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1.
Nature ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862025

RESUMO

The carbon skeleton of any organic molecule serves as the foundation for its three-dimensional structure, playing a pivotal role in determining its physical and biological properties.1As such, taxane diterpenes are one of the most well known natural product families, primarily owing to the success of their most prominent compound, paclitaxel, an effective anti-cancer therapeutic for more than 25 years.2-6 In contrast to classical taxanes, the bioactivity of cyclotaxanes (also referred to as complex taxanes) remains significantly underexplored. The carbon skeletons of these two groups of taxanes differ significantly, and so would typically their own distinct synthetic approaches. Here, we report a versatile synthetic strategy based on the interconversion of complex molecular frameworks, providing general access to the wider taxane diterpene family. A range of classical and cyclotaxane frameworks was prepared including, among others, the first total syntheses of taxinine K (2), canataxapropellane (5) and dipropellane C from a single advanced intermediate. The synthetic approach deliberately eschews biomimicry, emphasizing instead the power of stereoelectronic control in orchestrating the interconversion of polycyclic frameworks.

2.
PLoS Biol ; 20(9): e3001784, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36107993

RESUMO

Uncovering organizing principles of organelle assembly is a fundamental pursuit in the life sciences. Caenorhabditis elegans was key in identifying evolutionary conserved components governing assembly of the centriole organelle. However, localizing these components with high precision has been hampered by the minute size of the worm centriole, thus impeding understanding of underlying assembly mechanisms. Here, we used Ultrastructure Expansion coupled with STimulated Emission Depletion (U-Ex-STED) microscopy, as well as electron microscopy (EM) and electron tomography (ET), to decipher the molecular architecture of the worm centriole. Achieving an effective lateral resolution of approximately 14 nm, we localize centriolar and PeriCentriolar Material (PCM) components in a comprehensive manner with utmost spatial precision. We found that all 12 components analysed exhibit a ring-like distribution with distinct diameters and often with a 9-fold radial symmetry. Moreover, we uncovered that the procentriole assembles at a location on the centriole margin where SPD-2 and ZYG-1 also accumulate. Moreover, SAS-6 and SAS-5 were found to be present in the nascent procentriole, with SAS-4 and microtubules recruited thereafter. We registered U-Ex-STED and EM data using the radial array of microtubules, thus allowing us to map each centriolar and PCM protein to a specific ultrastructural compartment. Importantly, we discovered that SAS-6 and SAS-4 exhibit a radial symmetry that is offset relative to microtubules, leading to a chiral centriole ensemble. Furthermore, we established that the centriole is surrounded by a region from which ribosomes are excluded and to which SAS-7 localizes. Overall, our work uncovers the molecular architecture of the C. elegans centriole in unprecedented detail and establishes a comprehensive framework for understanding mechanisms of organelle biogenesis and function.


Assuntos
Proteínas de Caenorhabditis elegans , Centríolos , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Ciclo Celular/metabolismo , Centríolos/metabolismo , Centrossomo/metabolismo , Proteínas Quinases/metabolismo
3.
Nature ; 574(7777): 211-214, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31597976

RESUMO

About ten per cent of 'massive' stars (those of more than 1.5 solar masses) have strong, large-scale surface magnetic fields1-3. It has been suggested that merging of main-sequence and pre-main-sequence stars could produce such strong fields4,5, and the predicted fraction of merged massive stars is also about ten per cent6,7. The merger hypothesis is further supported by a lack of magnetic stars in close binaries8,9, which is as expected if mergers produce magnetic stars. Here we report three-dimensional magnetohydrodynamical simulations of the coalescence of two massive stars and follow the evolution of the merged product. Strong magnetic fields are produced in the simulations, and the merged star rejuvenates such that it appears younger and bluer than other coeval stars. This can explain the properties of the magnetic 'blue straggler' star τ Sco in the Upper Scorpius association that has an observationally inferred, apparent age of less than five million years, which is less than half the age of its birth association10. Such massive blue straggler stars seem likely to be progenitors of magnetars, perhaps giving rise to some of the enigmatic fast radio bursts observed11, and their supernovae may be affected by their strong magnetic fields12.

