Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 208
Filtrar
1.
Nature ; 586(7829): 424-428, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33029010

RESUMO

Since 1814, when rubella was first described, the origins of the disease and its causative agent, rubella virus (Matonaviridae: Rubivirus), have remained unclear1. Here we describe ruhugu virus and rustrela virus in Africa and Europe, respectively, which are, to our knowledge, the first known relatives of rubella virus. Ruhugu virus, which is the closest relative of rubella virus, was found in apparently healthy cyclops leaf-nosed bats (Hipposideros cyclops) in Uganda. Rustrela virus, which is an outgroup to the clade that comprises rubella and ruhugu viruses, was found in acutely encephalitic placental and marsupial animals at a zoo in Germany and in wild yellow-necked field mice (Apodemus flavicollis) at and near the zoo. Ruhugu and rustrela viruses share an identical genomic architecture with rubella virus2,3. The amino acid sequences of four putative B cell epitopes in the fusion (E1) protein of the rubella, ruhugu and rustrela viruses and two putative T cell epitopes in the capsid protein of the rubella and ruhugu viruses are moderately to highly conserved4-6. Modelling of E1 homotrimers in the post-fusion state predicts that ruhugu and rubella viruses have a similar capacity for fusion with the host-cell membrane5. Together, these findings show that some members of the family Matonaviridae can cross substantial barriers between host species and that rubella virus probably has a zoonotic origin. Our findings raise concerns about future zoonotic transmission of rubella-like viruses, but will facilitate comparative studies and animal models of rubella and congenital rubella syndrome.


Assuntos
Mamíferos/virologia , Filogenia , Vírus da Rubéola/classificação , Vírus da Rubéola/isolamento & purificação , Sequência de Aminoácidos , Animais , Animais de Zoológico/imunologia , Animais de Zoológico/virologia , Membrana Celular/virologia , Quirópteros/virologia , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito T/imunologia , Equidae/imunologia , Equidae/virologia , Evolução Molecular , Feminino , Mapeamento Geográfico , Alemanha , Especificidade de Hospedeiro , Humanos , Masculino , Mamíferos/imunologia , Marsupiais/imunologia , Marsupiais/virologia , Fusão de Membrana , Camundongos , Modelos Animais , Modelos Moleculares , Rubéola (Sarampo Alemão)/congênito , Rubéola (Sarampo Alemão)/virologia , Vírus da Rubéola/química , Vírus da Rubéola/imunologia , Alinhamento de Sequência , Uganda , Proteínas do Envelope Viral/química
2.
Nature ; 588(7836): E2, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33199919

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

3.
J Am Chem Soc ; 146(3): 1771-1775, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38181408

RESUMO

The search for a suitable replacement for the ubiquitous oxidizer ammonium perchlorate (AP) is a top priority to enable more sustainable solid rocket motors. The oxidizing salts ammonium nitrate (AN) and ammonium dinitramide (ADN) are regarded as potential green replacements for AP, but suffer from a plethora of handling and processing issues including poor stability and a needle-like crystal morphology which inhibits dense packing; these prevent their widespread use. In the present work, ionic cocrystallization is leveraged to produce the first cocrystals of these oxidizing salts with an energetic coformer and the first such cocrystals to maintain a positive oxygen balance. The azole-based energetic molecule 5,5'-dinitro-2H,2H'-3,3″-bi-1,2,4-triazole (DNBT) is successfully cocrystallized with AN to yield the cocrystal 2AN:DNBT. Differential scanning calorimetry data confirms that AN, which in its pure form suffers from a problematic solid-state phase transition, is stabilized in the cocrystal. Application of this cocrystallization strategy to ADN produces 2ADN:DNBT, which has the highest oxygen balance of any organic cocrystal.

