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1.
Int J Biometeorol ; 68(5): 871-882, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38311643

RESUMO

Phenological research in temperate-deciduous forests typically focuses on upper canopy trees, due to their overwhelming influence on ecosystem productivity and function. However, considering that shrubs leaf out earlier and remain green longer than trees, they play a pivotal role in ecosystem productivity, particularly at growing season extremes. Furthermore, an extended growing season of non-native shrubs provides a competitive advantage over natives. Here, we report spring phenology, budburst, leaf-out, and full-leaf unfolded (2017-2021) of a range of co-occurring species of tree (ash, American basswood, red oak, white oak, and boxelder) and shrub (native species: chokecherry, pagoda dogwood, nannyberry, American wild currant and Eastern wahoo, and non-native species: buckthorn, honeysuckle, European privet, and European highbush cranberry) in an urban woodland fragment in Wisconsin, USA, to determine how phenology differed between plant groups. Our findings show that all three spring phenophases of shrubs were 3 weeks earlier (p < 0.05) than trees. However, differences between shrubs groups were only significant for the later phenophase; full-leaf unfolded, which was 6 days earlier (p < 0.05) for native shrubs. The duration of the spring phenological season was 2 weeks longer (p < 0.05) for shrubs than trees. These preliminary findings demonstrate that native shrubs, at this site, start full-leaf development earlier than non-native species suggesting that species composition must be considered when generalizing whether phenologies differ between vegetation groups. A longer time series would be necessary to determine future implications on ecosystem phenology and productivity and how this might impact forests in the future, in terms of species composition, carbon sequestration, and overall ecosystem dynamics.


Assuntos
Estações do Ano , Árvores , Árvores/crescimento & desenvolvimento , Wisconsin , Folhas de Planta/crescimento & desenvolvimento , Espécies Introduzidas , Florestas , Cidades
2.
Int J Biometeorol ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714612

RESUMO

The timing and duration of autumn leaf phenology marks important transitions in temperate deciduous forests, such as, start of senescence, declining productivity and changing nutrient cycling. Phenological research on temperate deciduous forests typically focuses on upper canopy trees, overlooking the contribution of other plant functional groups like shrubs. Yet shrubs tend to remain green longer than trees, while non-native shrubs, in particular, tend to exhibit an extended growing season that confers a competitive advantage over native shrubs. We monitored leaf senescence and leaf fall (2017-2020) of trees and shrubs (native and non-native) in an urban woodland fragment in Wisconsin, USA. Our findings revealed that, the start of leaf senescence did not differ significantly between vegetation groups, but leaf fall started (DOY 273) two weeks later in shrubs. Non-native shrubs exhibited a considerably delayed start (DOY 262) and end of leaf senescence (DOY 300), with leaf-fall ending (DOY 315) nearly four weeks later than native shrubs and trees. Overall, the duration of the autumn phenological season was longer for non-native shrubs than either native shrubs or trees. Comparison of the timing of spring phenophases with the start and end of leaf senescence revealed that when spring phenology in trees starts later in the season senescence also starts later and ends earlier. The opposite pattern was observed in native shrubs. In conclusion, understanding the contributions of plant functional groups to overall forest phenology requires future investigation to ensure accurate predictions of future ecosystem productivity and help address discrepancies with remote sensing phenometrics.

3.
Int J Biometeorol ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38656350

RESUMO

The decision to establish a network of researchers centers on identifying shared research goals. Ecologically specific regions, such as the USA's National Ecological Observatory Network's (NEON's) eco-climatic domains, are ideal locations by which to assemble researchers with a diverse range of expertise but focused on the same set of ecological challenges. The recently established Great Lakes User Group (GLUG) is NEON's first domain specific ensemble of researchers, whose goal is to address scientific and technical issues specific to the Great Lakes Domain 5 (D05) by using NEON data to enable advancement of ecosystem science. Here, we report on GLUG's kick off workshop, which comprised lightning talks, keynote presentations, breakout brainstorming sessions and field site visits. Together, these activities created an environment to foster and strengthen GLUG and NEON user engagement. The tangible outcomes of the workshop exceeded initial expectations and include plans for (i) two journal articles (in addition to this one), (ii) two potential funding proposals, (iii) an assignable assets request and (iv) development of classroom activities using NEON datasets. The success of this 2.5-day event was due to a combination of factors, including establishment of clear objectives, adopting engaging activities and providing opportunities for active participation and inclusive collaboration with diverse participants. Given the success of this approach we encourage others, wanting to organize similar groups of researchers, to adopt the workshop framework presented here which will strengthen existing collaborations and foster new ones, together with raising greater awareness and promotion of use of NEON datasets. Establishing domain specific user groups will help bridge the scale gap between site level data collection and addressing regional and larger ecological challenges.

