Persistent Vascular Collagen Accumulation Alters Hemodynamic Recovery from Chronic Hypoxia

Pulmonary arterial hypertension (PAH) is caused by narrowing and stiffening of the pulmonary arteries that increase pulmonary vascular impedance (PVZ). In particular, small arteries narrow and large arteries stiffen. Large pulmonary artery (PA) stiffness is the best current predictor of mortality from PAH. We have previously shown that collagen accumulation leads to extralobar PA stiffening at high strain (Ooi et al. 2010). We hypothesized that collagen accumulation would increase PVZ, including total pulmonary vascular resistance (Z0), characteristic impedance (ZC), pulse wave velocity (PWV) and index of global wave reflections (Pb/Pf), which contribute to increased right ventricular afterload. We tested this hypothesis by exposing mice unable to degrade type I collagen (Col1a1R/R) to 21 days of hypoxia (hypoxia), some of which were allowed to recover for 42 days (recovery). Littermate wild-type mice (Col1a1+/+) were used as controls. In response to hypoxia, mean PA pressure (mPAP) increased in both mouse genotypes with no changes in cardiac output (CO) or PA inner diameter (ID); as a consequence, Z0 (mPAP/CO) increased by ∼100% in both genotypes (pZC, PWV and Pb/Pf did not change. However, with recovery, ZC and PWV decreased in the Col1a1+/+ mice and remained unchanged in the Col1a1R/R mice. Z0 decreased with recovery in both genotypes. Microcomputed tomography measurements of large PAs did not show evidence of stiffness changes as a function of hypoxia exposure or genotype. We conclude that hypoxia-induced PA collagen accumulation does not affect the pulsatile components of pulmonary hemodynamics but that excessive collagen accumulation does prevent normal hemodynamic recovery, which may have important consequences for right ventricular function

Multimodal epigenetic changes and altered NEUROD1 chromatin binding in the mouse hippocampus underlie FOXG1 syndrome

Forkhead box G1 (FOXG1) has important functions in neuronal differentiation and balances excitatory/inhibitory network activity. Thus far, molecular processes underlying FOXG1 function are largely unexplored. Here, we present a multiomics data set exploring how FOXG1 impacts neuronal maturation at the chromatin level in the mouse hippocampus. At a genome-wide level, FOXG1 i) both represses and activates transcription, ii) binds mainly to enhancer regions, iii) reconfigures the epigenetic landscape through bidirectional alteration of H3K27ac, H3K4me3, and chromatin accessibility, and iv) operates synergistically with NEUROD1. Interestingly, we could not detect a clear hierarchy of FOXG1 and NEUROD1, but instead, provide the evidence that they act in a highly cooperative manner to control neuronal maturation. Genes affected by the chromatin alterations impact synaptogenesis and axonogenesis. Inhibition of histone deacetylases partially rescues transcriptional alterations upon FOXG1 reduction. This integrated multiomics view of changes upon FOXG1 reduction reveals an unprecedented multimodality of FOXG1 functions converging on neuronal maturation. It fuels therapeutic options based on epigenetic drugs to alleviate, at least in part, neuronal dysfunction

TOI-2374 b and TOI-3071 b: two metal-rich sub-Saturns well within the Neptunian desert

We report the discovery of two transiting planets detected by the Transiting Exoplanet Survey Satellite (TESS), TOI-2374 b and TOI-3071 b, orbiting a K5V and an F8V star, respectively, with periods of 4.31 and 1.27 d, respectively. We confirm and characterize these two planets with a variety of ground-based and follow-up observations, including photometry, precise radial velocity monitoring and high-resolution imaging. The planetary and orbital parameters were derived from a joint analysis of the radial velocities and photometric data. We found that the two planets have masses of (57 ± 4) M⊕ or (0.18 ± 0.01) MJ, and (68 ± 4) M⊕ or (0.21 ± 0.01) MJ, respectively, and they have radii of (6.8 ± 0.3) R⊕ or (0.61 ± 0.03) RJ and (7.2 ± 0.5) R⊕ or (0.64 ± 0.05) RJ, respectively. These parameters correspond to sub-Saturns within the Neptunian desert, both planets being hot and highly irradiated, with Teq  ≈ 745 K and Teq  ≈ 1812 K, respectively, assuming a Bond albedo of 0.5. TOI-3071 b has the hottest equilibrium temperature of all known planets with masses between 10 and 300 M⊕ and radii less than 1.5 RJ. By applying gas giant evolution models we found that both planets, especially TOI-3071 b, are very metal-rich. This challenges standard formation models which generally predict lower heavy-element masses for planets with similar characteristics. We studied the evolution of the planets’ atmospheres under photoevaporation and concluded that both are stable against evaporation due to their large masses and likely high metallicities in their gaseous envelopes

