bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppressive actions of eicosapentaenoic acid on lipid droplet formation in 3T3-L1 adipocytes
Authors: Manickam Elizabeth , Sinclair Andrew J , Cameron-Smith David 
Published: June 2010

Abstract

Background
Lipid droplet (LD) formation and size regulation reflects both lipid influx and efflux, and is central in the regulation of adipocyte metabolism, including adipokine secretion. The length and degree of dietary fatty acid (FA) unsaturation is implicated in LD formation and regulation in adipocytes. The aims of this study were to establish the impact of eicosapentaenoic acid (EPA; C20:5n-3) in comparison to SFA (STA; stearic acid, C18:0) and MUFA (OLA; oleic acid, C18:1n-9) on 3T3-L1 adipocyte LD formation, regulation of genes central to LD function and adipokine responsiveness. Cells were supplemented with 100 μM FA during 7-day differentiation.

Results
EPA markedly reduced LD size and total lipid accumulation, suppressing PPARγ, Cidea and D9D/SCD1 genes, distinct from other treatments. These changes were independent of alterations of lipolytic genes, as both EPA and STA similarly elevated LPL and HSL gene expressions. In response to acute lipopolysaccharide exposure, EPA-differentiated adipocytes had distinct improvement in inflammatory response shown by reduction in monocyte chemoattractant protein-1 and interleukin-6 and elevation in adiponectin and leptin gene expressions.

Conclusions
This study demonstrates that EPA differentially modulates adipogenesis and lipid accumulation to suppress LD formation and size. This may be due to suppressed gene expression of key proteins closely associated with LD function. Further analysis is required to determine if EPA exerts a similar influence on LD formation and regulation in-vivo.
A rapid and scalable method for selecting recombinant mouse monoclonal antibodies
Authors: Crosnier Cécile , Staudt Nicole , Wright Gavin J 
Published: June 2010

AbstractBackgroundMonoclonal antibodies with high affinity and selectivity that work on wholemount fixed tissues are valuable reagents to the cell and developmental biologist, and yet isolating them remains a long and unpredictable process. Here we report a rapid and scalable method to select and express recombinant mouse monoclonal antibodies that are essentially equivalent to those secreted by parental IgG-isotype hybridomas.ResultsIncreased throughput was achieved by immunizing mice with pools of antigens and cloning - from small numbers of hybridoma cells - the functionally rearranged light and heavy chains into a single expression plasmid. By immunizing with the ectodomains of zebrafish cell surface receptor proteins expressed in mammalian cells and screening for formalin-resistant epitopes, we selected antibodies that gave expected staining patterns on wholemount fixed zebrafish embryos.ConclusionsThis method can be used to quickly select several high quality monoclonal antibodies from a single immunized mouse and facilitates their distribution using plasmids.
Multifocal Stevens-Johnson syndrome after concurrent phenytoin and cranial and thoracic radiation treatment, a case report
Authors: Kandil Abdullah O , Dvorak Tomas , Mignano John , Wu Julian K , Zhu Jay-Jiguang 
Published: June 2010

Abstract
A 46 year old male patient with metastatic prostate cancer developed Stevens-Johnson syndrome (SJS), initially in three well-demarcated areas on his scalp, chest and back, corresponding to ports of radiation therapy while on phenytoin. The rash spread from these locations and became more generalized and associated with pain and sloughing in the mucous lining of the mouth. There is a documented association between phenytoin administration with concurrent cranial radiation therapy and development of SJS. Erythema multiforme (EM) associated with phenytoin and cranial radiation therapy (EMPACT) is the term that describes this reaction. However, this term may not cover the full spectrum of the disease since it describes EM associated with phenytoin and only cranial radiation therapy. This case report presents evidence that SJS may be induced by radiation to other parts of the body in addition to the cranium while phenytoin is administered concomitantly. With increasing evidence that phenytoin and levetiracetam are equally efficacious for seizure treatment and prophylaxis, and since there is no link identified so far of an association between levetiracetam and SJS, we believe that levetiracetam is a better option for patients who need anticonvulsant medication(s) while undergoing radiation therapy, especially cranial irradiation.
Effectiveness of an e-learning course in evidence-based medicine for foundation (internship) training
Authors: Hadley Julie , Kulier Regina , Zamora Javier , Coppus Sjors FPJ , Weinbrenner Susanne , Meyerrose Berrit , Decsi Tamas , Horvath Andrea R , Nagy Eva , Emparanza Jose I , Arvanitis Theodoros N , Burls Amanda , Cabello Juan B , Kaczor Marcin , Zanrei Gianni , Pierer Karen , Kunz Regina , Wilkie Veronica , Wall David , Mol Ben WJ , Khan Khalid S 
Published: June 2010

