133 research outputs found
SAR-Based Estimation of Above-Ground Biomass and Its Changes in Tropical Forests of Kalimantan Using L- and C-Band
Kalimantan poses one of the highest carbon emissions worldwide since its landscape is strongly endangered by deforestation and degradation and, thus, carbon release. The goal of this study is to conduct large-scale monitoring of above-ground biomass (AGB) from space and create more accurate biomass maps of Kalimantan than currently available. AGB was estimated for 2007, 2009, and 2016 in order to give an overview of ongoing forest loss and to estimate changes between the three time steps in a more precise manner. Extensive field inventory and LiDAR data were used as reference AGB. A multivariate linear regression model (MLR) based on backscatter values, ratios, and Haralick textures derived from Sentinel-1 (C-band), ALOS PALSAR (Advanced Land Observing Satellite's Phased Array-type L-band Synthetic Aperture Radar), and ALOS-2 PALSAR-2 polarizations was used to estimate AGB across the country. The selection of the most suitable model parameters was accomplished considering VIF (variable inflation factor), p-value, R-2, and RMSE (root mean square error). The final AGB maps were validated by calculating bias, RMSE, R-2, and NSE (Nash-Sutcliffe efficiency). The results show a correlation (R-2) between the reference biomass and the estimated biomass varying from 0.69 in 2016 to 0.77 in 2007, and a model performance (NSE) in a range of 0.70 in 2016 to 0.76 in 2007. Modelling three different years with a consistent method allows a more accurate estimation of the change than using available biomass maps based on different models. All final biomass products have a resolution of 100 m, which is much finer than other existing maps of this region (>500 m). These high-resolution maps enable identification of even small-scaled biomass variability and changes and can be used for more precise carbon modelling, as well as forest monitoring or risk managing systems under REDD+ (Reducing Emissions from Deforestation, forest Degradation, and the role of conservation, sustainable management of forests, and enhancement of forest carbon stocks) and other programs, protecting forests and analyzing carbon release
Differences in the thoracic aorta by region and sex in a murine model of Marfan Syndrome
Marfan syndrome (MFS) is a hereditary disorder of the connective tissue that causes life-threatening aortic aneurysm, which initiates at the aortic root and can progress into the ascending portion. However, analysis of ascending aorta reactivity in animal models of MFS has remained elusive. Epidemiologic evidence suggests that although MFS is equally prevalent in men and women, men are at a higher risk of aortic complications than non-pregnant women. Nevertheless, there is no experimental evidence to support this hypothesis. The aim of this study was to explore whether there are regional and sex differences in the thoracic aorta function of mice heterozygous for the fibrillin 1 (Fbn1) allele encoding a missense mutation (Fbn1C1039G/+), the most common class of mutation in MFS. Ascending and descending thoracic aorta reactivity was evaluated by wire myography. Ascending aorta mRNA and protein levels, and elastic fiber integrity were assessed by qRT-PCR, Western blotting, and Verhoeff-Van Gieson histological staining, respectively. MFS differently altered reactivity in the ascending and descending thoracic aorta by either increasing or decreasing phenylephrine contractions, respectively. When mice were separated by sex, contractions to phenylephrine increased progressively from 3 to 6 months of age in MFS ascending aortas of males, whereas contractions in females were unchanged. Endothelium-dependent relaxation was unaltered in the MFS ascending aorta of either sex; an effect related to augmented endothelium-dependent hyperpolarization-type dilations. In MFS males, the non-selective cyclooxygenase (COX) inhibitor indomethacin prevented the MFS-induced enhancement of phenylephrine contractions linked to increased COX-2 expression. In MFS mice of both sexes, the non-selective nitric oxide synthase inhibitor L-NAME revealed negative feedback of nitric oxide on phenylephrine contractions, which was associated with upregulation of eNOS in females. Finally, MFS ascending aortas showed a greater number of elastic fiber breaks than the wild-types, and males exhibited more breaks than females. These results show regional and sex differences in Fbn1C1039G/+ mice thoracic aorta contractility and aortic media injuries. The presence of more pronounced aortic alterations in male mice provides experimental evidence to support that male MFS patients are at increased risk of suffering aortic complications
Scaling of local interface width of statistical growth models
We discuss the methods to calculate the roughness exponent alpha and the
dynamic exponent z from the scaling properties of the local roughness, which is
frequently used in the analysis of experimental data. Through numerical
simulations, we studied the Family, the restricted solid-on-solid (RSOS), the
Das Sarma-Tamborenea (DT) and the Wolf-Villain (WV) models in one- and two
dimensional substrates, in order to compare different methods to obtain those
