bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Aegean Islands (Prehistoric to Roman)
Authors: Archibald Zosia 
Published: November 2013

Strabo, who visited the island of Gyaros in 31 BC, described it as a village (kōmion, κώμιον Strabo 10.5.3) inhabited by fishermen. This comes as no surprise to anyone familiar with the Aegean islands today. Modern photographic promotions give local fish specialities, and the modest, traditionally whitewashed homes of the fishermen responsible for fresh catches, plenty of colourful emphasis. Not all the fish on offer in the islands are locally caught today, and many visitors arrive by air, rather than by boat, following one of the principal maritime itineraries (which do not, as it happens, normally include Gyaros).More surprising, perhaps, is the fact that Strabo refers to Gyaros at all. This little island, no more than 17km2 and thus never big enough to provide much of a land-based way of life, even for a small community, lies midway, as the crow flies, between Kea to the west, Kythnos to the southwest and Syros to the south, and is flanked to the northeast by the long chain of islands which in effect extend the mountains of Euboea southeastwards into the heart of the Aegean — Andros, Tenos and Mykonos (map of the Cyclades). The geographer was simply articulating a memorable anecdote, according to which the Gyarians sent their own ambassador to Octavian in the hope of getting a reduction of the 150 dr tribute that had been laid on the inhabitants' reluctant shoulders. The Gyarians were not quite as inconspicuous as they wanted to appear in the eyes of Octavian, or as miserable as they looked to Strabo.
Exposure of MC4R to agonist in the endoplasmic reticulum stabilizes an active conformation of the receptor that does not desensitize
Authors: Granell Susana , Molden Brent M. , Baldini Giulia 
Published: November 2013

Significance
Melanocortin-4 receptor (MC4R) is a cell-surface hormone receptor in the brain that is central to the control of appetite. Upstream pathways sensing energy balance in the organism lead to the secretion of α-melanocyte–stimulating hormone (α-MSH), which stimulates MC4R activity and leads to decreased appetite. Previously, it was found that MC4R becomes resistant to treatment with extracellular agonists by a mechanism that may involve desensitization of the receptor, arguing against their usefulness in treating obesity. In this study, we show that exposing MC4R to α-MSH in the endoplasmic reticulum leads to constant signaling of MC4R without desensitization. Our results indicate that the cellular localization where agonist binding initially takes place affects the conformation and the desensitization properties of MC4R, suggesting a target for therapy.
Early Postnatal Calcium and Phosphorus Metabolism in Preterm Infants
Authors: Christmann Viola , de Grauw Anne M. , Visser Reina , Matthijsse René P. , van Goudoever Johannes B. , van Heijst Arno F.J. 
Published: November 2013

ABSTRACTObjectives:Bone mineralisation in preterm infants is related to the supply of calcium (Ca) and phosphorus (P). We increased the amount of minerals in parenteral nutrition (PN) for preterm infants and evaluated postnatal Ca and P metabolism in relation to mineral and vitamin D (vitD) intake.Methods:Preterm infants, included on their first day of life, received standard PN, providing a maximum Ca/P intake of 3/1.92 mmol · kg−1 · day−1 on day 3. Ca/P content of formula was 2.5/1.6 mmol/dL, and fortified human milk was 2.4/1.95 mmol/dL. PN supplied 80 IU · kg−1 · day−1 vitD. Formula and fortified human milk contained 200 IU/dL of vitD. During a 5‐week period, serum concentrations and urinary excretion of Ca/P were registered and related to the intake of minerals and vitD.Results:During 12 months, 79 infants (mean gestational age 29.8 ± 2.2 weeks, mean birth weight 1248 ± 371 g) were included. The recommended intake for minerals was achieved by day 5 and for vitD by 4 weeks. Infants developed hypercalcaemia, hypercalciuria, and hypophosphataemia during the first postnatal week, leading to the additional P supplementation in 49 infants. The renal tubular reabsorption of P was >95% until day 9 but decreased <70% after the second week. Alkaline phosphatase was normal at birth, increased to a maximum of 450 IU/L by day 14, and remained above the normal range for the remaining period.Conclusions:Parenteral intake of P appeared to be too low, leading to mineral imbalances in the early postnatal period, and vitD intake was also below recommendations.
Soil aggregate stratification of nematodes and ammonia oxidizers affects nitrification in an acid soil
Authors: Jiang Yuji , Jin Chen , Sun Bo 
Published: November 2013

SummaryNitrification plays a central role in global nitrogen cycle, which is affected by interaction between soil microfauna and microorganisms. The impact of synchronized changes in nematodes and ammonia oxidizers within aggregate fractions on nitrification was investigated in an acid soil under 10‐year manure application. Nematodes, ammonia oxidizers and potential nitrification activity (PNA) were examined in three soil aggregate fractions under four fertilization regimes. Pyrosequencing data revealed that the dominant bacterial amoA operational taxonomic units (OTUs) were related to Nitrosospira species, while archaeal OTUs were affiliated with Nitrososphaera and Nitrosotalea species. PNA was more strongly correlated with ammonia‐oxidizing bacteria (AOB) abundance than ammonia‐oxidizing archaea (AOA) abundance, although AOA were dominant in the acid soil. Plant parasites had a negative effect on AOB abundance; however, bacterivores stimulated AOB abundance and contributed more to PNA than plant parasites. Aggregate fractions exerted significant impacts on AOA abundance and AOB community composition. Total carbon content strongly affected the abundance and composition of AOA community, while soil pH primarily affected that of AOB community. Soil variables explained 62.7% and 58.1% variations, and nematode variables explained 11.7% and 19.5% variations in the AOA and AOB community composition respectively.
Identifying 2 Prenylflavanones as Potential Hepatotoxic Compounds in the Ethanol Extract of Sophora flavescens
Authors: Yu Qianqian , Cheng Nengneng , Ni Xiaojun 
Published: November 2013

AbstractZhixue capsule is a prescription for hemorrhoid commonly used in traditional Chinese medicine. This drug was recalled by the State Food and Drug Administration in 2008 because of severe adverse hepatic reactions. Zhixue capsule is composed of ethanol extracts of Cortex Dictamni (ECD) and Sophora flavescens (ESF). In our preliminary study, we observed the hepatotoxic effects of ESF on rat primary hepatocytes. However, ECD did not exhibit hepatotoxicity at the same concentration range. In this study, ESF was evaluated for its potential hepatotoxic effects on rats. Bioassay‐guided isolation was used to identify the material basis for hepatotoxicity. Treatment with 1.25 g/kg and 2.5 g/kg ESF significantly elevated the alanine aminotransferase and aspartate aminotransferase levels in the serum. The changes in the levels of transaminases were supported by the remarkable fatty degeneration of liver histopathology. Further investigations using bioassay‐guided isolation and analysis indicated that prenylated flavanones accounted for the positive hepatotoxic results. Two isolated compounds were identified, kurarinone and sophoraflavanone G, using nuclear magnetic resonance and mass spectrometry techniques. These compounds have potent toxic effects on primary rat hepatocytes (with IC50 values of 29.9 μM and 16.5 μM) and human HL‐7702 liver cells (with IC50 values of 48.2 μM and 40.3 μM), respectively. Consequently, the hepatotoxic constituents of S. flavescens were determined to be prenylated flavanones, kurarinone, and sophoraflavanone G.
Molecular characterization of a microbial consortium involved in methane oxidation coupled to denitrification under micro‐aerobic conditions
Authors: Liu Jingjing , Sun Faqian , Wang Liang , Ju Xi , Wu Weixiang , Chen Yingxu 
Published: November 2013

SummaryMethane can be used as an alternative carbon source in biological denitrification because it is nontoxic, widely available and relatively inexpensive. A microbial consortium involved in methane oxidation coupled to denitrification (MOD) was enriched with nitrite and nitrate as electron acceptors under micro‐aerobic conditions. The 16S rRNA gene combined with pmoA phylogeny of methanotrophs and nirK phylogeny of denitrifiers were analysed to reveal the dominant microbial populations and functional microorganisms. Real‐time quantitative polymerase chain reaction results showed high numbers of methanotrophs and denitrifiers in the enriched consortium. The 16S rRNA gene clone library revealed that Methylococcaceae and Methylophilaceae were the dominant populations in the MOD ecosystem. Phylogenetic analyses of pmoA gene clone libraries indicated that all methanotrophs belonged to Methylococcaceae, a type I methanotroph employing the ribulose monophosphate pathway for methane oxidation. Methylotrophic denitrifiers of the Methylophilaceae that can utilize organic intermediates (i.e. formaldehyde, citrate and acetate) released from the methanotrophs played a vital role in aerobic denitrification. This study is the first report to confirm micro‐aerobic denitrification and to make phylogenetic and functional assignments for some members of the microbial assemblages involved in MOD.
The environments of loess uplands to the north and east of the Carpathians during the penultimate interglacial (MOIS 7) in palaeopedological and palaeobotanical records
Authors: Łanczont M. , Madeyska T. , Komar M. , Bogucki A. B. 
Published: November 2013

