bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developmental nonlinearity drives phenotypic robustness
Authors: Green Rebecca M. , Fish Jennifer L. , Young Nathan M. , Smith Francis J. , Roberts Benjamin , Dolan Katie , Choi Irene , Leach Courtney L. , Gordon Paul , Cheverud James M. , Roseman Charles C. , Williams Trevor J. , Marcucio Ralph S. , Hallgrímsson Benedikt 
Published: November 2017

AbstractRobustness to perturbation is a fundamental feature of complex organisms. Mutations are the raw material for evolution, yet robustness to their effects is required for species survival. The mechanisms that produce robustness are poorly understood. Nonlinearities are a ubiquitous feature of development that may link variation in development to phenotypic robustness. Here, we manipulate the gene dosage of a signaling molecule, Fgf8, a critical regulator of vertebrate development. We demonstrate that variation in Fgf8 expression has a nonlinear relationship to phenotypic variation, predicting levels of robustness among genotypes. Differences in robustness are not due to gene expression variance or dysregulation, but emerge from the nonlinearity of the genotype–phenotype curve. In this instance, embedded features of development explain robustness differences. How such features vary in natural populations and relate to genetic variation are key questions for unraveling the origin and evolvability of this feature of organismal development.
Galectin-3 impacts Cryptococcus neoformans infection through direct antifungal effects
Authors: Almeida Fausto , Wolf Julie M. , da Silva Thiago Aparecido , DeLeon-Rodriguez Carlos M. , Rezende Caroline Patini , Pessoni André Moreira , Fernandes Fabrício Freitas , Silva-Rocha Rafael , Martinez Roberto , Rodrigues Marcio L. , Roque-Barreira Maria Cristina , Casadevall Arturo 
Published: November 2017

AbstractCryptococcus neoformans is an encapsulated fungal pathogen that causes cryptococcosis, which is a major opportunistic infection in immunosuppressed individuals. Mammalian β-galactoside-binding protein Galectin-3 (Gal-3) modulates the host innate and adaptive immunity, and plays significant roles during microbial infections including some fungal diseases. Here we show that this protein plays a role also in C. neoformans infection. We find augmented Gal-3 serum levels in human and experimental infections, as well as in spleen, lung, and brain tissues of infected mice. Gal-3-deficient mice are more susceptible to cryptococcosis than WT animals, as demonstrated by the higher fungal burden and lower animal survival. In vitro experiments show that Gal-3 inhibits fungal growth and exerts a direct lytic effect on C. neoformans extracellular vesicles (EVs). Our results indicate a direct role for Gal-3 in antifungal immunity whereby this molecule affects the outcome of C. neoformans infection by inhibiting fungal growth and reducing EV stability, which in turn could benefit the host.
Non motor symptoms in progressive supranuclear palsy: prevalence and severity
Authors: Radicati Fabiana Giada , Martinez Martin Pablo , Fossati Chiara , Chaudhuri Kallol Ray , Torti Margherita , Rodriguez Blazquez Carmen , Vacca Laura , Stocchi Fabrizio 
Published: November 2017

AbstractNMSs have been extensively studied in PD patients but not in other forms of parkinsonism such as Progressive Supranuclear Palsy (PSP). The primary objective of this study was to analyze the frequency, severity and the type of non-motor symptoms (NMS) in PSP patients using the non-motor symptoms scale (NMSS). The secondary objective was to differentiate NMS between PSP and Parkinson’s disease (PD). We enrolled in this cross-sectional study 50 consecutive PSP and 100 matched Parkinson’s disease (PD) patients, in the proportion PSP/PD = 1/2, matched in age, sex, and disease duration. Motor and Non Motor symptoms (different scales for each disease) were evaluated at baseline using PSP scale, SCOPA Motor, Montreal Cognitive Assessment (MOCA), HADS, Hamilton, and Non Motor Symptom scale (NMSS). Comparative analysis was done using chi-squared test, Mann-Whitney test and Fisher’s exact test. Fifty PSP (56% female) and 100 PD (59% female) patients completed the study protocol and were included for statistical analysis. The NMSS total domains score in the PSP group was 77.58 ± 42.95 (range 14–163) with NMS burden grade: 4, very severe, and the in the PD group was 41.97 ± 35.45 (range: 0–215) with NMS burden grade: 3, severe. The comparative analysis showed that NMS total score (p < 0.0001), Sleep/Fatigue (p = 0.0007), Mood/Apathy (p = 0.0001), Gastrointestinal (p < 0.0001), and Urinary dysfunction (p = 0.0001) domains were significantly more severe in PSP patients than in PD. This observational study reports that NMSs are very frequent in PSP patients hence the higher burden of NMS in PSP specifically related to mood/apathy, attention/memory, gastrointestinal, urinary disturbances compared to PD.
Integrative gene network analysis identifies key signatures, intrinsic networks and host factors for influenza virus A infections
Authors: Forst Christian V. , Zhou Bin , Wang Minghui , Chou Tsui-Wen , Mason Guy , Song Won-min , Schadt Eric , Ghedin Elodie , Zhang Bin 
Published: November 2017

