Origin and pathways of the mineral dust transport to two Spanish EARLINET sites: Effect on the observed columnar and range-resolved dust optical properties

In this paper, is presented a method for estimation of the effect of the transport process to aerosol optical properties. Aerosol optical data retrieved by lidars and sun-photometer measurements, are applied to Saharan dust events observed simultaneously at the two EARLINET/AERONET sites of Barcelona and Granada during the periods of June–September of 2012 and 2013. For this purpose, elastic lidar profiles and sun-photometer columnar retrievals are analyzed together with satellite observations and dust forecast models. Granada presents more than twice Saharan dust outbreaks compared to Barcelona. The scenarios favoring the Saharan dust outbreaks are identified in both places. The mineral dust originating in the Sahara region and arriving at both stations is usually transport wither over the Atlas Mountains or through an Atlantic pathway. Analyses of dust events affecting both stations reveal how differences in the transport process lead to differences in the aerosol optical properties measured at each station. Mean dust related Ångström exponent is 1.8 times higher in Barcelona than in Granada. This difference is a result of the additional contribution of anthropogenic aerosol, mainly in the aerosol fine mode, during the transport of the mineral dust plume over the Iberian Peninsula.Andalusia Regional Government through the project P12-RNM-2409Spanish Ministry of Economy and Competitiveness through the project CGL2013-45410-

Sarcoma classification by DNA methylation profiling

Sarcomas are malignant soft tissue and bone tumours affecting adults, adolescents and children. They represent a morphologically heterogeneous class of tumours and some entities lack defining histopathological features. Therefore, the diagnosis of sarcomas is burdened with a high inter-observer variability and misclassification rate. Here, we demonstrate classification of soft tissue and bone tumours using a machine learning classifier algorithm based on array-generated DNA methylation data. This sarcoma classifier is trained using a dataset of 1077 methylation profiles from comprehensively pre-characterized cases comprising 62 tumour methylation classes constituting a broad range of soft tissue and bone sarcoma subtypes across the entire age spectrum. The performance is validated in a cohort of 428 sarcomatous tumours, of which 322 cases were classified by the sarcoma classifier. Our results demonstrate the potential of the DNA methylation-based sarcoma classification for research and future diagnostic applications

Role of pericytes in the modulation of capillary blood flow in the cerebral cortex of the mouse

