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High cardiorespiratory fitness (CRF) in adulthood is important for survival from major chronic diseases and preserving good health. We examined how childhood CRF tracks, or persists, into adulthood. Among a cohort of 748 school children followed over 34 years, we found child CRF correlated with young- (r = 0.30) and mid-adulthood (r = 0.16) CRF.
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Capacidad Cardiovascular , Humanos , Niño , Aptitud FísicaRESUMEN
HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive, neuroinflammatory demyelinating condition of the spinal cord. We have previously shown that aberrant expression and activity of immune checkpoint (ICP) molecules such as PD-1 and PD-L1/PD-L2, negatively associates with the cytolytic potential of T cells in individuals with HAM/TSP. Interestingly, ICPs can exist in a soluble cell-free form and can be carried on extracellular vesicles (EVs) and exosomes (small EVs, <300nm) while maintaining their immunomodulatory activity. Therefore, we investigated the role of soluble and exosomal ICPs in HTLV-1 associated neuroinflammation. For the very first time, we demonstrate a unique elevated presence of several stimulatory (CD27, CD28, 4-1BB) and inhibitory (BTLA, CTLA-4, LAG-3, PD-1, PD-L2) ICP receptors in HAM/TSP sera, and in purified exosomes from a HAM/TSP-derived HTLV-1-producing (OSP2) cells. These ICPs were found to be co-localized with the endosomal sorting complex required for transport (ESCRT) pathway proteins and exhibited functional binding with their respective ligands. Viral proteins and cytokines (primarily IFNγ) were found to be present in purified exosomes. IFNγ exposure enhanced the release of ICP molecules while antiretroviral drugs (Azidothymidine and Lopinavir) significantly inhibited this process. HTLV-1 b-Zip protein (HBZ) has been linked to factors that enhance EV release and concurrent knockdown here led to the reduced expression of ESCRT associated genes (eg. Hrs, Vsp4, Alix, Tsg101) as well as abrogated the release of ICP molecules, suggesting HBZ involvement in this process. Moreso, exosomes from OSP2 cells adversely affected CD8 T-cell functions by dimishing levels of cytokines and cytotoxic factors. Collectively, these findings highlight exosome-mediated immunmodulation of T-cell functions with HBZ and ESCRT pathways as an underlying mechanism in the context of HTLV-1-induced neuroinflammation.
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OBJECTIVE: Primary mitochondrial diseases (PMDs) are heterogeneous disorders caused by inherited mitochondrial dysfunction. Classically defined neuropathologically as subacute necrotizing encephalomyelopathy, Leigh syndrome spectrum (LSS) is the most frequent manifestation of PMD in children, but may also present in adults. A major challenge for accurate diagnosis of LSS in the genomic medicine era is establishing gene-disease relationships (GDRs) for this syndrome with >100 monogenic causes across both nuclear and mitochondrial genomes. METHODS: The Clinical Genome Resource (ClinGen) Mitochondrial Disease Gene Curation Expert Panel (GCEP), comprising 40 international PMD experts, met monthly for 4 years to review GDRs for LSS. The GCEP standardized gene curation for LSS by refining the phenotypic definition, modifying the ClinGen Gene-Disease Clinical Validity Curation Framework to improve interpretation for LSS, and establishing a scoring rubric for LSS. RESULTS: The GDR with LSS across the nuclear and mitochondrial genomes was classified as definitive for 31 of 114 GDRs curated (27%), moderate for 38 (33%), limited for 43 (38%), and disputed for 2 (2%). Ninety genes were associated with autosomal recessive inheritance, 16 were maternally inherited, 5 were autosomal dominant, and 3 were X-linked. INTERPRETATION: GDRs for LSS were established for genes across both nuclear and mitochondrial genomes. Establishing these GDRs will allow accurate variant interpretation, expedite genetic diagnosis of LSS, and facilitate precision medicine, multisystem organ surveillance, recurrence risk counseling, reproductive choice, natural history studies, and determination of eligibility for interventional clinical trials. ANN NEUROL 2023;94:696-712.