4.
Electrophoresis ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573014

RESUMO

Mass spectrometry (MS) has revolutionized analytical chemistry, enabling precise identification and quantification of chemical species, which is pivotal for biomarker discovery and understanding complex biological systems. Despite its versatility, the presence of background ions in MS analysis hinders the sensitive detection of low-abundance analytes. Therefore, studies aimed at lowering background ion levels have become increasingly important. Here, we utilized the commercially available Active Background Ion Reduction Device (ABIRD) to suppress background ions and assess its effect on the liquid chromatography-electrospray ionization (LC-ESI)-MS analyses of N-glycans on the Q Exactive HF mass spectrometer. We also investigated the effect of different solvent vapors in the ESI source on N-glycan analysis by MS. ABIRD generally had no effect on high-mannose and neutral structures but reduced the intensity of some structures that contained sialic acid, fucose, or both when methanol vapor filled the ESI source. Based on our findings on the highest number of identified N-glycans from human serum, methanol vapor in the ion source compartment may enhance N-glycan LC-ESI-MS analyses by improving the desolvation of droplets formed during the ESI process due to its high volatility. This protocol may be further validated and extended to advanced bottom-up proteomic/glycoproteomic studies for the analysis of peptide/glycopeptide ions by MS.

5.
Ecol Appl ; 34(2): e2947, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38305124

RESUMO

Revegetation plantings are a key activity in farmland restoration and are commonly assumed to support biotic communities that, with time, replicate those of reference habitats. Restoration outcomes, however, can be highly variable and difficult to predict; hence there is value in quantifying restoration success to improve future efforts. We test the expectation that, over time, revegetation will restore bird communities to match those in reference habitats; and assess whether specific planting attributes enhance restoration success. We surveyed birds in 255 sites in south-east Australia, arranged along a restoration gradient encompassing three habitat types: unrestored farmland (paddocks), revegetation plantings (comprising a chronosequence up to 52 years old) and reference habitats (remnant native vegetation). Surveys were undertaken in 2006/2007 and again in 2019, with data used to compare bird assemblages between habitat types. We also determined whether, in the intervening 12 years, bird communities in revegetation had shifted toward reference habitats on the restoration gradient. Our results showed that each habitat contained a unique bird community and that, over time, assemblages in revegetation diverged away from those in unrestored farmland and converged toward those in reference habitats. Two planting attributes influenced this transition: the bird assemblages of revegetation were more likely to have diverged away from those of unrestored farmland (with scattered mature trees) 12 years later if they were located in areas with more surrounding tree cover, and were mostly ungrazed by livestock (compared with grazed plantings). Our results highlight three key ways in which revegetation contributes to farmland restoration: (1) by supporting richer and more diverse bird assemblages than unrestored farmland, (2) by enhancing beta diversity in rural landscapes through the addition of a unique bird community, and (3) by shifting bird assemblages toward those found in reference habitats over time. However, revegetation plantings did not replicate reference habitats by ~40-50 years in our region, and complete convergence may take centuries. These findings have implications for environmental offset programs and mean that effective conservation in farmland environments depends on the retention and protection of natural and seminatural habitats as a parallel management strategy to complement restoration.


Assuntos
Biota , Aves , Animais , Fazendas , Gado , Árvores
6.
Chemistry ; 29(27): e202300076, 2023 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-36812052

RESUMO

In contrast to the mature predictive frameworks applied to neutral cocrystals, ionic cocrystals, those including an ion pair, are difficult to design. Furthermore, they are generally excluded categorically from studies which correlate specific molecular properties to cocrystal formation, leaving the prospective ionic cocrystal engineer with few clear avenues to success. Herein ammonium nitrate, an energetic oxidizing salt, is targeted for cocrystallization in a potential coformer group selected based on likely interactions with the nitrate ion as revealed in the Cambridge Structural Database; six novel ionic cocrystals were discovered. Molecular descriptors previously identified as being related to neutral cocrystal formation were examined across the screening group but showed no relationship with ionic cocrystal formation. High packing coefficient is shown to be a constant among the successful coformers in the set and is utilized to directly target two more successful coformers, bypassing the need for a large screening group.

7.
Learn Mem ; 29(10): 367-378, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36180130

RESUMO

Novel tests of semantic memory (SM)-for example, memory for news events (NE; news facts) or famous personalities-are useful for estimating the severity of retrograde amnesia. Individuals with mild cognitive impairment exhibit relatively intact SM/language on traditional neuropsychological tests but exhibit consistent impairment on novel tests of SM, suggesting novel SM tests are dissimilar from traditional SM tests. To identify the relationship between NE memory and traditional cognitive measures, older adults (N = 51) completed a traditional neuropsychological battery and the Retrograde Memory News Events Test (RM-NET; a new test that robustly measures NE memory across the adult life span with high temporal resolution), and the relationship between performance on these tests was examined. Total RM-NET scores were more closely aligned with episodic memory scores than SM scores. The strength of the association between NE scores and episodic memory scores decreased as the age of NE memory increased. Tests of news events appear to reflect performance on traditional tests of episodic memory rather than SM, especially when recent news events are tested.