TOI-2374 b and TOI-3071 b: two metal-rich sub-Saturns well within the Neptunian desert

We report the discovery of two transiting planets detected by the Transiting Exoplanet Survey Satellite (TESS), TOI-2374 b and TOI-3071 b, orbiting a K5V and an F8V star, respectively, with periods of 4.31 and 1.27 days, respectively. We confirm and characterize these two planets with a variety of ground-based and follow-up observations, including photometry, precise radial velocity monitoring and high-resolution imaging. The planetary and orbital parameters were derived from a joint analysis of the radial velocities and photometric data. We found that the two planets have masses of $(57 \pm 4)$ $M_\oplus$ or $(0.18 \pm 0.01)$ $M_J$, and $(68 \pm 4)$ $M_\oplus$ or $(0.21 \pm 0.01)$ $M_J$, respectively, and they have radii of $(6.8 \pm 0.3)$ $R_\oplus$ or $(0.61 \pm 0.03)$ $R_J$ and $(7.2 \pm 0.5)$ $R_\oplus$ or $(0.64 \pm 0.05)$ $R_J$, respectively. These parameters correspond to sub-Saturns within the Neptunian desert, both planets being hot and highly irradiated, with $T_{\rm eq} \approx 745$ $K$ and $T_{\rm eq} \approx 1812$ $K$, respectively, assuming a Bond albedo of 0.5. TOI-3071 b has the hottest equilibrium temperature of all known planets with masses between $10$ and $300$ $M_\oplus$ and radii less than $1.5$ $R_J$. By applying gas giant evolution models we found that both planets, especially TOI-3071 b, are very metal-rich. This challenges standard formation models which generally predict lower heavy-element masses for planets with similar characteristics. We studied the evolution of the planets' atmospheres under photoevaporation and concluded that both are stable against evaporation due to their large masses and likely high metallicities in their gaseous envelopes.Comment: 24 pages, 22 figures, 10 tables, accepted for publication in MNRA

Supporting Spartina: Interdisciplinary perspective shows Spartina as a distinct solid genus

In 2014 a DNA-based phylogenetic study confirming the paraphyly of the grass subtribe Sporobolinae proposed the creation of a large monophyletic genus Sporobolus, including (among others) species previously included in the genera Spartina, Calamovilfa, and Sporobolus. Spartina species have contributed substantially (and continue contributing) to our knowledge in multiple disciplines, including ecology, evolutionary biology, molecular biology, biogeography, experimental ecology, environmental management, restoration ecology, history, economics, and sociology. There is no rationale so compelling to subsume the name Spartina as a subgenus that could rival the striking, global iconic history and use of the name Spartina for over 200 years. We do not agree with the arguments underlying the proposal to change Spartina to Sporobolus. We understand the importance of taxonomy and of formalized nomenclature and hope that by opening this debate we will encourage positive feedback that will strengthen taxonomic decisions with an interdisciplinary perspective. We consider the strongly distinct, monophyletic clade Spartina should simply and efficiently be treated as the genus Spartina

DLR's Advancements in Space Robotic Manipulation

Given the accumulation of space debris in key orbits around the Earth, robots capable of in-orbit repair, refueling and assembly are crucial for sustainable space exploration. DLR's contributions to space manipulation began in 1993 with the ROTEX experiment. A small six-axis robotic arm was launched aboard the D2 Space Shuttle mission, where it performed grasping of a free-floating object using various control modes, including teleoperation, shared autonomy and full autonomy modes. This was followed by ROKVISS, a two-joint arm mounted outside the ISS for more than five years. This experiment provided valuable scientific data on the behavior of torque-controlled joints in the harsh space environment. DLR's latest space robot, the CAESAR robotic arm developed in 2018, is a lightweight, compliant and fully redundant seven-joint manipulator designed for on-orbit operations. Ground testing of the space-destined CAESAR is performed using a cable-driven Motion Suspension System, which minimizes the torques acting on the joints. This allows complex tasks such as docking, latching and grasping to be validated in 3D space. This video details the advances in orbital manipulation made by DLR's Robotic and Mechatronics Center over the past 30 years, paving the way for the development of robotic technology for space sustainability

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Modelos de velocidad radial para la detección de planetas extrasolares de baja masa

La motivación de este trabajo es inferir de manera robusta las características físicas de los exoplanetas que se encuentran en órbita de una muestra de tres estrellas enanas de tipo M: GJ 1132, LHS 1140 y L 98-59. Para este objetivo se construyeron, optimizaron y contrastaron modelos de complejidad creciente de velocidades radiales a partir de datos de cada estrella obtenidos con los espectrógrafos HARPS y ESPRESSO y a través una variedad de herramientas de regresión lineal, estadística bayesiana y técnicas de muestreo. Se lograron detectar los planetas reportados en la bibliografía y recuperar sus parámetros físicos con valores consistentes con los reportados en los artículos de base. Particularmente, para el sistema GJ1132 se detectó una nueva señal con un periodo de 2.8 días. Si futuras observaciones confirman el carácter planetario de esta señal, se trataría de un planeta con masa menor a la de la Tierra.Fil: Hacker, Alejandro. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina

Within-plant bottom-up effects mediate non-consumptive impacts of top-down control of soybean aphids

Citation: Costamagna, A., McCornack, B., & Ragsdale, D. (2013). Within-Plant Bottom-Up Effects Mediate NonConsumptive Impacts of Top-Down Control of Soybean Aphids. PLoS ONE 8(2), e56394 - e56394. https://doi.org/10.1371/journal.pone.0056394There is increasing evidence that top-down controls have strong non-consumptive effects on herbivore populations. However, little is known about how these non-consumptive effects relate to bottom-up influences. Using a series of field trials, we tested how changes in top-down and bottom-up controls at the within-plant scale interact to increase herbivore suppression. In the first experiment, we manipulated access of natural populations of predators (primarily lady beetles) to controlled numbers of A. glycines on upper (i.e. vigorous-growing) versus lower (i.e. slow-growing) soybean nodes and under contrasting plant ages. In a second experiment, we measured aphid dispersion in response to predation. Bottom-up and top-down controls had additive effects on A. glycines population growth. Plant age and within-plant quality had significant bottom-up effects on aphid size and population growth. However, top-down control was the dominant force suppressing aphid population growth, and completely counteracted bottom-up effects at the plant and within-plant scales. The intensity of predation was higher on upper than lower soybean nodes, and resulted in a non-consumptive reduction in aphid population growth because most of the surviving aphids were located on lower plant nodes, where rates of increase were reduced. No effects of predation on aphid dispersal among plants were detected, suggesting an absence of predator avoidance behavior by A. glycines. Our results revealed significant non-consumptive predator impacts on aphids due to the asymmetric intensity of predation at the within-plant scale, suggesting that low numbers of predators are highly effective at suppressing aphid populations

Integrative multi-omics analyses reveal multi-modal FOXG1 functions acting on epigenetic processes and in concert with NEUROD1 to regulate synaptogenesis in the mouse hippocampus

AbstractBackgroundFOXG1 has important functions for neuronal differentiation and balances excitatory/inhibitory network activity. Mutations in the human FOXG1 gene cause a rare neurodevelopmental disorder, FOXG1-syndrome, which manifests differing phenotypes, including severe cognitive dysfunction, microencephaly, social withdrawal, and communication and memory deficits. Changes at the molecular level underlying these functional abnormalities upon FOXG1 haploinsufficiency are largely unexplored, in human patients as well as in animals modelling the debilitating disease.MethodsWe present multi-omics data and explore comprehensively how FOXG1 impacts neuronal maturation at the chromatin level in the adult mouse hippocampus. We used RNA-, ATAC- and ChIP-sequencing of primary hippocampal neurons and co-immunoprecipitation to explore various levels of epigenetic changes and transcription factor networks acting to alter neuronal differentiation upon reduction of FOXG1.ResultsWe provide the first comprehensive multi-omics data set exploring FOXG1 presence at the chromatin and identifying the consequences of reduced FOXG1 expression in primary hippocampal neurons. Analyzing the multi-omics data, our study reveals that FOXG1 uses various different ways to regulate transcription at the chromatin level. On a genome-wide level, FOXG1 (i) both represses and activates transcription, (ii) binds mainly to enhancer regions, and (iii) bidirectionally alters the epigenetic landscape in regard to levels of H3K27ac, H3K4me3, and chromatin accessibility. Genes affected by the chromatin alterations upon FOXG1 reduction impact synaptogenesis and axonogenesis. This finding emphasizes the importance of FOXG1 to integrate and coordinate transcription of genes necessary for proper neuronal function by acting on a genome-wide level. Interestingly, FOXG1 acts through histone deacetylases (HDACs) and inhibition of HDACs partly rescued transcriptional alterations observed upon FOXG1 reduction. On a more detailed level of analysis, we show that FOXG1 (iv) operates synergistically with NEUROD1. Interestingly, we could not detect a clear hierarchy of these two key transcription factors, but instead provide first evidence that they act in highly concerted and orchestrated manner to control neuronal differentiation.ConclusionsThis integrative and multi-omics view of changes upon FOXG1 reduction reveals an unprecedented multimodality of FOXG1 functions converging on neuronal maturation, fueling novel therapeutic options based on epigenetic drugs to alleviate, at least in part, neuronal dysfunctions.</jats:sec