bluuebunny/crossref_metadata_2025_split huggingface dataset:
Forcing contacts between mitochondria and the endoplasmic reticulum extends lifespan in a Drosophila model of Alzheimer’s disease
Authors: Garrido-Maraver Juan , Loh Samantha H. Y. , Martins L. Miguel 
Published: July 2019

ABSTRACTEukaryotic cells are complex systems containing internal compartments with specialised functions. Among these compartments, the endoplasmic reticulum (ER) plays a major role in processing proteins for modification and delivery to other organelles, whereas mitochondria generate energy in the form of ATP. Mitochondria and the ER form physical interactions, defined as mitochondria-ER contact sites (MERCS) to exchange metabolites such as calcium ions (Ca2+) and lipids. Sites of contact between mitochondria and the ER can regulate biological processes such as ATP generation and mitochondrial division. The interactions between mitochondria and the ER are dynamic and respond to the metabolic state of cells. Changes in MERCS have been linked to metabolic pathologies such as diabetes, neurodegenerative diseases and sleep disruption.Here we explored the consequences of increasing contacts between mitochondria and the ER in flies using a synthetic linker. We showed that enhancing MERCS increases locomotion and extends lifespan. We also showed that, in a Drosophila model of Alzheimer’s disease linked to toxic amyloid beta (Aβ), linker expression can suppress motor impairment and extend lifespan. We conclude that strategies for increasing contacts between mitochondria and the ER may ameliorate symptoms of diseases associated with mitochondria dysfunction.
Regulation of lipid saturation without sensing membrane fluidity
Authors: Ballweg Stephanie , Sezgin Erdinc , Wunnicke Dorith , Hänelt Inga , Ernst Robert 
Published: July 2019

Abstract/SummaryCells maintain membrane fluidity by regulating lipid saturation, but the molecular mechanisms of this homeoviscous adaptation remain poorly understood. Here, we have reconstituted the core machinery for sensing and regulating lipid saturation in baker’s yeast to directly characterize its response to defined membrane environments. Using spectroscopic techniques andin vitroubiquitylation, we uncover a unique sensitivity of the transcriptional regulator Mga2 to the abundance, position, and configuration of double bonds in lipid acyl chains and provide unprecedented insight into the molecular rules of membrane adaptivity. Our data challenge the prevailing hypothesis that membrane viscosity serves as the measured variable for regulating lipid saturation. Rather, we show that the signaling output of Mga2 correlates with the size of a single sensor residue in the transmembrane helix, which senses the lateral pressure and/or compressibility profile in a defined region of the membrane. Our findings suggest that membrane property sensors have evolved remarkable sensitivities to highly specific aspects of membrane structure and dynamics, thus paving the way toward the development of genetically encoded reporters for such membrane properties in the future.
MATE-Seq: Microfluidic Antigen-TCR Engagement Sequencing
Authors: Ng Alphonsus H.C. , Peng Songming , Xu Alexander M. , Noh Won Jun , Guo Katherine , Bethune Michael T. , Chour William , Choi Jongchan , Yang Sung , Baltimore David , Heath James R. 
Published: July 2019

AbstractAdaptive immunity is based on peptide antigen recognition. Our ability to harness the immune system for therapeutic gain relies on the discovery of the T cell receptor (TCR) genes that selectively target antigens from infections, mutated proteins, and foreign agents. Here we present a method that selectively labels peptide antigen-specific CD8+ T-cells in human blood using magnetic nanoparticles functionalized with peptide-MHC tetramers, isolates these specific cells within an integrated microfluidic device, and directly amplifies the TCR genes for sequencing. Critically, the identity of the peptide recognized by the TCR is preserved, providing the link between peptide and gene. The platform requires inputs on the order of just 100,000 CD8+ T cells, can be multiplexed for simultaneous analysis of multiple peptides, and performs sorting and isolation on chip. We demonstrate 1000-fold sensitivity enhancement of antigen-specific T-cell receptor detection and simultaneous capture of two virus antigen-specific T-cell receptors from samples of human blood.
Gut-Liver physiomimetics reveal paradoxical modulation of IBD-related inflammation by short-chain fatty acids
Authors: Trapecar Martin , Communal Catherine , Velazquez Jason , Maass Christian Alexander , Huang Yu-Ja , Schneider Kirsten , Wright Charles W. , Eng George , Yilmaz Omer , Trumper David , Griffith Linda G. 
Published: July 2019