SummaryThe stratigraphic rank of warming, distinguished in marine deposits as ‘marine oxygen isotope stage 7’ (MOIS 7) and recorded in terrestrial deposits as a palaeosol, has been discussed for a long time. The purpose of this paper is to describe the climate and environment of the time, determined from palaeopedological and palynological investigations of loess‐palaeosol sequences in the peri‐ and metha‐Carpathian zones, and to correlate these sequences with the Pleistocene stratigraphic units. The changes in chemical composition of the deposits were used to reconstruct the processes of chemical weathering and translocation of mobile elements during pedogenesis in three sections (Orzechowce, Galych and Velykyi Glybochok). The variability of the mean annual temperature and precipitation was estimated from the changes of elemental ratios resulting from chemical weathering and vegetation composition. From micromorphological analysis, the stages of palaeosol development and their transformation in cold periods were reconstructed. Pollen analysis carried out for the Velykyi Glyboczok, Maksymivka and Stari Kodaky sites, was used to reconstruct the vegetation cover and the temperature changes of the coldest and warmest months were calculated. The results indicate that the penultimate interglacial period, correlated with MOIS 7, comprised two warming periods separated by a profound cooling period. Warm periods were cooler than the last interglacial and more recent conditions. Vegetation was characterized by the co‐occurrence in changing proportions of patches of mixed forests and steppe vegetation. In the cold period, permafrost developed in places and cryogenic structures were formed. Regional differentiation of biotope environments, resulting from the increase in the continental nature of the climate towards the east, occurred during the whole interglacial period.
Encapsulated galanin‐producing cells attenuate focal epileptic seizures in the hippocampus
Authors: Nikitidou Litsa , Torp Malene , Fjord‐Larsen Lone , Kusk Philip , Wahlberg Lars U. , Kokaia Mérab 
Published: November 2013

SummaryPurposeEncapsulated cell biodelivery (ECB) is a relatively safe approach, since the devices can be removed in the event of adverse effects. The main objectives of the present study were to evaluate whether ECB could be a viable alternative of cell therapy for epilepsy. We therefore developed a human cell line producing galanin, a neuropeptide that has been shown to exert inhibitory effects on seizures, most likely acting via decreasing glutamate release from excitatory synapses. To explore whether ECB of genetically modified galanin‐producing human cell line could provide seizure‐suppressant effects, and test possible translational prospect for clinical application, we implanted ECB devices bilaterally into the hippocampus of rats subjected to rapid kindling, a model for recurrent temporal lobe seizures.MethodsTwo clones from a genetically modified human cell line secreting different levels of galanin were tested. Electroencephalography (EEG) recordings and stimulations were performed by electrodes implanted into the hippocampus at the same surgical session as ECB devices. One week after the surgery, rapid kindling stimulations were initiated.Key FindingsEnzyme‐linked immunosorbent assay (ELISA) measurements prior to device implantation showed a release of galanin on average of 8.3 ng/mL/24 h per device for the low‐releasing clone and 12.6 ng/mL/24 h per device for the high‐releasing clone. High‐releasing galanin‐producing ECB devices moderately decreased stimulation‐induced focal afterdischarge duration, whereas low‐releasing ECB devices had no significant effect.SignificanceOur study shows that galanin‐releasing ECB devices moderately suppress focal stimulation‐induced recurrent seizures. Despite this moderate effect, the study provides conceptual proof that ECB could be a viable alternative approach to cell therapy in humans, with the advantage that the treatment could be terminated by removing these devices from the brain. Thereby, this strategy provides a higher level of safety for future therapeutic applications, in which genetically modified human cell lines that are optimized to produce and release antiepileptic compounds could be clinically evaluated for their seizure‐suppressant effects.A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
Excessive use of nitrogen in Chinese agriculture results in high N2O/(N2O+N2) product ratio of denitrification, primarily due to acidification of the soils
Authors: Qu Zhi , Wang Jingguo , Almøy Trygve , Bakken Lars R 
Published: November 2013

