bluuebunny/crossref_metadata_2025_split huggingface dataset:
In VitroPlatform Establishes Antigen-Specific CD8+T Cell Cytotoxicity to Encapsulated Cells via Indirect Antigen Recognition
Authors: Li Ying , Frei Anthony W. , Yang Ethan Y. , Labrada-Miravet Irayme , Sun Chuqiao , Rong Yanan , Samojlik Magdalena M. , Bayer Allison L. , Stabler Cherie L. 
Published: December 2019

AbstractCell replacement therapy has the potential to cure diseases caused by the absence or malfunction of specialized cells. A substantial impediment to the success of any non-autologous cellular transplant is the need for systemic immunosuppressive drugs to prevent host-mediated rejection of the foreign cells. Cellular encapsulation, i.e., the entrapment of cells within stable polymeric hydrogels, has been clinically explored to prevent host immune recognition and attack, but the efficacy of these encapsulated grafts is poor. While several studies have explored improvements in innate immune acceptance of these encapsulated cells, little attention has been paid to the roles of adaptive immune responses, specifically graft-targeting T cell activation, in graft destabilization. Herein, we established an efficient, single-antigenin vitroplatform capable of delineating direct and indirect host T cell recognition to microencapsulated cellular grafts and evaluating their consequential impacts. Using alginate as the model hydrogel, encapsulated membrane-bound ovalbumin (mOVA) stimulator cells were incubated with antigen-specific OTI lymphocytes and subsequent OVA-specific CD8+T cell activation and effector function were quantified. We established that alginate microencapsulation abrogates direct T cell activation by interrupting donor-host interaction; however, indirect T cell activation mediated by host antigen presenting cells (APCs) primed with shed donor antigens still occurs. These activated T cells imparted cytotoxicity on the encapsulated cells, likely via diffusion of cytotoxic solutes. Overall, this platform delivers unique mechanistic insight into the impacts of hydrogel encapsulation on host adaptive immune responses, as well as a tool for the efficient immune screening on new encapsulation methods and/or synergistic immunomodulatory agents.
Efficient coding of natural scene statistics predicts discrimination thresholds for grayscale textures
Authors: Teşileanu Tiberiu , Conte Mary M. , Briguglio John J. , Hermundstad Ann M. , Victor Jonathan D. , Balasubramanian Vijay 
Published: December 2019

AbstractPreviously, in [1], we showed that when sampling is limiting, the efficient coding principle leads to a “variance is salience” hypothesis, and that this hypothesis accounts for visual sensitivity to binary image statistics. Here, using extensive new psychophysical data and image analysis, we show that this hypothesis accounts for visual sensitivity to a large set of grayscale image statistics at a striking level of detail, and also identify the limits of the prediction. We define a 66-dimensional space of local grayscale light-intensity correlations, and measure the relevance of each direction to natural scenes. The “variance is salience” hypothesis predicts that two-point correlations are most salient, and predicts their relative salience. We tested these predictions in a texture-segregation task using un-natural, synthetic textures. As predicted, correlations beyond second order are not salient, and predicted thresholds for over 300 second-order correlations match psychophysical thresholds closely (median fractional error < 0.13).
Modeling uniquely human gene regulatory function in humanized mice
Authors: Dutrow Emily V. , Emera Deena , Yim Kristina , Uebbing Severin , Kocher Acadia A. , Krenzer Martina , Nottoli Timothy , Burkhardt Daniel B. , Krishnaswamy Smita , Louvi Angeliki , Noonan James P. 
Published: December 2019

AbstractThe evolution of uniquely human traits likely entailed changes in developmental gene regulation. Human Accelerated Regions (HARs), which include transcriptional enhancers harboring a significant excess of human-specific sequence changes, are leading candidates for driving gene regulatory modifications in human development. However, insight into whether HARs alter the level, distribution and timing of endogenous gene expression remains limited. We examined the role of the HARHACNS1(HAR2) in human evolution by interrogating its molecular functions in a humanized mouse model. We find thatHACNS1maintains its human-specific enhancer activity in humanized mice and that it modifies expression ofGbx2, which encodes a homeobox transcription factor, during limb development. Using single-cell RNA-sequencing, we demonstrate thatGbx2is upregulated in the chondrogenic mesenchyme of humanized limbs, supporting thatHACNS1alters gene expression in cell types involved in skeletal patterning. Our findings illustrate that humanized mouse models provide mechanistic insight into how HARs modified gene expression in human evolution.
Honest signalling of trustworthiness
Authors: Roberts Gilbert 
Published: December 2019

