bluuebunny/crossref_metadata_2025_split huggingface dataset:
Premature aging in telomerase-deficient zebrafish
Authors: Anchelin Monique , Alcaraz-Pérez Francisca , Martínez Carlos M. , Bernabé-García Manuel , Mulero Victoriano , Cayuela María L. 
Published: June 2013

Summary
The study of telomere biology is crucial to the understanding of aging and cancer. In the pursuit of greater knowledge in the field of human telomere biology, the mouse has been used extensively as a model. However, there are fundamental differences between mouse and human cells. Therefore, additional models are required. In light of this, we have characterized telomerase-deficient zebrafish (Danio rerio) as the second vertebrate model for human telomerase-driven diseases. We found that telomerase-deficient zebrafish show p53-dependent premature aging and reduced lifespan in the first generation, as occurs in humans but not in mice, probably reflecting the similar telomere length in fish and humans. Among these aging symptoms, spinal curvature, liver and retina degeneration, and infertility were the most remarkable. Although the second-generation embryos died in early developmental stages, restoration of telomerase activity rescued telomere length and survival, indicating that telomerase dosage is crucial. Importantly, this model also reproduces the disease anticipation observed in humans with dyskeratosis congenita (DC). Thus, telomerase haploinsufficiency leads to anticipation phenomenon in longevity, which is related to telomere shortening and, specifically, with the proportion of short telomeres. Furthermore, p53 was induced by telomere attrition, leading to growth arrest and apoptosis. Importantly, genetic inhibition of p53 rescued the adverse effects of telomere loss, indicating that the molecular mechanisms induced by telomere shortening are conserved from fish to mammals. The partial rescue of telomere length and longevity by restoration of telomerase activity, together with the feasibility of the zebrafish for high-throughput chemical screening, both point to the usefulness of this model for the discovery of new drugs able to reactivate telomerase in individuals with DC.
Timing of mTOR activation affects tuberous sclerosis complex neuropathology in mouse models
Authors: Magri Laura , Cominelli Manuela , Cambiaghi Marco , Cursi Marco , Leocani Letizia , Minicucci Fabio , Poliani Pietro Luigi , Galli Rossella 
Published: June 2013

Summary
Tuberous sclerosis complex (TSC) is a dominantly inherited disease with high penetrance and morbidity, and is caused by mutations in either of two genes, TSC1 or TSC2. Most affected individuals display severe neurological manifestations – such as intractable epilepsy, mental retardation and autism – that are intimately associated with peculiar CNS lesions known as cortical tubers (CTs). The existence of a significant genotype-phenotype correlation in individuals bearing mutations in either TSC1 or TSC2 is highly controversial. Similar to observations in humans, mouse modeling has suggested that a more severe phenotype is associated with mutation in Tsc2 rather than in Tsc1. However, in these mutant mice, deletion of either gene was achieved in differentiated astrocytes. Here, we report that loss of Tsc1 expression in undifferentiated radial glia cells (RGCs) early during development yields the same phenotype detected upon deletion of Tsc2 in the same cells. Indeed, the same aberrations in cortical cytoarchitecture, hippocampal disturbances and spontaneous epilepsy that have been detected in RGC-targeted Tsc2 mutants were observed in RGC-targeted Tsc1 mutant mice. Remarkably, thorough characterization of RGC-targeted Tsc1 mutants also highlighted subventricular zone (SVZ) disturbances as well as STAT3-dependent and -independent developmental-stage-specific defects in the differentiation potential of ex-vivo-derived embryonic and postnatal neural stem cells (NSCs). As such, deletion of either Tsc1 or Tsc2 induces mostly overlapping phenotypic neuropathological features when performed early during neurogenesis, thus suggesting that the timing of mTOR activation is a key event in proper neural development.
Solvate Ionic Liquid, [Li(triglyme)1][NTf2], as Electrolyte for Rechargeable Li–Air Battery: Discharge Depth and Reversibility
Authors: Tatara Ryoichi , Tachikawa Naoki , Kwon Hoi-Min , Ueno Kazuhide , Dokko Kaoru , Watanabe Masayoshi 
Published: June 2013

Abstract
This study reports a reversible oxygen reduction–oxygen evolution reaction (ORR–OER) that uses a solvate ionic liquid, [Li(triglyme)1][NTf2], as an electrolyte for a rechargeable Li–air (O2) battery. Significantly, it was found that the reversibility and capacity retention for ORR–OER in the solvate ionic liquid was greatly improved with a decrease in the ORR discharge depth; the discharge to 2.2 V vs. Li/Li+ gave much better reversibility than that to 2.0 V vs. Li/Li+.
Reviews
Authors: Dolezal Luna , Gassan Richard , Nepa Stephen , Yates Alexia , Berger Molly W. 
Published: June 2013

