bluuebunny/crossref_metadata_2025_split huggingface dataset:
The p400/Brd8 Chromatin Remodeling Complex Promotes Adipogenesis by Incorporating Histone Variant H2A.Z at PPARγ Target Genes
Authors: Couture Jean-Philippe , Nolet Guylaine , Beaulieu Elaine , Blouin Richard , Gévry Nicolas 
Published: October 2012

AbstractAdipogenesis, the biological process by which preadipocytes differentiate into mature fat cells, is coordinated by a tightly regulated gene expression program. Indeed, it has been reported that a large number of genetic events, from fat cell-specific transcription factors expression, such as the master regulator of fat cell differentiation peroxisome proliferator-activated receptor (PPAR)γ2 to epigenetic modifications, govern the acquisition of a mature adipocyte phenotype. Here, we provide evidence that the E1A-binding protein p400 (p400) complex subunit bromo-containing protein 8 (Brd8) plays an important role in the regulation of PPARγ target genes during adipogenesis by targeting and incorporating the histone variant H2A.Z in transcriptional regulatory regions. The results reported here indicate that expression of both Brd8 and p400 increases during fat cell differentiation. In addition, small hairpin RNA-mediated knockdown of Brd8 or H2A.Z completely abrogated the ability of 3T3-L1 preadipocyte to differentiate into mature adipocyte, as evidenced by a lack of lipid accumulation. Chromatin immunoprecipitation experiments also revealed that the knockdown of Brd8 blocked the accumulation of PPARγ, p400, and RNA polymerase II and prevented the incorporation of H2A.Z at two PPARγ target genes. Taken together, these results indicate that the incorporation of the histone variant H2A.Z at the promoter regions of PPARγ target genes by p400/Brd8 is essential to allow fat cell differentiation.
Thyroid Peroxidase Gene Expression Is Induced by Lipopolysaccharide Involving Nuclear Factor (NF)-κB p65 Subunit Phosphorylation
Authors: Nazar Magalí , Nicola Juan Pablo , Vélez María Laura , Pellizas Claudia Gabriela , Masini-Repiso Ana María 
Published: October 2012

Abstract
Thyroid peroxidase (TPO), a tissue-specific enzyme expressed in differentiated thyroid follicular cells, is a major antigen that has been linked to autoimmune thyroid disease. We have previously reported the functional expression of the lipopolysaccharide (LPS) receptor Toll-like receptor 4 on thyroid follicular cells. Here we investigated the effect of LPS in TPO expression and analyzed the mechanisms involved. We found a dose-dependent enhancement of TSH-induced TPO expression in response to LPS stimulation. EMSAs demonstrated that LPS treatment increased thyroid transcription factor-1 and -2 binding to the B and Z regions of TPO promoter, respectively. Moreover, LPS increased TSH-stimulated TPO promoter activity. Using bioinformatic analysis, we identified a conserved binding site for transcription nuclear factor-κB (NF-κB) in the TPO promoter. Chemical inhibition of NF-κB signaling and site-directed mutagenesis of the identified κB-cis-acting element abolished LPS stimulation. Furthermore, chromatin immunoprecipitation assays confirmed that TPO constitutes a novel NF-κB p65 subunit target gene in response to LPS. Additionally, our results indicate that p65 phosphorylation of serine 536 constitutes an essential step in the p65-dependent, LPS-induced transcriptional expression of TPO. In conclusion, here we demonstrated that LPS increases TPO expression, suggesting a novel mechanism involved in the regulation of a major thyroid autoantigen. Our results provide new insights into the potential effects of infectious processes on thyroid homeostasis.
A Major Lineage of Enteroendocrine Cells Coexpress CCK, Secretin, GIP, GLP-1, PYY, and Neurotensin but Not Somatostatin
Authors: Egerod Kristoffer L. , Engelstoft Maja S. , Grunddal Kaare V. , Nøhr Mark K. , Secher Anna , Sakata Ichiro , Pedersen Jens , Windeløv Johanne A. , Füchtbauer Ernst-Martin , Olsen Jørgen , Sundler Frank , Christensen Jan P. , Wierup Nils , Olsen Jesper V. , Holst Jens J. , Zigman Jeffrey M. , Poulsen Steen S. , Schwartz Thue W. 
Published: October 2012