4.
Int J Biometeorol ; 65(3): 343-355, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31209600

RESUMO

Temperate deciduous shrub phenology plays a pivotal role in forest ecology by regulating the timing of suitable habitat and food of a range of organisms as well as influencing the timing and duration of the carbon uptake period especially in early spring and late autumn when trees are leafless. However, given the overwhelming influence of canopy trees on forest ecosystem functioning, shrubs are often ignored in ecosystem modeling. Isolating the shrub contribution to C flux or satellite-derived forest phenology is challenging. In addition, since shrubs are more likely to be invasive than trees, future changes to shrub species composition are likely, with consequent implications for both over- and understory species composition and ecosystem functioning. Surprisingly, given their multifaceted role, our review revealed that studies on temperate deciduous shrub phenology are limited with the majority focusing on managing invasive shrubs in USA forests. In addition, results of some studies using a large number of species from a range of geographical locations suggested that, in general, invasive shrubs leafed out earlier and retained leaves longer than native species. However, this may not be directly applicable to local conditions with a smaller range of locally adapted species. Therefore, in order to fully understand the role of shrub phenology in temperate deciduous forests, in terms of invasive species, response to climate change and subsequent influence on C balance it will be necessary to establish phenological monitoring sites in which both tree and shrub phenology are recorded concurrently across a range of geographical locations.


Assuntos
Ecossistema , Florestas , Mudança Climática , Folhas de Planta , Estações do Ano , Árvores
5.
Int J Biometeorol ; 64(5): 713-727, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32072321

RESUMO

Common approaches currently used to monitor forest phenology include direct field observation and indirect approaches such as satellite remote sensing and carbon flux measurements. However, differences in both temporal and spatial scales of these methods make direct comparison challenging. In order to evaluate the reliability of indirect measures of autumn phenology in estimating direct observations, we compared the timing of three transition dates and the rate of autumn progression derived from (i) satellite data (MOD13Q1 006 enhanced vegetation index (EVI) and normalized difference vegetation index (NDVI) products, 2000-2017), (ii) carbon flux measurements (net ecosystem exchange (NEE) and gross primary production (GPP), 1997-2016), and (iii) field observation (2010, 2012 for the north site and 2010, 2012, and 2013 for the south site) from a mixed forest in northern Wisconsin, USA. Overall, the transition dates and progression rates derived from NDVI were closest to that of field observations. Furthermore, the start of autumn derived from satellite data was earlier than directly observed leaf coloration (LC), which resulted from species-specific canopy senescence patterns and the sensitivity of the vegetation indices. Even after full leaf fall was reached, EVI continued to detect coloring which was likely due to the presence of understory plant species. Finally, NEE and GPP changes tended to start before LC as a result of tree physiological and environmental changes and continued after full leaf fall possibly due to understory and coniferous activity. These results highlight the need for long-term field observations of both trees and understory species, information on species-specific canopy senescence patterns, and species composition in understanding the efficiency of indirect approaches in estimating autumn forest phenology.


