bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti–citrullinated protein antibodies bind surface‐expressed citrullinated Grp78 on monocyte/macrophages and stimulate tumor necrosis factor α production
Authors: Lu Ming‐Chi , Lai Ning‐Sheng , Yu Hui‐Chun , Huang Hsien‐Bin , Hsieh Song‐Chou , Yu Chia‐Li 
Published: March 2010

AbstractObjectiveAnti–citrullinated protein antibodies (ACPAs), which are the most specific autoantibody marker in patients with rheumatoid arthritis (RA), correlate with disease activity; however, the role of ACPAs in RA pathogenesis has not been elucidated. We hypothesized that ACPAs may directly stimulate mononuclear cells to produce inflammatory cytokines. Thus, we identified cognate antigens of ACPAs on monocyte/macrophages and examined their immunopathologic roles in the pathogenesis of RA.MethodsACPAs were purified from pooled ACPA‐positive RA sera by cyclic citrullinated peptide–conjugated affinity column. After coculture of U937 cells with ACPAs, the tumor necrosis factor α (TNFα) production and NF‐κB DNA binding activity of the cells were measured by enzyme‐linked immunosorbent assay. The cognate antigens of ACPAs on the U937 cell surface were probed by ACPAs, and the reactive bands were examined via proteomic analysis.ResultsACPAs specifically enhanced TNFα production and increased the DNA‐binding activity of NF‐κB in U937 cells. Proteomic analysis revealed that Grp78 protein (72 kd) was one of the cognate antigens of ACPAs. The truncated form of cell surface–expressed Grp78 (55 kd) on U937 cells contained citrulline capable of binding with ACPAs. After citrullination, glutathione S‐transferase–tagged recombinant Grp78 (97.52 kd) became a 72‐kd fragment and bound with ACPAs. ACPAs also bound to human monocytes and lymphocytes to promote TNFα production.ConclusionWe clearly demonstrated that ACPAs enhance NF‐κB activity and TNFα production in monocyte/macrophages via binding to surface‐expressed citrullinated Grp78.
Incorporating radiology into medical gross anatomy: Does the use of cadaver CT scans improve students' academic performance in anatomy?
Authors: Lufler Rebecca S. , Zumwalt Ann C. , Romney Carla A. , Hoagland Todd M. 
Published: March 2010

AbstractRadiological images show anatomical structures in multiple planes and may be effective for teaching anatomical spatial relationships, something that students often find difficult to master. This study tests the hypotheses that (1) the use of cadaveric computed tomography (CT) scans in the anatomy laboratory is positively associated with performance in the gross anatomy course and (2) dissection of the CT‐scanned cadaver is positively associated with performance on this course. One hundred and seventy‐nine first‐year medical students enrolled in gross anatomy at Boston University School of Medicine were provided with CT scans of four cadavers, and students were given the opportunity to choose whether or not to use these images. The hypotheses were tested using logistic regression analysis adjusting for student demographic characteristics. Students who used the CT scans were more likely to score greater than 90% as an average practical examination score (odds ratio OR 3.6; 95% CI 1.4, 9.2), final course grade (OR 2.6; 95% CI 1.01, 6.8), and on spatial anatomy examination questions (OR 2.4; 95% CI 1.03, 5.6) than were students who did not use the CT scans. There were no differences in performance between students who dissected the scanned cadavers and those who dissected a different cadaver. These results demonstrate that the use of CT scans in medical gross anatomy is predictive of performance in the course and on questions requiring knowledge of anatomical spatial relationships, but it is not necessary to scan the actual cadaver dissected by each student. Anat Sci Educ 3: 56–63, 2010. © 2010 American Association of Anatomists.
Comparative efficacy of group and individual feedback in gross anatomy for promoting medical student professionalism
Authors: Camp Christopher L. , Gregory Jeremy K. , Lachman Nirusha , Chen Laura P. , Juskewitch Justin E. , Pawlina Wojciech 
Published: March 2010