4.
J Am Chem Soc ; 146(10): 6444-6448, 2024 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-38427590

RESUMO

The first total synthesis of the potent antimicrobial agent dynobactin A is disclosed. This synthesis enlists a singular aziridine ring opening strategy to access the two disparate ß-aryl-branched amino acids present within this complex decapeptide. Featuring a number of unique maneuvers to navigate inherently sensitive and epimerizable functional groups, this convergent approach proceeds in only 16 steps (LLS) from commercial materials and should facilitate the synthesis of numerous analogues for medicinal chemistry studies.


Assuntos
Aminoácidos , Anti-Infecciosos , Anti-Infecciosos/síntese química
5.
J Am Chem Soc ; 144(32): 14458-14462, 2022 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-35926121

RESUMO

A concise, modular synthesis of the novel antibiotic darobactin A is disclosed. The synthesis successfully forges the hallmark strained macrocyclic ring systems in a sequential fashion. Key transformations include two atroposelective Larock-based macrocyclizations, one of which proceeds with exquisite regioselectivity despite bearing an unprotected alkyne. The synthesis is designed with medicinal chemistry considerations in mind, appending key portions of the molecule at a late stage. Requisite unnatural amino acid building blocks are easily prepared in an enantiopure form using C-H activation and decarboxylative cross-coupling tactics.


Assuntos
Alcinos , Aminoácidos , Alcinos/química , Ciclização , Fenilpropionatos
6.
Acc Chem Res ; 54(10): 2347-2360, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-33942612

RESUMO

The taxane diterpenes are a pharmaceutically vital family of natural products, consisting of more than 550 congeners. All taxane diterpenes are isolated from slow growing evergreen shrubs (genus Taxus) commonly known as "yews" and have a history of over 50 years as potent anticancer compounds. The most prominent congener, taxol (paclitaxel = PTX), has been used in clinics for more than 25 years and is one of the top-selling anticancer drugs worldwide, with annual sales reaching 1.5 billion USD in 1999. Within the taxane diterpene family 11 different scaffolds originating from rearrangements, fragmentations, or transannular C-C bond formations of the "classical taxane core" are known. Among them, five different scaffolds alone belong to the so-called complex or cyclotaxane subfamily, their signature structural feature bearing different types and numbers of transannular C-C bonds across the classical taxane backbone. For synthetic chemists, these five scaffolds represent by far the most challenging of all and have thus evaded total synthesis as well as detailed pharmaceutical evaluation-the latter due to extremely poor sourcing from natural producers. The cousinship of complex taxanes to taxol renders them potentially interesting compounds for drug research in the fight against cancer.This Account specifically summarizes the work on nonclassical taxanes from a biosynthetic, as well as a synthetic, point and provides a synthetic perspective on complex taxanes. Special attention is given to the biosynthetic relationship of complex taxanes and their biological emergence from classical taxanes. The transannular C-C bond forming events in the biosynthesis leading to the five individual scaffolds within this subfamily are structured on the basis of the exact type and number of these specific C-C bond formations. Since functionalization of the classical taxane core in the "oxidase phase" of the biosynthesis precedes the formation of complex taxanes, and is in part prerequisite for these transannular cyclization events, a detailed discussion of these oxidations of the classical taxane backbone is provided. Synthetic efforts toward nonclassical taxanes are scarce in literature and are thus presented in a comprehensive manner for abeotaxanes and complex taxanes. The last part of this Account deals with a synthetic perspective on the synthesis of complex taxanes (cyclotaxanes) and how these most intricate scaffolds can potentially be obtained via a deconvolution strategy. This discussion involves in part unpublished results by our group and is based upon synthetic studies in the literature. The deconvolution strategy we advocate aims for selective fragmentations of the signature transannular C-C bonds of the most intricate scaffold represented by the natural product canataxpropellane, which has recently been synthesized by our group. This strategy represents the converse process of the biosynthesis of complex taxanes (e.g., transannular cyclizations) and is enabled and feasible due to our approach to the canataxpropellane scaffold. We show that, by following this deconvolution strategy, all five scaffolds of complex taxanes can thereby be accessed.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Produtos Biológicos/farmacologia , Diterpenos/farmacologia , Neoplasias/tratamento farmacológico , Taxoides/farmacologia , Antineoplásicos Fitogênicos/química , Produtos Biológicos/química , Proliferação de Células/efeitos dos fármacos , Diterpenos/química , Humanos , Neoplasias/patologia , Taxoides/química
7.
Ecol Appl ; 31(6): e02379, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34013632