Assuntos
Ecossistema , Florestas , Carbono , Ciclo do Carbono , Folhas de Planta , Reprodutibilidade dos Testes , Estações do Ano , Árvores , Wisconsin
6.
Mol Cell ; 37(3): 333-43, 2010 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-20159553

RESUMO

Saccharomyces WEE1 (Swe1), the only "true" tyrosine kinase in budding yeast, is an Hsp90 client protein. Here we show that Swe1(Wee1) phosphorylates a conserved tyrosine residue (Y24 in yeast Hsp90 and Y38 in human Hsp90alpha) in the N domain of Hsp90. Phosphorylation is cell-cycle associated and modulates the ability of Hsp90 to chaperone a selected clientele, including v-Src and several other kinases. Nonphosphorylatable mutants have normal ATPase activity, support yeast viability, and productively chaperone the Hsp90 client glucocorticoid receptor. Deletion of SWE1 in yeast increases Hsp90 binding to its inhibitor geldanamycin, and pharmacologic inhibition/silencing of Wee1 sensitizes cancer cells to Hsp90 inhibitor-induced apoptosis. These findings demonstrate that Hsp90 chaperoning of distinct client proteins is differentially regulated by specific posttranslational modification of a unique subcellular pool of the chaperone, and they provide a strategy to increase the cellular potency of Hsp90 inhibitors.


Assuntos
Proteínas de Ciclo Celular/fisiologia , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas Tirosina Quinases/fisiologia , Proteínas de Saccharomyces cerevisiae/fisiologia , Tirosina/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Dimerização , Proteínas de Choque Térmico HSP90/fisiologia , Humanos , Proteínas Nucleares/antagonistas & inibidores , Proteínas Nucleares/genética , Proteínas Nucleares/fisiologia , Fosforilação , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteínas Tirosina Quinases/antagonistas & inibidores , Proteínas Tirosina Quinases/genética , Interferência de RNA , Proteínas de Saccharomyces cerevisiae/antagonistas & inibidores , Proteínas de Saccharomyces cerevisiae/genética , Ubiquitinação
7.
Int J Biometeorol ; 62(7): 1221-1228, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29532257

RESUMO

A national biodiversity and climate change adaptation plan is being developed for Ireland by the Department of Communications, Climate Action, and Environment. In order to inform such a plan, it was necessary to review and synthesize some of the recent literature pertaining to the impact of climate change on biodiversity in Ireland. Published research on this topic fell within three broad categories: (i) changes in the timing of life-cycle events (phenology) of plants, birds, and insects; (ii) changes in the geographic range of some bird species; and (iii) changes in the suitable climatic zones of key habitats and species. The synthesis revealed evidence of (i) a trend towards earlier spring activity of plants, birds, and insects which may result in a change in ecosystem function; (ii) an increase in the number of bird species; and (iii) both increases and decreases in the suitable climatic area of key habitats and species, all of which are expected to impact Ireland's future biodiversity. This process identified data gaps and limitations in available information both of which could be used to inform a focused research strategy. In addition, it raises awareness of the potential implications of climate change for biodiversity in Ireland and elsewhere and demonstrates the need for biodiversity conservation plans to factor climate change into future designs.


Assuntos
Biodiversidade , Mudança Climática , Animais , Aves , Ecossistema , Insetos , Irlanda
8.
Int J Biometeorol ; 61(Suppl 1): 29-50, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28527153

RESUMO

In recent decades, phenology has become an important tool by which to measure both the impact of climate change on ecosystems and the feedback of ecosystems to the climate system. However, there has been little attempt to date to systematically quantify the increase in the number of scientific publications with a focus on phenology and climate change. In order to partially address this issue, we examined the number of articles (original papers, reviews and short communications) containing the terms 'phenology' and 'climate change' in the title, abstract or keywords, published in the International Journal of Biometeorology in the 60 years since its inception in 1957. We manually inspected all issues prior to 1987 for the search terms and subsequently used the search facility on the Web of Science online database. The overall number of articles published per decade remained relatively constant (255-378) but rose rapidly to 1053 in the most recent decade (2007-2016), accompanied by an increase (41-172) in the number of articles containing the search terms. A number of factors may have contributed to this rise, including the recognition of the value of phenology as an indicator of climate change and the initiation in 2010 of a series of conferences focusing on phenology which subsequently led to two special issues of the journal. The word 'phenology' was in use from the first issue, whereas 'climate change' only emerged in 1987 and peaked in 2014. New technologies such as satellite remote sensing and the internet led to an expansion of and greater access to a growing reservoir of phenological information. The application of phenological data included determining the impact of warming of phenophases, predicting wine quality and the pollen season, demonstrating the potential for mismatch to occur and both reconstructing and forecasting climate. Even though this analysis was limited to one journal, it is likely to be indicative of a similar trend across other scientific publications.


