bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exome analysis of HIV patients submitted to dendritic cells therapeutic vaccine reveals an association of CNOT1 gene with response to the treatment
Authors: Moura Ronald , Pontillo Alessandra , D'Adamo Pio , Pirastu Nicola , Coelho Antonio Campos , Crovella Sergio 
Published: January 2014

IntroductionWith the aim of searching genetic factors associated with the response to an immune treatment based on autologous monocyte‐derived dendritic cells pulsed with autologous inactivated HIV, we performed exome analysis by screening more than 240,000 putative functional exonic variants in 18 HIV‐positive Brazilian patients that underwent the immune treatment.MethodsExome analysis has been performed using the ILLUMINA Infinium HumanExome BeadChip. zCall algorithm allowed us to recall rare variants. Quality control and SNP‐centred analysis were done with GenABEL R package. An in‐house implementation of the Wang method permitted gene‐centred analysis.ResultsCCR4‐NOT transcription complex, subunit 1 (CNOT1) gene (16q21), showed the strongest association with the modification of the response to the therapeutic vaccine (p=0.00075). CNOT1 SNP rs7188697 A/G was significantly associated with DC treatment response. The presence of a G allele indicated poor response to the therapeutic vaccine (p=0.0031; OR=33.00; CI=1.74–624.66), and the SNP behaved in a dominant model (A/A vs. A/G+G/G p=0.0009; OR=107.66; 95% CI=3.85–3013.31), being the A/G genotype present only in weak/transient responders, conferring susceptibility to poor response to the immune treatment.DiscussionCNOT1 is known to be involved in the control of mRNA deadenylation and mRNA decay. Moreover, CNOT1 has been recently described as being involved in the regulation of inflammatory processes mediated by tristetraprolin (TTP). The TTP‐CCR4‐NOT complex (CNOT1 in the CCR4‐NOT complex is the binding site for TTP) has been reported as interfering with HIV replication, through post‐transcriptional control. Therefore, we can hypothesize that genetic variation occurring in the CNOT1 gene could impair the TTP‐CCR4‐NOT complex, thus interfering with HIV replication and/or host immune response.ConclusionsBeing aware that our findings are exclusive to the 18 patients studied with a need for replication, and that the genetic variant of CNOT1 gene, localized at intron 3, has no known functional effect, we propose a novel potential candidate locus for the modulation of the response to the immune treatment, and open a discussion on the necessity to consider the host genome as another potential variant to be evaluated when designing an immune therapy study.
Assessing lidar‐based classification schemes for polar stratospheric clouds based on 16 years of measurements at Esrange, Sweden
Authors: Achtert P. , Tesche M. 
Published: January 2014

AbstractLidar measurements of polar stratospheric clouds (PSCs) are commonly analyzed in classification schemes that apply the backscatter ratio and the particle depolarization ratio. This similarity of input data suggests comparable results of different classification schemes—despite measurements being performed with a variety of mostly custom‐made instruments. Based on a time series of 16 years of lidar measurements at Esrange (68°N, 21°E), Sweden, we show that PSC classification differs substantially depending on the applied scheme. The discrepancies result from varying threshold values of lidar‐derived parameters used to define certain PSC types. The resulting inconsistencies could impact the understanding of long‐term PSC observations documented in the literature. We identify two out of seven considered classification schemes that are most likely to give reliable results and should be used in future lidar‐based studies. Using polarized backscatter ratios gives the advantage of increased contrast for observations of weakly backscattering and weakly depolarizing particles. Improved confidence in PSC classification can be achieved by a more comprehensive consideration of the effect of measurement uncertainties. The particle depolarization ratio is the key to a reliable identification of different PSC types. Hence, detailed information on the calibration of the polarization‐sensitive measurement channels should be provided to assess the findings of a study. Presently, most PSC measurements with lidar are performed at 532 nm only. The information from additional polarization‐sensitive measurements in the near infrared could lead to an improved PSC classification. Coincident lidar‐based temperature measurements at PSC level might provide useful information for an assessment of PSC classification.
Probiotic manipulation of the chronic rhinosinusitis microbiome
Authors: Cleland Edward John , Drilling Amanda , Bassiouni Ahmed , James Craig , Vreugde Sarah , Wormald Peter‐John 
Published: January 2014