RESUMO

Ecosystems globally are under threat from ongoing anthropogenic environmental change. Effective conservation management requires more thorough biodiversity surveys that can reveal system-level patterns and that can be applied rapidly across space and time. Using modern ecological models and community science, we integrate environmental DNA and Earth observations to produce a time snapshot of regional biodiversity patterns and provide multi-scalar community-level characterization. We collected 278 samples in spring 2017 from coastal, shrub, and lowland forest sites in California, a complex ecosystem and biodiversity hotspot. We recovered 16,118 taxonomic entries from eDNA analyses and compiled associated traditional observations and environmental data to assess how well they predicted alpha, beta, and zeta diversity. We found that local habitat classification was diagnostic of community composition and distinct communities and organisms in different kingdoms are predicted by different environmental variables. Nonetheless, gradient forest models of 915 families recovered by eDNA analysis and using BIOCLIM variables, Sentinel-2 satellite data, human impact, and topographical features as predictors, explained 35% of the variance in community turnover. Elevation, sand percentage, and photosynthetic activities (NDVI32) were the top predictors. In addition to this signal of environmental filtering, we found a positive relationship between environmentally predicted families and their numbers of biotic interactions, suggesting environmental change could have a disproportionate effect on community networks. Together, these analyses show that coupling eDNA with environmental predictors including remote sensing data has capacity to test proposed Essential Biodiversity Variables and create new landscape biodiversity baselines that span the tree of life.


Assuntos
DNA Ambiental , Ecossistema , Biodiversidade , California , Código de Barras de DNA Taxonômico , Monitoramento Ambiental
8.
New Phytol ; 224(2): 570-584, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31112309

RESUMO

Global ecology - the study of the interactions among the Earth's ecosystems, land, atmosphere and oceans - depends crucially on global observations: this paper focuses on space-based observations of global terrestrial ecosystems. Early global ecology relied on an extrapolation of detailed site-level observations, using models of increasing complexity. Modern global ecology has been enabled largely by vegetation indices (greenness) from operational space-based imagery but current capabilities greatly expand scientific possibilities. New observations from spacecraft in orbit allowed an estimation of gross carbon fluxes, photosynthesis, biomass burning, evapotranspiration and biomass, to create virtual eddy covariance sites in the sky. Planned missions will reveal the dimensions of the diversity of life itself. These observations will improve our understanding of the global productivity and carbon storage, land use, carbon cycle-climate feedback, diversity-productivity relationships and enable improved climate forecasts. Advances in remote sensing challenge ecologists to relate information organised by biome and species to new data arrayed by pixels and develop theory to address previously unobserved scales.


