2,538 research outputs found

    Cardiac cellularity is dependent upon biological sex and is regulated by gonadal hormones.

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    AIMS: Sex differences have been consistently identified in cardiac physiology and incidence of cardiac disease. However, the underlying biological causes for the differences remain unclear. We sought to characterize the cardiac non-myocyte cellular landscape in female and male hearts to determine whether cellular proportion of the heart is sex-dependent and whether endocrine factors modulate the cardiac cell proportions. METHODS AND RESULTS: Utilizing high-dimensional flow cytometry and immunofluorescence imaging, we found significant sex-specific differences in cellular composition of the heart in adult and juvenile mice, that develops postnatally. Removal of systemic gonadal hormones by gonadectomy results in rapid sex-specific changes in cardiac non-myocyte cellular proportions including alteration in resident mesenchymal cell and leucocyte populations, indicating gonadal hormones and their downstream targets regulate cardiac cellular composition. The ectopic reintroduction of oestrogen and testosterone to female and male mice, respectively, reverses many of these gonadectomy-induced compositional changes. CONCLUSION: This work shows that the constituent cell types of the mouse heart are hormone-dependent and that the cardiac cellular landscapes are distinct in females and males, remain plastic, and can be rapidly modulated by endocrine factors. These observations have implications for strategies aiming to therapeutically alter cardiac cellular heterogeneity and underscore the importance of considering biological sex for studies examining cardiac physiology and stress responses

    Sacral Fractures and Associated Injuries.

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    STUDY DESIGN: Literature review. OBJECTIVE: The aim of this review is to describe the injuries associated with sacral fractures and to analyze their impact on patient outcome. METHODS: A comprehensive narrative review of the literature was performed to identify the injuries associated with sacral fractures. RESULTS: Sacral fractures are uncommon injuries that result from high-energy trauma, and that, due to their rarity, are frequently underdiagnosed and mistreated. Only 5% of sacral fractures occur in isolation. Injuries most often associated with sacral fractures include neurologic injuries (present in up to 50% of sacral fractures), pelvic ring disruptions, hip and lumbar spine fractures, active pelvic/ abdominal bleeding and the presence of an open fracture or significant soft tissue injury. Diagnosis of pelvic ring fractures and fractures extending to the lumbar spine are key factors for the appropriate management of sacral fractures. Importantly, associated systemic (cranial, thoracic, and abdominopelvic) or musculoskeletal injuries should be promptly assessed and addressed. These associated injuries often dictate the management and eventual outcome of sacral fractures and, therefore, any treatment algorithm should take them into consideration. CONCLUSIONS: Sacral fractures are complex in nature and often associated with other often-missed injuries. This review summarizes the most relevant associated injuries in sacral fractures and discusses on their appropriate management

    An Abundant Tissue Macrophage Population in the Adult Murine Heart with a Distinct Alternatively-Activated Macrophage Profile

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    Cardiac tissue macrophages (cTMs) are a previously uncharacterised cell type that we have identified and characterise here as an abundant GFP+ population within the adult Cx3cr1GFP/+ knock-in mouse heart. They comprise the predominant myeloid cell population in the myocardium, and are found throughout myocardial interstitial spaces interacting directly with capillary endothelial cells and cardiomyocytes. Flow cytometry-based immunophenotyping shows that cTMs exhibit canonical macrophage markers. Gene expression analysis shows that cTMs (CD45+CD11b+GFP+) are distinct from mononuclear CD45+CD11b+GFP+ cells sorted from the spleen and brain of adult Cx3cr1GFP/+ mice. Gene expression profiling reveals that cTMs closely resemble alternatively-activated anti-inflammatory M2 macrophages, expressing a number of M2 markers, including Mrc1, CD163, and Lyve-1. While cTMs perform normal tissue macrophage homeostatic functions, they also exhibit a distinct phenotype, involving secretion of salutary factors (including IGF-1) and immune modulation. In summary, the characterisation of cTMs at the cellular and molecular level defines a potentially important role for these cells in cardiac homeostasis

    A protocol for rapid and parallel isolation of myocytes and non-myocytes from multiple mouse hearts.

