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1.
Hum Reprod ; 37(1): 178-189, 2021 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-34755185

RESUMO

STUDY QUESTION: Do bi-allelic variants in the genes encoding the MSH4/MSH5 heterodimer cause male infertility? SUMMARY ANSWER: We detected biallelic, (likely) pathogenic variants in MSH5 (4 men) and MSH4 (3 men) in six azoospermic men, demonstrating that genetic variants in these genes are a relevant cause of male infertility. WHAT IS KNOWN ALREADY: MSH4 and MSH5 form a heterodimer, which is required for prophase of meiosis I. One variant in MSH5 and two variants in MSH4 have been described as causal for premature ovarian insufficiency (POI) in a total of five women, resulting in infertility. Recently, pathogenic variants in MSH4 have been reported in infertile men. So far, no pathogenic variants in MSH5 had been described in males. STUDY DESIGN, SIZE, DURATION: We utilized exome data from 1305 men included in the Male Reproductive Genomics (MERGE) study, including 90 males with meiotic arrest (MeiA). Independently, exome sequencing was performed in a man with MeiA from a large consanguineous family. PARTICIPANTS/MATERIALS, SETTING, METHODS: Assuming an autosomal-recessive mode of inheritance, we screened the exome data for rare, biallelic coding variants in MSH4 and MSH5. If possible, segregation analysis in the patients' families was performed. The functional consequences of identified loss-of-function (LoF) variants in MSH5 were studied using heterologous expression of the MSH5 protein in HEK293T cells. The point of arrest during meiosis was determined by γH2AX staining. MAIN RESULTS AND THE ROLE OF CHANCE: We report for the first time (likely) pathogenic, homozygous variants in MSH5 causing infertility in 2 out of 90 men with MeiA and overall in 4 out of 902 azoospermic men. Additionally, we detected biallelic variants in MSH4 in two men with MeiA and in the sister of one proband with POI. γH2AX staining revealed an arrest in early prophase of meiosis I in individuals with pathogenic MSH4 or MSH5 variants. Heterologous in vitro expression of the detected LoF variants in MSH5 showed that the variant p.(Ala620GlnTer9) resulted in MSH5 protein truncation and the variant p.(Ser26GlnfsTer42) resulted in a complete loss of MSH5. LARGE SCALE DATA: All variants have been submitted to ClinVar (SCV001468891-SCV001468896 and SCV001591030) and can also be accessed in the Male Fertility Gene Atlas (MFGA). LIMITATIONS, REASONS FOR CAUTION: By selecting for variants in MSH4 and MSH5, we were able to determine the cause of infertility in six men and one woman, leaving most of the examined individuals without a causal diagnosis. WIDER IMPLICATIONS OF THE FINDINGS: Our findings have diagnostic value by increasing the number of genes associated with non-obstructive azoospermia with high clinical validity. The analysis of such genes has prognostic consequences for assessing whether men with azoospermia would benefit from a testicular biopsy. We also provide further evidence that MeiA in men and POI in women share the same genetic causes. STUDY FUNDING/COMPETING INTEREST(S): This study was carried out within the frame of the German Research Foundation sponsored Clinical Research Unit 'Male Germ Cells: from Genes to Function' (DFG, CRU326), and supported by institutional funding of the Research Institute Amsterdam Reproduction and Development and funds from the LucaBella Foundation. The authors declare no conflict of interest.


Assuntos
Azoospermia , Infertilidade Masculina , Azoospermia/genética , Proteínas de Ciclo Celular/genética , Reparo de Erro de Pareamento de DNA , Feminino , Células HEK293 , Humanos , Infertilidade Masculina/genética , Masculino , Meiose/genética , Proteína MutS de Ligação de DNA com Erro de Pareamento/genética
2.
Bull Entomol Res ; 108(6): 831-842, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29402336

RESUMO

A wide variety of abiotic and biotic factors act on insect pests to regulate their populations. Knowledge of the time and magnitude of these factors is fundamental to understanding population dynamics and developing efficient pest management systems. We investigate the natural mortality factors, critical pest stages, and key mortality factors that regulate Chrysodeixis includens populations via ecological life tables. The total mortality caused by natural factors was 99.99%. Natural enemies were the most important mortality factors in all pest stages. The critical stages of C. includens mortality were second and fourth instars. The key mortality factors were predation by ants in the second instar and predation by Vespidae in the fourth instar. The elimination of these factors can cause an increase of 77.52 and 85.17% of C. includens population, respectively. This study elucidates the importance of natural enemies and other natural mortality factors in C. includens population regulation. These factors should be considered in developing and implementing C. includens management strategies and tactics in order to achieve effective and sustainable pest control.


Assuntos
Controle de Insetos , Mariposas/fisiologia , Controle Biológico de Vetores , Animais , Formigas/fisiologia , Brasil , Cadeia Alimentar , Larva/crescimento & desenvolvimento , Larva/fisiologia , Mariposas/crescimento & desenvolvimento , Comportamento Predatório , Vespas/fisiologia
3.
Am J Transplant ; 15(3): 606-17, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25656824

RESUMO

Intrabone (IB) hematopoietic cell transplantation (HCT) of umbilical cord blood in humans remains experimental and the technique has not been optimized. It is unknown whether hematopoietic progenitor cells (HPCs) injected IB are initially retained in the marrow or rapidly enter into the venous circulation before homing to the marrow. To develop an IB-injection technique that maximizes HPC marrow-retention, we tracked radiolabeled human HPCs following IB-injection into swine. We developed a method to radionuclide-label HPCs using a long-lived positron emitter (89) Zr and protamine sulfate that resulted in cellular-retention of low-dose radioactivity. This approach achieved radioactivity levels sufficient for detection by positron emission tomography with both high sensitivity and spatial resolution when fused with computed tomography. We found that conditions utilized in pilot IB-HCT clinical trials conducted by others led to both rapid drainage into the central venous circulation and cellular extravasation into surrounding muscle and soft tissues. By optimizing the needle design, using continuous real-time intra-marrow pressure monitoring, and by reducing the infusion-volume and infusion-rate, we overcame this limitation and achieved high retention of HPCs in the marrow. This method of IB cellular delivery is readily applicable in the clinic and could be utilized in future investigational IB-HCT trials aimed at maximizing marrow retention of HPCs.


Assuntos
Osso e Ossos/metabolismo , Transplante de Células-Tronco Hematopoéticas , Modelos Animais , Radioisótopos/química , Zircônio/química , Animais , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Suínos , Tomografia Computadorizada por Raios X
4.
J Econ Entomol ; 108(4): 1728-38, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26470314

RESUMO

Western bean cutworm, Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), is a native, univoltine pest of corn and dry beans in North America. The current degree-day model for predicting a specified percentage of yearly moth flight involves heat unit accumulation above 10°C after 1 May. However, because the moth's observed range has expanded into the northern and eastern United States, there is concern that suitable temperatures before May could allow for significant S. albicosta development. Daily blacklight moth catch and temperature data from four Nebraska locations were used to construct degree-day models using simple or sine-wave methods, starting dates between 1 January and 1 May, and lower (-5 to 15°C) and upper (20 to 43.3°C) developmental thresholds. Predicted dates of flight from these models were compared with observed flight dates using independent datasets to assess model performance. Model performance was assessed with the concordance correlation coefficient to concurrently evaluate precision and accuracy. The best model for predicting timing of S. albicosta flight used simple degree-day calculations beginning on 1 March, a 3.3°C (38°F) lower threshold, and a 23.9°C (75°F) upper threshold. The revised cumulative flight model indicated field scouting to estimate moth egg density at the time of 25% flight should begin when 1,432 degree-days (2,577 degree-days °F) have accumulated. These results underscore the importance of assessing multiple parameters in phenological models and utilizing appropriate assessment methods, which in this case may allow for improved timing of field scouting for S. albicosta.


Assuntos
Voo Animal , Modelos Biológicos , Mariposas/fisiologia , Distribuição Animal , Animais , Feminino , Masculino , Nebraska
5.
J Econ Entomol ; 107(5): 1985-91, 2014 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-26309290

RESUMO

Changes in protein content, peroxidase activity, and isozyme profiles in response to soybean aphid feeding were documented at V1 (fully developed leaves at unifoliate node, first trifoliate leaf unrolled) and V3 (fully developed leaf at second trifoliate node, third trifoliate leaf unrolled) stages of soybean aphid-tolerant (KS4202) and -susceptible (SD76R) soybeans. Protein content was similar between infested and control V1 and V3 stage plants for both KS4202 and SD76R at 6, 16, and 22 d after aphid introduction. Enzyme kinetics studies documented that control and aphid-infested KS4202 V1 stage and SD76R V1 and V3 stages had similar levels of peroxidase activity at the three time points evaluated. In contrast, KS4202 aphid-infested plants at the V3 stage had significantly higher peroxidase activity levels than control plants at 6 and 22 d after aphid introduction. The differences in peroxidase activity observed between infested and control V3 stage KS4202 plants at these two time points suggest that peroxidases may be playing multiple roles in the tolerant plant. Native gels stained for peroxidase were able to detect differences in the isozyme profiles of aphid-infested and control plants for both KS4202 and SD76R.


Assuntos
Antibiose , Afídeos/fisiologia , Glycine max/genética , Herbivoria , Peroxidases/genética , Proteínas de Plantas/genética , Animais , Feminino , Peroxidases/metabolismo , Proteínas de Plantas/metabolismo , Glycine max/metabolismo
6.
J Neural Transm (Vienna) ; 120(2): 291-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22842675

RESUMO

IncobotulinumtoxinA (Xeomin®) and onabotulinumtoxinA (BOTOX®) are unique botulinum neurotoxin type A (BoNT/A)-derived drugs. IncobotulinumtoxinA utilizes the naked 150 kDa holotoxin portion of BoNT/A, whereas onabotulinumtoxinA uses the complete native 900 kDa complex as drug substance. On the basis of purportedly similar pharmacological characteristics, these formulations were evaluated for potency by LD50 and mouse Digit Abduction Score (DAS) bioassays. DAS was also used to assess antigenicity. Full-range DAS dose-response profiles were achieved with four lots of each product, with similar observations between lots for a given product. Between products, however, the mean DAS potency of incobotulinumtoxinA (ED50 range 7.0-10.2 U/kg) was significantly lower than that of onabotulinumtoxinA (ED50 range 4.4-6.4 U/kg), consistent with lower measured potencies in the LD50 assay for incobotulinumtoxinA (potency range 62-82 U). In assessments of DAS duration of effect at similar unit doses, the observed lower potency of incobotulinumtoxinA translated into decreased peak efficacy and dose effect over time (i.e. shorter duration). In contrast, at equi-efficacious doses yielding near-maximal DAS responses, both toxin formulations were uniformly inhibited in a statistically significant manner when preincubated with rabbit-derived, onabotulinumtoxinA-neutralizing antibodies, supporting the position that inhibition of 150 kDa holotoxin serves as the common basis for neutralization and, therefore, incobotulinumtoxinA would not be expected to be effective in onabotulinumtoxinA-immunoresistant subjects (and vice versa). Further, with lower lot-to-lot relative potency, incobotulinumtoxinA is not dose-equivalent or interchangeable with onabotulinumtoxinA, suggesting that various aspects of drug product formulation may influence observed pharmacology.


Assuntos
Toxinas Botulínicas Tipo A/farmacologia , Animais , Bioensaio , Relação Dose-Resposta a Droga , Feminino , Dose Letal Mediana , Camundongos
7.
Anaerobe ; 23: 20-2, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23933434

RESUMO

Here we describe a study examining the antibiotic resistance gene carriage in anaerobes collected during a clinical study. The results demonstrated that genes normally associated with anaerobes were most prevalent such as tetQ, cepA and cblA although several genes associated with Enterobacteriaceae including sul2, blaSHV and strB were also detected.


Assuntos
Antibacterianos/uso terapêutico , Bactérias Anaeróbias/efeitos dos fármacos , Farmacorresistência Bacteriana , Fezes/microbiologia , Adulto , Antibacterianos/farmacologia , Bactérias Anaeróbias/isolamento & purificação , Feminino , Genes Bacterianos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
J Econ Entomol ; 106(3): 1274-85, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23865192

RESUMO

Western bean cutworm, Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), is a native pest of dry beans (Phaseolus vulgaris L.) and corn (Zea mays L.). Historically, the western bean cutworm was distributed in the western United States, but since 1999 eastward expansion has been observed. In corn, economic impact is caused by larval ear feeding. Information on western bean cutworm biology, ecology, and economic impact is relatively limited, and the development of economic injury levels (EILs) and economic thresholds (ETs) is required for more effective management. Studies during 2008-2011, across three ecoregions of Nebraska, sought to characterize western bean cutworm survival and development of EILs and ETs. Calculations of EILs and ETs incorporated the dynamics of corn price, management cost, and pest survival. The results from the current study demonstrated low larval survival of this species (1.51-12.82%). The mean yield loss from one western bean cutworm larva per plant was 945.52 kg/ha (15.08 bu/acre), based on 74,100 plants per ha. Economic thresholds are expressed as a percentage of plants with at least one egg mass. This study is the first study that explicitly incorporates variable management costs and crop values into western bean cutworm EIL calculations, and larval survival into ET calculations.


Assuntos
Agricultura/economia , Controle de Insetos/métodos , Mariposas/fisiologia , Zea mays/crescimento & desenvolvimento , Animais , Ecossistema , Comportamento Alimentar , Herbivoria , Larva/crescimento & desenvolvimento , Larva/fisiologia , Mariposas/crescimento & desenvolvimento , Nebraska , Óvulo/crescimento & desenvolvimento , Óvulo/fisiologia
9.
J Econ Entomol ; 106(2): 1036-44, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23786098

RESUMO

The soybean aphid, Aphis glycines Matsumura, has become the most significant soybean [Glycine max (L.) Merrill] insect pest in the north central soybean production region of North America. The objectives of this research were to measure selected genotypes for resistance to the soybean aphid in the later vegetative and reproductive stages under field conditions, and confirm the presence of tolerance in KS4202. The results from 2007 to 2011 indicate that KS4202 can support aphid populations with minimal yield loss at levels where significant yield loss would be expected in most other genotypes. The common Nebraska cultivar, 'Asgrow 2703', appears to show signs of tolerance as well. None of the yield parameters were significantly different between the aphid infested and noninfested treatments. Based on our results, genotypes may compensate for aphid feeding in different ways. Asgrow 2703 appears to produce a similar number of seeds as its noninfested counterpart, although the seeds produced are slightly smaller. Field evaluation of tolerance in KS4202 indicated a yield loss of only 13% at 34,585-53,508 cumulative aphid-days, when 24-36% yield loss would have been expected.


Assuntos
Antibiose , Afídeos/fisiologia , Glycine max/genética , Animais , Comportamento Alimentar , Nebraska , Ninfa/crescimento & desenvolvimento , Controle Biológico de Vetores , Densidade Demográfica , Estações do Ano , Glycine max/fisiologia
10.
J Econ Entomol ; 106(6): 2384-90, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24498738

RESUMO

Since its discovery in North America in 2000, the soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), has rapidly become an important pest of soybean [Glycine max (L.) Merrill], sometimes resulting in significant yield losses. Previous research has documented the toxicity of neonicotinoid seed treatments to soybean aphids, but control under field conditions has been inconsistent. Imidacloprid, a popular neonicotinoid insecticide, has been shown to exhibit antifeedant effects on aphids. Antifeedant activity has not been demonstrated for other neonicotinoids, including thiamethoxam. This research investigated the effects of a thiamethoxam seed treatment on soybean aphid feeding behavior by using electronic penetration graphs (EPG) to visualize stylet penetration behavior. Soybean aphid feeding behavior was assessed for 9 h on thiamethoxam-treated and untreated soybeans (V2 and V4 stages). Because results were inconclusive from initial experiments, a study was conducted to document the effects of thiamethoxam-treated soybeans on soybean aphid survival. The seed treatment was shown to negatively affect aphid survival at 4, 8, and 11 d after aphid introduction. A subsequent EPG study then was designed to document soybean aphid feeding behavior for 15 h, after an initial exposure of 9 h to thiamethoxam-treated soybeans. In this study, the exposed aphids exhibited significant differences in feeding behavior compared with those aphids feeding on untreated soybeans. Soybean aphids on thiamethoxam-treated soybeans spent significantly less time feeding in the sieve element phase, with a greater duration of nonprobing events. These studies suggest soybean aphids are unable to ingest phloem sap, which may be another important element in seed treatment protection.


Assuntos
Afídeos/efeitos dos fármacos , Inseticidas/toxicidade , Nitrocompostos/toxicidade , Oxazinas/toxicidade , Tiazóis/toxicidade , Animais , Afídeos/fisiologia , Fenômenos Eletrofisiológicos , Comportamento Alimentar , Feminino , Neonicotinoides , Glycine max , Tiametoxam
11.
Vet Pathol ; 49(3): 492-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22194357

RESUMO

A private zoological facility experienced an outbreak of malignant catarrhal fever (MCF) in 3 bongo antelope (Tragelaphus eurycerus). All cases were periparturient bongos that presented acutely anorectic beginning ~6 weeks after being housed with a Nubian ibex. Disease quickly progressed to respiratory distress and death within 24-72 hours of onset of clinical signs. Consistent gross findings in affected bongos were pulmonary edema and small pale tan foci in the livers. Histological lesions included a nonsuppurative vasculitis in multiple tissues, which is well recognized in MCF, but additionally included necrotizing cholangiohepatitis and neutrophilic, necrotizing myocarditis. Ibex-associated viral DNA was detected by polymerase chain reaction and was identical in sequence whether derived from bongos or ibex. The sequence closely matched an MCF viral DNA fragment that had been amplified from an ibex and bongo in a previous case report.


Assuntos
Animais de Zoológico/virologia , Antílopes , Herpesviridae/genética , Fígado/patologia , Febre Catarral Maligna/patologia , Febre Catarral Maligna/transmissão , Animais , Sequência de Bases , DNA Viral/genética , Evolução Fatal , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/veterinária , Análise de Sequência de DNA/veterinária
12.
Proc Natl Acad Sci U S A ; 106(11): 4171-6, 2009 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-19237555

RESUMO

Cyclin-dependent kinase 4 (CDK4)/cyclin D complexes are expressed early in the G(1) phase of the cell cycle and stimulate the expression of genes required for G(1) progression by phosphorylation of the product of the retinoblastoma gene, pRb. To elaborate the molecular pathway of CDK4 activation and substrate selection we have determined the structure of nonphosphorylated CDK4/cyclin D3. This structure of an authentic CDK/cyclin complex shows that cyclin binding may not be sufficient to drive the CDK active site toward an active conformation. Phosphorylated CDK4/cyclin D3 is active as a pRb kinase and is susceptible to inhibition by p27(Kip1). Unlike CDK2/cyclin A, CDK4/cyclin D3 can be inactivated by treatment with lambda-phosphatase, implying that phosphorylated T172 is accessible to a generic phosphatase while bound to a cyclin. Taken together, these results suggest that the structural mechanism of CDK4/cyclin D3 activation differs markedly from that of previously studied CDK/cyclin complexes.


Assuntos
Quinase 4 Dependente de Ciclina/química , Ciclinas/química , Domínio Catalítico , Cristalização , Cristalografia por Raios X , Ciclina D3 , Ativação Enzimática , Humanos , Monoéster Fosfórico Hidrolases/farmacologia , Fosforilação , Conformação Proteica
13.
J Dairy Sci ; 95(6): 3454-66, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22612981

RESUMO

Twelve 200-L barrels were used to determine the effects of N content and straw addition on changes in chemical composition and volatile losses measured by mass balance of dairy manure during a 136-d storage period. In addition, on d 0, 3, 6, 12, 28, 56, and 136, rate of NH3-N emission was measured, and core samples were collected to characterize fermentation pattern. High N (3.06% N, HN) and low N (2.75% N, LN) manures were obtained from cows fed diets with 17.2 and 15.2% crude protein (dry matter basis), respectively. On d 0, manure scraped from a freestall barn floor was diluted with water to 10% dry matter and loaded in barrels with (+S) or without (-S) mixing 22g of chopped wheat straw per kilogram of undiluted manure. Data were analyzed as a randomized complete block with a 2×2 factorial arrangement of treatments and 3 replications. We observed no interaction between treatments for the reported measurements, but several day-of-storage by treatment interactions were found. Throughout storage, total NH3-N (TAN, NH3-N + NH4⁺-N; 71.9 vs. 104.3 mg/dL), pH (6.40 vs. 6.74), and total volatile fatty acids (TVFA, starting on d 12) were lower for LN relative to HN manure. In the presence of straw, crust formation occurred between d 12 and 28, and pH became lower and TVFA became higher starting on d 56, compared with no straw. Treatments did not influence loss of organic matter, organic N, organic C, or N, which averaged 31, 29, 26, and 20%, respectively. However, neutral detergent fiber loss was 44% higher for +S relative to -S manure. Consistent reductions in the C:N ratio indicated proportionally higher volatile C loss than volatile N loss during storage. Overall rate of NH3-N emission was 36% lower for LN than for HN manure. In the presence of straw, rate of NH3-N emission did not differ until after crust formation, but was 67% lower on d 56 and 95% lower on d 136, when it was barely detectable, compared with manure with no straw. Manure pH was highly correlated with TVFA:TAN ratio (r=-0.78), and rate of NH3-N emission was correlated with pH, TVFA:TAN, TVFA, and TAN (r=0.47, -0.44, -0.23, and 0.28, respectively). In this trial, both microbial fermentation and crust formation influenced NH3-N emission rate and other measured responses, highlighting the importance of long-term sampling to evaluate treatment effects in manure storage studies.


Assuntos
Amônia/análise , Esterco/análise , Nitrogênio/análise , Animais , Bovinos , Indústria de Laticínios/métodos , Meio Ambiente , Poaceae , Fatores de Tempo
15.
Int J Clin Pharmacol Ther ; 49(10): 594-604, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21961484

RESUMO

OBJECTIVE: This was a singledose, randomized, positive- and placebo-controlled, double-dummy, double-blinded, 3-period crossover thorough QT study of exenatide, a glucagon-like peptide-1 receptor agonist for the treatment of Type 2 diabetes that enhances insulin secretion in a glucose- dependent fashion. METHODS: Healthy subjects (n = 70) underwent an initial tolerability screening, receiving subcutaneous exenatide 10 µg daily for 3 consecutive days. Subjects who passed tolerability screening (n = 62) received exenatide 10 µg, placebo, and moxifloxacin (400 mg orally; positive control) separated by washout periods of approximately 5 days. Twelve-lead electrocardiograms and blood samples for plasma exenatide, glucose, and insulin were collected. QT intervals were heart rate-corrected using Fridericia's correction (QTcF) and an individual correction (QTcI) and were analyzed as change from predose (ΔQTcF, or ΔQTcI). The relationships between the QTc interval and plasma exenatide, glucose, and insulin concentrations were also explored. RESULTS: Based on ΔQTcF and ΔQTcI assessments, exenatide 10 µg did not show a clinically significant prolongation of QT compared with placebo; the upper bound of the 2-sided 90% confidence interval (CI) for the largest mean difference from placebo was < 10 msec with both corrections. A positive slope was observed between plasma exenatide and ΔΔQTcF (0.02 (95% CI 0.01, 0.03), p < 0.001); no significant slope was observed between plasma exenatide concentrations and ΔΔQTcI (0.01 (95% CI 0.00, 0.02), p = 0.064). The plasma exenatide versus QTc analyses may be confounded by exenatide's glucose-lowering effect. A negative slope was observed between plasma glucose and [delta]QTcF (-1.5 (95% CI -2.2, -0.7), p < 0.001) and between plasma glucose and ΔQTcI (-1.6 (95% CI -2.3, -0.9), p < 0.0001). Plasma insulin and ΔQTcF were not correlated. CONCLUSION: This study demonstrated that single-dose exenatide 10 µg was not associated with clinically meaningful prolongation of the QTc interval.


Assuntos
Eletrocardiografia/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Peptídeos/farmacologia , Receptores de Glucagon/agonistas , Peçonhas/farmacologia , Adolescente , Adulto , Idoso , Glicemia/análise , Estudos Cross-Over , Método Duplo-Cego , Exenatida , Feminino , Receptor do Peptídeo Semelhante ao Glucagon 1 , Frequência Cardíaca/efeitos dos fármacos , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Peptídeos/efeitos adversos , Peptídeos/farmacocinética , Peçonhas/efeitos adversos , Peçonhas/farmacocinética
16.
J Econ Entomol ; 104(6): 1900-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22299351

RESUMO

Striacosta albicosta (Smith) (Lepidoptera: Noctuidae), is a native pest of dry beans (Phaseolus vulgaris L.) and corn (Zea mays L.). As a result of larval feeding damage on corn ears, S. albicosta has a narrow treatment window; thus, early detection of the pest in the field is essential, and egg mass sampling has become a popular monitoring tool. Three action thresholds for field and sweet corn currently are used by crop consultants, including 4% of plants infested with egg masses on sweet corn in the silking-tasseling stage, 8% of plants infested with egg masses on field corn with approximately 95% tasseled, and 20% of plants infested with egg masses on field corn during mid-milk-stage corn. The current monitoring recommendation is to sample 20 plants at each of five locations per field (100 plants total). In an effort to develop a more cost-effective sampling plan for S. albicosta egg masses, several alternative binomial sampling plans were developed using Wald's sequential probability ratio test, and validated using Resampling for Validation of Sampling Plans (RVSP) software. The benefit-cost ratio also was calculated and used to determine the final selection of sampling plans. Based on final sampling plans selected for each action threshold, the average sample number required to reach a treat or no-treat decision ranged from 38 to 41 plants per field. This represents a significant savings in sampling cost over the current recommendation of 100 plants.


Assuntos
Controle de Insetos/métodos , Mariposas/crescimento & desenvolvimento , Zea mays , Animais , Distribuição Binomial , Colorado , Controle de Insetos/economia , Nebraska , Óvulo/crescimento & desenvolvimento , Densidade Demográfica , Tamanho da Amostra , Estudos de Amostragem
17.
Neotrop Entomol ; 50(1): 5-20, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32737866

RESUMO

Soybean is considered one of today's most important crops. Planted on millions of hectares worldwide, the management of soybean pests usually requires large amounts of chemicals. However, a key component to meet the increasing demand for food due to the rapidly growing global population is protecting crops from pests while maintaining environmental quality through ecologically and economically sound integrated pest management (IPM) practices. Not only can IPM result in more profitable agriculture due to the reduction of pest control costs but also assures equitable, secure, sufficient, and stable flows of both food and ecosystem services. Despite those ecological and economic benefits, the vast areas of cultivated soybean as well as the convenience of spraying insecticides are encouraging the adoption of prophylactic pest control as a relatively inexpensive safeguard compared to IPM practices. Thus, in this forum, we discuss the reasons for soybean IPM not reaching its potential. We give examples of how we can revive this once successful pest management program with a focus on experiences in Brazil and the USA. We analyze IPM case studies to illustrate the need for growers to have easy and fast access to IPM information on its medium- and long-term benefits. Overall, this forum highlights the importance of IPM for agricultural sustainability including ecological and financial benefits.


Assuntos
Agricultura , Glycine max , Controle de Pragas/métodos , Animais , Brasil , Produtos Agrícolas , Insetos , Estados Unidos
18.
J Exp Med ; 176(5): 1381-6, 1992 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-1402683

RESUMO

Recent attention has focused on the T helper type 2 (Th2) lymphocyte as a source of interleukin 4 (IL-4) in allergic disease. However, Th2 cells themselves require a pulse of IL-4 to initiate this synthesis. Here we provide immunohistochemical evidence of IL-4 localization to human mast cells of the skin and respiratory tract, and demonstrate that immunoglobulin E-dependent stimulation of purified human lung mast cells leads to the rapid release of IL-4 into the extracellular environment. We propose that mast cell activation in an allergic response provides a rapid and local pulse of IL-4 into the local environment essential for the triggering of T lymphocytes into sustained IL-4 production and to initiate inflammatory cell accumulation and activation.


Assuntos
Interleucina-4/metabolismo , Mastócitos/metabolismo , Técnicas de Cultura , Humanos , Imuno-Histoquímica , Interleucina-4/análise , Interleucina-4/imunologia
19.
J Econ Entomol ; 103(4): 1405-11, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20857755

RESUMO

We evaluated selected soybean, Glycine max (L.) Merr., genotypes during their reproductive stages for resistance to the soybean aphid, Aphis glycines Matsumura (Hemiptera: Aphididae), under greenhouse conditions and documented the categories of aphid-resistant soybean. Two screening studies were performed to assess the level of resistance to the soybean aphid on six soybean genotypes during the reproductive stages of development. Significant differences in aphid damage ratings were detected among the soybean evaluated in the screening studies. Three genotypes (KS4202, K-1639-2, and K1621) were considered moderately resistant based on the assessed damage ratings. Two of these genotypes (K-1639-2 and KS4202), along with a commercial variety ('Asgrow 2703') were used in a follow-up greenhouse study to test for antibiosis and tolerance. For the antibiosis evaluation, KS4202 had significantly more nymphs than Asgrow 2703 and K-1639-2. In fact, KS4202 had a threefold difference in the number of nymphs compared with Asgrow 2703 (81.8 +/- 14.7 and 26.2 +/- 13.9 nymphs, respectively) and a fivefold difference compared with K-1639-2 (15.6 +/- 13.9). Although not significant, Asgrow 2703 had more nymphs than K-1639-2. The lower aphid numbers on infested K-1639-2 plants compared with aphid numbers on Asgrow 2703 and KS4202 plants indicates antibiosis for this genotype. No significant differences in average seed weight, number of seeds per pod, or plant damage were observed between infested and control KS4202 plants; however, significant differences in biomass, total seed weight, number of pods per plant, and number of seeds per plant were detected.


Assuntos
Afídeos/fisiologia , Genótipo , Glycine max/genética , Glycine max/parasitologia , Animais , Predisposição Genética para Doença , Interações Hospedeiro-Parasita/genética , Doenças das Plantas/genética
20.
Int J Cardiol Heart Vasc ; 26: 100447, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32140547

RESUMO

BACKGROUND: Recent studies have suggested an association between sleep apnea (SA) and atrial fibrillation (AF). We aimed to study the prevalence, characteristics, risk factors and type of sleep apnea (SA) in ablation candidates with paroxysmal AF. METHODS/RESULTS: We prospectively studied 579 patients with paroxysmal AF, including 157 women (27.1%) and 422 men (72.9%). Mean age was 59.9 ± 9.6 years and mean body mass index (BMI) 28.5 ± 4.5 kg/m2. SA was diagnosed using polygraphy for two nights at home. The Epworth Sleepiness Scale (ESS), STOP-Bang Questionnaire, and Berlin Questionnaire (BQ) assessed the degree of SA symptoms. A total of 479 (82.7%) patients had an apnea-hypopnea index (AHI) ≥ 5, whereas moderate-severe SA (AHI ≥ 15) was diagnosed in 244 patients (42.1%). The type of SA was predominantly obstructive, with a median AHI of 12.1 (6.7-20.6) (range 0.4-85.8). The median central apnea index was 0.3 (0.1-0.7). AHI increased with age, BMI, waist and neck circumference, body and visceral fat. Using the Atrial Fibrillation Severity Scale and the SF-36, patients with more severe SA had a higher AF burden, severity and symptom score and a lower Physical-Component Summary score. Age, male gender, BMI, duration of AF, and habitual snoring were independent risk factors in multivariate analysis (AHI ≥ 15). We found no association between ESS and AHI (R2 = 0.003, p = 0.367). CONCLUSIONS: In our AF population, SA was highly prevalent and predominantly obstructive. The high prevalence of SA detected in this study may indicate that SA is under-recognized in patients with AF. None of the screening questionnaires predicted SA reliably.

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