Assuntos
Planeta Terra , Ecossistema , Modelos Biológicos , Plantas , Imagens de Satélites
9.
Mol Pharm ; 13(11): 3945-3954, 2016 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-27607892

RESUMO

Subunit vaccines typically show insufficient immunogenicity. To address this issue, we developed a novel self-adjuvanting particulate carrier system based upon the lipids phytantriol (Phy) and mannide monooleate (MaMo). Phy is a lipid known to form nonlamellar phases in fully hydrated systems, whereas MaMo has been found to promote immune responses in emulsion form. A bulk phase composition of Phy/MaMo (14 wt %) showed hexagonal (HII) phase behavior over a practical temperature range (including room and body temperature), and was therefore used for particle development. Hexosomes stabilized with different concentrations of either poloxamer 407, Myrj 59, or Pluronic F108 were successfully prepared. To demonstrate the versatile nature of these systems, the particles were further modified with either positively or negatively charged lipids and loaded with model antigens, while maintaining the HII structure. These hexosomes are structurally robust and amenable to customization, rendering them suitable as antigen delivery carriers.


Assuntos
Portadores de Fármacos/química , Vacinas/química , Microscopia Crioeletrônica , Difusão Dinâmica da Luz , Álcoois Graxos/química , Cristais Líquidos/química , Cristais Líquidos/ultraestrutura , Manitol/análogos & derivados , Manitol/química , Ácidos Oleicos/química , Tamanho da Partícula
10.
Mol Cancer ; 14: 17, 2015 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-25645196

RESUMO

BACKGROUND: The Wnt/beta-catenin and the Hedgehog (Hh) pathway interact in various cell types while eliciting opposing or synergistic cellular effects. Both pathways are known as exclusive drivers of two distinct molecular subtypes of medulloblastoma (MB). In sonic hedgehog (Shh)-driven MB, activation of Wnt signaling has been shown to suppress tumor growth by either beta-catenin-dependent or -independent inhibition of Shh signaling. However, mechanistic insight in how beta-catenin inhibits the Hh pathway is not known. FINDINGS: Here we show that beta-catenin stabilization by the glycogen synthase kinase 3 inhibitor lithium chloride (LiCl) reduced growth of primary hedgehog-driven MB tumor spheres from patched heterozygous mice (Ptch(+/-)) in vitro. LiCl treatment of MB spheres down-regulated the Hh target Gli1, whereas the repressive Gli3 protein (Gli3R) was increased. Mechanistically, we show by co-immunoprecipitation and proximity ligation assay that stabilized beta-catenin physically interacts with Gli1, leading to Gli1 sequestration and inhibition of its transcriptional activity. Reduction of Hh signaling upon LiCl stimulation resulted in reduced proliferation, sphere self renewal, a G2/M arrest and induction of a senescent-like state, indicated by p21 upregulation and by increased staining of senescence-associated beta-galactosidase (SA-betaGal). Moreover, LiCl treatment of subcutaneously transplanted MB cells significantly reduced tumor initiation defined as "tumor take". Although tumor progression was similar, LiCl-treated tumors showed decreased mitotic figures and phospho-histone H3 staining. CONCLUSION: We propose that beta-catenin stabilization increases its physical interaction with Gli1, leading to Gli1 degradation and inhibition of Hh signaling, thereby promoting tumor cell senescence and suppression of "tumor take" in mice.


Assuntos
Proliferação de Células/genética , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/patologia , Fatores de Transcrição Kruppel-Like/metabolismo , Meduloblastoma/metabolismo , Meduloblastoma/patologia , beta Catenina/metabolismo , Animais , Pontos de Checagem do Ciclo Celular/genética , Neoplasias Cerebelares/genética , Regulação para Baixo/genética , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas Hedgehog/metabolismo , Meduloblastoma/genética , Camundongos , Transdução de Sinais/genética , Transcrição Gênica/genética , Regulação para Cima/genética , Proteína GLI1 em Dedos de Zinco
11.
Cell Mol Life Sci ; 70(10): 1705-25, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23475067

RESUMO

Vascular endothelial growth factors (VEGFs), initially thought to act specifically on the vascular system, exert trophic effects on neural cells during development and adulthood. Therefore, the VEGF system serves as a promising therapeutic target for brain pathologies, but its simultaneous action on vascular cells paves the way for harmful side effects. To circumvent these deleterious effects, many studies have aimed to clarify whether VEGFs directly affect neural cells or if the effects are mediated secondarily via other cell types, like vascular cells. A great number of reports have shown the expression and function of VEGF receptors (VEGFRs), mainly VEGFR-1 and -2, in neural cells, where VEGFR-2 has been described as the major mediator of VEGF-A signals. This review aims to summarize and compare the divergent roles of VEGFR-1 and -2 during CNS development and homeostasis.


