Richard J. Smith  Joy S. Singarayer  Francis E. Mayle 《Global Change Biology》2022,28(1):201-226

There is a major concern for the fate of Amazonia over the coming century in the face of anthropogenic climate change. A key area of uncertainty is the scale of rainforest dieback to be expected under a future, drier climate. In this study, we use the middle Holocene (ca. 6000 years before present) as an approximate analogue for a drier future, given that palaeoclimate data show much of Amazonia was significantly drier than present at this time. Here, we use an ensemble of climate and vegetation models to explore the sensitivity of Amazonian biomes to mid-Holocene climate change. For this, we employ three dynamic vegetation models (JULES, IBIS, and SDGVM) forced by the bias-corrected mid-Holocene climate simulations from seven models that participated in the Palaeoclimate Modelling Intercomparison Project 3 (PMIP3). These model outputs are compared with a multi-proxy palaeoecological dataset to gain a better understanding of where in Amazonia we have most confidence in the mid-Holocene vegetation simulations. A robust feature of all simulations and palaeodata is that the central Amazonian rainforest biome is unaffected by mid-Holocene drought. Greater divergence in mid-Holocene simulations exists in ecotonal eastern and southern Amazonia. Vegetation models driven with climate models that simulate a drier mid-Holocene (100–150 mm per year decrease) better capture the observed (palaeodata) tropical forest dieback in these areas. Based on the relationship between simulated rainfall decrease and vegetation change, we find indications that in southern Amazonia the rate of tropical forest dieback was ~125,000 km² per 100 mm rainfall decrease in the mid-Holocene. This provides a baseline sensitivity of tropical forests to drought for this region (without human-driven changes to greenhouse gases, fire, and deforestation). We highlight the need for more palaeoecological and palaeoclimate data across lowland Amazonia to constrain model responses.  相似文献   

    

Hideaki Milton Arai  Alberto JS Duarte  Valéria Maria Natale 《Immunity & ageing : I & A》2006,3(1):9-7

Background  

a decline in immune and endocrine function occurs with aging. The main purpose of this study was to investigate the impact of long-term endurance training on the immune and endocrine system of elderly men. The possible interaction between these systems was also analysed.  相似文献   

  总被引：8，自引：0，他引：8  

Delarbre  C; Kashi  Y; Boursot  P; Beckmann  JS; Kourilsky  P; Bonhomme  F; Gachelin  G 《Molecular biology and evolution》1988,5(2):120-133

We have examined the phylogenetic distribution of two t-specific markersamong representatives of various taxa belonging to the genus Mus. Thecentromeric TCP-1a marker (a testicular protein variant specific for allt-haplotypes so far studied) has also been apparently detected in severalnon-t representatives of the Mus IVA, Mus IVB, and probably M. cervicolorspecies. By contrast, a t-specific restriction- fragment-lengthpolymorphism allele (RFLP) of the telomeric alpha- globin pseudogene DNAmarker alpha-psi-4 was found only in animals belonging to the M.musculus-complex species either bearing genuine t- haplotypes or, like theM. m. bactrianus specimen studied here, likely to do so. This t-specificalpha-psi-4 RFLP allele was found to be as divergent from the RFLP allelesof the latter, non-t, taxonomical groups as it is from Mus 4A, Mus 4B, orM. spretus ones. These results suggest the presence of t-haplotypes and oft-specific markers in populations other than those belonging to the M. m.domesticus and M. m. musculus subspecies, implying a possible origin fort-haplotypes prior to the radiation of the most recent offshoot of the Musgenus (i.e., the spretus/domesticus divergence), some 1-3 Myr ago.  相似文献   

    