HOSPITALITY OF THE MATRIX: PHILOSOPHY, BIOMEDICINE AND CULTURE, IRINA ARISTARKHOVA (2012) New York: Columbia University Press, 248 pp., ISBN: 978-0-231-15929-6, p/bk, $29.50/£20.50, ISBN: 978-0-231-15928-9, h/bk, $89.50/£62.00
RICHARD GASSAN, STEPHEN NEPA,
ALEXIA YATES AND MOLLY W. BERGER
HOTEL DREAMS: LUXURY, TECHNOLOGY, AND URBAN AMBITION IN AMERICA, 1829–1929, MOLLY W. BERGER (2011) Baltimore: Johns Hopkins University Press, 318 pp., ISBN: 978-0-8018-9987-4, h/bk, $60.00
Optical Properties of Nanostructured Electrodes
Authors: Khosroabadi Akram A. , Gangopadhyay Palash , Duong Binh , Thomas Jayan , Norwood Robert A. 
Published: June 2013

ABSTRACTA versatile and powerful new lithographic fabrication method has been used to fabricate a number of nano-architectured ordered 2-D indium tin oxide (ITO) and silver (Ag) electrodes. By careful tuning of the dimensions of the nanofeatures in the electrodes, the surface area can be enhanced as desired, in-turn changing resistivity and free carrier concentrations accordingly. Absorption spectra of the samples show the existence of a new optical bandgap, in addition to the bulk bandgap, that is smaller. Nanostructured electrodes show enhanced transparency compared to their planar counterparts and demonstrate typical surface plasmon characteristics. The resonance frequency can be tuned as well by changing the dimensions of the nanofeatures in the electrodes.
Mapping the Geometry and Lithostratigraphy of a Paleovalley with a Time-domain Electromagnetic Technique in an Area with Small Resistivity Contrasts, Groundbirch, British Columbia, Canada
Authors: Hickin Adrian S. , Best Melvyn E. 
Published: June 2013

The purpose of this paper is to evaluate the effectiveness of large loop, ground-based, time-domain electromagnetic surveys for modeling of paleovalley geometry and valley fills as a basis for determining groundwater potential. The electromagnetic (EM) survey was successful, despite limited resistivity contrast between adjacent valley-fill units, as well as the limited contrast between the valley-fill and bedrock. Thin, coarse-grained units and low contrast in the resistivity present challenges for constraining 1-D inversions. Thin units cannot be resolved and are merged, resulting in simplified models that reflect averaged apparent resistivity. Supplementary data (e.g., borehole resistivity logs) are useful for constraining complex multi-layer inversions, but where absent, complex models are not realistic. As the ratio of the resistivity of two layers decreases, there is more uncertainty in the placement of layer boundaries even though the root mean squared standard error of fit for the model may remain small (<6%). Nonetheless, when 1-D inversions are combined into resistivity-depth sections we interpret four generalized lithologies: 1) bedrock (∼10–30 ohm-m); 2) fine-grained sediment (clay, silt, fine sand, and diamict; 30–50 ohm-m); 3) medium-grained sediment (silt and sand; 40–80 ohm-m); and 4) coarse-grained sediment (sand and possibly gravel; 90 to >350 ohm-m). When the 2-D resistivity-depth sections are combined, there is 3-D continuity and the geometry of the Groundbirch Paleovalley can be traced. The valley is approximately 3–4 km wide with a maximum depth of about 120 m. The data suggest a local basal aquifer (medium- to coarse-grained unit) in the central survey area and possibly an unconfined aquifer towards the northwest region of the survey area. The EM-based model is consistent with models based on water well logs and field observations. Although the EM data remain exploratory, the resulting EM models provide clear guidance for groundwater resources management strategies.
"The Righteous Among the Nations": Bonhoeffer, Yad Vashem and the Church
Authors: Lindsay Mark 
Published: June 2013

