bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rescue from galactose-induced death of Leigh Syndrome patient cells by pyruvate and NAD+
Authors: Iannetti Eligio F. , Smeitink Jan A. M. , Willems Peter H. G. M. , Beyrath Julien , Koopman Werner J. H. 
Published: November 2018

AbstractCell models of mitochondrial complex I (CI) deficiency display activation of glycolysis to compensate for the loss in mitochondrial ATP production. This adaptation can mask other relevant deficiency-induced aberrations in cell physiology. Here we investigated the viability, mitochondrial morphofunction, ROS levels and ATP homeostasis of primary skin fibroblasts from Leigh Syndrome (LS) patients with isolated CI deficiency. These cell lines harbored mutations in nuclear DNA (nDNA)-encoded CI genes (NDUFS7, NDUFS8, NDUFV1) and, to prevent glycolysis upregulation, were cultured in a pyruvate-free medium in which glucose was replaced by galactose. Following optimization of the cell culture protocol, LS fibroblasts died in the galactose medium, whereas control cells did not. LS cell death was dose-dependently inhibited by pyruvate, malate, oxaloacetate, α-ketoglutarate, aspartate, and exogenous NAD+ (eNAD), but not by lactate, succinate, α-ketobutyrate, and uridine. Pyruvate and eNAD increased the cellular NAD+ content in galactose-treated LS cells to a different extent and co-incubation studies revealed that pyruvate-induced rescue was not primarily mediated by NAD+. Functionally, in LS cells glucose-by-galactose replacement increased mitochondrial fragmentation and mass, depolarized the mitochondrial membrane potential (Δψ), increased H2DCFDA-oxidizing ROS levels, increased mitochondrial ATP generation, and reduced the total cellular ATP content. These aberrations were differentially rescued by pyruvate and eNAD, supporting the conclusion that these compounds rescue galactose-induced LS cell death via different mechanisms. These findings establish a cell-based strategy for intervention testing and enhance our understanding of CI deficiency pathophysiology.
Customizing supercontinuum generation via on-chip adaptive temporal pulse-splitting
Authors: Wetzel Benjamin , Kues Michael , Roztocki Piotr , Reimer Christian , Godin Pierre-Luc , Rowley Maxwell , Little Brent E. , Chu Sai T. , Viktorov Evgeny A. , Moss David J. , Pasquazi Alessia , Peccianti Marco , Morandotti Roberto 
Published: November 2018

AbstractModern optical systems increasingly rely on complex physical processes that require accessible control to meet target performance characteristics. In particular, advanced light sources, sought for, for example, imaging and metrology, are based on nonlinear optical dynamics whose output properties must often finely match application requirements. However, in these systems, the availability of control parameters (e.g., the optical field shape, as well as propagation medium properties) and the means to adjust them in a versatile manner are usually limited. Moreover, numerically finding the optimal parameter set for such complex dynamics is typically computationally intractable. Here, we use an actively controlled photonic chip to prepare and manipulate patterns of femtosecond optical pulses that give access to an enhanced parameter space in the framework of supercontinuum generation. Taking advantage of machine learning concepts, we exploit this tunable access and experimentally demonstrate the customization of nonlinear interactions for tailoring supercontinuum properties.
Using single nucleotide variations in single-cell RNA-seq to identify subpopulations and genotype-phenotype linkage
Authors: Poirion Olivier , Zhu Xun , Ching Travers , Garmire Lana X. 
Published: November 2018