Assuntos
Mudança Climática , Publicações Periódicas como Assunto/tendências , Estações do Ano , Animais , Meteorologia , Plantas
9.
Int J Biometeorol ; 60(10): 1563-1575, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26936843

RESUMO

Land surface phenology has been widely used to evaluate the effects of climate change on terrestrial ecosystems in recent decades. Climate warming on the Tibetan Plateau (1960-2010, 0.2 °C/decade) has been found to be greater than the global average (1951-2012, 0.12 °C/decade), which has had a significant impact on the timing of spring greenup. However, the magnitude and direction of change in spring phenology and its response to warming temperature and precipitation are currently under scientific debate. In an attempt to explore this issue further, we detected the onset of greenup based on the time series of daily two-band enhanced vegetation index (EVI2) from the advanced very high resolution radiometer (AVHRR) long-term data record (LTDR; 1982-1999) and Moderate Resolution Imaging Spectroradiometer (MODIS) Climate Modeling Grid (CMG; 2000-2013) using hybrid piecewise logistic models. Further, we examined the temporal trend in greenup onset in both individual pixels and ecoregions across the entire Tibetan Plateau over the following periods: 1982-1999, 2000-2013, and 1982-2013. The interannual variation in greenup onset was linked to the mean temperature and cumulative precipitation in the preceding month, and total precipitation during winter and spring, respectively. Finally, we investigated the relationship between interannual variation in greenup onset dates and temperature and precipitation from 1982 to 2013 at different elevational zones for different ecoregions. The results revealed no significant trend in the onset of greenup from 1982 to 2013 in more than 86 % of the Tibetan Plateau. For each study period, statistically significant earlier greenup trends were observed mainly in the eastern meadow regions while later greenup trends mainly occurred in the southwestern steppe and meadow regions both with areal coverage of less than 8 %. Although spring phenology was negatively correlated with spring temperature and precipitation in the majority of pixels (>60 %), only 15 % and 10 % of these correlations were significant (P < 0.1), respectively. Climate variables had varying effects on the ecoregions with altitude. In the meadow ecoregion, greenup onset was significantly affected by both temperature and precipitation from 3500 to 4000 m altitude and by temperature alone from 4000 to 4500 m. In contrast, greenup onset across all elevational zones, in the steppe ecoregion, was not directly driven by either spring temperature or precipitation, which was likely impacted by soil moisture associated with warming temperature. These findings highlight the complex impacts of climate change on spring phenology in the Tibetan Plateau.


Assuntos
Mudança Climática , Desenvolvimento Vegetal , Estações do Ano , Imagens de Satélites , Neve , Temperatura , Tibet
10.
Int J Biometeorol ; 60(3): 335-49, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26219605

RESUMO

It is important to accurately determine the response of spring and autumn phenology to climate change in forest ecosystems, as phenological variations affect carbon balance, forest productivity, and biodiversity. We observed phenology intensively throughout spring and autumn in a temperate deciduous woodlot at Milwaukee, WI, USA, during 2007-2012. Twenty-four phenophase levels in spring and eight in autumn were recorded for 106 trees, including white ash, basswood, white oak, boxelder, red oak, and hophornbeam. Our phenological progression models revealed that accumulated degree-days and day length explained 87.9-93.4 % of the variation in spring canopy development and 75.8-89.1 % of the variation in autumn senescence. In addition, the timing of community-level spring and autumn phenophases and the length of the growing season from 1871 to 2012 were reconstructed with the models developed. All simulated spring phenophases significantly advanced at a rate from 0.24 to 0.48 days/decade (p ≤ 0.001) during the 1871-2012 period and from 1.58 to 2.00 days/decade (p < 0.02) during the 1970-2012 period; two simulated autumn phenophases were significantly delayed at a rate of 0.37 (mid-leaf coloration) and 0.50 (full-leaf coloration) days/decade (p < 0.01) during the 1970-2012 period. Consequently, the simulated growing season lengthened at a rate of 0.45 and 2.50 days/decade (p < =0.001), respectively, during the two periods. Our results further showed the variability of responses to climate between early and late spring phenophases, as well as between leaf coloration and leaf fall, and suggested accelerating simulated ecosystem responses to climate warming over the last four decades in comparison to the past 142 years.


