bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bioanalytical Support for BothIn VitroandIn VivoAssays Across Drug Discovery and Drug Development
Authors: Korfmacher Walter A. 
Published: November 2011

AbstractBioanalysis in a drug metabolism environment can be defined as the analytical techniques utilized to assay various samples that are the result ofin vitroorin vivostudies of one or more new chemical entities (NCEs). Bioanalysis has continued to evolve in response to the needs of the drug discovery and drug development teams, as well as the continuing improvement of the analytical technology that is used for the various assays. This chapter provides an overview of the various assays that are commonly used in various stages of drug discovery and drug development. The chapter is divided into three main sections: bioanalytical strategies,in vitroassays, andin vivoassays.For most of the assays discussed in this chapter, the analytical tool is high performance liquid chromatography (HPLC) combined with tandem mass spectrometry (MS/MS). It is common to have different levels of analytical acceptance criteria that become stricter as one moves from the early lead optimization arena into the development arena. By using this strategy, the higher throughput assays that are used in the screening stage would have minimal standards needed as part of the assay. As one goes to the higher levels, relatively smaller numbers of compounds are being assayed and the number of samples per compound is higher.There are multiplein vitroassays that are used for drug discovery screening of NCEs. The basic strategy for utilizing these variousin vitroassays is to use them to screen NCEs in order to select those that have druglike properties. These tests are commonly used as part of the absorption, distribution, metabolism, and excretion (ADME) optimization phase of new drug discovery. The most commonly used assays are designed to measure one of the following parameters: permeability, metabolic stability, enzyme inhibition, or metabolism. Each of these assay types are described in this chapter as a subtopics.In a drug discovery setting,in vivoassays are similar toin vitroassays in terms of the need for providing the results in a timely manner. The main difference betweenin vitroassays andin vivoassays is thatin vivoassays are often more challenging because the sample matrix is more complex. Mostin vivoassays rely on some form of HPLC‐MS/MS for the analytical step. The mainin vivotopics covered in this chapter are PK screening, PK studies, and metabolite identification.
Joint loading decreased by inexpensive and minimalist footwear in elderly women with knee osteoarthritis during stair descent
Authors: Sacco I. C. N. , Trombini‐Souza F. , Butugan M. K. , Pássaro A. C. , Arnone A. C. , Fuller R. 
Published: November 2011

AbstractObjectivePrevious studies indicate that flexible footwear, which mimics the biomechanics of walking barefoot, results in decreased knee loads in patients with knee osteoarthritis (OA) during walking. However, the effect of flexible footwear on other activities of daily living, such as descending stairs, remains unclear. Our objective was to evaluate the influence of inexpensive and minimalist footwear (Moleca) on knee adduction moment (KAM) during stair descent of elderly women with and without knee OA.MethodsThirty‐four elderly women were equally divided into an OA group and a control group (CG). Stair descent was evaluated in barefoot condition, while wearing the Moleca, and while wearing heeled shoes. Kinematics and ground reaction forces were measured to calculate KAM by using inverse dynamics.ResultsThe OA group experienced a higher KAM during midstance under the barefoot condition (233.3%; P = 0.028), the Moleca (379.2%; P = 0.004), and heeled shoes (217.6%; P = 0.007). The OA group had a similar knee load during early, mid, and late stance with the Moleca compared with the barefoot condition. Heeled shoes increased the knee loads during the early‐stance (versus barefoot [16.7%; P < 0.001] and versus the Moleca [15.5%; P < 0.001]), midstance (versus barefoot [8.6%; P = 0.014] and versus the Moleca [9.5%; P = 0.010]), and late‐stance phase (versus barefoot [10.6%; P = 0.003] and versus the Moleca [9.2%; P < 0.001]). In the CG, the Moleca produced a knee load similar to the barefoot condition only during the early‐stance phase.ConclusionBesides the general foot protection, the inexpensive and minimalist footwear contributes to decreasing knee loads in elderly women with OA during stair descent. The loads are similar to the barefoot condition and effectively decreased when compared with heeled shoes.
Independent association of serum retinol and β‐carotene levels with hyperuricemia: A national population study
Authors: Choi Woo‐Joo , Ford Earl S. , Curhan Gary , Rankin James I. , Choi Hyon K. 
Published: November 2011

AbstractObjectiveUses of synthetic vitamin A derivatives (e.g., isotretinoin used for severe acne) and high doses of preformed vitamin A have been implicated in the pathogenesis of hyperuricemia and gout, whereas a trial reported that β‐carotene may lower serum uric acid (UA) levels. We evaluated the potential population impact of these factors on serum UA in a nationally representative sample of US adults.MethodsUsing data from 14,349 participants ages ≥20 years in the Third National Health and Nutrition Examination Survey (1988–1994), we examined the relationship between serum retinol, β‐carotene, and UA levels using weighted linear regression. Additionally, we examined the relationship with hyperuricemia using weighted logistic regression.ResultsSerum UA levels increased linearly with increasing serum retinol levels, whereas serum UA levels decreased with increasing serum β‐carotene levels. After adjusting for age, sex, dietary factors, and other potential confounders, the serum UA level differences from the bottom (referent) to the top quintiles of serum retinol levels were 0, 0.16, 0.32, 0.43, and 0.71 mg/dl (P for trend <0.001), and for β‐carotene were 0, −0.15, −0.29, −0.27, and −0.40 mg/dl (P for trend <0.001), respectively. Similarly, the multivariate odds ratios of hyperuricemia from the bottom (referent) to top quintiles of serum retinol levels were 1.00, 1.30, 1.83, 2.09, and 3.22 (P for trend <0.001) and for β‐carotene were 1.00, 0.85, 0.68, 0.73, and 0.54 (P for trend <0.001), respectively. The graded associations persisted across subgroups according to cross‐classification by both serum retinol and β‐carotene levels.ConclusionThese nationally representative data raise concerns that vitamin A supplementation and food fortification may contribute to the high frequency of hyperuricemia in the US population, whereas β‐carotene intake may be beneficial against hyperuricemia. The use of β‐carotene as a novel preventive treatment for gout deserves further investigation.
Identification of two new arthritis severity loci that regulate levels of autoantibodies, interleukin‐1β, and joint damage in pristane‐ and collagen‐induced arthritis
Authors: Brenner Max , Laragione Teresina , Shah Anish , Mello Adriana , Remmers Elaine F. , Wilder Ronald L. , Gulko Pércio S. 
Published: November 2011

AbstractObjectiveCia3 is a locus on rat chromosome 4 that regulates severity and joint damage in collagen‐ and pristane‐induced arthritis (CIA and PIA). This study was undertaken to refine the Cia3 gene–containing interval toward gene identification and obtain insights into its mode of action.MethodsFive DA.F344(Cia3) subcongenic rat strains were generated and studied using the PIA and CIA models. Levels of antibodies against type II collagen (both allo‐ and autoantibodies) were measured. Joints and synovial tissue were collected 32 days after the induction of PIA (chronic stage) for histologic and quantitative polymerase chain reaction analysis of interleukin‐1β (IL‐1β) and matrix metalloproteinase (MMP) levels.ResultsThree subcongenic strains sharing the centromeric Cia3d interval were protected and 2 subcongenic strains sharing the telomeric Cia3g interval, which did not overlap with Cia3d, were also protected, developing significantly less severe CIA and PIA. Normal joint architecture was preserved in DA.F344(Cia3) and DA.F344(Cia3d) congenic rats with PIA, while DA rats had pronounced synovial hyperplasia, angiogenesis, inflammatory infiltration, and bone or cartilage erosions. The DA.F344(Cia3d) and DA.F344(Cia3g) strains had significantly lower synovial levels of IL‐1β (5‐fold and nearly 2‐fold, respectively [the latter not reaching statistical significance]), MMP‐1 (expressed predominantly in DA rats), MMP‐3 (79‐fold and 8‐fold, respectively), and MMP‐14 (21‐fold and 1.4‐fold, respectively) and reduced levels of pathogenic autoantibodies against type II collagen, compared with DA rats.ConclusionWe have identified 2 new arthritis severity and articular damage loci within Cia3. These loci regulate pathogenic processes in 2 different models of rheumatoid arthritis, and the identification of these genes has the potential to generate new targets for therapies aimed at reducing disease severity and articular damage, and may additionally have prognostic value.
Quantification of protein interaction in living cells by two‐photon spectral imaging with fluorescent protein fluorescence resonance energy transfer pair devoid of acceptor bleed‐through
Authors: Kim Jiho , Li Xiaolan , Kang Moon‐Sik , Im Kang‐Bin , Genovesio Auguste , Grailhe Regis 
Published: November 2011

