bluuebunny/crossref_metadata_2025_split huggingface dataset:
"RETRACTED ARTICLE: Vibrio parahaemolyticus RhsP represents a widespread group of pro-effectors for type VI secretion systems
Authors: Jiang Nan , Tang Le , Xie Ruiqiang , Li Zhi , Burkinshaw Brianne , Liang Xiaoye , Sosa Dylan , Aravind L. , Dong Tao , Zhang Dapeng , Zheng Jun 
Published: September 2018

AbstractType VI secretion systems (T6SSs) translocate effector proteins, such as Rhs toxins, to eukaryotic cells or prokaryotic competitors. All T6SS Rhs-type effectors characterized thus far contain a PAAR motif or a similar structure. Here, we describe a T6SS-dependent delivery mechanism for a subset of Rhs proteins that lack a PAAR motif. We show that the N-terminal Rhs domain of protein RhsP (or VP1517) from Vibrio parahaemolyticus inhibits the activity of the C-terminal DNase domain. Upon auto-proteolysis, the Rhs fragment remains inside the cells, and the C-terminal region interacts with PAAR2 and is secreted by T6SS2; therefore, RhsP acts as a pro-effector. Furthermore, we show that RhsP contributes to the control of certain “social cheaters” (opaR mutants). Genes encoding proteins with similar Rhs and PAAR-interacting domains, but diverse C-terminal regions, are widely distributed among Vibrio species.
Analysis of extracellular mRNA in human urine reveals splice variant biomarkers of muscular dystrophies
Authors: Antoury Layal , Hu Ningyan , Balaj Leonora , Das Sudeshna , Georghiou Sofia , Darras Basil , Clark Tim , Breakefield Xandra O. , Wheeler Thurman M. 
Published: September 2018

AbstractUrine contains extracellular RNA (exRNA) markers of urogenital cancers. However, the capacity of genetic material in urine to identify systemic diseases is unknown. Here we describe exRNA splice products in human urine as a source of biomarkers for the two most common forms of muscular dystrophies, myotonic dystrophy (DM) and Duchenne muscular dystrophy (DMD). Using a training set, RT-PCR, droplet digital PCR, and principal component regression, we identify ten transcripts that are spliced differently in urine exRNA from patients with DM type 1 (DM1) as compared to unaffected or disease controls, form a composite biomarker, and develop a predictive model that is 100% accurate in our independent validation set. Urine also contains mutation-specificDMDmRNAs that confirm exon-skipping activity of the antisense oligonucleotide drug eteplirsen. Our results establish that urine mRNA splice variants can be used to monitor systemic diseases with minimal or no clinical effect on the urinary tract.
An orbitally derived single-atom magnetic memory
Authors: Kiraly Brian , Rudenko Alexander N. , van Weerdenburg Werner M. J. , Wegner Daniel , Katsnelson Mikhail I. , Khajetoorians Alexander A. 
Published: September 2018

AbstractA magnetic atom epitomizes the scaling limit for magnetic information storage. Individual atomic spins have recently exhibited magnetic remanence, a requirement for magnetic memory. However, such memory has been only realized on thin insulating surfaces, removing potential tunability via electronic gating or exchange-driven magnetic coupling. Here, we show a previously unobserved mechanism for single-atom magnetic storage based on bistability in the orbital population, or so-called valency, of an individual Co atom on semiconducting black phosphorus (BP). Ab initio calculations reveal that distance-dependent screening from the BP surface stabilizes the two distinct valencies, each with a unique orbital population, total magnetic moment, and spatial charge density. Excellent correspondence between the measured and predicted charge densities reveal that such orbital configurations can be accessed and manipulated without a spin-sensitive readout mechanism. This orbital memory derives stability from the energetic barrier to atomic relaxation, demonstrating the potential for high-temperature single-atom information storage.
Lnk/Sh2b3 deficiency restores hematopoietic stem cell function and genome integrity in Fancd2 deficient Fanconi anemia
Authors: Balcerek Joanna , Jiang Jing , Li Yang , Jiang Qinqin , Holdreith Nicholas , Singh Brijendra , Chandra Vemika , Lv Kaosheng , Ren Jian-gang , Rozenova Krasimira , Li Weihua , Greenberg Roger A. , Tong Wei 
Published: September 2018