JK MELICHAR  JS MYLES  CB EAP  DJ NUTT 《Addiction biology》2003,8(1):59-66

Substitute methadone prescribing is one of the main modes of treatment for opiate dependence. This study examined the relationship between methadone dose (measured by daily dose and methadone's active (R)‐enantiomer blood levels) and opiate receptor function. Nine subjects on substitute methadone (30‐90 mg daily) received three subcutaneous injections 1.5 hours apart (saline, 5 mg and 10 mg hydromorphone, a short‐acting opiate agonist) followed by measures of functional response in particular saccadic eye movements (SEMs), as well as self‐report measures. Ten mg of hydromorphone significantly slowed SEM parameters (peak velocity by 15%, p <0.005; peak acceleration by 20%, p <0.025; peak deceleration by 26%, p <0.025) and the SEM velocity changes correlated significantly with (R)‐methadone levels (r =0.844, p <0.005) and with the oral dose of methadone being taken (r =0.829, p <0.005). Although a similar trend was observed for 5 mg, this was not significant. These finding suggest that, at higher methadone doses (resulting in higher plasma concentrations), there is significant tolerance to the action of agonists. Such studies may help in refining our understanding of the actions of methadone and the SEM measure could help in defining the degree of tolerance in individuals using street heroin.  相似文献   

  总被引：3，自引：1，他引：3  

Rush  JS; van Leyen  K; Ouerfelli  O; Wolucka  B; Waechter  CJ 《Glycobiology》1998,8(12):1195-1205

The results described in the accompanying article support the model inwhich glucosylphosphoryldolichol (Glc-P-Dol) is synthesized on thecytoplasmic face of the ER, and functions as a glucosyl donor for threeGlc-P-Dol:Glc0-2Man9-GlcNAc2-P-P-Dol glucosyltransferases (GlcTases) in thelumenal compartment. In this study, the enzymatic synthesis and structuralcharacterization by NMR and electrospray-ionization tandem massspectrometry of a series of water-soluble beta-Glc-P-Dol analogs containing2-4 isoprene units with either the cis - or trans - stereoconfiguration inthe beta-position are described. The water- soluble analogs were (1) usedto examine the stereospecificity of the Glc-P-Dol:Glc0-2Man9GlcNAc2-P-P-Dolglucosyltransferases (GlcTases) and (2) tested as potential substrates fora membrane protein(s) mediating the transbilayer movement of Glc-P-Dol insealed ER vesicles from rat liver and pig brain. The Glc-P-Dol-mediatedGlcTases in pig brain microsomes utilized [3H]Glc-labeled Glc-P-Dol10,Glc-P-(omega, c )Dol15, Glc-P(omega, t,t )Dol20, and Glc-P-(omega, t,c)Dol20as glucosyl donors with [3H]Glc3Man9GlcNAc2-P-P-Dol the major productlabeled in vitro. A preference was exhibited for C15-20 substratescontaining an internal cis -isoprene unit in the beta-position. Inaddition, the water-soluble analog, Glc-P-Dol10, was shown to enter thelumenal compartment of sealed microsomal vesicles from rat liver and pigbrain via a protein-mediated transport system enriched in the ER. Theproperties of the ER transport system have been characterized. Glc-P-Dol10was not transported into or adsorbed by synthetic PC-liposomes orbovine erythrocytes. The results of these studies indicate that (1) theinternal cis -isoprene units are important for the utilization of Glc-P-Dolas a glucosyl donor and (2) the transport of the water- soluble analog mayprovide an experimental approach to assay the hypothetical \"flippase\"proposed to mediate the transbilayer movement of Glc-P-Dol from thecytoplasmic face of the ER to the lumenal monolayer.  相似文献   

    

Suki MY Lee  Renee WY Chan  Jennifer L Gardy  Cheuk-kin Lo  Alan DL Sihoe  Sara SR Kang  Timothy KW Cheung  Yi Guan  Michael CW Chan  Robert EW Hancock  Malik JS Peiris 《Respiratory research》2010,11(1):147

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Keri Dame  Alexandre JS Ribeiro 《Experimental biology and medicine (Maywood, N.J.)》2021,246(3):317

