bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic variation in innate immunity and inflammation pathways associated with lung cancer risk
Authors: Shiels Meredith S. , Engels Eric A. , Shi Jianxin , Landi Maria Teresa , Albanes Demetrius , Chatterjee Nilanjan , Chanock Stephen J. , Caporaso Neil E. , Chaturvedi Anil K. 
Published: October 2012

AbstractBACKGROUND:Pulmonary inflammation may contribute to lung cancer etiology. The authors conducted a broad evaluation of the association of single nucleotide polymorphisms (SNPs) in innate immunity and inflammation pathways with lung cancer risk and conducted comparisons with a lung cancer genome‐wide association study (GWAS).METHODS:In total, 378 patients with lung cancer (cases) and a group of 450 controls from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial were included. A proprietary oligonucleotide pool assay was used to genotype 1429 SNPs. Odds ratios and 95% confidence intervals were estimated for each SNP, and P values for trend (Ptrend) were calculated. For statistically significant SNPs (Ptrend < .05), the results were replicated with genotyped or imputed SNPs in the GWAS, and P values were adjusted for multiple testing.RESULTS:In the PLCO analysis, a significant association was observed between lung cancer and 81 SNPs located in 44 genes (Ptrend < .05). Of these 81 SNPS, there was evidence for confirmation in the GWAS for 10 SNPs. However, after adjusting for multiple comparisons, the only SNP that retained a significant association with lung cancer in the replication phase was reference SNP rs4648127 (nuclear factor of kappa light polypeptide gene enhancer of B‐cells 1 [NFKB1]) (multiple testing‐adjusted Ptrend = .02). The cytosine‐thymine (CT)/TT genotype of NFKB1 was associated with reduced odds of lung cancer in the PLCO study (odds ratio, 0.56; 95% confidence interval, 0.37‐0.86) and the in the GWAS (odds ratio, 0.79; 95% confidence interval, 0.69‐0.90).CONCLUSIONS:A significant association was observed between a variant in the NFKB1 gene and the risk of lung cancer. The current findings add to evidence implicating inflammation and immunity in lung cancer etiology. Cancer 2012. Published 2012 by the American Cancer Society.
Loss of Gsx1 and Gsx2 function rescues distinct phenotypes in Dlx1/2 mutants
Authors: Wang Bei , Long Jason E. , Flandin Pierre , Pla Ramon , Waclaw Ronald R. , Campbell Kenneth , Rubenstein John L.R. 
Published: October 2012

AbstractMice lacking the Dlx1 and Dlx2 homeobox genes (Dlx1/2 mutants) have severe deficits in subpallial differentiation, including overexpression of the Gsx1 and Gsx2 homeobox genes. To investigate whether Gsx overexpression contributes to the Dlx1/2 mutant phenotypes, we made compound loss‐of‐function mutants. Eliminating Gsx2 function from the Dlx1/2 mutants rescued the increased expression of Ascl1 and Hes5 (Notch signaling mediators) and Olig2 (oligodendrogenesis mediator). In addition, Dlx1/2;Gsx2 mutants, like Dlx1/2;Ascl1 mutants, exacerbated the Gsx2 and Dlx1/2 patterning and differentiation phenotypes, particularly in the lateral ganglionic eminence (LGE) caudal ganglionic eminence (CGE), and septum, including loss of GAD1 expression. On the other hand, eliminating Gsx1 function from the Dlx1/2 mutants (Dlx1/2;Gsx1 mutants) did not severely exacerbate their phenotype; on the contrary, it resulted in a partial rescue of medial ganglionic eminence (MGE) properties, including interneuron migration to the cortex. Thus, despite their redundant properties, Gsx1 and ‐2 have distinct interactions with Dlx1 and ‐2. Gsx2 interaction is strongest in the LGE, CGE, and septum, whereas the Gsx1 interaction is strongest in the MGE. From these studies, and earlier studies, we present a model of the transcriptional network that regulates early steps of subcortical development. J. Comp. Neurol. 521:1561–1584, 2013. © 2012 Wiley Periodicals, Inc.
ON cone bipolar cell axonal synapses in the OFF inner plexiform layer of the rabbit retina
Authors: Lauritzen J. Scott , Anderson James R. , Jones Bryan W. , Watt Carl B. , Mohammed Shoeb , Hoang John V. , Marc Robert E. 
Published: October 2012

