bluuebunny/crossref_metadata_2025 huggingface dataset:
GP41-Specific Antibody Blocks Cell-Free HIV Type 1 Transcytosis through Human Rectal Mucosa and Model Colonic Epithelium
Authors: Shen Ruizhong , Drelichman Ernesto R. , Bimczok Diane , Ochsenbauer Christina , Kappes John C. , Cannon Jamie A. , Tudor Daniela , Bomsel Morgane , Smythies Lesley E. , Smith Phillip D.
Published: March 2010

Monostratified epithelial cells translocate HIV type 1 (HIV-1) from the apical to the basolateral surface via vesicular transcytosis. Because acutely transmitted HIV-1 is almost exclusively CCR5-tropic and human intestinal epithelial cells preferentially transcytose CCR5-tropic virus, we established epithelial monolayers using polarized HT-29 cells transduced to express CCR5, and an explant system using normal human rectal mucosa, to characterize biological parameters of epithelial cell transcytosis of HIV-1 and assess antiviral Ab blockade of transcytosis. The amount of cell-free HIV-1 transcytosed through the epithelial monolayer increased linearly in relation to the amount of virus applied to the apical surface, indicating transcytosis efficiency was constant (r2 = 0.9846; p < 0.0001). The efficiency of HIV-1 transcytosis ranged between 0.05 and 1.21%, depending on the virus strain, producer cell type and gp120 V1–V3 loop signature. Inoculation of HIV-1 neutralizing Abs to the immunodominant region (7B2) or the conserved membrane proximal external region (2F5) of gp41 or to cardiolipin (IS4) onto the apical surface of epithelial monolayers prior to inoculation of virus significantly reduced HIV-1 transcytosis. 2F5 was the most potent of these IgG1 Abs. Dimeric IgA and monomeric IgA, but not polymeric IgM, 2F5 Abs also blocked HIV-1 transcytosis across the epithelium and, importantly, across explanted normal human rectal mucosa, with monomeric IgA substantially more potent than dimeric IgA in effecting transcytosis blockade. These findings underscore the potential role of transcytosis blockade in the prevention of HIV-1 transmission across columnar epithelium such as that of the rectum.
Fatty Acids from Very Low-Density Lipoprotein Lipolysis Products Induce Lipid Droplet Accumulation in Human Monocytes
Authors: den Hartigh Laura J. , Connolly-Rohrbach Jaime E. , Fore Samantha , Huser Thomas R. , Rutledge John C.
Published: March 2010

One mechanism by which monocytes become activated postprandially is by exposure to triglyceride-rich lipoproteins such as very low-density lipoproteins (VLDL). VLDL are hydrolyzed by lipoprotein lipase at the blood-endothelial cell interface, releasing free fatty acids. In this study, we examined postprandial monocyte activation in more detail, and found that lipolysis products generated from postprandial VLDL induce the formation of lipid-filled droplets within cultured THP-1 monocytes, characterized by coherent antistokes Raman spectroscopy. Organelle-specific stains revealed an association of lipid droplets with the endoplasmic reticulum, confirmed by electron microscopy. Lipid droplet formation was reduced when lipoprotein lipase-released fatty acids were bound by BSA, which also reduced cellular inflammation. Furthermore, saturated fatty acids induced more lipid droplet formation in monocytes compared with mono- and polyunsaturated fatty acids. Monocytes treated with postprandial VLDL lipolysis products contained lipid droplets with more intense saturated Raman spectroscopic signals than monocytes treated with fasting VLDL lipolysis products. In addition, we found that human monocytes isolated during the peak postprandial period contain more lipid droplets compared with those from the fasting state, signifying that their development is not limited to cultured cells but also occurs in vivo. In summary, circulating free fatty acids can mediate lipid droplet formation in monocytes and potentially be used as a biomarker to assess an individual’s risk of developing atherosclerotic cardiovascular disease.
Antibody Repertoire Development in Fetal and Neonatal Piglets. XI. The Relationship of Variable Heavy Chain Gene Usage and the Genomic Organization of the Variable Heavy Chain Locus
Authors: Eguchi-Ogawa Tomoko , Wertz Nancy , Sun Xiu-Zhu , Puimi Francois , Uenishi Hirohide , Wells Kevin , Chardon Patrick , Tobin Gregory J. , Butler John E.
Published: March 2010

In this study, we have mapped the 3′ H chain V region (VH) genes and those in the H chain diversity, H chain joining, and 5′ portion of the H chain constant locus. We show that swine possess only two functional H chain diversity segments and only one functional H chain joining segment. These data help to explain more than a decade of observations on the preimmune repertoire of this species and reveal the vulnerability of swine to natural or designed mutational events. The results are consistent with earlier studies on the region containing Enh, Cμ, and Cδ while revealing that the ancestral IgG3 is the most 5′ Cγ gene. We also observed a recent duplication (∼1.6 million years ago) in the VH locus that contains six of the seven VH genes that comprise 75% of the preimmune repertoire. Because there are no known transfers of immune regulators or Ags that cross the placenta as in mice and humans, fetal VH usage must be intrinsically regulated. Therefore, we quantified VH usage in fetal piglets and demonstrated that usage is independent of the position of VH genes in the genome; the most 3′ functional VH gene (IGHV2) is rarely used, whereas certain upstream genes (IGHV14 and IGHV15) are predominately used early in fetal liver but seldom thereafter. Similar to previous studies, three VH genes account for 40% of the repertoire and six for ∼70%. This limited combinatorial diversity of the porcine VH repertoire further emphasizes the dependence on CDR3 diversity for generating the preimmune Ab repertoire of this species.
Regulatory T Cells Inhibit T Cell Proliferation and Decrease Demyelination in Mice Chronically Infected with a Coronavirus
Authors: Trandem Kathryn , Anghelina Daniela , Zhao Jingxian , Perlman Stanley
Published: March 2010