Assuntos
Disfunção Cognitiva , Memória Episódica , Idoso , Amnésia Retrógrada , Disfunção Cognitiva/diagnóstico , Humanos , Idioma , Testes Neuropsicológicos
8.
Electrophoresis ; 43(1-2): 370-387, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34614238

RESUMO

Protein glycosylation is one of the most common posttranslational modifications, and plays an essential role in a wide range of biological processes such as immune response, intercellular signaling, inflammation, host-pathogen interaction, and protein stability. Glycoproteomics is a proteomics subfield dedicated to identifying and characterizing the glycans and glycoproteins in a given cell or tissue. Aberrant glycosylation has been associated with various diseases such as Alzheimer's disease, viral infections, inflammation, immune deficiencies, congenital disorders, and cancers. However, glycoproteomic analysis remains challenging because of the low abundance, site-specific heterogeneity, and poor ionization efficiency of glycopeptides during LC-MS analyses. Therefore, the development of sensitive and accurate approaches to efficiently characterize protein glycosylation is crucial. Methods such as metabolic labeling, enrichment, and derivatization of glycopeptides, coupled with different mass spectrometry techniques and bioinformatics tools, have been developed to achieve sophisticated levels of quantitative and qualitative analyses of glycoproteins. This review attempts to update the recent developments in the field of glycoproteomics reported between 2017 and 2021.


Assuntos
Glicopeptídeos , Proteômica , Cromatografia Líquida , Glicopeptídeos/química , Glicosilação , Espectrometria de Massas/métodos , Proteômica/métodos
9.
Liver Int ; 42(3): 507-521, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35048542

RESUMO

As the worldwide prevalence of chronic liver diseases is high and continuing to increase, there is an urgent need for treatment to prevent cirrhosis-related morbidity and mortality. Integrins are heterodimeric cell-surface proteins that are promising targets for therapeutic intervention. αv integrins are central in the development of fibrosis as they activate latent TGFß, a known profibrogenic cytokine. The αv subunit can form heterodimers with ß1, ß3, ß5, ß6 or ß8 subunits and one or more of these integrins are central to the development of liver fibrosis, however, their relative importance is not understood. This review summarises the current knowledge of αv integrins and their respective ß subunits in different organs, with a focus on liver fibrosis and the emerging preclinical and clinical data with regards to αv integrin inhibitors.


Assuntos
Integrinas , Preparações Farmacêuticas , Humanos , Integrina alfaV/metabolismo , Integrinas/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Fator de Crescimento Transformador beta/metabolismo
10.
Cancer Treat Res ; 184: 161-166, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36449196

RESUMO

Fluoroquinolones (FQs) are among the most commonly prescribed class of antibiotics and have regulatory approval to treat anthrax, pneumonia, unitary tract infections, and sinus infection among other uses.


Assuntos
Fluoroquinolonas , Humanos , Fluoroquinolonas/uso terapêutico , Marcadores Genéticos
11.
Cancer Treat Res ; 184: 1-39, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36449185

RESUMO

This study describes cases of individuals who report adverse events following consumption of the most commonly prescribed fluoroquinolone (FQ) antibiotics: ciprofloxacin, levofloxacin, or moxifloxacin. Fluoroquinolone (FQ) antibiotics are some of the most widely prescribed antibiotics in the world. Although these antibiotics have been on the market for more than 20 years, a wide range of serious FQ-associated adverse events first became apparent in 2006 and continued to be recognized for the next 15 years.