AbstractProfessionalism is a core competency of medical training that requires students to develop the skills of providing and receiving feedback. Our study evaluated the effectiveness of delivering feedback in a group setting compared with an individual setting. The first‐year class of Mayo medical students (n= 49) enrolled in gross anatomy (in dissection teams), completed weekly anonymous evaluations of themselves and their teammates regarding seven aspects of professionalism (altruism, compassion, respect, honesty/integrity, responsibility, commitment to excellence, and self‐reflection). Professionalism scores from these surveys were calculated using a six‐point Likert scale. Students were also asked to comment on strengths and possible areas for improvement on each peer. At the midpoint of the course, peer comments and professionalism scores were shared with students in debriefing sessions either individually or with their team. Analysis of preintervention and postintervention professionalism scores indicated that the students receiving feedback in a one‐on‐one setting (student and instructor) were more likely to demonstrate higher scores on subsequent evaluations as compared with those students receiving feedback in a group setting (all team members and one instructor). Our findings suggest that providing feedback to first‐year medical students on an individual basis is the best way to improve professional attitudes and behaviors. Anat Sci Educ 3: 64–72, 2010. © 2010 American Association of Anatomists.
Decomposition and Model Selection for Large Contingency Tables
Authors: Dahinden Corinne , Kalisch Markus , Bühlmann Peter 
Published: March 2010

AbstractLarge contingency tables summarizing categorical variables arise in many areas. One example is in biology, where large numbers of biomarkers are cross‐tabulated according to their discrete expression level. Interactions of the variables are of great interest and are generally studied with log–linear models. The structure of a log–linear model can be visually represented by a graph from which the conditional independence structure can then be easily read off. However, since the number of parameters in a saturated model grows exponentially in the number of variables, this generally comes with a heavy computational burden. Even if we restrict ourselves to models of lower‐order interactions or other sparse structures, we are faced with the problem of a large number of cells which play the role of sample size. This is in sharp contrast to high‐dimensional regression or classification procedures because, in addition to a high‐dimensional parameter, we also have to deal with the analogue of a huge sample size. Furthermore, high‐dimensional tables naturally feature a large number of sampling zeros which often leads to the nonexistence of the maximum likelihood estimate. We therefore present a decomposition approach, where we first divide the problem into several lower‐dimensional problems and then combine these to form a global solution. Our methodology is computationally feasible for log–linear interaction models with many categorical variables each or some of them having many levels. We demonstrate the proposed method on simulated data and apply it to a bio‐medical problem in cancer research.
In vivo bioassay to detect irinotecan‐stabilized DNA/topoisomerase I complexes in rats
Authors: Barth Stephan W. , Briviba Karlis , Watzl Bernhard , Jäger Nicole , Marko Doris , Esselen Melanie 
Published: March 2010

AbstractIrinotecan is an anticancer agent that stabilizes topoisomerase I/DNA complexes. So far, no test system has been reported for directly determining irinotecan‐induced stabilization of topoisomerase I/DNA complexes in organs in vivo. We adapted an ‘in vivo complexes of enzyme to DNA’ (ICE) bioassay to assess irinotecan activity in the stomach, duodenum, colon and liver of male Wistar rats after a single treatment with irinotecan (100 mg/kg body weight, intraperitoneally). This was compared to the control group receiving 0.9% sodium chloride intraperitoneally. In addition, the DNA strand breaking properties of irinotecan were measured in mucosal cells from the distal colon by single‐cell gel electrophoresis (comet assay) to investigate the association of topoisomerase poisoning and DNA damage in vivo. A single dose of irinotecan significantly increased amounts of topoisomerase I covalently bound to DNA in stomach, duodenum, colon and liver. Concomitantly, the irinotecan‐treated group showed significantly higher amounts of DNA strand breaks in colon mucosa cells compared to the control group. The ICE bioassay and the comet assay represent two test systems for investigating the impact of topoisomerase I poisons on DNA integrity in colon tissues of Wistar rats.
Highly efficient gene transfer into hepatocyte‐like HepaRG cells: New means for drug metabolism and toxicity studies
Authors: Laurent Veronique , Fraix Aurore , Montier Tristan , Cammas‐Marion Sandrine , Ribault Catherine , Benvegnu Thierry , Jaffres Paul‐Alain , Loyer Pascal 
Published: March 2010