Hepatic and cardiac drug adverse effects are among the leading causes of attrition in drug development programs, in part due to predictive failures of current animal or in vitro models. Hepatocytes and cardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs) hold promise for predicting clinical drug effects, given their human-specific properties and their ability to harbor genetically determined characteristics that underlie inter-individual variations in drug response. Currently, the fetal-like properties and heterogeneity of hepatocytes and cardiomyocytes differentiated from iPSCs make them physiologically different from their counterparts isolated from primary tissues and limit their use for predicting clinical drug effects. To address this hurdle, there have been ongoing advances in differentiation and maturation protocols to improve the quality and use of iPSC-differentiated lineages. Among these are in vitro hepatic and cardiac cellular microsystems that can further enhance the physiology of cultured cells, can be used to better predict drug adverse effects, and investigate drug metabolism, pharmacokinetics, and pharmacodynamics to facilitate successful drug development. In this article, we discuss how cellular microsystems can establish microenvironments for these applications and propose how they could be used for potentially controlling the differentiation of hepatocytes or cardiomyocytes. The physiological relevance of cells is enhanced in cellular microsystems by simulating properties of tissue microenvironments, such as structural dimensionality, media flow, microfluidic control of media composition, and co-cultures with interacting cell types. Recent studies demonstrated that these properties also affect iPSC differentiations and we further elaborate on how they could control differentiation efficiency in microengineered devices. In summary, we describe recent advances in the field of cellular microsystems that can control the differentiation and maturation of hepatocytes and cardiomyocytes for drug evaluation. We also propose how future research with iPSCs within engineered microenvironments could enable their differentiation for scalable evaluations of drug effects.  相似文献   

    

Michael CW Chan  Renee WY Chan  Wendy CL Yu  Carol CC Ho  WH Chui  CK Lo  Kit M Yuen  Yi Guan  John M Nicholls  JS Malik Peiris 《Respiratory research》2009,10(1):102

Background

Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease.

Aim

To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease.

Methods

We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces.

Results

We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium.

Conclusion

The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease.  相似文献   

    

Erin E. Saupe  Corinne E. Myers  A. Townsend Peterson  Jorge Sobern  Joy Singarayer  Paul Valdes  Huijie Qiao 《Global Ecology and Biogeography》2019,28(7):928-942

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Singarayer K. Florentine  Catherine L. Pohlman  Martin E. Westbrooke 《Restoration Ecology》2016,24(3):364-372

A long‐term rainforest restoration experiment was established on abandoned pasture in northeastern Queensland in 1993 to examine the effectiveness of five different restoration planting methods: (T1) control (no plantings); (T2) pioneer monoculture (planting seedlings of one pioneer species, Homalanthus novoguineensis, Euphorbiaceae); (T3) Homalanthus group framework method (H. novoguineensis and eight other pioneer species); (T4) Alphitonia group framework method (Alphitonia petriei, Rhamnaceae, with eight other pioneer species); and (T5) maximum diversity method (planting pioneers, middle‐phase species, and mature‐phase species). We investigated temporal patterns in the (1) fate of seedlings originally planted in 1993; (2) natural recruitment of native plant species; and (3) current habitat structure (canopy cover and ground cover of grasses and invasive plants) within each restoration treatment. A total of 97% of seedlings planted in T2 died within the first 13 years and all had died by 2014. A total of 72% of seedlings planted in T3, 55.5% of seedlings planted in T4, and 55% of seedlings planted in T5 also died by 2014. By 2014, 42 species from 21 families had recruited across the experimental site, and the abundance of recruits was almost twice that recorded in 2001 and 2006. Overall, T3, T4, and T5 had the greatest diversity and abundance of recruits. By 2014, canopy cover was greatest in T3, T4, and T5 but grass cover was least in T5. It is concluded that some restoration success measures increase with planting diversity, but overall the rate of recovery is similar in framework species and maximum diversity method.  相似文献