Assuntos
Antibacterianos , Fluoroquinolonas , Humanos , Fluoroquinolonas/efeitos adversos , Antibacterianos/efeitos adversos
12.
Oncologist ; 26(8): e1418-e1426, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33586299

RESUMO

Biosimilars are biologic drug products that are highly similar to reference products in analytic features, pharmacokinetics and pharmacodynamics, immunogenicity, safety, and efficacy. Biosimilar epoetin received Food and Drug Administration (FDA) approval in 2018. The manufacturer received an FDA nonapproval letter in 2017, despite receiving a favorable review by FDA's Oncologic Drugs Advisory Committee (ODAC) and an FDA nonapproval letter in 2015 for an earlier formulation. We discuss the 2018 FDA approval, the 2017 FDA ODAC Committee review, and the FDA complete response letters in 2015 and 2017; review concepts of litigation, naming, labeling, substitution, interchangeability, and pharmacovigilance; review European and U.S. oncology experiences with biosimilar epoetin; and review the safety of erythropoiesis-stimulating agents. In 2020, policy statements from AETNA, United Health Care, and Humana indicated that new epoetin oncology starts must be for biosimilar epoetin unless medical need for other epoetins is documented. Empirical studies report that as of 2012, reference epoetin use decreased from 40%-60% of all patients with cancer with chemotherapy-induced anemia to <5% of such patients because of safety concerns. Between 2018 and 2020, biosimilar epoetin use varied, increasing to 81% among one private insurer's patients covered by Medicare whose cancer care is administered with Oncology Analytics and to 41% with the same private insurer's patients with cancer covered by commercial health insurance and administered by the private insurer, to 0% in several Veterans Administration Hospitals, increasing to 100% in one large county hospital in California, and with yet-to-be-reported data from most oncology settings. We conclude that biosimilar epoetin appears to have overcome some barriers since 2015, although current uptake in the U.S. is variable. Pricing and safety considerations for all erythropoiesis-stimulating agents are primary determinants of biosimilar epoetin oncology uptake. IMPLICATIONS FOR PRACTICE: Few oncologists understand substitution and interchangeability of biosimilars with reference drugs. Epoetin biosimilar is new to the market, and physician and patient understanding is limited. The development of epoetin biosimilar is not familiar to oncologists.


Assuntos
Anemia , Antineoplásicos , Medicamentos Biossimilares , Neoplasias , Idoso , Anemia/induzido quimicamente , Anemia/tratamento farmacológico , Antineoplásicos/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Epoetina alfa/uso terapêutico , Humanos , Medicare , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Estados Unidos
13.
FASEB J ; 34(3): 3616-3630, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31957088

RESUMO

Mitochondria are considered as the power-generating units of the cell due to their key role in energy metabolism and cell signaling. However, mitochondrial components could be found in the extracellular space, as fragments or encapsulated in vesicles. In addition, this intact organelle has been recently reported to be released by platelets exclusively in specific conditions. Here, we demonstrate for the first time, that blood preparation with resting platelets, contains whole functional mitochondria in normal physiological state. Likewise, we show, that normal and tumor cultured cells are able to secrete their mitochondria. Using serial centrifugation or filtration followed by polymerase chain reaction-based methods, and Whole Genome Sequencing, we detect extracellular full-length mitochondrial DNA in particles over 0.22 µm holding specific mitochondrial membrane proteins. We identify these particles as intact cell-free mitochondria using fluorescence-activated cell sorting analysis, fluorescence microscopy, and transmission electron microscopy. Oxygen consumption analysis revealed that these mitochondria are respiratory competent. In view of previously described mitochondrial potential in intercellular transfer, this discovery could greatly widen the scope of cell-cell communication biology. Further steps should be developed to investigate the potential role of mitochondria as a signaling organelle outside the cell and to determine whether these circulating units could be relevant for early detection and prognosis of various diseases.


Assuntos
DNA Mitocondrial/genética , Mitocôndrias/metabolismo , Western Blotting , Linhagem Celular Tumoral , Genoma Mitocondrial/genética , Humanos , Cinética
14.
Ecol Appl ; 31(1): e02219, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32810887