Summary Aim To evaluate the educational effectiveness of a clinically integrated e-learning course for teaching basic evidence-based medicine (EBM) among postgraduate medical trainees compared to a traditional lecture-based course of equivalent content. Methods We conducted a cluster randomized controlled trial to compare a clinically integrated e-learning EBM course (intervention) to a lecture-based course (control) among postgraduate trainees at foundation or internship level in seven teaching hospitals in the UK West Midlands region. Knowledge gain among participants was measured with a validated instrument using multiple choice questions. Change in knowledge was compared between groups taking into account the cluster design and adjusted for covariates at baseline using generalized estimating equations (GEE) model. Results There were seven clusters involving teaching of 237 trainees (122 in the intervention and 115 in the control group). The total number of postgraduate trainees who completed the course was 88 in the intervention group and 72 in the control group. After adjusting for baseline knowledge, there was no difference in the amount of improvement in knowledge of EBM between the two groups. The adjusted post course difference between the intervention group and the control group was only 0.1 scoring points (95% CI −1.2–1.4). Conclusion An e-learning course in EBM was as effective in improving knowledge as a standard lecture-based course. The benefits of an e-learning approach need to be considered when planning EBM curricula as it allows standardization of teaching materials and is a potential cost-effective alternative to standard lecture-based teaching.
Some Remarks on Delayed Renewal Risk Models
Authors: Woo Jae-Kyung 
Published: June 2010

AbstractSome extensions to the delayed renewal risk models are considered. In particular, the independence assumption between the interclaim time and the subsequent claim size is relaxed, and the classical Gerber-Shiu penalty function is generalized by incorporating more variables. As a result, general structures regarding various joint densities of ruin related quantities as well as their probabilistic interpretations are provided. The numerical example in case of time-dependent claim sizes is provided, and also the usual delayed model with time-independent claim sizes is discussed including a special case with exponential claim sizes. Furthermore, asymptotic formulas for the associated compound geometric tail for the present model are derived using two alternative methods.
Unexpected Acceleration of Type 1 Diabetes by Transgenic Expression of B7-H1 in NOD Mouse Peri-Islet Glia
Authors: Yantha Jason , Tsui Hubert , Winer Shawn , Song Aihua , Wu Ping , Paltser Geoff , Ellis James , Dosch H.-Michael 
Published: June 2010

OBJECTIVE
Autoimmune target tissues in type 1 diabetes include pancreatic β-cells and peri-islet Schwann cells (pSC)—the latter active participants or passive bystanders in pre-diabetic autoimmune progression. To distinguish between these alternatives, we sought to suppress pSC autoimmunity by transgenic expression of the negative costimulatory molecule B7-H1 in NOD pSC.

RESEARCH DESIGN AND METHODS
A B7-H1 transgene was placed under control of the glial fibrillary acidic protein (GFAP) promoter. Transgenic and wild-type NOD mice were compared for transgene PD-1 affinities, diabetes development, insulitis, and pSC survival. Mechanistic studies included adoptive type 1 diabetes transfer, B7-H1 blockade, and T-cell autoreactivity and sublineage distribution.

RESULTS
Transgenic and endogenous B7-H1 bound PD-1 with equal affinities. Unexpectedly, the transgene generated islet-selective CD8+ bias with accelerated rather than suppressed diabetes progression. T-cells of diabetic transgenics transferred type 1 diabetes faster. There were no earlier pSC losses due to conceivable transgene toxicity, but transgenic pSC loss was enhanced by 8 weeks, preceded by elevated GFAP autoreactivity, with high-affinity T-cells targeting the major NOD Kd-GFAP epitope, p253–261. FoxP3+ regulatory T- and CD11c+ dendritic cell pools were unaffected.