exponents. The scaling at small length scales do not give reliable estimates of
alpha, suggesting that the usual methods to estimate that exponent from
experimental data may provide misleading conclusions concerning the
universality classes of the growth processes. On the other hand, we propose a
more efficient method to calculate the dynamic exponent z, based on the scaling
of characteristic correlation lengths, which gives estimates in good agreement
with the expected universality classes and indicates expected crossover
behavior. Our results also provide evidence of Edwards-Wilkinson asymptotic
behavior for the DT and the WV models in two-dimensional substrates.Comment: To appear in Surface Scienc
SFPQ and Tau: critical factors contributing to rapid progression of Alzheimer's disease
Dysfunctional RNA-binding proteins (RBPs) have been implicated in several neurodegenerative disorders. Recently, this paradigm of RBPs has been extended to pathophysiology of Alzheimer's disease (AD). Here, we identified disease subtype specific variations in the RNA-binding proteome (RBPome) of sporadic AD (spAD), rapidly progressive AD (rpAD), and sporadic Creutzfeldt Jakob disease (sCJD), as well as control cases using RNA pull-down assay in combination with proteomics. We show that one of these identified proteins, splicing factor proline and glutamine rich (SFPQ), is downregulated in the post-mortem brains of rapidly progressive AD patients, sCJD patients and 3xTg mice brain at terminal stage of the disease. In contrast, the expression of SFPQ was elevated at early stage of the disease in the 3xTg mice, and in vitro after oxidative stress stimuli. Strikingly, in rpAD patients' brains SFPQ showed a significant dislocation from the nucleus and cytoplasmic colocalization with TIA-1. Furthermore, in rpAD brain lesions, SFPQ and p-tau showed extranuclear colocalization. Of note, association between SFPQ and tau-oligomers in rpAD brains suggests a possible role of SFPQ in oligomerization and subsequent misfolding of tau protein. In line with the findings from the human brain, our in vitro study showed that SFPQ is recruited into TIA-1-positive stress granules (SGs) after oxidative stress induction, and colocalizes with tau/p-tau in these granules, providing a possible mechanism of SFPQ dislocation through pathological SGs. Furthermore, the expression of human tau in vitro induced significant downregulation of SFPQ, suggesting a causal role of tau in the downregulation of SFPQ. The findings from the current study indicate that the dysregulation and dislocation of SFPQ, the subsequent DNA-related anomalies and aberrant dynamics of SGs in association with pathological tau represents a critical pathway which contributes to rapid progression of AD
Inflammatory macrophages reprogram to immunosuppression by reducing mitochondrial translation
Acute inflammation can either resolve through immunosuppression or persist, leading to chronic inflammation. These transitions are driven by distinct molecular and metabolic reprogramming of immune cells. The anti-diabetic drug Metformin inhibits acute and chronic inflammation through mechanisms still not fully understood. Here, we report that the anti-inflammatory and reactive-oxygen-species-inhibiting effects of Metformin depend on the expression of the plasticity factor ZEB1 in macrophages. Using mice lacking Zeb1 in their myeloid cells and human patient samples, we show that ZEB1 plays a dual role, being essential in both initiating and resolving inflammation by inducing macrophages to transition into an immunosuppressed state. ZEB1 mediates these diverging effects in inflammation and immunosuppression by modulating mitochondrial content through activation of autophagy and inhibition of mitochondrial protein translation. During the transition from inflammation to immunosuppression, Metformin mimics the metabolic reprogramming of myeloid cells induced by ZEB1. Mechanistically, in immunosuppression, ZEB1 inhibits amino acid uptake, leading to downregulation of mTORC1 signalling and a decrease in mitochondrial translation in macrophages. These results identify ZEB1 as a driver of myeloid cell metabolic plasticity, suggesting that targeting its expression and function could serve as a strategy to modulate dysregulated inflammation and immunosuppression.The study was conducted at IDIBAPS’ Centre de
Recerca Biomèdica Cellex building, which was partly funded by the
Cellex Foundation. The different parts of this study were independently
funded by grants to AP from the Leo Foundation (LF-OC-19-000166), the
Catalan Agency for Management of University and Research Grants
(AGAUR) (2017-SGR-1174 and 2021-SGR-01328), and the Spanish State
Research Agency (AEI) of the Ministry of Science and Innovation
(MICINN) (PID2020-116338RB-I00) as part of MICINN’s National Scientific
and Technical Research and Innovation 2021-2023 Plan, which is cofinanced by the European Regional Development Fund (ERDF) of the
European Union Commission. AB is a recipient of a PhD scholarship from
AGAUR (FI Program, 2021 FI_B 00514
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The melanocortin pathway and energy homeostasis: From discovery to obesity therapy.
