A FRAP model to investigate reaction-diffusion of proteins within a bounded domain: a theoretical approach

Temporally and spatially resolved measurements of protein transport inside cells provide important clues to the functional architecture and dynamics of biological systems. Fluorescence Recovery After Photobleaching (FRAP) technique has been used over the past three decades to measure the mobility of macromolecules and protein transport and interaction with immobile structures inside the cell nucleus. A theoretical model is presented that aims to describe protein transport inside the nucleus, a process which is influenced by the presence of a boundary (i.e. membrane). A set of reaction-diffusion equations is employed to model both the diffusion of proteins and their interaction with immobile binding sites. The proposed model has been designed to be applied to biological samples with a Confocal Laser Scanning Microscope (CLSM) equipped with the feature to bleach regions characterised by a scanning beam that has a radially Gaussian distributed profile. The proposed model leads to FRAP curves that depend on the on- and off-rates. Semi-analytical expressions are used to define the boundaries of on- (off-) rate parameter space in simplified cases when molecules move within a bounded domain. The theoretical model can be used in conjunction to experimental data acquired by CLSM to investigate the biophysical properties of proteins in living cells.Comment: 25 pages. Abstracts Proceedings, The American Society for Cell Biology, 46th Annual Meeting, December 9-13, 2006, San Dieg

Diversidad de mariposas (Lepidoptera, Papilionoidea) y su relación con el paisaje de alta montaña en los Andes nororientales de Colombia

Diversitat de papallones (Lepidoptera, Papilionoidea) i la seva relació amb el paisatge d’alta muntanya als Andes nord-orientals de Colòmbia La regió andina es caracteritza per acollir una gran varietat d’ecosistemes entre els quals es compten les característiques zones d’alta muntanya, que mostren processos de transformació del sòl accelerats que han convertit els boscos natius en zones agrícoles i ramaderes, la qual cosa ha ocasionant un declivi de la diversitat biològica regional. L’ús d’indicadors de diversitat és adequat per avaluar els canvis en els paisatges d’alta muntanya i les papallones són un dels grups més importants per determinar els canvis que es produeixen en els diferents tipus d’ambients. A l’àrea d’estudi es van establir dotze punts de mostreig als complexos d’erms d’Almorzadero, Santurbán i Tamá de la regió nord-oriental de Colòmbia. Durant la fase de mostreig es van practicar captures d’individus adults de papallones en transsectes de 100 x 4 m en un gradient altitudinal de 500 m. Es van registrar 69 espècies, pertanyents a cinc famílies. Els valors de diversitat de la comunitat de papallones diürnes van variar a les diferents cobertures vegetals associades a cada transsecte. Així, les àrees amb cobertura vegetal conservada (per exemple, bosc dens, arbustos i matolls i erm i suberm) van presentar els valors més alts de diversitat, mentre que les zones amb cobertura alterada (per exemple, bosc fragmentat, pastures i àrees agrícoles) van presentar els valors de diversitat més baixos. Les anàlisis d’estructura de comunitats evidencien que les espècies de papallones endèmiques estan associades a àrees fragmentades a les zones d’alta muntanya. Aquest estudi és el primer del seu tipus que estableix canvis en la diversitat de les papallones en zones d’alta muntanya del nord-est de Colòmbia i s’ha fet amb el propòsit de generar estratègies de conservació en llocs que presenten un alt grau d’endemisme i diversitat.Diversity of butterflies (Lepidoptera, Papilionoidea) and their relationship with the highlands’ landscape in the northeastern Andes of Colombia The Andean region harbors a great variety of ecosystems, including the characteristic high mountain zones. The biological diversity in these zones, however, is declining as the result of changes in land use, particularly the introduction of agriculture and cattle ranching. Changes in the high mountain landscape can be appropriately monitored using diversity indicators such as butterflies, one of the most important indicator species. We chose twelve sampling points in the paramo (high altitude moor) complexes Almorzadero, Santurbán and El Tamá, located in the northeastern region of Colombia to collect adult butterflies within transects of 100 x 4 m, along an altitudinal gradient of 500 m. We recorded 69 species, from five families. Diversity values of the diurnal butterfly communities varied among  the different areas of vegetation coverage associated with each transect. Conserved vegetation coverage (i.e. dense forest, scrublands and scrublands, and paramo and subparamo) showed the highest values of diversity, while  perturbed coverage (i.e. fragmented forests, pastures and agriculture areas) presented the lowest values of diversity. Analysis of the community structure showed that endemic butterfly species were associated with fragmented areas in the high mountains. Findings from this study, the first of its kind to determine changes in butterfly diversity in highlands in northeastern Colombia, may help to generate conservation strategies in places where there is high endemism and diversityLa región andina se caracteriza por albergar una gran variedad de ecosistemas entre los que se cuentan las características zonas de alta montaña, que muestran acelerados procesos de transformación del suelo que han convertido los bosques nativos en zonas agrícolas y ganaderas ocasionando un declive de la diversidad biológica regional. El empleo de indicadores de diversidad es adecuado para evaluar los cambios en los paisajes de alta montaña, siendo las mariposas uno de los grupos más importantes para determinar los cambios que se producen en los diferentes tipos de ambientes. En el área de estudio se establecieron doce puntos de muestreo en los complejos de páramos del Almorzadero, Santurbán y Tamá de la región nororiental de Colombia. Durante la fase de muestreo se realizaron capturas de individuos adultos de mariposas en transectos de 100 x 4 m en un gradiente altitudinal de 500 m. Se registraron 69 especies, pertenecientes a cinco familias. Los valores de diversidad de la comunidad de mariposas diurnas variaron en las diferentes coberturas vegetales asociadas a cada transecto. Así, las áreas con cobertura vegetal conservada (por ejemplo, bosque denso, arbustos y matorrales y páramo y subpáramo) presentaron los valores más altos de diversidad, mientras que las zonas con cobertura alterada (por ejemplo, bosque fragmentado, pastos y áreas agrícolas) presentaron los valores de diversidad más bajos. Los análisis de estructura de comunidades evidencian que las especies de mariposas endémicas están asociadas a áreas fragmentadas en las zonas de alta montaña. Este estudio es el primero de su tipo que establece cambios en la diversidad de las mariposas en zonas de alta montaña del nordeste de Colombia y se ha realizado con el propósito de generar estrategias de conservación en lugares que presentan un alto grado de endemismo y diversidad

