bluuebunny/crossref_metadata_2025 huggingface dataset:
Embodied intersubjectivity, sedimentation and non-actual motion expressions
Authors: Zlatev Jordan , Blomberg Johan
Published: September 2016

As part of a long-term project investigating the relevance of phenomenology for (cognitive) linguistics we analyse two central, interrelated concepts:embodied intersubjectivity(intercorporeality) andsedimentation. With respect to the first, we spell out a number of different intercorporeal structures, emanating at the most fundamental level from the dualLeibkörpernature of the body. Further, we demonstrate that sedimentation is more than a ‘geological metaphor’ as meaning is intrinsically layered in human experience. This is first illustrated by reviewing evidence from ontogenetic semiotic development within the framework of the Mimesis Hierarchy model (Zlatev 2013). Then, we focus on the linguistic construal of situations lacking actual motion in dynamic terms through expressions of non-actual motion such asThe road goes through the forestandHe was uplifted by her smile. We review studies of non-actual motion in Swedish, English, French, Bulgarian and Thai extending and re-formulating previous analyses. We argue that the present analysis is more adequate than cognitive linguistic explanations in terms of ‘mental simulation’ and ‘conceptual metaphor’. We conclude by pointing out how our phenomenological investigation can help resolve a number of classical dilemmas in semantics: Is language primarily grounded in the body or in society? Is the ontology of linguistic meaning mental or social? What is the relationship between pre-linguistic experiences and linguistic conventions?
Hepatitis E in Norway: seroprevalence in humans and swine
Authors: LANGE H. , ØVERBØ J. , BORGEN K. , DUDMAN S. , HODDEVIK G. , URDAHL A. M. , VOLD L. , SJURSETH S. K.
Published: September 2016

In Norway, no published data on seroprevalence of hepatitis E virus (HEV) in humans and swine exists. Serum samples from blood donors, veterinarians, swine farm workers and swine were analysed by ELISA to estimate the seroprevalence of HEV in Norway and to investigate the association between direct contact with swine and HEV seroprevalence in humans. The seroprevalence of HEV IgG antibodies was 30% (24/79) in farm workers, 13% (21/163) in veterinarians, 14% (162/1200) in blood donors and 90% (137/153) in swine. Our results show a high seroprevalence of HEV in humans and swine in Norway. HEV seroprevalence in farm workers and blood donors increased with age, and veterinarians working with swine were twice as likely to be HEV seropositive compared to other veterinarians. High HEV seroprevalence in farm workers and veterinarians working with swine support previous reports suggesting swine as a reservoir for HEV infections in humans in Europe.
Group-Based Relaxation Response Skills Training for Pharmacologically-Resistant Depressed and Anxious Patients
Authors: Truzoli Roberto , Rovetta Cecilia , Viganò Caterina , Marinaccio Paola Marianna , Ba Gabriella , Reed Phil
Published: September 2016

Background: Drug-resistance for depression and anxiety is a major limitation in the treatment of these common disorders, and adjunct support interventions may be beneficial in the treatment of these patients. Aims: The purpose of this study was to evaluate the effects of a short-term (8 session) Relaxation Response Skills Training (RRST) programme for a population of psychiatric outpatients with anxiety and mood disorders who were unresponsive to drug treatment, and to test the feasibility of this intervention as complementary treatment for a psychiatric setting. Method: Forty patients were measured for overall psychopathological symptoms, depression, and anxiety, and were then given an 8-week course of RRST, while continuing their pharmacological treatment. Following the RRST intervention, participants were again assessed. Results: The results demonstrated reductions in overall symptoms (large effect size and reasonable clinically significant change), and also in depression and anxiety (medium effect sizes and clinically significant change). Conclusions: These results suggest that this short-term RRT offers a simple and cost-effective way to augment drug management for participants with common psychiatric disorders who are less responsive to the drug treatment.
Frailty and Social Care: Over- or Under-Familiar Terms?
Authors: Manthorpe Jill , Iliffe Steve , Harris Jess , Moriarty Jo , Stevens Martin
Published: September 2016

Definitions of frailty are much debated. The focus of this article is on the representation of frailty; who employs the terms ‘frail’ or ‘frailty’ in social care, about whom and with what meanings? We report secondary analysis of interview data from two waves of a longitudinal study starting in 2008. Study participants were 240 social care managers/practitioners working in four English localities. Social care managers and practitioners did not talk at length about frailty as characterising the increasing needs of care users. The minority who talked about frailty used the term in three ways: describing a physical state not including dementia; describing a stable state, as distinct from those dying; and as a combination of physical and mental disabilities (i.e. dementia). Differences among the participants in this study about the meaning of frailty could have implications for policy makers and for communication with other staff, health professionals, older people and their relatives.
Overfulfilling the Norm
Authors: Stavrova Olga , Köneke Vanessa , Schlösser Thomas
Published: September 2016

