Pulmonary Capillary Recruitment and Distention in Mammalian Lungs: Species Similarities

Pulmonary arterial pressure rises minimally during exercise. The pulmonary microcirculation accommodates increasing blood flow via recruitment of pulmonary capillaries and, at higher flows, by distention of already perfused capillaries. The flow transition range between recruitment and distention has not been studied or compared across mammalian species, including humans. We hypothesised that the range would be similar. Functional pulmonary capillary surface area (FCSA) can be estimated using validated metabolic techniques. We reviewed data from previous studies in three mammalian species (perfused rabbit lungs and dog lung lobes, and exercising humans) and generated blood flow-FCSA curves over a range of flows. We noted where the curves diverged from the theoretical line of pure recruitment (Recruitment) and determined the flow where the curve slope equalled 50% that of Recruitment, or equalled that of a theoretical curve representing full capillary distention (Distention). The three mammalian species have similar flow ranges for the transition from predominantly recruitment to predominantly distention, with dogs having the highest transition point. Within the physiological range of most daily activity, the species are similar and accommodate increasing blood flow mainly via recruitment, with progressive distention at higher flows. This is highly relevant to pulmonary physiology during exercise

First observation of 54Zn and its decay by two-proton emission

The nucleus 54Zn has been observed for the first time in an experiment at the SISSI/LISE3 facility of GANIL in the quasi-fragmentation of a 58Ni beam at 74.5 MeV/nucleon in a natNi target. The fragments were analysed by means of the ALPHA-LISE3 separator and implanted in a silicon-strip detector where correlations in space and time between implantation and subsequent decay events allowed us to generate almost background free decay spectra for about 25 different nuclei at the same time. Eight 54Zn implantation events were observed. From the correlated decay events, the half-life of 54Zn is determined to be 3.2 +1.8/-0.8 ms. Seven of the eight implantations are followed by two-proton emission with a decay energy of 1.48(2) MeV. The decay energy and the partial half-life are compared to model predictions and allow for a test of these two-proton decay models.Comment: 4 pages, 4 figures, accepted for publication in PR

The Paradox of Pulmonary Vascular Resistance: Restoration of Pulmonary Capillary Recruitment as a \u3ci\u3eSine Qua Non\u3c/i\u3e for True Therapeutic Success in Pulmonary Arterial Hypertension

Exercise-induced increases in pulmonary blood flow normally increase pulmonary arterial pressure only minimally, largely due to a reserve of pulmonary capillaries that are available for recruitment to carry the flow. In pulmonary arterial hypertension, due to precapillary arteriolar obstruction, such recruitment is greatly reduced. In exercising pulmonary arterial hypertension patients, pulmonary arterial pressure remains high and may even increase further. Current pulmonary arterial hypertension therapies, acting principally as vasodilators, decrease calculated pulmonary vascular resistance by increasing pulmonary blood flow but have a minimal effect in lowering pulmonary arterial pressure and do not restore significant capillary recruitment. Novel pulmonary arterial hypertension therapies that have mainly antiproliferative properties are being developed to try and diminish proliferative cellular obstruction in precapillary arterioles. If effective, those agents should restore capillary recruitment and, during exercise testing, pulmonary arterial pressure should remain low despite increasing pulmonary blood flow. The effectiveness of every novel therapy for pulmonary arterial hypertension should be evaluated not only at rest, but with measurement of exercise pulmonary hemodynamics during clinical trials

Accuracy of right atrial pressure estimation using a multi-parameter approach derived from inferior vena cava semi-automated edge-tracking echocardiography: a pilot study in patients with cardiovascular disorders

The echocardiographic estimation of right atrial pressure (RAP) is based on the size and inspiratory collapse of the inferior vena cava (IVC). However, this method has proven to have limits of reliability. The aim of this study is to assess feasibility and accuracy of a new semi-automated approach to estimate RAP. Standard acquired echocardiographic images were processed with a semi-automated technique. Indexes related to the collapsibility of the vessel during inspiration (Caval Index, CI) and new indexes of pulsatility, obtained considering only the stimulation due to either respiration (Respiratory Caval Index, RCI) or heartbeats (Cardiac Caval Index, CCI) were derived. Binary Tree Models (BTM) were then developed to estimate either 3 or 5 RAP classes (BTM3 and BTM5) using indexes estimated by the semi-automated technique. These BTMs were compared with two standard estimation (SE) echocardiographic methods, indicated as A and B, distinguishing among 3 and 5 RAP classes, respectively. Direct RAP measurements obtained during a right heart catheterization (RHC) were used as reference. 62 consecutive \u2018all-comers\u2019 patients that had a RHC were enrolled; 13 patients were excluded for technical reasons. Therefore 49 patients were included in this study (mean age 62.2\ua0\ub1\ua015.2\ua0years, 75.5% pulmonary hypertension, 34.7% severe left ventricular dysfunction and 51% right ventricular dysfunction). The SE methods showed poor accuracy for RAP estimation (method A: misclassification error, ME\ua0=\ua051%, R2\ua0=\ua00.22; method B: ME\ua0=\ua069%, R2\ua0=\ua00.26). Instead, the new semi-automated methods BTM3 and BTM5 have higher accuracy (ME\ua0=\ua014%, R2\ua0=\ua00.47 and ME\ua0=\ua022%, R2\ua0=\ua00.61, respectively). In conclusion, a multi-parametric approach using IVC indexes extracted by the semi-automated approach is a promising tool for a more accurate estimation of RAP