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Enfermedad de Leigh , Enfermedades Mitocondriales , Niño , Humanos , Enfermedad de Leigh/diagnóstico , Enfermedad de Leigh/genética , MitocondriasRESUMEN
Aphids are important herbivorous insects that can cause significant crop damage, leading to yield reduction and economic loss. One avenue being explored to reduce aphid impacts is the development of aphid-resistant plants. Under projected climate scenarios, it is expected that plants will be exposed to greater biotic and abiotic stress, including increased herbivorous insect infestation and exposure to prolonged periods of environmental stress, particularly drought. In response to these projections, plant-aphid interactions under drought conditions have been a subject of growing interest; however, few studies have looked at the impact of drought stress on plant resistance to aphids despite the potential importance for plant breeding. Here, we examine the latest scientific advances regarding variation in plant resistance to aphids under drought, emphasizing underlying mechanisms and functional trade-offs and propose a conceptual model relating plant tolerance to drought with plant resistance to aphids.
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Áfidos , Animales , Áfidos/fisiología , Sequías , Fitomejoramiento , Estrés Fisiológico , Herbivoria , PlantasRESUMEN
Among 9th-to 12th-grade students who completed an anonymous health risk and protective behavior survey (n = 2346), positive future orientation was significantly and inversely associated with multiple forms of interpersonal violence including youth, community, and sexual/relationship violence. Designing interventions to promote future orientation holds promise as a cross-cutting violence prevention strategy.
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Víctimas de Crimen/estadística & datos numéricos , Armas de Fuego/estadística & datos numéricos , Violencia de Pareja/estadística & datos numéricos , Delitos Sexuales/estadística & datos numéricos , Adolescente , Estudios Transversales/estadística & datos numéricos , Femenino , Humanos , Masculino , Conducta Sexual/estadística & datos numéricos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To establish the feasibility of a systematic, community health worker (CHW)-based hearing screening program that gathers Health Insurance Portability and Accountability Act-compliant electronic data (otoscopic images of tympanic membrane and audiometric evaluation) on a smartphone in an effort to streamline treatment options in resource-limited communities. METHODS: This is a cross-sectional study in which four schools were screened in Port-au-Prince, Haiti, during in April 2018. A total of 122 subjects (61% female) aged 5-17 years underwent an initial brief audiometric screen followed by a more comprehensive air conduction audiometric evaluation if they failed their initial screen. Participants with more than 35-dB loss in any frequency on their comprehensive audiometric evaluation received endoscopic otoscopy. RESULTS: Seventy-five percent of subjects (91/122) passed their initial screen. Of those who failed, 9% (4/44 ears) had a severe or profound hearing loss on comprehensive evaluation. Abnormal otoscopic findings (11/36 ears, 31%) included are cerumen impaction (n = 6), myringosclerosis (n = 3), tympanic membrane perforation (n = 1), and tympanic membrane retraction (n = 1). The average duration of the initial testing was 100 seconds (SD = 74 seconds), whereas the duration of comprehensive testing was 394 seconds (SD = 175 seconds). Extrapolating from these data, we estimate that a group of seven trained CHWs could gather formal audiologic and otologic data points for 100 children per hour using this protocol. CONCLUSIONS: A systematic approach that utilizes local resources (CHWs) and existing infrastructure (cell phones and the Internet) can significantly reduce the burden of hearing healthcare specialists while simultaneously facilitating early diagnosis and management of disabling hearing loss in low-resourced settings. LEVEL OF EVIDENCE: Level 4.
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When introduced into a naïve population, chikungunya virus generally spreads rapidly, causing large outbreaks of fever and severe polyarthralgia. We randomly selected households in the U.S. Virgin Islands (USVI) to estimate seroprevalence and symptomatic attack rate for chikungunya virus infection at approximately 1 year following the introduction of the virus. Eligible household members were administered a questionnaire and tested for chikungunya virus antibodies. Estimated proportions were calibrated to age and gender of the population. We enrolled 509 participants. The weighted infection rate was 31% (95% confidence interval [CI]: 26-36%). Among those with evidence of chikungunya virus infection, 72% (95% CI: 65-80%) reported symptomatic illness and 31% (95% CI: 23-38%) reported joint pain at least once per week approximately 1 year following the introduction of the virus to USVI. Comparing rates from infected and noninfected study participants, 70% (95% CI: 62-79%) of fever and polyarthralgia and 23% (95% CI: 9-37%) of continuing joint pain in patients infected with chikungunya virus were due to their infection. Overall, an estimated 43% (95% CI: 33-52%) of the febrile illness and polyarthralgia in the USVI population during the outbreak was attributable to chikungunya virus and only 12% (95% CI: 7-17%) of longer term joint pains were attributed to chikungunya virus. Although the rates of infection, symptomatic disease, and longer term joint symptoms identified in USVI are similar to other outbreaks of the disease, a lower proportion of acute fever and joint pain was found to be attributable to chikungunya virus.
