bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two structurally identical mannose-specific jacalin-related lectins display different effects on human T lymphocyte activation and cell death
Authors: Benoist Hervé , Culerrier Raphaël , Poiroux Guillaume , Ségui Bruno , Jauneau Alain , Van Damme Els J M , Peumans Willy J , Barre Annick , Rougé Pierre 
Published: April 2009

Abstract
Subtle changes in cell surface N-glycan recognition can modulate the T lymphocyte fate.
Plant lectins displaying similar single sugar-binding specificity and identical molecular structure might present various biological effects. To explore this possibility, the effects on human lymphocytes of two mannose-specific and structurally closely related lectins, Morniga M from Morus nigra and artocarpin from Artocarpus integrifolia were investigated. In silico analysis revealed that Morniga M presents a more largely open carbohydrate-binding cavity than artocarpin, probably allowing interactions with a broader spectrum of carbohydrate moieties. In vitro, Morniga M interacted strongly with the lymphocyte surface and was uptaken quickly by cells. Morniga M and artocarpin triggered the proliferation and activation of human T and NK lymphocytes. A minority of B lymphocytes was activated in artocarpin-treated culture, whereas Morniga M favored the emergence of CD4+ CD8+ T lymphocytes. Moreover, cell death occurred in activated PBMC, activated T lymphocytes, and Jurkat T leukemia cells incubated with Morniga M only. The biological effects of both lectins were dependent on carbohydrate recognition. The Morniga M-induced cell death resulted, at least in part, from caspase-dependent apoptosis and FADD-dependent receptor-mediated cell death. Finally, Morniga M, but not artocarpin, triggered AICD of T lymphocytes. In conclusion, both lectins trigger lymphocyte activation, but only Morniga M induces cell death. In spite of similar in vitro mannose-binding specificities and virtually identical structure, only Morniga M probably interacts with carbohydrate moieties bound to molecules able to induce cell death. The present data suggest that subtle alterations in N-glycans can distinguish activation and cell death molecules at the lymphocyte surface.
Hypoxia increases macrophage motility, possibly by decreasing the heparan sulfate proteoglycan biosynthesis
Authors: Asplund Annika , Östergren-Lundén Gunnel , Camejo Germán , Stillemark-Billton Pia , Bondjers Göran 
Published: April 2009

Abstract
Hypoxia-induced modifications of HSPG may be of relevance for the development of atherosclerotic lesions and tumor progression.
Macrophages are recruited and retained in hypoxic sites in atherosclerotic lesions and tumors. Furthermore, macrophages are suggested to be a major source of HSPG synthesis in atherosclerotic lesions. HSPG are, among other things, known to regulate cell motility, cell adhesion, and receptor interaction. The aim of this study was to investigate the effect of hypoxia on HSPG expression and macrophage motility. We also explored the potential regulation of HSPG by the transcription factor HIF-1α. The nondirected cell motility was increased in HMDM after 24 h exposure to hypoxia (0.5% O2) compared with normal cell culture condition (21% O2). Enzymatic degradation of HS GAG further increased the motility of the HMDM in hypoxia, indicating a role of reduced cell-associated HSPG in the increased HMDM motility. HMDM exposed to 24 h of hypoxia had lower mRNA expressions of syndecan-1 and −4 compared with cells exposed to normal cell culture conditions. Protein levels of syndecan-1 were also decreased significantly in response to hypoxia, and cells subjected to hypoxia had lower mRNA expression for key enzymes involved in HS biosynthesis. In addition, hypoxia was found to reduce the relative content of HS GAG. Transfecting THP-1 cells with siHIF-1α indicated that this transcription factor was not involved in the hypoxia-induced modifications of HSPG expression. Given the documented multiple functions of HSPG in macrophage behavior, the hypoxia-induced modifications of HSPG may be of relevance for the development of atherosclerotic lesions and tumor progression.
TLR2 ligands augment cPLA2α activity and lead to enhanced leukotriene release in human monocytes
Authors: Lindner Sabine C , Köhl Ulrike , Maier Thorsten J , Steinhilber Dieter , Sorg Bernd L 
Published: April 2009