AbstractDespite its popularity, characterization of subpopulations with transcript abundance is subject to a significant amount of noise. We propose to use effective and expressed nucleotide variations (eeSNVs) from scRNA-seq as alternative features for tumor subpopulation identification. We develop a linear modeling framework, SSrGE, to link eeSNVs associated with gene expression. In all the datasets tested, eeSNVs achieve better accuracies than gene expression for identifying subpopulations. Previously validated cancer-relevant genes are also highly ranked, confirming the significance of the method. Moreover, SSrGE is capable of analyzing coupled DNA-seq and RNA-seq data from the same single cells, demonstrating its value in integrating multi-omics single cell techniques. In summary, SNV features from scRNA-seq data have merits for both subpopulation identification and linkage of genotype-phenotype relationship.
BAFopathies’ DNA methylation epi-signatures demonstrate diagnostic utility and functional continuum of Coffin–Siris and Nicolaides–Baraitser syndromes
Authors: Aref-Eshghi Erfan , Bend Eric G. , Hood Rebecca L. , Schenkel Laila C. , Carere Deanna Alexis , Chakrabarti Rana , Nagamani Sandesh C. S. , Cheung Sau Wai , Campeau Philippe M. , Prasad Chitra , Siu Victoria Mok , Brady Lauren , Tarnopolsky Mark A. , Callen David J. , Innes A. Micheil , White Susan M. , Meschino Wendy S. , Shuen Andrew Y. , Paré Guillaume , Bulman Dennis E. , Ainsworth Peter J. , Lin Hanxin , Rodenhiser David I. , Hennekam Raoul C. , Boycott Kym M. , Schwartz Charles E. , Sadikovic Bekim 
Published: November 2018

AbstractCoffin–Siris and Nicolaides–Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B,SMARCB1, andSMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboringARID1Bdeletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening.
A third generation of radical fluorinating agents based on N-fluoro-N-arylsulfonamides
Authors: Meyer Daniel , Jangra Harish , Walther Fabian , Zipse Hendrik , Renaud Philippe 
Published: November 2018

AbstractRadical fluorination has been known for a long time, but synthetic applications were severely limited by the hazardous nature of the first generation of reagents such as F2 and the strongly electrophilic nature of the second generation of reagents such as N-fluorobenzenesulfonimide (NFSI) and Selecfluor®. Here, we report the preparation, use and properties of N-fluoro-N-arylsulfonamides (NFASs), a class of fluorinating reagents suitable for radical fluorination under mild conditions. Their N–F bond dissociation energies (BDE) are 30–45 kJ mol−1 lower than the N–F BDE of the reagents of the second generation. This favors clean radical fluorination processes over undesired side reactions. The utility of NFASs is demonstrated by a metal-free radical hydrofluorination of alkenes including an efficient remote C–H fluorination via a 1,5-hydrogen atom transfer. NFASs have the potential to become the reagents of choice in many radical fluorination processes.
Retroactive and graded prioritization of memory by reward
Authors: Braun Erin Kendall , Wimmer G. Elliott , Shohamy Daphna 
Published: November 2018

AbstractMany decisions are based on an internal model of the world. Yet, how such a model is constructed from experience and represented in memory remains unknown. We test the hypothesis that reward shapes memory for sequences of events by retroactively prioritizing memory for objects as a function of their distance from reward. Human participants encountered neutral objects while exploring a series of mazes for reward. Across six data sets, we find that reward systematically modulates memory for neutral objects, retroactively prioritizing memory for objects closest to the reward. This effect of reward on memory emerges only after a 24-hour delay and is stronger for mazes followed by a longer rest interval, suggesting a role for post-reward replay and overnight consolidation, as predicted by neurobiological data in animals. These findings demonstrate that reward retroactively prioritizes memory along a sequential gradient, consistent with the role of memory in supporting adaptive decision-making.
Bimodal sensing of guidance cues in mechanically distinct microenvironments
Authors: Tabdanov Erdem D. , Puram Vikram V. , Win Zaw , Alamgir Ashab , Alford Patrick W. , Provenzano Paolo P. 
Published: November 2018

AbstractContact guidance due to extracellular matrix architecture is a key regulator of carcinoma invasion and metastasis, yet our understanding of how cells sense guidance cues is limited. Here, using a platform with variable stiffness that facilitates uniaxial or biaxial matrix cues, or competing E-cadherin adhesions, we demonstrate distinct mechanoresponsive behavior. Through disruption of traction forces, we observe a profound phenotypic shift towards a mode of dendritic protrusion and identify bimodal processes that govern guidance sensing. In contractile cells, guidance sensing is strongly dependent on formins and FAK signaling and can be perturbed by disrupting microtubule dynamics, while low traction conditions initiate fluidic-like dendritic protrusions that are dependent on Arp2/3. Concomitant disruption of these bimodal mechanisms completely abrogates the contact guidance response. Thus, guidance sensing in carcinoma cells depends on both environment architecture and mechanical properties and targeting the bimodal responses may provide a rational strategy for disrupting metastatic behavior.
Autapses enhance bursting and coincidence detection in neocortical pyramidal cells
Authors: Yin Luping , Zheng Rui , Ke Wei , He Quansheng , Zhang Yi , Li Junlong , Wang Bo , Mi Zhen , Long Yue-sheng , Rasch Malte J. , Li Tianfu , Luan Guoming , Shu Yousheng 
Published: November 2018