RESUMO

Ecosystem engineers physically modify their environment, thereby altering habitats for other organisms. Increasingly, "engineers" are recognized as an important focus for conservation and ecological restoration because their actions affect a range of ecosystem processes and thereby influence how ecosystems function. The Superb Lyrebird Menura novaehollandiae is proposed as an ecosystem engineer in forests of southeastern Australia due to the volume of soil and litter it turns over when foraging. We measured the seasonal and spatial patterns of foraging by Lyrebirds and the amount of soil displaced in forests in the Central Highlands, Victoria. We tested the effects of foraging on litter, soil nutrients and soil physical properties by using an experimental approach with three treatments: Lyrebird exclusion, Lyrebird exclusion with simulated foraging, and non-exclusion reference plots. Treatments were replicated in three forest types in each of three forest blocks. Lyrebirds foraged extensively in all forest types in all seasons. On average, Lyrebirds displaced 155.7 Mg/ha of litter and soil in a 12-month period. Greater displacement occurred where vegetation complexity (<50 cm height) was low. After two years of Lyrebird exclusion, soil compaction (top 7.5 cm) increased by 37% in exclusion plots compared with baseline measures, while in unfenced plots it decreased by 22%. Litter depth was almost three times greater in fenced than unfenced plots. Soil moisture, pH, and soil nutrients showed no difference between treatments. The enormous extent of litter and soil turned over by the Superb Lyrebird is unparalleled by any other vertebrate soil engineer in terrestrial ecosystems globally. The profound influence of such foraging activity on forest ecosystems is magnified by its year-round pattern and widespread distribution. The disturbance regime that Lyrebirds impose has implications for diverse ecosystem processes including decomposition and nutrient cycling, the composition of litter- and soil-dwelling invertebrate communities, the shaping of ground-layer vegetation patterns, and fire behavior and post-fire ecosystem recovery. Maintaining Lyrebird populations as a key facilitator of ecosystem function is now timely and critical as unprecedented wildfires in eastern Australia in summer 2019-2020 have severely burned ~12 million ha of forest, including ~30% of the geographic range of the Superb Lyrebird.


Assuntos
Ecossistema , Incêndios , Florestas , Solo , Árvores , Vitória
15.
Ecol Appl ; 31(4): e02308, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33605500

RESUMO

To mitigate the impact of severe wildfire on human society and the environment, prescribed fire is widely used in forest ecosystems to reduce fuel loads and limit fire spread. To avoid detrimental effects on conservation values, it is imperative to understand how prescribed fire affects taxa having a range of different adaptations to disturbance. Such studies will have greatest benefit if they extend beyond short-term impacts of burning. We used a field study to examine the effects of prescribed fire on birds and plants across a 36-yr post-fire chronosequence in a temperate dry forest ecosystem in southeastern Australia, and by making comparison with long-unburned reference sites (79 yr since wildfire). We modeled changes in the relative abundance of 22 bird species and the cover of 39 plant species, and examined how individual species, functional groups, species richness and community composition differed between sites with different fire history. For most individual bird and plant species modeled, relative abundance or cover at sites subject to prescribed fire did not change significantly with time since fire or differ from that of long-unburned vegetation. When bird species were pooled into functional groups, time since prescribed fire had strong effects on birds that forage in the lower-midstorey, facultative-resprouting shrubs and obligate-seeding shrubs. Species richness for both taxa did not differ between sites subject to prescribed fire and those in long-unburned vegetation. Bird communities varied significantly between the youngest (0-3 yr) and oldest (79 yr) post-fire age classes, driven by species associated with understorey vegetation. Plant community composition showed little evidence of a post-fire successional trajectory. The prevalence of bird species with broad habitat and dietary niches and plant regeneration through resprouting, make bird and plant communities in these forests relatively resilient to small and patchy prescribed fires they have experienced to date. Application of prescribed fire will be most compatible with maintaining biodiversity by taking a landscape approach that (1) plans for a geographic spread of stands with a range of between-prescribed-fire intervals to ensure provision of suitable habitat for all taxa, and (2) avoids burning in moist gullies to maintain their value as fire refuges.


Assuntos
Ecossistema , Incêndios , Animais , Austrália , Aves , Florestas , Humanos
16.
Arch Virol ; 166(12): 3513-3566, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34463877

RESUMO

In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.


Assuntos
Mononegavirais , Vírus , Humanos
17.
BMC Health Serv Res ; 21(1): 495, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34030667