AbstractHepaRG progenitor cells are capable of differentiating into hepatocyte‐like cells that express a large set of liver‐specific functions. These cells, however, only express small amounts of an important cytochrome P450, the CYP2E1, which limits their use for toxicological studies of drugs metabolized by this pathway. Our aim was to establish an efficient transfection protocol to increase CYP2E1 expression in HepaRG cells. Transfection protocols of the green fluorescent protein (GFP) reporter gene were evaluated using electroporation and cationic lipids belonging to the lipophosphonates, lipophosphoramidates and lipids derived from glycine betaine. Following optimization of the charge ratios, plasmid DNA and formulations with neutral co‐lipids, the lipophosphoramidate compounds KLN47 and BSV10, allowed expression of the GFP in ∼50% of adherent progenitor HepaRG cells, while electroporation targeted GFP expression in ∼85% of both progenitor and differentiated cells in suspension. Transient enforced expression of active CYP2E1 was also achieved in progenitors and/or differentiated HepaRG cells using the electroporation and the lipophosphoramidate compound BSV10. Importantly, in electroporated cells, CYP2E1 expression level was correlated with a significant increase in CYP2E1‐specific enzymatic activity, which opens new perspectives for this CYP‐dependent drug metabolism and toxicity studies using HepaRG cells.
Sugar‐Based Synthesis of Tamiflu and Its Inhibitory Effects on Cell Secretion
Authors: Ma Jimei , Zhao Yanying , Ng Simon , Zhang Jing , Zeng Jing , Than Aung , Chen Peng , Liu Xue‐Wei 
Published: March 2010

AbstractTamiflu is currently the most effective drug for the treatment of influenza, but the insufficient supply and side‐effects of this drug demand urgent solutions. We present a practical synthesis of Tamiflu by using novel synthetic routes, cheap reagents, and the abundantly available starting material D‐glucal. The strategy features a Claisen rearrangement of hexose to obtain the cyclohexene backbone and introduction of diamino groups through tandem intramolecular aziridination and ring opening. In addition, this synthetic protocol allows late‐stage functionalization for the flexible synthesis of Tamiflu analogues. By using the synthesized Tamiflu and its active metabolite (oseltamivir carboxylate), we investigated their influences on neuroendocrine PC12 cells in various aspects. It was discovered that oseltamivir carboxylate significantly inhibits the vesicular exocytosis (regulated secretion) of PC12 cells, and suggests a mechanism underlying the Tamiflu side‐effects, in particular its possible adverse influences on neurotransmitter release in the central nervous system.
Hybrid rheological model for non‐Newtonian turbulent pipe flow
Authors: Wilson K. C. , Thomas A. D. 
Published: March 2010

AbstractMany slurry rheograms do not follow the Bingham model, but are curved (convex upwards) at low‐strain rates. Alternate models such as the yield‐power law (YPL), provide a good fit to the low‐strain rate data, but they tend to underestimate apparent viscosities at high‐strain rates. The current paper considers a hybrid rheological model consisting of a cubic‐spline fit to the low‐strain rate data merging into a Bingham linear model above a limiting strain rate. This model predicts turbulent flow well, depending only on the area difference between the Bingham rheogram and the cubic spline.
A multiscale model for quantifying helium diffusion in porous unsintered glass
Authors: Doorwar Shashvat , Chakraborty Saikat , Neogi Sudarsan 
Published: March 2010

AbstractHelium‐aided sintering of porous unsintered glass is a complex multiscale process, characterised by three different timescales, namely, that of helium diffusion, heat conduction, and radial shrinkage of the glass core. This work presents a multiscale model for quantifying heat and helium diffusion in a shrinking core system by decoupling the timescales based on their orders of magnitude. We obtain analytical solutions of our model, which allow us to quantify the spatio‐temporal profiles of temperature and helium concentration in the glass during the sintering process. Our results show that the introduction of helium increases the sintering rate of glass, and we conclude that pre‐sintering heating followed by helium‐aided sintering is better than simultaneous heating and helium diffusion. We also show that the pre‐sintering heating process for a standard glass sample should not be longer than an hour for the sake of heat economy, following which we may switch to the helium‐aided sintering process, where the sintering should occur under isothermal conditions for approximately 6 h. We perform dynamic simulations using glass porosity as a parameter, and find the sintering rate to be directly proportional to the initial porosity of the glass sample.
Smectic phases of liquid crystals based on dinuclear palladium(II) complexes with carboxylato bridge
Authors: Cîrcu V. , Simonescu C. M. 
Published: March 2010