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

Is socioeconomic status associated with biological aging as measured by telomere length?

It has been hypothesized that one way in which lower socioeconomic status (SES) affects health is by increasing the rate of biological aging. A widely used marker of biological aging is telomere length. Telomeres are structures at the ends of chromosomes that erode with increasing cell proliferation and genetic damage. We aimed to identify, through systematic review and meta-analysis, whether lower SES (greater deprivation) is associated with shorter telomeres. Thirty-one articles, including 29 study populations, were identified. We conducted 3 meta-analyses to compare the telomere lengths of persons of high and low SES with regard to contemporaneous SES (12 study populations from 10 individual articles), education (15 study populations from 14 articles), and childhood SES (2 study populations from 2 articles). For education, there was a significant difference in telomere length between persons of high and low SES in a random-effects model (standardized mean difference (SMD) = 0.060, 95% confidence interval (CI): 0.002, 0.118; P = 0.042), although a range of sensitivity analyses weakened this association. There was no evidence for an association between telomere length and contemporaneous SES (SMD = 0.104, 95% CI: −0.027, 0.236; P = 0.119) or childhood SES (SMD = −0.037, 95% CI: −0.143, 0.069; P = 0.491). These results suggest weak evidence for an association between SES (as measured by education) and biological aging (as measured by telomere length), although there was a lack of consistent findings across the SES measures investigated here

Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+) T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3(+) T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+) T-cells in PBMC cultures required 'classical' CD14(+) monocytes, which enhanced T-cell activation. CD3(+) T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+) T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease

Tailoring 3D modelling techniques for epigraphic texts restitution. Case studies in deteriorated roman inscriptions

Digital Image Modelling is becoming a standard approach in epigraphic studies, mostly expressed in the diffusion practice of research groups which want their materials being publicly accessible. However, there is an important lack of works which seek for the use of 3D tools to improve the epigraphic analysis and text reading. Therefore, this paper attempts to show the application of Photogrammetry Structure from Motion and Digital Image Modelling to 3D record and analyse inscriptions that are in poor state of preservation, aiming to resolve some text-restitution problems and contribute towards the definition of new methodologies in Roman epigraphy

Selective blockade of interferon-α and -β reveals their non-redundant functions in a mouse model of West Nile virus infection

Although type I interferons (IFNs) were first described almost 60 years ago, the ability to monitor and modulate the functional activities of the individual IFN subtypes that comprise this family has been hindered by a lack of reagents. The major type I IFNs, IFN-β and the multiple subtypes of IFN-α, are expressed widely and induce their effects on cells by interacting with a shared heterodimeric receptor (IFNAR). In the mouse, the physiologic actions of IFN-α and IFN-β have been defined using polyclonal anti-type I IFN sera, by targeting IFNAR using monoclonal antibodies or knockout mice, or using Ifnb-/- mice. However, the corresponding analysis of IFN-α has been difficult because of its polygenic nature. Herein, we describe two monoclonal antibodies (mAbs) that differentially neutralize murine IFN-β or multiple subtypes of murine IFN-α. Using these mAbs, we distinguish specific contributions of IFN-β versus IFN-α in restricting viral pathogenesis and identify IFN-α as the key mediator of the antiviral response in mice infected with West Nile virus. This study thus suggests the utility of these new reagents in dissecting the antiviral and immunomodulatory roles of IFN-β versus IFN-α in murine models of infection, immunity, and autoimmunity

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Patients with chronic kidney disease (CKD) are predisposed to heart rhythm disorders, including atrial fibrillation (AF)/atrial flutter, supraventricular tachycardias, ventricular arrhythmias, and sudden cardiac death (SCD). While treatment options, including drug, device, and procedural therapies, are available, their use in the setting of CKD is complex and limited. Patients with CKD and end-stage kidney disease (ESKD) have historically been under-represented or excluded from randomized trials of arrhythmia treatment strategies,1 although this situation is changing.2 Cardiovascular society consensus documents have recently identified evidence gaps for treating patients with CKD and heart rhythm disorders [...