AbstractAnalysis of the rabbit retinal connectome RC1 reveals that the division between the ON and the OFF inner plexiform layer (IPL) is not structurally absolute. ON cone bipolar cells make noncanonical axonal synapses onto specific targets and receive amacrine cell synapses in the nominal OFF layer, creating novel motifs, including inhibitory crossover networks. Automated transmission electron microscopic imaging, molecular tagging, tracing, and rendering of ∼400 bipolar cells reveals axonal ribbons in 36% of ON cone bipolar cells, throughout the OFF IPL. The targets include γ‐aminobutyrate (GABA)‐positive amacrine cells (γACs), glycine‐positive amacrine cells (GACs), and ganglion cells. Most ON cone bipolar cell axonal contacts target GACs driven by OFF cone bipolar cells, forming new architectures for generating ON–OFF amacrine cells. Many of these ON–OFF GACs target ON cone bipolar cell axons, ON γACs, and/or ON–OFF ganglion cells, representing widespread mechanisms for OFF to ON crossover inhibition. Other targets include OFF γACs presynaptic to OFF bipolar cells, forming γAC‐mediated crossover motifs. ON cone bipolar cell axonal ribbons drive bistratified ON–OFF ganglion cells in the OFF layer and provide ON drive to polarity‐appropriate targets such as bistratified diving ganglion cells (bsdGCs). The targeting precision of ON cone bipolar cell axonal synapses shows that this drive incidence is necessarily a joint distribution of cone bipolar cell axonal frequency and target cell trajectories through a given volume of the OFF layer. Such joint distribution sampling is likely common when targets are sparser than sources and when sources are coupled, as are ON cone bipolar cells. J. Comp. Neurol. 521:977–1000, 2013. © 2012 Wiley Periodicals, Inc.
Etching Silicon with HF–HNO3–H2SO4/H2O Mixtures – Unprecedented Formation of Trifluorosilane, Hexafluorodisiloxane, and Si–F Surface Groups
Authors: Lippold Marcus , Böhme Uwe , Gondek Christoph , Kronstein Martin , Patzig‐Klein Sebastian , Weser Martin , Kroke Edwin 
Published: October 2012

AbstractThe etching behaviour of sulfuric‐acid‐containing HF–HNO3 solutions towards crystalline silicon surfaces has been studied over a wide range of H2SO4 concentrations. For mixtures with low sulfuric acid concentration, NO2/N2O4, N2O3, NO and N2O have been detected by means of FTIR spectroscopy. Increasing concentrations of nitric acid lead to high etching rates and to an enhanced formation of NO2/N2O4. Different products were observed for the etching of silicon with sulfuric‐acid‐rich mixtures [c(H2SO4) > 13 mol L–1]. Trifluorosilane and hexafluorodisiloxane were identified by FTIR spectroscopy as additional reaction products. In contrast to the commonly accepted wet chemical etching mechanism, the formation of trifluorosilane is not accompanied by the formation of molecular hydrogen (according to Raman spectroscopy). Thermodynamic calculations and direct reactions of F3SiH with the etching solution support an intermediate oxidation of trifluorosilane and the formation of hexafluorodisiloxane. The etched silicon surfaces were investigated by diffuse reflection FTIR and X‐ray photoelectron spectroscopy (XPS). Surprisingly, no SiH terminations were observed after etching in sulfuric‐acid‐rich mixtures. Instead, a fluorine‐terminated surface was found.
Synthesis of Biotinylated Multipodal Glycoclusters on a Solid Support
Authors: Karskela Marika , von Usedom Miriam , Virta Pasi , Lönnberg Harri 
Published: October 2012

AbstractTrivalent glycoconjugates, each bearing a biotin side arm in addition to three different sugar ligands, have been synthesized on a solid support. The conjugates were assembled on an orthogonally protected pentaerythrityl tetramine core that was anchored to the support through a backbone amide linker. Peptide coupling chemistry was applied to elongate three of the branches with β‐alanine and a fully acylated glycosylacetic acid. The fourth branch was levulinoylated and oximated with aminooxy‐derivatized D‐biotin, followed by acidolytic release into solution. The acyl protecting groups were removed by methoxide‐catalyzed transesterification in methanol.
Consecutive SNH and Suzuki–Miyaura Cross‐Coupling Reactions – an Efficient Synthetic Strategy to Pyrimidines Bearing Pyrrole and Indole Fragments
Authors: Verbitskiy Egor V. , Rusinov Gennady L. , Charushin Valery N. , Chupakhin Oleg N. , Cheprakova Ekaterina M. , Slepukhin Pavel A. , Pervova Marina G. , Ezhikova Marina A. , Kodess Mikhail I. 
Published: October 2012