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    This protocol features parallel isolation of myocytes and non-myocytes from murine hearts. It was designed with considerations for (1) time required to extract cardiac cells, (2) cell viability, and (3) protocol scalability. Here, a peristaltic pump and 3D-printed elements are combined to perfuse the heart with enzymes to dissociate cells. Myocytes and non-myocytes extracted using this protocol are separated by centrifugation and/or fluorescence-activated cell sorting for use in downstream applications including single-cell omics or other bio-molecular analyses. For complete details on the use and execution of this protocol, please refer to McLellan et al. (2020)

    Expanding distribution of lethal amphibian fungus Batrachochytrium salamandrivorans in Europe

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    Emerging fungal diseases can drive amphibian species to local extinction. During 2010-2016, we examined 1,921 urodeles in 3 European countries. Presence of the chytrid fungus Batrachochytrium salamandrivorans at new locations and in urodeles of different species expands the known geographic and host range of the fungus and underpins its imminent threat to biodiversity

    Insulin-like growth factor 1 gene (CA)n repeats and a variable number of tandem repeats of the insulin gene in Brazilian children born small for gestational age

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    OBJECTIVE: To investigate the influence of (CA)n repeats in the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene on birth size in children who are small or adequate-sized for gestational age and to correlate these polymorphisms with serum insulin-like growth factor 1 levels and insulin sensitivity in children who are small for gestational age, with and without catch-up growth. PATIENTS AND METHODS: We evaluated 439 infants: 297 that were adequate-sized for gestational age and 142 that were small for gestational age (66 with and 76 without catch-up). The number of (CA)n repeat in the insulin-like growth factor 1 gene and a variable number of tandem repeats in the insulin gene were analyzed using GENESCAN software and polymerase chain reaction followed by enzymatic digestion, respectively. Clinical and laboratory data were obtained from all patients. RESULTS: The height, body mass index, paternal height, target height and insulin-like growth factor 1 serum levels were higher in children who were small for gestational age with catch-up. There was no difference in the allelic and genotypic distributions of both polymorphisms between the adequate-sized and small infants or among small infants with and without catch-up. Similarly, the polymorphisms were not associated with clinical or laboratory variables. CONCLUSION: Polymorphisms of the (CA)n repeats of the insulin-like growth factor 1 gene and a variable number of tandem repeats of the insulin gene, separately or in combination, did not influence pre- or postnatal growth, insulin-like growth factor 1 serum levels or insulin resistance

    Metric analysis of the information visibility and diffusion about the European Higher Education Area on Spanish university websites.

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    The purpose of the study proposed in this paper is to evaluate the Spanish public university websites dedicated to the European Higher Education Area (EHEA). To do so, the quality of these resources has been analysed in the light of data provided by a series of indicators grouped in seven criteria, most of which were used to determine what information is made available and in what way. The criteria used in our analysis are: visibility, authority, updatedness, accesibility, correctness and completeness, quality assessment and navigability. All in all, the results allow us to carry out an overall diagnosis of the situation and also provide us with information about the situation at each university, thus revealing their main strengths, namely authority and navegability, and also their chief shortcomings: updatedness, accessibility and quality assessment. In this way it is possible to detect the best practices in each of the aspects evaluated so that they can serve as an example and guide for universities with greater deficiencies and thus help them to improve their EHEA websites

