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1.
J Environ Qual ; 44(4): 1049-62, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26437086

RESUMO

We make the case that phosphorus (P) is inextricably linked to an increasingly fragile, interconnected, and interdependent nexus of water, energy, and food security and should be managed accordingly. Although there are many other drivers that influence water, energy, and food security, P plays a unique and under-recognized role within the nexus. The P paradox derives from fundamental challenges in meeting water, energy, and food security for a growing global population. We face simultaneous dilemmas of overcoming scarcity of P to sustain terrestrial food and biofuel production and addressing overabundance of P entering aquatic systems, which impairs water quality and aquatic ecosystems and threatens water security. Historical success in redistributing rock phosphate as fertilizer to enable modern feed and food production systems is a grand societal achievement in overcoming inequality. However, using the United States as the main example, we demonstrate how successes in redistribution of P and reorganization of farming systems have broken local P cycles and have inadvertently created instability that threatens resilience within the nexus. Furthermore, recent expansion of the biofuels sector is placing further pressure on P distribution and availability. Despite these challenges, opportunities exist to intensify and expand food and biofuel production through recycling and better management of land and water resources. Ultimately, a strategic approach to sustainable P management can help address the P paradox, minimize tradeoffs, and catalyze synergies to improve resilience among components of the water, energy, and food security nexus.

2.
Clin Infect Dis ; 59(11): 1579-87, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25192745

RESUMO

BACKGROUND: Simeprevir is an oral, once-daily, hepatitis C virus (HCV) NS3/4A protease inhibitor for the treatment of chronic HCV genotype 1 infection. Human immunodeficiency virus (HIV) coinfection accelerates progression of liver disease. This uncontrolled, open-label trial explored the safety and efficacy of simeprevir in patients with HCV genotype 1/HIV type 1 (HIV-1) coinfection. METHODS: Patients received simeprevir (150 mg once daily) with pegylated interferon alfa-2a/ribavirin (peg-IFN/RBV) for 12 weeks. Noncirrhotic HCV treatment-naive patients and prior relapsers received response-guided therapy (RGT) with peg-IFN/RBV for 24 or 48 weeks. Prior null responders, prior partial responders, and patients with cirrhosis received peg-IFN/RBV for 48 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). RESULTS: One hundred and six patients (93 on antiretroviral therapy) were enrolled and treated. SVR12 rates were 79.2% in HCV treatment-naive patients, 57.1% in prior null responders, 86.7% in prior relapsers, and 70.0% in prior partial responders. Fifty-four of 61 eligible patients (88.5%) met RGT criteria for 24 weeks of peg-IFN/RBV, of whom 87.0% (47/54) achieved SVR12. SVR12 rates were 80.0% (36/45) and 63.6% (14/22) for patients with METAVIR scores of F0-F2 and F3-F4, respectively. Common adverse event (AE) rates were consistent with peg-IFN/RBV therapy (fatigue, headache, nausea, neutropenia). Most AEs were grade 1/2; serious AEs occurred in 5.7% of patients, none of which were fatal. CONCLUSIONS: Simeprevir was generally well tolerated with safety similar to that observed in HCV-monoinfected patients and high SVR12 rates in HCV treatment-naive patients, prior relapsers, prior partial responders, and prior null responders with HIV-1 coinfection. CLINICAL TRIALS REGISTRATION: NCT01479868.


Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1/isolamento & purificação , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Sulfonamidas/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Feminino , Infecções por HIV/virologia , Hepatite C Crônica/virologia , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Ribavirina/efeitos adversos , Simeprevir , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Adulto Jovem
3.
Environ Sci Technol ; 48(22): 13280-8, 2014 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-25325669

RESUMO

In 1999 we used the MAGIC (Model of Acidification of Groundwater In Catchments) model to project acidification of acid-sensitive European surface waters in the year 2010, given implementation of the Gothenburg Protocol to the Convention on Long-Range Transboundary Air Pollution (LRTAP). A total of 202 sites in 10 regions in Europe were studied. These forecasts can now be compared with measurements for the year 2010, to give a "ground truth" evaluation of the model. The prerequisite for this test is that the actual sulfur and nitrogen deposition decreased from 1995 to 2010 by the same amount as that used to drive the model forecasts; this was largely the case for sulfur, but less so for nitrogen, and the simulated surface water [NO3(-)] reflected this difference. For most of the sites, predicted surface water recovery from acidification for the year 2010 is very close to the actual recovery observed from measured data, as recovery is predominantly driven by reductions in sulfur deposition. Overall these results show that MAGIC successfully predicts future water chemistry given known changes in acid deposition.


Assuntos
Ácidos/química , Água Subterrânea/química , Modelos Teóricos , Poluentes Químicos da Água/análise , Simulação por Computador , Monitoramento Ambiental/métodos , Europa (Continente) , Previsões , Geografia
4.
Health Equity ; 7(1): 61-69, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36744235

RESUMO

History and experience teach us that our Constitution and laws can be instruments of racial discrimination and oppression as well as tools for advancing freedom and equality. The substance of our laws matters, and there is much to be learned from innovative policies and legal strategies around the country. In addition to laws promoting health equity and racial justice at the state, tribal, and local levels, a new federal Executive Order has the potential to drive major positive change if fully and properly implemented. Just as important, however, is linking legal advocacy with dynamic social movements, shrewd communication strategies, and courageous civic leadership that insists on transformative change. In this article, I briefly recount the turbulent relationship between law and equity in our nation; discuss the elements that can lead to major progress through law; and recommend specific steps that different actors can take to move an equity and opportunity agenda forward.

5.
iScience ; 26(6): 106798, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37235053

RESUMO

Ensuring global food security and environmental sustainability is dependent upon the contribution of the world's hundred million smallholder farms, but the contributions of smallholder farms to global agricultural greenhouse gas (GHG) emissions have been understudied. We developed a localized agricultural life cycle assessment (LCA) database to calculate GHG emissions and made the first extensive assessment of the smallholder farms' GHG emission reduction potentials by coupling crop and livestock production (CCLP), a redesign of current practices toward sustainable agriculture in China. CCLP can reduce the GHG emission intensity by 17.67%, with its own feed and manure returning to the field as an essential path. Scenario analysis verified that greater GHG emission reduction (28.09%-41.32%) will be achieved by restructuring CCLP. Therefore, this mixed farming is a mode with broader benefits to provide sustainable agricultural practices for reducing GHG emissions fairly.

6.
Front Pharmacol ; 13: 764540, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35784686

RESUMO

Antibody-drug conjugates (ADCs) have begun to fulfil their promise as targeted cancer therapeutics with ten clinical approvals to date. As the field matures, much attention has focused upon the key factors required to produce safe and efficacious ADCs. Recently the role that linker-payload reagent design has on the properties of ADCs has been highlighted as an important consideration for developers. We have investigated the effect of incorporating hydrophilic macrocycles into reagent structures on the in vitro and in vivo behavior of ADCs. Bis-sulfone based disulfide rebridging reagents bearing Val-Cit-PABC-MMAE linker-payloads were synthesized with a panel of cyclodextrins and crown ethers integrated into their structures via a glutamic acid branching point. Brentuximab was selected as a model antibody and ten ADCs with a drug-to-antibody ratio (DAR) of 4 were prepared for biological evaluation. In vitro, the ADCs prepared showed broadly similar potency (range: 16-34 pM) and were comparable to Adcetris® (16 pM). In vivo, the cyclodextrin containing ADCs showed greater efficacy than Adcetris® and the most efficacious variant (incorporating a 3'-amino-α-cyclodextrin component) matched a 24-unit poly(ethylene glycol) (PEG) containing comparator. The ADCs bearing crown ethers also displayed enhanced in vivo efficacy compared to Adcetris®, the most active variant (containing a 1-aza-42-crown-14 macrocycle) was superior to an analogous ADC with a larger 24-unit PEG chain. In summary, we have demonstrated that hydrophilic macrocycles can be effectively incorporated into ADC reagent design and offer the potential for enhanced alternatives to established drug-linker architectures.

7.
Mol Pharm ; 7(5): 1734-46, 2010 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-20695423

RESUMO

Poly(amidoamine) (PAMAM) dendrimers are promising multipotent gene delivery vectors, providing favorable DNA condensation properties also in combination with the possibility of conjugation of different targeting ligands to their surface. They have been used for transfection both in vitro and in vivo, but their application is currently somewhat limited due to inherent cytotoxicity. In this work we investigate how two types of surface modification, acetylation and PEGylation, affect the DNA binding characteristics, the cytotoxicity and the in vitro transfection efficiency of generation 4 and 5 PAMAM dendrimers. Particularly, we address how the morphology of DNA-dendrimer complexes, formed under low salt conditions, changes upon dilution in cell growth medium, an event that inevitably occurs before the complexes reach the cell surface in any transfection experiment. We find that acetylation and PEGylation essentially eliminates the inherent dendrimer cytotoxicity. However, the transfection efficiency of the modified dendrimers is lower than that of the corresponding unmodified dendrimers, which can be rationally understood by our observations that DNA is less condensed when complexed with these modified dendrimers. Although small DNA-dendrimer particles are formed, the availability for ethidium intercalation and nuclease degradation is significantly higher in the modified DNA-dendrimer complexes than in unmodified ones. Dilution in cell growth medium has a drastic effect on these electrostatically assembled complexes, resulting in increase in size and DNA availability. Our results strongly add to the notion that it is of importance to perform a biophysical characterization under conditions as close to the transfection situation as possible, to enable conclusions regarding structure-activity relations of gene delivery vectors.


Assuntos
DNA/administração & dosagem , Dendrímeros/administração & dosagem , Dendrímeros/química , Acetilação , Animais , Materiais Biocompatíveis/administração & dosagem , Materiais Biocompatíveis/química , Materiais Biocompatíveis/toxicidade , Fenômenos Biofísicos , Células CHO , Cricetinae , Cricetulus , DNA/genética , DNA/metabolismo , Dendrímeros/toxicidade , Sistemas de Liberação de Medicamentos , Técnicas de Transferência de Genes , Vetores Genéticos , Teste de Materiais , Polietilenoglicóis/química , Transfecção
8.
Environ Int ; 138: 105621, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32142913

RESUMO

Substantial perfluoroalkyl acids (PFAAs) production still occurs in China, and the consumption of aquatic products is a critical exposure pathway of PFAAs in humans. In this study, specimens of 16 freshwater and 40 marine species were collected in the river-estuary-sea environment affected by a mega fluorochemical industry park in China in 2015, and the edible tissues of these organisms were analyzed for PFAA levels. Perfluorooctanoic acid (PFOA) was the dominating contaminant with an overall contribution of more than 90%, and concentrations as high as 2161 ng/g wet weight (measured in the freshwater winkle). All species with the greatest PFOA levels were benthic. The trophic magnification factor (TMF) of PFOA was 1.10 for freshwater species and 1.28 for marine species, indicating that PFOA was slightly magnifying. Analysis of carbon source indicated that freshwater species were more benthic feeding, while marine species were more pelagic feeding. Aquatic food consumption screening values of PFOA were modified according to estimated daily intake (EDI) values, which generated recommendations for limited meal categories and the do-not-eat category. Thus, this study provides recommendations for mitigating the health risks of PFAA-contaminated aquatic food, ranging from food selection to consumption frequency and proper food processing.


Assuntos
Ácidos Alcanossulfônicos , Fluorocarbonos , Poluentes Químicos da Água , Caprilatos/análise , Caprilatos/toxicidade , China , Monitoramento Ambiental , Estuários , Fluorocarbonos/análise , Fluorocarbonos/toxicidade , Humanos , Rios , Poluentes Químicos da Água/análise
10.
Environ Pollut ; 255(Pt 2): 113235, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31561036

RESUMO

The role of sediment-bound organic phosphorus (Po) as an additional nutrient source is a component of internal P budgets in lake system that is usually neglected. Here we examined the relative importance of sediment Po to internal P load and the role of bioavailable Po in algal growth in Lake Erhai, China. Lake Erhai sediment extractable Po accounted for 11-43% (27% average) of extractable total P, and bioavailable Po accounted for 21-66% (40%) of Po. The massive storage of bioavailable Po represents an important form of available P, essential to internal loads. The bioavailable Po includes mainnly labile monoester P and diester P was identified in the sequential extractions by H2O, NaHCO3, NaOH, and HCl. 40% of H2O-Po, 39% of NaHCO3-Po, 43% of NaOH-Po, and 56% of HCl-Po can be hydrolyzed to labile monoester and diester P, suggesting that the bioavailability of Po fractions was in decreasing order as follows: HCl-Po > NaOH-Po > H2O-Po > NaHCO3-Po. It is implied that traditional sequential fractionation of Po might overestimate the availability of labile Po in sediments. Furthermore, analysis of the environmental processes of bioavailable Po showed that the stabler structure of dissloved organic matter (DOM) alleviated the degradation and release of diester P, abundant alkaline phosphatase due to higher algal biomass promoted the degradation of diester P. The stability of DOM structure and the degradation of diester P might responsible for the spatial differences of labile monoester P. The biogeochemical cycle of bioavailable Po replenishs available P pools in overlying water and further facilitate algal growth during the algal blooms. Therefore, to control the algal blooms in Lake Erhai, an effective action is urgently required to reduce the accumulation of Po in sediments and interrupt the supply cycle of bioavailable Po to algal growth.


Assuntos
Monitoramento Ambiental , Eutrofização , Poluentes Químicos da Água/análise , Disponibilidade Biológica , Biomassa , Fracionamento Químico , China , Sedimentos Geológicos/química , Hidrólise , Lagos/química , Fósforo/análise
11.
Sci Adv ; 5(8): eaau9413, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31457075

RESUMO

After 40 years of reform and "opening up," China has made remarkable economic progress. Such economic prosperity, however, has been coupled with environmental degradation. We analyze diverse long-term data to determine whether China is experiencing a decoupling of economic growth and environmental impacts, and where China stands with respect to the Sustainable Development Goals (SDGs) in terms of reducing regional division, urban-rural gap, social inequality, and land-based impacts on oceans. The results highlight that China's desire to achieve "ecological civilization" has resulted in a decoupling trend for major pollutants since 2015, while strong coupling remains with CO2 emissions. Progress has been made in health care provision, poverty reduction, and gender equity in education, while income disparity continues between regions and with rural-urban populations. There is a considerable way to go toward achieving delivery of the SDGs; however, China's progress toward economic prosperity and concomitant sustainability provides important insights for other countries.

12.
Mol Pain ; 4: 3, 2008 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-18199335

RESUMO

Resiniferatoxin (RTX) is an ultrapotent capsaicin analog that binds to the transient receptor potential channel, vanilloid subfamily member 1 (TRPV1). There is a large body of evidence supporting a role for TRPV1 in noxious-mediated and inflammatory hyperalgesic responses. In this study, we evaluated low, graded, doses of perineural RTX as a method for regional pain control. We hypothesized that this approach can provide long-term, but reversible, blockade of a portion of nociceptive afferent fibers within peripheral nerves when given at a site remote from the neuronal perikarya in the dorsal root ganglia. Following perineural RTX application to the sciatic nerve, we demonstrated a significant inhibition of inflammatory nociception that was dose- and time-dependent. At the same time, treated animals maintained normal proprioceptive sensations and motor control, and other nociceptive responses were largely unaffected. Using a range of mechanical and thermal algesic tests, we found that the most sensitive measure following perineural RTX administration was inhibition of inflammatory hyperalgesia. Recovery studies showed that physiologic sensory function could return as early as two weeks post-RTX treatment, however, immunohistochemical examination of the DRG revealed a partial, but significant reduction in the number of the TRPV1-positive neurons. We propose that this method could represent a beneficial treatment for a range of chronic pain problems, including neuropathic and inflammatory pain not responding to other therapies.


Assuntos
Diterpenos/farmacologia , Hiperalgesia/prevenção & controle , Nervos Periféricos/efeitos dos fármacos , Administração Cutânea , Animais , Comportamento Animal/efeitos dos fármacos , Capsaicina/farmacologia , Diterpenos/administração & dosagem , Relação Dose-Resposta a Droga , Edema , Estimulação Elétrica , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/patologia , Temperatura Alta , Inflamação/prevenção & controle , Masculino , Inflamação Neurogênica/prevenção & controle , Ratos , Ratos Sprague-Dawley , Teste de Desempenho do Rota-Rod , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Canais de Cátion TRPV/metabolismo , Fatores de Tempo
13.
Mol Pain ; 4: 43, 2008 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-18828909

RESUMO

BACKGROUND: Rodent models of orofacial pain typically use methods adapted from manipulations to hind paw; however, limitations of these models include animal restraint and subjective assessments of behavior by the experimenter. In contrast to these methods, assessment of operant responses to painful stimuli has been shown to overcome these limitations and expand the breadth of interpretation of the behavioral responses. In the current study, we used an operant model based on a reward-conflict paradigm to assess nociceptive responses in three strains of mice (SKH1-Hrhr, C57BL/6J, TRPV1 knockout). We previously validated this operant model in rats and hypothesized in this study that wild-type mice would demonstrate a similar thermal stimulus-dependent response and similar operant pain behaviors. Additionally, we evaluated the effects on operant behaviors of mice manipulated genetically (e.g., TRPV1 k.o.) or pharmacologically with resiniferatoxin (RTX), a lesioning agent for TRPV1-expressing neurons. During the reward-conflict task, mice accessed a sweetened milk reward solution by voluntarily position their face against a neutral or heated thermode (37-55 degrees C). RESULTS: As the temperature of the thermal stimulus became noxiously hot, reward licking events in SKH1-Hrhr and C57BL/6J mice declined while licking events in TRPV1 k.o. mice were insensitive to noxious heat within the activation range of TRPV1 (37-52 degrees C). All three strains displayed nocifensive behaviors at 55 degrees C, as indicated by a significant decrease in reward licking events. Induction of neurogenic inflammation by topical application of capsaicin reduced licking events in SKH1-Hrhr mice, and morphine rescued this response. Again, these results parallel what we previously documented using rats in this operant system. Following intracisternal treatment with RTX, C57BL/6J mice demonstrated a block of noxious heat at both 48 and 55 degrees C. RTX-treated TRPV1 k.o. mice and all vehicle-treated mice displayed similar reward licking events as compared to the pre-treatment baseline levels. Both TRPV1 k.o. and RTX-treated C57BL/6J had complete abolishment of eye-wipe responses following corneal application of capsaicin. CONCLUSION: Taken together, these results indicate the benefits of using the operant test system to investigate pain sensitivity in mice. This ability provides an essential step in the development of new treatments for patients suffering from orofacial pain disorders.


Assuntos
Condicionamento Operante , Dor Facial/etiologia , Neurônios/química , Canais de Cátion TRPV/deficiência , Canais de Cátion TRPV/fisiologia , Animais , Aprendizagem da Esquiva , Modelos Animais de Doenças , Diterpenos/farmacologia , Temperatura Alta , Camundongos , Camundongos Knockout , Medição da Dor
15.
Sci Total Environ ; 613-614: 352-360, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28917174

RESUMO

Climate change and emissions rates of contaminants are expected to affect distribution and fate of Persistent Organic Pollutants (POPs) in the environment, however, studies on these combined factors are rare. In this study, Perfluorooctane Sulfonate (PFOS) is used as an example to assess how those two factors synthetically affect fate and disposition of POPs in the Bohai Rim of China by using the Berkeley-Trent-Urban-Rural (BETR-Urban-Rural) model. We set up three climate change scenarios and four emission scenarios to conduct the simulations. The results show that climate change could have significant effects on the transport and fate of PFOS mainly including advection, inter-compartmental transfer under the "worst case" emission scenario. For most grids, a remarkable decrease in concentrations of PFOS are predicted for fresh water and urban soil in the future, with precipitation and temperature being predominant factors, whilst for coastal water and rural soil, an increasing trend is predicted. Additionally, predicted sum of sources to the Bohai Sea increases greater than removals from the Bohai Sea in the future, adding evidence that concentrations of PFOS in coastal water will increase more in the future. Under scenarios of reduced emissions and climate change, concentrations of PFOS in each compartment decreased more rapidly over time. We suggest that assessment of future climate change impacts on fate of PFOS could take emission reductions into consideration.

16.
Behav Brain Funct ; 3: 49, 2007 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-17883847

RESUMO

BACKGROUND: Management of pain involves a balance between inhibition of pain and minimization of side effects; therefore, in developing new analgesic compounds, one must consider the effects of treatment on both pain processing and behavior. The purpose of this study was to evaluate the effects of the mu and kappa-2 opioid receptor agonists on general and pain behavioral outcomes. METHODS: As a general behavioral assessment, we modified the cylinder rearing assay and recorded the number and duration of rearing events. Thermal sensitivity was evaluated using either a reflexive measure of hindpaw withdrawal latency to a radiant heat source or using an orofacial operant thermal assay. Acetic acid-induced visceral pain and capsaicin-induced neurogenic inflammatory pain were used as painful stimuli. The mu-opioid receptor agonist, morphine or the kappa-2 receptor agonist GR89696 was administered 30 min prior to testing. A general linear model repeated measures analysis was completed for baseline session comparisons and an analysis of variance was used to evaluate the effects of treatment on each outcome measure (SPSS Inc). When significant differences were found, post-hoc comparisons were made using the Tukey honestly significant difference test. *P < 0.05 was considered significant in all instances. RESULTS: We found that morphine and GR89,696 dose-dependently decreased the number of reaching events and rearing duration. Rearing behavior was not affected at 0.5 mg/kg for morphine, 1.25 x 10-4 mg/kg for GR89,696. Hindpaw thermal sensitivity was significantly increased only at the highest doses for each drug. At the highest dose that did not significantly influence rearing behavior, we found that visceral and neurogenic inflammatory pain was not affected following GR89,696 administration and morphine was only partially effective for blocking visceral pain. CONCLUSION: This study demonstrated that high levels of the opioids produced significant untoward effects and made distinguishing an analgesic versus a more general effect more difficult. Quantification of rearing behavior in conjunction with standard analgesic assays can help in gaining a better appreciation of true analgesic efficacy of experimental drugs.

17.
Environ Sci Process Impacts ; 19(10): 1300-1311, 2017 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-28858346

RESUMO

Eutrophication has become one of the most serious threats to aquatic ecosystems in the world. With the combined drivers of climate change and human activities, eutrophication has expanded from warm shallow lakes to cold-water lakes in relatively high latitude regions and has raised greater concerns over lake aquatic ecosystem health. A two-year field study was carried out to investigate water quality, phytoplankton characteristics and eutrophication status in a typical alpine glacial lake of Tianchi, a scenic area and an important drinking water source in the Xinjiang Autonomous Region of China, in 2014 and 2015. Clear seasonal and annual variations of nutrients and organic pollutants were found especially during rainy seasons. For the phytoplankton community, Bacillariophyta held the dominant position in terms of both species and biomass throughout the year, suggesting the dominant characteristics of diatoms in the phytoplankton structure in such a high-altitude cold-water lake. This was quite different from plain and warm lakes troubled with cyanobacterial blooming. Moreover, the dominant abundance of Cyclotella sp. in Tianchi might suggest regional warming caused by climate change, which might have profound effects on the local ecosystems and hydrological cycle. Based on water quality parameters, a comprehensive trophic level index TLI (Σ) was calculated to estimate the current status of eutrophication, and the results inferred emerging eutrophication in Tianchi. Results from Canonical Correspondence Analysis (CCA) and correlation analysis of phytoplankton genera and physico-chemical variables of water indicated that abiotic factors significantly influenced the phytoplankton community and its succession in Tianchi Lake. These abiotic factors could explain 77.82% of the total variance, and ammonium was identified as the most discriminant variable, which could explain 41% of the total variance followed by TP (29%). An estimation of annual nutrient loadings to Tianchi was made, and the results indicated that about 212.97 t of total nitrogen and 32.14 t of total phosphorus were transported into Tianchi Lake annually. Human socio-economic activities (runoff caused by historical overgrazing and increasing tourism) were identified as the most important contributors to Tianchi nutrient loadings.


Assuntos
Monitoramento Ambiental/métodos , Lagos/química , Fitoplâncton/crescimento & desenvolvimento , Poluentes Químicos da Água/análise , Qualidade da Água , Altitude , Biomassa , China , Mudança Climática , Cianobactérias/efeitos dos fármacos , Cianobactérias/crescimento & desenvolvimento , Diatomáceas/efeitos dos fármacos , Diatomáceas/crescimento & desenvolvimento , Ecossistema , Eutrofização , Camada de Gelo , Nitrogênio/análise , Fósforo/análise , Fitoplâncton/efeitos dos fármacos , Estações do Ano
18.
PLoS One ; 12(5): e0176753, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28472061

RESUMO

The detection of cool temperatures is thought to be mediated by primary afferent neurons that express the cool temperature sensing protein Transient Receptor Potential Cation Channel, Subfamily M, Member 8 (TRPM8). Using mice, this study tested the hypothesis that sex differences in sensitivity to cool temperatures were mediated by differences in neurons that express TRPM8. Ion currents from TRPM8 expressing trigeminal ganglion (TRG) neurons in females demonstrated larger hyperpolarization-activated cyclic nucleotide-gated currents (Ih) than male neurons at both 30° and 18°C. Additionally, female neurons' voltage gated potassium currents (Ik) were suppressed by cooling, whereas male Ik was not significantly affected. At the holding potential tested (-60mV) TRPM8 currents were not visibly activated in either sex by cooling. Modeling the effect of Ih and Ik on membrane potentials demonstrated that at 30° the membrane potential in both sexes is unstable. At 18°, female TRPM8 TRG neurons develop a large oscillating pattern in their membrane potential, whereas male neurons become highly stable. These findings suggest that the differences in Ih and Ik in the TRPM8 TRG neurons of male and female mice likely leads to greater sensitivity of female mice to the cool temperature. This hypothesis was confirmed in an operant reward/conflict assay. Female mice contacted an 18°C surface for approximately half the time that males contacted the cool surface. At 33° and 10°C male and female mice contacted the stimulus for similar amounts of time. These data suggest that sex differences in the functioning of Ih and Ik in TRPM8 expressing primary afferent neurons leads to differences in cool temperature sensitivity.


Assuntos
Neurônios/metabolismo , Canais de Cátion TRPM/metabolismo , Gânglio Trigeminal/metabolismo , Animais , Feminino , Masculino , Camundongos , Camundongos Transgênicos , Canais de Cátion TRPM/genética , Gânglio Trigeminal/citologia
19.
J Control Release ; 253: 160-164, 2017 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-28257988

RESUMO

Antibody-drug conjugates (ADCs) are a promising class of anticancer agents which have undergone substantial development over the past decade and are now achieving clinical success. The development of novel site-specific conjugation technologies enables the systematic study of architectural features within the antibody conjugated drug linker that may affect overall therapeutic indices. Here we describe the results of a systematic study investigating the impact of drug-linker design on the in vivo properties of a series of homogeneous ADCs with a conserved site of conjugation, a monodisperse drug loading, a lysosomal release functionality and monomethyl auristatin E as a cytotoxic payload. The ADCs, which differed only in the relative position of certain drug-linker elements within the reagent, were first evaluated in vitro using anti-proliferation assays and in vivo using mouse pharmacokinetics (PK). Regardless of the position of a discrete polymer unit, the ADCs showed comparable in vitro potencies, but the in vivo PK properties varied widely. The best performing drug-linker design was further used to prepare ADCs with different drug loadings of 4, 6 and 8 drugs per antibody and compared to Adcetris® in a Karpas-299 mouse xenograft model. The most efficacious ADC showed complete tumor regression and 10/10 tumor free survivors at a single 0.5mg/kg dose. This study revealed drug-linker design as a critical parameter in ADC development, with the potential to enhance ADC in vivo potency for producing more efficacious ADCs.


Assuntos
Antineoplásicos , Imunoconjugados , Oligopeptídeos , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Desenho de Fármacos , Humanos , Imunoconjugados/química , Imunoconjugados/farmacocinética , Imunoconjugados/uso terapêutico , Imunoglobulina G/química , Imunoglobulina G/uso terapêutico , Antígeno Ki-1/imunologia , Camundongos SCID , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Oligopeptídeos/química , Oligopeptídeos/farmacocinética , Oligopeptídeos/uso terapêutico , Polietilenoglicóis/química , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Water Res ; 40(1): 153-61, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16386776

RESUMO

Understanding the process controls on episodic fluxes of faecal indicator organisms (FIOs) is becoming increasingly important for the sustainable management and accurate modelling of water quality in both recreational and shellfish harvesting waters. Both environments exhibit transitory non-compliance with microbiological standards after rainfall episodes despite significant expenditures on control of sewage derived pollutant loadings in recent years. This paper demonstrates the role of wave propagation in the entrainment of FIOs from river channel beds as a contributor to episodes of poor microbial water quality. Previously reported data is reviewed in the light of relationships between wave and mean water travel velocities. High flows and rapid changes in river flow, driven by releases of bacterially pure reservoir water, resulted in elevated FIO concentrations and transient peaks in concentration. The new interpretation of these data suggest three modes of entrainment: (i) immediate wave-front disturbance, (ii) wave propagation lift and post-wave transport at mean flow velocity, and (iii) stochastic erosional mechanisms that maintain elevated bacterial concentrations under steady high flow conditions. This is a significant advance on the previously proposed mechanisms. Understanding these mechanisms provides an aid to managing streams intended for recreational use and emphasises the need to control the timing of high flow generation prior to use of the water body for e.g. canoeing events. In addition the processes highlighted have relevance for the protection of shellfish nurseries, drinking water supply intakes and episodes of poor bathing water quality, and associated health risks.


Assuntos
Fezes/microbiologia , Contaminação de Alimentos , Recreação , Frutos do Mar , Movimentos da Água , Animais , Bactérias/crescimento & desenvolvimento , Monitoramento Ambiental , Pesqueiros , Humanos , Modelos Teóricos , Controle de Qualidade , Rios , Reino Unido , Microbiologia da Água , Abastecimento de Água
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