bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bronchoalveolar lavage in infants with recurrent lower respiratory symptoms
Authors: Malmström Kristiina , Lehto Maili , Majuri Marja‐Leena , Paavonen Timo , Sarna Seppo , Pelkonen Anna S , Malmberg L Pekka , Lindahl Harry , Kajosaari Merja , Saglani Sejal , Alenius Harri , Mäkelä Mika J 
Published: October 2014

AbstractBackgroundFew data are available about the inflammatory cytokine profile of bronchoalveolar lavage (BAL) from young children with frequent wheeze. The first aim was to investigate the BAL cellular and cytokine profiles in infants with recurrent lower respiratory symptoms in whom bronchoscopy was indicated for clinical symptom evaluation. The second aim was to relate the BAL results with the histological findings of the endobronchial carina biopsies.MethodsThirty‐nine infants (median age 0.9 years) underwent lung function testing by whole‐body plethysmography prior to the bronchoscopy. The BAL differential cell counts and cytokine levels were quantified. These findings were compared with the histological findings of the endobronchial carina biopsies.ResultsThe differential cytology reflected mainly that described for healthy infants with lymphocyte counts at the upper range level. A positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement membrane was found. Detectable levels of pro‐inflammatory cytokine proteins IL‐1β, IL‐17A, IL‐18, IL‐23, and IL‐33 were found, whereas levels of Th2‐type cytokine proteins were low. Frequent wheeze was the only clinical characteristic significantly related to detectable combined pro‐inflammatory cytokine profile. Lung function did not correlate with any cytokine.ConclusionsA positive association between BAL CD8+ lymphocytes and neutrophils and endobronchial reticular basement thickness was found. Detectable production of pro‐inflammatory cytokines associated positively with frequent wheeze.
Leptin induces upregulation of sphingosine kinase 1 in oestrogen receptor-negative breast cancer via Src family kinase-mediated, janus kinase 2-independent pathway
Authors: Alshaker Heba , Krell Jonathan , Frampton Adam E , Waxman Jonathan , Blyuss Oleg , Zaikin Alexey , Winkler Mathias , Stebbing Justin , Yagüe Ernesto , Pchejetski Dmitri 
Published: October 2014

Abstract
Introduction
Obesity is a known risk factor for breast cancer. Sphingosine kinase 1 (SK1) is an oncogenic lipid kinase that is overexpressed in breast tumours and linked with poor prognosis, however, its role in obesity-driven breast cancer was never elucidated.

Methods
Human primary and secondary breast cancer tissues were analysed for SK1 and leptin receptor expression using quantitative real-time polymerase chain reaction (qRT-PCR) assay. Leptin-induced signalling was analysed in human oestrogen receptor (ER)-positive and negative breast cancer cells using Western blotting, qRT-PCR and radiolabelling assays.

Results
Our findings show for the first time that human primary breast tumours and associated lymph node metastases exhibit a strong correlation between SK1 and leptin receptor expression (Pearson R = 0.78 and R = 0.77, respectively, P <0.001). Both these genes are elevated in metastases of ER-negative patients and show a significant increase in patients with higher body mass index (BMI). Leptin induces SK1 expression and activation in ER-negative breast cancer cell lines MDAMB-231 and BT-549, but not in ER-positive cell lines. Pharmacological inhibition and gene knockdown showed that leptin-induced SK1 activity and expression are mediated by activation of extracellular signal-regulated kinases 1/2 (ERK1/2) and Src family kinase (SFK) pathways, but not by the major pathways downstream of leptin receptor (LEPR) - janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). Src-homology 2 domain-containing phosphatase 2 (SHP2) appeared to be key to SK1 activation, and may function as an adaptor protein between SFKs and LEPR. Importantly, leptin-induced breast cancer cell proliferation was abrogated by SK1-specific small interfering RNA (siRNA).

