The Molecular Basis of Monopolin Recruitment to the Kinetochore

The monopolin complex is a multifunctional molecular crosslinker, which in S. pombe binds and organises mitotic kinetochores to prevent aberrant kinetochore-microtubule interactions. In the budding yeast S. cerevisiae, whose kinetochores bind a single microtubule, the monopolin complex crosslinks and mono-orients sister kinetochores in meiosis I, enabling the biorientation and segregation of homologs. Here, we show that both the monopolin complex subunit Csm1 and its binding site on the kinetochore protein Dsn1 are broadly distributed throughout eukaryotes, suggesting a conserved role in kinetochore organisation and function. We find that budding yeast Csm1 binds two conserved motifs in Dsn1, one (termed Box 1) representing the ancestral, widely conserved monopolin binding motif and a second (termed Box 2-3) with a likely role in enforcing specificity of sister kinetochore crosslinking. We find that Box 1 and Box 2-3 bind the same conserved hydrophobic cavity on Csm1, suggesting competition or handoff between these motifs. Using structure-based mutants, we also find that both Box 1 and Box 2-3 are critical for monopolin function in meiosis. We identify two conserved serine residues in Box 2-3 that are phosphorylated in meiosis and whose mutation to aspartate stabilises Csm1-Dsn1 binding, suggesting that regulated phosphorylation of these residues may play a role in sister kinetochore crosslinking specificity. Overall, our results reveal the monopolin complex as a broadly conserved kinetochore organiser in eukaryotes, which budding yeast have co-opted to mediate sister kinetochore crosslinking through the addition of a second, regulatable monopolin binding interface

Beneficial or detrimental activity of regulatory T cells, indoleamine 2,3-dioxygenase, and heme oxygenase-1 in the lungs is influenced by the level of virulence of Mycobacterium tuberculosis strain infection

Tuberculosis (TB) caused by the complex Mycobacterium tuberculosis (Mtb) is the main cause of death by a single bacterial agent. Last year, TB was the second leading infectious killer after SARS-CoV-2. Nevertheless, many biological and immunological aspects of TB are not completely elucidated, such as the complex process of immunoregulation mediated by regulatory T cells (Treg cells) and the enzymes indoleamine 2,3-dioxygenase (IDO) and heme oxygenase 1 (HO-1). In this study, the contribution of these immunoregulatory factors was compared in mice infected with Mtb strains with different levels of virulence. First Balb/c mice were infected by intratracheal route, with a high dose of mild virulence reference strain H37Rv or with a highly virulent clinical isolate (strain 5186). In the lungs of infected mice, the kinetics of Treg cells during the infection were determined by cytofluorometry and the expression of IDO and HO-1 by RT-PCR and immunohistochemistry. Then, the contribution of immune-regulation mediated by Treg cells, IDO and HO-1, was evaluated by treating infected animals with specific cytotoxic monoclonal antibodies for Treg cells depletion anti-CD25 (PC61 clone) or by blocking IDO and HO-1 activity using specific inhibitors (1-methyl-D,L-tryptophan or zinc protoporphyrin-IX, respectively). Mice infected with the mild virulent strain showed a progressive increment of Treg cells, showing this highest number at the beginning of the late phase of the infection (28 days), the same trend was observed in the expression of both enzymes being macrophages the cells that showed the highest immunostaining. Animals infected with the highly virulent strain showed lower survival (34 days) and higher amounts of Treg cells, as well as higher expression of IDO and HO-1 one week before. In comparison with non-treated animals, mice infected with strain H37Rv with depletion of Treg cells or treated with the enzymes blockers during late infection showed a significant decrease of bacilli loads, higher expression of IFN-g and lower IL-4 but with a similar extension of inflammatory lung consolidation determined by automated morphometry. In contrast, the depletion of Treg cells in infected mice with the highly virulent strain 5186 produced diffuse alveolar damage that was similar to severe acute viral pneumonia, lesser survival and increase of bacillary loads, while blocking of both IDO and HO-1 produced high bacillary loads and extensive pneumonia with necrosis. Thus, it seems that Treg cells, IDO and HO-1 activities are detrimental during late pulmonary TB induced by mild virulence Mtb, probably because these factors decrease immune protection mediated by the Th1 response. In contrast, Treg cells, IDO and HO-1 are beneficial when the infection is produced by a highly virulent strain, by regulation of excessive inflammation that produced alveolar damage, pulmonary necrosis, acute respiratory insufficiency, and rapid death