AbstractThe combination of the Suzuki–Miyaura cross‐coupling and nucleophilic aromatic substitution of hydrogen reactions is a versatile tool for the syntheses of 4‐(1R‐pyrrol‐2‐yl)‐ and 4‐(1R‐indol‐3‐yl)‐5‐(hetero)aryl‐substituted pyrimidines from commercially available 5‐bromopyrimidine. The SNH [AE, (addition–elimination)] and SNH [AO, (addition–oxidation)] reactions of 5‐bromopyrimidine with pyrroles and indoles were studied by gas chromatography–mass spectrometry. The structures of the intermediate σH adducts as well as the pyrrole‐(hetero)arylpyrimidine and indole‐(hetero)arylpyrimidine dyads were established for the first time by X‐ray crystal structure analysis.
Large ice‐contact slope movements: glacial buttressing, deformation and erosion
Authors: McColl Samuel T. , Davies Timothy R. H. 
Published: October 2012

ABSTRACTGlaciers and slope movements may act simultaneously to erode and modify glaciated slopes. Undercutting by glaciers can destabilize slopes but the extent to which slope failure may progress prior to subsequent glacier withdrawal has not hitherto been considered. The traditional view has been that the buttressing effect of ice prevents slope movement. The problem with this view is that ice is one‐third the density of rock and flows under low applied stress. Consequently, failed slopes may move into the glacier if they exert a stress in excess of the resistance provided by the glacier. Slope movement rate depends on ice rheology and other factors influencing driving and resisting stresses. Simple viscous equations are used to investigate these variables. The equations predict that small (<125 000 m3) ice‐contact rockslides can deform ice at several mm/year, increasing to several m/year for very large (>108 m3) rockslides. To test these estimates, field evidence is presented of slope movements in glaciated valleys of New Zealand; narrowing or squeezing of glaciers adjacent to unstable rock slopes is demonstrated and considered to be the result of slope movement. For one site, geomorphic mapping and slope movement monitoring data show that movement rates are of similar order of magnitude to those predicted by the viscous equations; closer agreement could be achieved with the application of modelling techniques that can more realistically model the complex slope geometries and stability factors encountered, or by obtaining additional empirical data to calibrate the models. This research implies that, while the concept of glacial debuttressing – the reduction of slope support from withdrawal of glaciers – is valid, complete debuttressing is not a prerequisite for the movement of ice‐contact rock slopes. These slope movements may contribute to the erosional processes of glaciers and the evolution of glaciated slopes in a previously unrecognized way. Copyright © 2012 John Wiley & Sons, Ltd.
Threshold of erosion of submarine bedrock landscapes by tidal currents
Authors: Mitchell Neil C. , Huthnance John M. , Schmitt Thierry , Todd Brian 
Published: October 2012

ABSTRACTSince sea level stabilized 7000 yr bp, shelf seas experiencing semi‐diurnal tides will have been affected by streaming four times per day. If tidal erosion of bedrock were even only marginally efficient, the ~10 million streamings since then should have left geomorphological imprints. We examine high‐resolution multibeam sonar data from three areas with extreme tidal currents. The Minas Passage (Bay of Fundy) experiencing 8‐knot surface tidal currents was surveyed in 2007 with a multibeam sonar. In an area near to transverse dunes, which are evidence for bedload transport, the data show local overhanging surfaces near to the sediment‐rock contact, potentially created by abrasion by saltating particles. However, they are uncommon. In the Straits of Messina, where surface currents reach 10 knots, surveying revealed ridges lying oblique to the flow that are not obviously broken into separate outcrops by erosion. In the Bristol Channel, UK, sonar data collected where currents reach 3·4 knots at 1·5 m above the bed reveal outcrops of limestone with superimposed sand dunes, but only minor rounding of blocks.Holocene tidal currents have apparently been generally ineffective at eroding bedrock. We examine this issue further by compiling extreme tidal streams around the UK and from them estimate shear stresses, representing a macro‐tidal environment where peak surface currents reach 9·7 knots. Those data are compared with shear stresses in mountainous rivers where long‐term rates of erosion are comparable with tectonic uplift rates and are thus geomorphologically significant. Whereas river stresses reach 102–103 Pa, the largest tidal stresses are generally 101 and only rarely approach 102 Pa, too small for quarrying to operate generally. However, the vertical faces in the Minas Passage may represent the onset of abrasion. Given this limited evidence for abrasion, we explore conditions in the geological past for tides that may have locally eroded bedrock. Copyright © 2012 John Wiley & Sons, Ltd.
Auf der Spur von Multitalenten
Authors: Blume Alfred , Kreßler Jörg 
Published: October 2012