In 1986, twenty-three years after establishing the Righteous Among the Nations project, Yad Vashem brought down the first of its many decisions to deny the title to the martyred Lutheran theologian Dietrich Bonhoeffer. As recently as October 2003, when the Israeli Supreme Court ruled that the summary of the reasons behind the committee's rejection could be published, Yad Vashem has consistently maintained that Bonhoeffer falls outside the scope of the legal definition. While he does deserve recognition as a meritorious fighter against the Nazi regimeaccording to Mordecai Paldiel, he was "one ofthe good guys"l -Bonhoeffer simply does not fit the criteria of righteous, as established by the Yad Vashem Law (5713/1953) of August 1953. Curiously, Bonhoeffer's own ecclesiastical authorities adopted a similar stance during the Nazi era. As Victoria Barnett has noted, neither Bonhoeffer's nor Niemoeller's names were included in churches' weekly Fürbittenlisten because their resistance was deemed to be political rather than theological. As far as the bishops were concerned, Bonhoeffer did not deserve prayerful intercession within the context of corporate worship, as his imprisonment had nothing to do with his faith. The intent of this article is neither to argue against Yad Vashem's decision (with which I nonetheless disagree), nor to explore the ecclesiastical-political context which gave rise to the general malaise from which the German churches suffered during the Nazi period. Rather, this paper will suggest that Bonhoeffer's reflections on the Beatitudes provide a more appropriate paradigm of ~hKawcruVll (righteousness) and correlative ethical praxis than either the Church or Yad Vashem have to date permitted. The key texts that will be considered are Nachfolge, Ethics, Letters and Papers from Prison — and, of course, the text of Bonhoeffer's own life.
Serum Hepatitis B Surface Antigen Kinetics in Severe Reactivation of Hepatitis B E Antigen Negative Chronic Hepatitis B Patients Receiving Nucleoside/Nucleotide Analogues
Authors: Wong Grace L-H , Chan Henry L-Y , Lo Angeline O-S , Chan Hoi-Yun , Tse Chi-Hang , Chim Angel M-L , Wong Vincent W-S 
Published: June 2013

Background Kinetics of serum hepatitis B surface antigen (HBsAg) level in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients presented with severe reactivation and received oral antiviral therapy is unknown. We aimed to investigate the kinetics of HBsAg level among these patients. Methods HBeAg-negative patients on antiviral therapy with follow-up for 2 years were studied. Those presented with severe reactivation (alanine aminotransferase [ALT] ≥5 times of normal) were compared to those with mild hepatitis. Serum HBsAg level was measured by Elecsys HBsAg II Quant assay (Roche) at baseline and 6-monthly. Results A total of 192 (74 severe reactivation) patients were studied. Eighty-one (42%), 74 (39%) and 37 (19%) patients were on lamivudine, entecavir and telbivudine, respectively. Forty-four (23%) patients had early HBsAg decline, that is, ≥0.5 log10 reduction, at month 6. Patients with severe reactivation had higher serum baseline ALT (1,415 ±897 versus 73 ±39 IU/l), HBV DNA (6.4 ±1.6 versus 5.2 ±1.2 log10 IU/ml) and HBsAg (3.3 ±1.0 versus 2.9 ±0.6 log10 IU/ml), as well as an earlier HBsAg decline (50% versus 6%; all P<0.001) than those without. The HBsAg change of patients with severe reactivation was higher at months 0-6 (-0.58 ±-1.26 versus -0.01 ±-0.26 log10 IU/ml; P<0.001) but then became comparable from months 6–24 (-0.19 ±-0.60 versus -0.13 ±-0.19 log10 IU/ml; P=0.85), compared to those presented with mild hepatitis. Conclusions Patients who presented with severe reactivation of HBeAg-negative hepatitis were more likely to develop early HBsAg decline during antiviral therapy. It may indicate a transient strong immune clearance with rapid initial reduction in serum HBsAg, which cannot be sustained due to a faster clearance of serum HBsAg.
Reduced Toll-Like Receptor 3 Expression in Chronic Hepatitis B Patients and Its Restoration by Interferon Therapy
Authors: Huang Yi-Wen , Lin Shih-Chang , Wei Shu-Chen , Hu Jui-Ting , Chang Han-Yu , Huang Shih-Hung , Chen Ding-Shinn , Chen Pei-Jer , Hsu Ping-Ning , Yang Sien-Sing , Kao Jia-Horng 
Published: June 2013