AbstractInfluenza A virus, with the limited coding capacity of 10–14 proteins, requires the host cellular machinery for many aspects of its life cycle. Knowledge of these host cell requirements not only reveals molecular pathways exploited by the virus or triggered by the immune system, but also provides further targets for antiviral drug development. To uncover novel pathways and key targets of influenza infection, we assembled a large amount of data from 12 cell-based gene-expression studies of influenza infection for an integrative network analysis. We systematically identified differentially expressed genes and gene co-expression networks induced by influenza infection. We revealed the dedicator of cytokinesis 5 (DOCK5) played potentially an important role for influenza virus replication. CRISPR/Cas9 knockout of DOCK5 reduced influenza virus replication, indicating that DOCK5 is a key regulator for the viral life cycle. DOCK5’s targets determined by the DOCK5 knockout experiments strongly validated the predicted gene signatures and networks. This study systematically uncovered and validated fundamental patterns of molecular responses, intrinsic structures of gene co-regulation, and novel key targets in influenza virus infection.
Exosomes from antigen-pulsed dendritic cells induce stronger antigen-specific immune responses than microvesicles in vivo
Authors: Wahlund Casper J. E. , Güclüler Gözde , Hiltbrunner Stefanie , Veerman Rosanne E. , Näslund Tanja I. , Gabrielsson Susanne 
Published: November 2017

AbstractExtracellular vesicles (EV), including exosomes and microvesicles (MV), represent a rapidly expanding field of research with diagnostic and therapeutic applications. Although many aspects of EV function remain to be revealed and broad investigations are warranted, most published findings focus on only one vesicle category or a non-separated mix of EVs. In this paper, we investigated both MVs and exosomes from Ovalbumin (OVA)-pulsed dendritic cells for their immunostimulatory potential side-by-side in vivo. Only exosomes induced antigen-specific CD8+ T-cells, and were more efficient than MVs in eliciting antigen-specific IgG production. Further, mainly exosome-primed mouse splenocytes showed significant ex vivo interferon gamma production in response to antigen restimulation. Exosomes carried high levels of OVA, while OVA in MVs was barely detectable, which could explain the more potent antigen-specific response induced by exosomes. Moreover, exosomes induced increased germinal center B cell proportions, whereas MVs had no such effect. Immunisation with both vesicle types combined showed neither inhibitory nor synergistic effects. We conclude that DC-derived MVs and exosomes differ in their capacity to incorporate antigen and induce immune responses. The results are of importance for understanding the role of EVs in vivo, and for future design of vesicle-based immunotherapies and vaccines.
Hydrogen motion in rutile TiO2
Authors: Hupfer A. J. , Monakhov E. V. , Svensson B. G. , Chaplygin I. , Lavrov E. V. 
Published: November 2017

AbstractUniaxial-stress experiments have been performed for the 3287- and 2445-cm−1 local vibrational modes assigned to the positive charge state of interstitial hydrogen $$({{\rm{H}}}_{i}^{+})$$
(

H

i

+

)
and deuterium $$({{\rm{D}}}_{i}^{+})$$
(

D

i

+

)
, respectively, occurring in mono-crystalline rutile TiO2. The onset of the defect alignment under the stress applied perpendicular to the [001] axis is detected at 165 K (185 K), which corresponds to the activation energy of 0.53 eV (0.58 eV) for interstitial hydrogen (deuterium). Based on these findings the diffusion constants of $${{\rm{H}}}_{i}^{+}$$

H

i

+

and $${{\rm{D}}}_{i}^{+}$$

D

i

+

along the [001] axis of TiO2 are determined. The experimental data are complemented by density-functional theory calculations and compared with the earlier results on the diffusion of $${{\rm{H}}}_{i}^{+}$$

H

i

+

/$${{\rm{D}}}_{i}^{+}$$

D

i

+

at elevated temperatures up to 700 °C. It is found that the activation energy value deduced from our low-temperature stress measurements yields a very good agreement with the high-temperature data, covering a dynamic range of 12 orders of magnitude.
Reducing biomass recalcitrance by heterologous expression of a bacterial peroxidase in tobacco (Nicotiana benthamiana)
Authors: Ligaba-Osena Ayalew , Hankoua Bertrand , DiMarco Kay , Pace Robert , Crocker Mark , McAtee Jesse , Nagachar Nivedita , Tien Ming , Richard Tom L. 
Published: November 2017

AbstractCommercial scale production of biofuels from lignocellulosic feed stocks has been hampered by the resistance of plant cell walls to enzymatic conversion, primarily owing to lignin. This study investigated whether DypB, the lignin-degrading peroxidase fromRodococcus jostii, depolymerizes lignin and reduces recalcitrance in transgenic tobacco (Nicotiana benthamiana). The protein was targeted to the cytosol or the ER using ER-targeting and retention signal peptides. For each construct, five independent transgenic lines were characterized phenotypically and genotypically. Our findings reveal that expression of DypB in the cytosol and ER does not affect plant development. ER-targeting increased protein accumulation, and extracts from transgenic leaves showed higher activity on classic peroxidase substrates than the control. Intriguingly,in situDypB activation and subsequent saccharification released nearly 200% more fermentable sugars from transgenic lines than controls, which were not explained by variation in initial structural and non-structural carbohydrates and lignin content. Pyrolysis-GC-MS analysis showed more reduction in the level of lignin associated pyrolysates in the transgenic lines than the control primarily when the enzyme is activated prior to pyrolysis, consistent with increased lignin degradation and improved saccharification. The findings reveal for the first time that accumulation andin situactivation of a peroxidase improves biomass digestibility.
All-optical control of light on a graphene-on-silicon nitride chip using thermo-optic effect
Authors: Qiu Ciyuan , Yang Yuxing , Li Chao , Wang Yifang , Wu Kan , Chen Jianping 
Published: November 2017

AbstractAll-optical signal processing avoids the conversion between optical signals and electronic signals and thus has the potential to achieve a power efficient photonic system. Micro-scale all-optical devices for light manipulation are the key components in the all-optical signal processing and have been built on the semiconductor platforms (e.g., silicon and III-V semiconductors). However, the two-photon absorption (TPA) effect and the free-carrier absorption (FCA) effect in these platforms deteriorate the power handling and limit the capability to realize complex functions. Instead, silicon nitride (Si3N4) provides a possibility to realize all-optical large-scale integrated circuits due to its insulator nature without TPA and FCA. In this work, we investigate the physical dynamics of all-optical control on a graphene-on-Si3N4 chip based on thermo-optic effect. In the experimental demonstration, a switching response time constant of 253.0 ns at a switching energy of ~50 nJ is obtained with a device dimension of 60 μm × 60 μm, corresponding to a figure of merit (FOM) of 3.0 nJ mm. Detailed coupled-mode theory based analysis on the thermo-optic effect of the device has been performed.
Bias induced ferromagnetism and half-metallicity in graphene nano-ribbons
Authors: Maji Rita , Bhattacharjee Joydeep 
Published: November 2017

AbstractTowards spin selective electronics made of three coordinated carbon atoms, here we computationally propose robust and reversibly bias driven evolution of pristine undoped graphene nano-ribbons(GNR) into ferromagnetic-semiconductor, metal or a half metal, irrespective of their edge configurations. The evolution is a result of a rare ferromagnetic(FM) order emerging among nearest neighbouring(n-n) sites, in positively biased regions in their in-homogeneous bias unit-cells, in attempt to cooperatively minimise on-site Coulomb repulsion and kinetic energy, while maximising localization of electrons at the positively biased sites. The phenomenon appears to be a general property of in-homogeneously biased Coulomb correlated bipartite systems. Consequences are particularly rich in zigzag edged graphene nano-ribbons(ZGNR) due to the contest of bias driven n-n FM order and the inter-edge antiferromagnetic order inherent to ZGNRs, leading to systematic closing of gap for one of the spins, amounting to bias controlled unmissable opening of window for FM-semiconducting and half-metallic transport.
Suppression of Stochastic Domain Wall Pinning Through Control of Gilbert Damping
Authors: Broomhall T. J. , Hayward T. J. 
Published: November 2017

AbstractFinite temperature micromagnetic simulations were used to investigate the magnetisation structure, propagation dynamics and stochastic pinning of domain walls in rare earth-doped Ni80Fe20 nanowires. We first show how the increase of the Gilbert damping, caused by the inclusion rare-earth dopants such as holmium, acts to suppress Walker breakdown phenomena. This allows domain walls to maintain consistent magnetisation structures during propagation. We then employ finite temperature simulations to probe how this affects the stochastic pinning of domain walls at notch-shaped artificial defect sites. Our results indicate that the addition of even a few percent of holmium allows domain walls to pin with consistent and well-defined magnetisation configurations, thus suppressing dynamically-induced stochastic pinning/depinning phenomena. Together, these results demonstrate a powerful, materials science-based solution to the problems of stochastic domain wall pinning in soft ferromagnetic nanowires.
Polarization response and scaling law of chirality for a nanofibre optical interface
Authors: Sadgrove Mark , Sugawara Masakazu , Mitsumori Yasuyoshi , Edamatsu Keiichi 
Published: November 2017

AbstractTwo port optical devices couple light to either port dependent on the input photon state. An important class of two-port devices is that of evanescently-coupled interfaces where chirality of photon coupling can lead to important technological applications. Here, we perform a fundamental characterization of such an interface, reconstructing the two-port polarization response over the surface of the Poincaré sphere for an optical nanofibre. From this result, we derive a chirality measure which is universal, obeying a one parameter scaling law independent of the exact parameters of the nanofibre and wavelength of light. Additionally, we note that the polarization response differs qualitatively for single and multiple coupled emitters, with possible implications for sensing and the characterization of waveguide coupled spins.
Inhibiting mevalonate pathway enzymes increases stromal cell resilience to a cholesterol-dependent cytolysin
Authors: Griffin Sholeem , Preta Giulio , Sheldon Iain Martin 
Published: November 2017

AbstractAnimal health depends on the ability of immune cells to kill invading pathogens, and on the resilience of tissues to tolerate the presence of pathogens. Trueperella pyogenes causes tissue pathology in many mammals by secreting a cholesterol-dependent cytolysin, pyolysin (PLO), which targets stromal cells. Cellular cholesterol is derived from squalene, which is synthesized via the mevalonate pathway enzymes, including HMGCR, FDPS and FDFT1. The present study tested the hypothesis that inhibiting enzymes in the mevalonate pathway to reduce cellular cholesterol increases the resilience of stromal cells to PLO. We first verified that depleting cellular cholesterol with methyl-β-cyclodextrin increased the resilience of stromal cells to PLO. We then used siRNA to deplete mevalonate pathway enzyme gene expression, and used pharmaceutical inhibitors, atorvastatin, alendronate or zaragozic acid to inhibit the activity of HMGCR, FDPS and FDFT1, respectively. These approaches successfully reduced cellular cholesterol abundance, but mevalonate pathway enzymes did not affect cellular resilience equally. Inhibiting FDFT1 was most effective, with zaragozic acid reducing the impact of PLO on cell viability. The present study provides evidence that inhibiting FDFT1 increases stromal cell resilience to a cholesterol-dependent cytolysin.
A catch-up illusion arising from a distance-dependent perception bias in judging relative movement
Authors: Meilinger Tobias , Garsoffky Bärbel , Schwan Stephan 
Published: November 2017

AbstractThe perception of relative target movement from a dynamic observer is an unexamined psychological three body problem. To test the applicability of explanations for two moving bodies participants repeatedly judged the relative movements of two runners chasing each other in video clips displayed on a stationary screen. The chased person always ran at 3 m/s with an observer camera following or leading at 4.5, 3, 1.5 or 0 m/s. We harmonized the chaser speed in an adaptive staircase to determine the point of subjective equal movement speed between runners and observed (i) an underestimation of chaser speed if the runners moved towards the viewer, and (ii) an overestimation of chaser speed if the runners moved away from the viewer, leading to a catch-up illusion in case of equidistant runners. The bias was independent of the richness of available self-movement cues. Results are inconsistent with computing individual speeds, relying on constant visual angles, expansion rates, occlusions, or relative distances but are consistent with inducing the impression of relative movement through perceptually compressing and enlarging inter-runner distance. This mechanism should be considered when predicting human behavior in complex situations with multiple objects moving in depth such as driving or team sports.
The SWI/SNF subunit Bcl7a contributes to motor coordination and Purkinje cell function
Authors: Wischhof Lena , Maida Simona , Piazzesi Antonia , Gioran Anna , Barragan Sanz Kristina , Irsen Stephan , Beyer Marc , Schultze Joachim L. , Dyer Martin J. , Salomoni Paolo , Ehninger Dan , Nicotera Pierluigi , Bano Daniele 
Published: November 2017

AbstractChromatin remodelers have emerged as prominent regulators of epigenetic processes and potential drivers of various human pathologies. The multi-subunit chromatin-remodeling SWI/SNF complex determines gene expression programs and, consequently, contributes to the differentiation, maturation and plasticity of neurons. Here, we investigate the elusive biological function of Bcl7a and Bcl7b, two newly identified subunits of the SWI/SNF complex that are highly expressed throughout the brain. We generated ubiquitous and neuron-specific Bcl7a and Bcl7b single and double knockout mice. We provide evidence that Bcl7b is dispensable for animal survival as well as behavioral plasticity. Conversely, ubiquitous Bcl7a knockout results in perinatal lethality, while genetic deletion of Bcl7a in postmitotic neurons elicits motor abnormalities and affects dendritic branching of Purkinje cells, with no obvious synergistic relationship with Bcl7b. Collectively, our findings reveal novel insights into the cellular processes linked to BCL7-containing SWI/SNF complexes and their unrecognized roles in the brain.
Prophylactic Active Tau Immunization Leads to Sustained Reduction in Both Tau and Amyloid-β Pathologies in 3xTg Mice
Authors: Rajamohamedsait Hameetha , Rasool Suhail , Rajamohamedsait Wajitha , Lin Yan , Sigurdsson Einar M. 
Published: November 2017

AbstractAmyloid-β (Aβ) and tau pathologies are intertwined in Alzheimer’s disease, and various immunotherapies targeting these hallmarks are in clinical trials. To determine if tau pathology influences Aβ burden and to assess prophylactic benefits, 3xTg and wild-type mice received tau immunization from 2–6 months of age. The mice developed a high IgG titer that was maintained at 22 months of age. Pronounced tau and Aβ pathologies were primarily detected in the subiculum/CA1 region, which was therefore the focus of analysis. The therapy reduced histopathological tau aggregates by 70–74% overall (68% in males and 78–86% in females), compared to 3xTg controls. Likewise, western blot analysis revealed a 41% clearance of soluble tau (38–76% in males and 48% in females) and 42–47% clearance of insoluble tau (47–58% in males and 49% in females) in the immunized mice. Furthermore, Aβ burden was reduced by 84% overall (61% in males and 97% in females). These benefits were associated with reductions in microgliosis and microhemorrhages. In summary, prophylactic tau immunization not only prevents tau pathology but also Aβ deposition and related pathologies in a sustained manner, indicating that tau pathology can promote Aβ deposition, and that a short immunization regimen can have a long-lasting beneficial effect.
Characterization of Large Copy Number Variation in Mexican Type 2 Diabetes subjects
Authors: de Jesús Ascencio-Montiel Iván , Pinto Dalila , Parra Esteban J. , Valladares-Salgado Adán , Cruz Miguel , Scherer Stephen W. 
Published: November 2017

AbstractThe effect of Copy Number Variants (CNVs) on Type 2 Diabetes (T2D) remains little explored. The present study characterized large rare CNVs in 686 T2D and 194 non-T2D subjects of Mexican ancestry genotyped using the Affymetrix Genome-Wide Human SNP array 5.0. Rare CNVs with ≥ 100 kb length were identified using a stringent strategy based on merging CNVs calls generated using Birdsuit, iPattern and PennCNV algorithms. We applied three different strategies to evaluate the distribution of CNVs in the T2D and non-T2D samples: 1) Burden analysis, 2) Identification of CNVs in loci previously associated to T2D, and 3) Identification of CNVs observed only in the T2D group. In the CNV burden analysis, the T2D group showed a higher proportion of CNVs, and also a higher proportion of CNVs overlapping at least one gene than the non T2D group. Five of the six loci previously associated with T2D had duplications or deletions in the T2D sample, but not the non-T2D sample. A gene-set analysis including genes with CNVs observed only in the T2D group highlighted gene-sets related with sensory perception (olfactory receptors, OR) and phenylpyruvate tautomerase/dopachrome isomerase activity (MIF and DDT genes).