bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Polymorphisms in Estrogen Metabolic Pathway Associated with Risks of Alzheimer's Disease: Evidence from a Southern Chinese Population
Authors: Chen Lu Hua , Fan Yan Hui , Kao Patrick Yu Ping , Ho Deborah Tip Yin , Ha Joyce Cheuk Tung , Chu Leung Wing , Song You‐Qiang 
Published: January 2017

ObjectivesTo investigate whether genetic variations on the estrogen metabolic pathway would be associated with risk of Alzheimer's disease (AD).DesignCross‐sectional study.SettingIndividuals were recruited at the Memory Clinic, Queen Mary Hospital, Hong Kong.ParticipantsChinese individuals with (n = 426) and without (n = 350) AD.MeasurementsAll subjects underwent a standardized cognitive assessment and genotyping of four candidate genes on the estrogen metabolic pathway (estrogen receptor α gene (ESR1), estrogen receptor β gene (ESR2), cytochrome P450 19A1 gene (CYP19A1), cytochrome P450 11A1 gene (CYP11A1)).ResultsApart from consistent results showing an association between apolipoprotein (APO)E and AD, strong evidence of disease associations were found for polymorphisms in ESR2 and CYP11A1 based on the entire data set. For ESR2, significant protective effects were found for A alleles of rs4986938 (permuted P = .02) and rs867443 (permuted P = .02). For CYP11A1, significant risk effects were found for G alleles of rs11638442 (permuted P = .03) and rs11632698 (permuted P = .03). Stratifying subjects according to APOE ε4 status, their genetic effects continued to be significant in the APOE ε4‐negative subgroup. Associations between CYP11A1 polymorphisms (rs2279357, rs2073475) and risk of AD were detected in women but not men. Further gene‐level analysis confirmed the above association between ESR2 and CYP11A1, and pathway‐level analysis highlighted the genetic effect of the estrogen metabolic pathway on disease susceptibility (permuted pathway‐level P = .03).ConclusionConsistent with previous biological findings for sex steroid hormones in the central nervous system, genetic alterations on the estrogen metabolic pathway were revealed in the Chinese population. Confirmation of these present findings in an independent population is warranted to elucidate disease pathogenesis and to explore the potential of hormone therapy in the treatment of AD.
Microdiamond on Åreskutan confirms regional UHP metamorphism in the Seve Nappe Complex of the Scandinavian Caledonides
Authors: Klonowska I. , Janák M. , Majka J. , Petrík I. , Froitzheim N. , Gee D. G. , Sasinková V. 
Published: January 2017

AbstractMetamorphic diamond in crustal rocks provides important information on the deep subduction of continental crust. Here, we present a new occurrence of diamond within the Seve Nappe Complex (SNC) of the Scandinavian Caledonides, on Åreskutan in Jämtland County, Sweden. Microdiamond is found in situ as single and composite (diamond+carbonate) inclusions within garnet, in kyanite‐bearing paragneisses. The rocks preserve the primary peak pressure assemblage of Ca,Mg‐rich garnet+phengite+kyanite+rutile, with polycrystalline quartz surrounded by radial cracks indicating breakdown of coesite. Calculated P–T conditions for this stage are 830–840 °C and 4.1–4.2 GPa, in the diamond stability field. The ultrahigh‐pressure (UHP) assemblage has been variably overprinted under granulite facies conditions of 850–860 °C and 1.0–1.1 GPa, leading to formation of Ca,Mg‐poor garnet+biotite+plagioclase+K‐feldspar+sillimanite+ilmenite+quartz. This overprint was the result of nearly isothermal decompression, which is corroborated by Ti‐in‐quartz thermometry. Chemical Th–U–Pb dating of monazite yields ages between 445 and 435 Ma, which are interpreted to record post‐UHP exhumation of the diamond‐bearing rocks. The new discovery of microdiamond on Åreskutan, together with other evidence of ultrahigh‐pressure metamorphism (UHPM) within gneisses, eclogites and peridotites elsewhere in the SNC, provide compelling arguments for regional (at least 200 km along strike of the unit) UHPM of substantial parts of this far‐travelled allochthon. The occurrence of UHPM in both rheologically weak (gneisses) and strong lithologies (eclogites, peridotites) speaks against the presence of large tectonic overpressure during metamorphism.
Mapping the intermediate digestion phases of human healthy intestinal contents from distal ileum and caecum at fasted and fed state conditions
Authors: Tran Thuy , Fatouros Dimitrios G , Vertzoni Maria , Reppas Christos , Müllertz Anette 
Published: January 2017

Abstract

Objectives
To investigate at the ultrastructural level, the colloidal phases formed in the lumen of the distal ileum and caecum of healthy adults.

Methods
Cryogenic transmission electron microscopy (Cryo-TEM) was employed to image the intermediate colloidal phases of human intestinal contents collected from distal ileum and caecum of two healthy volunteers under fasted and fed state conditions.

Key findings
In samples collected both in the fasted and fed states, Cryo-TEM study revealed the presence of large spherical unilamellar and occasionally bi-lamellar and oligolamellar vesicles with diameters ranging from 50 to 200 nm for both volunteers in distal ileum and caecum. Bilayer fragments were frequently observed in caecal samples. Plate-like structures resembling the morphology of cholesterol plates were visualised in all samples. Elongated structures were observed in the fed state in distal ileum and caecum for both volunteers, whereas no micellar structures could be detected for all samples.

Conclusions
This study provides a framework for understanding the structure of colloidal phases, and it may assist in elucidating the role of dosing conditions on drug absorption from the distal ileum and caecum.
Limitations of polyethylene glycol-induced precipitation as predictive tool for protein solubility during formulation development
Authors: Hofmann Melanie , Winzer Matthias , Weber Christian , Gieseler Henning 
Published: January 2017

Abstract

Objective
Polyethylene glycol (PEG)-induced protein precipitation is often used to extrapolate apparent protein solubility at specific formulation compositions. The procedure was used for several fields of application such as protein crystal growth but also protein formulation development. Nevertheless, most studies focused on applicability in protein crystal growth. In contrast, this study focuses on applicability of PEG-induced precipitation during high-concentration protein formulation development.

Methods
In this study, solubility of three different model proteins was investigated over a broad range of pH. Solubility values predicted by PEG-induced precipitation were compared to real solubility behaviour determined by either turbidity or content measurements.

Key findings
Predicted solubility by PEG-induced precipitation was confirmed for an Fc fusion protein and a monoclonal antibody. In contrast, PEG-induced precipitation failed to predict solubility of a single-domain antibody construct. Applicability of PEG-induced precipitation as indicator of protein solubility during formulation development was found to be not valid for one of three model molecules.

Conclusions
Under certain conditions, PEG-induced protein precipitation is not valid for prediction of real protein solubility behaviour. The procedure should be used carefully as tool for formulation development, and the results obtained should be validated by additional investigations.
The Inevitability and Indeterminacy of Game-Theoretic Accounts of Legal Order
Authors: Levinson Daryl 
Published: January 2017

How is legal order possible? Why do people comply with law when it prevents them from doing what they think best? Two important books show how these questions can—and from some methodological perspectives must—be answered in the form of game-theoretic accounts that show how legal compliance can be compatible with the broad self-interest of officials and citizens. Unfortunately, however, these books also serve to demonstrate that game-theoretic accounts along these lines lack the resources to explain how real-world legal systems emerge and evolve or the various institutional shapes these systems take. The fundamental limitation of game theory, in this context and more generally, is its inability to predict or explain the size and shape of cooperative equilibria.
Mechanism of type‐III protein secretion: Regulation of FlhA conformation by a functionally critical charged‐residue cluster
Authors: Erhardt Marc , Wheatley Paige , Kim Eun A , Hirano Takanori , Zhang Yang , Sarkar Mayukh K. , Hughes Kelly T. , Blair David F. 
Published: January 2017

SummaryThe bacterial flagellum contains a specialized secretion apparatus in its base that pumps certain protein subunits through the growing structure to their sites of installation beyond the membrane. A related apparatus functions in the injectisomes of gram‐negative pathogens to export virulence factors into host cells. This mode of protein export is termed type‐III secretion (T3S). Details of the T3S mechanism are unclear. It is energized by the proton gradient; here, a mutational approach was used to identify proton‐binding groups that might function in transport. Conserved proton‐binding residues in all the membrane components were tested. The results identify residues R147, R154 and D158 of FlhA as most critical. These lie in a small, well‐conserved cytoplasmic domain of FlhA, located between transmembrane segments 4 and 5. Two‐hybrid experiments demonstrate self‐interaction of the domain, and targeted cross‐linking indicates that it forms a multimeric array. A mutation that mimics protonation of the key acidic residue (D158N) was shown to trigger a global conformational change that affects the other, larger cytoplasmic domain that interacts with the export cargo. The results are discussed in the framework of a transport model based on proton‐actuated movements in the cytoplasmic domains of FlhA.
Extranational spaces and the disruption of national boundaries: Turkish immigrant media and claims against the state in 1980s West Germany
Authors: Foerster Amy , Miller Jennifer 
Published: January 2017

ABSTRACTAfter the 1980 coup that shook Turkey and almost twenty years after the bilateral ‘guest worker’ treaty shifted Germany's demographic make‐up, West German policy makers proposed increasingly restrictive regulations on the ‘guest workers’ who had heavily contributed to West Germany's economy. In this crucial historical moment, Turkish‐language newspapers, published in West Germany, created a politically motivated extranational public sphere in which they launched claims against both the West German and Turkish states. These claims shaped immigration and integration policy between the two countries, fostered diasporic activism and cross‐national religious and political organisations and gave rise to a variety of unexpected organisational outcomes that continue to impact both Germany and the Turkish Republic.
Immunoexpression of HDAC1, HDAC2, and HAT1 in actinic cheilitis and lip squamous cell carcinoma
Authors: Chrun ES , Modolo F , Vieira DSC , Borges‐Júnior ÁLS , Castro RG , Daniel FI 
Published: January 2017

BackgroundAcetylation and deacetylation are the most studied covalent histone modifications resulting in transcriptional regulation with histone deacetylases (HDAC) and histone acetyltransferases (HAT) as the main associated enzymes. These enzymes overexpression induces abnormal transcription of key genes that regulate important cellular functions, such as proliferation, cell cycle regulation, and apoptosis. Thus, the expression of different HATs and HDACs has been evaluated in various cancers.ObjectiveTo investigate HDAC1, HDAC2 and HAT1 expression in lip squamous cell carcinoma (LSCC) and actinic cheilitis (AC) and to demonstrate their correlation with DNA metyltransferases (DNMTs).Material and methodsThirty cases of lip squamous cell carcinoma (LSCC), thirty cases of actinic cheilitis (AC), and 28 cases of non‐neoplastic epithelium as control were selected for immunohistochemical investigation.ResultsNuclear HDAC2 immunopositivity was significantly higher in AC (75.07% ± 29.70) when compared with LSCC (51.06% ± 39.02). HDAC1 and HAT1 nuclear immunostaining were higher in AC, with no statistical significance. When comparing data with our previous study, we found a positive correlation between HDAC1 X DNMT1/DNMT3b, HDAC2 X DNMT3b, and HAT1 X DNMT1/DNMT3b for certain studied groups.ConclusionThis study showed higher levels of nuclear HDAC2 immunopositivity in AC, possibly indicating that this enzyme plays a key role in lip photocarcinogenesis early stages.
Novel Wx alleles induced by chemical mutagens in rice, Oryza sativa L.
Authors: Lin Bing‐nan , Hsu Yu‐chia , Kuo Su‐chen , Lin Yann‐rong , Wu Yong‐pei , Kuo Chie‐wei 
Published: January 2017

AbstractFrom mutant pools of two Taiwanese elite japonica cultivars, Tainung 67 and Taikeng 8, we identified 13 mutant lines possessing opaque endosperm with relatively low amylose contents (AC) ranging from 1.5% to 7.1%. Because of different AC, paste viscosities of these 13 mutant lines differed, as revealed by palatability and physicochemical properties. The mutated gene conferring opaque endosperm was isolated from the F2 population of one mutant line, WY1× indica cv. ‘Taichung Sen 17’, by positional cloning, revealing a G3018→A3018 substitution at exon 9 of Waxy leading to a non‐synonymous mutation from alanine to valine. Two additional alleles were identified from the other 12 mutant lines, for which single‐nucleotide substitutions G2708 → A2708 and G3029 → A3029 occurred in exons 8 and 9, leading to non‐synonymous mutations from arginine to histidine and glutamic acid to lysine, respectively. The three novel wx alleles had different effects on grain quality, specifically on eating and cooking quality, and could be applied in rice breeding programmes to develop new low AC varieties by marker‐assisted selection.
Exploiting cell cycle inhibitor genes of the KRP family to control root‐knot nematode induced feeding sites in plants
Authors: Coelho Roberta Ramos , Vieira Paulo , Antonino de Souza Júnior José Dijair , Martin‐Jimenez Cristina , De Veylder Lieven , Cazareth Julie , Engler Gilbert , Grossi‐de‐Sa Maria Fatima , de Almeida Engler Janice 
Published: January 2017

AbstractCell cycle control in galls provoked by root‐knot nematodes involves the activity of inhibitor genes like the Arabidopsis ICK/KRP members. Ectopic KRP1, KRP2 and KRP4 expression resulted in decreased gall size by inhibiting mitotic activity, whereas KRP6 induces mitosis in galls. Herein, we investigate the role of KRP3, KRP5 and KRP7 during gall development and compared their role with previously studied members of this class of cell cycle inhibitors. Overexpression of KRP3 and KRP7 culminated in undersized giant cells, with KRP3OE galls presenting peculiar elongated giant cells. Nuclei in KRP3OE and KRP5OE lines presented a convoluted and apparently connected phenotype. This appearance may be associated with the punctuated protein nuclear localization driven by specific common motifs. As well, ectopic expression of KRP3OE and KRP5OE affected nematode development and offspring. Decreased mitotic activity in galls of KRP3OE and KRP7OE lines led to a reduced gall size which presented distinct shapes – from more elongated like in the KRP3OE line to small rounded like in the KRP7OE line. Results presented strongly support the idea that induced expression of cell cycle inhibitors such as KRP3 and KRP7 in galls can be envisaged as a conceivable strategy for nematode feeding site control in crop species attacked by phytopathogenic nematodes.
Glutathione peroxidase‐like enzymes cover five distinct cell compartments and membrane surfaces in Arabidopsis thaliana
Authors: Attacha Safira , Solbach David , Bela Krisztina , Moseler Anna , Wagner Stephan , Schwarzländer Markus , Aller Isabel , Müller Stefanie J. , Meyer Andreas J. 
Published: January 2017

AbstractGlutathione peroxidase‐like enzymes (GPXLs) constitute a family of eight peroxidases in Arabidopsis thaliana. In contrast to the eponymous selenocysteine glutathione peroxidases in mammalian cells that use glutathione as electron donor, GPXLs rely on cysteine instead of selenocysteine for activity and depend on the thioredoxin system for reduction. Although plant GPXLs have been implicated in important agronomic traits such as drought tolerance, photooxidative tolerance and immune responses, there remain major ambiguities regarding their subcellular localization. Because their site of action is a prerequisite for an understanding of their function, we investigated the localization of all eight GPXLs in stable Arabidopsis lines expressing N‐terminal and C‐terminal fusions with redox‐sensitive green fluorescent protein 2 (roGFP2) using confocal microscopy. GPXL1 and GPXL7 were found in plastids, while GPXL2 and GPXL8 are cytosolic nuclear. The N‐terminal target peptide of GPXL6 is sufficient to direct roGFP2 into mitochondria. Interestingly, GPXL3, GPXL4 and GPXL5 all appear to be membrane bound. GPXL3 was found exclusively in the secretory pathway where it is anchored by a single N‐terminal transmembrane domain. GPXL4 and GPXL5 are anchored to the plasma membrane. Presence of an N‐terminal myristoylation motif and genetic disruption of membrane association through targeted mutagenesis point to myristoylation as essential for membrane localization.
Role of cytokine changes in clozapine‐induced fever: A cohort prospective study
Authors: Hung Yuan‐Pin , Wang Carol S‐M. , Yen Chia‐Nan , Chang Hsun‐Cheng , Chen Po See , Lee I Hui , Chen Kao Chin , Yang Yen Kuang , Lu Ru‐Band , Wang Tzu‐Yun 
Published: January 2017