SummaryAssociation between the microbiome, IBD and liver diseases are known, yet cause and effect remain elusive. By connecting human microphysiological systems of the gut, liver and circulating Treg/Th17 cells, we modeled progression of ulcerative colitis (UC) ex vivo. We show that microbiome-derived short-chain fatty acids (SCFA) may either improve or worsen disease severity, depending on the activation state of CD4 T cells. Employing multiomics, we found SCFA increased production of ketone bodies, glycolysis and lipogenesis, while markedly reducing innate immune activation of the UC gut. However, during acute T cell-mediated inflammation, SCFA exacerbated CD4+T cell effector function, partially through metabolic reprograming, leading to gut barrier disruption and hepatic injury. These paradoxical findings underscore the emerging utility of human physiomimetic technology in combination with systems immunology to study causality and the fundamental entanglement of immunity, metabolism and tissue homeostasis.
A unified approach for characterizing static/dynamic connectivity frequency profiles using filter banks
Authors: Faghiri Ashkan , Iraji Armin , Damaraju Eswar , Turner Jessica , Calhoun Vince D. 
Published: July 2019

AbstractStudying dynamic functional connectivity (dFC) has been the focus of many studies in recent years. The most commonly used estimator for dFC uses a sliding window in combination with a connectivity estimator such as Pearson correlation. Here, we propose a new approach to estimate connectivity while preserving its full frequency range and subsequently examine both static and dynamic connectivity in one unified approach. This approach which we call filter banked connectivity (FBC), implements frequency tiling directly in the connectivity domain contrary to other studies where frequency tiling is done in the activity domain. This leads to more accurate modeling, and a unified approach to capture connectivity ranging from static to highly dynamic, avoiding the need to pick a specific band as in a sliding window approach.First, we demonstrated that our proposed approach, can estimate connectivity at frequencies that sliding window approach fails. Next we evaluated the ability of the approach to identify group differences by using the FBC approach to estimate dFNC in a resting fMRI data set including schizophrenia patients (SZ, n=151) and typical controls (TC, n=163). To summarize the results, we used k-means to cluster the FBC values into different clusters. Some states showed very weak low frequency strength and as such SWPC was not well suited to capture them. Additionally, we found that SZs tend to spend more time in states exhibiting higher frequencies and engaging the default mode network and its anticorrelations with other networks compared to TCs which spent more time in lower frequency states which primarily includes strong intercorrelations within the sensorimotor domains. In summary, the proposed approach offers a novel way to estimate connectivity while unifying static and dynamic connectivity analyses and can provide additional otherwise missed information about the frequency profile of connectivity patterns.
Long-term culturing of porcine nodose ganglia
Authors: Kuan Shin-Ping , Atanasova Kalina R. , Guevara Maria V. , Collins Emily N. , Reznikov Leah R. 
Published: July 2019