Einleitung: Perizyten sind murale Zellen in den Kapillaren, die im zentralen Nervensystem die Endothelzellen umfassen und die zunehmend als wichtige zelluläre Bestandteile der neurovaskulären Funktionseinheit anerkannt werden. Sie sind an der Bildung und Regulation der Bluthirnschranke beteiligt. Perizyten sind kontraktile Zellen, und reagieren in organotypischen Hirnpräparaten auf Neurotransmitter mit Konstriktionen und Dilatationen. Somit sind diese Zellen grundsätzlich in der Lage, die stete Kopplung des zerebralen Blutflusses an die neuronale Aktivität zu bewirken. Diese Funktion der Perizyten ist jedoch noch nicht eindeutig in vivo geklärt worden. Es ist ebenfalls weitgehend unbekannt, wie diese Zellen im Rahmen von pathologischen Veränderungen im zentralen Nervensystem reagieren. Methoden: Wir haben mittels eines transgenen Tiermodells (die β-actin eGFP Maus) und intravitaler Zwei- Photonen Mikroskopie die kontraktilen Eigenschaften der Perizyten im zerebralen Kortex untersucht. Um einen weiteren Einblick in die Rolle von Perizyten in pathologischen Szenarien zu gewinnen, haben wir in einem Schlaganfallmodell und in humanem post-mortem Gewebe aus Patienten mit der neuropathologischen Diagnose eines Schlaganfalls die Reaktion von Perizyten histologisch charakterisiert. Ergebnisse: Perizyten in Kapillaren der β-actin eGFP Maus zeigten im Präparat des akuten Hirnschnitts oder in vivo kontraktile Fähigkeiten und modulierten in vivo wirksam den Blutfluss in einzelnen Kapillaren. Jedoch konnten wir in einem Modell von funktioneller Hyperämie keine Durchmesserveränderungen durch kapilläre Perizyten detektieren. Im experimentellen Schlaganfallmodell wie auch im humanen Schlaganfall konnten wir zeigen, dass kapilläre Perizyten im Kern des Infarktes akut dezimiert werden, während Zellen um große Gefäße im Kern des Infarktes proliferieren und mit der Ablagerung von fibrotischer extrazellulärer Matrix assoziiert sind. Schlussfolgerung: Unsere Arbeit suggeriert, dass Perizyten in Kapillaren nicht Mediatoren der funktionellen Hyperämie während neuronaler Aktivierung sind. Jedoch sind sie in der Lage, den Blutfluss in Kapillaren durch Kontraktion zu beeinflussen, was während pathologischer Zustände des zentralen Nervensystems von Bedeutung sein könnte. Perizyten werden in Rahmen von Ischämie beschädigt und sterben im Kern des Infarktes akut ab. Murale Zellen in großen Gefäßen, die auch Perizytenmarker exprimieren, generieren im ischämischen Parenchym eine bisher unbekannte Population von stromalen Zellen, die zur Transformation des ischämischen Kerns in fibrotisches Narbengewebe beitragen. Das stromale Narbengewebe unterscheidet sich von der klassischen astroglialen Narbe und bietet möglicherweise einen neuen therapeutischen Angriffspunkt, um das Regenerationspotential vom ischämischen Gewebe zu verbessern.Introduction: Pericytes, the mural cells of capillaries, are most abundant in the central nervous system, where they regulate the blood-brain barrier. They are contractile in vitro and respond to neurotransmitters in organ preparations. Therefore, it has been proposed that they may mediate the coupling of blood flow to neuronal activity, and further provoke impairment to blood flow after ischemic lesions to the central nervous system. However, their ability to modulate blood flow in the brain in vivo has not been demonstrated and it is largely unknown how lesions to the neural tissue may affect pericytes over time. Methods: We used two-photon microscopy to study pericytes and the dynamic changes of capillary diameter and blood flow in the cortex of anesthetized β-actin eGFP mice in real time, as well as in brain slices. In order to determine the reaction of pericytes at different time points after cerebral ischemia, we have used histological samples obtained from an experimental stroke model or from human post-mortem stroke tissue. Results: Pericytes caused localized decreases in capillary diameter in acute brain slices and in the brain of anaesthetized mice, where they effected changes in capillary red blood cell flow. In contrast, during brief bursts of neuronal activity, capillary red blood cell flow increased without pericyte- induced capillary diameter changes. The analysis of immunohistological stains of murine or human ischemic tissue demonstrated an acute loss of capillary pericytes. At the same time, cells in larger vessels, sharing common cell markers with pericytes, proliferate and give rise to a stromal cell population associated to the deposition of fibrous extracellular matrix. Conclusions: Our data suggest that mural cells in precapillary and penetrating arterioles, rather than pericytes in capillaries, are responsible for the blood flow increase induced by neural activity. However, we also show that pericytes can modulate capillary blood flow in the brain in vivo, which may be important under pathological conditions. In an experimental stroke model as well as in humans, the immunohistological analysis suggests that capillary pericytes are affected and succumb largely after brain ischemia. Vascular cells of large vessels expressing pericyte markers participate in the generation of previously unrecognized stromal scar tissue, which is distinct from the classic astroglial scar. The stromal scar tissue represents a novel potential target for therapies aimed at increasing the regenerative potential of brain tissue after stroke

Selective engraftment of donor-derived myeloid cells in the lesioned facial nucleus after HI.

<p><b>A</b>) Identification of GFP⁺ myeloid cells in the lesioned facial nucleus of HI chimeras at 7 and 14 days after BMT. Note the increase in F4/80 immunoreactivity at day 14 compared with day 7, indicating increased inflammation. The contralateral unlesioned facial nucleus is devoid of donor-derived GFP⁺ cells and shows minimal F4/80 immunoreactivity. Laser confocal microscopic images of areas of interest (white squares) are shown at increasing magnifications (scale bars: 100 µm – 25 µm). Seven days after BMT, amoeboid GFP⁺F4/80⁺ and GFP⁺Iba-1⁺ cells were detected in the lesioned facial nucleus. At 14 days after BMT, GFP⁺F4/80⁺ and GFP⁺Iba-1⁺ cells in the lesioned facial nucleus were highly ramified. All donor-derived GFP⁺ cells expressed the macrophage markers, F4/80 and Iba-1. Nuclei were counterstained with DAPI. <b>B</b>) Quantification of myeloid cell engraftment in the lesioned facial nucleus at 7 and 14 days after BMT in FNA, HI, HI + FNA and busulfan + FNA animals. Note that donor-derived GFP⁺ cells were only detected in HI + FNA mice. Data are means + SEM from 3-5 animals per group. n.d. = none detected. <b>C</b>) Quantitative real-time PCR of CXCL10 and CCL2 mRNA expression in the facial nucleus of animals with FNA (white bars), HI (grey bars) and HI + FNA (black bars) at 14 days after BMT. The mRNA expression levels were normalized to GAPDH mRNA and compared to naïve mice (fold induction). Increased chemokine mRNA levels were observed in the facial nucleus of HI + FNA mice compared to HI animals. Data are means + SEM from 3-5 animals per group. Statistical significance is indicated by asterisks (*p<0.05).</p

Blood chimerism in HI- and busulfan-conditioned mice with FNA.