AbstractEnteroendocrine cells such as duodenal cholecystokinin (CCK cells) are generally thought to be confined to certain segments of the gastrointestinal (GI) tract and to store and release peptides derived from only a single peptide precursor. In the current study, however, transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the CCK promoter demonstrated a distribution pattern of CCK-eGFP positive cells that extended throughout the intestine. Quantitative PCR and liquid chromatography-mass spectrometry proteomic analyses of isolated, FACS-purified CCK-eGFP-positive cells demonstrated expression of not only CCK but also glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide (GIP), peptide YY (PYY), neurotensin, and secretin, but not somatostatin. Immunohistochemistry confirmed this expression pattern. The broad coexpression phenomenon was observed both in crypts and villi as demonstrated by immunohistochemistry and FACS analysis of separated cell populations. Single-cell quantitative PCR indicated that approximately half of the duodenal CCK-eGFP cells express one peptide precursor in addition to CCK, whereas an additional smaller fraction expresses two peptide precursors in addition to CCK. The coexpression pattern was further confirmed through a cell ablation study based on expression of the human diphtheria toxin receptor under the control of the proglucagon promoter, in which activation of the receptor resulted in a marked reduction not only in GLP-1 cells, but also PYY, neurotensin, GIP, CCK, and secretin cells, whereas somatostatin cells were spared. Key elements of the coexpression pattern were confirmed by immunohistochemical double staining in human small intestine. It is concluded that a lineage of mature enteroendocrine cells have the ability to coexpress members of a group of functionally related peptides: CCK, secretin, GIP, GLP-1, PYY, and neurotensin, suggesting a potential therapeutic target for the treatment and prevention of diabetes and obesity.
Causation, Chance, and the Rational Significance of Supernatural Evidence
Authors: Price Huw 
Published: October 2012

In “A Subjectivist’s Guide to Objective Chance,” David Lewis says that he is “led to wonder whether anyone but a subjectivist is in a position to understand objective chance.” The present essay aims to motivate this same Lewisean attitude, and a similar degree of modest subjectivism, with respect to objective causation.
The essay begins with Newcomb problems, which turn on an apparent tension between two principles of choice: roughly, a principle sensitive to the causal features of the relevant situation, and a principle sensitive only to evidential factors. Two-boxers give priority to causal beliefs, and one-boxers to evidential beliefs. The essay notes that a similar issue can arise when the modality in question is chance, rather than causation. In this case, the conflict is between decision rules based on credences guided solely by chances, and rules based on credences guided by other sorts of probabilistic evidence. Far from excluding cases of the latter kind, Lewis’s Principal Principle explicitly allows for them, in the form of the caveat that credences should follow beliefs about chances only in the absence of “inadmissible evidence.”
The essay then exhibits a tension in Lewis’s views on these two matters, by presenting a class of decision problems—some of them themselves Newcomb problems—in which Lewis’s view of the relevance of inadmissible evidence seems in tension with his causal decision theory. It offers a diagnosis for this dilemma and proposes a remedy, based on an extension of a proposal due to Ned Hall and others from the case of chance to that of causation. The remedy suggests a new view of the relation between causal decision theory and evidential decision theory, namely, that they stand to each other much as chance stands to credence, being objective and subjective faces of the same practical coin. This has much the same metaphysical benefits as Lewis’s own view of chance and also throws interesting new light on Newcomb problems, providing an irenic resolution of the apparent disagreement between causal and evidential decision rules.
Bmi1overexpression in the cerebellar granule cell lineage of mice affects cell proliferation and survival without initiating medulloblastoma formation
Authors: Behesti Hourinaz , Bhagat Heeta , Dubuc Adrian M. , Taylor Michael D. , Marino Silvia 
Published: October 2012