AimClozapine‐associated fever is common but the specific cytokine changes and treatment durations that may cause fever remain unknown. We investigated the association between inflammatory cytokine changes and clozapine‐induced fever in patients who were treated with clozapine.MethodsForty‐three patients with schizophrenia or schizoaffective disorder, diagnosed by using the Chinese Version of the Mini International Neuropsychiatric Interview, were treated with clozapine for the first time (first‐time use group, n = 22) or for more than 6 months (long‐term use group, n = 21). The Positive and Negative Syndrome Scale, tympanic temperature, and levels of tumor necrosis factor‐α (TNF‐α), interferon‐γ (INF‐γ), interleukin‐2 (IL‐2), and interleukin‐6 (IL‐6) were determined at baseline and weeks 1, 2, 3, 4, and 6. A multiple linear regression with generalized estimating equation methods was used to analyze the association between the changes in the cytokine levels and clozapine‐induced fever in the different groups.ResultsThe IL‐6 level changes were significantly different between the two groups (P = 0.04). In the first‐time use group, the fever rate was increased (47.1%) compared with the long‐term use group (5.6%, P = 0.005). Moreover, in these patients, the TNF‐α, INF‐γ, IL‐2, and IL‐6 levels were significantly (P < 0.001) different from patients who did not develop a fever. An interaction effect with the different treatment duration groups and fever development was only significant for IL‐6 (P < 0.001).ConclusionPatients who were treated with clozapine for the first time have an increased rate of developing a fever, and IL‐6 might have a specific role in the interaction effect between treatment duration and fever development.
Expression of immune genes in skin of channel catfish immunized with live theronts of Ichthyophthirius multifiliis
Authors: Moreira G. S. A. , Shoemaker C. A. , Zhang D. , Xu D.‐H. 
Published: January 2017

SummaryThe objective of this study was to evaluate differential expression of innate and adaptive immune genes, including immunoglobulin, immune cell receptor, cytokine, inflammatory protein, toll‐like receptors (TLR) and recombination‐activating gene (RAG) in skin from channel catfish, Ictalurus punctatus after immunization with live theronts of Ichthyophthirius multifiliis (Ich) by intraperitoneal injection. The immunized catfish showed significantly higher survival rate (95%) than those of mock‐immunized control fish (0% survival) after the theront challenge. The gene expression of innate immune system, such as cytokines (IL‐1β type a, IL‐1β type b, IFN‐γ, TGF1‐β and TNF‐α) and inflammatory proteins (NF‐kB and iNOS 2), showed significant upregulation at day 1 (D1) post‐immunization. Expression of TLR genes exhibited a rapid increase from hour 4 (h4) to D10 post‐immunization. Genes of the adaptive response, such as the cell receptor MHC I, CD8+, CD4+ and TCR‐α, showed upregulation at D1, D6 and D10. The TCR‐β expression increased rapidly at h4 and remained upregulated until D10. Immunoglobulin IgM upregulation was detected from h4 until D2 while IgD expression was increased from D1 until D10. Rapid upregulation of innate and adaptive immune genes in skin of catfish following live theront vaccination was demonstrated in this study ultimately resulting in significant protection against Ich infection.
T‐cell clones in human trichinellosis: Evidence for a mixed Th1/Th2 response
Authors: Della Bella C. , Benagiano M. , De Gennaro M. , Gomez‐Morales M. A. , Ludovisi A. , D'Elios S. , Luchi S. , Pozio E. , D'Elios M. M. , Bruschi F. 
Published: January 2017

SummaryIn humans, studies on the cellular immune response against Trichinella are scarce. Aim of this study was to characterize the cytokine profile of T cells specific for Trichinella britovi in trichinellosis patients. Peripheral blood mononuclear cells (PBMC) were obtained from five patients involved in a trichinellosis outbreak caused by T. britovi, which occurred in 2013 in Tuscany (Italy). All the patients resulted positive for Trichinella‐specific IgG, IgE and presented eosinophilia. T cells were investigated for their proliferation to excretory/secretory antigens from Trichinella spiralis muscle larvae (TsES) and for their cytokine profile. A total of 284 CD4+ and 42 CD8+ T‐cell clones were obtained from the TsES‐specific T‐cell lines from PBMC. All T‐cell clones proliferated in response to mitogen. Of the 284 CD4+ T‐cell clones generated from TsES‐specific T‐cell lines, 135 (47%) proliferated significantly to TsES; 26% CD8+ T‐cell clones showed proliferation to TsES. In the series of the 135 TsES‐specific CD4+ clones, 51% expressed a Th2 profile, 30% a Th0 and 19% Th1. In the series of the 11 TsES‐specific CD8+ T‐cell clones, 18% were Tc2, 45% Tc0 and 36% Tc1. In human trichinellosis, the cellular immune response is, during the chronic phase, mixed Th1/Th2.