Cardiac multi-scale investigation of the right and left ventricle ex vivo: a review

The heart is a complex multi-scale system composed of components integrated at the subcellular, cellular, tissue and organ levels. The myocytes, the contractile elements of the heart, form a complex three-dimensional (3D) network which enables propagation of the electrical signal that triggers the contraction to efficiently pump blood towards the whole body. Cardiovascular diseases (CVDs), a major cause of mortality in developed countries, often lead to cardiovascular remodeling affecting cardiac structure and function at all scales, from myocytes and their surrounding collagen matrix to the 3D organization of the whole heart. As yet, there is no consensus as to how the myocytes are arranged and packed within their connective tissue matrix, nor how best to image them at multiple scales. Cardiovascular imaging is routinely used to investigate cardiac structure and function as well as for the evaluation of cardiac remodeling in CVDs. For a complete understanding of the relationship between structural remodeling and cardiac dysfunction in CVDs, multi-scale imaging approaches are necessary to achieve a detailed description of ventricular architecture along with cardiac function. In this context, ventricular architecture has been extensively studied using a wide variety of imaging techniques: ultrasound (US), optical coherence tomography (OCT), microscopy (confocal, episcopic, light sheet, polarized light), magnetic resonance imaging (MRI), micro-computed tomography (micro-CT) and, more recently, synchrotron X-ray phase contrast imaging (SR X-PCI). Each of these techniques have their own set of strengths and weaknesses, relating to sample size, preparation, resolution, 2D/3D capabilities, use of contrast agents and possibility of performing together with in vivo studies. Therefore, the combination of different imaging techniques to investigate the same sample, thus taking advantage of the strengths of each method, could help us to extract the maximum information about ventricular architecture and function. In this review, we provide an overview of available and emerging cardiovascular imaging techniques for assessing myocardial architecture ex vivo and discuss their utility in being able to quantify cardiac remodeling, in CVDs, from myocyte to whole organ

Behind the Intents: An In-depth Empirical Study on Software Refactoring in Modern Code Review

Code refactorings are of pivotal importance in modern code review. Developers may preserve, revisit, add or undo refactorings through changes’ revisions. Their goal is to certify that the driving intent of a code change is properly achieved. Developers’ intents behind refactorings may vary from pure structural improvement to facilitating feature additions and bug fixes. However, there is little understanding of the refactoring practices performed by developers during the code review process. It is also unclear whether the developers’ intents influence the selection, composition, and evolution of refactorings during the review of a code change. Through mining 1,780 reviewed code changes from 6 systems pertaining to two large open-source communities, we report the first in-depth empirical study on software refactoring during code review. We inspected and classified the developers’ intents behind each code change into 7 distinct categories. By analyzing data generated during the complete reviewing process, we observe: (i) how refactorings are selected, composed and evolved throughout each code change, and (ii) how developers’ intents are related to these decisions. For instance, our analysis shows developers regularly apply non-trivial sequences of refactorings that crosscut multiple code elements (i.e., widely scattered in the program) to support a single feature addition. Moreover, we observed that new developers’ intents commonly emerge during the code review process, influencing how developers select and compose their refactorings to achieve the new and adapted goals. Finally, we provide an enriched dataset that allows researchers to investigate the context and motivations behind refactoring operations during the code review process

The high-Eddington NLS1 Ark 564 has the coolest corona

Ark 564 is an archetypal narrow-line Seyfert 1 that has been well observed in soft X-rays from 0.3–10 keV, revealing a steep spectrum, strong soft excess, iron K emission line and dramatic variability on the order of hours. Because of its very steep spectrum, observations of the source above 10 keV have been sparse. We report here on the first NuSTAR observation of Ark 564. The source was observed for 200 ks with NuSTAR, 50 ks of which were concurrent with Suzaku observations. NuSTAR and Suzaku observed a dramatic flare, in which the hard emission is clearly delayed with respect to the soft emission, consistent with previous detections of a low-frequency hard lag found in XMM–Newton data. The NuSTAR spectrum is well described by a low-temperature Comptonization continuum (with an electron temperature of 15 ± 2 keV), which irradiates a highly ionized disc. No further relativistic broadening or ionized absorption is required. These spectral results show that Ark 564 has one of the lowest temperature coronae observed by NuSTAR to date. We discuss possible reasons for low-temperature coronae in high-Eddington sources.European Research Council (340442

A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries

Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration

Isotopic signature in isolated south-western populations of European brown bear (Ursus arctos)

Stable isotope analysis of animal tissue samples is increasingly used to study the trophic ecology of target species. The isotopic signatures respond to the type of diet, but also to the environmental conditions of their habitat. In the case of omnivorous, seasonal or opportunistic feeding species, the interpretation of isotopic values is more complex, as it is largely determined by food selection, either due to individual choice or because of availability. We analysed C and N isotopes in brown bear (Ursus arctos) hair from four isolated populations of south-western Europe (Cantabrian, Pyrenees, Central Apennines and Alpine) accounting for the geographical and climatic differences among the four areas. We found inter-population differences in isotopic signatures that cannot be attributed to climatic differences alone, indicating that at least some bears from relatively higher altitude populations experiencing higher precipitation (Pyrenees) show a greater consumption of animal foods than those from lower altitudes (Cantabrian and Apennines). The quantification of isotopic niche space using Layman's metrics identified significant similarities between the Cantabrian and Central Apennine samples that markedly differ from the Pyrenean and Alpine. Our study provides a baseline to allow further comparisons in isotopic niche spaces in a broad ranged omnivorous mammal, whose European distribution requires further conservation attention especially for southern isolated populations