AbstractFanconi anemia (FA) is a bone marrow failure (BMF) syndrome that arises from mutations in a network of FA genes essential for DNA interstrand crosslink (ICL) repair and replication stress tolerance. While allogeneic stem cell transplantation can replace defective HSCs, interventions to mitigate HSC defects in FA do not exist. Remarkably, we reveal here that Lnk (Sh2b3) deficiency restores HSC function in Fancd2−/− mice. Lnk deficiency does not impact ICL repair, but instead stabilizes stalled replication forks in a manner, in part, dependent upon alleviating blocks to cytokine−mediated JAK2 signaling. Lnk deficiency restores proliferation and survival of Fancd2−/− HSCs, while reducing replication stress and genomic instability. Furthermore, deletion of LNK in human FA-like HSCs promotes clonogenic growth. These findings highlight a new role for cytokine/JAK signaling in promoting replication fork stability, illuminate replication stress as a major underlying origin of BMF in FA, and have strong therapeutic implications.
Functional modulation of primary visual cortex by the superior colliculus in the mouse
Authors: Ahmadlou Mehran , Zweifel Larry S. , Heimel J. Alexander 
Published: September 2018

AbstractThe largest targets of retinal input in mammals are the dorsal lateral geniculate nucleus (dLGN), a relay to the primary visual cortex (V1), and the superior colliculus. V1 innervates and influences the superior colliculus. Here, we find that, in turn, superior colliculus modulates responses in mouse V1. Optogenetically inhibiting the superior colliculus reduces responses in V1 to optimally sized stimuli. Superior colliculus could influence V1 via its strong projection to the lateral posterior nucleus (LP/Pulvinar) or its weaker projection to the dLGN. Inhibiting superior colliculus strongly reduces activity in LP. Pharmacologically silencing LP itself, however, does not remove collicular modulation of V1. The modulation is instead due to a collicular gain modulation of the dLGN. Surround suppression operating in V1 explains the different effects for differently sized stimuli. Computations of visual saliency in the superior colliculus can thus influence tuning in the visual cortex via a tectogeniculate pathway.
An OB-fold complex controls the repair pathways for DNA double-strand breaks
Authors: Gao Shengxian , Feng Sumin , Ning Shaokai , Liu Jingyan , Zhao Huayu , Xu Yixi , Shang Jinfeng , Li Kejiao , Li Qing , Guo Rong , Xu Dongyi 
Published: September 2018

Abstract53BP1 with its downstream proteins, RIF1, PTIP and REV7, antagonizes BRCA1-dependent homologous recombination (HR) and promotes non-homologous end joining (NHEJ) in an unclear manner. Here we show that REV7 forms a complex with two proteins, FAM35A and C20ORF196. We demonstrate that FAM35A preferentially binds single-strand DNA (ssDNA) in vitro, and is recruited to DSBs as a complex with C20ORF196 and REV7 downstream of RIF1 in vivo. Epistasis analysis shows that both proteins act in the same pathway as RIF1 in NHEJ. The defects in HR pathway to repair DSBs and the reduction in resection of broken DNA ends in BRCA1-mutant cells can be largely suppressed by inactivating FAM35A or C20ORF196, indicating that FAM35A and C20ORF196 prevent end resection in these cells. Together, our data identified a REV7–FAM35A–C20ORF196 complex that binds and protects broken DNA ends to promote the NHEJ pathway for DSB repair.
Using both qualitative and quantitative data in parameter identification for systems biology models
Authors: Mitra Eshan D. , Dias Raquel , Posner Richard G. , Hlavacek William S. 
Published: September 2018

AbstractIn systems biology, qualitative data are often generated, but rarely used to parameterize models. We demonstrate an approach in which qualitative and quantitative data can be combined for parameter identification. In this approach, qualitative data are converted into inequality constraints imposed on the outputs of the model. These inequalities are used along with quantitative data points to construct a single scalar objective function that accounts for both datasets. To illustrate the approach, we estimate parameters for a simple model describing Raf activation. We then apply the technique to a more elaborate model characterizing cell cycle regulation in yeast. We incorporate both quantitative time courses (561 data points) and qualitative phenotypes of 119 mutant yeast strains (1647 inequalities) to perform automated identification of 153 model parameters. We quantify parameter uncertainty using a profile likelihood approach. Our results indicate the value of combining qualitative and quantitative data to parameterize systems biology models.
Caspase-1 inhibition alleviates cognitive impairment and neuropathology in an Alzheimer’s disease mouse model
Authors: Flores Joseph , Noël Anastasia , Foveau Bénédicte , Lynham Jeffrey , Lecrux Clotilde , LeBlanc Andréa C. 
Published: September 2018