SummaryBMI1 is a potent inducer of neural stem cell self-renewal and neural progenitor cell proliferation during development and in adult tissue homeostasis. It is overexpressed in numerous human cancers - including medulloblastomas, in which its functional role is unclear. We generated transgenic mouse lines with targeted overexpression of Bmi1 in the cerebellar granule cell lineage, a cell type that has been shown to act as a cell of origin for medulloblastomas. Overexpression of Bmi1 in granule cell progenitors (GCPs) led to a decrease in cerebellar size due to decreased GCP proliferation and repression of the expression of cyclin genes, whereas Bmi1 overexpression in postmitotic granule cells improved cell survival in response to stress by altering the expression of genes in the mitochondrial cell death pathway and of Myc and Lef-1. Although no medulloblastomas developed in ageing cohorts of transgenic mice, crosses with Trp53−/− mice resulted in a low incidence of medulloblastoma formation. Furthermore, analysis of a large collection of primary human medulloblastomas revealed that tumours with a BMI1high TP53low molecular profile are significantly enriched in Group 4 human medulloblastomas. Our data suggest that different levels and timing of Bmi1 overexpression yield distinct cellular outcomes within the same cellular lineage. Importantly, Bmi1 overexpression at the GCP stage does not induce tumour formation, suggesting that BMI1 overexpression in GCP-derived human medulloblastomas probably occurs during later stages of oncogenesis and might serve to enhance tumour cell survival.
Dysregulation of cholesterol balance in the brain: contribution to neurodegenerative diseases
Authors: Vance Jean E. 
Published: October 2012

SummaryDysregulation of cholesterol homeostasis in the brain is increasingly being linked to chronic neurodegenerative disorders, including Alzheimer’s disease (AD), Huntington’s disease (HD), Parkinson’s disease (PD), Niemann-Pick type C (NPC) disease and Smith-Lemli Opitz syndrome (SLOS). However, the molecular mechanisms underlying the correlation between altered cholesterol metabolism and the neurological deficits are, for the most part, not clear. NPC disease and SLOS are caused by mutations in genes involved in the biosynthesis or intracellular trafficking of cholesterol, respectively. However, the types of neurological impairments, and the areas of the brain that are most affected, differ between these diseases. Some, but not all, studies indicate that high levels of plasma cholesterol correlate with increased risk of developing AD. Moreover, inheritance of the E4 isoform of apolipoprotein E (APOE), a cholesterol-carrying protein, markedly increases the risk of developing AD. Whether or not treatment of AD with statins is beneficial remains controversial, and any benefit of statin treatment might be due to anti-inflammatory properties of the drug. Cholesterol balance is also altered in HD and PD, although no causal link between dysregulated cholesterol homeostasis and neurodegeneration has been established. Some important considerations for treatment of neurodegenerative diseases are the impermeability of the blood-brain barrier to many therapeutic agents and difficulties in reversing brain damage that has already occurred. This article focuses on how cholesterol balance in the brain is altered in several neurodegenerative diseases, and discusses some commonalities and differences among the diseases.
Exacerbated neuronal ceroid lipofuscinosis phenotype in Cln1/5 double knock-out mice
Authors: Blom Tea , Schmiedt Mia-Lisa , Wong Andrew M. , Kyttälä Aija , Soronen Jarkko , Jauhiainen Matti , Tyynelä Jaana , Cooper Jonathan D. , Jalanko Anu 
Published: October 2012

Summary
Both CLN1 and CLN5 deficiencies lead to severe neurodegenerative diseases of childhood, known as neuronal ceroid lipofuscinoses (NCLs). The broadly similar phenotypes of NCL mouse models, and the potential for interactions between NCL proteins, raise the possibility of shared or convergent disease mechanisms. To begin addressing these issues, we have developed a new mouse model lacking both Cln1 and Cln5 genes. These double-knockout (Cln1/5 dko) mice were fertile, showing a slight decrease in expected Mendelian breeding ratios, as well as impaired embryoid body formation by induced pluripotent stem cells derived from Cln1/5 dko fibroblasts. Typical disease manifestations of the NCLs, i.e. seizures and motor dysfunction, were detected at the age of 3 months, earlier than in either single knockout mouse. Pathological analyses revealed a similar exacerbation and earlier onset of disease in Cln1/5 dko mice, which exhibited a pronounced accumulation of autofluorescent storage material. Cortical demyelination and more pronounced glial activation in cortical and thalamic regions was followed by cortical neuron loss. Alterations in lipid metabolism in Cln1/5 dko showed a specific increase in plasma phospholipid transfer protein (PLTP) activity. Finally, gene expression profiling of Cln1/5 dko cortex revealed defects in myelination and immune response pathways, with a prominent downregulation of α-synuclein in Cln1/5 dko mouse brains. The simultaneous loss of both Cln1 and Cln5 genes might enhance the typical pathological phenotypes of these mice by disrupting or downregulating shared or convergent pathogenic pathways, which could potentially include interactions of CLN1 and CLN5.
Mice deficient in the H+-ATPase a4 subunit have severe hearing impairment associated with enlarged endolymphatic compartments within the inner ear
Authors: Lorente-Cánovas Beatriz , Ingham Neil , Norgett Elizabeth E. , Golder Zoe J. , Karet Frankl Fiona E. , Steel Karen P. 
Published: October 2012

