bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytosolic deglycosylation process of newly synthesized glycoproteins generates oligomannosides possessing one GlcNAc residue at the reducing end
Authors: DUVET Sandrine , LABIAU Odette , MIR Anne-Marie , KMIÉCIK Daniel , KRAG Sharon S. , VERBERT André , CACAN René 
Published: August 2015

Recent studies on the mechanism of degradation of newly synthesized glycoproteins suggest the involvement of a retrotranslocation of the glycoprotein from the lumen of the rough endoplasmic reticulum into the cytosol, where a deglycosylation process takes place. In the studies reported here, we used a glycosylation mutant of Chinese hamster ovary cells that does not synthesize mannosylphosphoryldolichol and has an increased level of soluble oligomannosides originating from glycoprotein degradation. In the presence of anisomycin, an inhibitor of protein synthesis, we observed an accumulation of glucosylated oligosaccharide-lipid donors (Glc3Man5GlcNAc2-PP-Dol), which are the precursors of the soluble neutral oligosaccharide material. Inhibition of rough endoplasmic reticulum glucosidase(s) by castanospermine led to the formation of Glc3Man5GlcNAc2(OSGn2) (in which OSGn2 is an oligomannoside possessing two GlcNAc residues at its reducing end), which was then retained in the lumen of intracellular vesicles. Thus they were protected during an 8 h chase period from the action of cytosolic chitobiase, which is responsible for the conversion of OSGn2 to oligomannosides possessing one GlcNAc residue at the reducing end (OSGn1). In contrast, when protein synthesis was maintained in the presence of castanospermine, glucosylated oligomannosides (Glc1–3Man5GlcNAc1) were recovered in cytosol. Except for monoglucosylated Man5 species, which are potential substrates for luminal calnexin and calreticulin, the pattern of oligomannosides was similar to that observed on glycoproteins. The occurrence in the cytosol of glucosylated species with one GlcNAc residue at the reducing end implies that the deglycosylation process that generates glucosylated OSGn1 from glycoproteins occurs in the cytosol.
Cholesterol regulates oxysterol binding protein (OSBP) phosphorylation and Golgi localization in Chinese hamster ovary cells: correlation with stimulation of sphingomyelin synthesis by 25-hydroxycholesterol
Authors: STOREY Margo K. , BYERS David M. , COOK Harold W. , RIDGWAY Neale D. 
Published: August 2015

Sphingomyelin (SM) and cholesterol content is positively correlated in cellular membranes, and in several pathological and experimental conditions there is evidence for coregulation. The potential role of oxysterols and oxysterol binding protein (OSBP) in mediating the coregulation of cholesterol and SM was examined using Chinese hamster ovary (CHO) and cholesterol auxotrophic, sterol regulatory defective (SRD) 6 cells. SRD 6 cells grown in the presence or absence of cholesterol for 24 h displayed a 30–50% reduction in SM synthesis compared with control CHO 7 cells. SM synthesis in CHO 7 and cholesterol-supplemented SRD 6 cells was stimulated 2-fold by 25-hydroxycholesterol, but cholesterol-starved SRD 6 cells were unresponsive. Basal and 25-hydroxycholesterol-stimulated SM synthesis was also inhibited in lovastatin-treated wild-type CHO-K1 cells. Lack of 25-hydroxycholesterol activation of SM synthesis in cholesterol-starved SRD 6 and lovastatin-treated CHO-K1 cells was correlated with dephosphorylation of OSBP. In SRD 6 cells, this was evident after 12 h of cholesterol depletion, it occurred equally at all phosphorylation sites and was exacerbated by 25-hydroxycholesterol. Unlike CHO 7 cells, where OSBP was observed in small vesicles and the cytoplasm, OSBP in cholesterol-starved SRD 6 cells was constitutively localized in the Golgi apparatus. Supplementation with non-lipoprotein cholesterol promoted redistribution to vesicles and the cytoplasm. Similarly, OSBP in CHO-K1 cells grown in delipidated serum was predominantly in the Golgi apparatus. Low-density lipoprotein (LDL) supplementation of CHO-K1 cells caused the redistribution of OSBP to the cytoplasm and small vesicles, and this effect was blocked by pharmacological agents {3-β-[2-(diethylamino)ethoxy]androst-5-en-17-one and progesterone}, which inhibited LDL cholesterol efflux from lysosomes. The results showed that localization of OSBP between the Golgi apparatus and a cytoplasmic/vesicular compartment was responsive to changes in cholesterol content and trafficking. In cholesterol depleted SRD 6 cells, this was accompanied by dephosphorylation of OSBP and attenuation of 25-hydroxycholesterol activation of SM synthesis.
Genomic organization, 5′-flanking region and chromosomal localization of the human glutathione transferase A4 gene
Authors: DESMOTS Fabienne , RAUCH Claudine , HENRY Catherine , GUILLOUZO André , MOREL Fabrice 
Published: August 2015

We have isolated and characterized a human glutathione transferase A4 (hGSTA4) subunit gene from a yeast artificial chromosome containing several other glutathione transferase alpha genes and pseudogenes. The homodimeric protein hGSTA4-4, is involved in the detoxification of 4-hydroxynonenal and other reactive electrophiles produced by oxidative metabolism, and may have a significant role in protecting intracellular components from oxidative damage. The hGSTA4 gene spans nearly 18 kb, contains seven exons, maps onto chromosome 6p12, and lies in close proximity to the 7SK small nuclear RNA gene in a head-to-tail orientation. The intron/exon borders conform to the standard rules, an open reading frame is present beginning at position 154 in exon 2, and the stop codon is at position 822 in exon 7. The transcription initiation site has been determined by primer extension analysis and is located 135 bp upstream of intron 1. Isolation and sequencing of the hGSTA4 gene 5´-flanking region revealed it to be devoid of TATA or CCAAT boxes but it does contain an initiator element overlapping the transcription start site, a GC box and putative binding sites for transcription factors AP1, STAT, GATA1 and NF-κB. Reverse transcription-PCR analysis revealed that hGSTA4 mRNA was present in all the tissues tested, although in low amounts, suggesting that this subunit may be ubiquitously expressed.
Monocyte–macrophage ferric reductase activity is inhibited by iron and stimulated by cellular differentiation
Authors: PARTRIDGE Jason , WALLACE Daniel F. , RAJA Kishor B. , DOOLEY James S. , WALKER Ann P. 
Published: August 2015

The enzyme ferric reductase catalyses the reduction of Fe(III) as a prerequisite to its transportation across the cell membrane. Duodenal mucosal biopsies from iron overloaded patients with genetic haemochromatosis (GH) have increased ferric reductase activity and iron absorption compared with controls, yet the GH mucosa is iron deficient. A similar GH-related iron deficiency is also seen in macrophages. The aim of this study was to investigate whether macrophage ferric reductase activity is altered in GH, and to determine ferric reductase activity in monocytes and differentiated macrophages. The erythroleukaemic K562 cell line was studied as a clonal reference cell line. The basal K562 ferric reductase activity is characteristic of a membrane bound enzyme, being both temperature and protease sensitive. Ferric reductase activity was also demonstrated in human leucocyte, monocyte and macrophage preparations. Assays of K562 and macrophage cell supernatants confirmed that the ferric reductase activity was not due to a secreted factor. Assay of ferric reductase in normalized-iron and iron-enriched (100 µM ferric citrate) conditions showed no significant difference between Cys282Tyr (Cys282 → Tyr) homozygous GH macrophages and Cys282-Tyr negative control activities (P&gt; 0.05). However, a 900% increase in ferric reductase activity was observed during monocyte to macrophage differentiation (P&lt; 0.05), possibly reflecting the co-ordinate up-regulation of iron metabolism in these cells. The demonstration of approx. 25% activity after macrophage differentiation at high free-iron concentrations compared with ‘normalized ’ iron is consistent with repression of human ferric reductase activity by iron. The identification of the human ferric reductase gene and its protein will ultimately provide insight into its regulation and role in mammalian iron metabolism.
Identification of an important cysteine residue in human glutamate–cysteine ligase catalytic subunit by site-directed mutagenesis
Authors: TU Zhongheng , ANDERS M. W. 
Published: August 2015

Glutamate–cysteine ligase (GLCL) catalyses the rate-limiting step in glutathione biosynthesis. To identify cysteine residues in GLCL that are involved in its activity, eight conserved cysteine residues in human GLCL catalytic subunit (hGLCLC) were replaced with glycine residues by PCR-based site-directed mutagenesis. Both recombinant hGLCLC and hGLCL holoenzyme were expressed and purified with a baculovirus expression system. The activity of purified hGLCL holoenzyme with the mutant hGLCLC-C553G was 110±12 µmol/h per mg of protein compared with 370±20 µmol/h per mg of protein for the wild-type. Holoenzymes with hGLCLC-C52G, -C248G, -C249G, -C295G, -C491G, -C501G or -C605G showed activities similar to the wild type. The Km values of hGLCL containing hGLCLC-C553G were slightly lower than those of the wild type, indicating that the replacement of cysteine-553 with Gly in hGLCLC did not significantly affect substrate binding by the enzyme. hGLCLC-C553G was more easily dissociated from hGLCLR than the wild-type hGLCLC. GLCL activity increased by 11% after hGLCLC-C553G was incubated with an equimolar amount of purified hGLCL regulatory subunit (hGLCLR) at room temperature for 30 min, but increased by 110% after wild-type hGLCLC was incubated with hGLCLR for 10 min. These results indicate that cysteine-553 in hGLCLC is involved in heterodimer formation between hGLCLC and hGLCLR.
Fermi‐level managed barrier diode for broadband and low‐noise terahertz‐wave detection
Authors: Ito H. , Ishibashi T. 
Published: August 2015

A novel Fermi‐level managed barrier diode has been developed for achieving broadband and low‐noise terahertz‐wave detection. The fabricated quasi‐optical module detected signals at frequencies from 200 GHz to 1 THz. The typical voltage sensitivity was 1020 V/W, and the current sensitivity for a 50 Ω load was 4.5 A/W at 300 GHz for a zero‐biased condition. Square‐law detection with good linearity was demonstrated at 300 GHz with an output current density exceeding 103 A/cm2.
Rules, Standards, and Lower Court Decisions
Authors: Smith Joseph L. , Todd James A. 
Published: August 2015

AbstractThis paper evaluates the impact of a higher court articulating doctrine as either a “rule” or a “standard.” The legal doctrine we evaluate concerns police searches based upon information supplied by confidential informants. The Supreme Court’s Aguilar-Spinelli test was a rule, and its Illinois v. Gates “totality of the circumstances” test is a standard. Using a data set of circuit court opinions from 1951 to 1999, we compare circuit-level implementation of these two doctrines. The results suggest that rules are more effective than standards at constraining ideological voting in lower courts.
Metric Sex Determination of the Human Coxal Bone on a Virtual Sample using Decision Trees
Authors: Savall Frédéric , Faruch‐Bilfeld Marie , Dedouit Fabrice , Sans Nicolas , Rousseau Hervé , Rougé Daniel , Telmon Norbert 
Published: August 2015

AbstractDecision trees provide an alternative to multivariate discriminant analysis, which is still the most commonly used in anthropometric studies. Our study analyzed the metric characterization of a recent virtual sample of 113 coxal bones using decision trees for sex determination. From 17 osteometric type I landmarks, a dataset was built with five classic distances traditionally reported in the literature and six new distances selected using the two‐step ratio method. A ten‐fold cross‐validation was performed, and a decision tree was established on two subsamples (training and test sets). The decision tree established on the training set included three nodes and its application to the test set correctly classified 92% of individuals. This percentage was similar to the data of the literature. The usefulness of decision trees has been demonstrated in numerous fields. They have been already used in sex determination, body mass prediction, and ancestry estimation. This study shows another use of decision trees enabling simple and accurate sex determination.
Cancer services in Western Australia: A comparison of regional outcomes with metropolitan Perth
Authors: Martin Hilary L. , Ohara Kanako , Chin Wee , Davidson Andrew , Bayliss Evan , Redfern Andrew , Khattak Muhammad Adnan 
Published: August 2015