AbstractAlzheimer's disease (AD) is an intractable progressive neurodegenerative disease characterized by cognitive decline and dementia. An inflammatory neurodegenerative pathway, involving Caspase-1 activation, is associated with human age-dependent cognitive impairment and several classical AD brain pathologies. Here, we show that the nontoxic and blood–brain barrier permeable small molecule Caspase-1 inhibitor VX-765 dose-dependently reverses episodic and spatial memory impairment, and hyperactivity in the J20 mouse model of AD. Cessation of VX-765 results in the reappearance of memory deficits in the mice after 1 month and recommencement of treatment re-establishes normal cognition. VX-765 prevents progressive amyloid beta peptide deposition, reverses brain inflammation, and normalizes synaptophysin protein levels in mouse hippocampus. Consistent with these findings, Caspase-1 null J20 mice are protected from episodic and spatial memory deficits, neuroinflammation and Aβ accumulation. These results provide in vivo proof of concept for Caspase-1 inhibition against AD cognitive deficits and pathologies.
GA-Hecate antiviral properties on HCV whole cycle represent a new antiviral class and open the door for the development of broad spectrum antivirals
Authors: Batista Mariana Nogueira , Sanches Paulo Ricardo da Silva , Carneiro Bruno Moreira , Braga Ana Cláudia Silva , Campos Guilherme Rodrigues Fernandes , Cilli Eduardo Maffud , Rahal Paula 
Published: September 2018

AbstractIn recent years, synthetic peptides have been considered promising targets for drug development that possess low side-effects, are cost-effective and are susceptible to rational design. Hecate was initially described as a potent bacterial inhibitor and subsequently as an anticancer drug with functions related to its lipid interaction property. Viruses, such as hepatitis C virus (HCV), have a lipid-dependent life cycle and could be affected by Hecate in many ways. Here, we assessed modifications on Hecate’s N-terminus region and its effects on HCV and hepatotoxicity. Gallic acid-conjugated Hecate was the most efficient Hecate-derivative, presenting high potential as an antiviral and inhibiting between 50 to 99% of all major steps within the HCV infectious cycle. However, the most promising aspect was GA-Hecate’s mechanism of action, which was associated with a balanced lipid interaction with the viral envelope and lipid droplets, as well as dsRNA intercalation, allowing for the possibility to affect other ssRNA viruses and those with a lipid-dependent cycle.
Fast stabilization of a high-energy ultrafast OPA with adaptive lenses
Authors: Negro Matteo , Quintavalla Martino , Mocci Jacopo , Ciriolo Anna G. , Devetta Michele , Muradore Riccardo , Stagira Salvatore , Vozzi Caterina , Bonora Stefano 
Published: September 2018

AbstractThe use of fast closed-loop adaptive optics has improved the performance of optical systems since its first application. Here we demonstrate the amplitude and carrier-envelope phase stabilization of a high energy IR optical parametric amplifier devoted to Attosecond Science exploiting two high speed adaptive optical systems for the correction of static and dynamic instabilities. The exploitation of multi actuator adaptive lenses allowed for a minimal impact on the optical setup.
Medium throughput breathing human primary cell alveolus-on-chip model
Authors: Stucki Janick D. , Hobi Nina , Galimov Artur , Stucki Andreas O. , Schneider-Daum Nicole , Lehr Claus-Michael , Huwer Hanno , Frick Manfred , Funke-Chambour Manuela , Geiser Thomas , Guenat Olivier T. 
Published: September 2018

AbstractOrgans-on-chips have the potential to improve drug development efficiency and decrease the need for animal testing. For the successful integration of these devices in research and industry, they must reproduce in vivo contexts as closely as possible and be easy to use. Here, we describe a ‘breathing’ lung-on-chip array equipped with a passive medium exchange mechanism that provide an in vivo-like environment to primary human lung alveolar cells (hAEpCs) and primary lung endothelial cells. This configuration allows the preservation of the phenotype and the function of hAEpCs for several days, the conservation of the epithelial barrier functionality, while enabling simple sampling of the supernatant from the basal chamber. In addition, the chip design increases experimental throughput and enables trans-epithelial electrical resistance measurements using standard equipment. Biological validation revealed that human primary alveolar type I (ATI) and type II-like (ATII) epithelial cells could be successfully cultured on the chip over multiple days. Moreover, the effect of the physiological cyclic strain showed that the epithelial barrier permeability was significantly affected. Long-term co-culture of primary human lung epithelial and endothelial cells demonstrated the potential of the lung-on-chip array for reproducible cell culture under physiological conditions. Thus, this breathing lung-on-chip array, in combination with patients’ primary ATI, ATII, and lung endothelial cells, has the potential to become a valuable tool for lung research, drug discovery and precision medicine.
Imagery of movements immediately following performance allows learning of motor skills that interfere
Authors: Sheahan Hannah R. , Ingram James N. , Žalalytė Goda M. , Wolpert Daniel M. 
Published: September 2018

AbstractMotor imagery, that is the mental rehearsal of a motor skill, can lead to improvements when performing the same skill. Here we show a powerful and complementary role, in which motor imagery of different movements after actually performing a skill allows learning that is not possible without imagery. We leverage a well-studied motor learning task in which subjects reach in the presence of a dynamic (force-field) perturbation. When two opposing perturbations are presented alternately for the same physical movement, there is substantial interference, preventing any learning. However, when the same physical movement is associated with follow-through movements that differ for each perturbation, both skills can be learned. Here we show that when subjects perform the skill and only imagine the follow-through, substantial learning occurs. In contrast, without such motor imagery there was no learning. Therefore, motor imagery can have a profound effect on skill acquisition even when the imagery is not of the skill itself. Our results suggest that motor imagery may evoke different neural states for the same physical state, thereby enhancing learning.
Platelet Lysate-Derived Neuropeptide y Influences Migration and Angiogenesis of Human Adipose Tissue-Derived Stromal Cells
Authors: Businaro Rita , Scaccia Eleonora , Bordin Antonella , Pagano Francesca , Corsi Mariangela , Siciliano Camilla , Capoano Raffaele , Procaccini Eugenio , Salvati Bruno , Petrozza Vincenzo , Totta Pierangela , Vietri Maria Teresa , Frati Giacomo , De Falco Elena 
Published: September 2018

AbstractNeuropeptide Y (NPY), a powerful neurotransmitter of the central nervous system, is a key regulator of angiogenesis and biology of adipose depots. Intriguingly, its peripheral vascular and angiogenic powerful activity is strictly associated to platelets, which are source of clinical hemoderivates, such as platelet lysate (PL), routinely employed in several clinical applications as wound healing, and to preserve ex vivo the progenitor properties of the adipose stromal cells pool. So far, the presence of NPY in PL and its biological effects on the adipose stromal cell fraction (ASCs) have never been investigated. Here, we aimed to identify endogenous sources of NPY such as PL-based preparations and to investigate which biological properties PL-derived NPY is able to exert on ASCs. The results show that PL contains a high amount of NPY, which is in part also excreted by ASCs when stimulated with PL. The protein levels of the three main NPY subtype receptors (Y1, Y2, Y5) are unaltered by stimulation of ASCs with PL, but their inhibition through selective pharmacological antagonists, considerably enhances migration, and a parallel reduction of angiogenic features of ASCs including decrease in VEGF mRNA and intracellular calcium levels, both downstream targets of NPY. The expression of VEGF and NPY is enhanced within the sites of neovascularisation of difficult wounds in patients after treatment with leuco-platelet concentrates. Our data highlight the presence of NPY in PL preparations and its peripheral effects on adipose progenitors.
Spectral Analysis of a Non-Equilibrium Stochastic Dynamics on a General Network
Authors: Seroussi Inbar , Sochen Nir 
Published: September 2018

AbstractUnravelling underlying complex structures from limited resolution measurements is a known problem arising in many scientific disciplines. We study a stochastic dynamical model with a multiplicative noise. It consists of a stochastic differential equation living on a graph, similar to approaches used in population dynamics or directed polymers in random media. We develop a new tool for approximation of correlation functions based on spectral analysis that does not require translation invariance. This enables us to go beyond lattices and analyse general networks. We show, analytically, that this general model has different phases depending on the topology of the network. One of the main parameters which describe the network topology is the spectral dimension $$\tilde{{\boldsymbol{d}}}$$

d
˜

. We show that the correlation functions depend on the spectral dimension and that only for $$\tilde{{\boldsymbol{d}}}$$

d
˜

> 2 a dynamical phase transition occurs. We show by simulation how the system behaves for different network topologies, by defining and calculating the Lyapunov exponents on the graph. We present an application of this model in the context of Magnetic Resonance (MR) measurements of porous structure such as brain tissue. This model can also be interpreted as a KPZ equation on a graph.
An Internally Controlled Quantitative Target Occupancy Assay for Covalent Inhibitors
Authors: Hansen Rasmus , Firdaus Sarah J. , Li Shuangwei , Janes Matthew R. , Zhang Jingchuan , Liu Yi , Zarrinkar Patrick P. 
Published: September 2018

AbstractAssessing target occupancy is critical for establishing proof-of-mechanism for novel inhibitors and to determine whether robust target inhibition can be achieved at tolerated doses. This is challenging in the clinic using conventional methods due to the need for untreated controls. We describe a new mass spectrometry approach to quantitatively assess target occupancy for covalent inhibitors that does not require untreated controls, and apply the method to the KRASG12C inhibitor ARS-1620.
Comparing the expression profiles of steroid hormone receptors and stromal cell markers in prostate cancer at different Gleason scores
Authors: Gevaert Thomas , Van Eycke Yves-Rémi , Vanden Broeck Thomas , Van Poppel Hein , Salmon Isabelle , Rorive Sandrine , Claessens Frank , De Ridder Dirk , Decaestecker Christine , Joniau Steven 
Published: September 2018

AbstractThe recent developments in anti-angiogenic and immunomodulatory drugs show that the tumour micro-environment (TME) becomes increasingly important in cancer research. Here we investigated the correlation between the Gleason score (GS) and the TME by comparing tissue expression profiles of steroid hormone receptors, cancer activated fibroblast (CAF) markers and vessel densities between different GS groups. Therefore, matched patient cohorts were composed for different GS (6-7-8). Tissue micro-arrays with 6 samples/patient were processed for immunohistochemistry. Stained slides were digitised, stroma and epithelium were selectively annotated, and all selected areas were quantitatively analysed for marker expression. The most striking findings were decreased stromal expression levels of several steroid hormone receptors, increased CAF-phenotypes and increased vessel densities in high GS prostate cancer compared to low GS prostate cancer and paired prostate non-tumour tissue. The present data reveal a complex correlation between prostate cancer differentiation and TME components and suggest that different GS can be associated with different possible actionable targets in the TME. The use of standardised digital image analysis tools generated robust and reproducible quantitative data, which is novel and more informative compared to the classic semi-quantitative and observer-dependent visual scoring of immunohistochemistry.
Verteporfin selectively kills hypoxic glioma cells through iron-binding and increased production of reactive oxygen species
Authors: Eales Katherine L. , Wilkinson Edward A. , Cruickshank Garth , Tucker James H. R. , Tennant Daniel A. 
Published: September 2018

AbstractGliomas are highly malignant brain tumours characterised by extensive areas of poor perfusion which subsequently leads to hypoxia and reduced survival. Therapies that address the hypoxic microenvironment are likely to significantly improve patient outcomes. Verteporfin, a benzoporphyrin-like drug, has been suggested to target the Yes-associated protein (YAP). Increased YAP expression and transcriptional activity has been proposed in other tumour types to promote malignant cell survival and thus YAP-inhibitor, verteporfin, may be predicted to impact glioma cell growth and viability. Due to the extensive hypoxic nature of gliomas, we investigated the effect of hypoxia on YAP expression and found that YAP transcription is increased under these conditions. Treatment of both primary and immortalised glioblastoma cell lines with verteporfin resulted in a significant decrease in viability but strikingly only under hypoxic conditions (1% O2). We discovered that cell death occurs through a YAP-independent mechanism, predominately involving binding of free iron and likely through redox cycling, contributes to production of reactive oxygen species. This results in disruption of normal cellular processes and death in cells already under oxidative stress – such as those in hypoxia. We suggest that through repurposing verteporfin, it represents a novel means of treating highly therapy-resistant, hypoxic cells in glioma.