Estudio molecular de la enfermedad ósea de Paget

[ES]La Enfermedad Ósea de Paget es una enfermedad que se define como un trastorno esquelético, focal y crónico. Se produce debido a que los osteoclastos aumentan en número, tamaño y actividad. El recambio óseo se acelera, con un gran aumento de la resorción ósea acoplada a una formación excesiva y desorganizada de hueso; lo que genera un hueso no laminar (plexiforme) muy vascularizado, aumentado de volumen y con resistencia disminuida. Sus principales manifestaciones clínicas son el dolor, la deformidad ósea y la fractura. El modelo más aceptado para explicar la etiopatogenia de la Enfermedad Ósea de Paget es la conjunción de factores ambientales y genéticos. El condicionamiento genético explicaría la susceptibilidad individual a desarrollar la enfermedad junto con la participación de los posibles factores ambientales participantes. Como resultado de nuestro estudio podemos concluir la existencia de un componente poligénico en el desarrollo de la enfermedad; los genes candidatos más plausibles cuya mutación explicaría el origen de la enfermedad son el gen del Sequestosoma1 (SQSTM1), el gen VAV3, el gen GSTM1, el gen ATG2B, el gen ATG16L1 y el gen ATG5. Estudios funcionales llevados a cabo en nuestro trabajo, también nos permiten concluir que la alteración del proceso de autofagia desempeña un papel crucial en el desarrollo de la Enfermedad Ósea de Paget

HoloTrap: Interactive hologram design for multiple dynamic optical trapping

This work presents an application that generates real-time holograms to be displayed on a holographic optical tweezers setup; a technique that allows the manipulation of particles in the range from micrometres to nanometres. The software is written in Java, and uses random binary masks to generate the holograms. It allows customization of several parameters that are dependent on the experimental setup, such as the specific characteristics of the device displaying the hologram, or the presence of aberrations. We evaluate the software's performance and conclude that real-time interaction is achieved. We give our experimental results from manipulating 5 micron-diametre microspheres using the program.Comment: 17 pages, 6 figure

Extending calibration-free force measurements to optically-trapped rod-shaped samples

Optical trapping has become an optimal choice for biological research at the microscale due to its non-invasive performance and accessibility for quantitative studies, especially on the forces involved in biological processes. However, reliable force measurements depend on the calibration of the optical traps, which is different for each experiment and hence requires high control of the local variables, especially of the trapped object geometry. Many biological samples have an elongated, rod-like shape, such as chromosomes, intracellular organelles (e.g., peroxisomes), membrane tubules, certain microalgae, and a wide variety of bacteria and parasites. This type of samples often requires several optical traps to stabilize and orient them in the correct spatial direction, making it more difficult to determine the total force applied. Here, we manipulate glass microcylinders with holographic optical tweezers and show the accurate measurement of drag forces by calibration-free direct detection of beam momentum. The agreement between our results and slender-body hydrodynamic theoretical calculations indicates potential for this force-sensing method in studying protracted, rod-shaped specimens

Artifact-free holographic light shaping through moving acousto-optic holograms

Holographic light modulation is the most efcient method to shape laser light into well-defned patterns and is therefore the means of choice for many intensity demanding applications. During the last two decades, spatial light modulators based on liquid crystals prevailed among several technologies and became the standard tool to shape light holographically. But in the near future, this status might be challenged by acousto-optic defectors. These devices are well known for their excelling modulation rates and high optical power resilience. But only few scattered precedents exist that demonstrate their holographic capabilities, despite the many interesting properties that they provide. We implemented a holographic acousto-optic light modulation (HALM) system, that is based on displaying holograms on acousto-optic defectors. We found that this system can eliminate the ubiquitous coherent artifacts that arise in holography through the inherent motion of acoustooptic holograms. That distinguishes our approach from any other holographic modulation technique and allows to reconstruct intensity patterns of the highest fdelity. A mathematical description of this efect is presented and experimentally confrmed by reconstructing images holographically with unprecedented quality. Our results suggest that HALM promotes acousto-optic defectors from highly specialized devices to full-fedged spatial light modulators, that can compete in a multitude of applications with LC-SLMs. Especially applications that require large optical output powers, high modulation speeds or accurate gray-scale intensity patterns will proft from this technology. We foresee that HALM may play a major role in future laser projectors and displays, structured illumination microscopy, laser material processing and optical trapping

