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1.
Photosynth Res ; 157(2-3): 85-101, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37212937

RESUMO

Photosynthetic responses across complex elevational gradients provides insight into fundamental processes driving responses of plant growth and net primary production to environmental change. Gas exchange of needles and twig water potential were measured in two widespread coniferous tree species, Pinus contorta and Picea engelmannii, over an 800-m elevation gradient in southeastern Wyoming, USA. We hypothesized that limitations to photosynthesis imposed by mesophyll conductance (gm) would be greatest at the highest elevation sites due to higher leaf mass per area (LMA) and that estimations of maximum rate of carboxylation (Vcmax) without including gm would obscure elevational patterns of photosynthetic capacity. We found that gm decreased with elevation for P. contorta and remained constant for P. engelmannii, but in general, limitation to photosynthesis by gm was small. Indeed, estimations of Vcmax when including gm were equivalent to those estimated without including gm and no correlation was found between gm and LMA nor between gm and leaf N. Stomatal conductance (gs) and biochemical demand for CO2 were by far the most limiting processes to photosynthesis at all sites along the elevation gradient. Photosynthetic capacity (A) and gs were influenced strongly by differences in soil water availability across the elevation transect, while gm was less responsive to water availability. Based on our analysis, variation in gm plays only a minor role in driving patterns of photosynthesis in P. contorta and P. engelmannii across complex elevational gradients in dry, continental environments of the Rocky Mountains and accurate modeling of photosynthesis, growth and net primary production in these forests may not require detailed estimation of this trait value.


Assuntos
Células do Mesofilo , Folhas de Planta , Células do Mesofilo/fisiologia , Folhas de Planta/fisiologia , Fotossíntese , Árvores/fisiologia , Água , Dióxido de Carbono
2.
Ann Bot ; 132(4): 671-683, 2023 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-36861500

RESUMO

BACKGROUND: The plant family Cactaceae provides some of the most striking examples of adaptive evolution, expressing undeniably the most spectacular New World radiation of succulent plants distributed across arid and semi-arid regions of the Americas. Cacti are widely regarded for their cultural, economic and ecological value, yet they are also recognized as one of the most threatened and endangered taxonomic groups on the planet. SCOPE: This paper reviews current threats to species of cacti that have distributions in arid to semi-arid subtropical regions. Our review focuses primarily on four global change forces: (1) increases in atmospheric CO2 concentrations; (2) increases in mean annual temperatures and heat waves; (3) increases in the duration, frequency and intensity of droughts; and (4) and increases in competition and wildfire frequency from invasion by non-native species. We provide a broad range of potential priorities and solutions for stemming the extinction risk of cacti species and populations. CONCLUSIONS: Mitigating ongoing and emerging threats to cacti will require not only strong policy initiatives and international cooperation, but also new and creative approaches to conservation. These approaches include determining species at risk from climate extremes, enhancing habitat quality after disturbance, approaches and opportunities for ex situ conservation and restoration, and the potential use of forensic tools for identifying plants that have been removed illegally from the wild and sold on open markets.


Assuntos
Cactaceae , Clima Desértico , Ecossistema , Secas
3.
Glob Chang Biol ; 28(20): 5991-6001, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35751572

RESUMO

The effects of climate change on plants and ecosystems are mediated by plant hydraulic traits, including interspecific and intraspecific variability of trait phenotypes. Yet, integrative and realistic studies of hydraulic traits and climate change are rare. In a semiarid grassland, we assessed the response of several plant hydraulic traits to elevated CO2 (+200 ppm) and warming (+1.5 to 3°C; day to night). For leaves of five dominant species (three graminoids and two forbs), and in replicated plots exposed to 7 years of elevated CO2 , warming, or ambient climate, we measured: stomatal density and size, xylem vessel size, turgor loss point, and water potential (pre-dawn). Interspecific differences in hydraulic traits were larger than intraspecific shifts induced by elevated CO2 and/or warming. Effects of elevated CO2 were greater than effects of warming, and interactions between treatments were weak or not detected. The forbs showed little phenotypic plasticity. The graminoids had leaf water potentials and turgor loss points that were 10% to 50% less negative under elevated CO2 ; thus, climate change might cause these species to adjust their drought resistance strategy away from tolerance and toward avoidance. The C4 grass also reduced allocation of leaf area to stomata under elevated CO2 , which helps explain observations of higher soil moisture. The shifts in hydraulic traits under elevated CO2 were not, however, simply due to higher soil moisture. Integration of our results with others' indicates that common species in this grassland are more likely to adjust stomatal aperture in response to near-term climate change, rather than anatomical traits; this contrasts with apparent effects of changing CO2 on plant anatomy over evolutionary time. Future studies should assess how plant responses to drought may be constrained by the apparent shift from tolerance (via low turgor loss point) to avoidance (via stomatal regulation and/or access to deeper soil moisture).


Assuntos
Dióxido de Carbono , Água , Carbono , Secas , Ecossistema , Pradaria , Fenótipo , Folhas de Planta/fisiologia , Solo , Água/fisiologia
4.
Br J Anaesth ; 126(3): 730-737, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33516455

RESUMO

BACKGROUND: Malnutrition in older hip fracture patients is associated with increased complication rates and mortality. As postoperative nutrition delivery is essential to surgical recovery, postoperative nutritional supplements including oral nutritional supplements or tube feeding formulas can improve postoperative outcomes in malnourished hip/femur fracture patients. The association between early postoperative nutritional supplements utilisation and hospital length of stay was assessed in malnourished hip/femur fracture patients. METHODS: This is a retrospective cohort study of malnourished hip/femur fracture patients undergoing surgery from 2008 to 2018. Patients were identified through International Classification of Diseases, Ninth Revision (ICD-9) and Tenth Revision (ICD-10) codes and nutritional supplement utilisation via hospital charge codes. The primary outcome was hospital length of stay. Secondary outcomes included infectious complications, hospital mortality, ICU admission, and costs. Propensity matching (1:1) and univariable analysis were performed. RESULTS: Overall, 160 151 hip/femur fracture surgeries were identified with a coded-malnutrition prevalence of 8.7%. Early postoperative nutritional supplementation (by hospital day 1) occurred in 1.9% of all patients and only 4.9% of malnourished patients. Propensity score matching demonstrated early nutritional supplements were associated with significantly shorter length of stay (5.8 [6.6] days vs 7.6 [5.8] days; P<0.001) without increasing hospital costs. No association was observed between early nutritional supplementation and secondary outcomes. CONCLUSION: Malnutrition is underdiagnosed in hip/femur fracture patients, and nutritional supplementation is underutilised. Early nutritional supplementation was associated with a significantly shorter hospital stay without an increase in costs. Nutritional supplementation in malnourished hip/femur fracture patients could serve as a key target for perioperative quality improvement.


Assuntos
Fraturas do Quadril/cirurgia , Desnutrição/terapia , Apoio Nutricional/métodos , Cuidados Pós-Operatórios/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Fraturas do Quadril/complicações , Fraturas do Quadril/epidemiologia , Mortalidade Hospitalar/tendências , Humanos , Tempo de Internação , Masculino , Desnutrição/complicações , Desnutrição/epidemiologia , Pessoa de Meia-Idade , Estado Nutricional , Apoio Nutricional/estatística & dados numéricos , Cuidados Pós-Operatórios/estatística & dados numéricos , Pontuação de Propensão , Estudos Retrospectivos , Prevenção Secundária , Resultado do Tratamento
5.
Plant Cell Environ ; 43(8): 1944-1957, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32394490

RESUMO

Resprouting is an ancestral trait in angiosperms that confers resilience after perturbations. As climate change increases stress, resprouting vigor is declining in many forest regions, but the underlying mechanism is poorly understood. Resprouting in woody plants is thought to be primarily limited by the availability of non-structural carbohydrate reserves (NSC), but hydraulic limitations could also be important. We conducted a multifactorial experiment with two levels of light (ambient, 2-3% of ambient) and three levels of water stress (0, 50 and 80 percent losses of hydraulic conductivity, PLC) on two Mediterranean oaks (Quercus ilex and Q. faginea) under a rain-out shelter (n = 360). The proportion of resprouting individuals after canopy clipping declined markedly as PLC increased for both species. NSC concentrations affected the response of Q. ilex, the species with higher leaf construction costs, and its effect depended on the PLC. The growth of resprouting individuals was largely dependent on photosynthetic rates for both species, while stored NSC availability and hydraulic limitations played minor and non-significant roles, respectively. Contrary to conventional wisdom, our results indicate that resprouting in oaks may be primarily driven by complex interactions between hydraulics and carbon sources, whereas stored NSC play a significant but secondary role.


Assuntos
Metabolismo dos Carboidratos/fisiologia , Raízes de Plantas/metabolismo , Quercus/fisiologia , Desidratação , Fotossíntese/fisiologia , Folhas de Planta/metabolismo , Quercus/crescimento & desenvolvimento , Espanha
6.
Blood ; 131(10): 1094-1105, 2018 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-29298756

RESUMO

Human CD19 antigen is a 95-kDa type I membrane glycoprotein in the immunoglobulin superfamily whose expression is limited to the various stages of B-cell development and differentiation and is maintained in the majority of B-cell malignancies, including leukemias and non-Hodgkin lymphomas of B-cell origin. Coupled with its differential and favorable expression profile, CD19 has rapid internalization kinetics and is not shed into the circulation, making it an ideal target for the development of antibody-drug conjugates (ADCs) to treat B-cell malignancies. ADCT-402 (loncastuximab tesirine) is a novel CD19-targeted ADC delivering SG3199, a highly cytotoxic DNA minor groove interstrand crosslinking pyrrolobenzodiazepine (PDB) dimer warhead. It showed potent and highly targeted in vitro cytotoxicity in CD19-expressing human cell lines. ADCT-402 was specifically bound, internalized, and trafficked to lysosomes in CD19-expressing cells and, following release of the PBD warhead, resulted in formation of DNA crosslinks that persisted for 36 hours. Bystander killing of CD19- cells by ADCT-402 was also observed. In vivo, single doses of ADCT-402 resulted in highly potent, dose-dependent antitumor activity in several subcutaneous and disseminated human tumor models with marked superiority to comparator ADCs delivering tubulin inhibitors. Dose-dependent DNA crosslinks and γ-H2AX DNA damage response were measured in tumors by 24 hours after single dose administration, whereas matched peripheral blood mononuclear cells showed no evidence of DNA damage. Pharmacokinetic analysis in rat and cynomolgus monkey showed excellent stability and tolerability of ADCT-402 in vivo. Together, these impressive data were used to support the clinical testing of this novel ADC in patients with CD19-expressing B-cell malignancies.


Assuntos
Antígenos CD19/biossíntese , Antineoplásicos , Regulação Leucêmica da Expressão Gênica , Imunoconjugados , Leucemia de Células B , Linfoma não Hodgkin , Proteínas de Neoplasias/biossíntese , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Imunoconjugados/farmacocinética , Imunoconjugados/farmacologia , Leucemia de Células B/tratamento farmacológico , Leucemia de Células B/metabolismo , Leucemia de Células B/patologia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/metabolismo , Linfoma não Hodgkin/patologia , Lisossomos/metabolismo , Lisossomos/patologia
7.
Am J Bot ; 107(9): 1238-1252, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32931042

RESUMO

PREMISE: The impact of elevated CO2 concentration ([CO2 ]) and climate warming on plant productivity in dryland ecosystems is influenced strongly by soil moisture availability. We predicted that the influence of warming on the stimulation of photosynthesis by elevated [CO2 ] in prairie plants would operate primarily through direct and indirect effects on soil water. METHODS: We measured light-saturated photosynthesis (Anet ), stomatal conductance (gs ), maximum Rubisco carboxylation rate (Vcmax ), maximum electron transport capacity (Jmax ) and related variables in four C3 plant species in the Prairie Heating and CO2 Enrichment (PHACE) experiment in southeastern Wyoming. Measurements were conducted over two growing seasons that differed in the amount of precipitation and soil moisture content. RESULTS: Anet in the C3 subshrub Artemisia frigida and the C3 forb Sphaeralcea coccinea was stimulated by elevated [CO2 ] under ambient and warmed temperature treatments. Warming by itself reduced Anet in all species during the dry year, but stimulated photosynthesis in S. coccinea in the wet year. In contrast, Anet in the C3 grass Pascopyrum smithii was not stimulated by elevated [CO2 ] or warming under wet or dry conditions. Photosynthetic downregulation under elevated [CO2 ] in this species countered the potential stimulatory effect under improved water relations. Warming also reduced the magnitude of CO2 -induced down-regulation in this grass, possibly by sustaining high levels of carbon utilization. CONCLUSIONS: Direct and indirect effects of elevated [CO2 ] and warming on soil water was an overriding factor influencing patterns of Anet in this semi-arid temperate grassland, emphasizing the important role of water relations in driving grassland responses to global change.


Assuntos
Dióxido de Carbono , Fotossíntese , Clima , Mudança Climática , Ecossistema , Pradaria , Solo
8.
J Urban Health ; 97(6): 814-822, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32367203

RESUMO

Drug overdoses are a national and global epidemic. However, while overdoses are inextricably linked to social, demographic, and geographical determinants, geospatial patterns of drug-related admissions and overdoses at the neighborhood level remain poorly studied. The objective of this paper is to investigate spatial distributions of patients admitted for drug-related admissions and overdoses from a large, urban, tertiary care center using electronic health record data. Additionally, these spatial distributions were adjusted for a validated socioeconomic index called the Area Deprivation Index (ADI). We showed spatial heterogeneity in patients admitted for opioid, amphetamine, and psychostimulant-related diagnoses and overdoses. While ADI was associated with drug-related admissions, it did not correct for spatial variations and could not account alone for this spatial heterogeneity.


Assuntos
Overdose de Drogas , Hospitalização , Áreas de Pobreza , Características de Residência , Transtornos Relacionados ao Uso de Substâncias , Estudos de Coortes , Overdose de Drogas/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Características de Residência/estatística & dados numéricos , Análise Espacial , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/terapia
9.
Tech Orthop ; 35(1): 15-18, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33967384

RESUMO

Despite evidence that malnutrition is associated with significant complications in orthopedic surgery1, unrecognized malnutrition continues to be a "silent epidemic", effecting up to 50% of hospitalized patients. Specifically, pre-surgical malnutrition is associated with increased risk for surgical site infections, increased length of hospital stay, and increased health care costs in patients following total joint arthroplasty. Serologic markers (i.e. serum albumin and total lymphocyte count), anthropometric measurements, (i.e. calf muscle circumference and triceps skin fold) and assessment and screening tools (i.e. The Rainey-MacDonald Nutritional Index, the Mini Nutrition Assessment Short Form, the Malnutrition Universal Screening Tool and the Nutrition Risk Screening 2002) have all been used to aid in the diagnosis of malnutrition in orthopedic patients, yet there is no universal gold standard for screening or assessing nutritional risk and no accepted guideline for perioperative nutritional optimization in this patient population. Recently, the Perioperative Nutrition Screen (PONS) was introduced2 as an easy and efficient way to preoperatively identify and risk stratify patients for malnutrition in order to guide perioperative nutrition optimization. Given malnutrition is associated with increased risk of surgical site infections and increased length of hospital stay, adequate assessment of perioperative risk for malnutrition and preoperative nutrition optimization, including structured weight loss in the obese population, consumption of high protein oral nutritional supplements, immunonutrition oral supplements and adequate glucose control, may improve perioperative outcomes. The presence of a Registered Dietician (RD) should be a standard of care in all pre-operative clinics to improve nutrition care and surgical outcomes.

10.
J Exp Bot ; 70(22): 6509-6519, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31269200

RESUMO

The plant family Cactaceae is considered among the most threatened groups of organisms on the planet. The threatened status of the cacti family has created a renewed interest in the highly evolved physiological and morphological traits that underpin their persistence in some of the harshest subtropical environments in the Americas. Among the most important anatomical features of cacti is the modification of leaves into spines, and previous work has shown that the stable isotope chemistry of cacti spines records potential variations in stem water balance, stress, and Crassulacean acid metabolism (CAM). We review the opportunities, challenges, and pitfalls in measuring δ 13C, δ 2H, and δ 18O ratios captured in spine tissues that potentially reflect temporal and spatial patterns of stomatal conductance, internal to atmospheric CO2 partial pressures, and subsequent patterns of photosynthetic gas exchange. We then evaluate the challenges in stable isotope analysis in spine tissues related to variation in CAM expression, stem water compartmentalization, and spine whole-tissue composition among other factors. Finally, we describe how the analysis of all three isotopes can be used in combination to provide potentially robust analysis of photosynthetic function in cacti, and other succulent-stemmed taxa across broad spatio-temporal environmental gradients.


Assuntos
Cactaceae/fisiologia , Clima Desértico , Temperatura Alta , Isótopos/metabolismo , América , Modelos Biológicos , Estações do Ano
11.
Curr Opin Anaesthesiol ; 32(3): 405-411, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30893119

RESUMO

PURPOSE OF REVIEW: As many as two of every three major surgery patients are malnourished preoperatively - a diagnosis rarely made and treated even less frequently. Unfortunately, perioperative malnutrition is perhaps the least often identified surgical risk factor and is among the most treatable to improve outcomes. RECENT FINDINGS: Two important perioperative nutrition guidelines were published recently. Both emphasize nutrition assessment as an essential component of preoperative screening. The recently published perioperative nutrition screen (PONS) readily identifies patients at malnutrition risk, allowing for preoperative nutritional optimization. The use of computerized tomography scan and ultrasound lean body mass (LBM) evaluation to identify sarcopenia associated with surgical risk and guide nutrition intervention is garnering further support. Preoperative nutrition optimization in malnourished patients, use of immunonutrition in all major surgery, avoidance of preoperative fasting, inclusion of postoperative high-protein nutritional supplements, and early postoperative oral intake have all recently been shown to improve outcomes and should be utilized. SUMMARY: The recent publication of new surgical nutrition guidelines, the PONS score, and use of LBM assessments will allow better identification and earlier intervention on perioperative malnutrition. It is essential that in the future no patient undergoes elective surgery without nutrition screening and nutrition intervention when malnutrition risk is identified.


Assuntos
Nutrição Enteral/normas , Desnutrição/diagnóstico , Avaliação Nutricional , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/prevenção & controle , Nutrição Enteral/métodos , Jejum/efeitos adversos , Jejum/fisiologia , Humanos , Desnutrição/epidemiologia , Desnutrição/fisiopatologia , Desnutrição/terapia , Assistência Perioperatória/normas , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Guias de Prática Clínica como Assunto , Período Pré-Operatório , Prevalência , Fatores de Risco , Procedimentos Cirúrgicos Operatórios/efeitos adversos
12.
Ecol Lett ; 21(5): 674-682, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29508508

RESUMO

Temporal variation in soil nitrogen (N) availability affects growth of grassland communities that differ in their use and reuse of N. In a 7-year-long climate change experiment in a semi-arid grassland, the temporal stability of plant biomass production varied with plant N turnover (reliance on externally acquired N relative to internally recycled N). Species with high N turnover were less stable in time compared to species with low N turnover. In contrast, N turnover at the community level was positively associated with asynchrony in biomass production, which in turn increased community temporal stability. Elevated CO2 and summer irrigation, but not warming, enhanced community N turnover and stability, possibly because treatments promoted greater abundance of species with high N turnover. Our study highlights the importance of plant N turnover for determining the temporal stability of individual species and plant communities affected by climate change.


Assuntos
Dióxido de Carbono , Nitrogênio , Água , Biomassa , Pradaria , Poaceae , Solo
13.
Am J Bot ; 105(10): 1688-1702, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30304560

RESUMO

PREMISE OF THE STUDY: Giant cacti species possess long cylindrical stems that store massive amounts of water and other resources to draw on for photosynthesis, growth, and reproduction during hot and dry conditions. Across all giant cacti taxa, stem photosynthetic surface area to volume ratio (S:V) varies by several fold. This broad morphological diversity leads to the hypothesis that giant cacti function along a predictable resource use continuum from a "safe" strategy reflected in low S:V, low relative growth rates (RGR), and low net assimilation rates (Anet ) to a high-risk strategy that is reflected in high S:V, RGR, and Anet . METHODS: To test this hypothesis, whole-plant gas exchange, chlorophyll fluorescence, and whole-spine-tissue carbon isotope ratios (δ13 C) were measured in four giant cacti species varying in stem morphology and RGR. Measurements were conducted on five well-watered, potted plants per species. KEY RESULTS: Under conditions of mild diel temperatures and low atmospheric vapor pressure deficit, Anet , transpiration (E), and stomatal conductance (Gs ) were significantly higher, and water-use efficiency (Anet : Gs ) was lower in fast-growing, multi-stemmed species compared to the slower growing, single-stemmed species. However, under warmer, less optimal conditions, gas exchange converged between stem types, and neither δ13 C nor chlorophyll fluorescence varied among species. CONCLUSIONS: The results add to a growing body of evidence that succulent-stemmed plants function along a similar economic spectrum as leaf-bearing plants such that functional traits including stem RGR, longevity, morphology, and gas exchange are correlated across species with varying life-history strategies.


Assuntos
Cactaceae/metabolismo , Características de História de Vida , Fotossíntese , Arizona , Cactaceae/anatomia & histologia , Isótopos de Carbono/análise , Especificidade da Espécie , Água/metabolismo
15.
Glob Chang Biol ; 23(8): 3092-3106, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-27992952

RESUMO

Determining whether the terrestrial biosphere will be a source or sink of carbon (C) under a future climate of elevated CO2 (eCO2 ) and warming requires accurate quantification of gross primary production (GPP), the largest flux of C in the global C cycle. We evaluated 6 years (2007-2012) of flux-derived GPP data from the Prairie Heating and CO2 Enrichment (PHACE) experiment, situated in a grassland in Wyoming, USA. The GPP data were used to calibrate a light response model whose basic formulation has been successfully used in a variety of ecosystems. The model was extended by modeling maximum photosynthetic rate (Amax ) and light-use efficiency (Q) as functions of soil water, air temperature, vapor pressure deficit, vegetation greenness, and nitrogen at current and antecedent (past) timescales. The model fits the observed GPP well (R2  = 0.79), which was confirmed by other model performance checks that compared different variants of the model (e.g. with and without antecedent effects). Stimulation of cumulative 6-year GPP by warming (29%, P = 0.02) and eCO2 (26%, P = 0.07) was primarily driven by enhanced C uptake during spring (129%, P = 0.001) and fall (124%, P = 0.001), respectively, which was consistent across years. Antecedent air temperature (Tairant ) and vapor pressure deficit (VPDant ) effects on Amax (over the past 3-4 days and 1-3 days, respectively) were the most significant predictors of temporal variability in GPP among most treatments. The importance of VPDant suggests that atmospheric drought is important for predicting GPP under current and future climate; we highlight the need for experimental studies to identify the mechanisms underlying such antecedent effects. Finally, posterior estimates of cumulative GPP under control and eCO2 treatments were tested as a benchmark against 12 terrestrial biosphere models (TBMs). The narrow uncertainties of these data-driven GPP estimates suggest that they could be useful semi-independent data streams for validating TBMs.


Assuntos
Ciclo do Carbono , Ecossistema , Pradaria , Dióxido de Carbono , Clima , Wyoming
16.
Bioorg Med Chem Lett ; 27(5): 1154-1158, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28188066

RESUMO

A novel pyrrolobenzodiazepine dimer payload, SG3227, was rationally designed based on the naturally occurring antitumour compound sibiromycin. SG3227 was synthesized from a dimeric core in an efficient fashion. An unexpected room temperature Diels-Alder reaction occurred during the final step of the synthesis and was circumvented by use of an iodoacetamide conjugation moiety in place of a maleimide. The payload was successfully conjugated to trastuzumab and the resulting ADC exhibited potent activity against a HER2-expressing human cancer cell line in vitro.


Assuntos
Aminoglicosídeos/química , Antineoplásicos/química , Benzodiazepinas/química , Imunoconjugados/química , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Humanos , Técnicas In Vitro
17.
Nature ; 476(7359): 202-5, 2011 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-21814202

RESUMO

Global warming is predicted to induce desiccation in many world regions through increases in evaporative demand. Rising CO(2) may counter that trend by improving plant water-use efficiency. However, it is not clear how important this CO(2)-enhanced water use efficiency might be in offsetting warming-induced desiccation because higher CO(2) also leads to higher plant biomass, and therefore greater transpirational surface. Furthermore, although warming is predicted to favour warm-season, C(4) grasses, rising CO(2) should favour C(3), or cool-season plants. Here we show in a semi-arid grassland that elevated CO(2) can completely reverse the desiccating effects of moderate warming. Although enrichment of air to 600 p.p.m.v. CO(2) increased soil water content (SWC), 1.5/3.0 °C day/night warming resulted in desiccation, such that combined CO(2) enrichment and warming had no effect on SWC relative to control plots. As predicted, elevated CO(2) favoured C(3) grasses and enhanced stand productivity, whereas warming favoured C(4) grasses. Combined warming and CO(2) enrichment stimulated above-ground growth of C(4) grasses in 2 of 3 years when soil moisture most limited plant productivity. The results indicate that in a warmer, CO(2)-enriched world, both SWC and productivity in semi-arid grasslands may be higher than previously expected.


Assuntos
Dióxido de Carbono/farmacologia , Dessecação , Ecossistema , Aquecimento Global , Fotossíntese/efeitos dos fármacos , Poaceae/efeitos dos fármacos , Poaceae/crescimento & desenvolvimento , Atmosfera/química , Biomassa , Dióxido de Carbono/metabolismo , Clima Desértico , Fotossíntese/fisiologia , Estômatos de Plantas/metabolismo , Transpiração Vegetal , Poaceae/metabolismo , Estações do Ano , Solo/química , Volatilização , Água/análise , Wyoming
18.
Cochrane Database Syst Rev ; 8: CD012539, 2017 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-28770975

RESUMO

BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents.As the leading cause of morbidity in children and adolescents in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications: nociceptive, neuropathic, idiopathic, visceral, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, and other unknown reasons.Paracetamol (acetaminophen) is one of the most widely used analgesics in both adults and children. The recommended dosage in the UK, Europe, Australia, and the USA for children and adolescents is generally 10 to 15 mg/kg every four to six hours, with specific age ranges from 60 mg (6 to 12 months old) up to 500 to 1000 mg (over 12 years old). Paracetamol is the only recommended analgesic for children under 3 months of age. Paracetamol has been proven to be safe in appropriate and controlled dosages, however potential adverse effects of paracetamol if overdosed or overused in children include liver and kidney failure. OBJECTIVES: To assess the analgesic efficacy and adverse events of paracetamol (acetaminophen) used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries. SELECTION CRITERIA: Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing paracetamol with placebo or an active comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and numbers needed to treat, using standard methods where data were available. We assessed GRADE (Grading of Recommendations Assessment, Development and Evaluation) and planned to create a 'Summary of findings' table. MAIN RESULTS: No studies were eligible for inclusion in this review. We rated the quality of the evidence as very low. We downgraded the quality of evidence by three levels due to the lack of data reported for any outcome. AUTHORS' CONCLUSIONS: There was no evidence from randomised controlled trials to support or refute the use of paracetamol (acetaminophen) to treat chronic non-cancer pain in children and adolescents. We are unable to comment about efficacy or harm from the use of paracetamol to treat chronic non-cancer pain in children and adolescents.We know from adult randomised controlled trials that paracetamol, can be effective, in certain doses, and in certain pain conditions (not always chronic).This means that no conclusions could be made about efficacy or harm in the use of paracetamol (acetaminophen) to treat chronic non-cancer pain in children and adolescents.


Assuntos
Acetaminofen/uso terapêutico , Analgésicos não Narcóticos/uso terapêutico , Dor Crônica/tratamento farmacológico , Adolescente , Criança , Humanos
19.
Proc Natl Acad Sci U S A ; 111(43): 15456-61, 2014 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-25313034

RESUMO

Climate controls vegetation distribution across the globe, and some vegetation types are more vulnerable to climate change, whereas others are more resistant. Because resistance and resilience can influence ecosystem stability and determine how communities and ecosystems respond to climate change, we need to evaluate the potential for resistance as we predict future ecosystem function. In a mixed-grass prairie in the northern Great Plains, we used a large field experiment to test the effects of elevated CO2, warming, and summer irrigation on plant community structure and productivity, linking changes in both to stability in plant community composition and biomass production. We show that the independent effects of CO2 and warming on community composition and productivity depend on interannual variation in precipitation and that the effects of elevated CO2 are not limited to water saving because they differ from those of irrigation. We also show that production in this mixed-grass prairie ecosystem is not only relatively resistant to interannual variation in precipitation, but also rendered more stable under elevated CO2 conditions. This increase in production stability is the result of altered community dominance patterns: Community evenness increases as dominant species decrease in biomass under elevated CO2. In many grasslands that serve as rangelands, the economic value of the ecosystem is largely dependent on plant community composition and the relative abundance of key forage species. Thus, our results have implications for how we manage native grasslands in the face of changing climate.


Assuntos
Dióxido de Carbono/farmacologia , Ecossistema , Poaceae/efeitos dos fármacos , Poaceae/crescimento & desenvolvimento , Análise de Variância , Biomassa , Mudança Climática , Chuva , Especificidade da Espécie , Temperatura , Fatores de Tempo
20.
J Cogn Neurosci ; 28(11): 1838-1848, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27417203

RESUMO

Distractibility can lead to accidents and academic failures as well as memory problems. Recent evidence suggests that intentional recognition memory can be biased by unintentional recognition of distracting stimuli in the same environment. It is unknown whether unintentional and intentional recognition depend on the same underlying neurocognitive mechanisms. We assessed whether human participants' recognition of previously seen (old) or not seen (new) target stimuli was affected by whether a to-be-ignored distractor was old or new. ERPs were recorded to investigate the neural correlates of this bias. The results showed that the old/new status of salient distractors had a biasing effect on target recognition accuracy. Both intentional and unintentional recognition elicited early ERP effects that are thought to reflect relatively automatic memory processes. However, only intentional recognition elicited the later ERP marker of conscious recollection, consistent with previous suggestions that recollection is under voluntary control. In contrast, unintentional recognition was associated with an enhanced late posterior negativity, which may reflect monitoring or evaluation of memory signals. The findings suggest that unintentional and intentional recognition involve dissociable memory processes.

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