BACKGROUND: Over the past 20 years, insights from human and mouse genetics have illuminated the central role of the brain leptin-melanocortin pathway in controlling mammalian food intake, with genetic disruption resulting in extreme obesity, and more subtle polymorphic variations influencing the population distribution of body weight. At the end of 2020, the U.S. Food and Drug Administration (FDA) approved setmelanotide, a melanocortin 4 receptor agonist, for use in individuals with severe obesity due to either pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) deficiency. SCOPE OF REVIEW: Herein, we chart the melanocortin pathway's history, explore its pharmacology, genetics, and physiology, and describe how a neuropeptidergic circuit became an important druggable obesity target. MAJOR CONCLUSIONS: Unravelling the genetics of the subset of severe obesity has revealed the importance of the melanocortin pathway in appetitive control; coupling this with studying the molecular pharmacology of compounds that bind melanocortin receptors has brought a new obesity drug to the market. This process provides a drug discovery template for complex disorders, which for setmelanotide took 25 years to transform from a single gene into an approved drug
Lattice Gas Automata for Reactive Systems
Reactive lattice gas automata provide a microscopic approachto the dynamics
of spatially-distributed reacting systems. After introducing the subject within
the wider framework of lattice gas automata (LGA) as a microscopic approach to
the phenomenology of macroscopic systems, we describe the reactive LGA in terms
of a simple physical picture to show how an automaton can be constructed to
capture the essentials of a reactive molecular dynamics scheme. The statistical
mechanical theory of the automaton is then developed for diffusive transport
and for reactive processes, and a general algorithm is presented for reactive
LGA. The method is illustrated by considering applications to bistable and
excitable media, oscillatory behavior in reactive systems, chemical chaos and
pattern formation triggered by Turing bifurcations. The reactive lattice gas
scheme is contrasted with related cellular automaton methods and the paper
concludes with a discussion of future perspectives.Comment: to appear in PHYSICS REPORTS, 81 revtex pages; uuencoded gziped
postscript file; figures available from [email protected] or
[email protected]
Patients’ and providers’ perspectives on medication relatedness and potential preventability of hospital readmissions within 30 days of discharge
Background: Hospital readmissions are increasingly used as an indicator of quality in health care. One potential risk factor of readmissions is polypharmacy. No studies have explored the patients’ perspectives on the medication relatedness and potential preventability of their readmissions. Objective: To compare the patients’ perspectives on the medication relatedness and potential preventability of their readmissions with the providers’ perspectives. Methods: Patients unplanned readmitted within 30 days after discharge at one of the participating departments of OLVG Hospital in Amsterdam were interviewed during their readmission. Patients’ perspectives regarding medication relatedness of their readmissions, the potential prevent
Antarctic extreme events
There is increasing evidence that fossil-fuel burning, and consequential global heating of 1.1°C to date, has led to the increased occurrence and severity of extreme environmental events. It is well documented how such events have impacted society outside Antarctica through enhanced levels of rainfall and flooding, heatwaves and wildfires, drought and water/food shortages and episodes of intense cooling. Here, we briefly examine evidence for extreme events in Antarctica and the Southern Ocean across a variety of environments and timescales. We show how vulnerable natural Antarctic systems are to extreme events and highlight how governance and environmental protection of the continent must take them into account. Given future additional heating of at least 0.4°C is now unavoidable (to contain heating to the “Paris Agreement 1.5°C” scenario), and may indeed be higher unless drastic action is successfully taken on reducing greenhouse gas emissions to net zero by mid-Century, we explain it is virtually certain that future Antarctic extreme events will be more pronounced than those observed to date
Effectiveness and safety of tocilizumab in patients with systemic sclerosis : a propensity score matched controlled observational study of the EUSTAR cohort
Objectives Tocilizumab showed trends for improving skin fibrosis and prevented progression of lung fibrosis in systemic sclerosis (SSc) in randomised controlled clinical trials. We aimed to assess safety and effectiveness of tocilizumab in a real-life setting using the European Scleroderma Trial and Research (EUSTAR) database. Methods Patients with SSc fulfilling the American College of Rheumatology (ACR)/EULAR 2013 classification criteria, with baseline and follow-up visits at 12±3 months, receiving tocilizumab or standard of care as the control group, were selected. Propensity score matching was applied. Primary endpoints were the modified Rodnan skin score (mRSS) and FVC at 12±3 months compared between the groups. Secondary endpoints were the percentage of progressive/regressive patients for skin and lung at 12±3 months. Results Ninety-three patients with SSc treated with tocilizumab and 3180 patients with SSc with standard of care fulfilled the inclusion criteria. Comparison between groups did not show significant differences, but favoured tocilizumab across all predefined primary and secondary endpoints: mRSS was lower in the tocilizumab group (difference -1.0, 95% CI -3.7 to 1.8, p=0.48). Similarly, FVC % predicted was higher in the tocilizumab group (difference 1.5 (-6.1 to 9.1), p=0.70). The percentage of progressive/regressive patients favoured tocilizumab over controls. These results were robust regarding the sensitivity analyses. Safety analysis confirmed previously reported adverse event profiles. Conclusion Although this large, observational, controlled, real-life EUSTAR study did not show significant effectiveness of tocilizumab on skin and lung fibrosis, the consistency of direction of all predefined endpoints generates hypothesis for potential effectiveness in a broader SSc population
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