AbstractZwischen Brücke und Barriere: Zellmembranen haben einen äußerst komplexen Aufbau. Ihre grundlegenden Eigenschaften lassen sich oft jedoch besser anhand von Modellmembranen mit geringerer Komplexität entschlüsseln. Dies hat nicht zuletzt hohe biomedizinische Relevanz.
mTOR kinase, a key player in the regulation of glial functions: Relevance for the therapy of multiple sclerosis
Authors: Dello Russo Cinzia , Lisi Lucia , Feinstein Douglas L. , Navarra Pierluigi 
Published: October 2012

AbstractThe mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase with a central role in the regulation of cell growth and proliferation, and several intracellular processes, such as mRNA transcription and translation, autophagy and cytoskeletal organization. The relevance of this pathway in the regulation of the immune system is well characterized. mTOR is essential for the proper activation and proliferation of effector T cells, restricts the development of regulatory T cells, and downregulates innate immune responses. Recently, a direct role of mTOR in the modulation of glial functions has also been recognized. Data from our group and others support the notion that mTOR is involved in microglial proinflammatory activation. The kinase regulates several intracellular processes in astrocytes, among which the rate of mRNA degradation of the inducible form of NO synthase. Therefore, the inhibition of mTOR kinase activity in glial cells results in anti‐inflammatory actions, suggesting possible beneficial effects of mTOR inhibitors (like rapamycin) in the treatment of inflammatory‐based pathologies of the central nervous system. In contrast, mTOR plays an important role in the regulation of oligodendrocyte development and myelination process as well as several neuronal functions, which may limit this therapeutic approach. Nevertheless, as reviewed here, there is robust evidence that rapamycin ameliorates the clinical course of both the relapsing‐remitting and the chronic experimental autoimmune encephalomyelitis (EAE), and significantly reduces the hyperalgesia observed before clinical development of EAE. These findings may have important clinical implications for the therapy of multiple sclerosis. © 2012 Wiley Periodicals, Inc.
Changes in bone sclerostin levels in mice after ovariectomy vary independently of changes in serum sclerostin levels
Authors: Jastrzebski Sandra , Kalinowski Judith , Stolina Marina , Mirza Faryal , Torreggiani Elena , Kalajzic Ivo , Won Hee Yeon , Lee Sun-Kyeong , Lorenzo Joseph 
Published: October 2012

Abstract
We examined the effects that ovariectomy had on sclerostin mRNA and protein levels in the bones of 8-week-old mice that were either sham-operated (SHAM) or ovariectomized (OVX) and then euthanized 3 or 6 weeks later. In this model, bone loss occurred between 3 and 5 weeks postsurgery. In calvaria, ovariectomy significantly decreased sclerostin mRNA levels at 6 weeks postsurgery (by 52%) but had no significant effect at 3 weeks. In contrast, sclerostin mRNA levels were significantly lower in OVX femurs at 3 weeks postsurgery (by 53%) but equal to that of SHAM at 6 weeks. The effects of ovariectomy on sclerostin were not a global response of osteocytes because they were not mimicked by changes in the mRNA levels for two other relatively osteocyte-specific genes: DMP-1 and FGF-23. Sclerostin protein decreased by 83% and 60%, at 3 and 6 weeks postsurgery in calvaria, respectively, and by 38% in lumbar vertebrae at 6 weeks. We also detected decreases in sclerostin by immunohistochemistry in cortical osteocytes of the humerus at 3 weeks postsurgery. However, there were no significant effects of ovariectomy on sclerostin protein in femurs or on serum sclerostin at 3 and 6 weeks postsurgery. These results demonstrate that ovariectomy has variable effects on sclerostin mRNA and protein in mice, which are dependent on the bones examined and the time after surgery. Given the discrepancy between the effects of ovariectomy on serum sclerostin levels and sclerostin mRNA and protein levels in various bones, these results argue that, at least in mice, serum sclerostin levels may not accurately reflect changes in the local production of sclerostin in bones. Additional studies are needed to evaluate whether this is also the case in humans. © 2013 American Society for Bone and Mineral Research.
Adaptor protein complex 2–mediated, clathrin-dependent endocytosis, and related gene activities, are a prominent feature during maturation stage amelogenesis
Authors: Lacruz Rodrigo S , Brookes Steven J , Wen Xin , Jimenez Jaime M , Vikman Susanna , Hu Ping , White Shane N , Lyngstadaas S Petter , Okamoto Curtis T , Smith Charles E , Paine Michael L 
Published: October 2012

