bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent random deformation model of cells crawling on a gel surface
Authors: Ebata Hiroyuki , Yamamoto Aki , Tsuji Yukie , Sasaki Saori , Moriyama Kousuke , Kuboki Thasaneeya , Kidoaki Satoru 
Published: March 2018

AbstractIn general, cells move on a substrate through extension and contraction of the cell body. Though cell movement should be explained by taking into account the effect of such shape fluctuations, past approaches to formulate cell-crawling have not sufficiently quantified the relationship between cell movement (velocity and trajectory) and shape fluctuations based on experimental data regarding actual shaping dynamics. To clarify this relationship, we experimentally characterized cell-crawling in terms of shape fluctuations, especially extension and contraction, by using an elasticity-tunable gel substrate to modulate cell shape. As a result, an amoeboid swimmer-like relation was found to arise between the cell velocity and cell-shape dynamics. To formulate this experimentally-obtained relationship between cell movement and shaping dynamics, we established a persistent random deformation (PRD) model based on equations of a deformable self-propelled particle adopting an amoeboid swimmer-like velocity-shape relationship. The PRD model successfully explains the statistical properties of velocity, trajectory and shaping dynamics of the cells including back-and-forth motion, because the velocity equation exhibits time-reverse symmetry, which is essentially different from previous models. We discuss the possible application of this model to classify the phenotype of cell migration based on the characteristic relation between movement and shaping dynamics.
Timing of the Saalian- and Elsterian glacial cycles and the implications for Middle – Pleistocene hominin presence in central Europe
Authors: Lauer Tobias , Weiss Marcel 
Published: March 2018

AbstractBy establishing a luminescence-based chronology for fluvial deposits preserved between the Elsterian- and Saalian tills in central Germany, we obtained information on the timing of both the Middle Pleistocene glacial cycles and early human appearance in central Europe. The luminescence ages illustrate different climatic driven fluvial aggradation periods during the Saalian glacial cycle spanning from 400–150 ka. The ages of sediments directly overlying the Elsterian till are approximately 400 ka and prove that the first extensive Fennoscandian ice sheet extension during the Quaternary correlates with MIS 12 and not with MIS 10. Furthermore, the 400 ka old fluvial units contain Lower Paleolithic stone artefacts that document the first human appearance in the region. In addition, we demonstrate that early MIS 8 is a potential date for the onset of the Middle Paleolithic in central Germany, as Middle Paleolithic stone artefacts are correlated with fluvial units deposited between 300 ka and 200 ka. However, the bulk of Middle Paleolithic sites date to MIS 7 in the region. The fluvial units preserved directly under the till of the southernmost Saalian ice yield an age of about 150 ka, and enable a correlation of the Drenthe stage to late MIS 6.
Environmental complexity buffers against stress-induced negative judgement bias in female chickens
Authors: Zidar Josefina , Campderrich Irene , Jansson Emelie , Wichman Anette , Winberg Svante , Keeling Linda , Løvlie Hanne 
Published: March 2018

AbstractCognitive processes are often biased by emotions. In humans, affective disorders are accompanied by pessimistic judgement, while optimistic judgement is linked to emotional stability. Similar to humans, animals tend to interpret ambiguous stimuli negatively after experiencing stressful events, although the long-lasting impact on judgement bias has rarely been investigated. We measure judgement bias in female chicks (Gallus gallus domesticus) after exposure to cold stress, and before and after exposure to additional unpredictable stressors. Additionally, we explore if brain monoamines can explain differences in judgement bias. Chicks exposed to cold stress did not differ in judgement bias compared to controls, but showed sensitivity to additional stressors by having higher motivation for social reinstatement. Environmental complexity reduced stress-induced negative judgement bias, by maintaining an optimistic bias in individuals housed in complex conditions even after stress exposure. Moreover, judgement bias was related to dopamine turnover rate in mesencephalon, with higher activity in individuals that had a more optimistic response. These results demonstrate that environmental complexity can buffer against negative effects of additive stress and that dopamine relates to judgement bias in chicks. These results reveal that both internal and external factors can mediate emotionally biased judgement in animals, thus showing similarities to findings in humans.
Identification of an Arg-Leu-Arg tripeptide that contributes to the binding interface between the cytokine MIF and the chemokine receptor CXCR4
Authors: Lacy Michael , Kontos Christos , Brandhofer Markus , Hille Kathleen , Gröning Sabine , Sinitski Dzmitry , Bourilhon Priscila , Rosenberg Eric , Krammer Christine , Thavayogarajah Tharshika , Pantouris Georgios , Bakou Maria , Weber Christian , Lolis Elias , Bernhagen Jürgen , Kapurniotu Aphrodite 
Published: March 2018