AbstractChina is the world's largest producer and consumer of fertilizer N, and decades of overuse has caused nitrate leaching and possibly soil acidification. We hypothesized that this would enhance the soils' propensity to emit N2O from denitrification by reducing the expression of the enzyme N2O reductase. We investigated this by standardized oxic/anoxic incubations of soils from five long‐term fertilization experiments in different regions of China. After adjusting the nitrate concentration to 2 mM, we measured oxic respiration (R), potential denitrification (D), substrate‐induced denitrification, and the denitrification product stoichiometry (NO, N2O, N2). Soils with a history of high fertilizer N levels had high N2O/(N2O+N2) ratios, but only in those field experiments where soil pH had been lowered by N fertilization. By comparing all soils, we found a strong negative correlation between pH and the N2O/(N2O+N2) product ratio (r2 = 0.759, P < 0.001). In contrast, the potential denitrification (D) was found to be a linear function of oxic respiration (R), and the ratio D/R was largely unaffected by soil pH. The immediate effect of liming acidified soils was lowered N2O/(N2O+N2) ratios. The results provide evidence that soil pH has a marginal direct effect on potential denitrification, but that it is the master variable controlling the percentage of denitrified N emitted as N2O. It has been known for long that low pH may result in high N2O/(N2O+N2) product ratios of denitrification, but our documentation of a pervasive pH‐control of this ratio across soil types and management practices is new. The results are in good agreement with new understanding of how pH may interfere with the expression of N2O reductase. We argue that the management of soil pH should be high on the agenda for mitigating N2O emissions in the future, particularly for countries where ongoing intensification of plant production is likely to acidify the soils.
Immunohistochemical expression of homeoproteins Six1 and Pax3 in breast phyllodes tumours correlates with histological grade and clinical outcome
Authors: Tan Wai Jin , Thike Aye Aye , Bay Boon Huat , Tan Puay Hoon 
Published: November 2013

AimsHomeoproteins are transcription factors which critically regulate developmental processes. Deregulated expression of homeoproteins is observed in several malignancies, such as breast cancer and rhabdomyosarcoma, and contributes to malignant progression. We aimed to investigate the expression and prognostic importance of Six1 and Pax3 homeoproteins in phyllodes tumours – a group of uncommon biphasic tumours comprising both epithelial and stromal components.Methods and resultsA total of 272 cases diagnosed from January 2003 to December 2010 were included in this study – 189 (69.5%) benign, 60 (22.1%) borderline and 23 (8.4%) malignant tumours. Immunohistochemistry was performed on tissue microarray sections using antibodies against Six1 and Pax3. Staining H‐score was assessed in epithelium and stroma separately, and correlated with tumour grade, clinicopathological parameters and prognosis. Tumour grade was associated positively with stromal cytoplasmic expression (P < 0.001; P = 0.011) but correlated negatively with epithelial nuclear expression (P = 0.013; P = 0.007) of both Six1 and Pax3. High stromal cytoplasmic expression of Six1 was associated with metastasis (P = 0.044) and shorter time to recurrence (P = 0.056). Pax3 stromal cytoplasmic expression was associated with poorer overall survival (P = 0.033).ConclusionsSix1 and Pax3 expression is correlated with tumour grade, unfavourable clinicopathological parameters and poorer clinical outcome, suggesting that both proteins may play a role in malignant progression.
Progression of liver fibrosis in HIV/hepatitis C virus‐coinfected individuals on antiretroviral therapy with early stages of liver fibrosis at baseline
Authors: Sanmartín R , Tor J , Sanvisens A , López JJ , Jou A , Muga R , Ojanguren I , Barluenga E , Videla S , Planas R , Clotet B , Tural C 
Published: November 2013

