bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exchanging ligand-binding specificity between a pair of mouse olfactory receptor paralogs reveals odorant recognition principles
Authors: Baud Olivia , Yuan Shuguang , Veya Luc , Filipek Slawomir , Vogel Horst , Pick Horst 
Published: October 2015

AbstractA multi-gene family of ~1000 G protein-coupled olfactory receptors (ORs) constitutes the molecular basis of mammalian olfaction. Due to the lack of structural data its remarkable capacity to detect and discriminate thousands of odorants remains poorly understood on the structural level of the receptor. Using site-directed mutagenesis we transferred ligand specificity between two functionally related ORs and thereby revealed amino acid residues of central importance for odorant recognition and discrimination of the two receptors. By exchanging two of three residues, differing at equivalent positions of the putative odorant binding site between the mouse OR paralogs Olfr73 (mOR-EG) and Olfr74 (mOR-EV), we selectively changed ligand preference but remarkably also signaling activation strength in both ORs. Computer modeling proposed structural details at atomic resolution how the very same odorant molecule might interact with different contact residues to induce different functional responses in two related receptors. Our findings provide a mechanistic explanation of how the olfactory system distinguishes different molecular aspects of a given odorant molecule and unravel important molecular details of the combinatorial encoding of odorant identity at the OR level.
Identification of cellular microRNA-136 as a dual regulator of RIG-I-mediated innate immunity that antagonizes H5N1 IAV replication in A549 cells
Authors: Zhao Lianzhong , Zhu Jiping , Zhou Hongbo , Zhao Zongzheng , Zou Zhong , Liu Xiaokun , Lin Xian , Zhang Xue , Deng Xuexia , Wang Ruifang , Chen Huanchun , Jin Meilin 
Published: October 2015

AbstractH5N1 influenza A virus (IAV) causes severe respiratory diseases and high mortality rates in animals and humans. MicroRNAs are being increasingly studied to evaluate their potential as therapeutic entities to combat viral infection. However, mechanistic studies delineating the roles of microRNAs in regulating host-H5N1 virus interactions remain scarce. Here, we performed microRNA microarray analysis using A549 human lung epithelial cells infected with a highly pathogenic avian influenza virus. The microRNA expression profile of infected cells identified a small number of microRNAs being dysregulated upon H5N1 influenza A virus infection. Of the differentially expressed microRNAs, miR-136 was up-regulated 5-fold and exhibited potent antiviral activity in vitro against H5N1 influenza A virus, as well as vesicular stomatitis virus. On the one hand, 3′-untranslated region (UTR) reporter analysis revealed a miR-136 binding site in the 3′ UTR of IL-6. However, on the other hand, we subsequently determined that miR-136 meanwhile acts as an immune agonist of retinoic acid-inducible gene 1 (RIG-I), thereby causing IL-6 and IFN-β accumulation in A549 cells. Overall, this study implicates the dual role of miRNA-136 in the regulation of host antiviral innate immunity and suggests an important role for the microRNA-activated pathway in viral infection via pattern recognition receptors.
Role of supplemental foods and habitat structural complexity in persistence and coexistence of generalist predatory mites
Authors: Pozzebon Alberto , Loeb Gregory M. , Duso Carlo 
Published: October 2015

AbstractPlant traits can influence the interactions between herbivore arthropods and their natural enemies. In these interactions generalist predators are often present, preying on herbivores and also on other arthropods in the same trophic guild. Variation in the strength of intraguild predation (IGP) may be related to habitat structural complexity and to additional resources outside the narrow predator-prey relationship. In this paper we study the food web interactions on grape, which involves two generalist predatory mites. We evaluated the effects of grape powdery mildew (GPM) as supplemental food and habitat structural complexity provided by domatia. The inoculation of GPM resulted in higher predatory mite densities and reduced the negative impact of unfavorable leaf structure for one species. Access to domatia was the main factor in promoting population abundance and persistence of predatory mites. Access to domatia and GPM availability favored the coexistence of predatory mites at a low density of the intraguild prey. Our findings suggest that structural and nutritional diversity/complexity promote predatory mite abundance and can help to maintain the beneficial mites - plants association. The effect of these factors on coexistence between predators is influenced by the supplemental food quality and relative differences in body size of interacting species.
Density-gradient centrifugation enables the purification of cultured corneal endothelial cells for cell therapy by eliminating senescent cells
Authors: Okumura Naoki , Kusakabe Ayaka , Hirano Hiroatsu , Inoue Ryota , Okazaki Yugo , Nakano Shinichiro , Kinoshita Shigeru , Koizumi Noriko 
Published: October 2015

