bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liquid chromatography mass spectrometry‐based O‐glycomics to evaluate glycosylation alterations in gastric cancer
Authors: He Yun , Xie Qin , Wang Yanping , Liang Yong , Xu Xiukun , Li Yong , Miao Jinsheng , Chen Zijun , Li Yunsen 
Published: August 2015

PurposeGastric cancer is the fourth most common malignant cancer worldwide. Important for tumorigenesis and progression, aberrant glycosylation occurs frequently in cancers. We investigated the differences in O‐glycosylation in the serum of 157 gastric cancer patients (GC) and 144 healthy donors.Experimental designWe used the method of labeling O‐glycans (released from proteins) with 1‐phenyl‐3‐methyl‐5‐pyrazolone followed by LC‐MS analysis. Analyzing the LC‐MS data by partial least squares discriminant and unpaired Student t test, combined with the structural information of O‐glycans from LC‐MS/MS in positive mode.ResultsThe expression level of core1, core2, ST antigen, and core2 complex O‐glycans (m/z 733.33, m/z 809.42) were increased significantly (p < 0.0001), whereas m/z 529.75 and diST‐antigen were decreased in the serum of GC compared with controls (p < 0.001). In addition, there were significant correlations between the abundance of the O‐glycans and glycoproteins (MUC1, CEA) in the serum of GC.Conclusion and clinical relevanceGlycomics approaches identified multiple candidate antigens for patients with GC. The O‐glycan structures are increased in the serum of GC, they may be candidates for carbohydrate tumor markers.
Intracellular pH modulates quinary structure
Authors: Cohen Rachel D. , Guseman Alex J. , Pielak Gary J. 
Published: August 2015

AbstractNMR spectroscopy can provide information about proteins in living cells. pH is an important characteristic of the intracellular environment because it modulates key protein properties such as net charge and stability. Here, we show that pH modulates quinary interactions, the weak, ubiquitous interactions between proteins and other cellular macromolecules. We use the K10H variant of the B domain of protein G (GB1, 6.2 kDa) as a pH reporter in Escherichia coli cells. By controlling the intracellular pH, we show that quinary interactions influence the quality of in‐cell 15N–1H HSQC NMR spectra. At low pH, the quality is degraded because the increase in attractive interactions between E. coli proteins and GB1 slows GB1 tumbling and broadens its crosspeaks. The results demonstrate the importance of quinary interactions for furthering our understanding of protein chemistry in living cells.
Differential backbone dynamics of companion helices in the extended helical coiled‐coil domain of a bacterial chemoreceptor
Authors: Bartelli Nicholas L. , Hazelbauer Gerald L. 
Published: August 2015

AbstractCytoplasmic domains of transmembrane bacterial chemoreceptors are largely extended four‐helix coiled coils. Previous observations suggested the domain was structurally dynamic. We probed directly backbone dynamics of this domain of the transmembrane chemoreceptor Tar from Escherichia coli using site‐directed spin labeling and electron paramagnetic resonance (EPR) spectroscopy. Spin labels were positioned on solvent‐exposed helical faces because EPR spectra for such positions reflect primarily polypeptide backbone movements. We acquired spectra for spin‐labeled, intact receptor homodimers solubilized in detergent or inserted into native E. coli lipid bilayers in Nanodiscs, characterizing 16 positions distributed throughout the cytoplasmic domain and on both helices of its helical hairpins, one amino terminal to the membrane‐distal tight turn (N‐helix), and the other carboxyl terminal (C‐helix). Detergent solubilization increased backbone dynamics for much of the domain, suggesting that loss of receptor activities upon solubilization reflects wide‐spread destabilization. For receptors in either condition, we observed an unanticipated difference between the N‐ and C‐helices. For bilayer‐inserted receptors, EPR spectra from sites in the membrane‐distal protein‐interaction region and throughout the C‐helix were typical of well‐structured helices. In contrast, for approximately two‐thirds of the N‐helix, from its origin as the AS‐2 helix of the membrane‐proximal HAMP domain to the beginning of the membrane‐distal protein‐interaction region, spectra had a significantly mobile component, estimated by spectral deconvolution to average approximately 15%. Differential helical dynamics suggests a four‐helix bundle organization with a pair of core scaffold helices and two more dynamic partner helices. This newly observed feature of chemoreceptor structure could be involved in receptor function.
Investor perceptions of CEO successor selection in the wake of integrity and competence failures: A policy capturing study
Authors: Connelly Brian L. , Ketchen David J. , Gangloff K. Ashley , Shook Christopher L. 
Published: August 2015

Research summary: Drawing on theory about signaling, sensemaking, and the romance of leadership, we extend inquiry on investors' perceptions of CEO succession following misconduct. Whereas past studies have treated misconduct monolithically, we examine failures of integrity and competence separately. Using a policy capturing methodology that isolates investors' decision making from potential confounds, we find that, following an integrity failure, investors perceive outside and interim successors positively but inside successors negatively. Following a competence failure, investors perceive outside successors positively but are ambivalent toward inside and interim successors. Our findings indicate that whether an act of misconduct was an integrity failure or a competence failure, and what type of successor the firm chooses, are important considerations when using CEO succession as a means to restore investor confidence.Managerial summary: Business headlines regularly feature episodes of organizational misconduct, such as product safety problems, environmental violations, employee mistreatment, and securities lawsuits, and their aftermath. In such scenarios, shareholders demand answers from the people at the top, even if those people were not directly responsible for the problem. As a result, companies often fire the CEO as a means to restore investor confidence. Does this work? It depends on the type of misconduct and who is the CEO's successor. Following a competence failure, investors welcome the appointment of an outsider, but they are indifferent to inside and interim successors. Following an integrity failure, shareholders greet outside and interim CEO successors favorably while frowning on the promotion of insiders. Copyright © 2015 John Wiley & Sons, Ltd.
Prediction and Validation of the Austenite Phase Fraction upon Intercritical Annealing of Medium Mn Steels
Authors: Farahani Hussein , Xu Wei , van der Zwaag Sybrand 
Published: August 2015

Abstract

In this research, the effects of Mn and Si concentration and that of the isothermal intercritical holding temperature on the austenite-to-ferrite (γ → α) and the martensite-to-austenite (α′ → γ) phase transformations are studied for a series of Fe-C-Mn-Si steels with up to 7 wt pct Mn. The model is based on the local equilibrium (LE) concept. The model predictions are compared to experimental observations. It is found that the austenite volume fraction at the end of intercritical annealing depends significantly on the initial microstructure. For Mn concentrations between 3 and 7 wt pct, the LE model is qualitatively correct. However, at higher Mn levels the discrepancy between the predicted austenite fractions and the experimental values increases, in particular for the α′ → γ transformation. Intragrain nucleation is held responsible for the higher austenite fractions observed experimentally. Silicon is found have a much smaller effect on the kinetics of the intercritical annealing than Mn.
Drug trafficking in Guinea-Bissau, 1998–2014: the evolution of an elite protection network
Authors: Shaw Mark 
Published: August 2015

ABSTRACTGuinea-Bissau has been regularly described as a ‘narco-state’. Yet, few studies analyse how drug trafficking has evolved here. Based on extensive interviews in Guinea-Bissau over several years, this paper documents the process. It concludes that using the term ‘narco-state’, where much of the state has little or no capacity, is inappropriate. A better approach is to analyse the actions of key players as an elite protection network. In Guinea-Bissau, that network did not act on its own, but relied on a series of ‘entrepreneurs' who operated as an interface between traffickers and the elite. While the military as an institution is often said to be in charge of trafficking, exclusive control by high-ranking military personnel within the elite network only occurred relatively late. Senior soldiers' attempts to provide more than just protection, and to enter the drug market themselves, led to the network's undoing.
Between party capitalism and market reforms – understanding sector differences in Rwanda
Authors: Behuria Pritish 
Published: August 2015

ABSTRACTDifferent strategies have been used by the Rwandan government to promote capitalist accumulation. In some sectors, party and military owned enterprises are predominant. In others, the government has chosen to embrace market-led reforms. Ultimately, the vulnerability experienced by ruling elites contributes to the choice of how capital accumulation is promoted in different sectors. Ruling elites use party and military enterprises to centralise rents and establish control over the direction of economic policy. However, centralising rents is a political choice and excludes individuals from developing access to rents. The pyrethrum sector shows that the use of such groups has resulted in unequal outcomes despite increases in productivity. Reduced international prices have stunted further productivity. Conversely, the mining sector shows evidence of the pursuit of market-led reforms. These reforms have been accompanied by rapid growth in domestic production and exports. Foreign investment was necessary in order to bring capital and expertise to the sector. However, the government has struggled to retain the capacity to enforce legislation and discipline foreign investors in line with national priorities. Both sectors show evidence that ruling elites have been prompted by vulnerability to commit to economic development. Constraints that have accompanied strategies pursued in these sectors have forced the government to work ‘reactively’ to achieve strategic targets.
High diversity stabilizes the thermal resilience of pollinator communities in intensively managed grasslands
Authors: Kühsel Sara , Blüthgen Nico 
Published: August 2015

AbstractThe resilience of ecosystems depends on the diversity of species and their specific responses to environmental variation. Here we show that the diversity of climatic responses across species contributes to a higher projected resilience of species-rich pollinator communities in real-world ecosystems despite land-use intensification. We determined the thermal niche of 511 pollinator species (flies, bees, beetles and butterflies) in 40 grasslands. Species in intensively used grasslands have broader thermal niches and are also more complementary in their thermal optima. The observed increase in thermal resilience with land-use intensification is mainly driven by the dominant flies that prefer cooler temperatures and compensate for losses of other taxa. Temperature explained 84% of the variation in pollinator activity across species and sites. Given the key role of temperature, quantifying the diversity of thermal responses within functional groups is a promising approach to assess the vulnerability of ecosystems to land-use intensification and climate change.
Bacterioplankton community shifts associated with epipelagic and mesopelagic waters in the Southern Ocean
Authors: Yu Zheng , Yang Jun , Liu Lemian , Zhang Wenjing , Amalfitano Stefano 
Published: August 2015

AbstractThe Southern Ocean is among the least explored marine environments on Earth and still little is known about regional and vertical variability in the diversity of Antarctic marine prokaryotes. In this study, the bacterioplankton community in both epipelagic and mesopelagic waters was assessed at two adjacent stations by high-throughput sequencing and quantitative PCR. Water temperature was significantly higher in the superficial photic zone, while higher salinity and dissolved oxygen were recorded in the deeper water layers. The highest abundance of the bacterioplankton was found at a depth of 75 m, corresponding to the deep chlorophyll maximum layer. Both Alphaproteobacteria and Gammaproteobacteria were the most abundant taxa throughout the water column, while more sequences affiliated to Cyanobacteria and unclassified bacteria were identified from surface and the deepest waters, respectively. Temperature was the most significant environmental variable affecting the bacterial community structure. The bacterial community composition displayed significant differences at the epipelagic layers between two stations, whereas those in the mesopelagic waters were more similar to each other. Our results indicated that the epipelagic bacterioplankton might be dominated by short-term environmental variable conditions, whereas the mesopelagic communities appeared to be structured by longer water-mass residence time and relative stable environmental factors.
Gene expression in breastmilk cells is associated with maternal and infant characteristics
Authors: Twigger Alecia-Jane , Hepworth Anna R. , Tat Lai Ching , Chetwynd Ellen , Stuebe Alison M. , Blancafort Pilar , Hartmann Peter E. , Geddes Donna T. , Kakulas Foteini 
Published: August 2015

AbstractBreastmilk is a rich source of cells with a heterogeneous composition comprising early-stage stem cells, progenitors and more differentiated cells. The gene expression profiles of these cells and their associations with characteristics of the breastfeeding mother and infant are poorly understood. This study investigated factors associated with the cellular dynamics of breastmilk and explored variations amongst women. Genes representing different breastmilk cell populations including mammary epithelial and myoepithelial cells, progenitors and multi-lineage stem cells showed great variation in expression. Stem cell markers ESRRB and CK5, myoepithelial marker CK14 and lactocyte marker α-lactalbumin were amongst the genes most highly expressed across all samples tested. Genes exerting similar functions, such as either stem cell regulation or milk production, were found to be closely associated. Infant gestational age at delivery and changes in maternal bra cup size between pre-pregnancy and postpartum lactation were associated with expression of genes controlling stemness as well as milk synthesis. Additional correlations were found between genes and dyad characteristics, which may explain abnormalities related to low breastmilk supply or preterm birth. Our findings highlight the heterogeneity of breastmilk cell content and its changes associated with characteristics of the breastfeeding dyad that may reflect changing infant needs.
Tumor Suppressor WWOX inhibits osteosarcoma metastasis by modulating RUNX2 function
Authors: Del Mare Sara , Aqeilan Rami I. 
Published: August 2015

AbstractOsteosarcoma (OS) is among the most frequently occurring primary bone tumors, primarily affecting adolescents and young adults. This malignant osteoid forming tumor is characterized by its metastatic potential, mainly to lungs. We recently demonstrated that WW domain-containing oxidoreductase (WWOX) is frequently inactivated in human OS and that WWOX restoration in WWOX-negative OS cells suppresses tumorigenicity. Of note, WWOX levels are reduced in paired OS samples of post-treatment metastastectomies as compared to pre-treatment biopsies suggesting that decreased WWOX levels are associated with a more aggressive phenotype at the metastatic site. Nevertheless, little is known about WWOX function in OS metastasis. Here, we investigated the role of tumor suppressor WWOX in suppressing pulmonary OS metastasis bothin vitroandin vivo. We demonstrated that ectopic expression of WWOX in OS cells, HOS and LM-7, inhibits OS invasion and cell migration in vitro. Furthermore, WWOX expression reduced tumor burden in vivo and inhibited metastases’ seeding and colonization. Mechanistically, WWOX function is associated with reduced levels of RUNX2 metastatic target genes implicated in adhesion and motility. Our results suggest that WWOX plays a critical role in determining the aggressive phenotype of OS and its expression could be an attractive therapeutic target to combat this devastating adolescent disease.
White matter alterations in first episode treatment-naïve patients with deficit schizophrenia: a combined VBM and DTI study
Authors: Lei Wei , Li Na , Deng Wei , Li Mingli , Huang Chaohua , Ma Xiaohong , Wang Qiang , Guo Wanjun , Li Yinfei , Jiang Lijun , Zhou Yi , Hu Xun , Mary McAlonan Grainne , Li Tao 
Published: August 2015

AbstractCategorizing ‘deficit schizophrenia’ (DS) as distinct from ‘non-deficit’ schizophrenia (NDS) may help reduce heterogeneity within schizophrenia. However, it is unknown if DS has a discrete white matter signature. Here we used MRI to compare white matter volume (voxel-based morphometry) and microstructural integrity (fractional anisotropy, FA) in first-episode treatment-naïve patients with DS and NDS and their unaffected relatives to control groups of similar age. We found that white matter disruption was prominent in DS compared to controls; the DS group had lower volumes in the cerebellum, bilateral extra-nuclear and bilateral frontoparietal regions and lower FA in the body of corpus callosum, posterior superior longitudinal fasciculus and uncinate fasciculus. The DS group also had lower volume in bilateral extra-nuclear regions compared to NDS and the volume of these clusters was negatively correlated with deficit symptom ratings. NDS patients however, had no significant volume alterations and limited disruption of microstructural integrity compared to controls. Finally, first-degree relatives of those with DS shared volume abnormalities in right extra-nuclear white matter. Thus, white matter pathology in schizophrenia is most evident in the deficit condition and lower extra-nuclear white matter volumes in both DS patients and their relatives may represent a brain structural ‘endophenotype’ for DS.
miR-378a-3p modulates tamoxifen sensitivity in breast cancer MCF-7 cells through targeting GOLT1A
Authors: Ikeda Kazuhiro , Horie-Inoue Kuniko , Ueno Toshihide , Suzuki Takashi , Sato Wataru , Shigekawa Takashi , Osaki Akihiko , Saeki Toshiaki , Berezikov Eugene , Mano Hiroyuki , Inoue Satoshi 
Published: August 2015

AbstractBreast cancer is a hormone-dependent cancer and usually treated with endocrine therapy using aromatase inhibitors or anti-estrogens such as tamoxifen. A majority of breast cancer, however, will often fail to respond to endocrine therapy. In the present study, we explored miRNAs associated with endocrine therapy resistance in breast cancer. High-throughput miRNA sequencing was performed using RNAs prepared from breast cancer MCF-7 cells and their derivative clones as endocrine therapy resistant cell models, including tamoxifen-resistant (TamR) and long-term estrogen-deprived (LTED) MCF-7 cells. Notably, miR-21 was the most abundantly expressed miRNA in MCF-7 cells and overexpressed in TamR and LTED cells. We found that miR-378a-3p expression was downregulated in TamR and LTED cells as well as in clinical breast cancer tissues. Additionally, lower expression levels of miR-378a-3p were associated with poor prognosis for tamoxifen-treated patients with breast cancer. GOLT1A was selected as one of the miR-378a-3p candidate target genes by in silico analysis. GOLT1A was overexpressed in breast cancer specimens and GOLT1A-specific siRNAs inhibited the growth of TamR cells. Low GOLT1A levels were correlated with better survival in patients with breast cancer. These results suggest that miR-378a-3p-dependent GOLT1A expression contributes to the mechanisms underlying breast cancer endocrine resistance.
Activation mechanisms for the cystic fibrosis transmembrane conductance regulator protein involve direct binding of cAMP
Authors: Pereira Malcolm M. C. , Parker Jody , Stratford Fiona L. L. , McPherson Margaret , Dormer Robert L. 
Published: August 2015

The CFTR [CF (cystic fibrosis) transmembrane conductance regulator] chloride channel is activated by cyclic nucleotide-dependent phosphorylation and ATP binding, but also by non-phosphorylation-dependent mechanisms. Other CFTR functions such as regulation of exocytotic protein secretion are also activated by cyclic nucleotide elevating agents. A soluble protein comprising the first NBD (nucleotide-binding domain) and R-domain of CFTR (NBD1–R) was synthesized to determine directly whether CFTR binds cAMP. An equilibrium radioligand-binding assay was developed, firstly to show that, as for full-length CFTR, the NBD1–R protein bound ATP. Half-maximal displacement of [3H]ATP by non-radioactive ATP at 3.5 μM and 3.1 mM was demonstrated. [3H]cAMP bound to the protein with different affinities from ATP (half-maximal displacement by cAMP at 2.6 and 167 μM). Introduction of a mutation (T421A) in a motif predicted to be important for cyclic nucleotide binding decreased the higher affinity binding of cAMP to 9.2 μM. The anti-CFTR antibody (MPNB) that inhibits CFTR-mediated protein secretion also inhibited cAMP binding. Thus binding of cAMP to CFTR is consistent with a role in activation of protein secretion, a process defective in CF gland cells. Furthermore, the binding site may be important in the mechanism by which drugs activate mutant CFTR and correct defective ΔF508-CFTR trafficking.
The effects of truncations of the small subunit on m-calpain activity and heterodimer formation
Authors: ELCE John S. , DAVIES Peter L. , HEGADORN Carol , MAURICE Donald H. , ARTHUR J. Simon C. 
Published: August 2015

In order to study subunit interactions in calpain, the effects of small subunit truncations on m-calpain activity and heterodimer formation have been measured. It has been shown previously that active calpain is formed by co-expression of the large subunit (80 kDa) of rat m-calpain with a δ86 form (21 kDa) of the small subunit. cDNA for the full-length 270 amino acid (28.5 kDa) rat calpain small subunit has now been cloned, both with and without an N-terminal histidine tag (NHis10). The full-length small subunit constructs yielded active calpains on co-expression with the large subunit, and the small subunit was autolysed to 20 kDa on exposure of these calpains to Ca2+. A series of deletion mutants of the small subunit, NHis10-δ86,-δ99, -δ107, and -δ116, gave active heterodimeric calpains with unchanged specific activities, although in decreasing yield, and with a progressive decrease in stability. NHis10-δ125 formed a heterodimer which was inactive and unstable. Removal of 25 C-terminal residues from δ86, leaving residues 87–245, abolished both activity and heterodimer formation. The results show that: (a) generation of active m-calpain in Escherichia coli requires heterodimer formation; (b) small subunit residues between 94 and 116 contribute to the stability of the active heterodimer but do not directly affect the catalytic mechanism; (c) residues in the region 245–270 are essential for subunit binding. Finally, it was shown that an inactive mutant Cys105 → Ser-80k/δ86 calpain, used in order to preclude autolysis, did not dissociate in the presence of Ca2+, a result which does not support the proposal that Ca2+-induced dissociation is involved in calpain activation.