Influence of experimental parameters on the laser heating of an optical trap

In optical tweezers, heating of the sample due to absorption of the laser light is a major concern as temperature plays an important role at microscopic scale. A popular rule of thumb is to consider that, at the typical wavelength of 1064 nm, the focused laser induces a heating rate of B = 1 degrees C/100 mW. We analysed this effect under different routine experimental conditions and found a remarkable variability in the temperature increase. Importantly, we determined that temperature can easily rise by as much as 4 degrees C at a relatively low power of 100 mW, for dielectric, non-absorbing particles with certain sets of specific, but common, parameters. Heating was determined from measurements of light momentum changes under drag forces at different powers, which proved to provide precise and robust results in watery buffers. We contrasted the experiments with computer simulations and obtained good agreement. These results suggest that this remarkable heating could be responsible for changes in the sample under study and could lead to serious damage of live specimens. It is therefore advisable to determine the temperature increase in each specific experiment and avoid the use of a universal rule that could inadvertently lead to critical changes in the sample

Acousto-holographic optical tweezers

Acousto-optic deflectors (AODs) allow the creation of multiple optical traps by time-sharing, that is, by rapidly cycling the laser focus between designated spatial locations. The traps thus formed are not permanent. In this Letter, we successfully demonstrate the creation of multiple and permanent traps by means of AODs driven by specially encoded radio frequency signals. The generation of complex acoustic signals allows us to treat such devices as super-fast spatial light modulators. Using this technique, it is possible to generate several static optical trap arrays and switch them at kilohertz (kHz) rates, allowing independent control of each trap group. Additionally, we discuss the compatibility of this method with precise force and position measurements, and the improvement in their frequency bandwidth compared to time-sharing optical tweezers, especially when many objects are trappe

Design strategies for optimizing holographic optical tweezers setups

We provide a detailed account of the construction of a system of holographic optical tweezers. While much information is available on the design, alignment and calibration of other optical trapping configurations, those based on holography are relatively poorly described. Inclusion of a spatial light modulator in the setup gives rise to particular design trade-offs and constraints, and the system benefits from specific optimization strategies, which we discuss.Comment: 16 pages, 15 figure

Matrix metalloproteinases in age-related macular degeneration (AMD)

Producción CientíficaAge-related macular degeneration (AMD) is a complex, multifactorial and progressive retinal disease affecting millions of people worldwide. In developed countries, it is the leading cause of vision loss and legal blindness among the elderly. Although the pathogenesis of AMD is still barely understood, recent studies have reported that disorders in the regulation of the extracellular matrix (ECM) play an important role in its etiopathogenesis. The dynamic metabolism of the ECM is closely regulated by matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs). The present review focuses on the crucial processes that occur at the level of the Bruch’s membrane, with special emphasis on MMPs, TIMPs, and the polymorphisms associated with increased susceptibility to AMD development. A systematic literature search was performed, covering the years 1990–2020, using the following keywords: AMD, extracellular matrix, Bruch’s membrane, MMPs, TIMPs, and MMPs polymorphisms in AMD. In both early and advanced AMD, the pathological dynamic changes of ECM structural components are caused by the dysfunction of specific regulators and by the influence of other regulatory systems connected with both genetic and environmental factors. Better insight into the pathological role of MMP/TIMP complexes may lead to the development of new strategies for AMD treatment and prevention

Complications associated with the use of silicone oil in vitreoretinal surgery: A systemic review and meta‐analysis

Producción CientíficaSilicone oil (SO) still represents the main choice for long-term intraocular tamponade in complicated vitreoretinal surgery. This review compared the complications associated with the use of SO and other vitreous substitutes after pars plana vitrectomy in patients with different underlying diseases. Meta-analysis was conducted in accordance with PRISMA guidelines. We retrieved randomized clinical trials (RCTs), retrospective case–control and cohort studies evaluating the risk of using SO, published between 1994 and 2020, conducting a computer-based search of the following databases: PubMed, Web of Science, Scopus and Embase. Primary outcome was the rate of complications such as intraocular hypertension, retinal re-detachment, unexpected vision loss or hypotony. Secondary outcome was to compare the rate of adverse events of different SO viscosities, especially emulsification. Forty-three articles were included. There were significant differences in intraocular hypertension (p = 0.0002, OR = 1.66; 95% CI = 1.27–2.18) and the rate of retinal re-detachment (p < 0.0009, OR = 0.65; 95% CI = 0.50–0.64) between SO and other agents, including placebo. However, there were no differences in other complication rates. Silicone oil (SO)-emulsification rate was non-significantly higher in low than high SO viscosity, and results from other complications were comparable in both groups. The high quality of most of the studies included in this study is noteworthy, which provides some certainty to the conclusions. Among them is the high variability of the SO residence time. The fact that ocular hypertension and not hypotension is related to SO use. A clear relationship is not found for the so-called unexplained vision loss, which affects a significant percentage of eyes. Re-detachment cases are less if SO is used and that surprisingly there does not seem to be a relationship in the percentage of emulsification between the low- and high-viscosity silicones. All these data warrant more standardized prospective studies