AbstractFluorescence resonance energy transfer (FRET) between fluorescent proteins (FPs) is a powerful method to visualize and quantify protein–protein interaction in living cells. Unfortunately, the emission bleed‐through of FPs limits the usage of this complex technique. To circumvent undesirable excitation of the acceptor fluorophore, using two‐photon excitation, we searched for FRET pairs that show selective excitation of the donor but not of the acceptor fluorescent molecule. We found this property in the fluorescent cyan fluorescent protein (CFP)/yellow fluorescent protein (YFP) and YFP/mCherry FRET pairs and performed two‐photon excited FRET spectral imaging to quantify protein interactions on the later pair that shows better spectral discrimination. Applying non‐negative matrix factorization to unmix two‐photon excited spectral imaging data, we were able to eliminate the donor bleed‐through as well as the autofluorescence. As a result, we achieved FRET quantification by means of a single spectral acquisition, making the FRET approach not only easy and straightforward but also less prone to calculation artifacts. As an application of our approach, the intermolecular interaction of amyloid precursor protein and the adaptor protein Fe65 associated with Alzheimer's disease was quantified. We believe that the FRET approach using two‐photon and fluorescent YFP/mCherry pair is a promising method to monitor protein interaction in living cells. © 2011 International Society for Advancement of Cytometry
Terrestrial chemical cues help coral reef fish larvae locate settlement habitat surrounding islands
Authors: Dixson Danielle L. , Jones Geoffrey P. , Munday Philip L. , Pratchett Morgan S. , Srinivasan Maya , Planes Serge , Thorrold Simon R. 
Published: November 2011

AbstractUnderstanding the degree of connectivity between coastal and island landscapes and nearby coral reefs is vital to the integrated management of terrestrial and marine environments in the tropics. Coral reef fish are capable of navigating appropriate settlement habitats following their pelagic larval phase, but the mechanisms by which they do this are unclear. The importance of olfactory cues in settlement site selection has been demonstrated, and there is increasing evidence that chemical cues from terrestrial sources may be important for some species. Here, we test the olfactory preferences of eight island‐associated coral reef fish recruits and one generalist species to discern the capacity for terrestrial cue recognition that may aid in settlement site selection. A series of pairwise choice experiments were used to evaluate the potential role that terrestrial, water‐borne olfactory cues play in island–reef recognition. Olfactory stimuli tested included near‐shore water, terrestrial rainforest leaf litter, and olfactory cues collected from different reef types (reefs surrounding vegetated islands, and reefs with no islands present). All eight island‐associated species demonstrated high levels of olfactory discrimination and responded positively toward olfactory cues indicating the presence of a vegetated island. We hypothesize that although these fish use a suite of cues for settlement site recognition, one mechanism in locating their island/reef habitat is through the olfactory cues produced by vegetated islands. This research highlights the role terrestrial olfactory cues play in large‐scale settlement site selection and suggests a high degree of ecosystem connectivity.
Chelating C4‐Bound Imidazolylidene Complexes through Oxidative Addition of Imidazolium Salts to Palladium(0)
Authors: Krüger Anneke , Kluser Evelyne , Müller‐Bunz Helge , Neels Antonia , Albrecht Martin 
Published: November 2011