AbstractMIF is a chemokine-like cytokine that plays a role in the pathogenesis of inflammatory and cardiovascular disorders. It binds to the chemokine-receptors CXCR2/CXCR4 to trigger atherogenic leukocyte migration albeit lacking canonical chemokine structures. We recently characterized an N-like-loop and the Pro-2-residue of MIF as critical molecular determinants of the CXCR4/MIF binding-site and identified allosteric agonism as a mechanism that distinguishes CXCR4-binding to MIF from that to the cognate ligand CXCL12. By using peptide spot-array technology, site-directed mutagenesis, structure-activity-relationships, and molecular docking, we identified the Arg-Leu-Arg (RLR) sequence-region 87–89 that – in three-dimensional space – ‘extends’ the N-like-loop to control site-1-binding to CXCR4. Contrary to wildtype MIF, mutant R87A-L88A-R89A-MIF fails to bind to the N-terminal of CXCR4 and the contribution of RLR to the MIF/CXCR4-interaction is underpinned by an ablation of MIF/CXCR4-specific signaling and reduction in CXCR4-dependent chemotactic leukocyte migration of the RLR-mutant of MIF. Alanine-scanning, functional competition by RLR-containing peptides, and molecular docking indicate that the RLR residues directly participate in contacts between MIF and CXCR4 and highlight the importance of charge-interactions at this interface. Identification of the RLR region adds important structural information to the MIF/CXCR4 binding-site that distinguishes this interface from CXCR4/CXCL12 and will help to design MIF-specific drug-targeting approaches.
Surface enhanced Raman spectroscopy of Chlamydia trachomatis and Neisseria gonorrhoeae for diagnostics, and extra-cellular metabolomics and biochemical monitoring
Authors: Chen Y. , Premasiri W. R. , Ziegler L. D. 
Published: March 2018

AbstractSERS spectra excited at 785 nm of the bacteria Chlamydia trahomatis (elementary bodies, EB) and Neisseria gonorrheoae, the causative pathogens for the two most common sexually transmitted diseases (STD), chlamydia and gonorrhea, respectively, are reported. Although both are Gram-negative bacteria, the SERS signatures of C. trachomatis and N. gonorrheoae are completely different. N. gonorrheoae SERS spectra are due to the starvation induced nucleotide metabolites adenine and guanine, and the surface associated co-enzyme nicotinamide adenine dinucleotide and are very similar on Au and Ag although the spectrum appears more rapidly on Ag. The C. trachomatis SERS spectrum is dominated by the vibrational features of cell surface proteins. While features attributable to specific residues and the amide backbone characterize the C. trachomatis spectrum on Ag, the corresponding SERS spectrum on Au substrates displays vibrational characteristics of aggregated proteins. The prospects for the development of a SERS based platform for rapid (<one hour), low-cost bacterial STD diagnostics are promising based on these initial studies. Furthermore, this biomedical application demonstrates the potential for SERS to be a sensitive real time probe of the dynamics of biochemical activity in the cell wall and extracellular regions of microorganisms.
CD4+ and CD8+ T Cells Exert Regulatory Properties During Experimental Acute Aristolochic Acid Nephropathy
Authors: Baudoux Thomas , Husson Cécile , De Prez Eric , Jadot Inès , Antoine Marie-Hélène , Nortier Joëlle L. , Hougardy Jean-Michel 
Published: March 2018