Assuntos
Modelos Teóricos , Estações do Ano , Árvores/crescimento & desenvolvimento , Clima , Magnoliopsida/crescimento & desenvolvimento , Temperatura , Wisconsin
11.
Int J Biometeorol ; 59(8): 1007-17, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25380974

RESUMO

Effective ecosystem functioning relies on successful species interaction. However, this delicate balance may be disrupted if species do not respond to environmental change at a similar rate. Here we examine trends in the timing of spring phenophases of groups of species occupying three trophic levels as a potential indicator of ecosystem response to climate warming in Ireland. The data sets were of varying length (1976-2009) and from varying locations: (1) timing of leaf unfolding and May Shoot of a range of broadleaf and conifer tree species, (2) first appearance dates of a range of moth species, and (3) first arrival dates of a range of spring migrant birds. All three groups revealed a statistically significant (P<0.01 and P<0.001) advance in spring phenology that was driven by rising spring temperature (P<0.05; 0.45 °C /decade). However, the rate of advance was greater for moths (1.8 days/year), followed by birds (0.37 days/year) and trees (0.29 days/year). In addition, the length of time between (1) moth emergence and leaf unfolding and (2) moth emergence and bird arrival decreased significantly (P<0.05 and P<0.001, respectively), indicating a decrease in the timing between food supply and demand. These differing trophic level response rates demonstrate the potential for a mismatch in the timing of interdependent phenophases as temperatures rise. Even though these data were not specifically collected to examine climate warming impacts, we conclude that such data may be used as an early warning indicator and as a means to monitor the potential for future ecosystem disruption to occur as climate warms.


Assuntos
Aves/fisiologia , Mudança Climática , Cadeia Alimentar , Mariposas/fisiologia , Árvores/crescimento & desenvolvimento , Migração Animal , Animais , Irlanda , Folhas de Planta/crescimento & desenvolvimento , Estações do Ano , Temperatura
12.
Int J Biometeorol ; 58(4): 509-19, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24037345

RESUMO

In order to predict the impact of future climate warming on trees it is important to quantify the effect climate has on their development. Our understanding of the phenological response to environmental drivers has given rise to various mathematical models of the annual growth cycle of plants. These models simulate the timing of phenophases by quantifying the relationship between development and its triggers, typically temperature. In addition, other environmental variables have an important role in determining the timing of budburst. For example, photoperiod has been shown to have a strong influence on phenological events of a number of tree species, including Betula pubescens (birch). A recently developed model for birch (DORMPHOT), which integrates the effects of temperature and photoperiod on budburst, was applied to future temperature projections from a 19-member ensemble of regional climate simulations (on a 25 km grid) generated as part of the ENSEMBLES project, to simulate the timing of birch budburst in Ireland each year up to the end of the present century. Gridded temperature time series data from the climate simulations were used as input to the DORMPHOT model to simulate future budburst timing. The results showed an advancing trend in the timing of birch budburst over most regions in Ireland up to 2100. Interestingly, this trend appeared greater in the northeast of the country than in the southwest, where budburst is currently relatively early. These results could have implications for future forest planning, species distribution modeling, and the birch allergy season.