Abstract
Increased synthesis of inflammatory eicosanoids can be primed by innate immune receptor activation.
Toll-like receptors (TLRs) play an important role in innate immunity. They detect pathogen-associated receptor patterns (PAMPs) and initiate subsequent immune responses. Present studies investigate the influence of TLR2 ligands on leukotrienes (LT) formation in human monocytes. LTs are proinflammatory mediators derived from arachidonic acid (AA), which is released from membranes by phospholipase A2 (PLA2) enzymes. Pretreatment of MM6 cells with the TLR2 ligands LTA, FSL-1, or Pam3CSK4 resulted in an up to two- to threefold enhancement of ionophore-induced LT formation in a dose- and time-dependent manner and to an augmentation of ionophore-induced AA release with similar kinetics. Also in human peripheral blood mononuclear cells (hPBMC), TLR2 activators increased LT formation. Studies with PLA2 inhibitors indicated that the increase of AA release is a result of enhanced activity of group IV cPLA2 in MM6 cells. TLR2 ligands elicited the time-dependent activation of p38 MAPK and ERK1/2 pathways, which led to phosphorylation of cPLA2α at Ser505. Simultaneous inhibition of p38 MAPK and ERK1/2 pathways prevented the increase of cPLA2α phosphorylation and the augmentation of AA release. TLR2 ligand-induced increase of AA release was blocked by a neutralizing anti-hTLR2 antibody, indicating that TLR2 mediates augmented cPLA2 activation and subsequent LT biosynthesis.
PPARγ regulates retinoic acid-mediated DC induction of Tregs
Authors: Housley William J , O'Conor Catherine A , Nichols Frank , Puddington Lynn , Lingenheld Elizabeth G , Zhu Li , Clark Robert B 
Published: April 2009

Abstract
PPARγ plays a significant role in the induction of regulatory T cells (Tregs) by DC and can mediate enhanced conversion via secretion of retinoic acid.
CD4+ CD25+ Foxp3+ Tregs are critical regulators of immune responses and autoimmune diseases. nTregs are thymically derived; iTregs are converted in the periphery from CD4+ CD25– Foxp3– Teffs. Recent studies reported that GALT CD103+ DCs mediated enhanced iTreg conversion via the secretion of RA. However, the factors regulating RA secretion and hence, the induction of iTregs by DCs are not yet clear. Activation of the nuclear hormone receptor PPARγ has been shown to induce RA expression in human DCs, and thus, we postulated that PPARγ activation in DCs may be an important regulator of RA secretion and iTreg generation. Using in vitro and in vivo approaches, we now demonstrate that PPARγ activation enhances iTreg generation through increased RA synthesis from murine splenic DCs. In addition, we demonstrate that inhibition of DC PPARγ decreases iTreg generation, suggesting a role for endogenous PPARγ ligands in this process. Overall, our findings suggest that PPARγ may be important as a factor that stimulates DCs to produce RA and as a potential mechanism by which PPARγ ligands ameliorate autoimmunity.
Thromboembolism in Patients With Advanced Gastroesophageal Cancer Treated With Anthracycline, Platinum, and Fluoropyrimidine Combination Chemotherapy: A Report From the UK National Cancer Research Institute Upper Gastrointestinal Clinical Studies Group
Authors: Starling Naureen , Rao Sheela , Cunningham David , Iveson Timothy , Nicolson Marianne , Coxon Fareeda , Middleton Gary , Daniel Francis , Oates Jacqueline , Norman Andrew Richard 
Published: April 2009

Purpose Data concerning the prevalence of and outcomes related to thromboembolic events (TEs) in patients with advanced gastroesophageal cancer who are undergoing chemotherapy are limited. Patients and Methods This was a prospective, exploratory analysis of TEs in a randomized, controlled trial of 964 patients recruited between 2000 and 2005 and treated with epirubicin/platinum/fluoropyrimidine combination chemotherapy for advanced/locally advanced gastroesophageal cancer. Regimens were epirubicin (E), cisplatin (C), fluorouracil (F; ECF); E, C, capecitabine (X; ECX); E, F, oxaliplatin (O; EOF); and EOX. Continuously infused F was administered via a central venous access device (CVAD) with 1 mg of warfarin for thromboprophylaxis. The principal outcome was the incidence of TEs (venous and arterial) in the whole treated patient cohort, according to chemotherapy, associated with CVADs and TE-related prognoses. Results The incidences of any, of venous, and of arterial TEs among 964 treated patients were 12.1% (95% CI, 10.7 to 14.3), 10.1% (95% CI, 8.3 to 12.3), and 2.2% (95% CI, 1.4 to 3.4) respectively. There were fewer TEs in the O compared with the cisplatin groups (EOF/EOX v ECF/ECX: 7.6% v 15.1%; P = .0003). C was identified as a risk factor for TE in multivariate analysis (hazard ratio [HR], 0.51; 95% CI, 0.34 to 0.76; P = .001). There was no difference in the incidence of TEs for the F group compared with the capecitabine groups. The incidence of CVAD-related thrombosis was 7.0% (ECF/EOF arms). Overall survival was worse for patients who experienced TEs versus no TEs (median survival, 7.4 v 10.5 months; HR, 0.8; 95% CI, 0.64 to 0.99; P = .043). Conclusion This analysis has prospectively quantified the incidence/pattern of TEs among patients with advanced gastroesophageal cancer who were treated with four triplet regimens, has demonstrated a differential thrombogenic effect according to platinum use, and has noted a poorer outcome associated with TE during treatment. Chemotherapy-related TE should contribute to the risk/benefit assessment of treatment.
The Role of Genetic Variation in the Lamin A/C Gene in the Etiology of Polycystic Ovary Syndrome
Authors: Urbanek Margrit , Nampiaparampil Geetha , D'Souza Janine , Sefton Elizabeth , Ackerman Christine , Legro Richard S. , Dunaif Andrea 
Published: April 2009