BackgroundStaphylococcus aureus (SA) is a key pathogenic component of the chronic rhinosinusitis (CRS) microbiome and is associated with increased disease severity and poor postoperative outcomes. Probiotic treatments potentially offer a novel approach to the management of pathogenic bacteria in these recalcitrant patients through supporting a healthy community of commensal species. This study aims to investigate the probiotic properties of Staphylococcus epidermidis (SE) against SA in a mouse model of sinusitis.MethodsTwenty C57/BL6 mice received intranasal inoculations of phosphate buffered saline (PBS), SE, SA, or a combination of SE and SA (SE+SA) for 3 days. Following euthanasia, the mouse snouts were harvested and prepared for histological analysis. Counts of periodic acid–Schiff (PAS)‐positive goblet cells were the primary outcome measure.ResultsGoblet cell counts were significantly higher in both the SA and SE+SA groups compared to those receiving PBS or SE alone (p < 0.05). However, the SE+SA group demonstrated significantly lower goblet cell counts compared to the SA group (p < 0.05). Mice receiving SE alone did not show a significant difference to those receiving PBS (p > 0.05). The presence of SA postinoculation was confirmed by culture in both the SA and SE+SA groups.ConclusionThis study confirms the probiotic potential of SE against SA in a mouse model of sinusitis. Although the interactions that occur between many probiotic species and pathogens are yet to be fully understood, studies such as this support further exploration of ecologically‐based treatment paradigms for the management of CRS.
Nonclinical pharmacokinetics and metabolism of EPZ‐5676, a novel DOT1L histone methyltransferase inhibitor
Authors: Basavapathruni Aravind , Olhava Edward J. , Daigle Scott R. , Therkelsen Carly A. , Jin Lei , Boriack‐Sjodin P. Ann , Allain Christina J. , Klaus Christine R. , Raimondi Alejandra , Scott Margaret Porter , Dovletoglou Angelos , Richon Victoria M. , Pollock Roy M. , Copeland Robert A. , Moyer Mikel P. , Chesworth Richard , Pearson Paul G. , Waters Nigel J. 
Published: January 2014

ABSTRACT(2R,3R,4S,5R)‐2‐(6‐Amino‐9H‐purin‐9‐yl)‐5‐((((1r,3S)‐3‐(2‐(5‐(tert‐butyl)‐1H‐benzo[d]imidazol‐2‐yl)ethyl)cyclobutyl)(isopropyl)amino)methyl)tetrahydrofuran‐3,4‐diol (EPZ‐5676) is a novel DOT1L histone methyltransferase inhibitor currently in clinical development for the treatment of MLL‐rearranged leukemias. This report describes the preclinical pharmacokinetics and metabolism of EPZ‐5676, an aminonucleoside analog with exquisite target potency and selectivity that has shown robust and durable tumor growth inhibition in preclinical models. The in vivo pharmacokinetics in mouse, rat and dog were characterized following i.v. and p.o. administration; EPZ‐5676 had moderate to high clearance, low oral bioavailability with a steady‐state volume of distribution 2–3 fold higher than total body water. EPZ‐5676 showed biexponential kinetics following i.v. administration, giving rise to a terminal elimination half‐life (t1/2) of 1.1, 3.7 and 13.6 h in mouse, rat and dog, respectively. The corresponding in vitro ADME parameters were also studied and utilized for in vitro–in vivo extrapolation purposes. There was good agreement between the microsomal clearance and the in vivo clearance implicating hepatic oxidative metabolism as the predominant elimination route in preclinical species. Furthermore, low renal clearance was observed in mouse, approximating to fu‐corrected glomerular filtration rate (GFR) and thus passive glomerular filtration. The metabolic pathways across species were studied in liver microsomes in which EPZ‐5676 was metabolized to three monohydroxylated metabolites (M1, M3 and M5), one N‐dealkylated product (M4) as well as an N‐oxide (M6). Copyright © 2014 John Wiley & Sons, Ltd.
New flaxseed orbitides: Detection, sequencing, and 15N incorporation
Authors: Okinyo‐Owiti Denis P. , Young Lester , Burnett Peta‐Gaye G. , Reaney Martin J. T. 
Published: January 2014

ABSTRACTThree new orbitides (cyclolinopeptides 17, 18, and 19) were identified in flaxseed (Linum usitatissimum L.) extracts without any form of purification. Their structures were elucidated by a combination of 15N‐labeling experiments and extensive tandem mass spectrometry (MS/MS) with electrospray ionization (ESI). Putative linear peptide sequences of the new orbitides were used as the query in the Basic Local Alignment Search Tool (BLAST) searches of flax genome database. These searches returned linear sequences for the putative precursors of cyclolinopeptides 17 and 19 among others. Cyclolinopeptide 18 contains MetO (O) and is not directly encoded, but is a product of post‐translation modification of the Met present in 17. The identification of precursor proteins in flax mRNA transcripts and DNA sequences confirmed the occurrence and amino acid sequences of these orbitides as [1–9‐NαC]‐MLKPFFFWI, [1–9‐NαC]‐OLKPFFFWI, and [1–9‐NαC]‐GIPPFWLTL for cyclolinopeptides 17, 18, and 19, respectively. © 2014 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 102: 168–175, 2014.
Classification of AIDS‐related lymphoma cases between 1987 and 2012 in Japan based on the WHO classification of lymphomas, fourth edition
Authors: Ota Yasunori , Hishima Tsunekazu , Mochizuki Makoto , Kodama Yoshinori , Moritani Suzuko , Oyaizu Naoki , Mine Sohtaro , Ajisawa Atsushi , Tanuma Junko , Uehira Tomoko , Hagiwara Shotaro , Yajima Keishiro , Koizumi Yusuke , Shirasaka Takuma , Kojima Yuki , Nagai Hirokazu , Yokomaku Yoshiyuki , Shiozawa Yumiko , Koibuchi Tomohiko , Iwamoto Aikichi , Oka Shinichi , Hasegawa Hideki , Okada Seiji , Katano Harutaka 
Published: January 2014

AbstractThe introduction of combined antiretroviral therapy (ART) has reduced the mortality of patients with human immunodeficiency virus‐1 infection worldwide. However, malignant lymphoma is a severe and frequent complication seen in patients with acquired immunodeficiency syndrome (AIDS). The diagnostic criteria for some categories of AIDS‐related lymphoma were revised in the World Health Organization International Classification of Lymphoma, fourth edition. The purpose of this study was to assess the clinicopathological characteristics of Japanese patients with AIDS‐related lymphoma according to the revised classification. In this retrospective study, 207 AIDS‐related lymphoma cases diagnosed between 1987 and 2012 in Japan were subjected to histological subtyping and clinicopathological analyses. Diffuse large B‐cell lymphoma (DLBCL) was the predominant histological subtype throughout the study period (n = 104, 50%). Among the DLBCL cases, 24% were of the germinal center (GC) type and 76% were of the non‐GC type. Non‐GC‐type cases showed a significantly lower 1‐year survival rate (43%) than the GC‐type cases (82%). Cases of Burkitt lymphoma (n = 57, 28%), plasmablastic lymphoma (n = 16, 8%), primary effusion lymphoma (n = 9, 4%), Hodgkin lymphoma (n = 8, 4%), and large B‐cell lymphoma arising in Kaposi sarcoma‐associated herpesvirus‐associated multicentric Castleman disease (n = 2, 1%) were also observed. Hodgkin lymphoma was more common in patients receiving ART (11.1%) than in ART‐naïve patients (1.4%). Statistical analyses identified CD10 negativity, BCL‐6 negativity, Epstein–Barr virus positivity, and Kaposi sarcoma‐associated herpesvirus positivity as risk factors for poor prognosis. This information will help in the early diagnosis of lymphoma in patients with AIDS.
BMVC test, an improved fluorescence assay for detection of malignant pleural effusions
Authors: Lin I‐Ting , Tsai Yu‐Lin , Kang Chi‐Chih , Huang Wei‐Chun , Wang Chiung‐Lin , Lin Mei‐Ying , Lou Pei‐Jen , Shih Jin‐Yuan , Wang Hao‐Chien , Wu Huey‐Dong , Tsai Tzu‐Hsiu , Jan I‐Shiow , Chang Ta‐Chau 
Published: January 2014

AbstractThe diagnosis of malignant pleural effusions is an important issue in the management of malignancy patients. Generally, cytologic examination is a routine diagnostic technique. However, morphological interpretation of cytology is sometimes inconclusive. Here an ancillary method named BMVC test is developed for rapid detection of malignant pleural effusion to improve the diagnostic accuracy at low cost. A simple assay kit is designed to collect living cells from clinical pleural effusion and a fluorescence probe, 3,6‐Bis(1‐methyl‐4‐vinylpyridinium) carbazole diiodide (BMVC), is used to illuminate malignant cells. The fluorescence intensity is quantitatively analyzed by ImageJ program. This method yields digital numbers for the test results without any grey zone or ambiguities in the current cytology tests due to intra‐observer and inter‐observer variability. Comparing with results from double‐blind cytologic examination, this simple test gives a good discrimination between malignant and benign specimens with sensitivity of 89.4% (42/47) and specificity of 93.3% (56/60) for diagnosis of malignant pleural effusion. BMVC test provides accurate results in a short time period, and the digital output could assist cytologic examination to become more objective and clear‐cut. This is a convenient ancillary tool for detection of malignant pleural effusions.
Direct Energy Extraction from Brown Macroalgae‐Derived Alginate by Gold Nanoparticles on Functionalized Carbon Nanotubes
Authors: Hoa Le Quynh , Yoshikawa Hiroyuki , Saito Masato , Ueda Mitsuyoshi , Shibata Toshiyuki , Tamiya Eiichi 
Published: January 2014

AbstractThe front cover artwork for Issue 01/2014 is provided by the research group of Nano‐Bioengineering at the Department of Applied Physics, Osaka University (Japan). The image illustrates the concept of using gold nanoparticle‐decorated carbon nanotubes to directly electrochemically oxidize brown macroalgae derived‐alginate into valuable chemicals and simultaneously extract bioenergy. Read the full text of the article on page 135.
π‐Insertion Reactions of Benzynes into P=N and P=S Double Bonds
Authors: Lopez‐Leonardo Carmen , Raja Rosalia , López‐Ortiz Fernando , Ángel del Águila‐Sánchez Miguel , Alajarin Mateo 
Published: January 2014

AbstractThe π‐insertion reactions of in situ generated benzynes into the P=N bonds of N‐benzyl and N‐aryl iminophosphoranes and the P=S bonds of phosphane sulfides have been examined by using the Kobayashi benzyne precursors, (2‐trimethylsilyl)phenyl triflates. The reactions with iminophosphoranes afforded (2‐aminophenyl)phosphonium triflates under mild conditions, most probably by a [2+2]/retro [2+2] cycloaddition sequence and further N‐protonation by the solvent (CH3CN) or N‐phenylation by a second molecule of benzyne. The final products of the analogous reactions with P‐OCH3‐substituted iminophosphoranes were the respective (2‐aminophenyl)phosphane oxides, as result of a final O‐demethylation event of the putative phosphonium triflate. The reactions with phosphane sulfides involve a final S‐phenylation step to yield (2‐phenylthio)phenylphosphonium salts.
Shear tests of glulam at elevated temperatures
Authors: Dhima Dhionis , Audebert Maxime , Racher Patrick , Bouchaïr Abdelhamid , Taazount Mustapha 
Published: January 2014

SUMMARYExperimental investigations are conducted to characterize the evolution with temperature of the shear strength of glulam wood. To realize the tests, an original specimen with cylindrical shape has been developed and justified by a numerical study. The geometry allows obtaining thermal gradient within material to represent the real combustion of timber members, while keeping constant the temperature of sheared section. The experimental programs consider various parameters such as the presence or absence of moisture and the thermal gradient within the specimen. The experimental results are discussed and analyzed. They show the correlation between the density of the material and the reduction of its strength at high temperatures. The experimental failure loads are used to evaluate the reduction factors for wood strength depending on the temperature. These factors are compared with those given by EN1995‐1‐2 for the advanced calculations methods in fire situation. The comparisons show that the reduction factors given by EN1995‐1‐2 are conservative in comparison with the experimental results. Copyright © 2014 John Wiley & Sons, Ltd.
Long‐term recovery In critical illness myopathy is complete, contrary to polyneuropathy
Authors: Koch Susanne , Wollersheim Tobias , Bierbrauer Jeffrey , Haas Kurt , Mörgeli Rudolf , Deja Maria , Spies Claudia D. , Spuler Simone , Krebs Martin , Weber‐Carstens Steffen 
Published: January 2014

ABSTRACTIntroduction: Muscle weakness in critically ill patients after discharge varies. It is not known whether the electrophysiological distinction between critical illness myopathy (CIM) and critical illness polyneuropathy (CIP) during the early part of a patient's stay in the intensive care unit (ICU) predicts long‐term prognosis. Methods: This was a prospective cohort study of mechanically ventilated ICU patients undergoing conventional nerve conduction studies and direct muscle stimulation in addition to neurological examination during their ICU stay and 1 year after ICU discharge. Results: Twenty‐six patients (7 ICU controls, 8 CIM patients, and 11 CIM/CIP patients) were evaluated 1 year after discharge from the ICU. Eighty‐eight percent (n = 7) of CIM patients recovered within 1 year compared with 55% (n = 6) of CIM/CIP patients. Thirty‐six percent (n = 4) of CIM/CIP patients still needed assistance during their daily routine (P = 0.005). Conclusions: Early electrophysiological testing predicts long‐term outcome in ICU survivors. CIM has a significantly better prognosis than CIM/CIP. Muscle Nerve 50: 431–436, 2014
Identification and Anti‐oxidant Capacity Determination of Phenolics and their Glycosides in Elderflower by On‐line HPLC–CUPRAC Method
Authors: Esin Çelik S. , Özyürek Mustafa , Güçlü Kubilay , Çapanoğlu Esra , Apak Reşat 
Published: January 2014

AbstractIntroductionDevelopment and application of an on‐line cupric reducing anti‐oxidant capacity (CUPRAC) assay coupled with HPLC for separation and on‐line determination of phenolic anti‐oxidants in elderflower (Sambucus nigra L.) extracts for their anti‐oxidant capacity are significant for evaluating health‐beneficial effects. Moreover, this work aimed to assay certain flavonoid glycosides of elderflower that could not be identified/quantified by other similar on‐line HPLC methods (i.e. 2,2‐diphenyl‐1‐picrylhdrazyl and 2, 2'‐azino‐bis‐3‐ethylbenzothiazoline‐6‐sulphonic acid).ObjectiveTo identify anti‐oxidant constituents in elderflower by HPLC and to evaluate their individual anti‐oxidant capacities by on‐line HPLC–CUPRAC assay with a post‐column derivatisation system.MethodsThe separation and UV detection of polyphenols were performed on a C18‐column using gradient elution with two different mobile phase solutions, that is acetonitrile and 1% glacial acetic acid, with detection at 340 nm. The HPLC‐separated anti‐oxidant polyphenols in column effluent react with copper(II)‐neocuproine in a reaction‐coil to reduce the latter to copper(I)‐neocuproine (Cu(I)‐Nc) chelate having maximum absorption at 450 nm.ResultsThe detection limits of tested compounds at 450 nm after post‐column derivatisation were compared with those of at 340 nm UV‐detection without derivatisation. LOD values (µg/mL) of quercetin and its glycosides at 450 nm were lower than those of UV detection at 340 nm. This method was applied successfully to elderflower extract. The flavonol glycosides of quercetin and kaempferol bound to several sugar components (glucose, rhamnose, galactose and rutinose) were identified in the sample.ConclusionThe on‐line HPLC–CUPRAC method was advantageous over on‐line ABTS and DPPH methods for measuring the flavonoid glycosides of elderflower. Copyright © 2014 John Wiley & Sons, Ltd.
Green‐lighting green fluorescent protein: Faster and more efficient folding by eliminating a cis–trans peptide isomerization event
Authors: Rosenman David J. , Huang Yao‐ming , Xia Ke , Fraser Keith , Jones Victoria E. , Lamberson Colleen M. , Van Roey Patrick , Colón Wilfredo , Bystroff Christopher 
Published: January 2014

AbstractWild‐type green fluorescent protein (GFP) folds on a time scale of minutes. The slow step in folding is a cis–trans peptide bond isomerization. The only conserved cis‐peptide bond in the native GFP structure, at P89, was remodeled by the insertion of two residues, followed by iterative energy minimization and side chain design. The engineered GFP was synthesized and found to fold faster and more efficiently than its template protein, recovering 50% more of its fluorescence upon refolding. The slow phase of folding is faster and smaller in amplitude, and hysteresis in refolding has been eliminated. The elimination of a previously reported kinetically trapped state in refolding suggests that X‐P89 is trans in the trapped state. A 2.55 Å resolution crystal structure revealed that the new variant contains only trans‐peptide bonds, as designed. This is the first instance of a computationally remodeled fluorescent protein that folds faster and more efficiently than wild type.
An alternative structural isoform in amyloid‐like aggregates formed from thermally denatured human γD‐crystallin
Authors: Moran Sean D. , Zhang Tianqi O. , Zanni Martin T. 
Published: January 2014

AbstractThe eye lens protein γD‐crystallin contributes to cataract formation in the lens. In vitro experiments show that γD‐crystallin has a high propensity to form amyloid fibers when denatured, and that denaturation by acid or UV‐B photodamage results in its C‐terminal domain forming the β‐sheet core of amyloid fibers. Here, we show that thermal denaturation results in sheet‐like aggregates that contain cross‐linked oligomers of the protein, according to transmission electron microscopy and SDS‐PAGE. We use two‐dimensional infrared spectroscopy to show that these aggregates have an amyloid‐like secondary structure with extended β‐sheets, and use isotope dilution experiments to show that each protein contributes approximately one β‐strand to each β‐sheet in the aggregates. Using segmental 13C labeling, we show that the organization of the protein's two domains in thermally induced aggregates results in a previously unobserved structure in which both the N‐terminal and C‐terminal domains contribute to β‐sheets. We propose a model for the structural organization of the aggregates and attribute the recruitment of the N‐terminal domain into the fiber structure to intermolecular cross linking.