AbstractIn this paper we present the preparation and the investigation of the liquid crystal properties of a series of dinuclear carboxylato bridge Pd(II) complexes bearing six alkoxy peripheral chains in the molecule. Their structures were assigned based on elemental analysis, IR and 1H NMR spectroscopy whereas the thermal behaviour was investigated by polarizing optical microscopy and differential scanning calorimetry. The monotropic smectic A phase displayed by these materials was identified by miscibility studies with a previously reported mesogen. It was found that the transition temperatures and the SmA mesophase stability depend on the alkyl chain length of the carboxylato bridge. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Metastasis of colon cancer to the thyroid gland: A case diagnosed on fine‐needle aspirate by a combined cytological, immunocytochemical, and molecular approach
Authors: Cozzolino Immacolata , Malapelle Umberto , Carlomagno Chiara , Palombini Lucio , Troncone Giancarlo 
Published: March 2010

AbstractFine‐needle aspiration (FNA) with cytological evaluation reliably diagnoses primary and secondary thyroid neoplasms. However, identifying the primary origin of a metastatic process involving the thyroid gland is challenging. In particular, metastasis of colon cancer to the thyroid gland is very rare. In this case report, a right lobe solid thyroid nodule in a 66‐year‐old male was aspirated. FNA cytology showed necrosis and atypical tall columnar cells; since, the patient at age 60 had undergone surgery for a sigmoid‐rectal cancer metastasizing to the liver and subsequently to the lung, a suspicion of metastasis from colon cancer was raised. This was corroborated by cell‐block immunocytochemistry showing a cytokeratin (CK) 7 negative/CK20‐positive staining pattern; thyreoglobulin and TTF‐1 were both negative. Since KRAS codon 12/13 mutations frequently occur in colon cancer, whereas they are extremely uncommon in primary thyroid tumors, DNA was extracted from the aspirated cells, and KRAS mutational analysis was carried out. The codon 12 G12D mutation was found; the same mutation was evident in the primary cancer of the colon and in its liver and lung metastasis. Thus, a combined cytological, immunocytochemical and molecular approach unquestionably correlated metastatic adenocarcinoma cells aspirated from the thyroid to a colo‐rectal origin. Diagn. Cytopathol. 2010;38:932–935. © 2010 Wiley‐Liss, Inc.
A dual systems model of adolescent risk‐taking
Authors: Steinberg Laurence 
Published: March 2010

AbstractIt has been hypothesized that reward‐seeking and impulsivity develop along different timetables and have different neural underpinnings, and that the difference in their timetables helps account for heightened risk‐taking during adolescence. In order to test these propositions, age differences in reward‐seeking and impulsivity were examined in a socioeconomically and ethnically diverse sample of 935 individuals between the ages of 10 and 30, using self‐report and behavioral measures of each construct. Consistent with predictions, age differences in reward‐seeking follow a curvilinear pattern, increasing between preadolescence and mid‐adolescence, and declining thereafter. In contrast, age differences in impulsivity follow a linear pattern, with impulsivity declining steadily from age 10 on. Heightened vulnerability to risk‐taking in middle adolescence may be due to the combination of relatively higher inclinations to seek rewards and still maturing capacities for self‐control. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 216–224, 2010
E(nos)/CG4699 required for nanos function in the female germ line of Drosophila
Authors: Yu Lin , Song Yan , Wharton Robin P. 
Published: March 2010

AbstractReduction of Nanos activity causes germ line stem cell failure in the Drosophila ovary. Only a few cysts with Vasa‐positive (green) differentiating germ line cells remain. The adducin‐like molecule Hts, which marks membranes, is red and DNA is blue. See the article by Yu et al. in this issue.
The maize milkweed pod1 mutant reveals a mechanism to modify organ morphology
Authors: Johnston Robyn , Candela Héctor , Hake Sarah , Foster Toshi 
Published: March 2010