Objective: We performed this study to test the hypothesis that variation in the lamin a/c gene (LMNA) contributes to milder phenotypes of insulin resistance, hyperandrogenism, and/or metabolic syndrome associated with polycystic ovary syndrome (PCOS).Research Design and Methods: We resequenced the coding region, flanking intronic, and proximal promoter regions of the lamin a/c gene in 43 women with PCOS with evidence of upper-body obesity (waist circumference &gt;88 cm) and identified 56 variants, two of which were nonsynonymous substitutions (lmna11 exon1 E98D; lmna24 exon 7 R455C). We genotyped 53 single-nucleotide polymorphisms (44 identified through resequencing and nine included to maximize informativeness of the entire gene) in 624 index (PCOS) cases and 544 controls of European ancestry. We tested for association between these variants and PCOS. In a subset of individuals, we also tested for association with metabolic syndrome and quantitative traits (body mass index, waist circumference, total testosterone, dehydroepiandrosterone sulfate, fasting glucose and insulin, low-density lipoprotein, and total triglycerides).Results: After correction for multiple testing, none of the variants showed significant evidence for association with PCOS, the metabolic syndrome, or any of the quantitative traits tested.Conclusions: Whereas these studies cannot exclude the role of genetic variation in the lamin a/c gene in isolated cases of PCOS, we can conclude that common variation in the lamin a/c gene does not contribute to the etiology of PCOS in women of European ancestry.
Understanding Variation in Managers' Ambidexterity: Investigating Direct and Interaction Effects of Formal Structural and Personal Coordination Mechanisms
Authors: Mom Tom J. M. , van den Bosch Frans A. J. , Volberda Henk W. 
Published: April 2009

Previous research focuses on firm and business unit level ambidexterity. Therefore, conceptual and empirically validated understanding about ambidexterity at the individual level of analysis is very scarce. This paper addresses this gap in the literature by investigating managers' ambidexterity, delivering three contributions to theory and empirical research on ambidexterity: first, by proposing three related characteristics of ambidextrous managers; second, by developing a model and associated hypotheses on both the direct and interaction effects of formal structural and personal coordination mechanisms on managers' ambidexterity; and third, by testing the hypotheses based on a sample of 716 business unit level and operational level managers. Findings regarding the formal structural mechanisms indicate that a manager's decision-making authority positively relates to this manager's ambidexterity, whereas formalization of a manager's tasks has no significant relationship with this manager's ambidexterity. Regarding the personal coordination mechanisms, findings indicate that both the participation of a manager in cross-functional interfaces and the connectedness of a manager to other organization members positively relate to this manager's ambidexterity. Furthermore, results show positive interaction effects between the formal structural and personal coordination mechanisms on managers' ambidexterity. The paper's theoretical contributions and empirical results increase our understanding about managers' ambidexterity and about how different types and combinations of coordination mechanisms relate to variation in managers' ambidexterity.
Synthesis, crystal structure, spectroscopic and thermal characterization of (Hampy)2[Ni(pydc)2(H2O)2] · 2 H2O
Authors: Çolak Alper Tolga , Akduman Demet , Yesilel Okan Zafer , Büyükgüngör Orhan 
Published: April 2009