CONCLUSIONS
In contrast with transgenic B7-H1 in NOD mouse β-cells, transgenic B7-H1 in pSC promotes rather than protects from type 1 diabetes. Here, ectopic B7-H1 enhanced the pathogenicity of effector T-cells, demonstrating that pSC can actively impact diabetes progression—likely through modification of intraislet T-cell selection. Although pSC cells emerge as a new candidate for therapeutic targets, caution is warranted with regard to the B7-H1–PD1 axis, where B7-H1 overexpression can lead to accelerated autoimmune disease.
Increased β-Cell Mass by Islet Transplantation and PLAG1 Overexpression Causes Hyperinsulinemic Normoglycemia and Hepatic Insulin Resistance in Mice
Authors: Declercq Jeroen , Kumar Anujith , Van Diepen Janna A. , Vroegrijk Irene O.C.M. , Gysemans Conny , Di Pietro Caterina , Voshol Peter J. , Mathieu Chantal , Ectors Nadine , Van de Ven Wim J.M. , Verfaillie Catherine M. 
Published: June 2010

OBJECTIVE
It is believed that an organism remains normoglycemic despite an increase in the β-cell mass because of decreased insulin production by β-cells on a per-cell basis. However, some transgenic mouse models with β-cell hyperplasia suggest that insulin production remains excessive and that normoglycemia is maintained by insulin resistance.

METHODS
Here, we investigated the effect of an increased β-cell mass on glycemia and insulin resistance by grafting excess normal islets in normoglycemic mice, as well as using targeted PLAG1 expression in β-cells, which leads to β-cell expansion.

RESULTS
In both models, fasting plasma insulin levels were increased, even though animals were normoglycemic. After an intraperitoneal glucose tolerance test, plasma insulin levels increased, which was associated with improved glucose clearing. Under these conditions, normoglycemia is maintained by hepatic insulin resistance as demonstrated by hyperinsulinemic euglycemic clamp experiments.

CONCLUSIONS
In conclusion, we demonstrate that when excess β-cells are grafted, insulin production on a per β-cell basis is not sufficiently decreased, leading to hyperinsulinemia and hepatic insulin resistance. This observation might be important for the design of stem cell-based islet replacement therapies.
Control of Adipose Tissue Inflammation Through TRB1
Authors: Ostertag Anke , Jones Allan , Rose Adam J. , Liebert Maria , Kleinsorg Stefan , Reimann Anja , Vegiopoulos Alexandros , Diaz Mauricio Berriel , Strzoda Daniela , Yamamoto Masahiro , Satoh Takashi , Akira Shizuo , Herzig Stephan 
Published: June 2010

OBJECTIVEBased on its role as an energy storage compartment and endocrine organ, white adipose tissue (WAT) fulfills a critical function in the maintenance of whole-body energy homeostasis. Indeed, WAT dysfunction is connected to obesity-related type 2 diabetes triggered at least partly by an inflammatory response in adipocytes. The pseudokinase tribbles (TRB) 3 has been identified by us and others as a critical regulator of hepatic glucose homeostasis in type 2 diabetes and WAT lipid homeostasis. Therefore, this study aimed to test the hypothesis that the TRB gene family fulfills broader functions in the integration of metabolic and inflammatory pathways in various tissues.RESEARCH DESIGN AND METHODSTo determine the role of TRB family members for WAT function, we profiled the expression patterns of TRB13 under healthy and metabolic stress conditions. The differentially expressed TRB1 was functionally characterized in loss-of-function animal and primary adipocyte models.RESULTSHere, we show that the expression of TRB1 was specifically upregulated during acute and chronic inflammation in WAT of mice. Deficiency of TRB1 was found to impair cytokine gene expression in white adipocytes and to protect against high-fat diet–induced obesity. In adipocytes, TRB1 served as a nuclear transcriptional coactivator for the nuclear factor κB subunit RelA, thereby promoting the induction of proinflammatory cytokines in these cells.CONCLUSIONSAs inflammation is typically seen in sepsis, insulin resistance, and obesity-related type 2 diabetes, the dual role of TRB1 as both a target and a (co) activator of inflammatory signaling might provide a molecular rationale for the amplification of proinflammatory responses in WAT in these subjects.
Optimalized transient transfection of chondrogenic primary cell cultures
Authors: Juhász Tamás , Matta Csaba , Mészár Zoltán , Nagy Georgina , Szíjgyártó Zsolt , Molnár Zsanett , Kolozsvári Bernadett , Bakó Éva , Zákány Róza 
Published: June 2010