Assuntos
Betula/crescimento & desenvolvimento , Mudança Climática , Modelos Teóricos , Sistemas de Informação Geográfica , Irlanda , Fotoperíodo , Estações do Ano , Temperatura
13.
Int J Biometeorol ; 58(6): 1237-49, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23975107

RESUMO

Citizen science is proving to be an effective tool in tracking the rapid pace at which our environment is changing over large geographic areas. It is becoming increasingly popular, in places such as North America and some European countries, to engage members of the general public and school pupils in the collection of scientific data to support long-term environmental monitoring. Participants in such schemes are generally volunteers and are referred to as citizen scientists. The Christmas bird count in the US is one of the worlds longest running citizen science projects whereby volunteers have been collecting data on birds on a specific day since 1900. Similar volunteer networks in Ireland have been in existence since the 1960s and were established to monitor the number and diversity of birds throughout the country. More recently, initiatives such as Greenwave (2006) and Nature Watch (2009) invite school children and members of the general public respectively, to record phenology data from a range of common species of plant, insect and bird. In addition, the Irish butterfly and bumblebee monitoring schemes engage volunteers to record data on sightings of these species. The primary purpose of all of these networks is to collect data by which to monitor changes in wildlife development and diversity, and in the case of Greenwave to involve children in hands-on, inquiry-based science. Together these various networks help raise awareness of key environmental issues, such as climate change and loss of biodiversity, while at the same time promote development of scientific skills among the general population. In addition, they provide valuable scientific data by which to track environmental change. Here we examine the role of citizen science in monitoring biodiversity in Ireland and conclude that some of the data collected in these networks can be used to fulfil Ireland's statutory obligations for nature conservation. In addition, a bee thought previously to be extinct has been rediscovered and a range expansion of a different bee has been confirmed. However, it also became apparent that some of the networks play more of an educational than a scientific role. Furthermore, we draw on experience from a range of citizen science projects to make recommendations on how best to establish new citizen science projects in Ireland and strengthen existing ones.


Assuntos
Biodiversidade , Projetos de Pesquisa , Voluntários , Animais , Aves , Mudança Climática , Humanos , Insetos , Irlanda , Plantas , Controle de Qualidade
14.
BMC Cancer ; 11: 468, 2011 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-22039910

RESUMO

BACKGROUND: The molecular chaperone, heat shock protein 90 (Hsp90) has been shown to be overexpressed in a number of cancers, including prostate cancer, making it an important target for drug discovery. Unfortunately, results with N-terminal inhibitors from initial clinical trials have been disappointing, as toxicity and resistance resulting from induction of the heat shock response (HSR) has led to both scheduling and administration concerns. Therefore, Hsp90 inhibitors that do not induce the heat shock response represent a promising new direction for the treatment of prostate cancer. Herein, the development of a C-terminal Hsp90 inhibitor, KU174, is described, which demonstrates anti-cancer activity in prostate cancer cells in the absence of a HSR and describe a novel approach to characterize Hsp90 inhibition in cancer cells. METHODS: PC3-MM2 and LNCaP-LN3 cells were used in both direct and indirect in vitro Hsp90 inhibition assays (DARTS, Surface Plasmon Resonance, co-immunoprecipitation, luciferase, Western blot, anti-proliferative, cytotoxicity and size exclusion chromatography) to characterize the effects of KU174 in prostate cancer cells. Pilot in vivo efficacy studies were also conducted with KU174 in PC3-MM2 xenograft studies. RESULTS: KU174 exhibits robust anti-proliferative and cytotoxic activity along with client protein degradation and disruption of Hsp90 native complexes without induction of a HSR. Furthermore, KU174 demonstrates direct binding to the Hsp90 protein and Hsp90 complexes in cancer cells. In addition, in pilot in-vivo proof-of-concept studies KU174 demonstrates efficacy at 75 mg/kg in a PC3-MM2 rat tumor model. CONCLUSIONS: Overall, these findings suggest C-terminal Hsp90 inhibitors have potential as therapeutic agents for the treatment of prostate cancer.


Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Animais , Western Blotting , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Inibidores do Crescimento/farmacologia , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Masculino , Proteínas de Neoplasias/metabolismo , Novobiocina/farmacologia , Ligação Proteica/efeitos dos fármacos , Ratos
15.
Bioorg Med Chem ; 19(1): 684-92, 2011 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-21129982

RESUMO

Several Hsp90 modulators have been identified including the N-terminal ligand geldanamycin (GDA), the C-terminal ligand novobiocin (NB), and the co-chaperone disruptor celastrol. Other Hsp90 modulators elicit a mechanism of action that remains unknown. For example, the natural product gedunin and the synthetic anti-spermatogenic agent H2-gamendazole, recently identified Hsp90 modulators, manifest biological activity through undefined mechanisms. Herein, we report a series of biochemical techniques used to classify such modulators into identifiable categories. Such studies provided evidence that gedunin and H2-gamendazole both modulate Hsp90 via a mechanism similar to celastrol, and unlike NB or GDA.