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Anticuerpos Antivirales/sangre , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/inmunología , Virus Chikungunya/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Artralgia/epidemiología , Artralgia/virología , Virus Chikungunya/aislamiento & purificación , Niño , Preescolar , Brotes de Enfermedades , Composición Familiar , Femenino , Fiebre/epidemiología , Fiebre/virología , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Encuestas y Cuestionarios , Islas Virgenes de los Estados Unidos/epidemiología , Adulto JovenRESUMEN
Cross-reactivity within flavivirus antibody assays, produced by shared epitopes in the envelope proteins, can complicate the serological diagnosis of Zika virus (ZIKAV) infection. We assessed the utility of the plaque reduction neutralization test (PRNT) to confirm recent ZIKAV infections and rule out misleading positive immunoglobulin M (IgM) results in areas with various levels of past dengue virus (DENV) infection incidence. We reviewed PRNT results of sera collected for diagnosis of ZIKAV infection from 1 January through 31 August 2016 with positive ZIKAV IgM results, and ZIKAV and DENV PRNTs were performed. PRNT result interpretations included ZIKAV, unspecified flavivirus, DENV infection, or negative. For this analysis, ZIKAV IgM was considered false positive for samples interpreted as a DENV infection or negative. In U.S. states, 208 (27%) of 759 IgM-positive results were confirmed to be ZIKAV compared to 11 (21%) of 52 in the U.S. Virgin Islands (USVI), 15 (15%) of 103 in American Samoa, and 13 (11%) of 123 in Puerto Rico. In American Samoa and Puerto Rico, more than 80% of IgM-positive results were unspecified flavivirus infections. The false-positivity rate was 27% in U.S. states, 18% in the USVI, 2% in American Samoa, and 6% in Puerto Rico. In U.S. states, the PRNT provided a virus-specific diagnosis or ruled out infection in the majority of IgM-positive samples. Almost a third of ZIKAV IgM-positive results were not confirmed; therefore, providers and patients must understand that IgM results are preliminary. In territories with historically higher rates of DENV transmission, the PRNT usually could not differentiate between ZIKAV and DENV infections.
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Anticuerpos Antivirales/sangre , Virus del Dengue/inmunología , Dengue/epidemiología , Inmunoglobulina M/sangre , Infección por el Virus Zika/diagnóstico , Virus Zika/inmunología , Samoa Americana/epidemiología , Reacciones Cruzadas , Reacciones Falso Positivas , Femenino , Flavivirus/inmunología , Humanos , Incidencia , Masculino , Pruebas de Neutralización , Puerto Rico/epidemiología , Estados Unidos/epidemiología , Islas Virgenes de los Estados Unidos/epidemiología , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/virologíaRESUMEN
OBJECTIVE: To differentiate exposure to the newly introduced chikungunya virus from exposure to endemic dengue virus and other pathogens in Haiti. METHODS: We used a multiplex bead assay to detect immunoglobulin G (IgG) responses to a recombinant chikungunya virus antigen, two dengue virus-like particles and three recombinant Plasmodium falciparum antigens. Most (217) of the blood samples investigated were collected longitudinally, from each of 61 children, between 2011 and 2014 but another 127 were collected from a cross-sectional sample of children in 2014. FINDINGS: Of the samples from the longitudinal cohort, none of the 153 collected between 2011 and 2013 but 78.7% (48/61) of those collected in 2014 were positive for IgG responses to the chikungunya virus antigen. In the cross-sectional sample, such responses were detected in 96 (75.6%) of the children and occurred at similar prevalence across all age groups. In the same sample, responses to malarial antigen were only detected in eight children (6.3%) but the prevalence of IgG responses to dengue virus antigens was 60.6% (77/127) overall and increased steadily with age. Spatial analysis indicated that the prevalence of IgG responses to the chikungunya virus and one of the dengue virus-like particles decreased as the sampling site moved away from the city of Léogâne and towards the ocean. CONCLUSION: Serological evidence indicates that there had been a rapid and intense dissemination of chikungunya virus in Haiti. The multiplex bead assay appears to be an appropriate serological platform to monitor the seroprevalence of multiple pathogens simultaneously.