Mice infected with the neurotropic JHM strain of mouse hepatitis virus (JHMV) develop acute and chronic demyelinating diseases with histopathological similarities to multiple sclerosis. The process of demyelination is largely immune-mediated, as immunodeficient mice (RAG1−/− mice) do not develop demyelination upon infection; however, demyelination develops if these mice are reconstituted with either JHMV-immune CD4 or CD8 T cells. Because myelin destruction is a consequence of the inflammatory response associated with virus clearance, we reasoned that decreasing the amount of inflammation would diminish clinical disease and demyelination. Given that regulatory T cells (Tregs) have potent anti-inflammatory effects, we adoptively transferred Tregs into infected C57BL/6 and RAG1−/− mice. In both instances, transfer of Tregs decreased weight loss, clinical scores, and demyelination. Transferred Tregs were not detected in the CNS of infected RAG1−/− mice, but rather appeared to mediate their effects in the draining cervical lymph nodes. We show that Tregs dampen the inflammatory response mediated by transferred JHMV-immune splenocytes in infected RAG1−/− mice by decreasing T cell proliferation, dendritic cell activation, and proinflammatory cytokine/chemokine production, without inducing apoptosis. By extension, decreasing inflammation, whether by Treg transfer or by otherwise enhancing the anti-inflammatory milieu, could contribute to improved clinical outcomes in patients with virus-induced demyelination.
A Protease-Dependent Mechanism for Initiating T-Dependent B Cell Responses to Large Particulate Antigens
Authors: Catron Drew M. , Pape Kathryn A. , Fife Brian T. , van Rooijen Nico , Jenkins Marc K.
Published: March 2010

Ab production is critical for antimicrobial immunity, and the initial step in this process is the binding of Ag to the BCR. It has been shown that small soluble proteins can directly access the lymph node follicles to reach naive B cells, but virus particles must be translocated into follicles via subcapsular sinus macrophages. In this article, we explore how large particulate Ags generate humoral immune responses. Ag-specific follicular B cells rapidly acquired Ag, presented peptide:MHC class II ligands, and produced T-dependent Ab responses following s.c. injection of 1-μm, Ag-linked microspheres, despite the microspheres being confined to the subcapsular sinus. The mechanism of Ag acquisition did not require dendritic cells, subcapsular sinus macrophages, or B cell movement to the subcapsular sinus. Rather, B cell Ag acquisition was protease-dependent, suggesting that some protein Ags are cleaved from the surface of particles to directly initiate humoral immune responses.
Inductive Transfer Applied to Modeling River Discharge in Nova Scotia
Authors: Silver Daniel L. , Spooner Ian , Gaudette Lisa
Published: March 2010

Effective watershed management requires accurate modeling of river discharge. Many years of data collection are often required to capture variations in seasonal trends and produce accurate predictive and descriptive models. In this study artificial neural networks that employ inductive transfer are used to develop models that predict the discharge (flow rate) of streams in Nova Scotia from weather data. The models use two days of weather data to predict the discharge for the following day. The objective is to show that transfer of knowledge from previously learned models for streams can be used to reduce the time and cost associated with collecting large amounts of data for modeling the discharge of a nearby river.

Results show that models developed using only 180 days of training data with transfer from related streams perform as well on independent test data as models constructed using five years of training data and no transfer. The results also show that a considerable variance in stream discharge and stream morphology can be accommodated and that the induced models may be acceptable for management of the resource when little data are available. There is scope for improving the method of transfer by taking into consideration the degree of relatedness between the streams, watersheds, and their associated climate conditions.

RÉSUMÉ

Une bonne gestion des bassins versants exige une modélisation exacte du débit fluvial. Il faut souvent de nombreuses années de collecte de données pour rendre compte des variations saisonnières et produire des modèles de prévision et des modèles descriptifs exacts. Dans le cadre de cette étude, des réseaux neuronaux qui font appel au transfert induit de données météorologiques sont utilisés pour prédire le débit de cours d’eau en Nouvelle-Écosse. Les modèles retenus reposent sur deux journées de données météorologiques pour la formulation de prévisions du débit pour le lendemain. Il s’agit d’illustrer qu’il est possible d’utiliser des connaissances tirées d’autres modèles de cours d’eau déjà établis et de réduire ainsi le temps et les coûts associés à la collecte de données de modélisation du débit d’une rivière proche.

Les résultats indiquent que les modèles établis qui se fondent uniquement sur 180 jours de données de formation et tirées d’autres cours d’eau apparentés donnent d’aussi bons résultats à l’aide des données d’essai indépendant que par les données de modèles établis à partir de cinq années de données de formation, sans transfert. Les résultats établissent par ailleurs qu’il est possible de rendre compte d’un écart considérable dans le débit et la morphologie des cours d’eau et que les modèles produits à l’aide de données préalables sont acceptables pour la gestion de la ressource s’il y a peu de données. Il serait possible d’améliorer ce transfert de connaissances en tenant compte du degré de similitude entre les cours d’eau, les bassins versants et les conditions climatiques connexes.