AbstractOxidative addition of donor‐functionalised 4‐iodoimidazolium salts to palladium(0) provides a selective route for the preparation of abnormal chelating N‐heterocyclic carbene complexes and enables the introduction of a variety of donor groups. The activation of the C4 position does not necessitate protection of the imidazolium C2 position, thereby leaving this site available for further modification. While metallation of the unsubstituted C2 position of the N‐heterocyclic carbene ligand was unsuccessful when palladium was bound to the C4 carbon atom, sequential metallation of first the C2 position, by means of transmetallation, followed by C4–I oxidative addition, afforded a dimetallic complex comprised of two palladium centres bridged by a single NHC ligand.
A simple elastic membrane‐based microfluidic chip for the proliferation and differentiation of mesenchymal stem cells under tensile stress
Authors: Gao Xinghua , Zhang Xu , Tong Huiyu , Lin Bingcheng , Qin Jianhua 
Published: November 2011

AbstractThis work presents a simple membrane‐based microfluidic chip for the investigation of proliferation and differentiation of mesenchymal stem cells (MSCs) under mechanical stimuli. The cyclic tensile stress was generated by the deformation of elastic PDMS membrane sandwiched between the two layer microfluidic chip via actuated negative pressure, and the cultured MSCs on membrane were subjected to different orders of tensile stress. The results suggest that mechanical stimuli are attributed to the different phenomena of MSCs in cell proliferation and differentiation. The higher tensile stress (>3.5) promoted obvious proliferation, osteogenesis and reduced adipogenesis in MSCs, indicating the possible regulative role of tensile stress in modifying the osteogenesis/adipogenesis balance in the development of tissue organ.
Associations between variants in KITLG, SPRY4, BAK1, and DMRT1 and pediatric germ cell tumors
Authors: Poynter Jenny N. , Hooten Anthony J. , Lindsay Frazier A. , Ross Julie A. 
Published: November 2011

AbstractRecent genome wide association studies have identified susceptibility loci for adult testicular germ cell tumors (GCT) near KITLG, SPRY4, BAK1, and DMRT1. We evaluated variants in these four genes to determine whether these are also susceptibility loci for pediatric GCTs. DNA was isolated from 52 pediatric GCTs (ages 0–21 years) obtained from the Cooperative Human Tissue Network. Control DNA was isolated from de‐identified dried blood spots from 141 white newborns. Genotyping was conducted using TaqMan assays (rs4474514) or by PCR and sequencing (rs4324715, rs210138, and rs755383). Associations between variants and GCT were evaluated using logistic regression with adjustment for sex. We also evaluated whether the associations differed by age at GCT diagnosis (0–9 years, 10–21 years), sex, and tumor location (gonadal, non‐gonadal). We observed a significant association for rs210138 (BAK1) and pediatric GCT overall (odds ratio (OR) = 1.80, 95% confidence interval (CI) 1.10–2.95, P = 0.02) with non‐significant associations similar in magnitude in both the pediatric (P = 0.09) and adolescent (P = 0.06) age groups. The KITLG (rs4474514) and SPRY4 (rs4324715) variants were significantly associated with GCT only in the adolescent age group (rs4474514: OR = 2.28, 95% CI 1.09–4.79, P = 0.03 and rs4324715: OR = 2.40, 95% CI 1.19–4.83, P = 0.01). Associations were mostly similar when stratified by sex. This is the first study to suggest that these loci may also be important in susceptibility to GCTs in the adolescent (KITLG, SPRY4, and BAK1) and pediatric (BAK1) age groups. © 2011 Wiley Periodicals, Inc.
Glial cells in adult neurogenesis
Authors: Morrens Joachim , Van Den Broeck Wim , Kempermann Gerd 
Published: November 2011