    The Carnegie Supernova Project: First Near-Infrared Hubble Diagram to z~0.7

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    The Carnegie Supernova Project (CSP) is designed to measure the luminosity distance for Type Ia supernovae (SNe Ia) as a function of redshift, and to set observational constraints on the dark energy contribution to the total energy content of the Universe. The CSP differs from other projects to date in its goal of providing an I-band {rest-frame} Hubble diagram. Here we present the first results from near-infrared (NIR) observations obtained using the Magellan Baade telescope for SNe Ia with 0.1 < z < 0.7. We combine these results with those from the low-redshift CSP at z <0.1 (Folatelli et al. 2009). We present light curves and an I-band Hubble diagram for this first sample of 35 SNe Ia and we compare these data to 21 new SNe Ia at low redshift. These data support the conclusion that the expansion of the Universe is accelerating. When combined with independent results from baryon acoustic oscillations (Eisenstein et al. 2005), these data yield Omega_m = 0.27 +/- 0.0 (statistical), and Omega_DE = 0.76 +/- 0.13 (statistical) +/- 0.09 (systematic), for the matter and dark energy densities, respectively. If we parameterize the data in terms of an equation of state, w, assume a flat geometry, and combine with baryon acoustic oscillations, we find that w = -1.05 +/- 0.13 (statistical) +/- 0.09 (systematic). The largest source of systematic uncertainty on w arises from uncertainties in the photometric calibration, signaling the importance of securing more accurate photometric calibrations for future supernova cosmology programs. Finally, we conclude that either the dust affecting the luminosities of SNe Ia has a different extinction law (R_V = 1.8) than that in the Milky Way (where R_V = 3.1), or that there is an additional intrinsic color term with luminosity for SNe Ia independent of the decline rate.Comment: 44 pages, 23 figures, 9 tables; Accepted for publication in the Astrophysical Journa

    Heritage branding orientation: The case of Ach. Brito and the dynamics between corporate and product heritage brands

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    The notion of heritage branding orientation is introduced and explicated. Heritage branding orientation is designated as embracing both product and corporate brands and differs from corporate heritage brand orientation which has an explicit corporate focus. Empirical insights are drawn from an in-depth and longitudinal case study of Ach. Brito, a celebrated Portuguese manufacturer of soaps and toiletries. This study shows how, by the pursuance of a strategy derived from a heritage branding orientation Ach. Brito – after a prolonged period of decline – achieved a dramatic strategic turnaround. The findings reveal how institutional heritage can be a strategic resource via its adoption and activation at both the product and corporate levels. Moreover, the study showed how the bi-lateral interplay between product and corporate brand levels can be mutually reinforcing. In instrumental terms, the study shows how heritage can be activated and articulated in different ways. For instance, it can re-position both product and/or corporate brands; it can be meaningfully informed by product brand heritage and shape corporate heritage; and can be of strategic importance to both medium-sized and small enterprises

    Genetic divergence in two tropical maize composites after four cycles of reciprocal recurrent selection

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    First published: 6 January 2017; Open Access JournalTwo tropical maize composites were subjected to four cycles of reciprocal recurrent selection to develop divergent inbred lines with good combining ability. This study was conducted to examine the extent of genetic diversity, changes in allele composition and genetic structure, of 100 randomly selected S1 lines each from the original (C0) and advanced (C4) selection cycles of TZL COMP3 and TZL COMP4, genotyped using single nucleotide polymorphism (SNP) markers. Results revealed that the proportion of alleles at both low and high frequencies decreased from C0 to C4, whereas those at intermediate frequencies increased at C4 in the two composites. More unique and other alleles were lost at C4 in TZL COMP3 relative to those in TZL COMP4. The changes in different measures of genetic diversity were either small or negligible with selection in the two composites. The proportion of markers departing from Hardy–Weinberg equilibrium (HWE) decreased with selection, whereas the total number of pairs of markers in linkage disequilibrium increased with selection in the two composites. Examination of changes in population structures using a model-based approach as well as cluster and multivariate analyses found a high degree of concordance in stratifying the 400 S1 lines into four non-overlapping groups corresponding to the two selection cycles each within the reciprocal composites. The observed molecular-based divergence between cycles within the same composite and the clear differentiation between the complementary composites highlight the importance of reciprocal recurrent selection for preserving genetic diversity for long-term selection. This increases the potential of the advanced selection cycles to sustain genetic gain in productivity of hybrids adapted to the savannas in West and Central Africa
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