AbstractPlant lateral organs, such as leaves, have three primary axes of growth–proximal‐distal, medial‐‐lateral and adaxial‐abaxial (dorsal‐ventral). Although most leaves are planar, modified leaf forms, such as the bikeeled grass prophyll, can be found in nature. A detailed examination of normal prophyll development indicates that polarity is established differently in the keels than in other parts of the prophyll. Analysis of the maize HD‐ZIPIII gene rolled leaf1 (rld1) suggests that altered expression patterns are responsible for keel outgrowth. Recessive mutations in the maize (Zea mays) KANADI (KAN) gene milkweed pod1 (mwp1), which promotes abaxial cell identity, strongly affect development of the prophyll and silks (fused carpels). The prophyll is reduced to two unfused midribs and the silks are narrow and misshapen. Our data indicate that the prophyll and other fused organs are particularly sensitive to disruptions in adaxial‐abaxial polarity. In addition, lateral and proximal‐distal growth of most lateral organs is reduced in the mwp1‐R mutant, supporting a role for the adaxial‐abaxial boundary in promoting growth along both axes. We propose that the adaxial‐abaxial patterning mechanism has been co‐opted during evolution to generate diverse organ morphologies. genesis 48:416–423, 2010. © 2010 Wiley‐Liss, Inc.
Murine visceral leishmaniasis: IgM and polyclonal B‐cell activation lead to disease exacerbation
Authors: Deak Eszter , Jayakumar Asha , Cho Ka Wing , Goldsmith‐Pestana Karen , Dondji Blaise , Lambris John D. , McMahon‐Pratt Diane 
Published: March 2010

AbstractIn visceral leishmaniasis, the draining LN (DLN) is the initial site for colonization and establishment of infection after intradermal transmission by the sand fly vector; however, little is known about the developing immune response within this site. Using an intradermal infection model, which allows for parasite visceralization, we have examined the ongoing immune responses in the DLN of BALB/c mice infected with Leishmania infantum. Although not unexpected, at early times post‐infection there is a marked B‐cell expansion in the DLN, which persists throughout infection. However, the characteristics of this response were of interest; as early as day 7 post‐infection, polyclonal antibodies (TNP, OVA, chromatin) were observed and the levels appeared comparable to the specific anti‐leishmania response. Although B‐cell‐deficient JhD BALB/c mice are relatively resistant to infection, neither B‐cell‐derived IL‐10 nor B‐cell antigen presentation appear to be primarily responsible for the elevated parasitemia. However, passive transfer and reconstitution of JhD BALB/c with secretory immunoglobulins, (IgM or IgG; specific or non‐specific immune complexes) results in increased susceptibility to L. infantum infection. Further, JhD BALB/c mice transgenetically reconstituted to secrete IgM demonstrated exacerbated disease in comparison to WT BALB/c mice as early as 2 days post‐infection. Evidence suggests that complement activation (generation of C5a) and signaling via the C5a receptor (CD88) is related to the disease exacerbation caused by IgM rather than cytokine levels (IL‐10 or IFN‐γ). Overall these studies indicate that polyclonal B‐cell activation, which is known to be associated with human visceral leishmaniasis, is an early and intrinsic characteristic of disease and may represent a target for therapeutic intervention.
Aberrant splicing of the milk fat globule‐EGF factor 8 (MFG‐E8) gene in human systemic lupus erythematosus
Authors: Yamaguchi Hiroshi , Fujimoto Takashi , Nakamura Shinobu , Ohmura Koichiro , Mimori Tsuneyo , Matsuda Fumihiko , Nagata Shigekazu 
Published: March 2010

AbstractMilk fat globule‐EGF factor 8 (MFG‐E8) promotes the phagocytosis of apoptotic cells by serving as a bridging molecule between apoptotic cells and phagocytes. Many apoptotic cells are left unengulfed in the germinal centers of the spleen of MFG‐E8−/− mice, which develop a human systemic lupus erythematosus (SLE)‐like autoimmune disease. Here, we analyzed the MFG‐E8 gene in human SLE patients, and found in two out of 322 female patients a heterozygous intronic mutation, which caused a cryptic exon from intron 6 to be included in the transcript. The cryptic exon contained a premature termination codon, generating a C‐terminally truncated MFG‐E8 protein. The mutant MFG‐E8 was aberrantly glycosylated and sialylated, but bound to phosphatidylserine and enhanced the phagocytosis of apoptotic cells. When intravenously injected into mice, the mutant MFG‐E8 was sustained longer in the blood circulation than wild‐type MFG‐E8. Repeated administrations of the mutant MFG‐E8 protein induced the production of autoantibodies, such as anti‐cardiolipin and anti‐nuclear antibodies, at a lower dose than that required for the wild‐type protein. These results suggested that the intronic mutation in the human MFG‐E8 gene can lead to the development of SLE.