RESUMO

BACKGROUND: Past studies examining the health outcomes of diabetes mellitus (DM) patients found that social determinants of health disparities were associated with variabilities in health outcomes. However, improving access to healthcare, such as health insurance, should mitigate negative health outcomes. The aim of the study was to explore the association between four types of health insurance, namely, Medicare Fee-For-Service (FFS), Medicare Managed Care (MC), Private FFS, and Private MC plans, and the health outcomes of DM patients, controlling for patients' social determinants of health. METHODS: This is a retrospective cross-sectional archival record study to explore the relationships between types of health insurance and health outcomes of DM patients who were at least 65 years old, or the elderly. Data was drawn from the 2012 Maryland Clinical Public Use Data and received an exempt status from our Institutional Review Board. Elderly Maryland residents with chronic DM were included in the study, resulting in a sample size of 43,519 individuals. Predictor variables were four types of insurance and health outcome variables were length of hospital stay (LOS), 30-day readmission, and end-stage renal disease (ESRD). Control variables included hospital characteristics, patient characteristics, and social determinants of health. Student's t-tests determined the statistical differences for the control variables between the types of insurance. Multiple hierarchical regression analysis was applied to test the association between insurance plans and LOS, while logistic regression analyses were applied to test the association between insurance plans with 30-day readmission and ESRD. Statistical significance was set at p < 0.05. RESULTS: t-test results indicated minimal statistical differences between the health statuses of patients enrolled in different insurance plans. After factoring out the control variables, regression analyses indicated that Medicare FFS patients had the worst outcome for LOS, 30-day readmission, and ESRD rates. Although patients on Medicare MC plans had lower LOS, 30-day readmission, and ESRD rates compared to those on Medicare FFS, patients enrolled in Private MC plans had the lowest odds of a 30-day readmission and patients enrolled in Private FFS had the lowest odds of an ESRD. CONCLUSIONS: The data suggests that insurance plans were related to the health outcomes of elderly DM patients after considering their social determinants of health. Specifically, DM patients enrolled in managed care and private insurance plans had better health outcomes compared to those on Medicare FFS plans.


Assuntos
Diabetes Mellitus , Medicare , Idoso , Estudos Transversais , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Planos de Pagamento por Serviço Prestado , Humanos , Maryland/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Estados Unidos
18.
J Neuroinflammation ; 17(1): 316, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097087

RESUMO

BACKGROUND: Neuroinflammation is a critical feature of sensitisation of spinal nociceptive processing in chronic pain states. We hypothesised that the resolvin pathways, a unique endogenous control system, may ameliorate aberrant spinal processing of somatosensory inputs associated with chemotherapy-induced neuropathic pain (CINP). METHOD: The paclitaxel (PCX) model of CINP was established in male Sprague-Dawley rats and compared to control rats (n = 23 and 22, respectively). Behavioural pain responses were measured, and either single unit electrophysiological recordings of dorsal horn wide dynamic range (WDR) neurones were performed, or mRNA microarray analysis of the dorsal horn of the spinal cord was undertaken. RESULTS: PCX rats exhibited significant changes in behavioural responses to mechanical and cold stimuli. A higher proportion of WDR neurones in PCX rats were polymodal (generating post-discharge following a non-noxious mechanical stimulus, responding to non-noxious cold and exhibiting spontaneous activity) compared to control (p < 0.05). Microarray analysis revealed changes in proinflammatory pathways (Tlr, Tnfrsf1a, Nlrp1a, Cxcr1, Cxcr5, Ccr1, Cx3cr1) and anti-inflammatory lipid resolvin pathways (Alox5ap, Cyp2j4 and Ptgr1) compared to control (p < 0.05). Ingenuity pathway analysis predicted changes in glutamatergic and astrocyte signaling in the PCX group. Activation of the resolvin system via the spinal administration of aspirin-triggered resolvin D1 (AT-RvD1) markedly inhibited (73 ± 7% inhibition) normally non-noxious mechanically (8 g) evoked responses of WDR neurones only in PCX rats, whilst leaving responses to noxious mechanically induced stimuli intact. Inhibitory effects of AT-RvD1were comparable in magnitude to spinal morphine (84 ± 4% inhibition). CONCLUSION: The PCX model of CINP was associated with mechanical allodynia, altered neuronal responses and dysregulation of pro- and anti-inflammatory signalling in the spinal dorsal horn. The resolvin AT-RvD1 selectively inhibited low weight mechanical-evoked responses of WDR neurones in PCX rats, but not in controls. Our data support the targeting of spinal neuroinflammation via the activation of the resolvin system as a new therapeutic approach for CINP.