[Traduit par la redaction]
Study of Alterations in the Concentration of Ions in the Plasma and of the Induction of Micronucleus in Piaractus mesopotamicus Exposed to the Herbicide Atrazine
Authors: Moron Sandro Estevan , Polez V. L. P. , Artoni R. F. , Ribas J. L. C. , Takahashi H. K.
Published: March 2010

The pollution of the aquatic ecosystem has been increasing in the last years, mainly due to the industrial and agricultural development. The Atrazine pesticide is an important agent pollutant and it can harm the development and reproduction of several species of fish due to its toxicity. Piaractus mesopotamicus (pacu) is one of the species thoroughly comercialized and used in fish farms. The present study analyzed possible modifications in the concentration of ions in the plasma (Na+, Cl–, K+, Ca2+), in the blood pH and in the micronucleus frequency in pacu erythrocytes (N = 10 for group; Wt: 160.0 ± 5 g) exposed to the Atrazine herbicide (0.1 mg/L) during 96 hours in semi-static system. Samples of blood were collected, with aid of syringes heparinized, being centrifuged later and/or made smears for subsequent analysis of the micronucleus. The obtained plasma was used for the determinations of ions in the plasma. Cytological analyses showed significant differences (p < 0.0001) in the micronucleus frequency among the control group which was exposed to the atrazine herbicide. The blood pH stayed constant, but the ions concentration in the plasma Na+ and Cl– was, in relation to the control, significantly reduced (p < 0.05). The tested concentration of the herbicide probably provoked disturbances in the acid-base ionic balance and it can also be considered a clastogenic and poisonous product.
Toxicity Tests With Daphnia magna: a Tool to Evaluate a Experimental UASB Reactor
Authors: Laitano K. dos Santos , Matias William Gerson
Published: March 2010

Toxicity bioassay with aquatic organisms are an effective tool to assess, predict or simply detect pollution effects on living organisms. Although diverse systems of sewage treatment systems exist, the majority of them presents have functioning problems and they do not fulfill with its purpose of treatment and correct disposal of these residues. UASB reactors (Upflow Anaerobic Sludge Blanket) have been used to treat effluents and leachate deriving from other treatment systems. The aim of this research was evaluate the efficiency of an experimental UASB reactor in the leachate treatment, utilizing acute toxicity tests with Daphnia magna. Sixteen effluent samples were collected during six months, before and after the reactor’s treatment. The effluent toxicity evaluation allowed the detection of changes caused by the own treatment system operation. Results showed that the effluent treatment in this kind of reactor could reduce toxicity up to 80%, although low values of EC50 for carried tests showed high toxicity in all samples. The toxicity tests used in the present work are based on the whole effluent and can show a way to evaluate an effluent when there is no detailed information that the same contain. Efforts should address the increase of reactor’s efficiency, improving the quality of treated effluents in this system.
Lead Acetate Action in Embrionic Developmental Pattern of Gallus domesticus
Authors: Rivero L. B. D. , Schatz J. C. , Carvalho M. S. L. , Carvalho M. C. de , Müller Yara Maria Rauh
Published: March 2010

The contamination for lead has its origin mainly in the atmospheric emissions, being the air considered one of the main ways of transport and distribution of this heavy metal in the environment. Lead toxicicity in embryos and young individuals is very expressive, and can commitment the structural and functional pattern of species. Studies have demonstrated that only one exposition to lead in chick embryos, depending on the ingested dose, can result in malformations of face and limbs, hidrocefaly and reduction in the eclosion rate. The objective of this work was analized embryos of Gallus domesticus exposed to lead acetate in order to verify the commitment of the embryonic pattern as well as the teratologic actions of the metal. Studies in the Laboratório de Reprodução e Desenvolvimento Animal/UFSC had been carried through, where 143 embryos of Gallus domesticus had been exposed to lead acetate in the doses: 150 μg, 250 μg, 350 μg and 450 μg. The control group (n = 47) has received 0.1 ml saline solution in the same days. The embryos had been treated in 3rd or in 5rd day, monitorated during six days, when the integrity of the embryonic structures was evaluated. Of the total of individuals treated with lead acetate, 27 presented the normal pattern, 34 died and 82 had alterated the developmental pattern (developmental delay (3), malformations (14), hemorrhagic alterations (65)). Our studies show that the lead acetate in the doses utilizated modified the morphogenesis processes, causing characteristic morphological alterations, awareing to the use and the release of this metal in the environment.
Preliminary Appraisal of Imposex in Areas Under the Influence of Southern Brazilian Harbors
Authors: Castro I. B. de , Bemvenuti C. E. , Fillmann Gilberto
Published: March 2010

Imposex in gastropod mollusks is an efficient and low-cost biomarker for pollution by organotin compounds. Such substances are typically found in areas with an intense flux of vessels, such as marinas and harbors. This study preliminarily evaluated the occurrence of imposex in Stramonita haemastoma (Linnaeus, 1758) populations along the areas under the influence of the main harbors from southern Brazil (Paranaguá, PR; São Francisco do Sul, SC; Itajaí, SC; and Rio Grande, RS). Although no chemical analyses were performed so far to confirm the presence of organotins, the occurrence of imposex strongly suggests a contamination by these compounds in the studied areas and it is likely that the closest from the harbors (as the main sources) the more contaminated the environment. However, due to the limitations of S. haemastoma, it is important to assess the response of alternative species adapted to mesohaline environments and non-consolidated substrates, in order to make up for the lack of indicator species for some areas such as Patos Lagoon and Itajaí-Açu estuaries.
Molecular Similarity Methods andQSARModels As Tools for Virtual Screening
Authors: Bajorath Jürgen
Published: March 2010