Abstract. This research extends the better-than-average (BTA) effect commonly observed in judgments of abilities and personality traits to the domain of attitudes. Participants reported their attitudes toward 18 sociopolitical issues and estimated the attitudes of most other people toward these issues. Consistent with the research on pro-norm and anti-norm deviance, for issues high (vs. low) in the injunctive norm, participants perceived their attitudes to be more supportive (vs. deprecatory) than the attitudes of the majority. This effect was stronger for issues that participants judged to be personally important as well as when participants estimated others’ attitudes before indicating their own attitudes.
This Only Happens to Others
Authors: Le Barbenchon Emmanuelle , Milhabet Isabelle , Bry Clémentine
Published: September 2016

Abstract. This paper investigates the specific self-presentational situations in which people confirm or negate their comparative optimism in order to convey a favorable self-image. One pilot study and three experiments showed that people increase their comparative optimism to convey an image of competence, but not one of warmth (Pilot Study, Study 1), as well as to present an advantageous self-image in professional situations, although not in friendship situations (Studies 2–3). These effects occur in self-presentation situations involving both low (Studies 1–2) and high (Study 3) levels of accountability. Additional findings indicate that the presentation of a risk-taking self-image is unrelated to comparative optimism, whereas the presentation of a modest self-image leads people to decrease their comparative optimism estimates (Study 3). Results are discussed in the light of the underlying self-presentational motivations in specific situations.
Rock-Chomping Bees Burrow into Sandstone
Authors: Wendel JoAnna
Published: September 2016

A previously unknown species of rock-excavating bees, discovered 40 years ago but not reported in the scientific literature, finally gets the spotlight.
A multiscale 3D finite element analysis of fluid/solute transport in mechanically loaded bone
Authors: Fan Lixia , Pei Shaopeng , Lucas Lu X , Wang Liyun
Published: September 2016

The transport of fluid, nutrients, and signaling molecules in the bone lacunar–canalicular system (LCS) is critical for osteocyte survival and function. We have applied the fluorescence recovery after photobleaching (FRAP) approach to quantify load-induced fluid and solute transport in the LCS in situ, but the measurements were limited to cortical regions 30–50 μm underneath the periosteum due to the constrains of laser penetration. With this work, we aimed to expand our understanding of load-induced fluid and solute transport in both trabecular and cortical bone using a multiscaled image-based finite element analysis (FEA) approach. An intact murine tibia was first re-constructed from microCT images into a three-dimensional (3D) linear elastic FEA model, and the matrix deformations at various locations were calculated under axial loading. A segment of the above 3D model was then imported to the biphasic poroelasticity analysis platform (FEBio) to predict load-induced fluid pressure fields, and interstitial solute/fluid flows through LCS in both cortical and trabecular regions. Further, secondary flow effects such as the shear stress and/or drag force acting on osteocytes, the presumed mechano-sensors in bone, were derived using the previously developed ultrastructural model of Brinkman flow in the canaliculi. The material properties assumed in the FEA models were validated against previously obtained strain and FRAP transport data measured on the cortical cortex. Our results demonstrated the feasibility of this computational approach in estimating the fluid flux in the LCS and the cellular stimulation forces (shear and drag forces) for osteocytes in any cortical and trabecular bone locations, allowing further studies of how the activation of osteocytes correlates with in vivo functional bone formation. The study provides a promising platform to reveal potential cellular mechanisms underlying the anabolic power of exercises and physical activities in treating patients with skeletal deficiencies.
Decreased glutathione biosynthesis contributes to EGFR T790M-driven erlotinib resistance in non-small cell lung cancer
Authors: Li Hongde , Stokes William , Chater Emily , Roy Rajat , de Bruin Elza , Hu Yili , Liu Zhigang , Smit Egbert F , Heynen Guus JJE , Downward Julian , Seckl Michael J , Wang Yulan , Tang Huiru , Pardo Olivier E
Published: September 2016

Epidermal growth factor receptor (EGFR) inhibitors such as erlotinib are novel effective agents in the treatment of EGFR-driven lung cancer, but their clinical impact is often impaired by acquired drug resistance through the secondary T790M EGFR mutation. To overcome this problem, we analysed the metabonomic differences between two independent pairs of erlotinib-sensitive/resistant cells and discovered that glutathione (GSH) levels were significantly reduced in T790M EGFR cells. We also found that increasing GSH levels in erlotinib-resistant cells re-sensitised them, whereas reducing GSH levels in erlotinib-sensitive cells made them resistant. Decreased transcription of the GSH-synthesising enzymes (GCLC and GSS) due to the inhibition of NRF2 was responsible for low GSH levels in resistant cells that was directly linked to the T790M mutation. T790M EGFR clinical samples also showed decreased expression of these key enzymes; increasing intra-tumoural GSH levels with a small-molecule GST inhibitor re-sensitised resistant tumours to erlotinib in mice. Thus, we identified a new resistance pathway controlled by EGFR T790M and a therapeutic strategy to tackle this problem in the clinic.
Molecular determinants for the strictly compartmentalized expression of kainate receptors in CA3 pyramidal cells
Authors: Fièvre Sabine , Carta Mario , Chamma Ingrid , Labrousse Virginie , Thoumine Olivier , Mulle Christophe
Published: September 2016