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Sistemas de Liberação de Medicamentos/métodos , Mediadores da Inflamação/metabolismo , Neuralgia/induzido quimicamente , Neuralgia/metabolismo , Células do Corno Posterior/metabolismo , Animais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Mediadores da Inflamação/antagonistas & inibidores , Masculino , Neuralgia/tratamento farmacológico , Paclitaxel/toxicidade , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Células do Corno Posterior/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
19.
Glob Chang Biol ; 25(11): 3829-3843, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31215102

RESUMO

Wildfire refugia (unburnt patches within large wildfires) are important for the persistence of fire-sensitive species across forested landscapes globally. A key challenge is to identify the factors that determine the distribution of fire refugia across space and time. In particular, determining the relative influence of climatic and landscape factors is important in order to understand likely changes in the distribution of wildfire refugia under future climates. Here, we examine the relative effect of weather (i.e. fire weather, drought severity) and landscape features (i.e. topography, fuel age, vegetation type) on the occurrence of fire refugia across 26 large wildfires in south-eastern Australia. Fire weather and drought severity were the primary drivers of the occurrence of fire refugia, moderating the effect of landscape attributes. Unburnt patches rarely occurred under 'severe' fire weather, irrespective of drought severity, topography, fuels or vegetation community. The influence of drought severity and landscape factors played out most strongly under 'moderate' fire weather. In mesic forests, fire refugia were linked to variables that affect fuel moisture, whereby the occurrence of unburnt patches decreased with increasing drought conditions and were associated with more mesic topographic locations (i.e. gullies, pole-facing aspects) and vegetation communities (i.e. closed-forest). In dry forest, the occurrence of refugia was responsive to fuel age, being associated with recently burnt areas (<5 years since fire). Overall, these results show that increased severity of fire weather and increased drought conditions, both predicted under future climate scenarios, are likely to lead to a reduction of wildfire refugia across forests of southern Australia. Protection of topographic areas able to provide long-term fire refugia will be an important step towards maintaining the ecological integrity of forests under future climate change.


Assuntos
Incêndios , Incêndios Florestais , Secas , Florestas , Refúgio de Vida Selvagem , Austrália do Sul , Tempo (Meteorologia)
20.
Gen Comp Endocrinol ; 280: 82-90, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31002829

RESUMO

Conspicuous coloration can indicate phenotypic quality, and may reflect exposure or vulnerability to stress, or access to essential nutrients such as pigments. Although the production of pigmented colours is well understood, much less is known about how structural colours are affected by physiological state. In this study, we tested whether glucocorticoids (corticosterone) predicted expression of plumage coloration in an Australian parrot, the crimson rosella (Platycercus elegans). Parrots provide an interesting and unique test, as they possess conspicuous coloration produced by distinctive pigments known as psittacofulvins, in addition to structural coloration. We have previously documented that coloration in P. elegans is condition-dependent and responds to dietary manipulation. Here, n = 21 P. elegans underwent a dietary manipulation (including food restriction or carotenoid supplementation) during which they moulted, and the change in reflectance was measured for three structural and three pigmentary plumage patches. Stress-induced corticosterone (10 min after handling) measured at the start of the experiment predicted change in coloration in two pigmentary patches (crown and front). We also found that change in stress-induced corticosterone during the experiment was associated with the change in coloration of the crown and two structural patches (cheek and epaulette). Baseline corticosterone (<3 min after handling) was not associated with any measure of coloration. We found no effects of dietary manipulation on baseline or stress-induced corticosterone, but carotenoid supplementation was associated with an increase in a measure of chronic stress (heterophil/lymphocyte ratio), and the corticosterone response to handling decreased over the course of the study. Our results suggest that corticosterone may be linked to colour expression more broadly than previously recognised, including psittacofulvin and structural coloration in parrots, and they confirm the independence of plumage pigmentation in parrots from carotenoid accumulation. Moreover, our study provides new insight into the stress responses of Psittaciformes, one of the most highly threatened avian orders.


Assuntos
Carotenoides/metabolismo , Plumas/metabolismo , Glucocorticoides/metabolismo , Papagaios/metabolismo , Pigmentação , Animais , Cor , Corticosterona/metabolismo , Dieta , Plumas/efeitos dos fármacos , Imunidade/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Papagaios/imunologia , Fito-Hemaglutininas/farmacologia , Pigmentação/fisiologia , Estresse Fisiológico/efeitos dos fármacos , Fatores de Tempo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA