bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of the dissociation rate of unlabelled ligand–receptor complexes by a ‘two‐step’ competition binding approach
Authors: Packeu A , Wennerberg M , Balendran A , Vauquelin G 
Published: June 2010

BACKGROUND AND PURPOSEBecause thein vivoeffectiveness of ligands may also be determined by the rate by which they dissociate from their target receptors, drug candidates are being increasingly screened for this kinetic property. The dissociation rate of unlabelled ligand–receptor complexes can be estimated indirectly from their ability to slow the association of subsequently added radioligand molecules.EXPERIMENTAL APPROACHWe used the ‘two‐step competition’ binding approach consisting of pre‐incubating the receptor preparation with a wide range of ligand concentrations, washing off free ligand molecules, adding radioligand and monitoring its receptor binding after a fixed time. Based on the rationale that binding of both ligands is mutually exclusive and that they bind according to the law of mass action to a single class of sites, the unlabelled ligand's disociation rate can be estimated from the upward shift that the competition curve experiences after washing.KEY RESULTSThe relevance of the ‘two‐step competition’ approach was explored by computer simulations and by comparing the dissociation behaviour of unlabelled D2dopamine and CB1cannabinoid receptor antagonists in this and alternative approaches. Besides providing satisfactory estimations of dissociation rates, the method also detects the ability of the unlabelled ligand molecules to be released from ‘sinks’ such as the cell membrane.CONCLUSIONS AND IMPLICATIONSAs the ‘two‐step competition’ requires rapid intermediate washing steps and needs radioligand binding to be measured at only one time point, this approach is particularly suited for binding studies on intact plated cells.LINKED ARTICLESThis article is part of a themed section on Analytical Receptor Pharmacology in Drug Discovery. To view the other articles in this section visithttp://dx.doi.org/10.1111/bph.2010.161.issue‐6
Local Food, Local Engagement: Community‐Supported Agriculture in Eastern Iowa
Authors: Janssen Brandi 
Published: June 2010

AbstractThis paper examines some of the daily realities of operating a Community‐Supported Agriculture (CSA) farm in eastern Iowa and addresses the concept of community among growers. Popular depictions of local foods systems often emphasize the close relationships that develop between producers and consumers. This picture, however, may gloss over the necessary complexities of a healthy local food system. CSA has been promoted as a direct marketing strategy for small‐scale growers and touted as a way of developing positive relationships between producers and consumers. Nevertheless, it is also important to understand that successful CSA initiatives are often reliant on a broad network of support that includes more than just growers and eaters. Ethnographic descriptions of CSA farms presented here show how involvement by media and other organizations contribute to successful CSAs as well as an overall concept of “civic agriculture.” These descriptions also show that access to affordable, reliable labor tends to be among the greatest challenges for CSA growers.
The Changing Face of Community‐Supported Agriculture
Authors: Lang K. Brandon 
Published: June 2010

AbstractCommunity‐supported agriculture (CSA) establishes a direct connection between producers and consumers of locally grown produce. Members typically pay a seasonal fee in advance of the growing season in return for weekly shares of produce throughout the course of the growing season. This paper is based upon survey and interview data collected among members of From the Ground Up, a CSA located in Maryland. The main purpose of this paper is to answer two major research questions. “How has From the Ground Up CSA evolved?” and “Why have these changes occurred?”
Archeological Evidence for Dietary Use of Bigfoot Leopard Frog (Lithobates megapoda) in Postclassic and Colonial Central Mexico
Authors: Porcasi Judith F. 
Published: June 2010

AbstractAnalysis of archaeofaunal remains recovered from several geographically and culturally linked postclassic sites in the Laguna de Magdalena Basin, Jalisco, Mexico, reveals that indigenous agrarian people of this area incorporated substantial quantities of the robust bigfoot leopard frog (Lithobates megapoda) (Taylor 1942) in their diet during both prehispanic and colonial occupations. Even though residents of this area combined hunting and fishing with cultivation of both native and colonially introduced flora and fauna, more frog remains were recovered than any other small species. Furthermore, it appears that exploitation of the frog was most intensive during the colonial occupation. As in modern cuisine, the hindlimbs were the preferred portion. Mortuary frog effigies suggest that the frog may also have had iconic value.
Clinical evaluation of particulate allogeneic with and without autogenous bone grafts and resorbable collagen membranes for bone augmentation of atrophic alveolar ridges
Authors: Beitlitum Ilan , Artzi Zvi , Nemcovsky Carlos E. 
Published: June 2010

AbstractObjectives: The evaluate the clinical outcome of bone augmentation with the use of particulate mineralized freeze‐dried bone allograft (FDBA) with or without the addition of autogeneous bone chips, applied in a bi‐layered (BL) technique, covered by a resorbable cross‐linked collagen membrane.Material and methods: Fifty patients presenting with a vertical and/or lateral ridge deficiency of at least 3 mm were included: Group FDBA, N=27 patients, particulate FDBA was the only graft; and Group BL, N=23 patients, a BL bone grafting procedure where autogenous bone chips were the inner layer and FDBA the outer. Bone graft was covered with a ribose cross‐linked collagen barrier membrane. Ridge dimensions were clinically or radiographically (computerized tomography scan) measured at the time of the bone augmentation procedure and at implant placement or uncovering and the maximum linear vertical or horizontal calcified tissue gain was calculated. Statistical analysis consisted of linear regression analysis, with maximum bone gain being the dependent variable.Results: In the FDBA group, mean vertical bone gain was 3.47 mm (SD 1.25) and the horizontal, 5 mm (SD 1.28), while in the BL values were 3.5 mm (SD 1.2) and 3.6 mm (SD 1.72), respectively. Addition of autogenous bone does not appear to statistically significantly enhance the results. Spontaneous membrane exposure occurred in 24% of the cases and was the only variant that significantly influenced results (P<0.001).Conclusions: Large vertical and/or horizontal ridge deficiencies may be treated with FDBA and ribose cross‐linked collagen barrier membranes with good clinical outcome. No added effect of the application of a layer of autogenous bone in these bone augmentation procedures could be demonstrated.Spontaneous membrane exposure was the only parameter to affect the degree of new calcified tissue formation. To cite this article:
Beitlitum I, Artzi Z, Nemcovsky CE. Clinical evaluation of particulate allogeneic with and without autogenous bone grafts and resorbable collagen membranes for bone augmentation of atrophic alveolar ridges. Clin. Oral Impl. Res. 21, 2010; 1242–1250. doi: 10.1111/j.1600‐0501.2010.01936.x
Neuro‐developmental outcome and brain‐derived neurotrophic factor level in relation to feeding practice in early infancy
Authors: Nassar May Fouad , Younis Neveen Tawakol , El‐Arab Soha Ezz , Fawzi Fatma Asaad 
Published: June 2010

AbstractThis study was designed to assess brain‐derived neurotrophic factor (BDNF) as a possible candidate for enhanced cognition in breastfed infants. The study was conducted on 42 infants, 4–6 months old, who were classified according to their feeding pattern into breastfed group, formula‐fed group and mixed‐feeding group. Each infant was subjected to history taking, clinical examination, estimation of the level of BDNF by Enzyme‐Linked Immunosorbent Assay (ELISA) technique and assessment by Bayley scale of infant development‐second edition (BSID‐II). The current study revealed that breastfed group had higher BSID‐II scores followed by mixed‐fed group then formula‐fed one, yet these results reached statistical significance only in total behaviour rating scale (TBRS) and Motor Quality Percentile rank values. Additionally, breastfed infants had significantly higher values of BDNF when compared to those receiving formula milk. Negative correlations between BDNF and both weight for age and weight for length scores were detected. Furthermore, significant positive correlation was detected between BDNF and TBRS. Regression analysis studies revealed that breastfeeding is the most determinant factor for BDNF, TBRS and Motor Quality Percentile rank values. Serum BDNF levels are significantly higher in breastfed infants and shows positive correlations with the results of BSID‐II. Given that simultaneous increase in brain BDNF occurs due to onsite production, transport from the periphery or both, it is prudent to hypothesize that BDNF could be one of the factors responsible for the enhanced cognition detected in breastfed infants.
High dietary ratio of omega‐6 to omega‐3 polyunsaturated acids during pregnancy and prevalence of post‐partum depression
Authors: da Rocha Camilla M.M. , Kac Gilberto 
Published: June 2010

AbstractObservational studies suggest association between low concentrations of omega‐3 family fatty acids and greater risk for post‐partum depression (PPD). The objective was to investigate the effect of unbalanced dietary intake of omega‐6/omega‐3 ratio >9:1 in the prevalence for PPD. The study comprises a prospective cohort with four waves of follow‐up during pregnancy and one following delivery. PPD was evaluated according to the Edinburgh Post‐partum Depression Scale (PPD ≥ 11) in 106 puerperae between 2005 and 2007, in Rio de Janeiro, Brazil. Independent variables included socio‐demographic, obstetric, pre‐pregnancy body mass index (BMI) and dietary intake data, which were obtained by means of a food frequency questionnaire in the first trimester of pregnancy. Statistical analysis involved calculation of PPD prevalence and multivariate Poisson regression with robust variance. PPD prevalence amounted to 26.4% [n = 28; confidence interval (CI) 95%: 18.0–34.8], and higher prevalences of PPD were observed in women who consumed an omega‐6/omega‐3 ratio >9:1 (60.0%) and in those with pre‐pregnancy BMI <18.5 kg/m2 (66.7%). These variables held as factors associated to PPD in the multivariate model, elevating the chances of occurrence of the outcome in 2.50 (CI 95%: 1.21–5.14) and 4.01 times (CI 95%: 1.96–8.20), respectively. Analyses were adjusted for age, schooling, pre‐pregnancy BMI, lipids consumption and time elapsed since delivery. It verified an association between omega‐6/omega‐3 ratio above 9:1, the levels recommended by the Institute of Medicine, and the prevalence of PPD. These results add to the evidence regarding the importance of omega‐6 and omega‐3 fatty acids in the regulation of mental health mechanisms.
Public versus expert opinions regarding public involvement processes used in resource and wildlife management
Authors: Decker Stephen E. , Bath Alistair J. 
Published: June 2010

AbstractSuccessful public involvement efforts can reduce conflict and build trust between resource managers and the public. Differences of opinion between the public and wildlife managers regarding the importance of various characteristics and methods of public involvement have implications for managers wishing to design effective public involvement processes. We compared and contrasted the preferences of German public and European experts in large mammal management regarding characteristics and methods of public involvement. Expert participants attributed high levels of importance to including scientific information in decision making while general public respondents attributed high levels of importance to the cost effectiveness and representativeness of the public involvement effort. Differences were also observed regarding public involvement methods. Experts preferred task forces and advisory groups while the general public preferred information materials and public meetings. We discuss the likely causes of similarities and differences between these two groups and examine the consequent implications for managers.
Incorporating local tenure in the systematic design of marine protected area networks
Authors: Weeks Rebecca , Russ Garry R. , Bucol Abner A. , Alcala Angel C. 
Published: June 2010

AbstractAlthough the importance of socioeconomic factors in conservation planning is increasingly recognized, there are few examples demonstrating how such factors can be practically incorporated into the design of protected area networks. Here, we illustrate how spatial zoning software can be used to consider local marine tenure explicitly in the design of marine protected area (MPA) networks, using a case study from the Philippines. By stipulating the minimum area of fishing grounds that must remain open to each local fishing community, we were able to design MPA networks that impacted local resource users more equitably and were therefore more likely to be socioeconomically viable. MPA networks that considered local tenure boundaries had a greater overall area and cost than those that sought to minimize costs to small‐scale fishers as a single stakeholder group. However, in this context, established concepts of “efficiency” in conservation planning are likely to be less important than minimizing costs to each fishing community individually.
NagZ Inactivation Prevents and Reverts β-Lactam Resistance, Driven by AmpD and PBP 4 Mutations, in
Pseudomonas aeruginosa
Authors: Zamorano Laura , Reeve Thomas M. , Deng Lehua , Juan Carlos , Moyá Bartolomé , Cabot Gabriel , Vocadlo David J. , Mark Brian L. , Oliver Antonio 
Published: June 2010

ABSTRACT

AmpC hyperproduction is the most frequent mechanism of resistance to penicillins and cephalosporins in
Pseudomonas aeruginosa
and is driven by
ampD
mutations or the recently described inactivation of
dacB
, which encodes the nonessential penicillin-binding protein (PBP) PBP 4. Recent work showed that
nagZ
inactivation attenuates β-lactam resistance in
ampD
mutants. Here we explored whether the same could be true for the
dacB
mutants with
dacB
mutations alone or in combination with
ampD
mutations. The inactivation of
nagZ
restored the wild-type β-lactam MICs and
ampC
expression of PAO1
dacB
and
ampD
mutants and dramatically reduced the MICs (for example, the MIC for ceftazidime dropped from 96 to 4 μg/ml) and the level of
ampC
expression (from ca. 1,000-fold to ca. 50-fold higher than that for PAO1) in the
dacB
-
ampD
double mutant. On the other hand,
nagZ
inactivation had little effect on the inducibility of AmpC. The NagZ inhibitor
O
-(2-acetamido-2-deoxy-
d
-glucopyranosylidene)amino-
N
-phenylcarbamate attenuated the β-lactam resistance of the AmpC-hyperproducing strains, showing a greater effect on the
dacB
mutant (reducing the ceftazidime MICs from 24 to 6 μg/ml) than the
ampD
mutant (reducing the MICs from 8 to 4 μg/ml). Additionally,
nagZ
inactivation in the
dacB
mutant blocked the overexpression of
creD
(
blrD
), which is a marker of the activation of the CreBC (BlrAB) regulator involved in the resistance phenotype. Finally, through population analysis, we show that the inactivation of
nagZ
dramatically reduces the capacity of
P. aeruginosa
to develop ceftazidime resistance, since spontaneous mutants were not obtained at concentrations ≥8 μg/ml (the susceptibility breakpoint) for the
nagZ
mutant but were obtained with wild-type PAO1. Therefore, NagZ is envisaged to be a candidate target for preventing and reverting β-lactam resistance in
P. aeruginosa
.
Mycobacterium tuberculosis
Dihydrofolate Reductase Is Not a Target Relevant to the Antitubercular Activity of Isoniazid
Authors: Wang Feng , Jain Paras , Gulten Gulcin , Liu Zhen , Feng Yicheng , Ganesula Krishna , Motiwala Alifiya S. , Ioerger Thomas R. , Alland David , Vilchèze Catherine , Jacobs William R. , Sacchettini James C. 
Published: June 2010

ABSTRACT

Mycobacterium tuberculosis
enoyl-acyl-ACP reductase (InhA) has been demonstrated to be the primary target of isoniazid (INH). Recently, it was postulated that
M. tuberculosis
dihydrofolate reductase (DHFR) is also a target of INH, based on the findings that a 4R-INH-NADP adduct synthesized from INH by a nonenzymatic approach showed strong inhibition of DHFR
in vitro
, and overexpression of
M. tuberculosis dfrA
in
M. smegmatis
conferred a 2-fold increase of resistance to INH. In the present study, a plasmid expressing
M. tuberculosis dfrA
was transformed into
M. smegmatis
and
M. tuberculosis
strains, respectively. The transformant strains were tested for their resistance to INH. Compared to the wild-type strains, overexpression of
dfrA
in
M. smegmatis
and
M. tuberculosis
did not confer any resistance to INH based on the MIC values. Similar negative results were obtained with 14 other overexpressed proteins that have been proposed to bind some form of INH-NAD(P) adduct. An
Escherichia coli
cell-based system was designed that allowed coexpression of both
M. tuberculosis katG
and
dfrA
genes in the presence of INH. The DHFR protein isolated from the experimental sample was not found bound with any INH-NADP adduct by enzyme inhibition assay and mass spectroscopic analysis. We also used whole-genome sequencing to determine whether polymorphisms in
dfrA
could be detected in six INH-resistant clinical isolates known to lack mutations in
inhA
and
katG
, but no such mutations were found. The
dfrA
overexpression experiments, together with the biochemical and sequencing studies, conclusively demonstrate that DHFR is not a target relevant to the antitubercular activity of INH.
Defining the Role of Mutations inPlasmodium vivaxDihydrofolate Reductase-Thymidylate Synthase Gene Using an EpisomalPlasmodium falciparumTransfection System
Authors: Auliff Alyson M. , Adams John H. , O'Neil Michael T. , Cheng Qin 
Published: June 2010

ABSTRACTPlasmodium vivaxresistance to antifolates is prevalent throughout Australasia and is caused by point mutations within the parasite dihydrofolate reductase (DHFR)-thymidylate synthase. Several unique mutations have been reported inP. vivaxDHFR, and their roles in resistance to classic and novel antifolates are not entirely clear due, in part, to the inability to cultureP. vivax in vitro. In this study, we use a homologous system to episomally express both wild-type and various mutantP. vivax dhfr(pvdhfr) alleles in an antifolate-sensitive line ofP. falciparumand to assess their influences on the susceptibility of the recipientP. falciparumline to commonly used and new antifolate drugs. Although the wild-typepvdhfr-transfectedP. falciparumline was as susceptible to antifolate drugs as theP. falciparumparent line, the single (117N), double (57L/117T and 58R/117T), and quadruple (57L/58R/61M/117T) mutantpvdhfralleles conferred a marked reduction in their susceptibilities to antifolates. The resistance index increased with the number of mutations in these alleles, indicating that these mutations contribute to antifolate resistance directly. In contrast, the triple mutant allele (58R/61M/117T) significantly reversed the resistance to all antifolates, indicating that 61M may be a compensatory mutation. These findings help elucidate the mechanism of antifolate resistance and the effect of existing mutations in the parasite population on the current and new generation of antifolate drugs. It also demonstrates that the episomal transfection system has the potential to provide a rapid screening system for drug development and for studying drug resistance mechanisms inP. vivax.
In Vitro
Effect of Sulfamethoxazole-Trimethoprim against
Histoplasma capsulatum
var.
capsulatum
Authors: Nogueira Brilhante Raimunda Sâmia , Bezerra Fechine Maria Auxiliadora , de Aguiar Cordeiro Rossana , Gadelha Rocha Marcos Fábio , Ribeiro Joyce Fonteles , Jalles Monteiro André , de Lima Rita Amanda Chaves , Lima Mesquita Jacó Ricarte , de Camargo Zoilo Pires , Costa Sidrim José Júlio 
Published: June 2010

ABSTRACT

This study evaluated the
in vitro
effect of sulfamethoxazole-trimethoprim against
Histoplasma capsulatum
var.
capsulatum
isolated from HIV-positive patients. The drugs were tested by microdilution testing in accordance with the CLSI guidelines. All of the strains were inhibited by sulfamethoxazole-trimethoprim, with MIC ranges of 0.039 (sulfamethoxazole)/0.0078 (trimethoprim) mg/ml to 0.625/0.125 mg/ml for mycelial forms and 0.0025/0.0005 to 0.02/0.004 mg/ml for yeast-like forms. However,
in vivo
studies are necessary to evaluate the significance of these results.
Hydroxymethylnitrofurazone Is Active in a Murine Model of Chagas' Disease
Authors: Davies Carolina , Cardozo Rubén Marino , Negrette Olga Sánchez , Mora María Celia , Chung Man Chin , Basombrío Miguel Ángel 
Published: June 2010

ABSTRACT

The addition of a hydroxymethyl group to the antimicrobial drug nitrofurazone generated hydroxymethylnitrofurazone (NFOH), which had reduced toxicity when its activity against
Trypanosoma cruzi
was tested in a murine model of Chagas' disease. Four groups of 12 Swiss female mice each received 150 mg of body weight/kg/day of NFOH, 150 mg/kg/day of nitrofurazone (parental compound), 60 mg/kg/day of benznidazole (BZL), or the solvent as a placebo. Treatments were administered orally once a day 6 days a week until the completion of 60 doses. NFOH was as effective as BZL in keeping direct parasitemia at undetectable levels, and PCR results were negative. No histopathological lesions were seen 180 days after completion of the treatments, a time when the levels of anti-
T. cruzi
antibodies were very low in mice treated with either NFOH or BZL. Nitrofurazone was highly toxic, which led to an overall rate of mortality of 75% and necessitated interruption of the treatment. In contrast, the group treated with its hydroxymethyl derivative, NFOH, displayed the lowest mortality (16%), followed by the BZL (33%) and placebo (66%) groups. The findings of histopathological studies were consistent with these results, with the placebo group showing the most severe parasite infiltrates in skeletal muscle and heart tissue and the NFOH group showing the lowest. The present evidence suggests that NFOH is a promising anti-
T. cruzi
agent.