Assuntos
Encéfalo/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Encéfalo/crescimento & desenvolvimento , Movimento Celular , Sistema Nervoso Central/crescimento & desenvolvimento , Sistema Nervoso Central/metabolismo , Humanos , Neurogênese , Transdução de Sinais , Fatores de Crescimento do Endotélio Vascular/metabolismo
12.
JMIR Cancer ; 10: e52386, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38819907

RESUMO

BACKGROUND: Mobile health (mHealth) apps offer unique opportunities to support self-care and behavior change, but poor user engagement limits their effectiveness. This is particularly true for fully automated mHealth apps without any human support. Human support in mHealth apps is associated with better engagement but at the cost of reduced scalability. OBJECTIVE: This work aimed to (1) describe the theory-informed development of a fully automated relaxation and mindfulness app to reduce distress in people with cancer (CanRelax app 2.0), (2) describe engagement with the app on multiple levels within a fully automated randomized controlled trial over 10 weeks, and (3) examine whether engagement was related to user characteristics. METHODS: The CanRelax app 2.0 was developed in iterative processes involving input from people with cancer and relevant experts. The app includes evidence-based relaxation exercises, personalized weekly coaching sessions with a rule-based conversational agent, 39 self-enactable behavior change techniques, a self-monitoring dashboard with gamification elements, highly tailored reminder notifications, an educational video clip, and personalized in-app letters. For the larger study, German-speaking adults diagnosed with cancer within the last 5 years were recruited via the web in Switzerland, Austria, and Germany. Engagement was analyzed in a sample of 100 study participants with multiple measures on a micro level (completed coaching sessions, relaxation exercises practiced with the app, and feedback on the app) and a macro level (relaxation exercises practiced without the app and self-efficacy toward self-set weekly relaxation goals). RESULTS: In week 10, a total of 62% (62/100) of the participants were actively using the CanRelax app 2.0. No associations were identified between engagement and level of distress at baseline, sex assigned at birth, educational attainment, or age. At the micro level, 71.88% (3520/4897) of all relaxation exercises and 714 coaching sessions were completed in the app, and all participants who provided feedback (52/100, 52%) expressed positive app experiences. At the macro level, 28.12% (1377/4897) of relaxation exercises were completed without the app, and participants' self-efficacy remained stable at a high level. At the same time, participants raised their weekly relaxation goals, which indicates a potential relative increase in self-efficacy. CONCLUSIONS: The CanRelax app 2.0 achieved promising engagement even though it provided no human support. Fully automated social components might have compensated for the lack of human involvement and should be investigated further. More than one-quarter (1377/4897, 28.12%) of all relaxation exercises were practiced without the app, highlighting the importance of assessing engagement on multiple levels.