Assuntos
Proteínas de Choque Térmico HSP90/efeitos dos fármacos , Benzoquinonas/farmacologia , Linhagem Celular Tumoral , Cromatografia de Afinidade , Proteínas de Choque Térmico HSP90/química , Humanos , Hidrólise , Imunoprecipitação , Lactamas Macrocíclicas/farmacologia , Modelos Moleculares , Novobiocina/farmacologia , Triterpenos Pentacíclicos , Triterpenos/farmacologia
16.
Int J Biometeorol ; 55(5): 711-21, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21113629

RESUMO

The process of adaptation is the result of stabilising selection caused by two opposite forces: protection against an unfavourable season (survival adaptation), and effective use of growing resources (capacity adaptation). As plant species have evolved different life strategies based on different trade offs between survival and capacity adaptations, different phenological responses are also expected among species. The aim of this study was to compare budburst responses of two opportunistic species (Betula pubescens, and Salix x smithiana) with that of two long-lived, late successional species (Fagus sylvatica and Tilia cordata) and consider their ecological significance. Thus, we performed a series of experiments whereby temperature and photoperiod were manipulated during dormancy. T. cordata and F. sylvatica showed low rates of budburst, high chilling requirements and responsiveness to light intensity, while B. pubescens and S. x smithiana had high rates of budburst, low chilling requirements and were not affected by light intensity. In addition, budburst in B. pubescens and S. x smithiana was more responsive to high forcing temperatures than in T. cordata and F. sylvatica. These results suggest that the timing of growth onset in B. pubescens and S. x smithiana (opportunistic) is regulated through a less conservative mechanism than in T. cordata and F. sylvatica (long-lived, late successional), and that these species trade a higher risk of frost damage for the opportunity of vigorous growth at the beginning of spring, before canopy closure. This information should be considered when assessing the impacts of climate change on vegetation or developing phenological models.


Assuntos
Mudança Climática , Ecossistema , Modelos Biológicos , Fotoperíodo , Árvores/fisiologia , Adaptação Fisiológica , Germinação , Luz , Folhas de Planta/classificação , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/fisiologia , Plântula/classificação , Plântula/crescimento & desenvolvimento , Plântula/fisiologia , Temperatura , Árvores/classificação , Árvores/crescimento & desenvolvimento
17.
Int J Biometeorol ; 55(6): 805-17, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21509461

RESUMO

Mismatches in phenology between mutually dependent species, resulting from climate change, can have far-reaching consequences throughout an ecosystem at both higher and lower trophic levels. Rising temperatures, due to climate warming, have resulted in advances in development and changes in behaviour of many organisms around the world. However, not all species or phenophases are responding to this increase in temperature at the same rate, thus creating a disruption to previously synchronised interdependent key life-cycle stages. Mismatches have been reported between plants and pollinators, predators and prey, and pests and hosts. Here, we review mismatches between interdependent phenophases at different trophic levels resulting from climate change. We categorized the studies into (1) terrestrial (natural and agricultural) ecosystems, and (2) aquatic (freshwater and marine) ecosystems. As expected, we found reports of 'winners' and 'losers' in each system, such as earlier emergence of prey enabling partial avoidance of predators, potential reductions in crop yield if herbivore pests emerge before their predators and possible declines in marine biodiversity due to disruption in plankton-fish phenologies. Furthermore, in the marine environment rising temperatures have resulted in synchrony in a previously mismatched prey and predator system, resulting in an abrupt population decline in the prey species. The examples reviewed suggest that more research into the complex interactions between species in terrestrial and aquatic ecosystems is necessary to make conclusive predictions of how climate warming may impact the fragile balances within ecosystems in future.