Probing electron-phonon interactions away from the Fermi level with resonant inelastic x-ray scattering

Interactions between electrons and lattice vibrations are responsible for a wide range of material properties and applications. Recently, there has been considerable interest in the development of resonant inelastic x-ray scattering (RIXS) as a tool for measuring electron-phonon ( e -ph) interactions. Here, we demonstrate the ability of RIXS to probe the interaction between phonons and specific electronic states both near to, and away from, the Fermi level. We perform carbon K -edge RIXS measurements on graphite, tuning the incident x-ray energy to separately probe the interactions of the π ∗ and σ ∗ electronic states. Our high-resolution data reveal detailed structure in the multiphonon RIXS features that directly encodes the momentum dependence of the e -ph interaction strength. We develop a Green’s-function method to model this structure, which naturally accounts for the phonon and interaction-strength dispersions, as well as the mixing of phonon momenta in the intermediate state. This model shows that the differences between the spectra can be fully explained by contrasting trends of the e -ph interaction through the Brillouin zone, being concentrated at the Γ and K points for the π ∗ states while being significant at all momenta for the σ ∗ states. Our results advance the interpretation of phonon excitations in RIXS and extend its applicability as a probe of e -ph interactions to a new range of out-of-equilibrium situations

Introduction: Turnaround and let-down: making sense of Brazil and Africa after the surge

By improving political connections under a common South-South aegis, promoting new trade opportunities and expanding the disbursement of significant amounts of development cooperation, Brazil quickly secured a foothold of its own in Africa between 2003 and 2014. However, in the face of a political meltdown and of controversial judicial investigations back home, Brazil’s inversions in Africa have since then essentially collapsed. This abrupt turnaround calls for a more critical exegesis of the years of expansion. What were the main successes and failures of Brazil’s overall strategy towards Africa? And what does the dramatic change of events, with Brazil moving from a pivotal player to an almost invisible one in merely half a decade, tell us about the possibility of a new pick-up of interest for Africa? This introduction to the edited volume takes stock of the main trends in previous literature over the character and content of Brazil’s foreign policy towards the continent and sets the ground for the following chapters.info:eu-repo/semantics/acceptedVersio

The metabolic interplay between dietary carbohydrate and exercise and its role in acute appetite-regulation in males: a randomised controlled study

Understanding the metabolic determinants of post-exercise appetite-regulation would facilitate the development of adjunctive-therapeutics to supress compensatory eating behaviours and improve the efficacy of exercise as a weight loss treatment. Metabolic responses to acute exercise are however dependent on pre-exercise nutritional practices, including carbohydrate intake. We therefore aimed to determine the interactive effects of dietary carbohydrate and exercise on plasma hormonal and metabolite responses and explore mediators of exercise-induced changes in appetite-regulation across nutritional states. In this randomised crossover study, participants completed four 120 min visits: (i) control (water) followed by rest; (ii) control followed by exercise (30 min at ∼75% V̇O2 max); (iii) carbohydrate (75 g maltodextrin) followed by rest; and (iv) carbohydrate followed by exercise. An ad libitum meal was provided at the end of each 120 min visit, with blood sample collection and appetite assessment performed at pre-defined intervals. We found that dietary carbohydrate and exercise exerted independent effects on the hormones GLP-1 (Carbohydrate: 16.8 pmol/L, Exercise: 7.4 pmol/L), ghrelin (Carbohydrate: -48.8 pmol/L, Exercise: -22.7 pmol/L) and glucagon (Carbohydrate: 9.8 ng/L, Exercise: 8.2 ng/L) that were linked to the generation of distinct plasma 1H-NMR metabolic phenotypes. These metabolic responses were associated with changes in appetite and energy intake, and plasma acetate and succinate were subsequently identified as potential novel mediators of exercise-induced appetite and energy intake responses. In summary, dietary carbohydrate and exercise independently influence gastrointestinal hormones associated with appetite regulation. Future work is warranted to probe the mechanistic importance of plasma acetate and succinate in post-exercise appetite-regulation

Serial optical coherence microscopy for label-free volumetric histopathology

The observation of histopathology using optical microscope is an essential procedure for examination of tissue biopsies or surgically excised specimens in biological and clinical laboratories. However, slide-based microscopic pathology is not suitable for visualizing the large-scale tissue and native 3D organ structure due to its sampling limitation and shallow imaging depth. Here, we demonstrate serial optical coherence microscopy (SOCM) technique that offers label-free, high-throughput, and large-volume imaging of ex vivo mouse organs. A 3D histopathology of whole mouse brain and kidney including blood vessel structure is reconstructed by deep tissue optical imaging in serial sectioning techniques. Our results demonstrate that SOCM has unique advantages as it can visualize both native 3D structures and quantitative regional volume without introduction of any contrast agents