Influence of inflammation in the process of T lymphocyte differentiation: Proliferative, metabolic, and oxidative changes

T lymphocytes, from their first encounter with their specific antigen as naïve cell until the last stages of their differentiation, in a replicative state of senescence, go through a series of phases. In several of these stages, T lymphocytes are subjected to exponential growth in successive encounters with the same antigen. This entire process occurs throughout the life of a human individual and, earlier, in patients with chronic infections/pathologies through inflammatory mediators, first acutely and later in a chronic form. This process plays a fundamental role in amplifying the activating signals on T lymphocytes and directing their clonal proliferation. The mechanisms that control cell growth are high levels of telomerase activity and maintenance of telomeric length that are far superior to other cell types, as well as metabolic adaptation and redox control. Large numbers of highly differentiated memory cells are accumulated in the immunological niches where they will contribute in a significant way to increase the levels of inflammatory mediators that will perpetuate the new state at the systemic level. These levels of inflammation greatly influence the process of T lymphocyte differentiation from naïve T lymphocyte, even before, until the arrival of exhaustion or cell death. The changes observed during lymphocyte differentiation are correlated with changes in cellular metabolism and these in turn are influenced by the inflammatory state of the environment where the cell is located. Reactive oxygen species (ROS) exert a dual action in the population of T lymphocytes. Exposure to high levels of ROS decreases the capacity of activation and T lymphocyte proliferation; however, intermediate levels of oxidation are necessary for the lymphocyte activation, differentiation, and effector functions. In conclusion, we can affirm that the inflammatory levels in the environment greatly influence the differentiation and activity of T lymphocyte populations. However, little is known about the mechanisms involved in these processes. The elucidation of these mechanisms would be of great help in the advance of improvements in pathologies with a large inflammatory base such as rheumatoid arthritis, intestinal inflammatory diseases, several infectious diseases and even, cancerous processes

Fractura-Luxación de Monteggia en el Adulto: tratamiento con clavo cerrojado

Las lesiones traumáticas del antebrazo son cada día más frecuentes. Una variante tradicionalmente conocida como de Monteggia ofrece la particularidad en el adulto de la controversia en el tratamiento entre el yeso, la placa a compresión o el enclavado endomedular. En un intento de mejora de resultados hemos testado clínicamente un nuevo clavo cerrojado para el cúbito. Se han seguido prospectivamente 7 pacientes afectos de fractura de Monteggia durante un año como mínimo y dos como promedio. Todos los pacientes consolidaron sus fracturas en un plazo inferior a 4 meses, con un promedio de 2.5 meses. Siguiendo la cotación propia de los autores se han encontrado 3 buenos y 4 muy buenos resultados. La sencillez y la bondad del método hace aconsejable su uso extensivo a las fracturas diafisarias de cúbito.Traumatic lesions of the forearm are increasingly common. One variant of these, traditionally known as Monteggia fracture, has the particularity in adults of displaying controversy with respect to whethe r it should be treated with plaster, a compression plate or endomedullary nailing. In an attempt to improve the results, the authors tested clinically a new locking nail for the ulna. Seven patients with Monteggia fractures wer e followed over a minimum their fractures in less than 4 months, with a mean of 2.5 months. Following the authors' rating, 3 patients had good and 4 patients very good results. The simplicity and suitability of the method counsel its extensive us e in diaphyseal fractures of the ulna

Aislamiento de un extracto de BMP y estudio anatomopatológico del fenómeno de inducción ósea tras su implante en defectos óseos

El objetivo del presente trabajo fue determinar el potencial osteogénico de la proteína morfogenética ósea (BMP) en la reparación de grandes defectos diafisarios. Además, se investiga la acción coadyuvante de la fibronectina (FN). La BMP fue extraída a partir de hueso cortical bovino. Se utilizaron un total de 108 ratas Sprague Dawley. En cada animal, se resecó un segmento de diáfisis femoral de 1.5 cm, siendo inmovilizado el defecto óseo con una aguja en omega. Se rellenó el defecto implantando 25 mg de BMP con o sin 0.5 mg de FN en una cápsula de gelatina (36 animales en ambos grupos). Los resultados se compararon con los obtenidos en otro grupo (36 animales) en el que sólo se implantó FN que sirvió como grupo control. El proceso de reparación se evaluó mediante métodos histológicos y ultraestructurales. La aparición del fenómeno de inducción ósea con reconstrucción del defecto óseo fue mayor en el grupo con implante de BMP más FN (23 animales, 64%) que en el grupo en el que sólo se implantó BMP (20 animales, 56%). Ningún animal del grupo control manifestaba signos de inducción ósea.The aim of the present work was to evaluate the osteogenic potential of Bone Morphogenetic Protein (BMP) for reparation of large segmental bone defects. In addition, the coadjuvant efect of fibronectin (FN) was investigated. BMP was partially purified from bovine cortical bone. A total of 108 Sprague Dawley rats were used in the experiment. Diaphyseal segments of the femur (1.5 cm) were removed in each animal, manteinant the bone defect with a wire. A gelatine capsula containing 25 mg of BMP without or with 0.5 mg of FN, were implanted into the bone defect (36 animal in each group). Results were compared to those obtained in a control group (36 animals) in which FN alone was implanted. The bone repair process was assessed by histologic and ultrastructural methods. Bone induction with reconstruction of the defect was found more of ten in the group with both BMP and FN implanted (23 animals, 64%) than in the group with BMP implant alone (20 animals, 56%). Animals of the control group showed no bone induction. The results suggest that BMP augments the capacity of the host bed to sucessfully regenerate large segmental bone defects. FN seens to increase bone induction. This protein migth stabilize BMP locally improving contact between BMP and the surrounding cells