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Fiebre Chikungunya , Dengue , Exposición a Riesgos Ambientales , Malaria , Adolescente , Fiebre Chikungunya/diagnóstico , Fiebre Chikungunya/epidemiología , Virus Chikungunya/aislamiento & purificación , Niño , Preescolar , Estudios Transversales , Dengue/diagnóstico , Dengue/epidemiología , Exposición a Riesgos Ambientales/estadística & datos numéricos , Femenino , Haití/epidemiología , Humanos , Estudios Longitudinales , Malaria/diagnóstico , Malaria/epidemiología , Masculino , Plasmodium falciparum/aislamiento & purificaciónRESUMEN
PURPOSE: To describe the clinical signs of gelatinous drop-like corneal dystrophy (GDLD) in a consanguineous Colombian family and determine the underlying genetic cause. METHODS: We performed ocular examination of available family members and bidirectionally Sanger sequenced the GDLD-associated gene, TACSTD2. In one individual, the presence of subepithelial amyloid was confirmed with biopsy. RESULTS: The parents were consanguineous and 5 of their 10 children had GDLD. Typical mulberry subepithelial deposits with subepithelial vascularization were present in 3 individuals; 2 individuals only had mild polymorphic anterior stromal opacity. We identified a homozygous TACSTD2 missense mutation, c.551A>G, p.(Tyr184Cys), in the affected family members. Both parents were heterozygous for the mutation, and unaffected siblings were either heterozygous or homozygous wild-type for this allele. In the Colombian population, this mutation has a minor allele frequency of 0.53%. CONCLUSION: The clinical presentation of GDLD in this family was variable and does not solely support an age-dependent progression of the phenotype, suggesting that environmental or other genetic factors can modify phenotypic expression. The relatively high prevalence of this mutation in the Colombian population suggests that other individuals may have undiagnosed subclinical disease.
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Amiloidosis Familiar/genética , Antígenos de Neoplasias/genética , Moléculas de Adhesión Celular/genética , Distrofias Hereditarias de la Córnea/diagnóstico , Distrofias Hereditarias de la Córnea/genética , Mutación Missense , Adolescente , Adulto , Amiloidosis Familiar/diagnóstico , Amiloidosis Familiar/etnología , Niño , Preescolar , Colombia/epidemiología , Consanguinidad , Distrofias Hereditarias de la Córnea/etnología , Exones/genética , Femenino , Frecuencia de los Genes , Humanos , Masculino , Linaje , Reacción en Cadena de la Polimerasa , Adulto JovenRESUMEN
We used population genetics to assess historical and modern demography of the exploited wavy top snail, Megastraea undosa, which has a 5-10 day pelagic larval duration. Foot tissue was sampled from an average of 51 individuals at 17 sites across the range of M. undosa. Genetic structure at the mtDNA locus is strikingly high (ΦST of 0.19 across 1000 km), and a major cline occurs in northern Baja California (ΦCT of 0.29 between northern and southern populations). Genetic data indicate that the northern region is highly connected through larval dispersal, whereas the southern region exhibits low genetic structure. However, additional analyses based on patterns of haplotype diversity and relationships among haplotypes indicate that M. undosa has likely recently expanded into the Southern California Bight or expanded from a small refugial population, and analysis using isolation by distance to calculate dispersal distance indicates surprisingly short estimates of dispersal from 30 m to 3 km. This scenario of a northward expansion and limited larval dispersal is supported by coalescent-based simulations of genetic data. The different patterns of genetic variation between northern and southern populations are likely artifacts of evolutionary history rather than differences in larval dispersal and this may have applications to management of this species. Specifically, these data can help to inform the scale at which this species should be managed, and given the potentially very small dispersal distances, this species should be managed at local scales. Consideration of the evolutionary history of target species allows for a more accurate interpretation of genetic data for management.