AbstractObjectiveTo investigate whether any survival differences existed between advanced cancer patients treated in metropolitan Perth and those treated in regional Western Australia (WA).DesignRetrospective study.SettingAdvanced cancer patients treated through medical oncology clinics at Royal Perth Hospital and regional cancer centres (Kalgoorlie, Albany, Geraldton and Northam).ParticipantsPatients diagnosed with advanced melanoma, breast, colorectal, gastro‐oesophageal, prostate, lung and pancreatic cancers between 1 January 2007 and 31 December 2011.InterventionsNil.Main outcome measureMedian survival.ResultsData were available for 1581 patients with 75% living in a metropolitan setting and 25% in rural WA. Median overall survival was 8.3 months for metropolitan patients and 7.6 months for regional patients (P = 0.06, HR 0.89; 95% CI, 0.78–1.01). There was no statistically significant difference in median survival for different tumour types except pancreatic cancer: breast 22.1 months versus 21.3 months, colorectal 13.1 months versus 16.4 months, lung 5.1 months versus 3.1 months, upper GI 5.6 months versus 7.2 months, pancreatic 4.5 months versus 3 months (P = 0.02, HR 0.57; 95% CI, 0.32–0.99), melanoma 10.4 months versus 10.5 months, prostate 28.6 months versus 15.3 months. Rural cancer patients with breast and pancreatic cancers received fewer lines of anti‐cancer therapy compared to metropolitan patients. The three‐year survival rates for metropolitan compared to rural breast cancer patients were 34 and 23%, respectively (not statistically significant).ConclusionOur findings suggest a trend towards inferior survival for regional cancer patients in WA compared with metropolitan‐based patients.
Influence of metformin intake on the risk of bladder cancer in type 2 diabetes patients
Authors: Goossens Maria E. , Buntinx Frank , Zeegers Maurice P. , Driessen J.H.M. , De Bruin Marie L. , De Vries Frank 
Published: August 2015

AimThe aim of this study was to look at the influence of metformin intake and duration, on urinary bladder cancer (UBC) risk, with sulfonylurea (SU) only users as control using a new user design (inception cohort).MethodsWe conducted a retrospective cohort study using data from the UK Clinical Practice Research Datalink (CPRD) including all patients with at least one prescription of oral anti‐diabetic drugs (ADD) and/or insulin. The risk of UBC in different groups of ADD users (metformin alone (one), metformin in combination (two) with other ADD medication (glinides, glitazones, DPP‐4‐inhibitors, SUs, insulin or more than one combination), all metformin users (1 + 2) was compared with SU only users using Cox proportional hazards models. The estimates were adjusted for age, gender, smoking status, BMI and diabetes duration.ResultsThe inception cohort included 165 398 participants of whom 132 960 were metformin users and 32 438 were SU only users. During a mean follow‐up time of more than 5 years 693 patients developed UBC, 124 of the control group and 461 of the all metformin users. There was no association between metformin use and UBC risk (HR = 1.12, 95% CI 0.90, 1.40) compared with SU only users, even after adjustment for diabetes duration (HR = 1.13, 95% CI 0.90, 1.40). We found a pattern of decreasing risk of UBC with increasing duration of metformin intake, which was statistically not significant.ConclusionMetformin has no influence on the risk of UBC compared with SU in type 2 diabetes patients using a new user design.
Sparse Non‐rigid Registration of 3D Shapes
Authors: Yang Jingyu , Li Ke , Li Kun , Lai Yu‐Kun 
Published: August 2015

AbstractNon‐rigid registration of 3D shapes is an essential task of increasing importance as commodity depth sensors become more widely available for scanning dynamic scenes. Non‐rigid registration is much more challenging than rigid registration as it estimates a set of local transformations instead of a single global transformation, and hence is prone to the overfitting issue due to underdetermination. The common wisdom in previous methods is to impose an ℓ2‐norm regularization on the local transformation differences. However, the ℓ2‐norm regularization tends to bias the solution towards outliers and noise with heavy‐tailed distribution, which is verified by the poor goodness‐of‐fit of the Gaussian distribution over transformation differences. On the contrary, Laplacian distribution fits well with the transformation differences, suggesting the use of a sparsity prior. We propose a sparse non‐rigid registration (SNR) method with an ℓ1‐norm regularized model for transformation estimation, which is effectively solved by an alternate direction method (ADM) under the augmented Lagrangian framework. We also devise a multi‐resolution scheme for robust and progressive registration. Results on both public datasets and our scanned datasets show the superiority of our method, particularly in handling large‐scale deformations as well as outliers and noise.
A global synthesis of the effects of biological invasions on greenhouse gas emissions
Authors: Qiu Jiangxiao 
Published: August 2015