Conclusions
Overall, our findings demonstrate a novel SFK/ERK1/2-mediated pathway that links leptin signalling and expression of oncogenic enzyme SK1 in breast tumours and suggest the potential significance of this pathway in ER-negative breast cancer.
Ubiquitin-specific proteases as therapeutic targets for the treatment of breast cancer
Authors: Pal Anupama , Donato Nicholas J 
Published: October 2014

AbstractKey mediators of signaling pathways in breast cancer involve post-translational protein modification, primarily mediated through phosphorylation and ubiquitination. While previous studies focused on phosphorylation events, more recent analysis suggests that ubiquitin plays a parallel and equally important role in several signaling and cell regulatory events in breast cancer. Availability of new tools capable of sensitive detection of gene mutations and aberrant expression of genes and proteins coupled with gene-specific knockdown and silencing protocols have provided insight into the previously unexplored ubiquitin regulatory process within these tumors. Ubiquitin-specific proteases are one class of enzymes with protein deubiquitinating activity, making up the majority of protein deubiquitinating diversity within mammalian cells. Ubiquitin-specific proteases are also emerging as potential therapeutic targets in many diseases, including cancer. In this report, we summarize the involvement of this class of enzymes in breast cancer signaling and cell regulation and illustrate the potential for additional studies to define novel targets and approaches in breast cancer therapy.
Improved characterization of medically relevant fungi in the human respiratory tract using next-generation sequencing
Authors: Bittinger Kyle , Charlson Emily S , Loy Elizabeth , Shirley David J , Haas Andrew R , Laughlin Alice , Yi Yanjie , Wu Gary D , Lewis James D , Frank Ian , Cantu Edward , Diamond Joshua M , Christie Jason D , Collman Ronald G , Bushman Frederic D 
Published: October 2014

Abstract
Background
Fungi are important pathogens but challenging to enumerate using next-generation sequencing because of low absolute abundance in many samples and high levels of fungal DNA from contaminating sources.

Results
Here, we analyze fungal lineages present in the human airway using an improved method for contamination filtering. We use DNA quantification data, which are routinely acquired during DNA library preparation, to annotate output sequence data, and improve the identification and filtering of contaminants. We compare fungal communities and bacterial communities from healthy subjects, HIV+ subjects, and lung transplant recipients, providing a gradient of increasing lung impairment for comparison. We use deep sequencing to characterize ribosomal rRNA gene segments from fungi and bacteria in DNA extracted from bronchiolar lavage samples and oropharyngeal wash. Comparison to clinical culture data documents improved detection after applying the filtering procedure.

Conclusions
We find increased representation of medically relevant organisms, including Candida, Cryptococcus, and Aspergillus, in subjects with increasingly severe pulmonary and immunologic deficits. We analyze covariation of fungal and bacterial taxa, and find that oropharyngeal communities rich in Candida are also rich in mitis group Streptococci, a community pattern associated with pathogenic polymicrobial biofilms. Thus, using this approach, it is possible to characterize fungal communities in the human respiratory tract more accurately and explore their interactions with bacterial communities in health and disease.
mirMark: a site-level and UTR-level classifier for miRNA target prediction
Authors: Menor Mark , Ching Travers , Zhu Xun , Garmire David , Garmire Lana X 
Published: October 2014

AbstractMiRNAs play important roles in many diseases including cancers. However computational prediction of miRNA target genes is challenging and the accuracies of existing methods remain poor. We report mirMark, a new machine learning-based method of miRNA target prediction at the site and UTR levels. This method uses experimentally verified miRNA targets from miRecords and mirTarBase as training sets and considers over 700 features. By combining Correlation-based Feature Selection with a variety of statistical or machine learning methods for the site- and UTR-level classifiers, mirMark significantly improves the overall predictive performance compared to existing publicly available methods. MirMark is available from https://github.com/lanagarmire/MirMark.
Wastewater treatment using integrated anaerobic baffled reactor and Bio-rack wetland planted with Phragmites sp. and Typha sp.
Authors: Jamshidi Shervin , Akbarzadeh Abbas , Woo Kwang-Sung , Valipour Alireza 
Published: October 2014

Abstract
The purpose of this study is to examine the potential use of anaerobic baffled reactor (ABR) followed by Bio-rack wetland planted with Phragmites sp. and Typha sp. for treating domestic wastewater generated by small communities (751 mg COD/L, 500 SCOD mg/L, 348 mg BOD5/L). Two parallel laboratory-scale models showed that the process planted with Phragmites sp. and Typha sp. are capable of removing COD by 87% & 86%, SCOD by 90% & 88%, BOD5 by 93% & 92%, TSS by 88% & 86%, TN by 79% & 77%, PO4-P by 21% & 14% at an overall HRT of 21 (843 g COD/m3/day & 392 g BOD5/m3/day) and 27 (622 g COD/m3/day & 302 g BOD5/m3/day) hours, respectively. Microbial analysis indicated a high reduction in the MPN of total coliform and TVC as high as 99% at the outlet end of the processes. The vegetated system using Phragmites sp. showed significantly greater (p <0.05) pollutant removal efficiencies due to its extensive root and mass growth rate (p <0.05) of the plant compared to Typha sp. The Phragmites sp. indicated a higher relative growth rate (3.92%) than Typha sp. (0.90%). Microorganisms immobilized on the surface of the Bio-rack media (mean TVC: 2.33 × 107 cfu/cm2) were isolated, identified and observed using scanning electron microscopy (SEM). This study illustrated that the present integrated processes could be an ideal approach for promoting a sustainable decentralization, however, Phragmites sp. would be more efficient rather than Typha sp.
Characterization of B and plasma cells in blood, bone marrow, and secondary lymphoid organs of rhesus macaques by multicolor flow cytometry
Authors: Neumann Berit , Klippert Antonina , Raue Katharina , Sopper Sieghart , Stahl-Hennig Christiane 
Published: October 2014

Abstract
B cells, as an important part of the humoral immune response, are generated in the BM, migrate to secondary lymphoid organs, and upon activation, differentiate into antibody-producing memory B cells or plasma cells. Despite the pivotal roles that they play in different diseases, a comprehensive characterization in healthy rhesus macaques, which serve as valuable models for a variety of human diseases, is still missing. With the use of multiparameter flow cytometry, we analyzed B cells in BM collected from two locations, i.e., the iliac crest (BMca) and the femur (BMfem), PB, as well as secondary lymphoid organs of healthy rhesus macaques. We assessed the frequencies of immature and mature B cells, as well as CD19+ CD20– CD38+/++ CD138+/++ plasmablasts/plasma cells. Furthermore, we found site-specific differences in the expression of markers for B cell activation and proliferation, chemokine receptors and Igs, as well as the distribution of memory B cell subpopulations. As secondary lymphoid organs harbor the highest frequencies of naive B cells, expression of CD80, CD95, and Ki67 was lower compared with B cells in the periphery and BM, whereas expression of IgD, CXCR4 (CD184), and CCR7 (CD197) was higher. Interestingly, BMca differed from BMfem regarding frequencies of B cells, their expression of CD80 and CXCR4, T cells, and plasma cells. In summary, these data identify baseline values for the above-mentioned parameters and provide the foundation for future studies on B and plasma cells in different diseases.
Beta-casein nanocarriers of celecoxib for improved oral bioavailability
Authors: Perlstein Hadas , Bavli Yaelle , Turovsky Tanya , Rubinstein Abraham , Danino Dganit , Stepensky David , Barenholz Yechezkel 
Published: October 2014

AbstractBeta-casein (bCN) micelles were developed as a platform for improved oral bioavailability (BA) of poorly water-soluble drugs. Here we demonstrate a proof-of-concept using the NSAID celecoxib (Cx) loaded into bCN micelles (Cx/bCN). In a crossover pharmacokinetic (PK) study in pigs (n=4), dosed intraduodenally with either the commercial Cx formulation Celebra
Changes in Public Opinion and the Occurrence of International Terrorism
Authors: Malečková Jitka , Stanišić Dragana 
Published: October 2014

AbstractThis paper is a contribution to the study of the impact of public opinion and evolutions in opinion on the occurrence of international terrorism. First, we replicate Krueger and Malečková’s (2009) model of the relationship between attitudes towards world leaders and occurrences of international terrorist incidents, using more recent data-the Gallup Survey data from 2010 on public opinion in Middle Eastern and North African countries and the National Counterterrorism Center (NCTC) data on international terrorism from 2009 to 2011. The analysis confirms the model of the earlier study, although, due to the distribution of terrorist incidents in the new sample, the evidence of the correlation between terrorist attacks and public opinion weakens. Second, we exercise an out-of-sample prediction of terrorist attacks using the estimated model based on the data from the 2004 to 2008 period to predict the occurrence of attacks in 2009–2011. The findings suggest that Krueger and Malečková’s (2009) model is unstable, either due to the instability of the process or the problematic nature of terrorism data. Further research is necessary to explain and test these results.
Neuroinflammation and demyelination from the point of nitrosative stress as a new target for neuroprotection
Authors: Ljubisavljevic Srdjan , Stojanovic Ivana 
Published: October 2014

AbstractThe role of nitrosative stress in the early pathogenesis of neuroinflammation and demyelination is undoubtedly wide. This review summarizes and integrates the results, found in previously performed studies, which have evaluated nitrosative stress participation in neuroinflammation. The largest number of studies indicates that the supply of nitrosative stress inhibitors has led to the opposite clinical effects in experimental studies. Some results claim that attributing the protective role to nitric oxide, outside the total changes of redox oxidative processes and without following the clinical and paraclinical correlates of neuroinflammation, is an overrated role of this mediator. The fact is that the use of nitrosative stress inhibitors would be justified in the earlier phases of neuroinflammation. The ideal choice would be a specific inducible nitric oxide synthase (iNOS) inhibitor, because its use would preserve the physiological features of nitric oxide produced by the effects of constitutive NOS. This review discusses the antinitrosative therapy as a potential mode of therapy that aims to control neuroinflammation in early phases, delaying its later phases, which are accompanied with irreversible neurological disabilities. Some parameters of nitrosative stress might serve as surrogate biomarkers for neuroinflammation intensity and its radiological and clinical correlates.
Temperature- and moisture-dependency of CsLiB6O10. A new phase, β-CsLiB6O10
Authors: Sennova Natalia A. , Cordier Gerhard , Albert Barbara , Filatov Stanislav K. , Bubnova Rimma S. , Isaenko Ludmila I. , Gubenko Lyubov I. , Klöckner Jan-Peter , Prosenc Marc H. 
Published: October 2014

Abstract
The structural behavior of the non-linear optical, nanoporous compound CsLiB6O10 was studied in a wide temperature range. Both the highly anisotropic thermal expansion of the borate with temperature variation and the deterioration of its crystals were investigated. The electron density distribution was analyzed in detail. A reversible, partial transition to a new modification, β-CsLiB6O10, was observed during cooling crystalline and moist samples of CsLiB6O10 to –25 °C. The crystal structure of the new phase is described.
Microstructure-Scale In-Situ Image Correlation-Based Study of Grain Deformation and Crack Tip Displacements in Al–Cu Alloys
Authors: Gupta Vipul K. , Willard Scott A. , Hochhalter Jacob D. , Smith Stephen W. 
Published: October 2014

Abstract
Mechanistic understanding based on experimental measurements of grain and crack tip deformation at relevant length scales is critical for improvement of physics-based modeling of microstructurally-sensitive fatigue crack propagation and for the computationally-assisted design of more durable materials. In this study, single-crystal, bi-crystal, and large-grain multi-crystal specimens of Al–Cu alloys are fabricated, characterized using electron backscattered diffraction (EBSD), and mechanically tested. In addition to conventional optic al–imaging based 3D image correlation (IC), scanning electron microscope (SEM) based high-resolution 2D IC is used to measure displacements within grain interiors, near crack tips, and grain boundaries. The use of micro-scale IC and EBSD-based experiments is discussed as they relate to the development of crystal-plasticity-based finite element models (CP–FEMs). This article specifically highlights experimental methods that have been developed to obtain the relevant data needed for CP–FEM calibration and validation.
Visceral adiposity index and DHEAS are useful markers of diabetes risk in women with polycystic ovary syndrome
Authors: Amato M C , Magistro A , Gambino G , Vesco R , Giordano C 
Published: October 2014

ObjectiveOn the basis of the known diabetes risk in polycystic ovary syndrome (PCOS), recent guidelines of the Endocrine Society recommend the use of an oral glucose tolerance test (OGTT) to screen for impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) in all women with PCOS. However, given the high prevalence of PCOS, OGTT would have a high cost–benefit ratio. In this study, we identified, through a receiver operating characteristic analysis, simple predictive markers of the composite endpoint (impaired fasting glucose (IFG) or IGT or IFG+IGT or T2DM) in women with PCOS according to the Rotterdam criteria.DesignWe conducted a cross-sectional study of 241 women with PCOS in a university hospital setting.MethodsClinical, anthropometric, and metabolic (including OGTT) parameters were evaluated. The homeostasis model assessment of insulin resistance (HOMA2-IR), the Matsuda index of insulin sensitivity, and the oral dispositional index and visceral adiposity index (VAI) were determined.ResultsOut of 241 women included in this study, 28 (11.6%) had an IFG, 13 (5.4%) had IGT, four (1.7%) had IFG+IGT, and four (1.7%) had T2DM. Among the anthropometric variables examined, the VAI had a significantly higher C-statistic compared with BMI (0.760 (95% CI: 0.70–0.81) vs 0.613 (95% CI: 0.54–0.67);P=0.014) and waist circumference (0.760 (95% CI: 0.70–0.81) vs 0.619 (95% CI: 0.55–0.68);P=0.028). Among all the hormonal and metabolic serum variables examined, DHEAS showed the highest C-statistic (0.720 (95% CI: 0.65–0.77);P<0.001).ConclusionsIn addition to fasting glucose, the VAI and DHEAS may be considered useful tools for prescreening in all women with PCOS without the classical risk factors for diabetes.
A Novel Cholinergic Action of Alcohol and the Development of Tolerance to That Effect inCaenorhabditis elegans
Authors: Hawkins Edward G , Martin Ian , Kondo Lindsay M , Judy Meredith E , Brings Victoria E , Chan Chung-Lung , Blackwell GinaMari G , Bettinger Jill C , Davies Andrew G 
Published: October 2014

AbstractUnderstanding the genes and mechanisms involved in acute alcohol responses has the potential to allow us to predict an individual’s predisposition to developing an alcohol use disorder. To better understand the molecular pathways involved in the activating effects of alcohol and the acute functional tolerance that can develop to such effects, we characterized a novel ethanol-induced hypercontraction response displayed by Caenorhabditis elegans. We compared body size of animals prior to and during ethanol treatment and showed that acute exposure to ethanol produced a concentration-dependent decrease in size followed by recovery to their untreated size by 40 min despite continuous treatment. An increase in cholinergic signaling, leading to muscle hypercontraction, is implicated in this effect because pretreatment with mecamylamine, a nicotinic acetylcholine receptor (nAChR) antagonist, blocked ethanol-induced hypercontraction, as did mutations causing defects in cholinergic signaling (cha-1 and unc-17). Analysis of mutations affecting specific subunits of nAChRs excluded a role for the ACR-2R, the ACR-16R, and the levamisole-sensitive AChR and indicated that this excitation effect is dependent on an uncharacterized nAChR that contains the UNC-63 α-subunit. We performed a forward genetic screen and identified eg200, a mutation that affects a conserved glycine in EAT-6, the α-subunit of the Na+/K+ ATPase. The eat-6(eg200) mutant fails to develop tolerance to ethanol-induced hypercontraction and remains contracted for at least 3 hr of continuous ethanol exposure. These data suggest that cholinergic signaling through a specific α-subunit-containing nAChR is involved in ethanol-induced excitation and that tolerance to this ethanol effect is modulated by Na+/K+ ATPase function.
Protein Kinases Are Associated with Multiple, Distinct Cytoplasmic Granules in Quiescent Yeast Cells
Authors: Shah Khyati H , Nostramo Regina , Zhang Bo , Varia Sapna N , Klett Bethany M , Herman Paul K 
Published: October 2014

Abstract
The cytoplasm of the eukaryotic cell is subdivided into distinct functional domains by the presence of a variety of membrane-bound organelles. The remaining aqueous space may be further partitioned by the regulated assembly of discrete ribonucleoprotein (RNP) complexes that contain particular proteins and messenger RNAs. These RNP granules are conserved structures whose importance is highlighted by studies linking them to human disorders like amyotrophic lateral sclerosis. However, relatively little is known about the diversity, composition, and physiological roles of these cytoplasmic structures. To begin to address these issues, we examined the cytoplasmic granules formed by a key set of signaling molecules, the protein kinases of the budding yeast Saccharomyces cerevisiae. Interestingly, a significant fraction of these proteins, almost 20%, was recruited to cytoplasmic foci specifically as cells entered into the G0-like quiescent state, stationary phase. Colocalization studies demonstrated that these foci corresponded to eight different granules, including four that had not been reported previously. All of these granules were found to rapidly disassemble upon the resumption of growth, and the presence of each was correlated with cell viability in the quiescent cultures. Finally, this work also identified new constituents of known RNP granules, including the well-characterized processing body and stress granule. The composition of these latter structures is therefore more varied than previously thought and could be an indicator of additional biological activities being associated with these complexes. Altogether, these observations indicate that quiescent yeast cells contain multiple distinct cytoplasmic granules that may make important contributions to their long-term survival.