13.
BMC Psychol ; 11(1): 186, 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349832

RESUMO

BACKGROUND: Depression remains a global health problem, with its prevalence rising worldwide. Digital biomarkers are increasingly investigated to initiate and tailor scalable interventions targeting depression. Due to the steady influx of new cases, focusing on treatment alone will not suffice; academics and practitioners need to focus on the prevention of depression (i.e., addressing subclinical depression). AIM: With our study, we aim to (i) develop digital biomarkers for subclinical symptoms of depression, (ii) develop digital biomarkers for severity of subclinical depression, and (iii) investigate the efficacy of a digital intervention in reducing symptoms and severity of subclinical depression. METHOD: Participants will interact with the digital intervention BEDDA consisting of a scripted conversational agent, the slow-paced breathing training Breeze, and actionable advice for different symptoms. The intervention comprises 30 daily interactions to be completed in less than 45 days. We will collect self-reports regarding mood, agitation, anhedonia (proximal outcomes; first objective), self-reports regarding depression severity (primary distal outcome; second and third objective), anxiety severity (secondary distal outcome; second and third objective), stress (secondary distal outcome; second and third objective), voice, and breathing. A subsample of 25% of the participants will use smartwatches to record physiological data (e.g., heart-rate, heart-rate variability), which will be used in the analyses for all three objectives. DISCUSSION: Digital voice- and breathing-based biomarkers may improve diagnosis, prevention, and care by enabling an unobtrusive and either complementary or alternative assessment to self-reports. Furthermore, our results may advance our understanding of underlying psychophysiological changes in subclinical depression. Our study also provides further evidence regarding the efficacy of standalone digital health interventions to prevent depression. Trial registration Ethics approval was provided by the Ethics Commission of ETH Zurich (EK-2022-N-31) and the study was registered in the ISRCTN registry (Reference number: ISRCTN38841716, Submission date: 20/08/2022).


Assuntos
Ansiedade , Depressão , Humanos , Ansiedade/terapia , Depressão/diagnóstico , Depressão/terapia , Estudos Longitudinais , Autorrelato
14.
Nat Chem ; 15(8): 1179-1187, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37386282

RESUMO

Microtubules, a critical component of the cytoskeleton, carry post-translational modifications (PTMs) that are important for the regulation of key cellular processes. Long-lived microtubules, in neurons particularly, exhibit both detyrosination of α-tubulin and polyglutamylation. Dysregulation of these PTMs can result in developmental defects and neurodegeneration. Owing to a lack of tools to study the regulation and function of these PTMs, the mechanisms that govern such PTM patterns are not well understood. Here we produce fully functional tubulin carrying precisely defined PTMs within its C-terminal tail. We ligate synthetic α-tubulin tails-which are site-specifically glutamylated-to recombinant human tubulin heterodimers by applying a sortase- and intein-mediated tandem transamidation strategy. Using microtubules reconstituted with these designer tubulins, we find that α-tubulin polyglutamylation promotes its detyrosination by enhancing the activity of the tubulin tyrosine carboxypeptidase vasohibin/small vasohibin-binding protein in a manner dependent on the length of polyglutamyl chains. We also find that modulating polyglutamylation levels in cells results in corresponding changes in detyrosination, corroborating the link between the detyrosination cycle to polyglutamylation.


Assuntos
Microtúbulos , Tubulina (Proteína) , Humanos , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Microtúbulos/metabolismo , Processamento de Proteína Pós-Traducional , Ligação Proteica
15.
Mol Biol Cell ; 33(8): ar75, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35544302

RESUMO

The centriole is a minute cylindrical organelle present in a wide range of eukaryotic species. Most centrioles have a signature ninefold radial symmetry of microtubules that is imparted to the axonemes of the cilia and flagella they template, with nine centriolar microtubule doublets growing into nine axonemal microtubule doublets. There are exceptions to the ninefold symmetrical arrangement of axonemal microtubules in some species, with lower or higher fold symmetries. In the few cases where this has been examined, such alterations in axonemal symmetries are grounded in similar alterations in centriolar symmetries. Here, we examine the question of microtubule number continuity between centriole and axoneme in flagellated gametes of the gregarine Lecudina tuzetae, which have been reported to exhibit a sixfold radial symmetry of axonemal microtubules. We used time-lapse differential interference microscopy to identify the stage at which flagellated gametes are present. Thereafter, using electron microscopy and ultrastructure-expansion microscopy coupled to stimulated emission depletion superresolution imaging, we uncover that a six- or fivefold radial symmetry in the axoneme is accompanied by an eightfold radial symmetry in the centriole. We conclude that the transition between centriolar and axonemal microtubules can be characterized by unexpected plasticity.