Distinct subtypes of ionotropic glutamate receptors can segregate to specific synaptic inputs in a given neuron. Using functional mapping by focal glutamate uncaging in CA3 pyramidal cells (PCs), we observe that kainate receptors (KARs) are strictly confined to the postsynaptic elements of mossy fibre (mf) synapses and excluded from other glutamatergic inputs and from extrasynaptic compartments. By molecular replacement in organotypic slices from GluK2 knockout mice, we show that the faithful rescue of KAR segregation at mf-CA3 synapses critically depends on the amount of GluK2a cDNA transfected and on a sequence in the GluK2a C-terminal domain responsible for interaction with N-cadherin. Targeted deletion of N-cadherin in CA3 PCs greatly reduces KAR content in thorny excrescences and KAR-EPSCs at mf-CA3 synapses. Hence, multiple mechanisms combine to confine KARs at mf-CA3 synapses, including a stringent control of the amount of GluK2 subunit in CA3 PCs and the recruitment/stabilization of KARs by N-cadherins.
Protein kinase D regulates positive selection of CD4+ thymocytes through phosphorylation of SHP-1
Authors: Ishikawa Eri , Kosako Hidetaka , Yasuda Tomoharu , Ohmuraya Masaki , Araki Kimi , Kurosaki Tomohiro , Saito Takashi , Yamasaki Sho
Published: September 2016

Thymic selection shapes an appropriate T cell antigen receptor (TCR) repertoire during T cell development. Here, we show that a serine/threonine kinase, protein kinase D (PKD), is crucial for thymocyte positive selection. In T cell-specific PKD-deficient (PKD2/PKD3 double-deficient) mice, the generation of CD4 single positive thymocytes is abrogated. This defect is likely caused by attenuated TCR signalling during positive selection and incomplete CD4 lineage specification in PKD-deficient thymocytes; however, TCR-proximal tyrosine phosphorylation is not affected. PKD is activated in CD4+CD8+ double positive (DP) thymocytes on stimulation with positively selecting peptides. By phosphoproteomic analysis, we identify SH2-containing protein tyrosine phosphatase-1 (SHP-1) as a direct substrate of PKD. Substitution of wild-type SHP-1 by phosphorylation-defective mutant (SHP-1S557A) impairs generation of CD4+ thymocytes. These results suggest that the PKD–SHP-1 axis positively regulates TCR signalling to promote CD4+ T cell development.
Platelet clearance via shear-induced unfolding of a membrane mechanoreceptor
Authors: Deng Wei , Xu Yan , Chen Wenchun , Paul David S. , Syed Anum K. , Dragovich Matthew A. , Liang Xin , Zakas Philip , Berndt Michael C. , Di Paola Jorge , Ware Jerry , Lanza Francois , Doering Christopher B. , Bergmeier Wolfgang , Zhang X. Frank , Li Renhao
Published: September 2016

Mechanisms by which blood cells sense shear stress are poorly characterized. In platelets, glycoprotein (GP)Ib–IX receptor complex has been long suggested to be a shear sensor and receptor. Recently, a relatively unstable and mechanosensitive domain in the GPIbα subunit of GPIb–IX was identified. Here we show that binding of its ligand, von Willebrand factor, under physiological shear stress induces unfolding of this mechanosensory domain (MSD) on the platelet surface. The unfolded MSD, particularly the juxtamembrane ‘Trigger’ sequence therein, leads to intracellular signalling and rapid platelet clearance. These results illustrate the initial molecular event underlying platelet shear sensing and provide a mechanism linking GPIb–IX to platelet clearance. Our results have implications on the mechanism of platelet activation, and on the pathophysiology of von Willebrand disease and related thrombocytopenic disorders. The mechanosensation via receptor unfolding may be applicable for many other cell adhesion receptors.
Quantifying microstructural dynamics and electrochemical activity of graphite and silicon-graphite lithium ion battery anodes
Authors: Pietsch Patrick , Westhoff Daniel , Feinauer Julian , Eller Jens , Marone Federica , Stampanoni Marco , Schmidt Volker , Wood Vanessa
Published: September 2016

Despite numerous studies presenting advances in tomographic imaging and analysis of lithium ion batteries, graphite-based anodes have received little attention. Weak X-ray attenuation of graphite and, as a result, poor contrast between graphite and the other carbon-based components in an electrode pore space renders data analysis challenging. Here we demonstrate operando tomography of weakly attenuating electrodes during electrochemical (de)lithiation. We use propagation-based phase contrast tomography to facilitate the differentiation between weakly attenuating materials and apply digital volume correlation to capture the dynamics of the electrodes during operation. After validating that we can quantify the local electrochemical activity and microstructural changes throughout graphite electrodes, we apply our technique to graphite-silicon composite electrodes. We show that microstructural changes that occur during (de)lithiation of a pure graphite electrode are of the same order of magnitude as spatial inhomogeneities within it, while strain in composite electrodes is locally pronounced and introduces significant microstructural changes.
Tissue engineering of acellular vascular grafts capable of somatic growth in young lambs
Authors: Syedain Zeeshan , Reimer Jay , Lahti Matthew , Berry James , Johnson Sandra , Bianco Richard , Tranquillo Robert T.
Published: September 2016