SummaryMutations in the ATP6V0A4 gene lead to autosomal recessive distal renal tubular acidosis in patients, who often show sensorineural hearing impairment. A first Atp6v0a4 knockout mouse model that recapitulates the loss of H+-ATPase function seen in humans has been generated and recently reported (Norgett et al., 2012). Here, we present the first detailed analysis of the structure and function of the auditory system in Atp6v0a4-/- knockout mice. Measurements of the auditory brainstem response (ABR) showed significantly elevated thresholds in homozygous mutant mice, which indicate severe hearing impairment. Heterozygote thresholds were normal. Analysis of paint-filled inner ears and sections from E16.5 embryos revealed a marked expansion of cochlear and endolymphatic ducts in Atp6v0a4-/- mice. A regulatory link between Atp6v0a4, Foxi1 and Pds has been reported and we found that the endolymphatic sac of Atp6v0a4-/- mice expresses both Foxi1 and Pds, which suggests a downstream position of Atp6v0a4. These mutants also showed a lack of endocochlear potential, suggesting a functional defect of the stria vascularis on the lateral wall of the cochlear duct. However, the main K+ channels involved in the generation of endocochlear potential, Kcnj10 and Kcnq1, are strongly expressed in Atp6v0a4-/- mice. Our results lead to a better understanding of the role of this proton pump in hearing function.
Performance Criteria for Testosterone Measurements Based on Biological Variation in Adult Males: Recommendations from the Partnership for the Accurate Testing of Hormones
Authors: Yun Yeo-Min , Botelho Julianne Cook , Chandler Donald W , Katayev Alex , Roberts William L , Stanczyk Frank Z , Vesper Hubert W , Nakamoto Jon M , Garibaldi Luigi , Clarke Nigel J , Fitzgerald Robert L 
Published: October 2012

BACKGROUND
Testosterone measurements that are accurate, reliable, and comparable across methodologies are crucial to improving public health. Current US Food and Drug Administration–cleared testosterone assays have important limitations. We sought to develop assay performance requirements on the basis of biological variation that allow physiologic changes to be distinguished from assay analytical errors.

METHODS
From literature review, the technical advisory subcommittee of the Partnership for the Accurate Testing of Hormones compiled a database of articles regarding analytical and biological variability of testosterone. These data, mostly from direct immunoassay-based methodologies, were used to specify analytical performance goals derived from within- and between-person variability of testosterone.

RESULTS
The allowable limits of desirable imprecision and bias on the basis of currently available biological variation data were 5.3% and 6.4%, respectively. The total error goal was 16.7%. From recent College of American Pathologists proficiency survey data, most currently available testosterone assays missed these analytical performance goals by wide margins. Data from the recently established CDC Hormone Standardization program showed that although the overall mean bias of selected certified assays was within 6.4%, individual sample measurements could show large variability in terms of precision, bias, and total error.

CONCLUSIONS
Because accurate measurement of testosterone across a wide range of concentrations [approximately 2–2000 ng/dL (0.069–69.4 nmol/L)] is important, we recommend using available data on biological variation to calculate performance criteria across the full range of expected values. Additional studies should be conducted to obtain biological variation data on testosterone from women and children, and revisions should be made to the analytical goals for these patient populations.
Evaluating historic graffiti based on cultural significance and definitions of art
Authors: Vettese-Forster Samantha , Forster Alan M 
Published: October 2012

Many examples of historic graffiti have been shown to be worthy of attention and conservation. The examples discussed in this article have been selected for their previous academic study, enabling rational assessment. This work does not suggest that only those examples of historic graffiti
that have been subject to academic investigation can be evaluated and classified. This article, the result of a collaboration between two individuals with complementary interests in building conservation and contextual studies in art and design, brings together formal techniques used in the
assessment of cultural significance in traditional architectural conservation and established theories in the evaluation of art. It is the purpose of this work to help those who are attempting to evaluate the merit of graffiti to do so.
The current Scottish system that assesses cultural
significance may be incomplete in its evaluation of graffiti. This necessitates a supplementary investigation of the artistic characteristics and merit of graffiti.
Almost all graffiti could be said to be 'art', using established definitions, but not 'good' art. This evaluation may only
be undertaken by experts, as with other aspects of identification of cultural significance within the built environment.
One language, one history? On the uncertain future of social sciences in Europe
Authors: Bruhns Hinnerk 
Published: October 2012