Abstract
We aimed to find a transfection method which provides high efficiency with minimal cytotoxic and/or apoptotic effects for gene transfer into multilayer primary chondrogenic cell cultures. The pEGFP-C1 plasmid was introduced into the cell culture and the efficiency of transformation quantified by GFP fluorescence; the resulting nucleofection was effective but resulted in severe apoptosis. Two liposomal reagents designed to allow transfection into adherent cells did not deliver the plasmids sufficiently and cartilage formation did not occur. In addition, a third liposomal compound, recommended for transfection into either adherent or suspension cell cultures, lead to acceptable transfection efficiency but no cartilage formation. When an amphiphilic reagent was used however, there was acceptable transfection efficiency as well as cartilage formation. The viability of the cells which were transfected using the amphiphilic reagent remained unaffected but proliferation was severely diminished, particularly in the presence of GFP. In addition, the amount of cartilage decreased when GFP was expressed, despite unchanged levels of mRNAs of sox9 and aggrecan core protein, factors reflecting on the efficiency of chondrogenesis. Overexpression of both the constitutively active delta and gamma isoforms of catalytic subunit of calcineurin, a protein phosphatase described as a positive regulator of chondrogenesis, decreased protein level of Sox9 and subsequent cartilage formation. In conclusion, we found that amphiphilic reagent applied prior to the adhesion of cells provides a useful means to transfer plasmids to primary differentiating chondrogenic cells.
Integrin receptors play a role in the internalin B-dependent entry of Listeria monocytogenes into host cells
Authors: Auriemma Clementina , Viscardi Maurizio , Tafuri Simona , Pavone Luigi , Capuano Federico , Rinaldi Laura , Morte Rossella , Iovane Giuseppe , Staiano Norma 
Published: June 2010

AbstractListeria monocytogenes enters non-phagocytic cells by binding its surface proteins inlA (internalin) and inlB to the host’s E-cadherin and Met, respectively. The two internalins play either separate or cooperative roles in the colonization of infected tissues. Here, we studied bacterial uptake into HeLa cells using an L. monocytogenes mutant strain (ΔinlA) carrying a deletion in the gene coding for inlA. The ΔinlA mutant strain showed the capability to invade HeLa cells. The monoclonal anti-β3- and anti-β1-integrin subunit antibodies prevented bacterial uptake into the cells, while the anti-β2- and anti-β4-integrin subunit antibodies failed to affect L. monocytogenes entry into HeLa cells. Three structurally distinct disintegrins (kistrin, echistatin and flavoridin) also inhibited bacterial uptake, showing different potencies correlated to their selective affinity for the β3- and β1-integrin subunits. In addition to inducing Met phosphorylation, infection of cells by the L. monocytogenes ΔinlA mutant strain promoted the tyrosine phosphorylation of the focal adhesion-associated proteins FAK and paxillin. Our findings provide the first evidence that β3- and β1-integrin receptors play a role in the inlB-dependent internalization of L. monocytogenes into host cells.
Asymmetric synthesis of machilin C and its analogue
Authors: Xia Yamu , Wang Wei 
Published: June 2010

AbstractFull details of the asymmetric total synthesis of erythro-8-O-4′-neolignan, machilin C, and its analogue perseal A are reported. The synthesis was involved in the Sharpless dihydroxylation reaction that occurred with excellent asymmetric induction, and the Mitsunobu reaction which occurred with inversion of the absolute configuration from the threo to the erythro isomer. The synthesis was achieved from simple vanillin in eight to twelve steps.
Morphological characteristics of modified freeze-dried poly(N-isopropylacrylamide) microspheres studied by optical microscopy, SEM, and DLS
Authors: Musial Witold , Vincent Brian , Szumny Antoni , Voncina Bojana 
Published: June 2010