Treatment of congenital heart defects in children requiring right ventricular outflow tract reconstruction typically involves multiple open-heart surgeries because all existing graft materials have no growth potential. Here we present an ‘off-the-shelf’ vascular graft grown from donor fibroblasts in a fibrin gel to address this critical unmet need. In a proof-of-concept study, the decellularized grafts are implanted as a pulmonary artery replacement in three young lambs and evaluated to adulthood. Longitudinal ultrasounds document dimensional growth of the grafts. The lambs show normal growth, increasing body weight by 366% and graft diameter and volume by 56% and 216%, respectively. Explanted grafts display physiological strength and stiffness, complete lumen endothelialization and extensive population by mature smooth muscle cells. The grafts also show substantial elastin deposition and a 465% increase in collagen content, without signs of calcification, aneurysm or stenosis. Collectively, our data support somatic growth of this completely biological graft.
The mechanism of eutectic growth in highly anisotropic materials
Authors: Shahani Ashwin J. , Xiao Xianghui , Voorhees Peter W.
Published: September 2016

In the past 50 years, there has been increasing interest—both theoretically and experimentally—in the problem of pattern formation of a moving boundary, such as a solidification front. One example of pattern formation is that of irregular eutectic solidification, in which the solid–liquid interface is non-isothermal and the interphase spacing varies in ways that are poorly understood. Here, we identify the growth mode of irregular eutectics, using reconstructions from four-dimensional (that is, time and space resolved) X-ray microtomography. Our results show that the eutectic growth process can be markedly different from that seen in previously used model systems and theories based on the ex situ analysis of microstructure. In light of our experimental findings, we present a coherent growth model of irregular eutectic solidification.
Observation of a new superfluid phase for 3He embedded in nematically ordered aerogel
Authors: Zhelev N. , Reichl M. , Abhilash T. S. , Smith E. N. , Nguyen K. X. , Mueller E. J. , Parpia J. M.
Published: September 2016

In bulk superfluid 3He at zero magnetic field, two phases emerge with the B-phase stable everywhere except at high pressures and temperatures, where the A-phase is favoured. Aerogels with nanostructure smaller than the superfluid coherence length are the only means to introduce disorder into the superfluid. Here we use a torsion pendulum to study 3He confined in an extremely anisotropic, nematically ordered aerogel consisting of ∼10 nm-thick alumina strands, spaced by ∼100 nm, and aligned parallel to the pendulum axis. Kinks in the development of the superfluid fraction (at various pressures) as the temperature is varied correspond to phase transitions. Two such transitions are seen in the superfluid state, and we identify the superfluid phase closest to Tc at low pressure as the polar state, a phase that is not seen in bulk 3He.
Alterations in the hippocampus and thalamus in individuals at high risk for psychosis
Authors: Harrisberger Fabienne , Buechler Roman , Smieskova Renata , Lenz Claudia , Walter Anna , Egloff Laura , Bendfeldt Kerstin , Simon Andor E , Wotruba Diana , Theodoridou Anastasia , Rössler Wulf , Riecher-Rössler Anita , Lang Undine E , Heekeren Karsten , Borgwardt Stefan
Published: September 2016

Reduction in hippocampal volume is a hallmark of schizophrenia and already present in the clinical high-risk state. Nevertheless, other subcortical structures, such as the thalamus, amygdala and pallidum can differentiate schizophrenia patients from controls. We studied the role of hippocampal and subcortical structures in clinical high-risk individuals from two cohorts. High-resolution T1-weighted structural MRI brain scans of a total of 91 clinical high-risk individuals and 64 healthy controls were collected in two centers. The bilateral volume of the hippocampus, the thalamus, the caudate, the putamen, the pallidum, the amygdala, and the accumbens were automatically segmented using FSL-FIRST. A linear mixed-effects model and a prospective meta-analysis were applied to assess group-related volumetric differences. We report reduced hippocampal and thalamic volumes in clinical high-risk individuals compared to healthy controls. No volumetric alterations were detected for the caudate, the putamen, the pallidum, the amygdala, or the accumbens. Moreover, we found comparable medium effect sizes for group-related comparison of the thalamus in the two analytical methods. These findings underline the relevance of specific alterations in the hippocampal and subcortical volumes in the high-risk state. Further analyses may allow hippocampal and thalamic volumes to be used as biomarkers to predict psychosis.
Switching from weakly to strongly limited injection in self-aligned, nano-patterned organic transistors
Authors: Zojer Karin , Rothländer Thomas , Kraxner Johanna , Schmied Roland , Palfinger Ursula , Plank Harald , Grogger Werner , Haase Anja , Gold Herbert , Stadlober Barbara
Published: September 2016