AbstractAimEvidence is mounting that biological invasions profoundly alter the capacity of ecosystems to regulate or mitigate greenhouse gas (GHG) emissions – a crucial ecosystem service in a changing climate. However, the growing literature has revealed different, even contradictory results and the general pattern over large spatial scales remains obscure. This study synthesizes the effects of invasions by different alien taxa on major GHG emissions.LocationGlobal.MethodsA structured meta‐analysis of 68 case studies was performed to determine the generality of the effects of biological invasions on emissions of three GHGs and assess the extent to which the heterogeneity of effects can be explained by recipient ecosystems, invasive taxa, functional traits, climate and methodological aspects.ResultsInvasive alien species increased N2O emissions but promoted carbon sequestration. Effects on CH4 emissions remained inconclusive. Given the general trends, effects differed by ecosystems, with greater N2O emissions in invaded forest and higher increase in carbon stock in invaded grassland. Invasive taxa also mediated the effects of invasions: invasive plants enhanced carbon storage whereas animal invaders consistently showed negative effects. Focusing on exotic plant invasions, N‐fixing species caused greater N2O emissions than non‐N‐fixing species, and for carbon stock, N‐fixing and woody plants exerted stronger positive effects than non‐N‐fixing and herbaceous plants, respectively. Moreover, climatic factors explained the variation in effects of exotic plant invasions but not those of animal invasions. The effects of plant invasions on carbon content varied nonlinearly with climate, with more pronounced effects where temperature and precipitation were extremely high or low.Main conclusionsThis meta‐analysis reveals the overall magnitude and direction of the effects of biological invasions on major GHG emissions, demonstrates that the effects vary substantially by GHGs, biological and environmental factors and proposes avenues for future research. These results highlight the importance of considering species traits and local and climatic conditions in assessing and managing biological invaders.
HisTOOLogy: an open‐source tool for quantitative analysis of histological sections
Authors: MAGLIARO C. , TIRELLA A. , MATTEI G. , PIRONE A. , AHLUWALIA A. 
Published: August 2015

SummaryHisTOOLogy is an open‐source software for the quantification of digital colour images of histological sections. The simple graphical user interface enables both expert and non‐expert users to rapidly extract useful information from stained tissue sections. The software's main feature is a generalizable colour separation algorithm based on k‐means clustering which accurately and reproducibly returns the amount of colour per unit area for any stain, thus allowing the quantification of tissue components. Here we describe HisTOOLogy's algorithms and graphical user interface structure, showing how it can be used to separate different dye colours in several classical stains. In addition, to demonstrate how the tool can be employed to obtain quantitative information on biological tissues, the effect of different hepatic tissue decellularization protocols on cell removal and matrix preservation was assessed through image analysis using HisTOOLogy and compared with conventional DNA and total protein content assays. HisTOOLogy's performance was also compared with ImageJ's colour deconvolution plug‐in, demonstrating its advantages in terms of ease of use and speed of colour separation.
The Relationship Between Joint Stiffness and Muscle Activity in Unstable Ankles and Copers
Authors: Needle Alan R. , Kaminski Thomas W. , Baumeister Jochen , Higginson Jill S. , Farquhar William B. , Swanik C. Buz 
Published: August 2015

Context:Rolling sensations at the ankle are common after injury and represent failure in neural regulation of joint stiffness. However, deficits after ankle injury are variable and strategies for optimizing stiffness may differ across patients.Objective:To determine if ankle stiffness and muscle activation differ between patients with varying history of ankle injury.Patients:Fifty-nine individuals were stratified into healthy (CON, n = 20), functionally unstable (UNS, n = 19), and coper (COP, n = 20) groups.Main Outcome Measures:A 20° supination perturbation was applied to the ankle as position and torque were synchronized with activity of tibialis anterior, peroneus longus, and soleus. Subjects were tested with muscles relaxed, while maintaining 30% muscle activation, and while directed to react and resist the perturbation.Results:No group differences existed for joint stiffness (F = 0.07, P = .993); however, the UNS group had higher soleus and less tibialis anterior activation than the CON group during passive trials (P < .05). In addition, greater early tibialis anterior activation generally predicted higher stiffness in the CON group (P ≤ .03), but greater soleus activity improved stiffness in the UNS group (P = .03).Conclusion:Although previous injury does not affect the ability to stiffen the joint under laboratory conditions, strategies appear to differ. Generally, the COP has decreased muscle activation, whereas the UNS uses greater plantar-flexor activity. The results of this study suggest that clinicians should emphasize correct preparatory muscle activation to improve joint stiffness in injury-rehabilitation efforts.