Virtual screening has become a major attraction in pharmaceutical research for computational screening of compound source databases. This screening method provides significant computational ability at a low price. This article discusses virtual screening based on quantitative structure‐activity relationships (QSAR) and molecular similarity analysis.
Microwave Hybrid Post‐Heat Treatment of Reaction Sintered Alumina/Lanthanum Hexaaluminate Composite Ceramics
Authors: Negahdari Zahra , Willert‐Porada Monika
Published: March 2010

One of the main problems in development of in situ reaction sintered alumina/lanthanum hexaaluminate composite ceramics is achievement of simultaneous densification and in situ formation of lanthanum hexaaluminate (LHA) platelets inside the matrix. Microwave hybrid post‐sintering was investigated as a method to enhance the solid‐state reaction of LHA formation and the densification of composite ceramics with 2.8–80 vol% LHA. Comparison of the conventionally and microwave assisted sintered alumina/lanthanum hexaaluminate composite ceramics revealed that utilization of microwave heating in second stage of sintering could enhance the solid‐state reaction, the densification, and the anisotropic grain growth of the LHA platelets in ceramics containing more than 20 vol% LHA and for heat treatment at 1500 °C.
Nanomorphology and Charge Generation in Bulk Heterojunctions Based on Low‐Bandgap Dithiophene Polymers with Different Bridging Atoms
Authors: Morana Mauro , Azimi Hamed , Dennler Gilles , Egelhaaf Hans‐Joachim , Scharber Markus , Forberich Karen , Hauch Jens , Gaudiana Russell , Waller David , Zhu Zenghuo , Hingerl Kurt , van Bavel Svetlana S. , Loos Joachim , Brabec Christoph J.
Published: March 2010

Carbon bridged (C‐PCPDTBT) and silicon‐bridged (Si‐PCPDTBT) dithiophene donor–acceptor copolymers belong to a promising class of low bandgap materials. Their higher field‐effect mobility, as high as 10−2 cm2 V−1 s−1 in pristine films, and their more balanced charge transport in blends with fullerenes make silicon‐bridged materials better candidates for use in photovoltaic devices. Striking morphological changes are observed in polymer:fullerene bulk heterojunctions upon the substitution of the bridging atom. XRD investigation indicates increased π–π stacking in Si‐PCPDTBT compared to the carbon‐bridged analogue. The fluorescence of this polymer and that of its counterpart C‐PCPDTBT indicates that the higher photogeneration achieved in Si‐PCPDTBT:fullerene films (with either [C60]PCBM or [C70]PCBM) can be correlated to the inactivation of a charge‐transfer complex and to a favorable length of the donor–acceptor phase separation. TEM studies of Si‐PCPDTBT:fullerene blended films suggest the formation of an interpenetrating network whose phase distribution is comparable to the one achieved in C‐PCPDTBT:fullerene using 1,8‐octanedithiol as an additive. In order to achieve a balanced hole and electron transport, Si‐PCPDTBT requires a lower fullerene content (between 50 to 60 wt%) than C‐PCPDTBT (more than 70 wt%). The Si‐PCPDTBT:[C70]PCBM OBHJ solar cells deliver power conversion efficiencies of over 5%.
Universal Behavior and Electric‐Field‐Induced Structural Transition in Rare‐Earth‐Substituted BiFeO3
Authors: Kan Daisuke , Pálová Lucia , Anbusathaiah Varatharajan , Cheng Ching Jung , Fujino Shigehiro , Nagarajan Valanoor , Rabe Karin M. , Takeuchi Ichiro
Published: March 2010

The discovery of a universal behavior in rare‐earth (RE)‐substituted perovskite BiFeO3 is reported. The structural transition from the ferroelectric rhombohedral phase to an orthorhombic phase exhibiting a double‐polarization hysteresis loop and substantially enhanced electromechanical properties is found to occur independent of the RE dopant species. The structural transition can be universally achieved by controlling the average ionic radius of the A‐site cation. Using calculations based on first principles, the energy landscape of BiFeO3 is explored, and it is proposed that the origin of the double hysteresis loop and the concomitant enhancement in the piezoelectric coefficient is an electric‐field‐induced transformation from a paraelectric orthorhombic phase to the polar rhombohedral phase.
Bottom‐Up Engineering of Subnanometer Copper Diffusion Barriers Using NH2‐Derived Self‐Assembled Monolayers
Authors: Caro Arantxa Maestre , Armini Silvia , Richard Olivier , Maes Guido , Borghs Gustaaf , Whelan Caroline M. , Travaly Youssef
Published: March 2010

A 3‐aminopropyltrimethoxysilane‐derived self‐assembled monolayer (NH2SAM) is investigated as a barrier against copper diffusion for application in back‐end‐of‐line (BEOL) technology. The essential characteristics studied include thermal stability to BEOL processing, inhibition of copper diffusion, and adhesion to both the underlying SiO2 dielectric substrate and the Cu over‐layer. Time‐of‐flight secondary ion mass spectrometry and X‐ray spectroscopy (XPS) analysis reveal that the copper over‐layer closes at 1–2‐nm thickness, comparable with the 1.3‐nm closure of state‐of‐the‐art Ta/TaN Cu diffusion barriers. That the NH2SAM remains intact upon Cu deposition and subsequent annealing is unambiguously revealed by energy‐filtered transmission electron microscopy supported by XPS. The SAM forms a well‐defined carbon‐rich interface with the Cu over‐layer and electron energy loss spectroscopy shows no evidence of Cu penetration into the SAM. Interestingly, the adhesion of the Cu/NH2SAM/SiO2 system increases with annealing temperature up to 7.2 J m−2 at 400 °C, comparable to Ta/TaN (7.5 J m−2 at room temperature). The corresponding fracture analysis shows that when failure does occur it is located at the Cu/SAM interface. Overall, these results demonstrate that NH2SAM is a suitable candidate for subnanometer‐scale diffusion barrier application in a selective coating for copper advanced interconnects.
CFD simulation of transverse vibration effects on radial temperature profile and thermal entrance length in laminar flow
Authors: Eesa Muhammad , Barigou Mostafa
Published: March 2010

