It is a conundrum of the 21st Century that there is much left to discover and yet never before has our cultural and ecological patrimony been so threatened. This is especially true in tropical ...regions where heavy vegetation, inaccessibility, and rugged topography hamper investigation. Here we present two case studies that add to a growing body of literature demonstrating the utility of airborne mapping LiDAR (a.k.a. Airborne Laser Scanning) for rapid archaeological assessments in poorly documented regions. The first outlines a program of LiDAR scanning to better understand the urban center of Angamuco in the Mexican State of Michoacán. This work shows that (1) large urban centers with complex spatial organization were present centuries prior to the formation of the Purépecha Empire; (2) the settlement incorporates gardens and other landscape features within and around the settlement demonstrating a high degree of human environmental modification; and (3) current models for the evolution of social complexity in the region cannot account for the presence of Angamuco. The second presents the results of a LiDAR survey of a remote valley in the Mosquitia tropical wilderness of Honduras which has seen little archaeological research. Here we demonstrate that (1) though today the valley is a wilderness it was densely inhabited in the past; (2) this population was organized into a three-tiered system composed of 19 settlements dominated by a city; and (3) this occupation was embedded within a human engineered landscape. For both, LiDAR data fundamentally changed the understanding of coupled human/natural systems in these areas while providing critical baseline data for conservation and management.
Hepatic stellate cells (HSC) play a key role in the development of chronic liver disease (CLD). Liraglutide, well-established in type 2 diabetes, showed anti-inflammatory and anti-oxidant properties. ...We evaluated the effects of liraglutide on HSC phenotype and hepatic microvascular function using diverse pre-clinical models of CLD. Human and rat HSC were in vitro treated with liraglutide, or vehicle, and their phenotype, viability and proliferation were evaluated. In addition, liraglutide or vehicle was administered to rats with CLD. Liver microvascular function, fibrosis, HSC phenotype and sinusoidal endothelial phenotype were determined. Additionally, the effects of liraglutide on HSC phenotype were analysed in human precision-cut liver slices. Liraglutide markedly improved HSC phenotype and diminished cell proliferation. Cirrhotic rats receiving liraglutide exhibited significantly improved liver microvascular function, as evidenced by lower portal pressure, improved intrahepatic vascular resistance, and marked ameliorations in fibrosis, HSC phenotype and endothelial function. The anti-fibrotic effects of liraglutide were confirmed in human liver tissue and, although requiring further investigation, its underlying molecular mechanisms suggested a GLP1-R-independent and NF-κB-Sox9-dependent one. This study demonstrates for the first time that liraglutide improves the liver sinusoidal milieu in pre-clinical models of cirrhosis, encouraging its clinical evaluation in the treatment of chronic liver disease.
In this paper we present a description of a new multispectral airborne mapping light detection and ranging (lidar) along with performance results obtained from two years of data collection and test ...campaigns. The Titan multiwave lidar is manufactured by Teledyne Optech Inc. (Toronto, ON, Canada) and emits laser pulses in the 1550, 1064 and 532 nm wavelengths simultaneously through a single oscillating mirror scanner at pulse repetition frequencies (PRF) that range from 50 to 300 kHz per wavelength (max combined PRF of 900 kHz). The Titan system can perform simultaneous mapping in terrestrial and very shallow water environments and its multispectral capability enables new applications, such as the production of false color active imagery derived from the lidar return intensities and the automated classification of target and land covers. Field tests and mapping projects performed over the past two years demonstrate capabilities to classify five land covers in urban environments with an accuracy of 90%, map bathymetry under more than 15 m of water, and map thick vegetation canopies at sub-meter vertical resolutions. In addition to its multispectral and performance characteristics, the Titan system is designed with several redundancies and diversity schemes that have proven to be beneficial for both operations and the improvement of data quality.
The Mosquitia ecosystem of Honduras occupies the fulcrum between the American continents and as such constitutes a critical region for understanding past patterns of socio-political development and ...interaction. Heavy vegetation, rugged topography, and remoteness have limited scientific investigation. This paper presents prehistoric patterns of settlement and landuse for a critical valley within the Mosquitia derived from airborne LiDAR scanning and field investigation. We show that (i) though today the valley is a wilderness it was densely inhabited in the past; (ii) that this population was organized into a three-tiered system composed of 19 settlements dominated by a city; and, (iii) that this occupation was embedded within a human engineered landscape. We also add to a growing body of literature that demonstrates the utility of LiDAR as means for rapid cultural assessments in undocumented regions for analysis and conservation. Our ultimate hope is for our work to promote protections to safeguard the unique and critically endangered Mosquitia ecosystem and other similar areas in need of preservation.
Scope
Some polyphenol‐derived metabolites reach human breast cancer (BC) tissues at concentrations that induce cell senescence. However, this is unknown for isoflavones, curcuminoids, and lignans. ...Here, their metabolic profiling in normal (NT) and malignant (MT) mammary tissues of newly‐diagnosed BC patients and the tissue‐occurring metabolites’ anticancer activity are evaluated.
Methods and results
Patients (n = 26) consumed 3 capsules/day (turmeric, red clover, and flaxseed extracts plus resveratrol; 296.4 mg phenolics/capsule) from biopsy‐confirmed diagnosis to surgery (5 ± 2 days) or did not consume capsules (n = 13). NT and MT, blood, and urine are analyzed by UPLC‐QTOF‐MS using targeted metabolomics. Anticancer activity was tested in MCF‐7 and MDA‐MB‐231 BC cells. Mainly phase‐II metabolites were detected (108, 84, 49, and 47 in urine, plasma, NT, and MT, respectively). Total metabolite concentrations reached 10.7 ± 11.1 and 2.5 ± 2.4 µmol L–1 in NT and MT, respectively. Free curcumin, but not its glucuronide, was detected in the tissues (1.1 ± 1.8 and 0.2 ± 0.2 µmol L–1 in NT and MT, respectively). Breast tissue‐occurring metabolites’ antiproliferation was mainly exerted in p53‐wild‐type MCF‐7 cells by curcuminoids through cell cycle arrest, senescence, and apoptosis induction via p53/p21 induction, while isoflavone‐derived metabolites exerted estrogenic‐like activity.
Conclusion
Curcuminoids could be coadjuvants that might help fight BC upon regular consumption.
A total of 47 curcuminoid, isoflavone, resveratrol, and lignan‐derived metabolites, mostly conjugated, were detected in malignant mammary tissues of breast cancer patients. However, free curcumin, but not its glucuronide, was detected at micromolar concentration, likely due to a glucuronidation‐saturation process. Breast tissue‐occurring metabolites, mainly, curcuminoids, induced cell cycle arrest, senescence, and apoptosis via p53/p21, while isoflavone metabolites exerted estrogenic activity.
The preparation of MOFs including a metal with an easily exchangeable oxidation state, while maintaining the same crystal structure and stability, is of paramount importance for myriad applications. ...In this work, a new synthesis method is reported that can be used to prepare Ce/Zr‐MOFs (UiO‐66 structure) having only Ce(III), a mixed‐valence Ce(IV)/Ce(III), or only Ce(IV) cations, as desired. The materials are characterized using a large number of techniques, including X‐ray absorption and X‐ray photoelectron spectroscopies.
In this contribution, a synthetic method has been developed to introduce Ce cations with the desired oxidation state (Ce3 + or Ce4 +) in the structure of UiO‐66(Zr). This has only been possible with the help of powerful characterization techniques such as X‐ray absorption, which confirm the success of the synthetic method.
Tropical forests are globally important, but it is not clear whether biodiversity enhances carbon storage and sequestration in them. We tested this relationship focusing on components of functional ...trait biodiversity as predictors. Data are presented for three rain forests in Bolivia, Brazil and Costa Rica. Initial above‐ground biomass and biomass increments of survivors, recruits and survivors + recruits (total) were estimated for trees ≥10 cm d.b.h. in 62 and 21 1.0‐ha plots, respectively. We determined relationships of biomass increments to initial standing biomass (AGBᵢ), biomass‐weighted community mean values (CWM) of eight functional traits and four functional trait variety indices (functional richness, functional evenness, functional diversity and functional dispersion). The forest continuum sampled ranged from ‘slow’ stands dominated by trees with tough tissues and high AGBᵢ, to ‘fast’ stands dominated by trees with soft, nutrient‐rich leaves, lighter woods and lower AGBᵢ. We tested whether AGBᵢand biomass increments were related to the CWM trait values of the dominant species in the system (the biomass ratio hypothesis), to the variety of functional trait values (the niche complementarity hypothesis), or in the case of biomass increments, simply to initial standing biomass (the green soup hypothesis). CWMs were reasonable bivariate predictors of AGBᵢand biomass increments, with CWM specific leaf area SLA, CWM leaf nitrogen content, CWM force to tear the leaf, CWM maximum adult height Hₘₐₓand CWM wood specific gravity the most important. AGBᵢwas also a reasonable predictor of the three measures of biomass increment. In best‐fit multiple regression models, CWMHₘₐₓwas the most important predictor of initial standing biomass AGBᵢ. Only leaf traits were selected in the best models for biomass increment; CWM SLA was the most important predictor, with the expected positive relationship. There were no relationships of functional variety indices to biomass increments, and AGBᵢwas the only predictor for biomass increments from recruits. Synthesis. We found no support for the niche complementarity hypothesis and support for the green soup hypothesis only for biomass increments of recruits. We have strong support for the biomass ratio hypothesis. CWMHₘₐₓis a strong driver of ecosystem biomass and carbon storage and CWM SLA, and other CWM leaf traits are especially important for biomass increments and carbon sequestration.
We report on a large area of ancient Maya wetland field systems in Belize, Central America, based on airborne lidar survey coupled with multiple proxies and radiocarbon dates that reveal ancient ...field uses and chronology. The lidar survey indicated four main areas of wetland complexes, including the Birds of Paradise wetland field complex that is five times larger than earlier remote and ground survey had indicated, and revealed a previously unknown wetland field complex that is even larger. The field systems date mainly to the Maya Late and Terminal Classic (∼1,400–1,000 y ago), but with evidence from as early as the Late Preclassic (∼1,800 y ago) and as late as the Early Postclassic (∼900 y ago). Previous study showed that these were polycultural systems that grew typical ancient Maya crops including maize, arrowroot, squash, avocado, and other fruits and harvested fauna. The wetland fields were active at a time of population expansion, landscape alteration, and droughts and could have been adaptations to all of these major shifts in Maya civilization. These wetland-farming systems add to the evidence for early and extensive human impacts on the global tropics. Broader evidence suggests a wide distribution of wetland agroecosystems across the Maya Lowlands and Americas, and we hypothesize the increase of atmospheric carbon dioxide and methane from burning, preparing, and maintaining these field systems contributed to the Early Anthropocene.
The clinical presentation of COVID-19 in patients admitted to hospital is heterogeneous. We aimed to determine whether clinical phenotypes of patients with COVID-19 can be derived from clinical data, ...to assess the reproducibility of these phenotypes and correlation with prognosis, and to derive and validate a simplified probabilistic model for phenotype assignment. Phenotype identification was not primarily intended as a predictive tool for mortality.