Assuntos
Organismos Aquáticos/fisiologia , Ecossistema , Aquecimento Global , Animais , Organismos Aquáticos/classificação , Peixes/classificação , Peixes/fisiologia , Insetos/classificação , Insetos/fisiologia , Plâncton/classificação , Plâncton/fisiologia , Dinâmica Populacional , Comportamento Predatório/fisiologia
18.
Prostate ; 70(1): 27-36, 2010 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-19739131

RESUMO

PURPOSE: Hsp90 is important in the folding, maturation and stabilization of pro-tumorigenic client proteins and represents a viable drug target for the design of chemotherapies. Previously, we reported the development of novobiocin analogues designed to inhibit the C-terminal portion of Hsp90, which demonstrated the ability to decrease client protein expression. We now report the characterization of the novel novobiocin analogue, F-4, which demonstrates improved cytotoxicity in prostate cancer cell lines compared to the N-terminal inhibitor, 17-AAG. MATERIALS AND METHODS: LNCaP and PC-3 cells were treated with 17-AAG or F-4 in anti-proliferative, apoptosis, cell cycle and cytotoxicity assays. Western blot and prostate specific antigen (PSA) ELISAs were used to determine client protein degradation, induction of Hsp90 and to assess the functional status of the androgen receptor (AR) in response to F-4 treatment. Surface plasmon resonance (SPR) was also used to determine the binding properties of F-4 to Hsp90. RESULTS: F-4 demonstrated improved potency and efficacy compared to novobiocin in anti-proliferative assays and decreased expression of client proteins. PSA secretion was inhibited in a dose-dependent manner that paralleled a decrease in AR expression. The binding of F-4 to Hsp90 was determined to be saturable with a binding affinity (K(d)) of 100 microM. In addition, superior efficacy was demonstrated by F-4 compared to 17-AAG in experiments measuring cytotoxicity and apoptosis. CONCLUSIONS: These data reveal distinct modes of action for N-terminal and C-terminal Hsp90 inhibitors, which may offer unique therapeutic benefits for the treatment of prostate cancer.


Assuntos
Sistemas de Liberação de Medicamentos , Inibidores do Crescimento/farmacologia , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Novobiocina/análogos & derivados , Novobiocina/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/metabolismo , Humanos , Masculino , Neoplasias da Próstata/patologia , Spodoptera
19.
Mol Pharmacol ; 76(6): 1314-22, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19741006

RESUMO

The 90-kDa heat shock protein (Hsp90) assists in the proper folding of numerous mutated or overexpressed signal transduction proteins that are involved in cancer. Consequently, there is considerable interest in developing chemotherapeutic drugs that specifically disrupt the function of Hsp90. Here, we investigated the extent to which a novel novobiocin-derived C-terminal Hsp90 inhibitor, designated KU135, induced antiproliferative effects in Jurkat T-lymphocytes. The results indicated that KU135 bound directly to Hsp90, caused the degradation of known Hsp90 client proteins, and induced more potent antiproliferative effects than the established N-terminal Hsp90 inhibitor 17-allylamino-demethoxygeldanamycin (17-AAG). Closer examination of the cellular response to KU135 and 17-AAG revealed that only 17-AAG induced a strong up-regulation of Hsp70 and Hsp90. In addition, KU135 caused wild-type cells to undergo G(2)/M arrest, whereas cells treated with 17-AAG accumulated in G(1). Furthermore, KU135 but not 17-AAG was found to be a potent inducer of mitochondria-mediated apoptosis as evidenced, in part, by the fact that cell death was inhibited to a similar extent by Bcl-2/Bcl-x(L) overexpression or the depletion of apoptotic protease-activating factor-1 (Apaf-1). Together, these data suggest that KU135 inhibits cell proliferation by regulating signaling pathways that are mechanistically different from those targeted by 17-AAG and as such represents a novel opportunity for Hsp90 inhibition.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Novobiocina/análogos & derivados , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Western Blotting , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Cromatografia de Afinidade , Citometria de Fluxo , Humanos , Células Jurkat , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Novobiocina/metabolismo , Novobiocina/farmacologia , Ressonância de Plasmônio de Superfície
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