Radial heat transfer in laminar pipe flow is characterized by a wide temperature distribution over the pipe cross‐section. We use a validated Computational Fluid Dynamics (CFD) model to show that the superimposition of a transverse vibration on the steady laminar flow of a Newtonian fluid moving in a pipe with an isothermal wall, generates considerable chaotic flow and radial mixing which result in a large enhancement in wall heat transfer as well as a considerably more uniform radial temperature field. Transverse vibration also causes the temperature profile to develop very rapidly in the axial direction reducing the thermal entrance length by a large factor. These effects are dependent on vibration amplitude and frequency, and fluid viscosity. © 2010 American Institute of Chemical Engineers AIChE J, 2011
Implementation of new working methods in the floor‐laying trade: Long‐term effects on knee load and knee complaints
Authors: Jensen Lilli Kirkeskov , Friche Claus
Published: March 2010

Background

This study compared floor laying using new working methods involving standing up, to the traditional methods involving working on one's knees.

Methods

The study group, 216 subjects, completed a training class in the use of the new floor‐laying methods, and received free tools and advice in their use. The control group, 454 subjects, did not get any training, but were free to use the new methods if they wished. In a 2‐year‐follow‐up the effects were evaluated by questionnaires and by in‐depth interviews of industry representatives. Regression analysis was used to control for age, body mass index (BMI), and self‐reported stress. The quality of the work and time used to perform it comparing the new methods and the traditional methods was evaluated.

Results

Two years after the training, 38% of participants in the study group used the new working methods weekly or daily compared with 16% of the control group. The risk was at least double for serious knee complaints among floor layers who had not used the new working methods. There were no increased risks for other musculoskeletal complaints involving any other part of the body associated with the use of the new method.

Conclusions

Within a 2‐year time period, the introduction of new working methods in the floor‐laying trade has succeeded. More efforts are needed to sustain the use of the methods among those workers who have been trained and to introduce the methods to those workers who do not yet use them. Am. J. Ind. Med. 53: 615–627, 2010. © 2010 Wiley‐Liss, Inc.
Ethical issues faced by field primatologists: asking the relevant questions
Authors: Fedigan Linda Marie
Published: March 2010

Field primatologists face unusual ethical issues. We study animals rather than people and receive research approval from animal care rather than ethics committees. However, animal care evaluation forms are developed from concerns about laboratory animal research and are based on the “Three R's” for humane treatment of captive experimental subjects (replacement, reduction and refinement), which are only debatably relevant to field research. Scientists who study wild, free‐ranging primates in host countries experience many ethical dilemmas seldom dealt with in animal care forms. This paper reviews the ethical issues many field primatologists say they face and how these might be better addressed by animal care forms. The ethical issues arising for field researchers are divided into three categories: “Presence, Protocols and People” and for each the most frequent issues are described. The most commonly mentioned ethical concern arising from our presence in the field is the possibility of disease transmission. Although most primate field studies employ only observational protocols, the practice of habituating our study animals to close human presence is an ethical concern for many since it can lessen the animals' fear of all humans, thereby facilitating undesirable behaviors (e.g., crop‐raiding) and rendering them vulnerable to harm. Field primatologists who work in host countries must observe national laws and local traditions. As conservationists, primatologists must often negotiate between the resource needs and cultural practices of local people and the interests of the nonhuman primates. Many say they face more ethical dilemmas arising from human interactions than from research on the animals per se. This review concludes with suggestions for relevant questions to ask on animal care forms, and actions that field primatologists can take to better inform animal care committees about the common ethical issues we experience as well as how to develop guidelines for addressing them. Am. J. Primatol. 72:754–771, 2010. © 2010 Wiley‐Liss, Inc.
Adipocytokines, insulin resistance, and coronary atherosclerosis in rheumatoid arthritis
Authors: Rho Young Hee , Chung Cecilia P. , Solus Joseph F. , Raggi Paolo , Oeser Annette , Gebretsadik Tebeb , Shintani Ayumi , Stein C. Michael
Published: March 2010

Objective

The prevalence of subclinical coronary atherosclerosis is increased in patients with rheumatoid arthritis (RA), and the increased risk is associated with insulin resistance. Adipocytokines have been linked to obesity, insulin resistance, inflammation, and coronary heart disease in the general population. This study was undertaken to examine the hypothesis that adipocytokines affect insulin resistance and coronary atherosclerosis among patients with RA.

Methods

The coronary calcium score, homeostatic model assessment for insulin resistance (HOMA‐IR) index, and serum adipocytokine (leptin, adiponectin, resistin, and visfatin) concentrations were determined in 169 patients with RA. The independent effect of each adipocytokine on insulin resistance according to the HOMA‐IR index and on coronary artery calcification determined by electron beam computed tomography was assessed in models adjusted for age, race, sex, body mass index (BMI), traditional cardiovascular risk factors, and inflammation mediators. In addition, an interaction analysis was performed to evaluate whether the effect of the HOMA‐IR index on the coronary calcium score is moderated by adipocytokines.