Indicaciones Límite de las Fracturas de Húmero con Clavo Endomedular Cerrojado

El tratamiento de las fracturas diafisarias del húmero ha entrado en controversia en los últimos años, como lo refleja la literatura internacional. La problemática aumenta cuando se trata de fracturas diafisarias límites que alcanzan la zona metafisaria superior e inferior. En un intento de mejora terapéutica este grupo de autores ha testado un clavo cerrojado para el húmero diseñado por Seidel. El promedio de seguimiento ha sido de 12 meses con un mínimo de 6 meses. El número de casos evaluados ha sido 6. Siguiendo la cotación de Stewart, 4 de los seis pacientes obtuvieron resultados buenos o excelentes. Todos los pacientes consolidaron sus fracturas en un período de tiempo normal, entre 3 y 5 meses, con una media de 4 meses, 4 de los seis pacientes no se inmovilizaron con yeso en ningún momento. La bondad y sencillez del método hace augurar buenos resultados en otros grupos ampliando sus indicaciones.Treatment of dyaphyseal fractures of the humerus has been the source of considerable controversy in recent years. The problem increases in dimension when one is dealing with limiting diaphyseal fractures that invole the upper and lower metaphyseal zone. In an attempt to improve the therapy of this circunstance, the members of this research team have tested a locking nail for the humerus designed by Seidel. The mean follow-up time has been 12 months, with a minimum of six months. The number of cases evaluated was 6. According to the scale of Stewart, four of the cases obtained good or excellent results. All the patients consolidated their fractures within a normal period of time -between 3 and 5 months-, with a mean of 4 months. Four of the 6 patients wer e not immobilized with paster at any time. The goodness and simplicity of the method are suggestive of promising results in other groups by broadening its indications

A Spitzer Space Telescope far-infrared spectral atlas of compact sources in the Magellanic Clouds. I. The Large Magellanic Cloud

[abridged] We present 52-93 micron spectra obtained with Spitzer in the MIPS-SED mode, of a representative sample of luminous compact far-IR sources in the LMC. These include carbon stars, OH/IR AGB stars, post-AGB objects and PNe, RCrB-type star HV2671, OH/IR red supergiants WOHG064 and IRAS05280-6910, B[e] stars IRAS04530-6916, R66 and R126, Wolf-Rayet star Brey3a, Luminous Blue Variable R71, supernova remnant N49, a large number of young stellar objects, compact HII regions and molecular cores, and a background galaxy (z~0.175). We use the spectra to constrain the presence and temperature of cold dust and the excitation conditions and shocks within the neutral and ionized gas, in the circumstellar environments and interfaces with the surrounding ISM. Evolved stars, including LBV R71, lack cold dust except in some cases where we argue that this is swept-up ISM. This leads to an estimate of the duration of the prolific dust-producing phase ("superwind") of several thousand years for both RSGs and massive AGB stars, with a similar fractional mass loss experienced despite the different masses. We tentatively detect line emission from neutral oxygen in the extreme RSG WOHG064, with implications for the wind driving. In N49, the shock between the supernova ejecta and ISM is revealed by its strong [OI] 63-micron emission and possibly water vapour; we estimate that 0.2 Msun of ISM dust was swept up. Some of the compact HII regions display pronounced [OIII] 88-micron emission. The efficiency of photo-electric heating in the interfaces of ionized gas and molecular clouds is estimated at 0.1-0.3%. We confirm earlier indications of a low nitrogen content in the LMC. Evidence for solid state emission features is found in both young and evolved object; some of the YSOs are found to contain crystalline water ice.Comment: Accepted for publication in The Astronomical Journal. This paper accompanies the Summer 2009 SAGE-Spec release of 48 MIPS-SED spectra, but uses improved spectrum extraction. (Fig. 2 reduced resolution because of arXiv limit.