AbstractExperimental aristolochic acid nephropathy is characterized by transient acute proximal tubule necrosis and inflammatory cell infiltrates followed by interstitial fibrosis and tubular atrophy. The respective role of T-cell subpopulations has never been studied in the acute phase of the mouse model, and was heretofore exclusively investigated by the use of several depletion protocols. As compared to mice injected with aristolochic acids alone, more severe acute kidney injury was observed after CD4+ or CD8+ T-cells depletion. TNF-alpha and MCP-1 mRNA renal expressions were also increased. In contrast, regulatory T-cells depletion did not modify the severity of the aristolochic acids induced acute kidney injury, suggesting an independent mechanism. Aristolochic acids nephropathy was also associated with an increased proportion of myeloid CD11bhighF4/80mid and a decreased proportion of their counterpart CD11blowF4/80high population. After CD4+ T-cell depletion the increase in the CD11bhighF4/80mid population was even higher whereas the decrease in the CD11blowF4/80high population was more marked after CD8+ T cells depletion. Our results suggest that CD4+ and CD8+ T-cells provide protection against AA-induced acute tubular necrosis. Interestingly, T-cell depletion was associated with an imbalance of the CD11bhighF4/80mid and CD11blowF4/80high populations.
Exercise Mitigates Alcohol Induced Endoplasmic Reticulum Stress Mediated Cognitive Impairment through ATF6-Herp Signaling
Authors: George Akash K. , Behera Jyotirmaya , Kelly Kimberly E. , Mondal Nandan K. , Richardson Kennedy P. , Tyagi Neetu 
Published: March 2018

AbstractChronic ethanol/alcohol (AL) dosing causes an elevation in homocysteine (Hcy) levels, which leads to the condition known as Hyperhomocysteinemia (HHcy). HHcy enhances oxidative stress and blood-brain-barrier (BBB) disruption through modulation of endoplasmic reticulum (ER) stress; in part by epigenetic alternation, leading to cognitive impairment. Clinicians have recommended exercise as a therapy; however, its protective effect on cognitive functions has not been fully explored. The present study was designed to observe the protective effects of exercise (EX) against alcohol-induced epigenetic and molecular alterations leading to cerebrovascular dysfunction. Wild-type mice were subjected to AL administration (1.5 g/kg-bw) and subsequent treadmill EX for 12 weeks (5 day/week@7–11 m/min). AL affected mouse brain through increases in oxidative and ER stress markers, SAHH and DNMTs alternation, while decreases in CBS, CSE, MTHFR, tight-junction proteins and cellular H2S levels. Mechanistic study revealed that AL increased epigenetic DNA hypomethylation of Herp promoter. BBB dysfunction and cognitive impairment were observed in the AL treated mice. AL mediated transcriptional changes were abolished by administration of ER stress inhibitor DTT. In conclusion, exercise restored Hcy and H2S to basal levels while ameliorating AL-induced ER stress, diminishing BBB dysfunction and improving cognitive function via ATF6-Herp-signaling. EX showed its protective efficacy against AL-induced neurotoxicity.
Boson peak, heterogeneity and intermediate-range order in binary SiO2-Al2O3 glasses
Authors: Ando Mariana F. , Benzine Omar , Pan Zhiwen , Garden Jean-Luc , Wondraczek Katrin , Grimm Stephan , Schuster Kay , Wondraczek Lothar 
Published: March 2018

AbstractIn binary aluminosilicate liquids and glasses, heterogeneity on intermediate length scale is a crucial factor for optical fiber performance, determining the lower limit of optical attenuation and Rayleigh scattering, but also clustering and precipitation of optically active dopants, for example, in the fabrication of high-power laser gain media. Here, we consider the low-frequency vibrational modes of such materials for assessing structural heterogeneity on molecular scale. We determine the vibrational density of states VDoS g(ω) using low-temperature heat capacity data. From correlation with low-frequency Raman spectroscopy, we obtain the Raman coupling coefficient. Both experiments allow for the extraction of the average dynamic correlation length as a function of alumina content. We find that this value decreases from about 3.9 nm to 3.3 nm when mildly increasing the alumina content from zero (vitreous silica) to 7 mol%. At the same time, the average inter-particle distance increases slightly due to the presence of oxygen tricluster species. In accordance with Loewensteinian dynamics, this proves that mild alumina doping increases structural homogeneity on molecular scale.
A band of bound states in the continuum induced by disorder
Authors: Xiao Yi-Xin , Zhang Zhao-Qing , Chan C. T. 
Published: March 2018

AbstractBound states in the continuum usually refer to the phenomenon of a single or a few discrete bound states embedded in a continuous spectrum of extended states. Here we propose a simple mechanism to achieve a band of bound states in the continuum in a class of disordered quasi-1D and quasi-2D systems, where the bound states and extended states overlap completely in a spectral range. The systems are partially disordered in a way that a band of extended states always exists, not affected by the randomness, whereas the states in all other bands become localized and cover the entire spectrum of extended states. We demonstrate such disordered-induced bound states in the continuum in disordered multi-chain and multi-layer systems.
Lumenal exposed regions of the D1 protein of PSII are long enough to be degraded by the chloroplast Deg1 protease
Authors: Knopf Ronit Rimon , Adam Zach 
Published: March 2018

AbstractDegradation of the D1 protein of photosystem II (PSII) reaction center is a pre-requisite for the repair cycle from photoinhibition. Two types of thylakoid proteases, FtsH and Deg, have been demonstrated to participate in this process. However, the location of the proteolytic sites of the lumenal Deg1 protease within its internal sphere raised the question whether the lumenal-exposed regions of D1 are indeed long enough to reach these sites. Implanting these regions into the stable GFP rendered it sensitive to the presence of Deg1 in vitro, demonstrating that the flexible regions of D1 that protrude into the lumen can penetrate through the three side-openings of Deg1 and reach its internal proteolytic sites. This mode of action, facilitating cooperation between proteases on both sides of the thylakoid membranes, should be applicable to the degradation of other integral thylakoid membrane proteins as well.
Improved efficiency of in situ protein analysis by proximity ligation using UnFold probes
Authors: Klaesson Axel , Grannas Karin , Ebai Tonge , Heldin Johan , Koos Björn , Leino Mattias , Raykova Doroteya , Oelrich Johan , Arngården Linda , Söderberg Ola , Landegren Ulf 
Published: March 2018

AbstractWe have redesigned probes forin situproximity ligation assay (PLA), resulting in more efficient localized detection of target proteins.In situPLA depends on recognition of target proteins by pairs of antibody-oligonucleotide conjugates (PLA probes), which jointly give rise to DNA circles that template localized rolling circle amplification reactions. The requirement for dual recognition of the target proteins improves selectivity by ignoring any cross-reactivity not shared by the antibodies, and it allows detection of protein-protein interactions and post-translational modifications. We herein describe an improved design of the PLA probes –UnFold probes – where all elements required for formation of circular DNA strands are incorporated in the probes. Premature interactions between the UnFold probes are prevented by including an enzymatic “unfolding” step in the detection reactions. This allows DNA circles to form by pairs of reagents only after excess reagents have been removed. We demonstrate the performance of UnFold probes for detection of protein-protein interactions and post-translational modifications in fixed cells and tissues, revealing considerably more efficient signal generation. We also apply the UnFold probes to detect IL-6 in solution phase after capture on solid supports, demonstrating increased sensitivity over both normal sandwich enzyme-linked immunosorbent assays and conventional PLA assays.
Recurrence of task-related electroencephalographic activity during post-training quiet rest and sleep
Authors: Murphy Michael , Stickgold Robert , Parr Mittie Elaine , Callahan Cameron , Wamsley Erin J. 
Published: March 2018

AbstractOffline reactivation of task-related neural activity has been demonstrated in animals but is difficult to directly observe in humans. We sought to identify potential electroencephalographic (EEG) markers of offline memory processing in human subjects by identifying a set of characteristic EEG topographies (“microstates”) that occurred as subjects learned to navigate a virtual maze. We hypothesized that these task-related microstates would appear during post-task periods of rest and sleep. In agreement with this hypothesis, we found that one task-related microstate was increased in post-training rest and sleep compared to baseline rest, selectively for subjects who actively learned the maze, and not in subjects performing a non-learning control task. Source modeling showed that this microstate was produced by activity in temporal and parietal networks, which are known to be involved in spatial navigation. For subjects who napped after training, the increase in this task-related microstate predicted the magnitude of subsequent change in performance. Our findings demonstrate that task-related EEG patterns re-emerge during post-training rest and sleep.
LentiPro26: novel stable cell lines for constitutive lentiviral vector production
Authors: Tomás H. A. , Rodrigues A. F. , Carrondo M. J. T. , Coroadinha A. S. 
Published: March 2018

AbstractLentiviral vectors (LVs) are excellent tools to promote gene transfer and stable gene expression. Their potential has been already demonstrated in gene therapy clinical trials for the treatment of diverse disorders. For large scale LV production, a stable producer system is desirable since it allows scalable and cost-effective viral productions, with increased reproducibility and safety. However, the development of stable systems has been challenging and time-consuming, being the selection of cells presenting high expression levels of Gag-Pro-Pol polyprotein and the cytotoxicity associated with some viral components, the main limitations. Hereby is described the establishment of a new LV producer cell line using a mutated less active viral protease to overcome potential cytotoxic limitations. The stable transfection of bicistronic expression cassettes with re-initiation of the translation mechanism enabled the generation of LentiPro26 packaging populations supporting high titers. Additionally, by skipping intermediate clone screening steps and performing only one final clone screening, it was possible to save time and generate LentiPro26-A59 cell line, that constitutively produces titers above 106 TU.mL−1.day−1, in less than six months. This work constitutes a step forward towards the development of improved LV producer cell lines, aiming to efficiently supply the clinical expanding gene therapy applications.
Structural insights into the RNA methyltransferase domain of METTL16
Authors: Ruszkowska Agnieszka , Ruszkowski Milosz , Dauter Zbigniew , Brown Jessica A. 
Published: March 2018

AbstractN6-methyladenosine (m6A) is an abundant modification in messenger RNA and noncoding RNAs that affects RNA metabolism. Methyltransferase-like protein 16 (METTL16) is a recently confirmed m6A RNA methyltransferase that methylates U6 spliceosomal RNA and interacts with the 3′-terminal RNA triple helix of MALAT1 (metastasis-associated lung adenocarcinoma transcript 1). Here, we present two X-ray crystal structures of the N-terminal methyltransferase domain (residues 1–291) of human METTL16 (METTL16_291): an apo structure at 1.9 Å resolution and a post-catalyticS-adenosylhomocysteine-bound complex at 2.1 Å resolution. The structures revealed a highly conserved Rossmann fold that is characteristic of Class IS-adenosylmethionine-dependent methyltransferases and a large, positively charged groove. This groove likely represents the RNA-binding site and it includes structural elements unique to METTL16. In-depth analysis of the active site led to a model of the methyl transfer reaction catalyzed by METTL16. In contrast to the major m6A methyltransferase heterodimer METTL3/METTL14, full-length METTL16 forms a homodimer and METTL16_291 exists as a monomer based on size-exclusion chromatography. A native gel-shift assay shows that METTL16 binds to the MALAT1 RNA triple helix, but monomeric METTL16_291 does not. Our results provide insights into the molecular structure of METTL16, which is distinct from METTL3/METTL14.
Computational repositioning and preclinical validation of mifepristone for human vestibular schwannoma
Authors: Sagers Jessica E. , Brown Adam S. , Vasilijic Sasa , Lewis Rebecca M. , Sahin Mehmet I. , Landegger Lukas D. , Perlis Roy H. , Kohane Isaac S. , Welling D. Bradley , Patel Chirag J. , Stankovic Konstantina M. 
Published: March 2018

AbstractThe computational repositioning of existing drugs represents an appealing avenue for identifying effective compounds to treat diseases with no FDA-approved pharmacotherapies. Here we present the largest meta-analysis to date of differential gene expression in human vestibular schwannoma (VS), a debilitating intracranial tumor, and use these data to inform the first application of algorithm-based drug repositioning for this tumor class. We apply an open-source computational drug repositioning platform to gene expression data from 80 patient tumors and identify eight promising FDA-approved drugs with potential for repurposing in VS. Of these eight, mifepristone, a progesterone and glucocorticoid receptor antagonist, consistently and adversely affects the morphology, metabolic activity, and proliferation of primary human VS cells and HEI-193 human schwannoma cells. Mifepristone treatment reduces VS cell viability more significantly than cells derived from patient meningiomas, while healthy human Schwann cells remain unaffected. Our data recommend a Phase II clinical trial of mifepristone in VS.