In this study, we used data from two cohorts: the COVID-19@Spain cohort, a retrospective cohort including 4035 consecutive adult patients admitted to 127 hospitals in Spain with COVID-19 between Feb 2 and March 17, 2020, and the COVID-19@HULP cohort, including 2226 consecutive adult patients admitted to a teaching hospital in Madrid between Feb 25 and April 19, 2020. The COVID-19@Spain cohort was divided into a derivation cohort, comprising 2667 randomly selected patients, and an internal validation cohort, comprising the remaining 1368 patients. The COVID-19@HULP cohort was used as an external validation cohort. A probabilistic model for phenotype assignment was derived in the derivation cohort using multinomial logistic regression and validated in the internal validation cohort. The model was also applied to the external validation cohort. 30-day mortality and other prognostic variables were assessed in the derived phenotypes and in the phenotypes assigned by the probabilistic model.
Three distinct phenotypes were derived in the derivation cohort (n=2667)—phenotype A (516 19% patients), phenotype B (1955 73%) and phenotype C (196 7%)—and reproduced in the internal validation cohort (n=1368)—phenotype A (233 17% patients), phenotype B (1019 74%), and phenotype C (116 8%). Patients with phenotype A were younger, were less frequently male, had mild viral symptoms, and had normal inflammatory parameters. Patients with phenotype B included more patients with obesity, lymphocytopenia, and moderately elevated inflammatory parameters. Patients with phenotype C included older patients with more comorbidities and even higher inflammatory parameters than phenotype B. We developed a simplified probabilistic model (validated in the internal validation cohort) for phenotype assignment, including 16 variables. In the derivation cohort, 30-day mortality rates were 2·5% (95% CI 1·4–4·3) for patients with phenotype A, 30·5% (28·5–32·6) for patients with phenotype B, and 60·7% (53·7–67·2) for patients with phenotype C (log-rank test p<0·0001). The predicted phenotypes in the internal validation cohort and external validation cohort showed similar mortality rates to the assigned phenotypes (internal validation cohort: 5·3% 95% CI 3·4–8·1 for phenotype A, 31·3% 28·5–34·2 for phenotype B, and 59·5% 48·8–69·3 for phenotype C; external validation cohort: 3·7% 2·0–6·4 for phenotype A, 23·7% 21·8–25·7 for phenotype B, and 51·4% 41·9–60·7 for phenotype C).
Patients admitted to hospital with COVID-19 can be classified into three phenotypes that correlate with mortality. We developed and validated a simplified tool for the probabilistic assignment of patients into phenotypes. These results might help to better classify patients for clinical management, but the pathophysiological mechanisms of the phenotypes must be investigated.
Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Fundación SEIMC/GeSIDA.
We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate ...and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost.
13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization. End-points were safety, cellular and humoral immune responses to HIV-1 and vector antigens assessed by ELISPOT, intracellular cytokine staining (ICS) and ELISA performed before and 2, 4 and 12 weeks after receiving the boost.
Volunteers reported 64 adverse events (AEs), although none was a vaccine-related serious AE. After 4 years from the 1st dose of the vaccine, only 2 volunteers maintained low HIV-specific T-cell responses. After the late MVA-B boost, a modest increase in IFN-γ T-cell responses, mainly directed against Env, was detected by ELISPOT in 5/13 (38%) volunteers. ICS confirmed similar results with 45% of volunteers showing that CD4+ T-cell responses were mainly directed against Env, whereas CD8+ T cell-responses were similarly distributed against Env, Gag and GPN. In terms of antibody responses, 23.1% of the vaccinees had detectable Env-specific binding antibodies 4 years after the last MVA-B immunization with a mean titer of 96.5. The late MVA-B boost significantly improved both the response rate (92.3%) and the magnitude of the systemic binding antibodies to gp120 (mean titer of 11460). HIV-1 neutralizing antibodies were also enhanced and detected in 77% of volunteers. Moreover, MVA vector-specific T cell and antibody responses were boosted in 80% and 100% of volunteers respectively.
One boost of MVA-B four years after receiving 3 doses of the same vaccine was safe, induced moderate increases in HIV-specific T cell responses in 38% of volunteers but significantly boosted the binding and neutralizing antibody responses to HIV-1 and to the MVA vector.
ClinicalTrials.gov NCT01923610.
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