AbstractAdult neurogenesis is an exceptional feature of the adult brain and in an intriguing way bridges between neuronal and glial neurobiology. Essentially, all classes of glial cells are directly or indirectly linked to this process. Cells with astrocytic features, for example, serve as radial glia‐like stem cells in the two neurogenic regions of the adult brain, the hippocampal dentate gyrus and the subventricular zone of the lateral ventricles, producing new neurons, create a microenvironment permissive for neurogenesis, and are themselves generated alongside the new neurons in an associated but independently regulated process. Oligodendrocytes are generated from precursor cells intermingled with those generating neurons in an independent lineage. NG2 cells have certain precursor cell properties and are found throughout the brain parenchyma. They respond to extrinsic stimuli and injury but do not generate neurons even though they can express some preneuronal markers. Microglia have positive and negative regulatory effects as constituents of the “neurogenic niche”. Ependymal cells play incompletely understood roles in adult neurogenesis, but under certain conditions might exert (back‐up) precursor cell functions. Glial contributions to adult neurogenesis can be direct or indirect and are mediated by mechanisms ranging from gap‐junctional to paracrine and endocrine. As the two neurogenic regions differ between each other and both from the non‐neurogenic rest of the brain, the question arises in how far regionalization of both the glia‐like precursor cells as well as of the glial cells determines site‐specific “neurogenic permissiveness.” In any case, however, “neurogenesis” appears to be an essentially glial achievement. © 2011 Wiley Periodicals, Inc.
The Fill–Spill Hydrology of Prairie Wetland Complexes during Drought and Deluge
Authors: Shaw Dean A. , Vanderkamp Garth , Conly F. Malcolm , Pietroniro Al , Martz Lawrence 
Published: November 2011

AbstractThe fill–spill of surface depressions (wetlands) results in intermittent surface water connectivity between wetlands in the prairie wetland region of North America. Dynamic connectivity between wetlands results in dynamic contributing areas for runoff. However, the effect of fill–spill and the resultant variable or dynamic basin contributing area has largely been disregarded in the hydrological community.Long‐term field observations recorded at the St. Denis National Wildlife Area, Saskatchewan, allow fill–spill in the basin to be identified and quantified. Along with historical water‐level observations dating back to 1968, recent data collected for the basin include snow surveys, surface water survey and production of a light detection and ranging–derived digital elevation model. Data collection for the basin includes both wet and dry antecedent basin conditions during spring runoff events.A surface water survey at St. Denis in 2006 reveals a disconnected channel network during the spring freshet runoff event. Rather than 100% of the basin contributing runoff to the outlet, which most hydrological models assume, only approximately 39% of the basin contributes to the outlet. Anthropogenic features, such as culverts and roads, were found to influence the extent and spatial distribution of contributing areas in the basin. Historical pond depth records illustrate the effect of antecedent basin conditions on fill–spill and basin contributing area. A large pond at the outlet of the St. Denis basin, which only receives local runoff during dry years when upstream surface storage has not been satisfied, has pond runoff volumes that increase by a factor of 20 or more during wet years when upstream antecedent basin surface storage is satisfied and basin‐wide runoff contributes to the pond. Copyright © 2011 John Wiley & Sons, Ltd.
Impact of Seasonality on Artificial Drainage Discharge under Temperate Climate Conditions
Authors: Hirt Ulrike , Wetzig Annett , Devandra Amatya M. , Matranga Marisa 
Published: November 2011

AbstractArtificial drainage systems affect all components of the water and matter balance. For the proper simulation of water and solute fluxes, information is needed about artificial drainage discharge rates and their response times. However, there is relatively little information available about the response of artificial drainage systems to precipitation. To address this need, we analysed 11 datasets from artificial drainage study sites (daily or hourly resolution), one daily dataset from an open ditch system, and three datasets from rainfall simulations on tile‐drained fields.When we considered all 11 artificial drainage study sites, we found that artificial drainage discharge responded to 70% of all rainfall events during the year, and that the response rate differed significantly between 56% summer and 84% in winter. A median of 23% of the yearly precipitation rate is discharged by artificial drainage systems, varying from 9% of the precipitation in summer to 54% of the precipitation in winter. The artificial drainage systems usually started to respond within the first hour under rain fed conditions, and the response time increased at lower rainfall intensities (< 1 mm h–1). The peak outflow normally occurred within the first two days. The influence of soil texture and land use on artificial drainage discharge rates could not be reproduced properly, due to the spatial high variability caused by other site‐specific properties. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)