Assuntos
Apicomplexa , Centríolos , Axonema , Cílios , Flagelos , Microtúbulos
16.
J Geophys Res Biogeosci ; 127(1): e2021JG006622, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35865141

RESUMO

Bidirectional reflectance distribution function (BRDF) effects are a persistent issue for the analysis of vegetation in airborne imaging spectroscopy data, especially when mosaicking results from adjacent flightlines. With the advent of large airborne imaging efforts from NASA and the U.S. National Ecological Observatory Network (NEON), there is increasing need for methods that are flexible and automatable across images with diverse land cover. Flexible bidirectional reflectance distribution function (FlexBRDF) is built upon the widely used kernel method, with additional features including stratified random sampling across flightline groups, dynamic land cover stratification by normalized difference vegetation index (NDVI), interpolation of correction coefficients across NDVI bins, and the use of a reference solar zenith angle. We demonstrate FlexBRDF using nine long (150-400 km) airborne visible/infrared imaging spectrometer (AVIRIS)-Classic flightlines collected on 22 May 2013 over Southern California, where diverse land cover and a wide range of solar illumination yield significant BRDF effects. We further test the approach on additional AVIRIS-Classic data from California, AVIRIS-Next Generation data from the Arctic and India, and NEON imagery from Wisconsin. Comparison of overlapping areas of flightlines show that models built from multiple flightlines performed better than those built for single images (root mean square error improved up to 2.3% and mean absolute deviation 2.5%). Standardization to a common solar zenith angle among a flightline group improved performance, and interpolation across bins minimized between-bin boundaries. While BRDF corrections for individual sites suffice for local studies, FlexBRDF is an open source option that is compatible with bulk processing of large airborne data sets covering diverse land cover needed for calibration/validation of forthcoming spaceborne imaging spectroscopy missions.

17.
Nat Ecol Evol ; 6(5): 506-519, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35332280

RESUMO

Remote sensing has transformed the monitoring of life on Earth by revealing spatial and temporal dimensions of biological diversity through structural, compositional and functional measurements of ecosystems. Yet, many aspects of Earth's biodiversity are not directly quantified by reflected or emitted photons. Inclusive integration of remote sensing with field-based ecology and evolution is needed to fully understand and preserve Earth's biodiversity. In this Perspective, we argue that multiple data types are necessary for almost all draft targets set by the Convention on Biological Diversity. We examine five key topics in biodiversity science that can be advanced by integrating remote sensing with in situ data collection from field sampling, experiments and laboratory studies to benefit conservation. Lowering the barriers for bringing these approaches together will require global-scale collaboration.


Assuntos
Ecossistema , Tecnologia de Sensoriamento Remoto , Biodiversidade , Ecologia
18.
Am J Pathol ; 177(1): 404-14, 2010 07.
Artigo em Inglês | MEDLINE | ID: mdl-20508033

RESUMO

Wnt/beta-catenin signaling has been implicated in taste papilla development; however, its role in epithelial maintenance and tumor progression in the adult tongue remains elusive. We show Wnt/beta-catenin pathway activation in reporter mice and by nuclear beta-catenin staining in the epithelium and taste papilla of adult mouse and human tongues. beta-Catenin activation in APC(min/+) mice, which carry a mutation in adenomatous poliposis coli (APC), up-regulates Sonic hedgehog (Shh) and Jagged-2 (JAG2) in the tongue epithelium without formation of squamous cell carcinoma (SCC). We demonstrate that Shh suppresses beta-catenin transcriptional activity in a signaling-dependent manner in vitro and in vivo. A similar regulation and function was observed for JAG2, suggesting that both pathways negatively regulate beta-catenin, thereby preventing SCC formation in the tongue. This was supported by reduced nuclear beta-catenin in the tongue epithelium of Patched(+/-) mice, exhibiting dominant active Shh signaling. At the invasive front of human tongue cancer, nuclear beta-catenin and Shh were increased, suggesting their participation in tumor progression. Interestingly, Shh but not JAG2 was able to reduce beta-catenin signaling in SCC cells, arguing for a partial loss of negative feedback on beta-catenin transcription in tongue cancer. We show for the first time that the putative Wnt/beta-catenin targets Shh and JAG2 control beta-catenin signaling in the adult tongue epithelium, a function that is partially lost in lingual SCC.


