Chondrogenically Primed Human Mesenchymal Stem Cells Persist and Undergo Early Stages of Endochondral Ossification in an Immunocompetent Xenogeneic Model

Tissue engineering approaches using progenitor cells such as mesenchymal stromal cells (MSCs) represent a promising strategy to regenerate bone. Previous work has demonstrated the potential of chondrogenically primed human MSCs to recapitulate the process of endochondral ossification and form mature bone in vivo, using immunodeficient xenogeneic models. To further the translation of such MSC-based approaches, additional investigation is required to understand the impact of interactions between human MSC constructs and host immune cells upon the success of MSC-mediated bone formation. Although human MSCs are considered hypoimmunogenic, the potential of chondrogenically primed human MSCs to induce immunogenic responses in vivo, as well as the efficacy of MSC-mediated ectopic bone formation in the presence of fully competent immune system, requires further elucidation. Therefore, the aim of this study was to investigate the capacity of chondrogenically primed human MSC constructs to persist and undergo the process of endochondral ossification in an immune competent xenogeneic model. Chondrogenically differentiated human MSC pellets were subcutaneously implanted to wild-type BALB/c mice and retrieved at 2 and 12 weeks post-implantation. The percentages of CD4(+) and CD8(+) T cells, B cells, and classical/non-classical monocyte subsets were not altered in the peripheral blood of mice that received chondrogenic MSC constructs compared to sham-operated controls at 2 weeks post-surgery. However, MSC-implanted mice had significantly higher levels of serum total IgG compared to sham-operated mice at this timepoint. Flow cytometric analysis of retrieved MSC constructs identified the presence of T cells and macrophages at 2 and 12 weeks post-implantation, with low levels of immune cell infiltration to implanted MSC constructs detected by CD45 and CD3 immunohistochemical staining. Despite the presence of immune cells in the tissue, MSC constructs persisted in vivo and were not degraded/resorbed. Furthermore, constructs became mineralised, with longitudinal micro-computed tomography imaging revealing an increase in mineralised tissue volume from 4 weeks post-implantation until the experimental endpoint at 12 weeks. These findings indicate that chondrogenically differentiated human MSC pellets can persist and undergo early stages of endochondral ossification following subcutaneous implantation in an immunocompetent xenogeneic model. This scaffold-free model may be further extrapolated to provide mechanistic insight to osteoimmunological processes regulating bone regeneration and homeostasis

Constraints on Decaying Dark Matter from Fermi Observations of Nearby Galaxies and Clusters

We analyze the impact of Fermi gamma-ray observations (primarily non-detections) of selected nearby galaxies, including dwarf spheroidals, and of clusters of galaxies on decaying dark matter models. We show that the fact that galaxy clusters do not shine in gamma rays puts the most stringent limits available to-date on the lifetime of dark matter particles for a wide range of particle masses and decay final states. In particular, our results put strong constraints on the possibility of ascribing to decaying dark matter both the increasing positron fraction reported by PAMELA and the high-energy feature in the electron-positron spectrum measured by Fermi. Observations of nearby dwarf galaxies and of the Andromeda Galaxy (M31) do not provide as strong limits as those from galaxy clusters, while still improving on previous constraints in some cases.Comment: 27 pages, 5 figures, submitted to JCAP, revised version with some additions and correction

II Jornadas de la Sociedad Española para la Conservación y Estudio de Los Mamíferos (SECEM) Soria 7-9 diciembre 1995

Seguimiento de una reintroducción de corzo (Capreolus capreolus) en ambiente mediterráneo. Dispersión y área de campeoModelos de distribución de los insectívoros ern la Península IbéricaDieta anual del zorro, Vulpes vulpes, en dos hábitats del Parque Nacional de DoñanaDesarrollo juvenil del cráneo en las poblaciones ibéricas de gato montés, Felis silvestris Schreber, 1777Presencia y expansión del visón americano (Mustela vison) en las provincias de Teruel y Castellón (Este de España).Preferencias de hábitat invernal de la musaraña común (Crocidura russula) en un encinar fragmentado de la submeseta norteUso de cámaras automáticas para la recogida de información faunística.Dieta del lobo en dos zonas de Asturias (España) que difieren en carga ganadera.Consumo de frutos y dispersión de semillas de serbal (Sorbus aucuparia L.) por zorros y martas en la cordillera Cantábrica occidentalEvaluación de espermatozoides obtenidos postmorten en el ciervo.Frecuencia de aparición de diferentes restos de conejo en excrementos de lince y zorroAtlas preliminar de los mamíferos de Soria (España)Censo y distribución de la marmota alpina (Marmota marmota) en Navarra.Trampeo fotográfico del género Martes en el Parque Nacional de Aigüestortes i Estany de Sant Maurici (Lleida)Peer reviewe