Results

Increased concentrations of leptin were associated with a higher HOMA‐IR index, even after adjustment for age, race, sex, BMI, traditional cardiovascular risk factors, and inflammation mediators (P < 0.001), but concentrations of visfatin (P = 0.06), adiponectin (P = 0.55), and resistin (P = 0.98) showed no association with the HOMA‐IR index. None of the adipocytokines was independently associated with the coronary calcium score (all P > 0.05). Serum leptin concentrations showed a significant interaction with the HOMA‐IR index (P for multivariate interaction = 0.02). Increasing leptin concentrations attenuated the increased risk of coronary calcification related to insulin resistance. Serum concentrations of the other adipocytokines showed no significant interactions with the HOMA‐IR index (each P > 0.05).

Conclusion

Leptin is associated with insulin resistance in patients with RA but, paradoxically, attenuates the effects of insulin resistance on coronary calcification.
Frequency of varus and valgus thrust and factors associated with thrust presence in persons with or at higher risk of developing knee osteoarthritis
Authors: Chang Alison , Hochberg Marc , Song Jing , Dunlop Dorothy , Chmiel Joan S. , Nevitt Michael , Hayes Karen , Eaton Charles , Bathon Joan , Jackson Rebecca , Kwoh C. Kent , Sharma Leena
Published: March 2010

Objective

Varus thrust observed during gait has been shown to be associated with a 4‐fold increase in the risk of medial knee osteoarthritis (OA) progression. Valgus thrust is believed to be less common than varus thrust; the prevalence of each is uncertain. Racial differences in risk factors may help explain variations in the natural history of knee OA. We undertook this study to determine the frequency of varus and valgus thrust in African Americans and Caucasians and to identify factors associated with thrust presence.

Methods

The Osteoarthritis Initiative cohort includes men and women who have knee OA or are at increased risk of developing it. Trained examiners assessed thrust presence by gait observation. Logistic regression with generalized estimating equations was used to identify factors associated with thrust presence, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.

Results

Compared with Caucasians, African Americans had lower odds of varus thrust, controlling for age, sex, body mass index (BMI), injury, surgery, disease severity, strength, pain, and alignment in persons without knee OA (adjusted OR 0.50 [95% CI 0.36, 0.72]) and in those with knee OA (adjusted OR 0.46 [95% CI 0.34, 0.61]). Also independently associated with varus thrust were age, sex, BMI, disease severity, strength, and alignment. The odds of valgus thrust were greater for African Americans than for Caucasians in persons without knee OA (adjusted OR 1.69 [95% CI 1.02, 2.80]) and in those with knee OA (adjusted OR 1.98 [95% CI 1.35, 2.91]). Also independently associated with valgus thrust were disease severity and malalignment.

Conclusion

Compared with Caucasians, African Americans had lower odds of varus thrust and greater odds of valgus thrust. These findings may help explain the difference between these groups in the pattern of OA involvement at the knee.
Association of normal nailfold end row loop numbers with a shorter duration of untreated disease in children with juvenile dermatomyositis
Authors: Ostrowski Rochella A. , Sullivan Christine L. , Seshadri Roopa , Morgan Gabrielle A. , Pachman Lauren M.
Published: March 2010

Objective

To determine the association of normal numbers of end row loops (ERLs) in nailfold capillaries at the time of diagnosis of juvenile dermatomyositis (DM) with clinical findings in untreated children with the disease and to identify predictors of the development of decreased numbers of ERLs.

Methods

Clinical and laboratory data from 80 untreated children with juvenile DM were collected. ERL numbers were recorded at the time of diagnosis and at 24 months and 36 months thereafter. The 12 children who had normal ERLs at diagnosis were compared with the remaining 68 children. Outcomes included the duration of untreated disease, the duration of treatment with immunosuppressive medications, family medical history, Disease Activity Score (DAS) for juvenile DM, creatinine phosphokinase level, aldolase level, absolute number of CD3–CD56+/16+ natural killer cells, and von Willebrand factor antigen level. Cross‐sectional and longitudinal analyses were performed.

Results

At diagnosis, children with normal ERLs had a shorter duration of untreated disease (P = 0.03) and a lower skin DAS (P = 0.045). Over time, an increased likelihood of having decreased numbers of ERLs was associated with a longer duration of untreated disease and with a higher skin DAS.

Conclusion

The presence of a normal number of ERLs in juvenile DM appears to be associated with a shorter duration of symptoms and may be a useful indicator of disease chronicity in the newly diagnosed child. Normal ERLs is also associated with a lower skin DAS. The lack of association between normal ERLs and other variables indicates that normal findings on nailfold capillaroscopy should not be used as justification to delay immunosuppressive therapy in children with typical symptoms of juvenile DM.
Involvement of the renin–angiotensin system in the development of vascular damage in a rat model of arthritis: Effect of angiotensin receptor blockers
Authors: Sakuta Takeo , Morita Yoshitaka , Satoh Minoru , Fox David A. , Kashihara Naoki
Published: March 2010

Objective

To explore the involvement of the renin–angiotensin system (RAS) in the development of vascular damage in adjuvant‐induced arthritis (AIA) in rats.