Assuntos
Epitélio/metabolismo , Proteínas Hedgehog/metabolismo , Transdução de Sinais/fisiologia , Língua/anatomia & histologia , beta Catenina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Linhagem Celular , Feminino , Genes Reporter , Proteínas Hedgehog/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-2 , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Neoplasias da Língua/metabolismo , Neoplasias da Língua/patologia , Ativação Transcricional , beta Catenina/genética
19.
Ecol Evol ; 11(16): 10834-10867, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34429885

RESUMO

Trait-based ecology holds the promise to explain how plant communities work, for example, how functional diversity may support community productivity. However, so far it has been difficult to combine field-based approaches assessing traits at the level of plant individuals with limited spatial coverage and approaches using remote sensing (RS) with complete spatial coverage but assessing traits at the level of vegetation pixels rather than individuals. By delineating all individual-tree crowns within a temperate forest site and then assigning RS-derived trait measures to these trees, we combine the two approaches, allowing us to use general linear models to estimate the influence of taxonomic or environmental variation on between- and within-species variation across contiguous space.We used airborne imaging spectroscopy and laser scanning to collect individual-tree RS data from a mixed conifer-angiosperm forest on a mountain slope extending over 5.5 ha and covering large environmental gradients in elevation as well as light and soil conditions. We derived three biochemical (leaf chlorophyll, carotenoids, and water content) and three architectural traits (plant area index, foliage-height diversity, and canopy height), which had previously been used to characterize plant function, from the RS data. We then quantified the contributions of taxonomic and environmental variation and their interaction to trait variation and partitioned the remaining within-species trait variation into smaller-scale spatial and residual variation. We also investigated the correlation between functional trait and phylogenetic distances at the between-species level. The forest consisted of 13 tree species of which eight occurred in sufficient abundance for quantitative analysis.On average, taxonomic variation between species accounted for more than 15% of trait variation in biochemical traits but only around 5% (still highly significant) in architectural traits. Biochemical trait distances among species also showed a stronger correlation with phylogenetic distances than did architectural trait distances. Light and soil conditions together with elevation explained slightly more variation than taxonomy across all traits, but in particular increased plant area index (light) and reduced canopy height (elevation). Except for foliage-height diversity, all traits were affected by significant interactions between taxonomic and environmental variation, the different responses of the eight species to the within-site environmental gradients potentially contributing to the coexistence of the eight abundant species.We conclude that with high-resolution RS data it is possible to delineate individual-tree crowns within a forest and thus assess functional traits derived from RS data at individual level. With this precondition fulfilled, it is then possible to apply tools commonly used in field-based trait ecology to partition trait variation among individuals into taxonomic and potentially even genetic variation, environmental variation, and interactions between the two. The method proposed here presents a promising way of assessing individual-based trait information with complete spatial coverage and thus allowing analysis of functional diversity at different scales. This information can help to better understand processes shaping community structure, productivity, and stability of forests.

20.
Methods Ecol Evol ; 12(6): 1093-1102, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34262682

RESUMO

Ecosystem heterogeneity has been widely recognized as a key ecological indicator of several ecological functions, diversity patterns and change, metapopulation dynamics, population connectivity or gene flow.In this paper, we present a new R package-rasterdiv-to calculate heterogeneity indices based on remotely sensed data. We also provide an ecological application at the landscape scale and demonstrate its power in revealing potentially hidden heterogeneity patterns.The rasterdiv package allows calculating multiple indices, robustly rooted in Information Theory, and based on reproducible open-source algorithms.

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