Abstract
A supramolecular complex, bis(2-amino-3-methylpyridinium) diaquabis(pyridinedicarboxylato)nicke-late(II) dihydrate, (Hampy)2[Ni(pydc)2(H2O)2] · 2 H2O (ampy = 2-amino-3-methylpyridine, H2pydc = 2,5-pyridinedicarboxylic acid or isocinchomeronic acid) (1) has been prepared and characterized by elemental, spectral (IR and UV-vis.), thermal analysis, magnetic measurement and single crystal X-ray diffraction techniques. Ni(II) ion exhibits a distorted octahedral geometry coordinated by nitrogen and oxygen atoms of two pyridinedicarboxylate ligands, oxygen atoms from the two aqua ligands. The supramolecular network is constructed by N–H · · · O strong hydrogen bonds, π-π and C–H · · · π interactions.
2-Hydroxyacetophenone arylhydrazones. Supramolecular arrangements based on C–H · · · O(H), CH · · · O(NO), N–H · · · O(H), N–H · · · O(NO), C–H · · · π or π · · · π interactions
Authors: Baddeley Thomas C. , de Souza França Luciana , Howie R. Alan , de Lima Geraldo M. , Skakle Janet M.S. , de Souza Jose Dias , Wardell James L. , Wardell Solange M.S.V 
Published: April 2009

Abstract
Crystal structures, NMR and IR spectra and EI-MS+ of 2-hydroxyacetophenone arylhydrazones, 2-HOC6H4C(Me) = NNHC6H4Y (1: Y = 2-O2N, 3-O2N, 4-O2N, 4-Me, 4-MeO, H and 4-I) are reported. Two polymorphs of (1: Y = 2-O2N), triclinic and orthorhombic forms, have been identified. While strong intramolecular O–H · · · N(H) hydrogen bonds and layers of molecules are found for all solid 1, supramolecular arrangements of individual members are various and are derived from different combinations of intermolecular interactions, which include C–H · · · O(H), C–H · · · O(NO), N–H · · · O(H), N–H · · · O(NO) and C–H · · · π hydrogen bonds, as well as π · · · π stacking interactions. Intermolecular N–H · · · O hydrogen-bonds involving the phenolic OH group are present in (1: Y = H, 4-O2N, 4-Me, 4-MeO and 4-I), but are absent in ortho-and tri-(1: Y = 2-O2N) and (1: Y = 3-O2N). Instead, ortho-(1: Y = 2-O2N) exhibits intermolecular C–H · · · O(H) hydrogen bonds, while no intermolecular hydrogen bonds involving the OH group occur in either triclinic-(1: Y = 2-O2N) or (1: Y = 3-O2N). EI+-MS revealed the presence of oligomeric species, such as (nM + M′)+, where n is up to 4, and M′ = H, Na or K.
Mutation in Bovine β-Carotene Oxygenase 2 Affects Milk Color
Authors: Berry S D , Davis S R , Beattie E M , Thomas N L , Burrett A K , Ward H E , Stanfield A M , Biswas M , Ankersmit-Udy A E , Oxley P E , Barnett J L , Pearson J F , van der Does Y , MacGibbon A H K , Spelman R J , Lehnert K , Snell R G 
Published: April 2009

Abstract
β-Carotene biochemistry is a fundamental process in mammalian biology. Aberrations either through malnutrition or potentially through genetic variation may lead to vitamin A deficiency, which is a substantial public health burden. In addition, understanding the genetic regulation of this process may enable bovine improvement. While many bovine QTL have been reported, few of the causative genes and mutations have been identified. We discovered a QTL for milk β-carotene and subsequently identified a premature stop codon in bovine β-carotene oxygenase 2 (BCO2), which also affects serum β-carotene content. The BCO2 enzyme is thereby identified as a key regulator of β-carotene metabolism.
Evidence That Msh1p Plays Multiple Roles in Mitochondrial Base Excision Repair
Authors: Pogorzala Leah , Mookerjee Shona , Sia Elaine A 
Published: April 2009