Approaches to lowering the cost of large space telescopes

New development approaches, including launch vehicles and advances in sensors, computing, and software, have lowered the cost of entry into space, and have enabled a revolution in low-cost, high-risk Small Satellite (SmallSat) missions. To bring about a similar transformation in larger space telescopes, it is necessary to reconsider the full paradigm of space observatories. Here we will review the history of space telescope development and cost drivers, and describe an example conceptual design for a low cost 6.5 m optical telescope to enable new science when operated in space at room temperature. It uses a monolithic primary mirror of borosilicate glass, drawing on lessons and tools from decades of experience with ground-based observatories and instruments, as well as flagship space missions. It takes advantage, as do large launch vehicles, of increased computing power and space-worthy commercial electronics in low-cost active predictive control systems to maintain stability. We will describe an approach that incorporates science and trade study results that address driving requirements such as integration and testing costs, reliability, spacecraft jitter, and wavefront stability in this new risk-tolerant "LargeSat" context.Comment: Presented at SPIE, Optics+Photonics 2023, Astronomical Optics: Design, Manufacture, and Test of Space and Ground Systems IV in San Diego, CA, US

Surveillance of ‘women’s honesty’ by Almeria justice during the crisis of the Ancien Regime

En este trabajo se trata de comprobar, a la luz de la información que nos ofrecen los archivos históricos, cómo la mujer, en un lugar y en un momento históricos concretos (en almería y a finales del antiguo Régimen) estaba condicionada en sus comportamientos sexuales. Estos se intentaban reducir esencialmente en el marco del matrimonio y, de modo más concreto, para la procreación. todo el aparato de la administración de justicia estaba vigilante para atajar las posibles desviaciones de conductas que pudieran producirse imponiendo los consecuentes castigos.This paper tries to verify, in the light of the information that the historical archives offer us, how the woman, in a specific historical place and moment (in almeria and at the end of the Ancien Regime) was conditioned on her sexual behaviours. These were intended to be reduced essentially within the framework of marriage and, more specifically, for procreation. the apparatus of the justice administration was vigilant to tackle possible deviations of behaviours that could occur imposing the consequent punishments.info:eu-repo/semantics/publishedVersio

Estrategias de diseño urbano para la adaptación al cambio climático caso Buenaventura

Disponible en formato fisico (T ARQ 04 2016)En esta investigaciòn es importante abordar el tema sobre el cambio climático desde el marco de una crisis ecológica ya que se puede definir como la variación global del clima de la tierra, tales cambios se producen a muy diversas escalas de tiempo y sobre todo los parámetros climatologícas, precipitaciones, nubosidad, etc son debidos a causas naturales y se considera que en los últimos siglos, también a causas antropogénicas, es decir a la acción del hombre.Tabla de contenido INTRODUCCIÓN 7 CAPÍTULO 1: EL PROBLEMA 9 1.1 PLANTEAMIENTO DEL PROBLEMA 9 1.2. PREGUNTA DE INVESTIGACIÓN 11 1.3. OBJETIVO GENERAL 11 1.3.1 OBJETIVOS ESPECIFICOS 11 1.4 JUSTIFICACIÓN DE LA INVESTIGACIÓN 12 1.5 CRONOGRAMA DE ACTIVIDADES 12 1.6 METODOLOGÍA 13 CAPÍTULO 2: MARCO GENERAL 15 2.1 ESTADO DEL ARTE 15 2.1.1 CRITERIOS DE SELECCIÓN 15 2.2 REFERENTES 24 2.2.1 ESPACIO PÚBLICO INUNDABLE “PLAZA ACUÁTICA” (ROTTERDAM, PAISES BAJOS) 24 2.2.2 PARQUE DE LA AGUADA (CHILE) 26 2.2.3 VIVIENDA PALAFITICA (COLIUMO, CHILE) 29 2.3 MARCO TEÓRICO 30 2.3.1 CAMBIO CLIMÁTICO 30 2.3.2 INFLUENCIA ANTROPOGÉNICA EN EL CAMBIO CLIMÁTICO 33 2.3.3 VARIABILIDAD CLIMÁTICA 36 2.3.4 CÓMO AFECTA EN LAS CIUDADES 36 2.4 MARCO LEGAL 37 2.4.1 NORMATIVA INTERNACIONAL 37 2.4.2 NORMATIVA NACIONAL 38 2.5 MARCO HISTÓRICO 38 ACONTECIMIENTOS MÁS RELEVANTES DE LA HISTORIA DEL CAMBIO CLIMÁTICO 38 CAPÍTULO 3: CASO DE ESTUDIO / ANÁLISIS 45 3.1 PARAMETROS DE ANÁLISIS DEL DISEÑO URBANO ADAPTATIVO 45 3.1.1 INFRAESTRUCTURA 45 3.1.2 ZONAS VERDES 46 3.1.3 INUNDACIONES 48 3.1.4 ESPACIO PÚBLICO 52 3.2 REGISTROS CLIMÁTICOS HISTÓRICOS 53 3.3 ANÁLISIS Y DIAGNÓSTICO 55 3.3.1 ESCALA URBANA 55 3.3.2 ESCALA COMUNAL 55 3.3.3 SISTEMAS EQUIPAMIENTOS 56 3.3.4 SISTEMAS ESTRUCTURANTES 56 3.3.5 PLANOS LLENOS Y VACÍOS 57 3.4 NORMATIVA POT 57 3.5 ALTURAS 58 3.6 CONCLUSIONES DEL ANÁLISIS 59 4. PROPUESTA 61 4.1 BOULEVARD VERDE61 4.2 VIVIENDA PALAFITICA 62 4.3 ESPACIO PÚBLICO INUNDABLE 63 4.4 PROPUESTA UNIFICADA 64 BIBLIOGRAFÍA 66Tesis (Arquitectura) - Universidad del Pacífico. Facultad de Arquitectura e Ingeniería de sistemas, 2016PregradoArquitecto(a