AbstractAutapses are synaptic contacts of a neuron’s axon onto its own dendrite and soma. In the neocortex, self-inhibiting autapses in GABAergic interneurons are abundant in number and play critical roles in regulating spike precision and network activity. Here we examine whether the principal glutamatergic pyramidal cells (PCs) also form functional autapses. In patch-clamp recording from both rodent and human PCs, we isolated autaptic responses and found that these occur predominantly in layer-5 PCs projecting to subcortical regions, with very few in those projecting to contralateral prefrontal cortex and layer 2/3 PCs. Moreover, PC autapses persist during development into adulthood. Surprisingly, they produce giant postsynaptic responses (∼5 fold greater than recurrent PC-PC synapses) that are exclusively mediated by AMPA receptors. Upon activation, autapses enhance burst firing, neuronal responsiveness and coincidence detection of synaptic inputs. These findings indicate that PC autapses are functional and represent an important circuit element in the neocortex.
Crossover from positive to negative optical torque in mesoscale optical matter
Authors: Han Fei , Parker John A. , Yifat Yuval , Peterson Curtis , Gray Stephen K. , Scherer Norbert F. , Yan Zijie 
Published: November 2018

AbstractThe photons in circularly polarized light can transfer their quantized spin angular momentum to micro- and nanostructures via absorption and scattering. This normally exerts positive torque on the objects wher the sign (i.e., handedness or angular direction) follows that of the spin angular momentum. Here we show that the sign of the optical torque can be negative in mesoscopic optical matter arrays of metal nanoparticles (NPs) assembled in circularly polarized optical traps. Crossover from positive to negative optical torque, which occurs for arrays with different number, separation and configuration of the constituent particles, is shown to result from many-body interactions as clarified by electrodynamics simulations. Our results establish that both positive and negative optical torque can be readily realized and controlled in optical matter arrays. This property and reconfigurability of the arrays makes possible programmable materials for optomechanical, microrheological and biological applications.
Tailoring atomic layer growth at the liquid-metal interface
Authors: Cao Hai , Waghray Deepali , Knoppe Stefan , Dehaen Wim , Verbiest Thierry , De Feyter Steven 
Published: November 2018

AbstractEngineering atomic structures at metal surfaces represents an important step in the development of novel nanomaterials and nanodevices, but relies predominantly on atomic/molecular beam epitaxy under ultrahigh vacuum conditions, where controlling the deposition processes remains challenging. By using solution-borne nanosized gold clusters as a precursor, here we develop a wet deposition protocol to the fabrication of atomically flat gold nanoislands, so as to utilize the dynamic exchange of surface-active molecules at the liquid-metal interface for manipulating the growth kinetics of ultrathin metallic nanostructures. While remarkable shape and size selection of gold nanoislands is observed, our experimental and theoretical investigations provide compelling evidences that organic adsorbates can impart a bias to the island orientation by preferred adsorption and alignment and intervene in the assembly and disassembly of adatom islands by complexing with Au adatoms. This approach offers a simple solution to regulate atomic layer growth of metals at ambient conditions.
24-hour levodopa-carbidopa intestinal gel may reduce troublesome dyskinesia in advanced Parkinson’s disease
Authors: Cruse Belinda , Morales-Briceño Hugo , Chang Florence C F , Mahant Neil , Ha Ainhi D , Kim Samuel D , Wolfe Nigel , Kwan Vu , Tsui David S , Griffith Jane M , Galea Donna , Fung Victor S C 
Published: November 2018

AbstractLevodopa-carbidopa intestinal gel (LCIG) is effective for the control of motor fluctuations in Parkinson’s disease (PD). The objective of this study is to report the reduction of dyskinesias after transitioning from 16 to 24-h/day LCIG infusion. From a cohort of 74 PD patients treated with LCIG for motor fluctuations, we identified 12 patients that were treated with 24-h per day infusion with the aim to control troublesome daytime dyskinesia. Clinical, demographic, dyskinesia rating scales were evaluated. Daytime dyskinesia was reduced in 75% (9/12) patients following treatment with 24-h therapy, including 7 who were compared with 16-h therapy and 2 that were transitioned from oral dopaminergic therapy to 24-h LCIG. Combining the data from all 12 subjects, troublesome dyskinesias were reduced during 24-h LCIG; UPDRS 4.1 (time spent with dyskinesias) mean change was −1.5 ± 0.75, p = 0.010 (Wilcoxon signed-rank test) and UPDRS 4.2 (functional impact of dyskinesias) mean change was −1.7 ± 0.90, p = 0.016, without changing their UPDRS part 3 “ON” scores (p = 0.138) or H&Y (p = 0.157). In 5 patients, improvement in dyskinesia occurred despite an overall increase in the total daily levodopa dose. None of the patients had worsening of dyskinesia after a median follow-up of 28 months. 24-h per day infusion of LCIG may be a useful strategy in the management of troublesome dyskinesias in PD patients with disabling dyskinesias resistant to attempts to optimise 16-hours per day therapy. We postulate that this may be due to a pharmacodynamic as opposed to pharmacokinetic mechanism.
Extensional and shear rheology of okra polysaccharides in the presence of artificial saliva
Authors: Yuan Bo , Ritzoulis Christos , Chen Jianshe 
Published: November 2018

AbstractExtensional and shear viscosities were studied for mixtures comprising artificial saliva and okra mucilage, the latter acting as a model thick-liquid food. These experiments aimed to obtain information on the flow-behavior information of the systems, underpinning the texture sensation of foods as perceived by dysphagic and xerostomic populations. Mixing okra mucilage with artificial saliva dramatically increases the shear viscosity of artificial saliva throughout the studied ranges of concentrations and deformation rates. Particle tracking does not suggest direct interactions between the components of artificial saliva and of okra mucilage. The rheology of the okra polymer (OP)–artificial saliva (AS) mixture is dominated by its extensional viscosity: Trouton ratios are in the order of tens to hundreds, while they decrease with increasing okra-mucilage concentration; this highlighs the dominance of the extensional rheology and the increasing importance of the shear mechanics with increasing okra content. The relaxation times and extensional moduli are also reported for the systems under study. Extensional and shear flows are of equal importance concerning the elastic behavior.
Probing tumor microenvironment in patients with newly diagnosed glioblastoma during chemoradiation and adjuvant temozolomide with functional MRI
Authors: Ly K. Ina , Vakulenko-Lagun Bella , Emblem Kyrre E. , Ou Yangming , Da Xiao , Betensky Rebecca A. , Kalpathy-Cramer Jayashree , Duda Dan G. , Jain Rakesh K. , Chi Andrew S. , Plotkin Scott R. , Batchelor Tracy T. , Sorensen Gregory , Rosen Bruce R. , Gerstner Elizabeth R. 
Published: November 2018

AbstractFunctional MRI may identify critical windows of opportunity for drug delivery and distinguish between early treatment responders and non-responders. Using diffusion-weighted, dynamic contrast-enhanced, and dynamic susceptibility contrast MRI, as well as pro-angiogenic and pro-inflammatory blood markers, we prospectively studied the physiologic tumor-related changes in fourteen newly diagnosed glioblastoma patients during standard therapy. 153 MRI scans and blood collection were performed before chemoradiation (baseline), weekly during chemoradiation (week 1–6), monthly before each cycle of adjuvant temozolomide (pre-C1-C6), and after cycle 6. The apparent diffusion coefficient, volume transfer coefficient (Ktrans), and relative cerebral blood volume (rCBV) and flow (rCBF) were calculated within the tumor and edema regions and compared to baseline. Cox regression analysis was used to assess the effect of clinical variables, imaging, and blood markers on progression-free (PFS) and overall survival (OS). After controlling for additional covariates, high baseline rCBV and rCBF within the edema region were associated with worse PFS (microvessel rCBF: HR = 7.849, p = 0.044; panvessel rCBV: HR = 3.763, p = 0.032; panvessel rCBF: HR = 3.984; p = 0.049). The same applied to high week 5 and pre-C1 Ktrans within the tumor region (week 5 Ktrans: HR = 1.038, p = 0.003; pre-C1 Ktrans: HR = 1.029, p = 0.004). Elevated week 6 VEGF levels were associated with worse OS (HR = 1.034; p = 0.004). Our findings suggest a role for rCBV and rCBF at baseline and Ktrans and VEGF levels during treatment as markers of response. Functional imaging changes can differ substantially between tumor and edema regions, highlighting the variable biologic and vascular state of tumor microenvironment during therapy.
Enhanced fluorescent intensity of magnetic-fluorescent bifunctional PLGA microspheres based on Janus electrospraying for bioapplication
Authors: Li Kun , Li Ping , Jia Zhengtai , Qi Bing , Xu Junwei , Kang Danyue , Liu Meili , Fan Yubo 
Published: November 2018

AbstractMicrospheres with magnetic-fluorescent functions have received attention due to fluorescent tracking and target positioning. To improve the accuracy of optical imaging and the fluorescent tracking of drug release, it is essential to enhance the fluorescent intensity of microparticles. Magnetic-fluorescent bifunctional poly lactic-co-glycolic acid (PLGA) Janus microspheres [PLGA/TbLa3(Bim)12]//[PLGA/Fe3O4] with double chambers were fabricated with the double-needle electrospraying method. The fluorescent drug TbLa3(Bim)12 with dual rare earth ions was encapsulated in one chamber, while Fe3O4 magnetic nanoparticles (Fe3O4 MNPs) were simultaneously encapsulated in another chamber. In comparison, magnetic-fluorescent PLGA composite microspheres PLGA/TbLa3(Bim)12/Fe3O4 were also prepared, which encapsulated fluorescent drugs TbLa3(Bim)12 with dual rare earth (RE) ions and Fe3O4 MNPs in one chamber. The fluorescent intensity at 542 nm of Janus microspheres was about three times higher than that of composite microspheres due to a decrease in contact between fluorescent-labeling RE drug and MNPs. The fluorescent intensities of Janus microspheres with different contents of Fe3O4 MNPs and TbLa3(Bim)12 were investigated. Furthermore, the magnetic properties, thermostability, cell toxicity and hemolytic properties of Janus microspheres were also assayed to conduct a tentative exploration of their bioapplication. The Janus microspheres provide many opportunities for application in biofields such as drug delivery.
High-throughput sequencing for the molecular diagnosis of Usher syndrome reveals 42 novel mutations and consolidates CEP250 as Usher-like disease causative
Authors: Fuster-García Carla , García-García Gema , Jaijo Teresa , Fornés Neus , Ayuso Carmen , Fernández-Burriel Miguel , Sánchez-De la Morena Ana , Aller Elena , Millán José M. 
Published: November 2018

AbstractUsher syndrome is a rare disorder causing retinitis pigmentosa, together with sensorineural hearing loss. Due to the phenotypic and genetic heterogeneity of this disease, the best method to screen the causative mutations is by high-throughput sequencing. In this study, we tested a semiconductor chip based sequencing approach with 77 unrelated patients, as a molecular diagnosis routine. In addition, Multiplex Ligation-dependent Probe Amplification and microarray-based Comparative Genomic Hybridization techniques were applied to detect large rearrangements, and minigene assays were performed to confirm the mRNA processing aberrations caused by splice-site mutations. The designed panel included all the USH causative genes (MYO7A,USH1C,CDH23,PCDH15,USH1G,CIB2,USH2A,ADGRV1,WHRNandCLRN1) as well as four uncertainly associated genes (HARS,PDZD7,CEP250andC2orf71). The outcome showed an overall mutation detection ratio of 82.8% and allowed the identification of 42 novel putatively pathogenic mutations. Furthermore, we detected two novel nonsense mutations inCEP250in a patient with a disease mimicking Usher syndrome that associates visual impairment due to cone-rod dystrophy and progressive hearing loss. Therefore, this approach proved reliable results for the molecular diagnosis of the disease and also allowed the consolidation of theCEP250gene as disease causative for an Usher-like phenotype.