Abstract
Mitochondrial DNA is thought to be especially prone to oxidative damage by reactive oxygen species generated through electron transport during cellular respiration. This damage is mitigated primarily by the base excision repair (BER) pathway, one of the few DNA repair pathways with confirmed activity on mitochondrial DNA. Through genetic epistasis analysis of the yeast Saccharomyces cerevisiae, we examined the genetic interaction between each of the BER proteins previously shown to localize to the mitochondria. In addition, we describe a series of genetic interactions between BER components and the MutS homolog MSH1, a respiration-essential gene. We show that, in addition to their variable effects on mitochondrial function, mutant msh1 alleles conferring partial function interact genetically at different points in mitochondrial BER. In addition to this separation of function, we also found that the role of Msh1p in BER is unlikely to be involved in the avoidance of large-scale deletions and rearrangements.
The Impact of Consenter Characteristics and Experience on Patient Interest in Clinical Research
Authors: Rasco Drew W. , Xie Yang , Yan Jingsheng , Sayne Jennifer R. , Skinner Celette Sugg , Dowell Jonathan E. , Gerber David E. 
Published: April 2009

Learning Objectives
Enumerate patient characteristics associated with participation in clinical trials. Compare the ways in which consenter characteristics may affect patient participation in clinical research. Evaluate the role of consenter experience in the process of enrolling patients in clinical research studies.
This article is available for continuing medical education credit CCMMEE at CME.TheOncologist.com
Specific in vitro toxicity of crude and refined petroleum products. 1. Aryl hydrocarbon receptor—mediated responses
Authors: Vrabie Cozmina M. , Jonker Michiel T. O. , Murk Albertinka J. 
Published: April 2009

AbstractThe present study is the first in a series reporting on in vitro toxic potencies of oils. The objective was to determine whether 11 crude oils and refined products activate the aryl hydrocarbon receptor (AhR) in a dioxin receptor-mediated luciferase assay. Cells were exposed for 6 and 24 h to different oil concentrations to screen for polycyclic aromatic hydrocarbon-like or dioxin-like activity. Moreover, cytotoxicity of the oils was determined using rat hepatoma cells. Except for one crude oil, none of the oils appeared cytotoxic up to 100 mg/L, but all oils activated the AhR. Strong AhR induction was observed for most oils after 6 h, and responses decreased after 24 h, indicating the presence of metabolizable agonists. However, several oils still caused high responses after 24 h, also demonstrating the presence of persistent agonists. The potencies (calculated based on comparisons of concentrations at which 50% of the maximal effect was observed) of oils were found to be approximately 40 to 106 times lower than the potency of the assay's standards benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, considering that oils contain thousands of chemicals, the potencies of petrochemical agonists may be very high. Among the most potent oils were bunker and crude oils. Induction up to 200% as compared to the maximum induction caused by benzo[a]pyrene was observed for these oils. Such supermaximal responses suggest mixture effects that may not be receptor-mediated. Experiments in which oils were tested in combination with the standards demonstrated that oils acted via an antagonistic or additive mode. The results of the present study may help improve risk assessment of petroleum products and judge the necessity or priority of oil spill cleanup activities.
Allelic Depletion of grem1 Attenuates Diabetic Kidney Disease
Authors: Roxburgh Sarah A. , Kattla Jayesh J. , Curran Simon P. , O'Meara Yvonne M. , Pollock Carol A. , Goldschmeding Roel , Godson Catherine , Martin Finian , Brazil Derek P. 
Published: April 2009

OBJECTIVE
Gremlin (grem1) is an antagonist of the bone morphogenetic protein family that plays a key role in limb bud development and kidney formation. There is a growing appreciation that altered grem1 expression may regulate the homeostatic constraints on damage responses in diseases such as diabetic nephropathy.

RESEARCH DESIGN AND METHODS
Here we explored whether knockout mice heterozygous for grem1 gene deletion (grem1+/−) exhibit protection from the progression of diabetic kidney disease in a streptozotocin-induced model of type 1 diabetes.

RESULTS
A marked elevation in grem1 expression was detected in the kidneys and particularly in kidney tubules of diabetic wild-type mice compared with those of littermate controls. In contrast, diabetic grem1+/− mice displayed a significant attenuation in grem1 expression at 6 months of diabetes compared with that in age- and sex-matched wild-type controls. Whereas the onset and induction of diabetes were similar between grem1+/− and wild-type mice, several indicators of diabetes-associated kidney damage such as increased glomerular basement membrane thickening and microalbuminuria were attenuated in grem1+/− mice compared with those in wild-type controls. Markers of renal damage such as fibronectin and connective tissue growth factor were elevated in diabetic wild-type but not in grem1+/− kidneys. Levels of pSmad1/5/8 decreased in wild-type but not in grem1+/− diabetic kidneys, suggesting that bone morphogenetic protein signaling may be maintained in the absence of grem1.

CONCLUSIONS
These data identify grem1 as a potential modifier of renal injury in the context of diabetic kidney disease.