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Genética de Población , Caracoles/genética , Animales , California , ADN Mitocondrial/genética , Complejo IV de Transporte de Electrones/genética , Variación Genética , Haplotipos , Larva/genética , México , Dinámica PoblacionalRESUMEN
Expansion of cropland in tropical countries is one of the principal causes of biodiversity loss, and threatens to undermine progress towards meeting the Aichi Biodiversity Targets. To understand this threat better, we analysed data on crop distribution and expansion in 128 tropical countries, assessed changes in area of the main crops and mapped overlaps between conservation priorities and cultivation potential. Rice was the single crop grown over the largest area, especially in tropical forest biomes. Cropland in tropical countries expanded by c. 48,000 km(2) per year from 1999-2008. The countries which added the greatest area of new cropland were Nigeria, Indonesia, Ethiopia, Sudan and Brazil. Soybeans and maize are the crops which expanded most in absolute area. Other crops with large increases included rice, sorghum, oil palm, beans, sugar cane, cow peas, wheat and cassava. Areas of high cultivation potential-while bearing in mind that political and socio-economic conditions can be as influential as biophysical ones-may be vulnerable to conversion in the future. These include some priority areas for biodiversity conservation in tropical countries (e.g., Frontier Forests and High Biodiversity Wilderness Areas), which have previously been identified as having 'low vulnerability', in particular in central Africa and northern Australia. There are also many other smaller areas which are important for biodiversity and which have high cultivation potential (e.g., in the fringes of the Amazon basin, in the Paraguayan Chaco, and in the savanna woodlands of the Sahel and East Africa). We highlight the urgent need for more effective sustainability standards and policies addressing both production and consumption of tropical commodities, including robust land-use planning in agricultural frontiers, establishment of new protected areas or REDD+ projects in places agriculture has not yet reached, and reduction or elimination of incentives for land-demanding bioenergy feedstocks.
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Agricultura/métodos , Conservación de los Recursos Naturales/métodos , Productos Agrícolas/crecimiento & desarrollo , Clima Tropical , Agricultura/estadística & datos numéricos , Agricultura/tendencias , Biodiversidad , Brasil , Conservación de los Recursos Naturales/estadística & datos numéricos , Conservación de los Recursos Naturales/tendencias , Etiopía , Abastecimiento de Alimentos/estadística & datos numéricos , Geografía , Indonesia , Nigeria , Sudán , Árboles/crecimiento & desarrolloRESUMEN
The divergence-with-gene-flow model of speciation has a strong theoretical basis with a growing number of plausible examples in nature, but remains hotly debated. Darwin's finches of the Galápagos Archipelago have played an important role in our understanding of speciation processes. Recent studies suggest that this group may also provide insights into speciation via divergence with gene flow. On the island of Santa Cruz, recent studies found evidence for adaptive divergence in Darwin's small ground finch, Geospiza fuliginosa, between ecologically contrasting arid and humid zones. Despite the short geographical distance between these zones, strong disruptive selection during low rainfall periods is expected to generate and maintain adaptive divergence. Conversely, during high rainfall periods, when disruptive selection is predicted to be weakened, population divergence in adaptive traits is expected to break down. Because periods of low and high rainfall irregularly alternate, the geographical pattern of adaptive divergence can be assumed to break down and, importantly, regenerate in situ. Here, we use microsatellite allele frequency data to assess the genetic population structure of G. fuliginosa on Santa Cruz. We sample 21 sites and four ecological zones across the island. We reject hypotheses of population substructure linked to ecological and geographical differences among sites in favour of a single panmictic population. Panmixia implies high levels of gene flow within Santa Cruz, which favours selection over genetic drift as a valid process generating phenotypic divergence in G. fuliginosa on Santa Cruz. We discuss how our findings may support classic adaptation, phenotypic plasticity, matching habitat choice or any combination of these three processes.