The question of the future of European social sciences is taken up by examining two examples of 'futures past' that represent significant moments of two different 'histories' of the social sciences. The first one is that of Max Weber in the years about 1910 when he engaged himself in
the foundation of the German Sociological Association and in other initiatives. The second example is that of the efforts of Fernand Braudel, during the 1950s and 1960s, to reorganize social sciences and humanities in the frame of new institutions as the Ecole des Hautes Etudes en Sciences
sociales and the Foundation Maison des Sciences de l'Homme. Both initiatives, the German and the French, combined an intellectual with an institutional project, the first being a story of failure, the second a story of success.
The actual situation is then examined under the viewpoint of
the tensions between Eurocentrism and de-Europeanisation on the one side, monolingualism and pluri-lingualism on the other. Going back directly (and not via second hand lectures) to important intellectual projects as those of Weber and Braudel (or others) could be helpful for the design of
the future of European social sciences.
Adjustment of valence state of Pu and Np in nitric solution containing N,N-dimethylhydroxylamine and monomethylhydrazine by electrolysis
Authors: Zhang Hu , Ye Guo-an , Cong Hai-feng , Li L. , Yang He , Li Gao-liang , Zheng Wei-fang , Jiang De-xiang , Liu Xie-chun , Xiao Song-tao , Lan Tian 
Published: October 2012

Abstract
A study of the electrochemical behaviors of N,N-dimethylhydroxylamine (DMHAN) and monomethyl hydrazine (MMH) in nitric acid solution on Pt electrodes were carried out by cyclic voltammetry (CV) and linear sweep voltammetry (LSV) methods. The diffusion coefficients of DMHAN and MMH were obtained by CV. The values are found to be 0.53 × 106 cm2/s D(DMHAN) and 0.88 × 105 cm2/s D(MMH). The equilibrium potentials (+0.47 V vs. SCE for DMHAN and +0.31 V vs. SCE for MMH) were also measured using Tafel curves. Various valence states of Pu and Np in HNO3 solution containing DMHAN and MMH in the electrolytic process were investigated by an electrolytic cell using a platinum as the anode and a titanium plate as the cathode. In this procedure, MMH was first electro-oxidized on the Pt anode and Np(V) was reduced to Np(IV) on the Ti cathode. After MMH was entirely consumed, the accumulation of HNO2 (due to the electrochemical reduction of nitric acid on the Ti cathode) caused a significantly fast catalytic reaction of DMHAN with HNO3 to form HNO2. HNO2 can oxidize Pu(III) to Pu(IV) quickly. As a result, both oxidation states of Pu and Np were found to be tetravalent in the post-electrolysis solution. A convenient method to keep the post-electrolysis solution at 70 ºC was used to adjust the oxidation state of Np in it's pentavalent state while retaining the tetravalent state of Pu. This study developed an electrolytic process for the preparation of 2AF feed (the feed of Pu purification cycle) in APOR (Advanced Purex Process Based on Organic Reductants) process by electrochemically oxidizing Pu(III) and selectively adjusting the valence state of neptunium to either Np(IV) or Np(V).
Radiochemical studies relevant to cyclotron production of the therapeutic radionuclide 167Tm
Authors: Zandi Nadia , Sadeghi Mahdi , Afarideh Hossein , Yarmohamadi M. 
Published: October 2012

Abstract
Thulium-167, having a half-life of 9.25 d, is an important therapeutic radionuclide. It was produced via the natEr(p,xn)167Tm nuclear reaction by irradiation of a sedimented target with 15 MeV protons at a beam current of 20 μA. Radiochemical separation of 167Tm from a solution of the irradiated erbium target in hydrochloric acid was performed using di-(2-ethylhexyl) phosphoric acid (HDEHP) in n-hexane and in chloroform separately. The effect of different molarities of HDEHP on extraction efficiency was investigated. The radiochemical yield of 167Tm amounted to about 80 ± 5% while using n-hexane/HDEHP (1 M). The experimentally obtained production yield was about 3.2 MBq/μA h. It was comparable with the theoretical value of 4.1 MBq/μA h obtained from nuclear model calculations using the TALYS and EMPIRE codes.