AbstractTrust can transform conflicting interests into cooperation. But how can individuals know when to trust others? Here, I develop the theory that reputation building may signal cooperative intent, or ‘trustworthiness’. I model a simple representation of this theory in which individuals (1) optionally invest in a reputation by performing costly helpful behaviour (‘signalling’); (2) optionally use others’ reputations when choosing a partner; and (3) optionally cooperate with that partner. In evolutionary simulations, high levels of reputation building; of choosing partners based on reputation; and of cooperation within partnerships emerged. Costly helping behaviour evolved into an honest signal of trustworthiness when it was adaptive for cooperators, relative to defectors, to invest in the long-term benefits of a reputation for helping. I show using game theory that this occurs when cooperators gain larger marginal benefits from investing in signalling than do defectors. This happens without the usual costly signalling assumption that individuals are of two ‘types’ which differ in quality. Signalling of trustworthiness may help explain phenomena such as philanthropy, pro-sociality, collective action, punishment, and advertising in humans and may be particularly applicable to courtship in other animals.
Biofilm and Cell Adhesion Strength on Dental Implant Surfaces via the Laser Spallation Technique
Authors: Boyd J. D. , Miller C.S. , Grady M. E. 
Published: December 2019

AbstractObjectivesThe aim of this study is to quantify the adhesion strength differential between an oral bacterial biofilm and an osteoblast-like cell monolayer to a dental implant-simulant surface and develop a metric that quantifies the biocompatible efficacy of implant surfaces.MethodsHigh-amplitude short-duration stress waves generated by laser pulse absorption are used to spall bacteria and cells from titanium substrates. By carefully controlling laser fluence and calibration of laser fluence with applied stress, the adhesion difference between dental carryStreptococcus mutansbiofilms and MG 63 osteoblast-like cell monolayers on smooth and rough titanium substrates is obtained. The Adhesion Index consists of a ratio of cell adhesion strength to biofilm adhesion strength obtaining a nondimensionalized parameter for biocompatibility assessments.ResultsAdhesion strength of 145±42 MPa is measured for MG 63 on smooth titanium, which increases to 288±24 MPa on roughened titanium. Adhesion strength forS. mutanson smooth titanium is 315±9 MPa and remained relatively constant at 332±9 MPa on roughened titanium. The Adhesion Index for smooth titanium is 0.46±0.12 which increased to 0.87±0.05 on roughened titanium.SignificanceThe laser spallation technique provides a platform to examine the tradeoffs of adhesion modulators on both biofilm and cell adhesion. This tradeoff is characterized by the Adhesion Index, which is proposed to aid biocompatibility screening and could result in improved implantation outcomes. The Adhesion Index is implemented to determine surface factors that promote favorable adhesion of cells greater than biofilms. Here, an Adhesion Index >> 1 suggests favorable biocompatibility.Graphical AbstractHighlightsBiofilm and cell monolayer adhesion are measured via the laser spallation techniqueSmooth and roughened dental implant-mimicking titanium surfaces are investigatedSurface roughness increases cell adhesion but does not alter the adhesion of biofilmsAn Adhesion Index is developed to directly quantify the adhesive competition between bacteria and cells on an implant surface
The transcriptional legacy of developmental stochasticity
Authors: Ballouz Sara , Pena Maria T. , Knight Frank M. , Adams Linda B. , Gillis Jesse A. 
Published: December 2019

AbstractGenetic variation, epigenetic regulation and major environmental stimuli are key contributors to phenotypic variation, but the influence of minor perturbations or “noise” has been difficult to assess in mammals. In this work, we uncover one major axis of random variation with a large and permanent influence: developmental stochasticity. By assaying the transcriptome of wild monozygotic quadruplets of the nine-banded armadillo, we find that persistent changes occur early in development, and these give rise to clear transcriptional signatures which uniquely characterize individuals relative to siblings. Comparing these results to human twins, we find the transcriptional signatures which define individuals exhibit conserved co-expression, suggesting a substantial fraction of phenotypic and disease discordance within mammals arises from developmental stochasticity.One sentence summaryLongitudinal gene expression in identical armadillo quadruplets reveals a major role for developmental stochasticity.
Expansion and re-classification of the extracytoplasmic function (ECF) σ factor family
Authors: Casas-Pastor Delia , Müller Raphael Rene , Becker Anke , Buttner Mark , Gross Carol , Mascher Thorsten , Goesmann Alexander , Fritz Georg 
Published: December 2019

AbstractExtracytoplasmic function σ factors (ECFs) represent one of the major bacterial signal transduction mechanisms in terms of abundance, diversity and importance, particularly in mediating stress responses. Here, we performed a comprehensive phylogenetic analysis of this protein family by scrutinizing all proteins in the NCBI database. As result, we identified ∼10 ECFs per bacterial genome on average and classified them into 157 phylogenetic ECF groups that feature a conserved genetic neighborhood and a similar regulation mechanism. Our analysis expands the number of unique ECF sequences ∼50-fold relative to previous classification efforts, enriches many original ECF groups with previously unclassified proteins and identifies 22 entirely new ECF groups. The ECF groups are hierarchically related to each other and are further composed of subgroups with closely related sequences. This two-tiered classification allows for the accurate prediction of common promoter motifs and the inference of putative regulatory mechanisms across subgroups composing an ECF group. This comprehensive, high-resolution description of the phylogenetic distribution of the ECF family, together with the massive expansion of classified ECF sequences, enables the application ofin silicotools for the prediction of important functional residues, and serves as a powerful hypothesis-generator to guide future research in the field.
Localization of immunoreactive, dystonia-associated protein torsinA near the Golgi apparatus of cultured rodent astrocytes
Authors: Iwabuchi Sadahiro , Kawano Hiroyuki , Harata N. Charles 
Published: December 2019

ABSTRACTAn in-frame deletion of a single glutamic acid codon in theTOR1Agene causes the neurological disorder DYT1 dystonia, but the cellular pathophysiology of this disorder remains elusive. A current model postulates that the wild-type (WT) torsinA protein is mainly localized to the endoplasmic reticulum (ER), but that the mutant form (ΔE-torsinA) is diverted to the nuclear envelope and cytoplasmic inclusion bodies. This mis-localization has been observed by overexpressing the proteins in neuronal and non-neuronal cells. However, it is not clear whether this model is valid for the astrocytic glial cells that support and modify neuronal functions. Here we report, using rodent astrocytes in primary culture, that the overexpressed torsinA proteins were distributed as predicted by the mis-localization model. We also found by immunocytochemistry that the cultured astrocytes express torsinA endogenously. Most of the signals from endogenous protein, whether the WT or ΔE form, were localized near acis-Golgi marker GM130. Such localization of endogenous proteins was found in glial cells from several sources: the hippocampus of WT rats, the hippocampus and striatum of WT mice, and the hippocampus and striatum of ΔE-torsinA knock-in mice, a model of DYT1 dystonia. These results show that the mis-localization model is applicable to overexpressed torsinA proteins, but not applicable to those expressed at endogenous levels, at least in cultured rodent astrocytes. These discrepancies in the distribution of overexpressed versus endogenous torsinA proteins highlight the potential need for caution in interpreting the results of overexpression studies.
Flapping at Resonance: Measuring the Frequency Response of the Hymenoptera Thorax
Authors: Jankauski Mark A. 
Published: December 2019

AbstractInsects with asynchronous flight muscles are believed to flap at the fundamental frequency of their thorax or thorax-wing system. Flapping in this manner leverages the natural elasticity of the thorax to reduce the energetic requirements of flight. However, to the best of our knowledge, the fundamental frequency of the insect thorax has not been measured via vibration testing. Here, we measure the linear frequency response function (FRF) of several Hymenoptera (Apis mellifera, Polistes dominula, Bombus huntii) thoraxes about their equilibrium states in order to determine their fundamental frequencies. FRFs relate the input force to output acceleration at the insect tergum and are acquired via a mechanical vibration shaker assembly. When compressed 50μm, thorax fundamental frequencies in all specimens approximately 50-150% higher than reported wingbeat frequencies. We suspect that the measured fundamental frequencies are higher in the experiment than during flight due to experimental boundary conditions that stiffen the thorax. Thus, our results corroborate the idea that some insects flap at the fundamental frequency of their thorax. Next, we compress the thorax between 100 - 300 μm in 50 μm intervals to assess the sensitivity of the fundamental frequency to geometric modifications. For all insects considered, the thorax fundamental frequency increased nearly monotonically with respect to level of compression. This implies that the thorax behaves a nonlinear hardening spring, which we confirmed via static force-displacement testing. Hardening behavior may provide a simple mechanism for the insect to adjust wingbeat frequency, and implies the thorax may behave as a nonlinear Duffing oscillator excited at large amplitude. The Duffing oscillator exhibits amplitude-dependent resonance and may serve as a useful model to increase the flapping frequency bandwidth of small resonant-type flapping wing micro air vehicles.
GtcA is required for LTA glycosylation inListeria monocytogenesserovar 1/2a andBacillus subtilis
Authors: Rismondo Jeanine , Haddad Talal F. M. , Shen Yang , Loessner Martin J. , Gründling Angelika 
Published: December 2019

ABSTRACTThe cell wall polymers wall teichoic acid (WTA) and lipoteichoic acid (LTA) are often modified with glycosyl and D-alanine residues. Recent studies have shown that a three-component glycosylation system is used for the modification of LTA in several Gram-positive bacteria includingBacillus subtilisandListeria monocytogenes. In theL. monocytogenes1/2a strain 10403S, the cytoplasmic glycosyltransferase GtlA is thought to use UDP-galactose to produce the C55-P-galactose lipid intermediate, which is transported across the membrane by an unknown flippase. Next, the galactose residue is transferred onto the LTA backbone on the outside of the cell by the glycosyltransferase GtlB. Here we show that GtcA is necessary for the glycosylation of LTA inL. monocytogenes10403S andB. subtilis168 and we hypothesize that these proteins act as C55-P-sugar flippases. With this we revealed that GtcA is involved in the glycosylation of both teichoic acid polymers inL. monocytogenes10403S, namely WTA with N-acetylglucosamine and LTA with galactose residues. These findings indicate that theL. monocytogenesGtcA protein can act on different C55-P-sugar intermediates. Further characterization of GtcA inL. monocytogenesled to the identification of residues essential for its overall function as well as residues, which predominately impact WTA or LTA glycosylation.GRAPHICAL ABSTRACT
Direct antiviral activity of interferon stimulated genes is responsible for resistance to paramyxoviruses in ISG15-deficient cells
Authors: Holthaus David , Vasou Andri , Bamford Connor G. G. , Andrejeva Jelena , Paulus Christina , Randall Richard E. , McLauchlan John , Hughes David J. 
Published: December 2019

AbstractInterferons (IFNs), produced during viral infections, induce the expression of hundreds of IFN- stimulated genes (ISGs). Some ISGs have specific antiviral activity while others regulate the cellular response. Besides functioning as an antiviral effector, IFN-stimulated gene 15 (ISG15) is a negative regulator of IFN signalling and inherited ISG15-deficiency leads to autoinflammatory interferonopathies where individuals exhibit elevated ISG expression in the absence of pathogenic infection. We have recapitulated these effects in cultured human A549-ISG15-/-cells and (using A549-UBA7-/-cells) confirmed that posttranslational modification by ISG15 (ISGylation) is not required for regulation of the type-I IFN response. ISG15-deficient cells pre-treated with IFN-α were resistant to paramyxovirus infection. We also showed that IFN-α treatment of ISG15-deficient cells led to significant inhibition of global protein synthesis leading us to ask whether resistance was due to the direct antiviral activity of ISGs or whether cells were non-permissive due to translation defects. We took advantage of the knowledge that IFN-induced protein with tetratricopeptide repeats 1 (IFIT1) is the principal antiviral ISG for parainfluenza virus 5 (PIV5). Knockdown of IFIT1 restored PIV5 infection in IFN-α-pre-treated ISG15-deficient cells, confirming that resistance was due to the direct antiviral activity of the IFN response. However, resistance could be induced if cells were pre-treated with IFN-α for longer times, presumably due to inhibition of protein synthesis. These data show that the cause of virus resistance is two-fold; ISG15-deficiency leads to the ‘early’ over-expression of specific antiviral ISGs, but the later response is dominated by an unanticipated, ISG15- dependent, loss of translational control.Key pointsCell culture model of ISG15-deficiency replicate findings in ISG15-/-patient cellsCause of resistance in ISG15-/-cells differs depending on duration of IFN treatmentISG15-/-patients without serious viral disease don’t prove ISGylation is unimportant
An improved ATP FRET sensor for yeast shows heterogeneity during nutrient transitions
Authors: Botman Dennis , van Heerden Johan H. , Teusink Bas 
Published: December 2019

AbstractAdenosine 5-triphosphate (ATP) is the main free energy carrier in metabolism. In budding yeast, shifts to glucose-rich conditions cause dynamic changes in ATP levels, but it is unclear how heterogeneous these dynamics are at the single-cell level. Furthermore, pH also changes and affects readout of fluorescence-based biosensors for single-cell measurements. To measure ATP changes reliably in single yeast cells, we developed yAT1.03, an adapted version of the AT1.03 ATP biosensor, that is pH-insensitive. We show that pregrowth conditions largely affect ATP dynamics during transitions. Moreover, single-cell analyses showed a large variety in ATP responses, which implies large differences of glycolytic startup between individual cells. We found three clusters of dynamic responses, and show that a small subpopulation of wild type cells reached an imbalanced state during glycolytic startup, characterised by low ATP levels. These results confirm the need for new tools to study dynamic responses of individual cells in dynamic environments.
Viola unica (Violaceae L.), a very rare, high elevation, single-site new species endemic to the northern semi-desert Altiplano of Chile
Authors: Watson John Michael , Flores Ana Rosa 
Published: December 2019

AbstractWhile examining the Viola collection at the herbarium (SGO) of the Museo Nacional de Historia Natural (MNHN), Santiago, we encountered a folder with a single unidentified specimen consisting of a solitary rosette. It had been found in northern Chile near the border with Bolivia, where considerable mining activity takes place. The plant appeared to differ from all others related to it as known to ourselves, and on investigation it did indeed prove to be undescribed. It is presented herein, together with a detailed analysis and preliminary partial revision of related taxa, including a key.
Aurora B and C kinases regulate prophase exit and chromosome segregation during spermatogenesis
Authors: Wellard Stephen R. , Schindler Karen , Jordan Philip 
Published: December 2019

ABSTRACTPrecise control of chromosome dynamics during meiosis is critical for fertility. A gametocyte undergoing meiosis coordinates formation of the synaptonemal complex (SC) to promote efficient homologous chromosome recombination. Subsequent disassembly of the SC is required prior to meiotic divisions to ensure accurate segregation of chromosomes. We examined the requirements of the mammalian Aurora kinases (AURKA, B, and C) during SC disassembly and chromosome segregation using a combination of chemical inhibition and gene deletion approaches. We find that both mouse and human spermatocytes fail to disassemble SC lateral elements when AURKB and AURKC are inhibited. Interestingly, both Aurkb conditional knockout and Aurkc knockout spermatocytes successfully progress through meiosis and mice are fertile. In contrast, Aurkb, Aurkc double knockout spermatocytes failed to coordinate disassembly of SC lateral elements with chromosome segregation, resulting in delayed meiotic progression, spindle assembly checkpoint failure, chromosome missegregation, and abnormal spermatids. Collectively, our data demonstrates that AURKB and AURKC functionally compensate for one another ensuring successful mammalian spermatogenesis.SUMMARYChemical inhibition and gene deletion approaches show that Aurora B and Aurora C have overlapping functions that ensure timely disassembly of lateral element components of the synaptonemal complex in mouse and human spermatocytes and ensure accurate chromosome segregation during meiosis.