AbstractThe corneal endothelium is essential for maintaining corneal transparency; therefore, corneal endothelial dysfunction causes serious vision loss. Tissue engineering-based therapy is potentially a less invasive and more effective therapeutic modality. We recently started a first-in-man clinical trial of cell-based therapy for treating corneal endothelial dysfunction in Japan. However, the senescence of corneal endothelial cells (CECs) during the serial passage culture needed to obtain massive quantities of cells for clinical use is a serious technical obstacle preventing the push of this regenerative therapy to clinical settings. Here, we show evidence from an animal model confirming that senescent cells are less effective in cell therapy. In addition, we propose that density-gradient centrifugation can eliminate the senescent cells and purify high potency CECs for clinical use. This simple technique might be applicable for other types of cells in the settings of regenerative medicine.
Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure
Authors: Roth Caleb C. , Barnes Ronald A. , Ibey Bennett L. , Beier Hope T. , Christopher Mimun L. , Maswadi Saher M. , Shadaram Mehdi , Glickman Randolph D. 
Published: October 2015

AbstractThe mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane.
Phosphoregulation of the C. elegans cadherin–catenin complex
Authors: Callaci Sandhya , Morrison Kylee , Shao Xiangqiang , Schuh Amber L. , Wang Yueju , Yates John R. , Hardin Jeff , Audhya Anjon 
Published: October 2015

Adherens junctions play key roles in mediating cell–cell contacts during tissue development. In Caenorhabditis elegans embryos, the cadherin–catenin complex (CCC), composed of the classical cadherin HMR-1 and members of three catenin families, HMP-1, HMP-2 and JAC-1, is necessary for normal blastomere adhesion, gastrulation, ventral enclosure of the epidermis and embryo elongation. Disruption of CCC assembly or function results in embryonic lethality. Previous work suggests that components of the CCC are subject to phosphorylation. However, the identity of phosphorylated residues in CCC components and their contributions to CCC stability and function in a living organism remain speculative. Using mass spectrometry, we systematically identify phosphorylated residues in the essential CCC subunits HMR-1, HMP-1 and HMP-2 in vivo. We demonstrate that HMR-1/cadherin phosphorylation occurs on three sites within its β-catenin binding domain that each contributes to CCC assembly on lipid bilayers. In contrast, phosphorylation of HMP-2/β-catenin inhibits its association with HMR-1/cadherin in vitro, suggesting a role in CCC disassembly. Although HMP-1/α-catenin is also phosphorylated in vivo, phosphomimetic mutations do not affect its ability to associate with other CCC components or interact with actin in vitro. Collectively, our findings support a model in which distinct phosphorylation events contribute to rapid CCC assembly and disassembly, both of which are essential for morphogenetic rearrangements during development.
Histone deacetylase 3 indirectly modulates tubulin acetylation
Authors: Bacon Travis , Seiler Caroline , Wolny Marcin , Hughes Ruth , Watson Peter , Schwabe John , Grigg Ronald , Peckham Michelle 
Published: October 2015