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Pinzones/genética , Flujo Génico , Frecuencia de los Genes , Especiación Genética , Repeticiones de Microsatélite/genética , Animales , Ecosistema , Ecuador , Ambiente , Variación Genética , GeografíaRESUMEN
PURPOSE: Partial Epilepsy with Pericentral Spikes (PEPS) is a novel Mendelian idiopathic epilepsy with evidence of linkage to Chromosome 4p15. Our aim was to identify the causative mutation in this epilepsy syndrome. METHODS: We re-annotated all 42 genes in the linked chromosomal region and sequenced all genes within the linked interval. All exons, intron-exon boundaries and untranslated regions were sequenced in the original pedigree, and novel changes segregating correctly were subjected to bioinformatic analysis. Quantitative polymerase chain reaction was performed to examine for potential copy number variation (CNV). RESULTS: 29 previously undescribed variants correctly segregating with the linked haplotype were identified. Bioinformatic analysis demonstrated that six variants were non-synonymous coding sequence polymorphisms, one of which, in Q8IYL2 (Gly400Ala), was found in neither Caucasian (n=243) and ancestry-matched Brazilian (n=180) control samples, nor subjects from the 1000 Genome Project. No gene duplications or deletions were identified in the linked region. DISCUSSION: We postulate that Q8IYL2 is a causative gene for PEPS, after exhaustive resequencing and bioinformatic analysis. The function of this gene is unknown, but it is expressed in brain tissue.
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Variaciones en el Número de Copia de ADN , Epilepsias Parciales/genética , Salud de la Familia , Metiltransferasas/genética , Linaje , Alanina/genética , Brasil , Biología Computacional/métodos , Femenino , Ligamiento Genético , Genotipo , Glicina/genética , Humanos , MasculinoRESUMEN
Neurons are a diverse cell type exhibiting hugely different morphologies and neurotransmitter specifications. Their distinctive phenotypes are established during differentiation from pluripotent precursor cells. The signalling pathways that specify the lineage down which neuronal precursor cells differentiate remain to be fully elucidated. Among the many signals that impinge on the differentiation of neuronal cells, cytosolic calcium (Ca2+) has an important role. However, little is known about the nature of the Ca2+ signals involved in fate choice in neuronal precursor cells, or their sources. In this study, we show that activation of either muscarinic or platelet-derived growth factor (PDGF) receptors induces a biphasic increase in cytosolic Ca2+ that consists of release from intracellular stores followed by sustained entry across the plasma membrane. For both agonists, the prolonged Ca2+ entry occurred via a store-operated pathway that was pharmacologically indistinguishable from Ca2+ entry initiated by thapsigargin. However, muscarinic receptor-activated Ca2+ entry was inhibited by siRNA-mediated knockdown of TRPC6, whereas Ca2+ entry evoked by PDGF was not. These data provide evidence for agonist-specific activation of molecularly distinct store-operated Ca2+ entry pathways, and raise the possibility of privileged communication between these Ca2+ entry pathways and downstream processes.
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Canales de Calcio/efectos de los fármacos , Cloruro de Metacolina/farmacología , Agonistas Muscarínicos/farmacología , Neuronas/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/farmacología , Canales de Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Células Cultivadas , Humanos , Immunoblotting , Neuronas/citología , Neuronas/metabolismo , Factores de TiempoRESUMEN
Low-symmetry distortions are present in cubanes such as Fe(4)S(4), but their effects on electron delocalization properties are not well-understood. Mixed-valence cubanes often exhibit experimentally measurable "pair delocalization" of a delocalizable electron. An important question is, what is the role of physical interactions (vibronic, electronic, exchange) and symmetry distortions in determining the electron delocalization pattern? Semiclassical models are used to explore the electron delocalization patterns of S=1/2 tetragonally (D(2d)) distorted mixed-valence cubanes comprising four metal centers with bridging ligands, a single delocalizable "excess" electron, and either closed-shell or open-shell ion cores. Phase diagrams show that distorted S=1/2 ground state cubanes with antiferromagnetic exchange (as found in nature) have delocalization patterns qualitatively similar to those of an S=1/2 model with no Heisenberg exchange, suggesting that exchange is not necessarily a dominant factor in determining electron delocalization properties. The open-shell model reveals two types of pair delocalization for the S=1/2 ground state, with differing dimer subunit spins for compressed and elongated geometries. Previous studies emphasize the importance of exchange interactions for pair delocalization. Here, it is shown that electron exchange is not always necessary for pair delocalization and that it can be achieved with relatively small tetragonal distortions from tetrahedral (T(d)) symmetry. The results contradict those of an earlier theoretical study of distorted Fe(4)S(4) clusters, which concluded that distortions of lower symmetry than D(2d) are necessary to induce a transition to pair delocalization.