<p><b>A</b>) Overview of the experimental protocol. <i>HI</i>, <i>FNA</i> and <i>Tx</i> denote focal head irradiation, facial nerve axotomy and bone marrow transplantation, respectively. <b>B</b>) Flow cytometry of GFP expression in peripheral blood CD45⁺ cells at 2 weeks after BMT. The level of chimerism was significantly higher in the busulfan + FNA group compared with the HI + FNA group. FNA had no impact on blood chimerism. Data are means + SEM from 3-5 animals per group. Statistical significance is indicated by asterisks (****p<0.0001). <b>C</b>) Flow cytometric characterization of GFP-expressing cells in peripheral blood at 2 weeks after BMT. The vast majority of GFP⁺CD45⁺ cells express CD11b (>90%). Gating of this cell population reveals predominantly CD115⁺Ly6C^hiLy6G^- monocytes and CD115^-Ly6C⁺Ly6G⁺ neutrophils. Data are means + SEM from 3-5 animals per group. n.d. = none detected. No statistical differences were observed between the groups.</p

Gene expression profiles of cytokines and chemokines in the brain after HI and TBI.

<p><b>A</b>) Overview of the experimental protocol. <i>HI</i>, <i>TBI</i> and <i>Tx</i> denote focal head irradiation, total body irradiation and bone marrow transplantation, respectively. <b>B</b>) Quantitative real-time PCR of CCL2, CXCL10, CCL5 and TNF-α mRNA expression in brains of HI (grey columns) and TBI (white columns) animals at 1, 2, 4 and 16 weeks after irradiation and BMT. The mRNA expression levels were normalized to GAPDH mRNA and compared to naïve mice (fold induction). Reduced cytokine/chemokine mRNA levels were observed in HI brains compared to the TBI paradigm. Data are means + SEM from 3-5 animals per group. Statistical significance is indicated by asterisks (*p<0.05; **p<0.01; ***p<0.001).</p

The Influence of Emotional and Cognitive Factors on Limb Laterality Discrimination in Women with Fibromyalgia Syndrome: A Cross-Sectional Study Secondary Analysis

Previous scientific evidence has shown that patients with fibromyalgia syndrome (FMS) have alterations in the body schema. There have also been findings regarding the influence of psychological factors on pain, as well as evidence that patients with FMS have difficulty performing laterality discrimination tasks. The main objective of this study was to evaluate whether emotional and cognitive factors influence the limb laterality discrimination task in women with FMS. Seventeen of the participants were healthy female controls, and the other seventeen were women diagnosed with FMS. The main outcome measures were laterality discrimination, anxiety symptoms, depression symptoms, pain catastrophizing, and fear-related movement. The main analysis showed that patients with FMS had longer reaction times for laterality discrimination in hands (hand 20 images, p p p p p p < 0.0001)) disorders compared with healthy subjects. There was no correlation between limb laterality discrimination and psychological variables. In conclusion, patients with FMS showed impaired laterality discrimination, but psychological variables were not influenced. This could be due to the implicit nature of the task

PU.1 Level-Directed Chromatin Structure Remodeling at the Irf8 Gene Drives Dendritic Cell Commitment

Dendritic cells (DCs) are essential regulators of immune responses; however, transcriptional mechanisms that establish DC lineage commitment are poorly defined. Here, we report that the PU.1 transcription factor induces specific remodeling of the higher-order chromatin structure at the interferon regulatory factor 8 (Irf8) gene to initiate DC fate choice. An Irf8 reporter mouse enabled us to pinpoint an initial progenitor stage at which DCs separate from other myeloid lineages in the bone marrow. In the absence of Irf8, this progenitor undergoes DC-to-neutrophil reprogramming, indicating that DC commitment requires an active, Irf8-dependent escape from alternative myeloid lineage potential. Mechanistically, myeloid Irf8 expression depends on high PU.1 levels, resulting in local chromosomal looping and activation of a lineage- and developmental-stage-specific cis-enhancer. These data delineate PU.1 as a concentration-dependent rheostat of myeloid lineage selection by controlling long-distance contacts between regulatory elements and suggest that specific higher-order chromatin remodeling at the Irf8 gene determines DC differentiation