Histone deacetylase 3 (HDAC3), a member of the Class I subfamily of HDACs, is found in both the nucleus and the cytoplasm. Its roles in the nucleus have been well characterized, but its cytoplasmic roles are still not elucidated fully. We found that blocking HDAC3 activity using MI192, a compound specific for HDAC3, modulated tubulin acetylation in the human prostate cancer cell line PC3. A brief 1 h treatment of PC3 cells with MI192 significantly increased levels of tubulin acetylation and ablated the dynamic behaviour of microtubules in live cells. siRNA-mediated knockdown (KD) of HDAC3 in PC3 cells, significantly increased levels of tubulin acetylation, and overexpression reduced it. However, the active HDAC3–silencing mediator of retinoic and thyroid receptors (SMRT)–deacetylase-activating domain (DAD) complex did not directly deacetylate tubulin in vitro. These data suggest that HDAC3 indirectly modulates tubulin acetylation.
A Quasi-Universal Nonword Repetition Task as a Diagnostic Tool for Bilingual Children Learning Dutch as a Second Language
Authors: Boerma Tessel , Chiat Shula , Leseman Paul , Timmermeister Mona , Wijnen Frank , Blom Elma 
Published: October 2015

Purpose
This study evaluated a newly developed quasi-universal nonword repetition task (Q-U NWRT) as a diagnostic tool for bilingual children with language impairment (LI) who have Dutch as a 2nd language. The Q-U NWRT was designed to be minimally influenced by knowledge of 1 specific language in contrast to a language-specific NWRT with which it was compared.

Method
One hundred twenty monolingual and bilingual children with and without LI participated (30 per group). A mixed-design analysis of variance was used to investigate the effects of LI and bilingualism on the NWRTs. Receiver operating characteristic analyses were conducted to evaluate the instruments' diagnostic value.

Results
Large negative effects of LI were found on both NWRTs, whereas negative effects of bilingualism only occurred on the language-specific NWRT. Both instruments had high clinical accuracy in the monolingual group, but only the Q-U NWRT had high clinical accuracy in the bilingual group.

Conclusions
This study indicates that the Q-U NWRT is a promising diagnostic tool to help identify LI in bilingual children learning Dutch as a 2nd language. The instrument was clinically accurate in both a monolingual and bilingual group of children and seems better able to disentangle LI from language disadvantage than more language-specific measures.
Fusion with pep-1, a cell-penetrating peptide, enhances the transmembrane ability of human epidermal growth factor
Authors: Luo Xue-Gang , Ma De-Yun , Wang Yue , Li Wen , Wang Chong-Xi , He Ying-Ying , Gu Xiang-Chao , Li Xiu-Mei , Zhou Hao , Zhang Tong-Cun 
Published: October 2015

Abstract
Administration of macromolecule compositions in medicine and cosmetics always exhibited low bioavailability due to the limitation of transmembrane transport. Here, human epidermal growth factor (hEGF) was fused with glutathione S-transferase (GST) and Pep-1, the first commercial cell-penetrating peptide, in Escherichia coli. The fusion protein was firstly purified with the affinity chromatography, and then the GST tag was released by TEV protease. Final purification was achieved by the ion exchange chromatography. The biological activities and the transmembrane ability of the obtained products were determined using scratch wound-healing assay, MTT analysis, and immunofluorescence assay. The results showed that both rhEGF and Pep-1-fused hEGF were soluble expressed in E. coli. The fusion of Pep-1 could markedly increase the transmembrane ability of EGF, whereas it did not interfere with the growth-stimulating and migration-promoting functions of hEGF on fibroblasts. This research provided a novel strategy for the transmembrane transport of protein-derived cosmetics or drugs.
Analysis and characterization of anthocyanins and carotenoids in Japanese blue tomato
Authors: Ooe Emi , Ogawa Kenjirou , Horiuchi Tadashi , Tada Hiroyuki , Murase Hiromi , Tsuruma Kazuhiro , Shimazawa Masamitsu , Hara Hideaki 
Published: October 2015