Methods

Angiotensin II (Ang II; 0.25 or 1.0 mg/kg/day) was infused in control rats and rats with AIA for 21 days, and the impact of systemic inflammation on Ang II–induced hypertension, endothelial dysfunction, and vascular hypertrophy was evaluated. Expression of angiotensin II type 1 receptor (AT1R) and angiotensin‐converting enzyme (ACE) in the aortas of rats with AIA were examined by real‐time polymerase chain reaction (PCR) and Western blot analyses. Losartan (3 mg/kg/day) or irbesartan (5 mg/kg/day), both of which are AT1R blockers, was administered orally to rats with AIA for 21 days. In situ superoxide production in aortas was assessed according to the fluorogenic oxidation of dihydroethidium to ethidium. The expression and activity of NAD(P)H oxidases in aortas were examined by real‐time PCR analysis and lucigenin chemiluminescence assay. Endothelial function in rats with AIA treated in vivo or ex vivo with AT1R blockers was also determined.

Results

The Ang II–induced hypertensive response, endothelial dysfunction, and vascular hypertrophy were exacerbated in rats with AIA. Expression of AT1R and ACE was increased in the aortas of rats with AIA. Both losartan and irbesartan decreased the levels of superoxide and the expression and activity NAD(P)H oxidases in the aortas of rats with AIA. The endothelial dysfunction in AIA was improved by the in vivo or ex vivo treatment with AT1R blockers.

Conclusion

The locally activated RAS is involved in the increased vascular oxidative stress and endothelial dysfunction in AIA. Our findings have important implications for clinical approaches to the reduction of cardiovascular risk in patients with rheumatoid arthritis.
Expression of CD44 variant isoforms CD44v3 and CD44v6 is increased on T cells from patients with systemic lupus erythematosus and is correlated with disease activity
Authors: Crispín José C. , Keenan Brendan T. , Finnell Michele D. , Bermas Bonnie L. , Schur Peter , Massarotti Elena , Karlson Elizabeth W. , Fitzgerald Lisa M. , Ergin Sukran , Kyttaris Vasileios C. , Tsokos George C. , Costenbader Karen H.
Published: March 2010

Objective

To quantify the expression of CD44 and variant isoforms CD44v3 and CD44v6 on T cells from patients with systemic lupus erythematosus (SLE), and to assess correlations of the level of expression of these molecules with disease manifestations.

Methods

Information on clinical and demographic characteristics was collected, and blood samples were obtained from 72 patients with SLE and 32 healthy control subjects matched to the patients by sex, race, and age. Expression of CD44 and variants CD44v3 and v6 on T cell subsets was determined by flow cytometry, and Pearson's correlations of their expression levels with clinical variables, SLE Disease Activity Index (SLEDAI) scores, and presence of lupus nephritis were determined. Wilcoxon's rank sum tests and conditional multivariable regression analyses were applied to identify differences in the expression of CD44 between patients with SLE and healthy controls.

Results

Expression of CD44 was higher on CD4+ and CD8+ T cells from SLE patients compared with controls (P ≤ 0.03). Expression of CD44v3 and CD44v6 was also higher on total T cells and CD4+ and CD8+ T cells from SLE patients compared with controls (P ≤ 0.03). Cell surface levels of CD44v3 on total T cells, CD4+ T cells, and CD8+ T cells as well as cell surface expression of CD44v6 on total T cells and CD4+ T cells were correlated with the SLEDAI score (P < 0.05). The presence of lupus nephritis was associated with the expression of CD44v6 on total T cells, CD4+ T cells, and CD4−CD8− T cells (P < 0.05). Positivity for anti–double‐stranded DNA antibodies was associated with the expression levels of CD44v6 on T cells (P < 0.05).

Conclusion

These results indicate that expression levels of CD44v3 and CD44v6 on T cells may represent useful biomarkers of SLE activity.
ADAM15 exerts an antiapoptotic effect on osteoarthritic chondrocytes via up‐regulation of the X‐linked inhibitor of apoptosis
Authors: Böhm Beate , Hess Sandra , Krause Kristin , Schirner Andrea , Ewald Werner , Aigner Thomas , Burkhardt Harald
Published: March 2010

Objective

To investigate the capacity of ADAM15, a disintegrin metalloproteinase that is up‐regulated in osteoarthritic (OA) cartilage, to protect chondrocytes against apoptosis induced by growth factor deprivation and genotoxic stress.

Methods

Caspase 3/7 activity was determined in primary OA and ADAM15‐transfected T/C28a4 chondrocytes upon exposure to the DNA‐damaging agent camptothecin or serum withdrawal. Camptothecin‐induced cytotoxicity was determined by measuring cellular ATP content. (Anti‐)apoptotic proteins were analyzed by immunoblotting, and levels of messenger RNA (mRNA) for X‐linked inhibitor of apoptosis (XIAP) were determined using real‐time polymerase chain reaction. RNA interference was applied for down‐regulation of ADAM15 and XIAP expression. Immunohistochemistry analysis of normal and OA cartilage samples was performed using XIAP‐ and ADAM15‐specific antibodies.

Results

ADAM15‐transfected chondrocytes cultured on a collagen matrix displayed significantly reduced caspase 3/7 activity upon serum or intermittent matrix withdrawal, compared with vector‐transfected control cells. Apoptosis induction by camptothecin exposure also led to significantly elevated caspase 3/7 activity and reduced cell viability of the vector‐transfected compared with ADAM15‐transfected chondrocytes. Increased levels of activated caspase 3 and cleaved poly(ADP‐ribose) polymerase were detected in the vector controls. XIAP, an inhibitor of activated caspase 3, was significantly up‐regulated (∼3‐fold) at the protein and mRNA levels in ADAM15‐transfected chondrocytes upon camptothecin treatment. Specific down‐regulation of either ADAM15 or XIAP in OA chondrocytes led to significant sensitization to camptothecin‐induced caspase 3/7 activity. Immunohistochemical analysis revealed low to moderate XIAP expression in normal specimens and markedly increased XIAP staining, colocalizing with ADAM15, in OA cartilage.