ABSTRACTBackgroundNeuronal cell cultures are widely used in the field of neuroscience. Cell dissociation allows for the isolation of a desired cell type, yet the complexity that distinguishes the nervous system is often lost as a result. Thus, culturing neural tissues in ex vivo format provides a physiological context that more closely resembles the in vivo environment. Nodose ganglia neurons have been extensively studied both in dissociated form and acutely in slice format. However, methods to culture long-term ex vivo have not been established.New MethodWe developed a simple method to culture nodose ganglia neurons from neonatal pigs long-term in ex vivo format using an in-house media formulation derived from commercially available components.ResultsCultures were viable for approximately 12 months. mRNA expression for nestin, a marker of neural progenitor cells, was stable across time. Vasoactive intestinal peptide and tachykinin, markers of nodose neurons, showed either no statistically significant differences or decreased across time, respectively. mRNA expression for glia fibrillary acidic protein and myelin basic protein showed no statistically significant differences over time.Comparison with Existing Method(s)There are currently no methods that describe long-term culturing of porcine nodose ganglia. Further, the media formulation we developed is new and not previously reported.ConclusionsThe simple procedure we developed for culturing nodose ganglia will enable both short-term and long-term investigations aimed at understanding peripheral ganglia in vitro. It is also possible that the methods described herein can be applied to other animal models, adult samples, and other neural tissues.
Natural LXRβ agonist stigmasterol confers protection against excitotoxicity after hypoxia- reoxygenation (H/R) injury via regulation of mitophagy in primary hippocampal neurons
Authors: Haque Md. Nazmul , Hannan Md. Abdul , Dash Raju , Moon Il Soo 
Published: July 2019

AbstractIschemic brain injury represents insufficient oxygen supply to the brain and further damage occurs upon reoxygenation due to elevated intracellular levels excitatory neurotransmitter glutamate and subsequent production of reactive oxygen species (ROS) which has long been related to neuronal cell death of hippocampus brain region. Previously, using cell biological assay and transcriptomics analysis we reported that naturally occurring phytosterol Stigmasterol (ST) promotes brain development and function through the enhancement of neuronal cytoarchitectural complexity and functional maturation in rat hippocampal neurons by induction of immediate early genes (IEGs). In the present study we investigated the STs role in neuroprotection and found that ST also dose-dependently increased the neuronal viability in hypoxia reoxygenation (H/R) induced injury at hippocampal culture. ST, at an optimal concentration of 20 μM, significantly reduced the transport of vesicular glutamate (VGULT1), synaptic vesicle pool size, expression of GluN2B, rate of ROS formation (DCFDA) but restore mitochondrial membrane potential (JC1) and DNA fragmentation (H2AX) against H/R induced injury. More interestingly, ST also significantly induces the expression of autophagy marker protein LC3BII and the adaptor protein P62 but not HSC70 which indicates STs capability of induction of chaperon independent autophagy at H/R treated cultures. Furthermore densitometric analysis reveals ST also significantly increases PINK1 (PTEN induced protein kinase 1) expression therefore, indicates its role in mitophagy. In addition, molecular dynamic simulations study indicates that ST bind to LXRβ and forms hydrogen bonds with ASN239, GLU281, ARG319, THR316, SER278, ASN239 and SER278 residues at high occupancy with GLU281(20.21%) and ARG319 (21.04%,) residues, which is necessary for sterol binding to the LXRβ. Taken together these findings suggest that neuroprotective effect of ST might be associated with anti-excitatory and anti-oxidative actions on CNS neurons and could be a promising drug candidate for the treatment or prevention of ischemic stroke related neurological disorders.
Larger, but not better, implicit motor adaptation ability inherent in medicated Parkinson’s disease patients: a smart-device-based study
Authors: Takiyama Ken , Sakurada Takeshi , Shinya Masahiro , Sato Takaaki , Ogihara Hirofumi , Komatsu Taiki 
Published: July 2019

AbstractGenerating appropriate motor commands is an essential brain function. To achieve proper motor control in diverse situations, predicting future states of the environment and body and modifying the prediction are indispensable. The internal model is a promising hypothesis about brain function for generating and modifying the prediction. Although several findings support the involvement of the cerebellum in the internal model, recent results support the influence of other related brain regions on the internal model. A representative example is the motor adaptation ability in Parkinson’s disease (PD) patients. Although this ability provides some hints about how dopamine deficits affect the internal model, previous findings are inconsistent; some reported a deficit in the motor adaptation ability in PD patients, but others reported that the motor adaptation ability of PD patients is comparable to that of healthy controls. A possible factor causing this inconsistency is the difference in task settings, which yield different cognitive strategies in each study. Here, we demonstrate a larger, but not better, motor adaptation ability in PD patients than healthy controls while reducing the involvement of cognitive strategies and concentrating on implicit motor adaptation abilities. This study utilizes a smart-device-based experiment that enables motor adaptation experiments anytime and anywhere with less cognitive strategy involvement. The PD patients showed a significant response to insensible environmental changes, but the response was not necessarily suitable for adapting to the changes. Our findings support compensatory or paretic cerebellar functions in PD patients from the perspective of motor adaptation.
Shear forces drive precise patterning of hair cells in the mammalian inner ear
Authors: Cohen Roie , Amir-Zilberstein Liat , Hersch Micha , Woland Shiran , Taiber Shahar , Matsuzaki Fumio , Bergmann Sven , Avraham Karen B. , Sprinzak David 
Published: July 2019

AbstractPrecise cellular organizations are required for the function of many organs and tissues. It is often unclear, however, how such precise patterns emerge during development. The mammalian hearing organ, the organ of Corti, consists of a remarkably organized pattern of four rows of hair cells (HCs) interspersed by non-sensory supporting cells (SCs). This checkerboard-like pattern of HCs and SCs emerges from a disordered epithelium over several days, yet the transition to an ordered cellular pattern is not well understood. Using a combination of quantitative morphological analysis and time-lapse imaging of mouse cochlear explants, we show here that patterning of the organ of Corti involves dynamic reorganizations that include lateral shear motion, cell intercalations, and delaminations. A mathematical model, where tissue morphology is described in terms of the mechanical forces that act on cells and cellular junctions, suggests that global shear on HCs and local repulsion between HCs are sufficient to drive the tissue into the final checkerboard-like pattern. Our findings suggest that precise patterns can emerge during development from reorganization processes, driven by a combination of global and local forces in a process analogous to shear-induced crystallization.
FGF2 modulates simultaneously the mode, the rate of division and the growth fraction in cultures of Radial Glia
Authors: Ledesma-Terrón Mario , Peralta-Cañadas Nuria , Míguez David G. 
Published: July 2019

ABSTRACTRadial Glial progenitors in the mammalian developing neocortex have been shown to follow a deterministic differentiation program restricted to an asymmetric-only mode of division. This feature seems incompatible with their well known ability to expand in number when cultured in vitro, driven by Fibroblast Growth Factor 2 and other mitogenic signals. The changes in their differentiation dynamics that allow this transition from in vivo asymmetric-only division mode to an in vitro self-renewing culture have not been fully characterized. Here we combine experiments of Radial Glia cultures with theory and numerical models to show that Fibroblast Growth Factor 2 has a triple effect by simultaneously increasing the growth fraction, promoting symmetric divisions and shortening the length of the cell cycle. This combined effect of Fibroblast Growth Factor 2 in the differentiation dynamics of Radial Glial progenitors partner to establish and sustain a pool of rapidly proliferating in vitro pool of Radial Glial progenitors.
Cryo-EM structure of the Hedgehog release protein Dispatched
Authors: Cannac Fabien , Qi Chao , Falschlunger Julia , Hausmann George , Basler Konrad , Korkhov Volodymyr M. 
Published: July 2019

AbstractThe Hedgehog signaling pathway controls embryonic development and adult tissue homeostasis in multicellular organisms. In Drosophila melanogaster, the pathway is primed by secretion of a dually lipid-modified morphogen, Hedgehog (Hh), a process dependent on a membrane-integral protein Dispatched. Although Dispatched is a critical component of the pathway, the structural basis of its activity has so far not been described. Here, we describe a cryo-EM structure of the Drosophila melanogaster Dispatched at 3.2 Å resolution. The ectodomains of Dispatched adopt an open conformation suggestive of a receptor-chaperone role. A 3D reconstruction of Dispatched bound to Hh confirms the ability of Dispatched to bind Hh but using a unique mode distinct from those previously observed in structures of Hh complexes. The structure may represent the state of the complex that precedes shedding of Hh from the surface of the morphogen-releasing cell.
Few glitters are original gold
Authors: Ansari Aisha Rehman , Kashif Muhammad 
Published: July 2019

Purpose
The purpose of this paper is to investigate the role of brand identification (BI), brand knowledge (BK) and brand psychological ownership (BPO) to predict brand citizenship behaviours (BCB) in a mediating role of brand pride.

Design/methodology/approach
Using survey data collected from 372 front line employees (FLEs), employed in different banks in Pakistan, the path analysis through structural equation modelling procedures is used to perform data analysis.

Findings
The results show that BI, BK and BPO strongly predict BCB in a mediating role of brand pride.

Practical implications
The results have pragmatic value to guide managers and marketing policymakers to develop a brand culture where the company as a brand is internally owned by its employees. The supervisors should offer FLEs with opportunities to speak up and must socialize with them so that communication touch points can be established and strengthened. Furthermore, delegation of authority and positive enforcement are important tools to trigger psychological ownership among FLEs.

Originality/value
Three antecedents (i.e. BI, BK and BPO) to advocate and channelize brand-oriented citizenship behaviours are unique to this study. Furthermore, the mediating role of brand pride is yet another unique contribution.
Early bird or versioning
Authors: Chen Mingchun , Liu Zhiying , Ma Chaoliang 
Published: July 2019

Purpose
Crowdfunding, especially reward-based crowdfunding, has quickly evolved into a commonly used vehicle for innovating entrepreneurs to develop their products. Many crowdfunding platforms allow creators maximum flexibility in terms of the prices and rewards offered in a project to gain sufficient capital. However, creators need to understand how to design project rewards and how to select a pricing strategy, in addition to whether the creator should spend resources on designing multiple rewards of varying quality. The purpose of this paper is to address these issues by answering whether and why there are significant differences in the application of early-bird and versioning pricing strategies in crowdfunding.

Design/methodology/approach
This paper develops a two-stage dynamic game model with incomplete information, proposes a corollary calculated by analyzing a perfect Bayesian equilibrium, and then tests Corollary 1 by empirical analysis.

Findings
Contrary to the findings of other studies, the results show that an early-bird pricing strategy is likely better than a versioning pricing strategy for earning greater revenue in a crowdfunding context, on average. This finding means that creators do not have to spend as much in designing rewards of various qualities; rather, they should only provide multiple price options for high-quality rewards. However, if the heterogeneity of target backers’ valuations and the quality difference between two types of products are adequately high, a versioning pricing strategy may be a good choice for creators.

Practical implications
This paper provides a reference for creators regarding the selection of pricing strategies and the design of reward quality when launching crowdfunding projects.

Originality/value
This paper explains an interesting and practical issue in the design of reward quality and the selection of a pricing strategy after fully considering the role of the crowdfunding all-or-nothing mechanism and special backer behavior.
CSR, social ties and firm performance
Authors: Jang Soojeen Sarah , Ko Hyesoo , Chung Yanghon , Woo Chungwon 
Published: July 2019

PurposeThis paper aims to explore the effect of social ties on the relationship between corporate social responsibility (CSR) and firm performance in Korea.Design/methodology/approachSocial ties were measured from firm disclosures of 318 Korean firms from 2012 to 2015. Propensity score matching and regression analysis were used to investigate the moderating effects of social ties on the relationship between CSR and firm performance.FindingsThe result shows that social ties have more negative moderating effects on the relationship between CSR and firm performance in Chaebol firms than in non-Chaebol firms.Practical implicationsFirms need to enhance the monitoring of social ties within board members to assure the proper oversight of CSR.Originality/valueThis paper contributes to the CSR literature by providing empirical evidence of the negative aspects of social ties on the relationship between CSR and firm performance in Korea.