Abstract
Tomato (Solanum lycopersicum) is rich in anthocyanins, which are polyphenolic pigments. This study aimed to analyze and characterize the anthocyanin composition in cultivated blue tomato in Japan. The extracts of peel, seed, and pulp of tomatoes were purified following which anthocyanins and lycopene contents were analyzed using high-performance liquid chromatography and electrospray ionization mass spectrometry. Eleven types of anthocyanins were identified, including delphinidin, petunidin, and malvidin. Further, the antioxidant activity of anthocyanins was evaluated using 2,2′-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt radical quenching assays and electron spin resonance. “Blue tomato” extracts exert antioxidant activity. Thus, we showed that petunidin was present in the “blue tomato” peel while lycopene was present in the peel and pulp. Additionally, the blue tomato peel extract was found to significantly inhibit H2O2-induced cell death in vitro. This is the first study on cell protective effects of Japanese blue tomato extract and petunidin in murine photoreceptor cells.
Pathophysiological role of oxidative stress in systolic and diastolic heart failure and its therapeutic implications
Authors: Münzel Thomas , Gori Tommaso , Keaney John F. , Maack Christoph , Daiber Andreas 
Published: October 2015

Abstract
Systolic and diastolic myocardial dysfunction has been demonstrated to be associated with an activation of the circulating and local renin–angiotensin–aldosterone system (RAAS), and with a subsequent inappropriately increased production of reactive oxygen species (ROS). While, at low concentrations, ROS modulate important physiological functions through changes in cellular signalling and gene expression, overproduction of ROS may adversely alter cardiac mechanics, leading to further worsening of systolic and diastolic function. In addition, vascular endothelial dysfunction due to uncoupling of the nitric oxide synthase, activation of vascular and phagocytic membrane oxidases or mitochondrial oxidative stress may lead to increased vascular stiffness, further compromising cardiac performance in afterload-dependent hearts. In the present review, we address the potential role of ROS in the pathophysiology of myocardial and vascular dysfunction in heart failure (HF) and their therapeutic targeting. We discuss possible mechanisms underlying the failure of antioxidant vitamins in improving patients’ prognosis, the impact of angiotensin-converting enzyme inhibitors or AT1 receptor blockers on oxidative stress, and the mechanism of the benefit of combination of hydralazine/isosorbide dinitrate. Further, we provide evidence supporting the existence of differences in the pathophysiology of HF with preserved vs. reduced ejection fraction and whether targeting mitochondrial ROS might be a particularly interesting therapeutic option for patients with preserved ejection fraction.
The IFAO Excavations at Deir el-Medina
Authors: Gobeil Cédric 
Published: October 2015

Abstract
Through a thorough examination of the archive kept in the Institut français d’archéologie orientale (the French Archaeological Institute in Cairo; hereafter IFAO), this chapter details the history of the archaeological excavations and other field activities conducted by the Institute at the site of Deir el-Medina since the early 20th century. The chapter focuses in particular on the work of Bernard Bruyère, the central figure of this endeavor. Although the opportunity is given to go through the major discoveries that were made on the site and their contributions to the knowledge of daily life in ancient Egypt, the focus is also put on the photographic archives of Bruyère and on the information that can be drawn from them. A review of the work made after Bruyère is finally detailed, along with a summary of the ongoing activities on the site.
Efficient Generation and Selection of Virtual Populations in Quantitative Systems Pharmacology Models
Authors: Allen R.J. , Rieger T.R. , Musante C.J. 
Published: October 2015

AbstractQuantitative systems pharmacology models mechanistically describe a biological system and the effect of drug treatment on system behavior. Because these models rarely are identifiable from the available data, the uncertainty in physiological parameters may be sampled to create alternative parameterizations of the model, sometimes termed ‘Virtual Patients.’ In order to reproduce the statistics of a clinical population, Virtual Patients are often weighted to form a Virtual Population that reflects the baseline characteristics of the clinical cohort. Here we introduce a novel technique to efficiently generate Virtual Patients and, from this ensemble, demonstrate how to select a Virtual Population that matches the observed data without the need for weighting. This approach improves confidence in model predictions by mitigating the risk that spurious Virtual Patients become over-represented in Virtual Populations.
“We don’t get taught enough”: an assessment of drug education provision in schools in England
Authors: Thurman Ben , Boughelaf Jamila 
Published: October 2015

Purpose
– The purpose of this paper is to investigate the provision of drug education in schools in England by exploring the views of young people and teachers. The study synthesises the commonalities between experiences of teaching and learning and, in doing so, offers insight on policy and practice.

Design/methodology/approach
– The paper incorporates two pieces of research: a survey of 590 secondary school pupils in London that generated insight on the collective experience of drug education; and a survey of 288 teachers in primary and secondary schools throughout England, supplemented by 20 in-depth interviews. The paper also draws on learning from the practical implementation of the Alcohol and Drug Education and Prevention Information Service (ADEPIS).

Findings
– The research provides insight into the current status of drug education provision and outlines key constraints to effective delivery. The paper also presents ADEPIS as a potential framework for supporting schools.

Research limitations/implications
– The research incorporated a relatively small number of schools and only accessed the views of young people in London; the results therefore require further substantiation. There is also a need for further evaluation of ADEPIS, including comparison with schools that develop drug education practice independent of external guidance.

Practical implications
– The paper highlights the need for improvement in drug education, with implications for national policy, particularly in relation to subject-specific teacher training, increased central guidance, and the statutory status of PSHE.

Originality/value
– The research fulfils the need to represent the voices of young people in discussions on drug education, as well as contributing to wider debates around improving the quality of drug education.
The perceived effectiveness of the school based support program
Authors: Abu-Tineh Abdullah M. 
Published: October 2015

Purpose– This study aims to investigate the effectiveness of the school-based support program (SBSP) as perceived by teachers who participated in this program. SBSP was designed to collectively build the capacity and promote the overall quality of teaching and learning in identified independent schools in the State of Qatar.Design/methodology/approach– This study is quantitative in nature and was conducted using a survey methodology as its research design. A variety of statistical techniques were utilized in this research. Means, standard deviations,t-test, and one-way analysis of variance (ANOVA) were utilized to analyze gained data.Findings– The findings indicated that teachers perceived the effectiveness of SBSP to be moderate-to- high. Further, there was a significant difference between male and female teachers in their perceptions of the effectiveness of SBSP overall. Male participant teachers perceived SBSP overall to be more effective than female participant teachers did. However, there were no significant differences among participant teachers in perceiving the effectiveness of SBSP that is attributed to their teaching experience or academic qualifications.Originality/value– This study suggests a common level of satisfaction of the SBSP program that was launched just two years ago. At the same time, however, many recommendations and implications were discussed and suggested to enhance the effectiveness of the program.
Sensors for robotic perception. Part two: positional and environmental awareness
Authors: Bogue Robert 
Published: October 2015

Purpose
– The purpose of this article is to illustrate how sensors impart perceptive capabilities to robots. This is the second part of a two-part article. This second part considers positional awareness and sensing in the external environment, notably but not exclusively by autonomous, mobile robots.

Design/methodology/approach
– Following a short introduction, this article first discusses positional sensing and navigation by mobile robots, including self-driving cars, automated guided vehicles, unmanned aerial vehicles (UAVs) and autonomous underwater vehicles (AUVs). It then considers sensing with UAVs and AUVs, and finally discusses robots for hazard detection. Brief concluding comments are drawn.

Findings
– This shows that sensors based on a multitude of techniques confer navigational capabilities to mobile robots, including LIDARs, radar, sonar, imaging and inertial sensing devices. UAVs, AUVs and mobile terrestrial robots can be equipped with all manner of sensors to create detailed terrestrial and underwater maps, monitor air and water quality, locate pollution and detect hazards. While existing sensors are used widely, many new devices are now being developed to meet specific requirements and to comply with size, weight and cost restraints.

Originality/value
– The use of mobile robots is growing rapidly, and this article provides a timely account of how sensors confer them with positional awareness and allow them to act as mobile sensing platforms.