Organic thin-film transistors for high frequency applications require large transconductances in combination with minimal parasitic capacitances. Techniques aiming at eliminating parasitic capacitances are prone to produce a mismatch between electrodes, in particular gaps between the gate and the interlayer electrodes. While such mismatches are typically undesirable, we demonstrate that, in fact, device structures with a small single-sided interlayer electrode gap directly probe the detrimental contact resistance arising from the presence of an injection barrier. By employing a self-alignment nanoimprint lithography technique, asymmetric coplanar organic transistors with an intentional gap of varying size (< 0.2 μm) between gate and one interlayer electrode are fabricated. An electrode overlap exceeding 1 μm with the other interlayer has been kept. Gaps, be them source or drain-sided, do not preclude transistor operation. The operation of the device with a source-gate gap reveals a current reduction up to two orders of magnitude compared to a source-sided overlap. Drift-diffusion based simulations reveal that this marked reduction is a consequence of a weakened gate-induced field at the contact which strongly inhibits injection.
DNA methylation profile of triple negative breast cancer-specific genes comparing lymph node positive patients to lymph node negative patients
Authors: Mathe Andrea , Wong-Brown Michelle , Locke Warwick J. , Stirzaker Clare , Braye Stephen G. , Forbes John F. , Clark Susan J. , Avery-Kiejda Kelly A. , Scott Rodney J.
Published: September 2016

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with no targeted treatment available. Our previous study identified 38 TNBC-specific genes with altered expression comparing tumour to normal samples. This study aimed to establish whether DNA methylation contributed to these expression changes in the same cohort as well as disease progression from primary breast tumour to lymph node metastasis associated with changes in the epigenome. We obtained DNA from 23 primary TNBC samples, 12 matched lymph node metastases, and 11 matched normal adjacent tissues and assayed for differential methylation profiles using Illumina HumanMethylation450 BeadChips. The results were validated in an independent cohort of 70 primary TNBC samples. The expression of 16/38 TNBC-specific genes was associated with alteration in DNA methylation. Novel methylation changes between primary tumours and lymph node metastases, as well as those associated with survival were identified. Altered methylation of 18 genes associated with lymph node metastasis were identified and validated. This study reveals the important role DNA methylation plays in altered gene expression of TNBC-specific genes and lymph node metastases. The novel insights into progression of TNBC to secondary disease may provide potential prognostic indicators for this hard-to-treat breast cancer subtype.
Water uptake mechanism and germination of Erythrina velutina seeds treated with atmospheric plasma
Authors: Alves Junior Clodomiro , de Oliveira Vitoriano Jussier , da Silva Dinnara Layza Souza , de Lima Farias Mikelly , de Lima Dantas Nadjamara Bandeira
Published: September 2016

The effect of plasma applied to mulungu (Erythrina velutina) seeds was studied to verify its influence on the germination, water absorption, wettability and structure of the seeds. The plasma jet used in this study was produced by dielectric barrier discharge (DBD) in a helium gas flow of 0.03 L/s at a distance of 13 mm for 60 s. The plasma treatment significantly affected the seed germination rate, which was approximately 5% higher than that of the untreated group. Micropyle and hilum contributed a greater proportion to uptake. When sealed in the hilar or micropyle regions the amount of water absorbed into the seed decreased approximately 75% compared to the unsealed seed. This difference suggests that these two regions together act cooperatively in the water absorption. However, when plasma treated seed was blocked in the micropyle region, water absorption was higher higher than in seeds blocked hilum. This difference suggests that the plasma treatment changed the wettability of the hilum more effectively than it changed the micropyle. These results indicate that plasma can significantly change the hydrophilicity, water absorption and percentage of seed germination in E. velutina.
Integration and Typologies of Vulnerability to Climate Change: A Case Study from Australian Wheat Sheep Zones
Authors: Huai Jianjun
Published: September 2016

Although the integrated indicator methods have become popular for assessing vulnerability to climate change, their proliferation has introduced a confusing array of scales and indicators that cause a science-policy gap. I argue for a clear adaptation pathway in an “integrative typology” of regional vulnerability that matches appropriate scales, optimal measurements and adaptive strategies in a six-dimensional and multi-level analysis framework of integration and typology inspired by the “5W1H” questions: “Who is concerned about how to adapt to the vulnerability of what to what in some place (where) at some time (when)?” Using the case of the vulnerability of wheat, barley and oats to drought in Australian wheat sheep zones during 1978–1999, I answer the “5W1H” questions through establishing the “six typologies” framework. I then optimize the measurement of vulnerability through contrasting twelve kinds of vulnerability scores with the divergence of crops yields from their regional mean. Through identifying the socioeconomic constraints, I propose seven generic types of crop-drought vulnerability and local adaptive strategy. Our results illustrate that the process of assessing vulnerability and selecting adaptations can be enhanced using a combination of integration, optimization and typology, which emphasize dynamic transitions and transformations between integration and typology.
Devitalisation of human cartilage by high hydrostatic pressure treatment: Subsequent cultivation of chondrocytes and mesenchymal stem cells on the devitalised tissue
Authors: Hiemer B. , Genz B. , Jonitz-Heincke A. , Pasold J. , Wree A. , Dommerich S. , Bader R.
Published: September 2016

The regeneration of cartilage lesions still represents a major challenge. Cartilage has a tissue-specific architecture, complicating recreation by synthetic biomaterials. A novel approach for reconstruction is the use of devitalised cartilage. Treatment with high hydrostatic pressure (HHP) achieves devitalisation while biomechanical properties are remained. Therefore, in the present study, cartilage was devitalised using HHP treatment and the potential for revitalisation with chondrocytes and mesenchymal stem cells (MSCs) was investigated. The devitalisation of cartilage was performed by application of 480 MPa over 10 minutes. Effective cellular inactivation was demonstrated by the trypan blue exclusion test and DNA quantification. Histology and electron microscopy examinations showed undamaged cartilage structure after HHP treatment. For revitalisation chondrocytes and MSCs were cultured on devitalised cartilage without supplementation of chondrogenic growth factors. Both chondrocytes and MSCs significantly increased expression of cartilage-specific genes. ECM stainings showed neocartilage-like structure with positive AZAN staining as well as collagen type II and aggrecan deposition after three weeks of cultivation. Our results showed that HHP treatment caused devitalisation of cartilage tissue. ECM proteins were not influenced, thus, providing a scaffold for chondrogenic differentiation of MSCs and chondrocytes. Therefore, using HHP-treated tissue might be a promising approach for cartilage repair.
Complex Network Clustering by a Multi-objective Evolutionary Algorithm Based on Decomposition and Membrane Structure
Authors: Ju Ying , Zhang Songming , Ding Ningxiang , Zeng Xiangxiang , Zhang Xingyi
Published: September 2016

The field of complex network clustering is gaining considerable attention in recent years. In this study, a multi-objective evolutionary algorithm based on membranes is proposed to solve the network clustering problem. Population are divided into different membrane structures on average. The evolutionary algorithm is carried out in the membrane structures. The population are eliminated by the vector of membranes. In the proposed method, two evaluation objectives termed as Kernel J-means and Ratio Cut are to be minimized. Extensive experimental studies comparison with state-of-the-art algorithms proves that the proposed algorithm is effective and promising.
Identifying anticancer peptides by using improved hybrid compositions
Authors: Li Feng-Min , Wang Xiao-Qian
Published: September 2016

Cancer is one of the main causes of threats to human life. Identification of anticancer peptides is important for developing effective anticancer drugs. In this paper, we developed an improved predictor to identify the anticancer peptides. The amino acid composition (AAC), the average chemical shifts (acACS) and the reduced amino acid composition (RAAC) were selected to predict the anticancer peptides by using the support vector machine (SVM). The overall prediction accuracy reaches to 93.61% in jackknife test. The results indicated that the combined parameter was helpful to the prediction for anticancer peptides.
Arachidonic acid mediates the formation of abundant alpha-helical multimers of alpha-synuclein
Authors: Iljina Marija , Tosatto Laura , Choi Minee L. , Sang Jason C. , Ye Yu , Hughes Craig D. , Bryant Clare E. , Gandhi Sonia , Klenerman David
Published: September 2016

The protein alpha-synuclein (αS) self-assembles into toxic beta-sheet aggregates in Parkinson’s disease, while it is proposed that αS forms soluble alpha-helical multimers in healthy neurons. Here, we have made αS multimers in vitro using arachidonic acid (ARA), one of the most abundant fatty acids in the brain, and characterized them by a combination of bulk experiments and single-molecule Fӧrster resonance energy transfer (sm-FRET) measurements. The data suggest that ARA-induced oligomers are alpha-helical, resistant to fibril formation, more prone to disaggregation, enzymatic digestion and degradation by the 26S proteasome, and lead to lower neuronal damage and reduced activation of microglia compared to the oligomers formed in the absence of ARA. These multimers can be formed at physiologically-relevant concentrations, and pathological mutants of αS form less multimers than wild-type αS. Our work provides strong biophysical evidence for the formation of alpha-helical multimers of αS in the presence of a biologically relevant fatty acid, which may have a protective role with respect to the generation of beta-sheet toxic structures during αS fibrillation.
Caloric restriction promotes cell survival in a mouse model of normal tension glaucoma
Authors: Guo Xiaoli , Kimura Atsuko , Azuchi Yuriko , Akiyama Goichi , Noro Takahiko , Harada Chikako , Namekata Kazuhiko , Harada Takayuki
Published: September 2016

Glaucoma is characterized by progressive degeneration of retinal ganglion cells (RGCs) and their axons. We previously reported that loss of glutamate transporters (EAAC1 or GLAST) in mice leads to RGC degeneration that is similar to normal tension glaucoma and these animal models are useful in examining potential therapeutic strategies. Caloric restriction has been reported to increase longevity and has potential benefits in injury and disease. Here we investigated the effects of every-other-day fasting (EODF), a form of caloric restriction, on glaucomatous pathology in EAAC1−/−mice. EODF suppressed RGC death and retinal degeneration without altering intraocular pressure. Moreover, visual impairment was ameliorated with EODF, indicating the functional significance of the neuroprotective effect of EODF. Several mechanisms associated with this neuroprotection were explored. We found that EODF upregulated blood β-hydroxybutyrate levels and increased histone acetylation in the retina. Furthermore, it elevated retinal mRNA expression levels of neurotrophic factors and catalase, whereas it decreased oxidative stress levels in the retina. Our findings suggest that EODF, a safe, non-invasive and low-cost treatment, may be available for glaucoma therapy.
Thickness of Actinic Keratosis Does Not Predict Dysplasia Severity or P53 Expression
Authors: Heerfordt Ida M. , Nissen Christoffer V. , Poulsen Thomas , Philipsen Peter A. , Wulf Hans Christian
Published: September 2016

The severity of dysplasia and expression of p53 in actinic keratosis (AK) is of importance for the transformation to squamous cell carcinoma. It is assumed that it is most important to treat thick AKs as they are believed to be more dysplastic than thin AKs. However, a relation between AK thickness and dysplasia or the expression of p53 has never been demonstrated. The aim of this study was to investigate this possible relation. Sixty-six AKs were included for clinical and histological examination. Prior to performing a punch biopsy, the clinical thickness of each AK was measured objectively using two scale bars with a thickness of 0.5 mm and 1 mm. Subsequently, the thickness of the epidermis, the severity of dysplasia and the expression of p53 were assessed histologically. We found a strong and significant positive correlation between measured clinical thickness of the AKs and the histological thickness of epidermis (p < 0.0001). However, the clinical thickness did not correlate with either the severity of dysplasia (p = 0.7) or the expression of p53 (p = 0.5). In conclusion, thin AKs show the same severity of dysplasia and expression of p53 as thicker AK lesions. Consequently, clinical thickness cannot predict aggressiveness.
Aberrant Meiotic Prophase I Leads to Genic Male Sterility in the Novel TE5A Mutant of Brassica napus
Authors: Yan Xiaohong , Zeng Xinhua , Wang Shasha , Li Keqi , Yuan Rong , Gao Hongfei , Luo Junling , Liu Fang , Wu Yuhua , Li Yunjing , Zhu Li , Wu Gang
Published: September 2016

Genic male sterility (GMS) has already been extensively utilized for hybrid rapeseed production. TE5A is a novel thermo-sensitive dominant GMS line in Brassica napus, however, its mechanisms of GMS remain largely unclear. Histological and Transmission electron microscopy (TEM) analyses of anthers showed that the male gamete development of TE5A was arrested at meiosis prophase I. EdU uptake of S-phase meiocytes revealed that the TE5A mutant could accomplish DNA replication, however, chromosomal and fluorescence in situ hybridization (FISH) analyses of TE5A showed that homologous chromosomes could not pair, synapse, condense and form bivalents. We then analyzed the transcriptome differences between young floral buds of sterile plants and its near-isogenic fertile plants through RNA-Seq. A total of 3,841 differentially expressed genes (DEGs) were obtained, some of which were associated with homologous chromosome behavior and cell cycle control during meiosis. Dynamic expression changes of selected candidate DEGs were then analyzed at different anther developmental stages. The present study not only demonstrated that the TE5A mutant had defects in meiotic prophase I via detailed cytological analysis, but also provided a global insight into GMS-associated DEGs and elucidated the mechanisms of GMS in TE5A through RNA-Seq.
FAMSA: Fast and accurate multiple sequence alignment of huge protein families
Authors: Deorowicz Sebastian , Debudaj-Grabysz Agnieszka , Gudyś Adam
Published: September 2016

Rapid development of modern sequencing platforms has contributed to the unprecedented growth of protein families databases. The abundance of sets containing hundreds of thousands of sequences is a formidable challenge for multiple sequence alignment algorithms. The article introduces FAMSA, a new progressive algorithm designed for fast and accurate alignment of thousands of protein sequences. Its features include the utilization of the longest common subsequence measure for determining pairwise similarities, a novel method of evaluating gap costs, and a new iterative refinement scheme. What matters is that its implementation is highly optimized and parallelized to make the most of modern computer platforms. Thanks to the above, quality indicators, i.e. sum-of-pairs and total-column scores, show FAMSA to be superior to competing algorithms, such as Clustal Omega or MAFFT for datasets exceeding a few thousand sequences. Quality does not compromise on time or memory requirements, which are an order of magnitude lower than those in the existing solutions. For example, a family of 415519 sequences was analyzed in less than two hours and required no more than 8 GB of RAM. FAMSA is available for free at http://sun.aei.polsl.pl/REFRESH/famsa.
Characterization of aerosols containing Legionella generated upon nebulization
Authors: Allegra Séverine , Leclerc Lara , Massard Pierre André , Girardot Françoise , Riffard Serge , Pourchez Jérémie
Published: September 2016

Legionella pneumophila is, by far, the species most frequently associated with Legionnaires’ disease (LD). Human infection occurs almost exclusively by aerosol inhalation which places the bacteria in juxtaposition with alveolar macrophages. LD risk management is based on controlling water quality by applying standardized procedures. However, to gain a better understanding of the real risk of exposure, there is a need (i) to investigate under which conditions Legionella may be aerosolized and (ii) to quantify bacterial deposition into the respiratory tract upon nebulization. In this study, we used an original experimental set-up that enables the generation of aerosol particles containing L. pneumophila under various conditions. Using flow cytometry in combination with qPCR and culture, we determined (i) the size of the aerosols and (ii) the concentration of viable Legionella forms that may reach the thoracic region. We determined that the 0.26–2.5 μm aerosol size range represents 7% of initial bacterial suspension. Among the viable forms, 0.7% of initial viable bacterial suspension may reach the pulmonary alveoli. In conclusion, these deposition profiles can be used to standardize the size of inoculum injected in any type of respiratory tract model to obtain new insights into the dose response for LD.
Historical colonization and dispersal limitation supplement climate and topography in shaping species richness of African lizards (Reptilia: Agaminae)
Authors: Kissling W. Daniel , Blach-Overgaard Anne , Zwaan Roelof E. , Wagner Philipp
Published: September 2016

To what extent deep-time dispersal limitation shapes present-day biodiversity at broad spatial scales remains elusive. Here, we compiled a continental dataset on the distributions of African lizard species in the reptile subfamily Agaminae (a relatively young, Neogene radiation of agamid lizards which ancestors colonized Africa from the Arabian peninsula) and tested to what extent historical colonization and dispersal limitation (i.e. accessibility from areas of geographic origin) can explain present-day species richness relative to current climate, topography, and climate change since the late Miocene (~10 mya), the Pliocene (~3 mya), and the Last Glacial Maximum (LGM, 0.021 mya). Spatial and non-spatial multi-predictor regression models revealed that time-limited dispersal via arid corridors is a key predictor to explain macro-scale patterns of species richness. In addition, current precipitation seasonality, current temperature of the warmest month, paleo-temperature changes since the LGM and late Miocene, and topographic relief emerged as important drivers. These results suggest that deep-time dispersal constraints — in addition to climate and mountain building — strongly shape current species richness of Africa’s arid-adapted taxa. Such historical dispersal limitation might indicate that natural movement rates of species are too slow to respond to rates of ongoing and projected future climate and land use change.
Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies
Authors: Zhang Qingchun , Jin Bo , Shi Zhaotao , Wang Xiaofang , Liu Qiangqiang , Lei Shan , Peng Rufang
Published: September 2016

A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III) and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6-carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents.
Heat production and error probability relation in Landauer reset at effective temperature
Authors: Neri Igor , López-Suárez Miquel
Published: September 2016

The erasure of a classical bit of information is a dissipative process. The minimum heat produced during this operation has been theorized by Rolf Landauer in 1961 to be equal to kBT ln2 and takes the name of Landauer limit, Landauer reset or Landauer principle. Despite its fundamental importance, the Landauer limit remained untested experimentally for more than fifty years until recently when it has been tested using colloidal particles and magnetic dots. Experimental measurements on different devices, like micro-mechanical systems or nano-electronic devices are still missing. Here we show the results obtained in performing the Landauer reset operation in a micro-mechanical system, operated at an effective temperature. The measured heat exchange is in accordance with the theory reaching values close to the expected limit. The data obtained for the heat production is then correlated to the probability of error in accomplishing the reset operation.
Cell-free synthesis of functional human epidermal growth factor receptor: Investigation of ligand-independent dimerization in Sf21 microsomal membranes using non-canonical amino acids
Authors: Quast Robert B. , Ballion Biljana , Stech Marlitt , Sonnabend Andrei , Varga Balázs R. , Wüstenhagen Doreen A. , Kele Péter , Schiller Stefan M. , Kubick Stefan
Published: September 2016

Cell-free protein synthesis systems represent versatile tools for the synthesis and modification of human membrane proteins. In particular, eukaryotic cell-free systems provide a promising platform for their structural and functional characterization. Here, we present the cell-free synthesis of functional human epidermal growth factor receptor and its vIII deletion mutant in a microsome-containing system derived from cultured Sf21 cells. We provide evidence for embedment of cell-free synthesized receptors into microsomal membranes and asparagine-linked glycosylation. Using the cricket paralysis virus internal ribosome entry site and a repetitive synthesis approach enrichment of receptors inside the microsomal fractions was facilitated thereby providing analytical amounts of functional protein. Receptor tyrosine kinase activation was demonstrated by monitoring receptor phosphorylation. Furthermore, an orthogonal cell-free translation system that provides the site-directed incorporation of p-azido-L-phenylalanine is characterized and applied to investigate receptor dimerization in the absence of a ligand by photo-affinity cross-linking. Finally, incorporated azides are used to generate stable covalently linked receptor dimers by strain-promoted cycloaddition using a novel linker system.
Benchmarking Measures of Network Influence
Authors: Bramson Aaron , Vandermarliere Benjamin
Published: September 2016

Identifying key agents for the transmission of diseases (ideas, technology, etc.) across social networks has predominantly relied on measures of centrality on a static base network or a temporally flattened graph of agent interactions. Various measures have been proposed as the best trackers of influence, such as degree centrality, betweenness and k-shell, depending on the structure of the connectivity. We consider SIR and SIS propagation dynamics on a temporally-extruded network of observed interactions and measure the conditional marginal spread as the change in the magnitude of the infection given the removal of each agent at each time: its temporal knockout (TKO) score. We argue that this TKO score is an effective benchmark measure for evaluating the accuracy of other, often more practical, measures of influence. We find that none of the network measures applied to the induced flat graphs are accurate predictors of network propagation influence on the systems studied; however, temporal networks and the TKO measure provide the requisite targets for the search for effective predictive measures.