Direct and sequential radiative three-body reaction rates at low temperatures

We investigate the low-temperature reaction rates for radiative capture processes of three particles. We compare direct and sequential capture mechanisms and rates using realistic phenomenological parametrizations of the corresponding photodissociation cross sections.Energy conservation prohibits sequential capture for energies smaller than that of the intermediate two-body structure. A finite width or a finite temperature allows this capture mechanism. We study generic effects of positions and widths of two- and three-body resonances for very low temperatures. We focus on nuclear reactions relevant for astrophysics, and we illustrate with realistic estimates for the $\alpha$-$\alpha$-$\alpha$ and $\alpha$-$\alpha$-$n$ radiative capture processes. The direct capture mechanism leads to reaction rates which for temperatures smaller than 0.1 GK can be several orders of magnitude larger than those of the NACRE compilation.Comment: To be published in European Physical Journal

Extending the north-east limit of the chart of nuclides

The existence of nuclei with exotic combinations of protons and neutrons provides fundamental information on the forces acting between nucleons. The maximum number of neutrons a given number of protons can bind, neutron drip line1, is only known for the lightest chemical elements, up to oxygen. For heavier elements, the larger its atomic number, the farther from this limit is the most neutron-rich known isotope. The properties of heavy neutron-rich nuclei also have a direct impact on understanding the observed abundances of chemical elements heavier than iron in our Universe. Above half of the abundances of these elements are thought to be produced in rapid-neutron capture reactions, r-process, taking place in violent stellar scenarios2 where heavy neutron-rich nuclei, far beyond the ones known up today, are produced. Here we present a major step forward in the production of heavy neutron-rich nuclei: the discovery of 73 new neutron-rich isotopes of chemical elements between tantalum (Z=72) and actinium (Z=89). This result proves that cold-fragmentation reactions3 at relativistic energies are governed by large fluctuations in isospin and energy dissipation making possible the massive production of heavy neutron-rich nuclei, paving then the way for the full understanding of the origin of the heavier elements in our Universe. It is expected that further studies providing ground and structural properties of the nuclei presented here will reveal further details on the nuclear shell evolution along Z=82 and N=126, but also on the understanding of the stellar nucleosyntheis r-process around the waiting point at A~190 defining the speed of the matter flow towards heavier fissioning nuclei

Pluripotency factors regulate the onset of Hox cluster activation in the early embryo

Pluripotent cells are a transient population of the mammalian embryo dependent on transcription factors, such as OCT4 and NANOG, which maintain pluripotency while suppressing lineage specification. However, these factors are also expressed during early phases of differentiation, and their role in the transition from pluripotency to lineage specification is largely unknown. We found that pluripotency factors play a dual role in regulating key lineage specifiers, initially repressing their expression and later being required for their proper activation. We show that Oct4 is necessary for activation of HoxB genes during differentiation of embryonic stem cells and in the embryo. In addition, we show that the HoxB cluster is coordinately regulated by OCT4 binding sites located at the 3′ end of the cluster. Our results show that core pluripotency factors are not limited to maintaining the precommitted epiblast but are also necessary for the proper deployment of subsequent developmental programs.This work was funded by the Spanish government (grants BFU2017-84914-P and PID2020-115755GB-I00 to M.M.; BFU2016-74961-P and BFU2016-81887-REDT to J.L.G.-S.), the Andalusian government (grant BIO-396 to J.L.G.-S.), and the European Research Council (ERC; grant agreement 740041 to J.L.G.-S.). M.T. held Juan de la Cierva fellowships from the Spanish government (FJCI-2017-31791 and IJC2019-038897-I), R.R. and R.D.A. held FPU fellowships from the government, and J.V. was the recipient of a “La Caixa” fellowship. Work in the laboratory of J.L.G.-S. was supported by a María de Maetzu Unit of Excellence Grant (MDM-2016-0687) to the Department of Gene Regulation and Morphogenesis of the CABD. The CBMSO is supported by an institutional grant from the Fundación Ramon Areces, and the CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN), and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033). : With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2020-001041-S)

Pluripotency factors regulate the onset of Hox cluster activation in the early embryo

Pluripotent cells are a transient population of the mammalian embryo dependent on transcription factors, such as OCT4 and NANOG, which maintain pluripotency while suppressing lineage specification. However, these factors are also expressed during early phases of differentiation, and their role in the transition from pluripotency to lineage specification is largely unknown. We found that pluripotency factors play a dual role in regulating key lineage specifiers, initially repressing their expression and later being required for their proper activation. We show that Oct4 is necessary for activation of HoxB genes during differentiation of embryonic stem cells and in the embryo. In addition, we show that the HoxB cluster is coordinately regulated by OCT4 binding sites located at the 3′ end of the cluster. Our results show that core pluripotency factors are not limited to maintaining the precommitted epiblast but are also necessary for the proper deployment of subsequent developmental programs