Background Toll-like receptor (TLR)3 gene variants may correlate with clinical significance of chronic viral infections including HBV. We aimed to investigate the expression of TLR3 in peripheral blood mononuclear cells (PBMCs) and liver cells of chronic hepatitis B (CHB) patients and its response to pegylated interferon or nucleoside analogue therapy. Methods We consecutively enrolled 127 CHB patients and 64 hepatitis B surface antigen-negative, anti-HCV-negative healthy individuals as controls. We compared the TLR3 expressions on fresh PBMCs and liver cells from patients and controls, before and during pegylated interferon or nucleoside analogue therapy. Results Compared to controls, patients had a lower TLR3 mean fluorescence intensity (MFI) on PBMCs (mean ±sd 14.61 ±13.49 versus 9.70 ±4.61; P<0.001), independent of age, gender and alanine aminotransferase (ALT; -13.466, 95% CI -17.202, -9.730; P<0.001). Patients had limited TLR3 stains on Kupffer cells, whereas controls had diffuse stains on Kupffer and hepatocytes. Hepatic TLR3 messenger RNA was lower in patients than controls (0.47 ±0.30 versus 1-fold). Using pretreatment TLR3 MFI as a referent, among 5 of 12 pegylated-interferon-treated patients with sustained virological response (SVR), TLR3 MFI was restored to a mean of 1.5- to 1.7-folds immediately after treatment. Among seven non-responders or relapsers, TLR3 MFI reduced to a mean of 0.5- to 0.7-fold. Among 10 entecavir-treated patients with on-treatment virological response, TLR3 MFI gradually was restored to a mean of 1.2-folds during 48-week therapy. Conclusions CHB patients have reduced TLR3 expression on PBMCs, independent of age, gender and ALT, and on liver cells. Patients with pegylated-interferon-induced SVR have a more significant restoration of TLR3 expression than those under entecavir.
Penser le rôle des foires internationales dans la mondialisation de l'édition
Authors: Serry Hervé , Vincent Josée 
Published: June 2013

Depuis les années 1950, les foires internationales du livre sont devenues des lieux décisifs pour la structuration des marchés du livre dans une dynamique de mondialisation des marchés de l’édition. Depuis la renaissance de la Buchmesse de Francfort, au lendemain de la Seconde Guerre mondiale, les foires du livre organisent plus que des échanges de droit. À partir de cet épicentre allemand, des pratiques commerciales, des modèles professionnels, des règles économiques, des comportements normés d’échanges, des formes esthétiques et cognitives se sont diffusées. Une foire du livre situe les marchés et les acteurs nationaux dans un ensemble hiérarchisé et contraignant. À partir du cas des investissements québécois à Francfort, il s’agit de voir comment s’articulent les dimensions locales et globales, comment un acteur dominé, c’est-à-dire périphérique du point de vue de la langue et de la notoriété de sa production, peut exister sur le marché mondial des livres. L’étude s’appuie sur la consultation de plusieurs fonds d’archives déposés à Bibliothèque et Archives nationales du Québec et sur le dépouillement de la revue professionnelle Vient de paraître , publiée par le Conseil supérieur du livre de 1965 à 1978. Ainsi, nous montrerons qu’au-delà de la reconnaissance d’une littérature ou d’une culture considérée comme encore « marginale », la présence des éditeurs québécois à Francfort marque aussi la volonté d’imposer l’image d’une nation en devenir. La question se pose enfin de la circulation des modèles professionnels et des formes d’intégration de ceux-ci par le biais de ces espaces hiérarchisés que sont les foires du livre comme Francfort. Et donc des processus de rationalisation des pratiques éditoriales.
An Overview of the Fluctuating Fortunes of Viticulture in England and Wales
Authors: Clout Hugh 
Published: June 2013

Cet article analyse le passé et le présent de la viticulture en Angleterre et au Pays de Galles. Ces vignobles et établissements vinicoles n’y représentent qu’une partie infime de l’ensemble de la production viticole. En dépit de leur faible représentativité sur la scène mondiale, ils ont connu un succès modeste au cours des siècles passés et connaissent depuis les soixante dernières années un regain grâce aux efforts d’un nombre restreint de pionniers, dont les actions sont étudiées ici. La vigne moyenne est extrêmement petite, mais il existe également de plus grandes entreprises commerciales qui produisent des vins de table de qualité et des vins mousseux, quoiqu'en petite quantité. Quelques opérateurs ont développé le tourisme viticole de manière originale afin de contribuer à la diversification rurale. Les implications du « réchauffement global » peuvent favoriser le développement de la viticulture en Angleterre et au Pays de Galles dans les années à venir pourvu que les conditions de capital, de talent, de flair entreprenarial et de marché soient ouvertes.
Cryptococcus gattii Is Killed by Dendritic Cells, but Evades Adaptive Immunity by Failing To Induce Dendritic Cell Maturation
Authors: Huston Shaunna M. , Li Shu Shun , Stack Danuta , Timm-McCann Martina , Jones Gareth J. , Islam Anowara , Berenger Byron M. , Xiang Richard F. , Colarusso Pina , Mody Christopher H. 
Published: June 2013