Abstract
Molecular events defining enamel matrix removal during amelogenesis are poorly understood. Early reports have suggested that adaptor proteins (AP) participate in ameloblast-mediated endocytosis. Enamel formation involves the secretory and maturation stages, with an increase in resorptive function during the latter. Here, using real-time PCR, we show that the expression of clathrin and adaptor protein subunits are upregulated in maturation stage rodent enamel organ cells. AP complex 2 (AP-2) is the most upregulated of the four distinct adaptor protein complexes. Immunolocalization confirms the presence of AP-2 and clathrin in ameloblasts, with strongest reactivity at the apical pole. These data suggest that the resorptive functions of enamel cells involve AP-2 mediated, clathrin-dependent endocytosis, thus implying the likelihood of specific membrane-bound receptor(s) of enamel matrix protein debris. The mRNA expression of other endocytosis-related gene products is also upregulated during maturation including: lysosomal-associated membrane protein 1 (Lamp1); cluster of differentiation 63 and 68 (Cd63 and Cd68); ATPase, H+ transporting, lysosomal V0 subunit D2 (Atp6v0d2); ATPase, H+ transporting, lysosomal V1 subunit B2 (Atp6v1b2); chloride channel, voltage-sensitive 7 (Clcn7); and cathepsin K (Ctsk). Immunohistologic data confirms the expression of a number of these proteins in maturation stage ameloblasts. The enamel of Cd63-null mice was also examined. Despite increased mRNA and protein expression in the enamel organ during maturation, the enamel of Cd63-null mice appeared normal. This may suggest inherent functional redundancies between Cd63 and related gene products, such as Lamp1 and Cd68. Ameloblast-like LS8 cells treated with the enamel matrix protein complex Emdogain showed upregulation of AP-2 and clathrin subunits, further supporting the existence of a membrane-bound receptor-regulated pathway for the endocytosis of enamel matrix proteins. These data together define an endocytotic pathway likely used by ameloblasts to remove the enamel matrix during enamel maturation. © 2013 American Society for Bone and Mineral Research.
Annual intravenous zoledronic acid for three years increased cancellous bone matrix mineralization beyond normal values in the HORIZON biopsy cohort
Authors: Misof Barbara M , Roschger Paul , Gabriel Daniela , Paschalis Eleftherios P , Eriksen Erik F , Recker Robert R , Gasser Jürg A , Klaushofer Klaus 
Published: October 2012

Abstract
The efficacy of 3 years of annual intravenous administration of zoledronic acid (ZOL) in reducing vertebral and nonvertebral fractures in postmenopausal osteoporosis has been shown by the HORIZON pivotal fracture trial. Histomorphometric analysis of transiliac bone biopsies from the HORIZON participants revealed significantly improved trabecular architecture and reduced bone remodeling for the ZOL-treated versus placebo-treated patients. The aim of our study was to evaluate the cancellous and cortical bone mineralization density distribution (BMDD) in these biopsies by quantitative backscattered electron imaging (qBEI). The study cohort comprised 82 patients on active treatment (ZOL, yearly doses of 5 mg) and 70 treated with placebo, and all received adequate Ca and VitD supplementation. Comparison of ZOL-treated versus placebo-treated cancellous (Cn.) and cortical (Ct.) BMDD-derived variables resulted in significantly higher average (Cn.CaMean + 3.2%, Ct.CaMean + 2.7%) and mode calcium concentrations (Cn.CaPeak + 2.1%, Ct.CaPeak + 1.5%), increased percentages of highly mineralized bone areas (Cn.CaHigh + 64%, Ct.CaHigh + 31%), lower heterogeneity of mineralization (Cn.CaWidth −14%, Ct.CaWidth −13%), and decreased percentages of low mineralized bone areas (Cn.CaLow −22%, Ct.CaLow −26%) versus placebo (all p &lt; 0.001). Cn. BMDD from the patients on active treatment also revealed a statistically significant shift to higher Ca concentrations when compared to a historical normal reference BMDD. These differences in BMDD from ZOL patients compared to the other groups were in line with the correlation of BMDD variables with previously determined cancellous mineralizing surface per bone surface (Cn. MS/BS, a primary histomorphometric index for bone turnover), showing that those with lower Cn. MS/BS had a higher degree of bone matrix mineralization. However, the differences in BMDD variables between the study groups remained when adjusted for Cn. MS/BS, suggesting that other factors in addition to reduced bone turnover might contribute to the higher bone matrix mineralization after ZOL treatment. © 2013 American Society for Bone and Mineral Research.