Conclusion

ADAM15 conveys antiapoptotic properties to OA chondrocytes that might sustain their potential to better resist the influence of death‐inducing stimuli under pathophysiologic conditions.
The effect of alcohol on radiographic progression in rheumatoid arthritis
Authors: Nissen M. J. , Gabay C. , Scherer A. , Finckh A. ,   Swiss Clinical Quality Management Project in Rheumatoid Arthritis
Published: March 2010

Objective

Alcohol consumption reduces the risk of development of rheumatoid arthritis (RA) and significantly attenuates the development of erosive arthritis in animal models. It remains unknown whether alcohol consumption influences joint damage progression in RA. This study was undertaken to compare the rates of radiographic damage progression in alcohol drinkers and nondrinkers in a large prospective cohort of patients with RA.

Methods

All patients in the population‐based Swiss Clinical Quality Management in RA registry database with at least 2 sequential radiographs were included. Joint erosions were assessed in 38 joints in the hands and feet using a validated scoring method. The rate of progression of erosions was analyzed using multivariate regression models for longitudinal data and was adjusted for potential confounders.

Results

The study included 2,908 patients with RA with a mean of 4 sequential radiographs and 3.9 years of followup. A trend toward reduced radiographic progression existed in drinkers compared with nondrinkers, with a mean rate of erosive progression of 0.99% (95% confidence interval [95% CI] 0.89–1.09) and 1.13% (95% CI 1.01–1.26) at 1 year, respectively. Alcohol consumption displayed a J‐shaped dose‐response effect, with a more favorable evolution in occasional consumers (P= 0.01) and daily consumers (P= 0.001) as compared with nondrinkers, while heavy drinkers demonstrated worse radiographic evolution (P= 0.0001). We found significant effect modification by sex, with male drinkers displaying significantly less erosive progression compared with male nondrinkers (mean 0.86% [95% CI 0.70–1.03] versus 1.35% [95% CI 1.02–1.67];P= 0.007).

Conclusion

Our findings indicate a trend toward reduced radiographic progression in alcohol drinkers compared with nondrinkers, specifically in occasional and daily alcohol consumers. In particular, male patients with RA who consume alcohol demonstrate less radiographic progression than do male nondrinkers.
High‐speed rough clustering for very large document collections
Authors: Kishida Kazuaki
Published: March 2010

Document clustering is an important tool, but it is not yet widely used in practice probably because of its high computational complexity. This article explores techniques of high‐speed rough clustering of documents, assuming that it is sometimes necessary to obtain a clustering result in a shorter time, although the result is just an approximate outline of document clusters. A promising approach for such clustering is to reduce the number of documents to be checked for generating cluster vectors in the leader–follower clustering algorithm. Based on this idea, the present article proposes a modified Crouch algorithm and incomplete single‐pass leader–follower algorithm. Also, a two‐stage grouping technique, in which the first stage attempts to decrease the number of documents to be processed in the second stage by applying a quick merging technique, is developed. An experiment using a part of the Reuters corpus RCV1 showed empirically that both the modified Crouch and the incomplete single‐pass leader–follower algorithms achieve clustering results more efficiently than the original methods, and also improved the effectiveness of clustering results. On the other hand, the two‐stage grouping technique did not reduce the processing time in this experiment.
Cleft lip and palate results from Hedgehog signaling antagonism in the mouse: Phenotypic characterization and clinical implications
Authors: Lipinski Robert J. , Song Chihwa , Sulik Kathleen K. , Everson Joshua L. , Gipp Jerry J. , Yan Dong , Bushman Wade , Rowland Ian J.
Published: March 2010

BACKGROUND

The Hedgehog (Hh) pathway provides inductive signals critical for developmental patterning of the brain and face. In humans and in animal models interference with this pathway yields birth defects, among the most well‐studied of which fall within the holoprosencephaly (HPE) spectrum.

METHODS

Timed‐pregnant C57Bl/6J mice were treated with the natural Hh signaling antagonist cyclopamine by subcutaneous infusion from gestational day (GD) 8.25 to 9.5, or with a potent cyclopamine analog, AZ75, administered by oral gavage at GD 8.5. Subsequent embryonic morphogenesis and fetal central nervous system (CNS) phenotype were respectively investigated by scanning electron microscopy and high resolution magnetic resonance imaging (MRI).

RESULTS

In utero Hh signaling antagonist exposure induced a spectrum of craniofacial and brain malformations. Cyclopamine exposure caused lateral cleft lip and palate (CLP) defects attributable to embryonic deficiency of midline and lower medial nasal prominence tissue. The CLP phenotype was accompanied by olfactory bulb hypoplasia and anterior pituitary aplasia, but otherwise grossly normal brain morphology. AZ75 exposure caused alobar and semilobar HPE with associated median facial deficiencies. An intermediate phenotype of median CLP was produced infrequently by both drug administration regimens.

CONCLUSIONS

The results of this study suggest that interference with Hh signaling should be considered in the CLP differential and highlight the occurrence of CNS defects that are expected to be present in a cohort of patients having CLP. This work also illustrates the utility of fetal MRI‐based analyses and establishes a novel mouse model for teratogen‐induced CLP. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.