), representing 8 % and 18 % of the known species from Ecuador, respectively. We report distribution extensions for Sachatamia albomaculata, Hyalinobatrachium valerioi, Pristimantis muricatus, and P. rosadoi, and report the presence of several putatively undescribed species. We propose the Mache–Chindul mountains as a Key Biodiversity Area within the West Ecuadorian Endemic Area

Optimal box-covering algorithm for fractal dimension of complex networks

The self-similarity of complex networks is typically investigated through computational algorithms the primary task of which is to cover the structure with a minimal number of boxes. Here we introduce a box-covering algorithm that not only outperforms previous ones, but also finds optimal solutions. For the two benchmark cases tested, namely, the E. Coli and the WWW networks, our results show that the improvement can be rather substantial, reaching up to 15% in the case of the WWW network.Comment: 5 pages, 6 figure

HPM-Frame: A Decision Framework for Executing Software on Heterogeneous Platforms

Heterogeneous computing is one of the most important computational solutions to meet rapidly increasing demands on system performance. It typically allows the main flow of applications to be executed on a CPU while the most computationally intensive tasks are assigned to one or more accelerators, such as GPUs and FPGAs. The refactoring of systems for execution on such platforms is highly desired but also difficult to perform, mainly due the inherent increase in software complexity. After exploration, we have identified a current need for a systematic approach that supports engineers in the refactoring process -- from CPU-centric applications to software that is executed on heterogeneous platforms. In this paper, we introduce a decision framework that assists engineers in the task of refactoring software to incorporate heterogeneous platforms. It covers the software engineering lifecycle through five steps, consisting of questions to be answered in order to successfully address aspects that are relevant for the refactoring procedure. We evaluate the feasibility of the framework in two ways. First, we capture the practitioner's impressions, concerns and suggestions through a questionnaire. Then, we conduct a case study showing the step-by-step application of the framework using a computer vision application in the automotive domain.Comment: Manuscript submitted to the Journal of Systems and Softwar

Caracterización de la calidad de vida en adultos mayores con tratamiento de hemodiálisis en el Instituto del Riñon Inridi San Martín.

PdfEl caracterizar la calidad de vida en adultos mayores con tratamiento de hemodiálisis requirió investigar dos aspectos fundamentales, primero la terapia hemodialítica, que reciben tres veces por semana, cuatro horas cada vez conectados a una máquina, en una Unidad de Salud; y el segundo su vida cotidiana, principalmente, desde su hogar; en esto, quienes cumplieron un rol fundamental fueron los familiares, pues ellos, colaboraron para que los pacientes sigan las recomendaciones médicas y tuvieran las condiciones de vida, necesarias para su bienestar, pero, muy a pesar de eso, los adultos mayores, tanto por aspectos físicos, emocionales, motivacionales y sociales, no aprovecharon esa oportunidad.Para lograr nuestro objetivo, trabajamos con una investigación positivista, con un diseño no experimental, de tipo transversal descriptivo, esto nos permitió entender la vida cotidiana de los pacientes, sin modificar su entorno; el enfoque que se utilizó fue el cuantitativo, que nos permitió examinar los datos de manera numérica brindándonos información pertinente.Finalmente, el adulto mayor puede ser descrito como una persona con relaciones interpersonales no bien percibidas, se desmotivan fácilmente, son dependientes y exigentes; la capacidad para la ejecución de actividades cotidianas está disminuida y determinada por lo que los familiares le permiten o no realizar, por tanto, en su mayoría, son personas que viven sedentariamente; estos pacientes deben aprender a vivir con su realidad objetiva, a disfrutar de su entorno y a motivarse a seguir adelante.Characterizing the quality of life in older adults with hemodialysis required to investigate two aspects, first the hemodialysis therapy, receiving three times a week, four hours each time connected to a machine in a Health Unit; and the second their daily lives mainly from home; in this, who played a key role were the family, because they collaborated for patients to follow medical advice and have the living conditions necessary for their welfare, but in spite of that, the elderly, therefore physical, emotional, motivational and social aspects, not seize that opportunity.To achieve our goal, we work with a positivist research, with a non-experimental design, descriptive transversal, this allowed us to understand the daily life of patients, without modifying their environment; The approach used was quantitative, which allowed us to examine the data numerically giving us relevant information.Finally, the elderly can be described as a person not well perceived relationships, discourage easily, they are dependent and demanding; the capacity to perform daily activities is impaired and determined by what the family or not let you perform therefore mostly are people living sedentarily; these patients should learn to live with their objective reality, to enjoy their environment and motivated to keep going