ObjectivesThe aim of the study was to assess the progression of liver fibrosis in HIV/hepatitis C virus (HCV)‐coinfected patients with no or mild‐to‐moderate fibrosis (stages F0−F2).MethodsLiver fibrosis was reassessed by transient elastometry (TE) between January 2009 and November 2011 in HIV/HCV‐coinfected patients with stage F0−F2 fibrosis in a liver biopsy performed between January 1997 and December 2007. Patients with liver stiffness at the end of follow‐up < 7.1 kPa were defined as nonprogressors, and those with values ≥ 9.5 kPa or who died from liver disease were defined as progressors. Cirrhosis was defined as a cut‐off of 14.6 kPa. The follow‐up period was the time between liver biopsy and TE. Cox regression models adjusted for age, gender and liver fibrosis stage at baseline were applied.ResultsThe median follow‐up time was 7.8 years [interquartile range (IQR) 5.5–10 years]. The study population comprised 162 patients [115 (71%) nonprogressors and 47 (29%) progressors; 19 patients (11.7%) had cirrhosis]. The median time from the diagnosis of HCV infection to the end of follow‐up was 20 years (IQR 16.3–23.1 years). Three progressors died from liver disease (1.8%). The variables associated with a lower risk of progression were age ≤ 38 years (hazard ratio (HR) 0.32; 95% confidence interval (CI) 0.16–0.62; P = 0.001], having received interferon (HR 2.18; 95% CI 1.14–4.15; P = 0.017), being hepatitis B virus surface antigen (HBsAg) negative (HR 0.20; 95% CI 0.04–0.92; P = 0.039), and baseline F0−F1 (HR 0.43; 95% CI 0.28–0.86; P = 0.017).ConclusionsA high proportion of patients with stage F0−F2 fibrosis progress to advanced liver fibrosis. Advanced liver fibrosis must be included in the list of diseases associated with aging. Our results support the recommendation to offer HCV antiviral therapy to HIV/HCV‐coinfected patients at early stages of liver fibrosis.
The regulation of cytotoxicity and cyclooxygenase‐2 expression by 2‐hydroxy‐ethyl methacrylate in human osteoblasts are related to intracellular glutathione levels
Authors: Ho Y.‐C. , Huang F.‐M. , Lee S.‐S. , Chang Y.‐C. 
Published: November 2013

AbstractAimTo investigate the effects of 2‐hydroxy‐ethyl methacrylate (HEMA) on cytotoxicity and cyclooxygenase‐2 (COX‐2) protein expression in human osteoblasts.MethodologyCytotoxicity was judged using an Alamar Blue reduction assay on human osteoblast cell line U2OS. Western blot was used to evaluate the expression of COX‐2 protein by HEMA. To determine whether glutathione (GSH) levels were important in cytotoxicity and COX‐2 expression of HEMA, cells were pre‐treated with the GSH precursor, 2‐oxothiazolidine‐4‐carboxylic acid (OTZ), to boost thiol levels, or buthionine sulfoximine (BSO) to deplete GSH. Paired Student's t‐tests were applied for the statistical analysis of the results.ResultsHEMA demonstrated a cytotoxic effect to U2OS cells in a dose‐dependent manner (P < 0.05). The 50% inhibition concentration of HEMA was approximately 3 mmol L−1. HEMA was found to induce COX‐2 protein expression in U2OS cells (P < 0.05). The addition of OTZ acted as a protective effect on HEMA‐induced cytotoxicity and COX‐2 expression (P < 0.05). In contrast, the addition of BSO enhanced HEMA‐induced cytotoxicity and COX‐2 expression (P < 0.05).ConclusionTaken together, the levels of HEMA that were tested inhibited cell growth on U2OS cells. HEMA has a significant potential for periapical toxicity. The activation of COX‐2 protein expression may be one of the mechanisms of HEMA‐induced periapical inflammation. These inhibitory effects were associated with intracellular GSH levels.
Therapeutic potential of placenta‐derived stem cells for liver diseases: Current status and perspectives
Authors: Miki Toshio , Grubbs Brendan 
Published: November 2013

AbstractOver the last decade, there has been a growing interest in the human placenta as a unique source of stem cells. The placenta is a fetal organ that is normally discarded following delivery. Therefore, it is readily available as a source of cells without the ethical concerns normally associated with embryonic stem cells. These cells also carry less risk for age‐ and environmental‐related DNA damage. In addition to these practical advantages of placenta‐derived cells, amniotic epithelial cells possess unique stem cell‐like biological characteristics. In contrast to other parts of the placenta, cells from the amniotic epithelium are derived from pluripotent epiblasts and possess the ability to differentiate into all three germ layers. From a translational perspective, amnion‐derived stem cells are very attractive candidates for clinical application. These cells are genetically stable and do not demonstrate tumorigenicity upon transplantation, and may be endowed with immunomodulatory and/or anti‐inflammatory properties. These unique characteristics have made amniotic epithelial cells attractive for use as stem cell‐based therapies for liver disease. Human and rodent amniotic epithelial cells have already demonstrated their therapeutic efficacy in multiple animal models. Although the detailed mechanism by which the transplanted cells generate a therapeutic effect is not yet totally understood, these dramatic results have generated significant interest for consideration of these amnion‐derived stem cells for clinical applications. This review covers recent findings of the therapeutic potential of amnion‐derived stem cells for liver diseases, and provides perspectives for future developments.