Abstract
During adaptive immunity to pathogens, dendritic cells (DCs) capture, kill, process, and present microbial Ags to T cells. Ag presentation is accompanied by DC maturation driven by appropriate costimulatory signals. However, current understanding of the intricate regulation of these processes remains limited. Cryptococcus gattii, an emerging fungal pathogen in the Pacific Northwest of Canada and the United States, fails to stimulate an effective immune response in otherwise healthy hosts leading to morbidity or death. Because immunity to fungal pathogens requires intact cell-mediated immunity initiated by DCs, we asked whether C. gattii causes dysregulation of DC functions. C. gattii was efficiently bound and internalized by human monocyte-derived DCs, trafficked to late phagolysosomes, and killed. Yet, even with this degree of DC activation, the organism evaded pathways leading to DC maturation. Despite the ability to recognize and kill C. gattii, immature DCs failed to mature; there was no increased expression of MHC class II, CD86, CD83, CD80, and CCR7, or decrease of CD11c and CD32, which resulted in suboptimal T cell responses. Remarkably, no increase in TNF-α was observed in the presence of C. gattii. However, addition of recombinant TNF-α or stimulation that led to TNF-α production restored DC maturation and restored T cell responses. Thus, despite early killing, C. gattii evades DC maturation, providing a potential explanation for its ability to infect immunocompetent individuals. We have also established that DCs retain the ability to recognize and kill C. gattii without triggering TNF-α, suggesting independent or divergent activation pathways among essential DC functions.
Intrinsic Molecular Factors Cause Aberrant Expansion of the Splenic Marginal Zone B Cell Population in Nonobese Diabetic Mice
Authors: Stolp Jessica , Mariño Eliana , Batten Marcel , Sierro Frederic , Cox Selwyn L. , Grey Shane T. , Silveira Pablo A. 
Published: June 2013

Abstract
Marginal zone (MZ) B cells are an innate-like population that oscillates between MZ and follicular areas of the splenic white pulp. Differentiation of B cells into the MZ subset is governed by BCR signal strength and specificity, NF-κB activation through the B cell–activating factor belonging to the TNF family (BAFF) receptor, Notch2 signaling, and migration signals mediated by chemokine, integrin, and sphingosine-1-phosphate receptors. An imbalance in splenic B cell development resulting in expansion of the MZ subset has been associated with autoimmune pathogenesis in various murine models. One example is the NOD inbred mouse strain, in which MZ B cell expansion has been linked to development of type 1 diabetes and Sjögren’s syndrome. However, the cause of MZ B cell expansion in this strain remains poorly understood. We have determined that increased MZ B cell development in NOD mice is independent of T cell autoimmunity, BCR specificity, BCR signal strength, and increased exposure to BAFF. Rather, mixed bone marrow chimeras showed that the factor(s) responsible for expansion of the NOD MZ subset is B cell intrinsic. Analysis of microarray expression data indicated that NOD MZ and precursor transitional 2-MZ subsets were particularly dysregulated for genes controlling cellular trafficking, including Apoe, Ccbp2, Cxcr7, Lgals1, Pla2g7, Rgs13, S1pr3, Spn, Bid, Cd55, Prf1, and Tlr3. Furthermore, these B cell subsets exhibited an increased steady state dwell time within splenic MZ areas. Our data therefore reveal that precursors of mature B cells in NOD mice exhibit an altered migration set point, allowing increased occupation of the MZ, a niche favoring MZ B cell differentiation.
Cutting Edge: CD1d Restriction and Th1/Th2/Th17 Cytokine Secretion by Human Vδ3 T Cells
Authors: Mangan Bozgana A. , Dunne Margaret R. , O’Reilly Vincent P. , Dunne Pádraic J. , Exley Mark A. , O’Shea Donal , Scotet Emmanuel , Hogan Andrew E. , Doherty Derek G. 
Published: June 2013

Abstract
Human γδ T cells expressing the Vδ3 TCR make up a minor lymphocyte subset in blood but are enriched in liver and in patients with some chronic viral infections and leukemias. We analyzed the frequencies, phenotypes, restriction elements, and functions of fresh and expanded peripheral blood Vδ3 T cells. Vδ3 T cells accounted for ∼0.2% of circulating T cells, included CD4+, CD8+, and CD4−CD8− subsets, and variably expressed CD56, CD161, HLA-DR, and NKG2D but neither NKG2A nor NKG2C. Vδ3 T cells were sorted and expanded by mitogen stimulation in the presence of IL-2. Expanded Vδ3 T cells recognized CD1d but not CD1a, CD1b, or CD1c. Upon activation, they killed CD1d+ target cells, released Th1, Th2, and Th17 cytokines, and induced maturation of dendritic cells into APCs. Thus, Vδ3 T cells are glycolipid-reactive T cells with distinct Ag specificities but functional similarities to NKT cells.