Optimization of regular offshore wind-power plants using a non-discrete evolutionary algorithm

Offshore wind farms (OWFs) often present a regular configuration mainly due to aesthetical considerations. This paper presents a new evolutionary algorithm that optimizes the location, configuration and orientation of a rhomboid-shape OWF. Existing optimization algorithms were based on dividing the available space into a mess of cells and forcing the turbines to be located in the centre of a cell. However, the presented algorithm searches for the optimum within a continuous range of the eight parameters that define the OWF, which allows including a gradient-based local search operator to improve the optimization process. The study starts from a review of the economic data available in the bibliography relative to the most significant issues influencing the profitability of the investment in terms of the Internal Rate of Return (IRR). In order to address the distinctive characteristics of OWFs, specific issues arise which have been solved. The most important ones are: interpretation of nautical charts, utilization of the seabed map with different load-bearing capacities, and location of the shoreline transition

Fish communities in high-latitude mangrove in north-western Mexico

Studying fish communities in extreme habitats is important to better understand the variation in their ranges under climatic scenarios or anthropogenic pressure. In particular, the mangroves in Baja California Sur occupy the northernmost distribution range under two extreme conditions (temperate waters and arid weather). In this context, the aim of the presently reported study was to analyze the functional characteristics of ichthyofauna in two localities, La Paz Bay (BP) and Almejas Bay (BA), which are also located in different ecoregions. For both bays, the composition and frequency values were compiled from monthly samples and the literature. Eleven functional traits were assessed from the morphology of every fish species. Functional indices (Richness, Evenness, Divergence, and Originality) were used to evaluate different aspects of the community structure. A total of 83 species were found at both sites, with 54 in BP and 50 in BA. In BP, six species were residents, eight were temporal visitors, and 36 were occasional visitors. In BA, six species were residents, 15 species were temporal visitors, and 33 were occasional visitors. At both sites, 12% of the species were permanent residents; BA had a higher percentage of temporal residents (27%), while BP had a higher percentage of occasional visitors (72%). The functional analysis detected communities with specialized traits, but in comparison to BP, BA had higher evenness in the community structure. Although greater structural complexity was expected in the community during the warm months, because of the increase in richness and attributes, BA had higher values during the cold months, which was probably because the area is a transition zone and the fish communities are adapted to colder climates. In comparison to BA, BP had higher originality values, and colder months presented higher values than warmer months. Although the mangrove sites had the same northernmost latitudinal limits and both had extreme conditions compared to those in mangroves in tropical environments, the fish communities differed in their composition, frequency, and functionality with more extreme functional traits in colder weather than in warmer weather

The molecular basis of monopolin recruitment to the kinetochore.

The monopolin complex is a multifunctional molecular crosslinker, which in S. pombe binds and organises mitotic kinetochores to prevent aberrant kinetochore-microtubule interactions. In the budding yeast S. cerevisiae, whose kinetochores bind a single microtubule, the monopolin complex crosslinks and mono-orients sister kinetochores in meiosis I, enabling the biorientation and segregation of homologs. Here, we show that both the monopolin complex subunit Csm1 and its binding site on the kinetochore protein Dsn1 are broadly distributed throughout eukaryotes, suggesting a conserved role in kinetochore organisation and function. We find that budding yeast Csm1 binds two conserved motifs in Dsn1, one (termed Box 1) representing the ancestral, widely conserved monopolin binding motif and a second (termed Box 2-3) with a likely role in enforcing specificity of sister kinetochore crosslinking. We find that Box 1 and Box 2-3 bind the same conserved hydrophobic cavity on Csm1, suggesting competition or handoff between these motifs. Using structure-based mutants, we also find that both Box 1 and Box 2-3 are critical for monopolin function in meiosis. We identify two conserved serine residues in Box 2-3 that are phosphorylated in meiosis and whose mutation to aspartate stabilises Csm1-Dsn1 binding, suggesting that regulated phosphorylation of these residues may play a role in sister kinetochore crosslinking specificity. Overall, our results reveal the monopolin complex as a broadly conserved kinetochore organiser in eukaryotes, which budding yeast have co-opted to mediate sister kinetochore crosslinking through the addition of a second, regulatable monopolin binding interface