AbstractInfluence of the initiator and additional hydrophobic copolymer on the morphology of thermosensitive poly(N-isopropylacrylamide) (pNIPAM) microspheres, and their presumed application for the stabilization of biologically active molecules were evaluated in this study. Three different types of pNIPAM were synthesized, applying various components: PN1 is a polymer with terminal anionic groups resulting from potassium persulfate initiator; PN2 was synthesized with a 2,2′-azobis(2-methylpropionamidine) dihydrochloride initiator introducing cationic amidine terminal groups; in the PN3 polymer, anionic terminals were implemented, however, increased hydrophobicity was maintained using N-tert-butyl functional groups. Turbidity measurements of the obtained dispersions confirmed specific thermosensitivity of synthesized microspheres in the range of 32–33°C. The polymerization course was proved by infrared spectroscopy and 1H NMR assessments, whereas the size of the synthesized microspheres, expressed as planar area, was evaluated by dynamic light scattering (DLS), scanning electron microscopy (SEM) and optical microscopy (OM). The respective surface patterns of the freeze-dried microspheres were evaluated by SEM. Planar area of the synthesized macromolecules was in the range between 0.41–3.22 μm, depending on the substrates composition and the method applied for the measurements. The assessments performed in the dry stage gave higher values of the diameter and planar area of the observed microspheres. The measured diameter and planar area increased in the following order for the PN3 microspheres: DLS, OM, SEM. In the case of PN1 and PN2, the observed diameters were positioned as: DLS, SEM, OM. These differences were assigned both to varied intramolecular hydrophobic-hydrophilic interactions of the polymer chains and to the environment, i.e. low pressure in the SEM conditions and aqueous solvent in the DLS measurements. The observed gaps in the freeze-dried PN2 polymer resulted in an attempt to evaluate the application of this polymer for mechanical stabilization of certain macromolecules or nanocrystals in the size range between 10 nm and 20 nm.
Reduced renal function after preeclampsia does not result from accelerated age‐dependent renal function loss
Authors: Spaan Julia J. , Ekhart Timo , Spaanderman Marc E.A. , Peeters Louis L.H. 
Published: June 2010

AbstractPreeclampsia is associated with later kidney disease. This study tested the hypothesis that the normal decline in renal function with age is more rapid in formerly preeclamptic women than in controls. Four groups were compared cross‐sectionally: young women with a history of preeclampsia (n = 34), young controls (n = 12), middle‐aged women with a history of preeclampsia (n = 22) and middle‐aged controls (n = 29). We measured blood pressure (semi‐automatic device), effective renal plasma flow (ERPF, para‐aminohippurate clearance), glomerular filtration rate (GFR, creatinine clearance) and cardiac output (Doppler echocardiography). ERPF was lower in both young and middle‐aged women with a history of preeclampsia relative to controls. The decrease in both GFR and ERPF with age was comparable in both groups. In conclusion, the lower renal function in middle‐aged formerly preeclamptic women does not result from accelerated age‐dependent renal function loss, but from an already reduced renal function relative to parous controls at young age.
Menstruation‐related spontaneous pneumothorax and diaphragmatic endometriosis
Authors: Härkki Päivi , Jokinen Janne J. , Salo Jarmo A. , Sihvo Eero 
Published: June 2010

AbstractMenstruation‐related spontaneous pneumothorax (MSP), also termed catamenial pneumothorax, is a syndrome of spontaneous pneumothorax during menstruation due to endometriotic lesions in the diaphragm and thoracic cavity. Previously MSP was considered rare, and to cause only 3–6% of all spontaneous pneumothoraces in otherwise healthy women. Current data suggest that the incidence is substantially higher and MSP might be the reason for spontaneous pneumothoraces in up to 25–33% of all cases in women of reproductive age. The typical characteristics are a high recurrence rate and diaphragmatic spread of endometriotic lesions. We report six patients who had been diagnosed to have diaphragmatic endometriosis and four of them had developed MSP. Optimal management requires flexible collaboration between thoracic surgeons and gynecologists. Although treatment is primarily surgical, long‐lasting and successful management requires that amenorrhea is induced with hormonal therapy, either by continuous contraceptives, progestins, the levonorgestrel‐releasing intrauterine device or GnRH‐agonists.
Creating a Consolidated Online Catalogue for the University Press Community
Authors: Esposito Joseph J. 
Published: June 2010

This essay derives from a feasibility study into the possibility of creating a consolidated online catalogue for university presses and was underwritten by the Andrew W. Mellon Foundation and sponsored by The Monterey Institute for Technology and Education; the essay is an abridgement of the report submitted to Mellon and MITE. For more information on the background, see the acknowledgments and disclosures at the end of this paper. The aim of this study was to identify a means by which university presses could sell more books and, specifically, whether the creation of a consolidated online catalogue of press titles would help in this regard. The presses at this time vary considerably in terms of size, resources, and familiarity with online marketing, though all of them are active to some degree online and most identify Amazon as their largest customer. Despite this activity, however, and even for the very largest presses, a press-wide catalogue would augment sales by exploiting greater scale, enabling more effective search-engine and other online marketing, by opening up new promotional vehicles, and by strengthening individual press brands by bringing more robust technology to each institution's efforts.