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Hidrocarburos Aromáticos con Puentes/química , Electrones , Modelos Moleculares , Ligandos , Magnetismo , Propiedades de SuperficieRESUMEN
Neurons are a diverse cell type exhibiting hugely different morphologies and neurotransmitter specifications. Their distinctive phenotypes are established during differentiation from pluripotent precursor cells. The signalling pathways that specify the lineage down which neuronal precursor cells differentiate remain to be fully elucidated. Among the many signáis that impinge on the differentiation of neuronal cells, cytosolic calcium (Ca2+) has an important role. However, little is known about the nature of the Ca2+ signáis involved in fate choice in neuronal precursor cells, or their sources. In this study, we show that activation of either muscarinic or platelet-derived growth factor (PDGF) receptors induces a biphasic increase in cytosolic Ca2+ that consists of reléase from intracellular stores followed by sustained entry across the plasma membrane. For both agonists, the prolonged Ca2+ entry occurred via a store-operated pathway that was pharmacologically indistinguishable from Ca2+ entry initiated by thapsigargin. However, muscarinic receptor-activated Ca2+ entry was inhibited by siRNA-mediated knockdown of TRPC6, whereas Ca2+ entry evoked by PDGF was not. These data provide evidence for agonist-specific activation of molecularly distinct store-operated Ca2+ entry pathways, and raise the possibility of privileged communication between these Ca2+ entry pathways and downstream processes.
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Humanos , Canales de Calcio/efectos de los fármacos , Cloruro de Metacolina/farmacología , Agonistas Muscarínicos/farmacología , Neuronas/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/farmacología , Células Cultivadas , Canales de Calcio/metabolismo , Señalización del Calcio/efectos de los fármacos , Immunoblotting , Neuronas/citología , Neuronas/metabolismo , Factores de TiempoRESUMEN
Many species vary in their ecology across their geographic ranges in response to gradients in environmental conditions. Such variation, which can influence life history traits and subsequent demography of populations, usually occurs over large spatial scales. However, describing and understanding the causes of such variation is difficult precisely because it occurs over such large spatial scales. In this study, we document spatial variation in the ecology of a common reef fish, Stegastes beebei, in the Galápagos Islands and test a number of potential causal mechanisms. The pattern resembles that seen in latitudinal variation: individuals are larger, occur in higher densities, and live longer in the coldest region of the islands than those in the warmest region. However, in this system, demography varies among regional populations separated by <150 km. Preferred nutritious algae are more available in the cold region and comprise a greater proportion of the diet of fish in this region. Per gram reproductive effort appears to be strongly related to temperature, despite differences in the gross magnitude and timing of reproduction in different regions. A model of reproductive output suggests that fish in the warmest region are allocating a greater proportion of available energy to reproduction, resulting in apparent regional life history tradeoffs. Our data suggest that regional demographic differences in S. beebei may be driven by a combination of variation in food availability and an environmentally mediated life history tradeoff.
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Ambiente , Perciformes/fisiología , Densidad de Población , Reproducción/fisiología , Animales , Tamaño Corporal , Ecuador , Observación , Análisis de Regresión , TemperaturaRESUMEN
The complex tetracyclic carbon skeleton of colombiasin A is conveniently accessed through an enantioselective intermolecular Diels-Alder-sulfoxide elimination-intramolecular Diels-Alder (DA-E-IMDA) sequence.