NKG2D expression in CD4+ T lymphocytes as a marker of senescence in the aged immune system

Human aging is characterized by changes in the immune system which have a profound impact on the T-cell compartment. These changes are more frequently found in CD8+ T cells, and there are not well-defined markers of differentiation in the CD4+ subset. Typical features of cell immunosenescence are characteristics of pathologies in which the aberrant expression of NKG2D in CD4+ T cells has been described. To evaluate a possible age-related expression of NKG2D in CD4+ T cells, we compared their percentage in peripheral blood from 100 elderly and 50 young adults. The median percentage of CD4+ NKG2D+ in elders was 5.3% (interquartile range (IR): 8.74%) versus 1.4% (IR: 1.7%) in young subjects (p < 0.3 × 10−10). CD28 expression distinguished two subsets of CD4+ NKG2D+ cells with distinct functional properties and differentiation status. CD28+ cells showed an immature phenotype associated with high frequencies of CD45RA and CD31. However, most of the NKG2D+ cells belonged to the CD28null compartment and shared their phenotypical properties. NKG2D+ cells represented a more advanced stage of maturation and exhibited greater response to CMV (5.3 ± 3.1% versus 3.4 ± 2%, p = 0.037), higher production of IFN-γ (40.56 ± 13.7% versus 24 ± 8.8%, p = 0.015), lower activation threshold and reduced TREC content. Moreover, the frequency of the CD4+ NKG2D+ subset was clearly related to the status of the T cells. Higher frequencies of the NKG2D+ subset were accompanied with a gradual decrease of NAIVE and central memory cells, but also with a higher level of more differentiated subsets of CD4+ T cells. In conclusion, CD4+ NKG2D+ represent a subset of highly differentiated T cells which characterizes the senescence of the immune system

The European Solar Telescope

The European Solar Telescope (EST) is a project aimed at studying the magnetic connectivity of the solar atmosphere, from the deep photosphere to the upper chromosphere. Its design combines the knowledge and expertise gathered by the European solar physics community during the construction and operation of state-of-the-art solar telescopes operating in visible and near-infrared wavelengths: the Swedish 1m Solar Telescope, the German Vacuum Tower Telescope and GREGOR, the French Télescope Héliographique pour l'Étude du Magnétisme et des Instabilités Solaires, and the Dutch Open Telescope. With its 4.2 m primary mirror and an open configuration, EST will become the most powerful European ground-based facility to study the Sun in the coming decades in the visible and near-infrared bands. EST uses the most innovative technological advances: the first adaptive secondary mirror ever used in a solar telescope, a complex multi-conjugate adaptive optics with deformable mirrors that form part of the optical design in a natural way, a polarimetrically compensated telescope design that eliminates the complex temporal variation and wavelength dependence of the telescope Mueller matrix, and an instrument suite containing several (etalon-based) tunable imaging spectropolarimeters and several integral field unit spectropolarimeters. This publication summarises some fundamental science questions that can be addressed with the telescope, together with a complete description of its major subsystems

TP53 abnormalities are underlying the poor outcome associated with chromothripsis in chronic lymphocytic leukemia patients with complex karyotype

Simple Summary Chromothripsis, a genomic event that generates massive chromosomal rearrangements, has been described in 1-3% of CLL patients and is associated with poor prognostic factors (e.g., TP53 abnormalities and genomic complexity). However, previous studies have not assessed its role in CLL patients with complex karyotypes. Herein, we aimed to describe the genetic characteristics of 33 CLL patients with high genomic complexity and chromothripsis. Moreover, we analyzed the clinical impact of chromothripsis, comparing these patients against a cohort of 129 patients with complex karyotypes not presenting this catastrophic event. Nine cases were also assessed via the novel cytogenomic methodology known as optical genome mapping. We confirmed that this phenomenon is heterogeneous and associated with a shorter time to first treatment. Nonetheless, our findings suggested that TP53 abnormalities, rather than chromothripsis itself, underlie the dismal outcome. Chromothripsis (cth) has been associated with a dismal outcome and poor prognosis factors in patients with chronic lymphocytic leukemia (CLL). Despite being correlated with high genome instability, previous studies have not assessed the role of cth in the context of genomic complexity. Herein, we analyzed a cohort of 33 CLL patients with cth and compared them against a cohort of 129 non-cth cases with complex karyotypes. Nine cth cases were analyzed using optical genome mapping (OGM). Patterns detected by genomic ..

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality