RESUMO
This paper describes the 30-year evolution of Supplemental Nutrition Assistance Program-Education (SNAP-Ed) to provide evidence to support our perspective that SNAP-Ed has earned its position as a pillar of the public health infrastructure in the US. Legislatively designated as a nutrition education and obesity prevention program, its focus is the nearly 90 million Americans with limited income. This audience experiences ongoing health disparities and is disproportionately affected by public health crises. The SNAP-Ed program works to reduce nutrition-related health disparities at all levels of the Social-Ecological Model, follows a robust evaluation framework, and leverages strong partnerships between state-based practitioners, state agencies, and the US Department of Agriculture. The expansion of SNAP-Ed would enable the program to reach more Americans so that our nation can end hunger and reduce diet-related health disparities.
Assuntos
Assistência Alimentar , Educação em Saúde , Saúde Pública , Humanos , Assistência Alimentar/história , Educação em Saúde/história , Educação em Saúde/métodos , Ciências da Nutrição/educação , Ciências da Nutrição/história , Obesidade/prevenção & controle , Pobreza , Saúde Pública/história , Saúde Pública/métodos , Infraestrutura de Saúde Pública , Estados Unidos , História do Século XX , História do Século XXIRESUMO
OBJECTIVE: To understand Supplemental Nutrition Assistance Program-Education (SNAP-Ed) Implementing Agencies'(SIAs) use of the SNAP-Ed Evaluation Framework (Framework), which is a tool that includes 51 indicators that SNAP-Ed programs can use to measure the success of their programs in the first 5 years after its release. METHODS: A repeated cross-sectional study design was utilized to administer electronic surveys to between 124 and 154 SIAs who received SNAP-Ed funding in fiscal years 2017, 2019, and 2021. Analyses included descriptive statistics and tests of proportions. RESULTS: Most SIAs indicated that they used the Framework to inform both data collection instruments and program planning decisions and the rates remained relatively constant over the 3 time points (> 80%). The most common specific use of the Framework across all 3 time points was to define, count, or measure the work accomplished, but this statistically decreased from 2017 (76%) to 2021 (57%) (z-scoreâ¯=â¯3.31; P < 0.001). CONCLUSIONS AND IMPLICATIONS: The results of this analysis confirmed that 5 years after its introduction, uptake and use of the Framework was high and that, as a whole, SIAs focused on priority indicators set by the US Department of Agriculture, with no notable increases in addressing and measuring longer-term, multisector, and population-wide outcomes. The systematic study of the Framework's usability over time has a broader application to other national health promotion initiatives with shared frameworks.
Assuntos
Assistência Alimentar , Humanos , Estudos Transversais , Promoção da Saúde/métodos , Educação em Saúde , Inquéritos e QuestionáriosRESUMO
The Genomics Education Partnership (GEP) engages students in a course-based undergraduate research experience (CURE). To better understand the student attributes that support success in this CURE, we asked students about their attitudes using previously published scales that measure epistemic beliefs about work and science, interest in science, and grit. We found, in general, that the attitudes students bring with them into the classroom contribute to two outcome measures, namely, learning as assessed by a pre- and postquiz and perceived self-reported benefits. While the GEP CURE produces positive outcomes overall, the students with more positive attitudes toward science, particularly with respect to epistemic beliefs, showed greater gains. The findings indicate the importance of a student's epistemic beliefs to achieving positive learning outcomes.
RESUMO
This paper focuses on effective messaging practices identified in data collected after 10 years of implementing a gain-framed messaging campaign encouraging healthier behaviors in middle-aged and older adults. In Study 1, we measured message recall and intended health behaviors in an intercept survey of 733 adults. Binary logistic regression indicated that women were more likely than men to report intent to change behavior. Recalling messages from billboards or fliers was associated with a lower likelihood of intended behavior change, and media type was associated with intended behavior for those who saw the message online (reducing screen time) or on television (increasing physical activity and ceasing smoking). Study 2 focused on adult generational differences in response to the campaign and types of media used to access information. Data from an intercept survey of 604 clients at agencies serving low-income adults were segmented into three age groups: under 35, ages 35-54, and ages 55+. Recall and reaction to campaign materials differed by age group, and the influence of life stage factors and health costs varied across age groups. Television and newspapers were most frequently reported by the oldest group, and social media and online news/blogs were most frequently chosen by the youngest group. Campaign response of adults older than age 35 aligned with goals of improving health behaviors. Together, these studies indicate that diffuse messaging strategies may raise overall awareness, and targeted strategies may be more influential in motivating behavior change. Influential factors and media should be differentially leveraged to target different age cohorts of adults.
Assuntos
Motivação , Saúde Pública , Adulto , Publicidade , Idoso , Feminino , Comportamentos Relacionados com a Saúde , Promoção da Saúde , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: Hyperkalemia more commonly affects patients with a glomerular filtration rate of less than 60 mL/min. Using intravenous (IV) insulin to shift potassium intracellularly may cause hypoglycemia, requiring additional treatment or longer hospitalization. Literature on insulin dosing in this context is limited, with one previous study indicating that 5 units of IV insulin might be as effective and result in less hypoglycemia than the standard dose of 10 units of IV insulin. The hyperkalemia treatment pathway at our institution was revised in May 2018 to include a reduced-dose option (5 units of insulin) for patients with end-stage renal disease. This study aimed to compare the prevalence of hypoglycemia between patients who received standard-dose vs reduced-dose IV insulin. METHODS: This single-center, retrospective, quasi-experimental study evaluated the impact of revision of the hyperkalemia treatment pathway by assessing rates of hypoglycemia during the 6 months before and after implementation of the revised pathway. The primary endpoint was prevalence of hypoglycemia, defined as a blood glucose level of less than or equal to 70 mg/dL. RESULTS: There was no statistically significant difference in the occurrence of hypoglycemia when comparing the pre- and postimplementation groups (36 [17.7%] patients vs 34 [18.7%] patients; P = 0.7924). The postimplementation group had a statistically significant lower reduction in potassium levels after treatment than the preimplementation group (mean [interquartile range], -0.9 [-1.3, -0.5] mEq/L vs -0.6 [-1.2, -0.2] mEq/L; P = 0.0095). Baseline potassium levels were similar between the groups. CONCLUSION: Administration of reduced-dose IV insulin for treatment of hyperkalemia was significantly less effective in lowering serum potassium levels and did not decrease prevalence of hypoglycemia. When accounting for potential confounders, the only variable that was associated with hypoglycemia was pretreatment glucose level.
Assuntos
Hiperpotassemia , Hipoglicemia , Glicemia , Humanos , Hiperpotassemia/diagnóstico , Hiperpotassemia/tratamento farmacológico , Hiperpotassemia/epidemiologia , Hipoglicemia/induzido quimicamente , Hipoglicemia/diagnóstico , Hipoglicemia/tratamento farmacológico , Insulina , Potássio , Estudos RetrospectivosRESUMO
The dissimilatory sulfate-reducing deltaproteobacterium Desulfovibrio vulgaris Hildenborough (ATCC 29579) was chosen by the research collaboration ENIGMA to explore tools and protocols for bringing this anaerobe to model status. Here, we describe a collection of genetic constructs generated by ENIGMA that are available to the research community.
RESUMO
OBJECTIVE: Provide the first baseline census of Supplemental Nutrition Assistance Program Education (SNAP-Ed) state implementing agencies' (SIAs) intent to use and evaluate 51 indicators described in the SNAP-Ed Evaluation Framework. METHODS: A cross-sectional study design was used to administer electronic surveys to 124 SIAs who received SNAP-Ed funding in 2017. Descriptive statistics were used to analyze the results. RESULTS: Of 51 indicators, SIAs reported their intent to impact an average of 19 indicators and evaluate an average of 12. More SIAs reported the intention to impact indicators at the individual (59%) and environmental levels (48%), compared with the sectors of influence (20%) and population levels (30%) of the framework. In addition, more SIAs intended to impact and evaluate short- or medium-term indicators, compared with long-term indicators. CONCLUSIONS AND IMPLICATIONS: These findings illustrate the progress made toward aggregating metrics to measure the collective impact of SNAP-Ed.
Assuntos
Assistência Alimentar , Política Nutricional , Estudos Transversais , Abastecimento de Alimentos , Educação em Saúde , Humanos , Intenção , PolíticasRESUMO
A hallmark of the research experience is encountering difficulty and working through those challenges to achieve success. This ability is essential to being a successful scientist, but replicating such challenges in a teaching setting can be difficult. The Genomics Education Partnership (GEP) is a consortium of faculty who engage their students in a genomics Course-Based Undergraduate Research Experience (CURE). Students participate in genome annotation, generating gene models using multiple lines of experimental evidence. Our observations suggested that the students' learning experience is continuous and recursive, frequently beginning with frustration but eventually leading to success as they come up with defendable gene models. In order to explore our "formative frustration" hypothesis, we gathered data from faculty via a survey, and from students via both a general survey and a set of student focus groups. Upon analyzing these data, we found that all three datasets mentioned frustration and struggle, as well as learning and better understanding of the scientific process. Bioinformatics projects are particularly well suited to the process of iteration and refinement because iterations can be performed quickly and are inexpensive in both time and money. Based on these findings, we suggest that a dynamic of "formative frustration" is an important aspect for a successful CURE.
RESUMO
The United States Department of Agriculture's Supplemental Nutrition Assistance Program Education, known as SNAP-Ed, is the country's largest and most diverse community nutrition program. In 2017, nearly 140 SNAP-Ed implementing agencies (SIAs) and hundreds of contractors delivered nutrition education to almost 5 million people in nearly 60,000 low-resource sites. Millions more were impacted with social marketing campaigns and policy, systems, and environmental changes. This article introduces and describes the benefits of the newly developed SNAP-Ed Evaluation Framework (Framework) and companion Interpretive Guide to consistently measure SNAP-Ed outcomes across different settings. The Framework uses the social ecological model as its underlying theory and features 51 indicators across four levels: Individual, Environmental Supports, Sectors of Influence, and Population Results. Topline findings from the first-year Census to track Framework adoption found that most SIAs intended to impact indicators closer to the inner levels of influence: Individual (mean = 59% of SIAs; SD = 22%) and Environmental Settings (mean = 48%; SD = 23%). As yet, few SIAs targeted outcomes for long-term indicators (mean = 26%; SD = 15%), Sectors of Influence (mean = 20%; SD = 12%), or Population Results (mean = 30%; SD = 11%). An in-depth example of how one state is using the Framework is described. The SNAP-Ed Evaluation Framework offers a new suite of evaluation measures toward eliminating disparities that contribute to poor diet, physical inactivity, food insecurity and obesity. Practitioners will need technical assistance to implement the Framework, especially to measure longer-term, multi-sector and population results, and to maximize effectiveness in SNAP-Ed.
Assuntos
Assistência Alimentar/organização & administração , Educação em Saúde/estatística & dados numéricos , Obesidade/prevenção & controle , Avaliação de Programas e Projetos de Saúde , Abastecimento de Alimentos , Humanos , Política Nutricional , Pobreza , Estados UnidosRESUMO
The Missouri AgrAbility program links the Cooperative Extension Service at a land-grant university with a nonprofit disability organization to provide practical education and assistance that promotes rural independence. This project utilized Photovoice to describe how Missouri AgrAbility clients perceived how the program impacts their lives. This article relates clients' perceptions of the impact of the AgrAbility program on their lives to the socio-ecologic model framework. Although the primary focus of AgrAbility is to help individuals who have disabilities maintain their independence, all levels of the socio-ecological model are integral in meeting the needs of program participants.
Assuntos
Agricultura , Pessoas com Deficiência/psicologia , Agricultura/economia , Agricultura/organização & administração , Humanos , Vida Independente , Missouri , Organizações sem Fins Lucrativos , Avaliação de Programas e Projetos de Saúde , Qualidade de Vida , População Rural , Fatores Socioeconômicos , Recursos HumanosRESUMO
Hydrogenases are highly active enzymes for hydrogen production and oxidation. [NiFeSe] hydrogenases, in which selenocysteine is a ligand to the active site Ni, have high catalytic activity and a bias for H2 production. In contrast to [NiFe] hydrogenases, they display reduced H2 inhibition and are rapidly reactivated after contact with oxygen. Here we report an expression system for production of recombinant [NiFeSe] hydrogenase from Desulfovibrio vulgaris Hildenborough and study of a selenocysteine-to-cysteine variant (Sec489Cys) in which, for the first time, a [NiFeSe] hydrogenase was converted to a [NiFe] type. This modification led to severely reduced Ni incorporation, revealing the direct involvement of this residue in the maturation process. The Ni-depleted protein could be partly reconstituted to generate an enzyme showing much lower activity and inactive states characteristic of [NiFe] hydrogenases. The Ni-Sec489Cys variant shows that selenium has a crucial role in protection against oxidative damage and the high catalytic activities of the [NiFeSe] hydrogenases.
Assuntos
Biocatálise , Desulfovibrio vulgaris/enzimologia , Hidrogenase/química , Hidrogenase/metabolismo , Selenocisteína/metabolismo , Desulfovibrio vulgaris/metabolismo , Ligantes , Modelos Moleculares , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Selenocisteína/químicaRESUMO
Flavin-based electron bifurcation (FBEB) is an important mechanism for the energy metabolism of anaerobes. A new family of NADH dehydrogenases, the flavin oxidoreductase (FlxABCD, previously called FloxABCD), was proposed to perform FBEB in sulphate-reducing organisms coupled with heterodisulfide reductase (HdrABC). We found that the hdrABC-flxABCD gene cluster is widespread among anaerobic bacteria, pointing to a general and important role in their bioenergetics. In this work, we studied FlxABCD of Desulfovibrio vulgarisâ Hildenborough. The hdr-flx genes are part of the same transcriptional unit and are increased in transcription during growth in ethanol-sulfate, and to a less extent during pyruvate fermentation. Two mutant strains were generated: one where expression of the hdr-flx genes was interrupted and another lacking the flxA gene. Both strains were unable to grow with ethanol-sulfate, whereas growth was restored in a flxA-complemented strain. The mutant strains also produced very reduced amounts of ethanol compared with the wild type during pyruvate fermentation. Our results show that in D. vulgaris, the FlxABCD-HdrABC proteins are essential for NADH oxidation during growth on ethanol, probably involving a FBEB mechanism that leads to reduction of ferredoxin and the small protein DsrC, while in fermentation they operate in reverse, reducing NAD(+) for ethanol production.
Assuntos
Desulfovibrio vulgaris/enzimologia , Etanol/metabolismo , FMN Redutase/metabolismo , NADH Desidrogenase/metabolismo , Oxirredutases/metabolismo , Desulfovibrio vulgaris/genética , Elétrons , Metabolismo Energético/genética , Metabolismo Energético/fisiologia , Ferredoxinas/metabolismo , NAD/metabolismo , NADH Desidrogenase/genética , Oxirredução , Oxirredutases/genética , Ácido Pirúvico/metabolismo , Sulfatos/metabolismoRESUMO
PURPOSE: This phase I study investigated the safety, dose-limiting toxicity, and efficacy in three cohorts all treated with the mTOR inhibitor everolimus that was delivered (1) in combination with 5-fluorouracil with leucovorin (5-FU/LV), (2) with mFOLFOX6 (5-FU/LV + oxaliplatin), and (3) with mFOLFOX6 + panitumumab in patients with refractory solid tumors. METHODS: Patients were accrued using a 3-patient cohort design consisting of two sub-trials in which the maximum tolerated combination (MTC) and dose-limiting toxicity (DLT) of everolimus and 5-FU/LV was established in Sub-trial A and of everolimus in combination with mFOLFOX6 and mFOLFOX6 plus panitumumab in Sub-trial B. RESULTS: Thirty-six patients were evaluable for toxicity, 21 on Sub-trial A and 15 on Sub-trial B. In Sub-trial A, DLT was observed in 1/6 patients enrolled on dose level 1A and 2/3 patients in level 6A. In Sub-trial B, 2/3 patients experienced DLT on level 1B and subsequent patients were enrolled on level 1B-1 without DLT. Three of six patients in cohort 2B-1 experienced grade 3 mucositis, and further study of the combination of everolimus, mFOLFOX6 and panitumumab was aborted. Among the 24 patients enrolled with refractory metastatic colorectal cancer, the median time on treatment was 2.7 months with 45 % of patients remaining on treatment with stable disease for at least 3 months. CONCLUSIONS: While a regimen of everolimus in addition to 5-FU/LV and mFOLFOX6 appears safe and tolerable, the further addition of panitumumab resulted in an unacceptable level of toxicity that cannot be recommended for further study. Further investigation is warranted to better elucidate the role which mTOR inhibitors play in patients with refractory solid tumors, with a specific focus on mCRC as a potential for the combination of this targeted and cytotoxic therapy in future studies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Sirolimo/análogos & derivados , Serina-Treonina Quinases TOR/antagonistas & inibidores , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Coortes , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Término Precoce de Ensaios Clínicos , Everolimo , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mucosite/induzido quimicamente , Mucosite/fisiopatologia , Metástase Neoplásica , Neoplasias/tratamento farmacológico , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Oxaliplatina , Panitumumabe , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Índice de Gravidade de Doença , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Sirolimo/uso terapêuticoRESUMO
Sulfate-reducing bacteria such as Desulfovibrio vulgaris Hildenborough are often found in environments with limiting growth nutrients. Using lactate as the electron donor and carbon source, and sulfate as the electron acceptor, wild type D. vulgaris shows motility on soft agar plates. We evaluated this phenotype with mutants resulting from insertional inactivation of genes potentially related to motility. Our study revealed that the cheA3 (DVU2072) kinase mutant was impaired in the ability to form motility halos. Insertions in two other cheA loci did not exhibit a loss in this phenotype. The cheA3 mutant was also non-motile in capillary assays. Complementation with a plasmid-borne copy of cheA3 restores wild type phenotypes. The cheA3 mutant displayed a flagellum as observed by electron microscopy, grew normally in liquid medium, and was motile in wet mounts. In the growth conditions used, the D. vulgaris ΔfliA mutant (DVU3229) for FliA, predicted to regulate flagella-related genes including cheA3, was defective both in flagellum formation and in forming the motility halos. In contrast, a deletion of the flp gene (DVU2116) encoding a pilin-related protein was similar to wild type. We conclude that wild type D. vulgaris forms motility halos on solid media that are mediated by flagella-related mechanisms via the CheA3 kinase. The conditions under which the CheA1 (DVU1594) and CheA2 (DVU1960) kinase function remain to be explored.
RESUMO
To understand the energy conversion activities of the anaerobic sulfate-reducing bacteria, it is necessary to identify the components involved in electron flow. The importance of the abundant type I tetraheme cytochrome c3 (TpIc3) as an electron carrier during sulfate respiration was questioned by the previous isolation of a null mutation in the gene encoding TpIc3, cycA, in Desulfovibrio alaskensis G20. Whereas respiratory growth of the CycA mutant with lactate and sulfate was little affected, growth with pyruvate and sulfate was significantly impaired. We have explored the phenotype of the CycA mutant through physiological tests and transcriptomic and proteomic analyses. Data reported here show that electrons from pyruvate oxidation do not reach adenylyl sulfate reductase, the enzyme catalyzing the first redox reaction during sulfate reduction, in the absence of either CycA or the type I cytochrome c3:menaquinone oxidoreductase transmembrane complex, QrcABCD. In contrast to the wild type, the CycA and QrcA mutants did not grow with H2 or formate and sulfate as the electron acceptor. Transcriptomic and proteomic analyses of the CycA mutant showed that transcripts and enzymes for the pathway from pyruvate to succinate were strongly decreased in the CycA mutant regardless of the growth mode. Neither the CycA nor the QrcA mutant grew on fumarate alone, consistent with the omics results and a redox regulation of gene expression. We conclude that TpIc3 and the Qrc complex are D. alaskensis components essential for the transfer of electrons released in the periplasm to reach the cytoplasmic adenylyl sulfate reductase and present a model that may explain the CycA phenotype through confurcation of electrons.
Assuntos
Desulfovibrio/metabolismo , Transporte de Elétrons , Sulfatos/metabolismo , Desulfovibrio/crescimento & desenvolvimento , Deleção de Genes , Lactatos/metabolismo , Redes e Vias Metabólicas , Modelos Biológicos , Oxirredução , Proteoma , Ácido Pirúvico/metabolismo , TranscriptomaRESUMO
The adenosine 5'-phosphosulfate reductase (AprAB) is the enzyme responsible for the reduction of adenosine 5'-phosphosulfate (APS) to sulfite in the biological process of dissimilatory sulfate reduction, which is carried out by a ubiquitous group of sulfate reducing prokaryotes. The electron donor for AprAB has not been clearly identified, but was proposed to be the QmoABC membrane complex, since an aprBA-qmoABC gene cluster is found in many sulfate reducing and sulfur-oxidizing bacteria. The QmoABC complex is essential for sulfate reduction, but electron transfer between QmoABC and AprAB has not been reported. In this work we provide the first direct evidence that QmoABC and AprAB interact in Desulfovibrio spp., using co-immunoprecipitation, cross-linking Far-Western blot, tag-affinity purification, and surface plasmon resonance studies. This showed that the QmoABC-AprAB complex has a strong steady-state affinity (K(D) = 90 ± 3 nM), but has a transient character due to a fast dissociation rate. Far-Western blot identified QmoA as the Qmo subunit most involved in the interaction. Nevertheless, electron transfer from menaquinol analogs to APS through anaerobically purified QmoABC and AprAB could not be detected. We propose that this reaction requires the involvement of a third partner to allow electron flow driven by a reverse electron bifurcation process, i.e., electron confurcation. This process is deemed essential to allow coupling of APS reduction to chemiosmotic energy conservation.
RESUMO
Progress in the genetic manipulation of the Desulfovibrio strains has provided an opportunity to explore electron flow pathways during sulfate respiration. Most bacteria in this genus couple the oxidation of organic acids or ethanol with the reduction of sulfate, sulfite, or thiosulfate. Both fermentation of pyruvate in the absence of an alternative terminal electron acceptor, disproportionation of fumarate and growth on H(2) with CO(2) during sulfate reduction are exhibited by some strains. The ability to produce or consume H(2) provides Desulfovibrio strains the capacity to participate as either partner in interspecies H(2) transfer. Interestingly the mechanisms of energy conversion, pathways of electron flow and the parameters determining the pathways used remain to be elucidated. Recent application of molecular genetic tools for the exploration of the metabolism of Desulfovibrio vulgaris Hildenborough has provided several new datasets that might provide insights and constraints to the electron flow pathways. These datasets include (1) gene expression changes measured in microarrays for cells cultured with different electron donors and acceptors, (2) relative mRNA abundances for cells growing exponentially in defined medium with lactate as carbon source and electron donor plus sulfate as terminal electron acceptor, and (3) a random transposon mutant library selected on medium containing lactate plus sulfate supplemented with yeast extract. Studies of directed mutations eliminating apparent key components, the quinone-interacting membrane-bound oxidoreductase (Qmo) complex, the Type 1 tetraheme cytochrome c(3) (Tp1-c(3)), or the Type 1 cytochrome c(3):menaquinone oxidoreductase (Qrc) complex, suggest a greater flexibility in electron flow than previously considered. The new datasets revealed the absence of random transposons in the genes encoding an enzyme with homology to Coo membrane-bound hydrogenase. From this result, we infer that Coo hydrogenase plays an important role in D. vulgaris growth on lactate plus sulfate. These observations along with those reported previously have been combined in a model showing dual pathways of electrons from the oxidation of both lactate and pyruvate during sulfate respiration. Continuing genetic and biochemical analyses of key genes in Desulfovibrio strains will allow further clarification of a general model for sulfate respiration.
RESUMO
Desulfovibrio alaskensis G20 (formerly Desulfovibrio desulfuricans G20) is a Gram-negative mesophilic sulfate-reducing bacterium (SRB), known to corrode ferrous metals and to reduce toxic radionuclides and metals such as uranium and chromium to sparingly soluble and less toxic forms. We present the 3.7-Mb genome sequence to provide insights into its physiology.
Assuntos
Desulfovibrio/classificação , Desulfovibrio/genética , Genoma Bacteriano , Sequência de Bases , Desulfovibrio/fisiologia , Dados de Sequência MolecularRESUMO
Sulfate reducing bacteria (SRB) are physiologically important given their nearly ubiquitous presence and have important applications in the areas of bioremediation and bioenergy. This chapter provides details on the steps used for homologous-recombination mediated chromosomal manipulation of Desulfovibrio vulgaris Hildenborough, a well-studied sulfate reducer. More specifically, we focus on the implementation of a "parts" based approach for suicide vector assembly, important aspects of anaerobic culturing, choices for antibiotic selection, electroporation-based DNA transformation, as well as tools for screening and verifying genetically modified constructs. These methods, which in principle may be extended to other SRB, are applicable for functional genomics investigations, as well as metabolic engineering manipulations.
Assuntos
Cromossomos Bacterianos , Desulfovibrio/genética , Desulfovibrio/metabolismo , Engenharia Genética/métodos , Sulfatos/metabolismo , Biodegradação Ambiental , Técnicas de Cultura de Células , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Desulfovibrio/fisiologia , Eletroporação/métodos , Deleção de Genes , Engenharia Genética/instrumentação , Vetores Genéticos , Plasmídeos/genética , Plasmídeos/metabolismo , Recombinação GenéticaRESUMO
PURPOSE: Epidermal growth factor receptor (EGFR) inhibition may overcome chemotherapy resistance by inhibiting important anti-apoptotic signals that are constitutively activated by an overstimulated EGFR pathway. METHODS: This phase I dose escalation trial assessed the safety and efficacy of vinflunine, a novel vinca alkaloid microtubule inhibitor, with erlotinib, an EGFR tyrosine kinase inhibitor, in patients with refractory solid tumors. RESULTS: Seventeen patients were treated, 10 with continuous erlotinib, and 7 with intermittent erlotinib. At dose level 1, vinflunine 280 mg/m(2) IV day 1 and erlotinib 75 mg PO days 2-21 ("continuous erlotinib") in 21 day cycles, two of four patients experienced DLTs. At dose level -1 (vinflunine 250 mg/m(2) every 21 days and erlotinib 75 mg/day), two of six patients experienced DLTs. The study was amended to enroll to "intermittent erlotinib" dosing: vinflunine day 1 and erlotinib days 2-15 of a 21 day cycle. Two of seven experienced DLTs and the study was terminated. One patient with breast cancer had a partial response; three had stable disease ≥ 6 cycles. All were treated in the continuous erlotinib group. CONCLUSIONS: Given the marked toxicity in our patient population, the combination of vinflunine and erlotinib cannot be recommended for further study with these dosing schemas.