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

7th Drug hypersensitivity meeting: part two

No abstract availabl

DLG4-related synaptopathy: a new rare brain disorder

PURPOSE: Postsynaptic density protein-95 (PSD-95), encoded by DLG4, regulates excitatory synaptic function in the brain. Here we present the clinical and genetic features of 53 patients (42 previously unpublished) with DLG4 variants.METHODS: The clinical and genetic information were collected through GeneMatcher collaboration. All the individuals were investigated by local clinicians and the gene variants were identified by clinical exome/genome sequencing.RESULTS: The clinical picture was predominated by early onset global developmental delay, intellectual disability, autism spectrum disorder, and attention deficit-hyperactivity disorder, all of which point to a brain disorder. Marfanoid habitus, which was previously suggested to be a characteristic feature of DLG4-related phenotypes, was found in only nine individuals and despite some overlapping features, a distinct facial dysmorphism could not be established. Of the 45 different DLG4 variants, 39 were predicted to lead to loss of protein function and the majority occurred de novo (four with unknown origin). The six missense variants identified were suggested to lead to structural or functional changes by protein modeling studies.CONCLUSION: The present study shows that clinical manifestations associated with DLG4 overlap with those found in other neurodevelopmental disorders of synaptic dysfunction; thus, we designate this group of disorders as DLG4-related synaptopathy.Genetics of disease, diagnosis and treatmen

First measurement of θ<inf>13</inf> from delayed neutron capture on hydrogen in the Double Chooz experiment

The Double Chooz experiment has determined the value of the neutrino oscillation parameter θ13 from an analysis of inverse beta decay interactions with neutron capture on hydrogen. This analysis uses a three times larger fiducial volume than the standard Double Chooz assessment, which is restricted to a region doped with gadolinium (Gd), yielding an exposure of 113.1 GW-ton-years. The data sample used in this analysis is distinct from that of the Gd analysis, and the systematic uncertainties are also largely independent, with some exceptions, such as the reactor neutrino flux prediction. A combined rate- and energy-dependent fit finds sin22θ13=0.097±0.034 (stat.)±0.034 (syst.), excluding the no-oscillation hypothesis at 2.0. This result is consistent with previous measurements of sin22θ13

Graminoid invasion in an insular endemism hotspot and its protected areas

Invasive plant species are increasingly altering species composition and the functioning of ecosystems from a local to a global scale. The grass species Pennisetum setaceum has recently raised concerns as an invader on dierent archipelagos worldwide. Among these aected archipelagos are the Canary Islands, which are a hotspot of endemism. Consequently, conservation managers and stakeholders are interested in the potential spreading of this species in the archipelago. We identify the current extent of the suitable habitat for P. setaceum on the island of La Palma to assess how it affects island ecosystems, protected areas (PAs), and endemic plant species richness. We recorded in situ occurrences of P. setaceum from 2010 to 2018 and compiled additional ones from databases at a 500 m x 500 m resolution. To assess the current suitable habitat and possible distribution patterns of P. setaceum on the island, we built an ensemble model. We projected habitat suitability for island ecosystems and PAs and identified risks for total as well as endemic plant species richness. The suitable habitat for P. setaceum is calculated to cover 34.7% of the surface of La Palma. In open ecosystems at low to mid elevations, where native ecosystems are already under pressure by land use and human activities, the spread of the invader will likely lead to additional threats to endemic plant species. Forest ecosystems (e.g., broadleaved evergreen and coniferous forests) are not likely to be aected by the spread of P. setaceum because of its heliophilous nature. Our projection of suitable habitat of P. setaceum within ecosystems and PAs on La Palma supports conservationists and policymakers in prioritizing management and control measures and acts as an example for the potential threat of this graminoid invader on other islands

Identifying genes suitable for constructing pH and salt tolerant Rhizobium inoculants for improving French bean cultivation under semiarid conditions

Boesten B, Schlüter A, Prell J, Krämer M, Lipka V, Priefer UB. Identifying genes suitable for constructing pH and salt tolerant Rhizobium inoculants for improving French bean cultivation under semiarid conditions. In: Olivares J, Palomares AJ, eds. Proceedings of the Fourth European Nitrogen Fixation Conference. 2000: 319

3. reunion de biologia molecular de plantas

AbstractsCentro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai