bluuebunny/crossref_metadata_2025_split huggingface dataset:
Birth and Resuscitation of (p)ppGpp Induced Antibiotic Tolerant Persister Cells
Authors: Svenningsen Mikkel Skjoldan , Veress Alexandra , Harms Alexander , Mitarai Namiko , Semsey Szabolcs 
Published: April 2019

AbstractTransient antibiotic treatment typically eradicates most sensitive bacteria except a few survivors called persisters. The second messenger (p)ppGpp plays a key role in persister formation in Escherichia coli populations but the underlying mechanisms have remained elusive. In this study we induced (p)ppGpp synthesis by modulating tRNA charging and then directly observed the stochastic appearance, antibiotic tolerance, and resuscitation of persister cells using live microscopy. Different physiological parameters of persister cells as well as their regularly growing ancestors and sisters were continuously monitored using fluorescent reporters. Our results confirmed previous findings that high (p)ppGpp levels are critical for persister formation, but the phenomenon remained strikingly stochastic without any correlation between (p)ppGpp levels and antibiotic tolerance on the single-cell level. We could not confirm previous notions that persisters exhibit markedly low concentrations of intracellular ATP or were linked to post-transcriptional effects of (p)ppGpp through the activation of small genetic elements known as toxin-antitoxin (TA) modules. Instead, we suggest that persister cell formation under regular conditions is driven by the transcriptional response to increased (p)ppGpp levels.
c-Jun N-terminal kinase (JNK)-dependent internalization and Rab5-dependent endocytic sorting mediate long-distance retrograde neuronal death induced by axonal BDNF-p75 signaling
Authors: Escudero C. A. , Cabeza C. , Moya-Alvarado G. , Maloney M. T. , Flores C. M. , Wu C. , Court F. A. , Mobley W. C. , Bronfman F. C. 
Published: April 2019

AbstractDuring the development of the sympathetic nervous system, signals from tropomyosin-related kinase receptors (Trks) and p75 neurotrophin receptors (p75) compete to regulate survival and connectivity. During this process, nerve growth factor (NGF)- TrkA signaling in axons communicates NGF-mediated trophic responses in signaling endosomes. Whether axonal p75 signaling contributes to neuronal death and how signaling endosomes contribute to p75 signaling has not been established. Using compartmentalized sympathetic neuronal cultures (CSCGs) as a model, we observed that the addition of BDNF to axons increased the transport of p75 and induced death of sympathetic neurons in a dynein-dependent manner. In cell bodies, internalization of p75 required the activity of JNK, a downstream kinase mediating p75 death signaling in neurons. Additionally, the activity of Rab5, the key GTPase regulating early endosomes, was required for p75 death signaling. In axons, JNK and Rab5 were required for retrograde transport and death signaling mediated by axonal BDNF-p75 in CSCGs. JNK was also required for the proper axonal transport of p75-positive endosomes. Thus, our findings provide evidence that the activation of JNK by p75 in cell bodies and axons is required for internalization to a Rab5-positive signaling endosome and the further propagation of p75-dependent neuronal death signals.
Azithromycin resistance levels and mechanisms in Escherichia coli
Authors: Gomes Cláudia , Ruiz-Roldán Lidia , Mateu Judit , Ochoa Theresa J. , Ruiz Joaquim 
Published: April 2019

AbstractDespite azithromycin being used in some countries to treat infections caused by Gram-negative pathogens, no resistance breakpoint forEscherichia coliexists. The aim of this study was to analyse the levels and mechanisms of azithromycin resistance inE. coli. The presence of chromosomal (rplD, rplVand23S rRNA) mutations, 10 macrolide resistance genes (MRGs) and efflux pump overexpression was determined in 343E. coliisolates. Overall, 89 (25.9%) isolates had MICs ≥ 32 mg/L to azithromycin, decreasing to 42 (12.2%) when assayed in the presence of Phe-Arg-β-Napthylamide, with 35 of these 42 possessing at least one MRG. Efflux pumps played a role in azithromycin resistance affecting the Minimal Inhibitory Concentration (MIC) levels of 91.2% isolates whereas chromosomal alterations seem to have a minimal role. At least one MRG was found in 22.7% of the isolates withmph(A) being the most commonly found gene. Themph(A) gene plays the main role in the development of azithromycin resistance and 93% of themph(A)-carrying isolates showed a MIC of 32 mg/L. In the absence of a specific resistance breakpoint our results suggest a MIC of 32 mg/L to be considered in order to detect isolates carrying mechanisms able to confer azithromycin resistance.
Three-dimensional partitioning of resources by congeneric forest predators with recent sympatry
Authors: Jenkins Julianna M. A. , Lesmeister Damon B. , Wiens J. David , Kane Jonathan T. , Kane Van R. , Verschuyl Jake 
Published: April 2019

AbstractCoexistence of ecologically similar species can be maintained by partitioning along one or more niche axes. Three-dimensional structural complexity is central to facilitating resource partitioning between many forest species, but is underrepresented in field-based studies. We examined resource selection by sympatric northern spotted owls (Strix occidentalis caurina), a threatened species under the US Endangered Species Act, and nonnative barred owls (S. varia) in western Oregon, USA to explore the relative importance of canopy heterogeneity, vertical complexity of forest, and abiotic features to resource selection and identify potential differences that may facilitate long-term coexistence. We predicted that within home range selection of understory densities, measured with airborne lidar, would differ between species based on proportional differences in arboreal and terrestrial prey taken by each owl species. We used discrete choice models and telemetry data from 41 spotted owls and 38 barred owls monitored during 2007–2009 and 2012–2015. Our results suggested that while both species used tall canopy areas more often than low canopy areas, spotted owls were more commonly found in areas with lower tree cover, more developed understory, and steeper slopes. This is the first evidence of fine-scale partitioning based on structural forest properties by northern spotted owls and barred owls.
The perceptual neural trace of memorable unseen scenes
Authors: Mohsenzadeh Yalda , Mullin Caitlin , Oliva Aude , Pantazis Dimitrios 
Published: April 2019

AbstractSome scenes are more memorable than others: they cement in minds with consistencies across observers and time scales. While memory mechanisms are traditionally associated with the end stages of perception, recent behavioral studies suggest that the features driving these memorability effects are extracted early on, and in an automatic fashion. This raises the question: is the neural signal of memorability detectable during early perceptual encoding phases of visual processing? Using the high temporal resolution of magnetoencephalography (MEG), during a rapid serial visual presentation (RSVP) task, we traced the neural temporal signature of memorability across the brain. We found an early and prolonged memorability related signal under a challenging ultra-rapid viewing condition, across a network of regions in both dorsal and ventral streams. This enhanced encoding could be the key to successful storage and recognition.
Platelet proteome reveals specific proteins associated with platelet activation and the hypercoagulable state in β-thalassmia/HbE patients
Authors: Chanpeng Puangpaka , Svasti Saovaros , Paiboonsukwong Kittiphong , Smith Duncan R. , Leecharoenkiat Kamonlak 
Published: April 2019

AbstractA hypercoagulable state leading to a high risk of a thrombotic event is one of the most common complications observed in β-thalassemia/HbE disease, particularly in patients who have undergone a splenectomy. However, the hypercoagulable state, as well as the molecular mechanism of this aspect of the pathogenesis of β-thalassemia/HbE, remains poorly understood. To address this issue, fifteen non-splenectomized β-thalassemia/HbE patients, 8 splenectomized β-thalassemia/HbE patients and 20 healthy volunteers were recruited to this study. Platelet activation and hypercoagulable parameters including levels of CD62P and prothrombin fragment 1 + 2 were analyzed by flow cytometry and ELISA, respectively. A proteomic analysis was conducted to compare the platelet proteome between patients and normal subjects, and the results were validated by western blot analysis. The β-thalassemia/HbE patients showed significantly higher levels of CD62P and prothrombin fragment 1 + 2 than normal subjects. The levels of platelet activation and hypercoagulation found in patients were strongly associated with splenectomy status. The platelet proteome analysis revealed 19 differential spots which were identified to be 19 platelet proteins, which included 10 cytoskeleton proteins, thrombin generation related proteins, and antioxidant enzymes. Our findings highlight markers of coagulation activation and molecular pathways known to be associated with the pathogenesis of platelet activation, the hypercoagulable state, and consequently with the thrombosis observed in β-thalassemia/HbE patients.
Cardiac inflammatory CD11b/c cells exert a protective role in hypertrophied cardiomyocyte by promoting TNFR2- and Orai3- dependent signaling
Authors: Keck Mathilde , Flamant Mathilde , Mougenot Nathalie , Favier Sophie , Atassi Fabrice , Barbier Camille , Nadaud Sophie , Lompré Anne-Marie , Hulot Jean-Sébastien , Pavoine Catherine 
Published: April 2019

AbstractEarly adaptive cardiac hypertrophy (EACH) is initially a compensatory process to optimize pump function. We reported the emergence of Orai3 activity during EACH. This study aimed to characterize how inflammation regulates store-independent activation of Orai3-calcium influx and to evaluate the functional role of this influx. Isoproterenol infusion or abdominal aortic banding triggered EACH. TNFα or conditioned medium from cardiac CD11b/c cells activated either in vivo [isolated from rats displaying EACH], or in vitro [isolated from normal rats and activated with lipopolysaccharide], were added to adult cardiomyocytes before measuring calcium entry, cell hypertrophy and cell injury. Using intramyocardial injection of siRNA, Orai3 was in vivo knockdown during EACH to evaluate its protective activity in heart failure. Inflammatory CD11b/c cells trigger a store-independent calcium influx in hypertrophied cardiomyocytes, that is mimicked by TNFα. Pharmacological or molecular (siRNA) approaches demonstrate that this calcium influx, depends on TNFR2, is Orai3-driven, and elicits cardiomyocyte hypertrophy and resistance to oxidative stress. Neutralization of Orai3 inhibits protective GSK3β phosphorylation, impairs EACH and accelerates heart failure. Orai3 exerts a pathophysiological protective impact in EACH promoting hypertrophy and resistance to oxidative stress. We highlight inflammation arising from CD11b/c cells as a potential trigger of TNFR2- and Orai3-dependent signaling pathways.
Water walking as a new mode of free surface skipping
Authors: Hurd Randy C. , Belden Jesse , Bower Allan F. , Holekamp Sean , Jandron Michael A. , Truscott Tadd T. 
Published: April 2019

AbstractDeformable elastomeric spheres are evaluated experimentally as they skip multiple times over a lake surface. Some spheres are embedded with small inertial measurement units to measure the acceleration experienced during water surface impact. A model for multiple impact events shows good agreement between measured acceleration, number of skipping events and distanced traveled. The experiment reveals a new mode of skipping, “water walking”, which is observed for relatively soft spheres impacting at low impact angles. The mode occurs when the sphere gains significant angular velocity over the first several impacts, causing the sphere to maintain a deformed, oblong shape. The behavior is characterized by the sphere moving nearly parallel to the water surface with the major axis tips dipping below the water surface with each rotation while the shorter sides pass just above, giving the impression that the sphere is walking across the water surface.
Functional Evaluation of Two Corneal Endothelial Cell-Based Therapies: Tissue-Engineered Construct and Cell Injection
Authors: Peh Gary S. L. , Ong Hon Shing , Adnan Khadijah , Ang Heng-Pei , Lwin Chan N. , Seah Xin-Yi , Lin Shu-Jun , Mehta Jodhbir S. 
Published: April 2019

AbstractRestoration of vision due to corneal blindness from corneal endothelial dysfunction can be achieved via a corneal transplantation. However, global shortage of donor tissues has driven the development cell-based therapeutics. With the capacity to propagate regulatory compliant human corneal endothelial cells (CEnCs), this study evaluated the functionality of propagated CEnCs delivered via tissue-engineered endothelial keratoplasty (TE-EK) or corneal endothelial cell injection (CE-CI) within a rabbit model of bullous keratopathy. For animals with TE-EK grafts, central corneal thickness (CCT) increased to >1000 μm post-operatively. Gradual thinning with improvements in corneal clarity was observed from week 1. CCT at week 3 was 484.3 ± 73.7 μm. In rabbits with CE-CI, corneal clarity was maintained throughout, and CCT at week 3 was 582.5 ± 171.5 μm. Control corneas remained significantly edematous throughout the study period compared to their respective experimental groups (p < 0.05). Characterization of excised corneas showed a monolayer with heterogeneously shaped CEnCs in both TE-EK and CE-CI groups. Immunohistochemistry demonstrated reactivity to anti-human specific nuclei antibody attributing corneal recovery to the functional human CEnCs. This study showed that regulatory compliant cell-based therapy for corneal endothelial dysfunction can be delivered by both TE-EK and CE-CI, and holds great promise as an alternative to traditional corneal transplantation.
All-passive transformable optical mapping near-eye display
Authors: Cui Wei , Gao Liang 
Published: April 2019

AbstractWe present an all-passive, transformable optical mapping (ATOM) near-eye display based on the “human-centric design” principle. By employing a diffractive optical element, a distorted grating, the ATOM display can project different portions of a two-dimensional display screen to various depths, rendering a real three-dimensional image with correct focus cues. Thanks to its all-passive optical mapping architecture, the ATOM display features a reduced form factor and low power consumption. Moreover, the system can readily switch between a real-three-dimensional and a high-resolution two-dimensional display mode, providing task-tailored viewing experience for a variety of VR/AR applications.
Systematic evaluation of 2′-Fluoro modified chimeric antisense oligonucleotide-mediated exon skipping in vitro
Authors: Chen Suxiang , Le Bao T. , Chakravarthy Madhuri , Kosbar Tamer R. , Veedu Rakesh N. 
Published: April 2019

AbstractAntisense oligonucleotide (AO)-mediated splice modulation has been established as a therapeutic approach for tackling genetic diseases. Recently, Exondys51, a drug that aims to correct splicing defects in the dystrophin gene was approved by the US Food and Drug Administration (FDA) for the treatment of Duchenne muscular dystrophy (DMD). However, Exondys51 has relied on phosphorodiamidate morpholino oligomer (PMO) chemistry which poses challenges in the cost of production and compatibility with conventional oligonucleotide synthesis procedures. One approach to overcome this problem is to construct the AO with alternative nucleic acid chemistries using solid-phase oligonucleotide synthesis via standard phosphoramidite chemistry. 2′-Fluoro (2′-F) is a potent RNA analogue that possesses high RNA binding affinity and resistance to nuclease degradation with good safety profile, and an approved drug Macugen containing 2′-F-modified pyrimidines was approved for the treatment of age-related macular degeneration (AMD). In the present study, we investigated the scope of 2′-F nucleotides to construct mixmer and gapmer exon skipping AOs with either 2′-O-methyl (2′-OMe) or locked nucleic acid (LNA) nucleotides on a phosphorothioate (PS) backbone, and evaluated their efficacy in inducing exon-skipping in mdx mouse myotubes in vitro. Our results showed that all AOs containing 2′-F nucleotides induced efficient exon-23 skipping, with LNA/2′-F chimeras achieving better efficiency than the AOs without LNA modification. In addition, LNA/2′-F chimeric AOs demonstrated higher exonuclease stability and lower cytotoxicity than the 2′-OMe/2′-F chimeras. Overall, our findings certainly expand the scope of constructing 2′-F modified AOs in splice modulation by incorporating 2′-OMe and LNA modifications.
Shape Dynamics of Bouncing Droplets
Authors: Svintradze David V. 
Published: April 2019

AbstractOscillating shape motion of a freely falling and bouncing water droplet has long fascinated and inspired scientists. We propose dynamic non-linear equations for closed, two-dimensional surfaces in gravity and apply it to analyze shape dynamics of freely falling and bouncing drops. The analytic and numerical solutions qualitatively well explain why drops oscillate among prolate/oblate morphology and display a number of features consistent with experiments. In addition, numerical solutions for simplified equations indicate nonlinear effects of nonperiodic/asymmetric motion and the growing amplitude in the surface density oscillations and well agree to previous experimental data.
Comprehensive analysis of Fc-mediated IgM binding to the Plasmodium falciparum erythrocyte membrane protein 1 family in three parasite clones
Authors: Quintana Maria del Pilar , Ecklu-Mensah Gertrude , Tcherniuk Sergey O. , Ditlev Sisse Bolm , Oleinikov Andrew V. , Hviid Lars , Lopez-Perez Mary 
Published: April 2019

AbstractPfEMP1 is a family of adhesive proteins expressed on the surface of Plasmodium falciparum-infected erythrocytes (IEs), where they mediate adhesion of IEs to a range of host receptors. Efficient PfEMP1-dependent IE sequestration often depends on soluble serum proteins, including IgM. Here, we report a comprehensive investigation of which of the about 60 var gene-encoded PfEMP1 variants per parasite genome can bind IgM via the Fc part of the antibody molecule, and which of the constituent domains of those PfEMP1 are involved. We erased the epigenetic memory of var gene expression in three distinct P. falciparum clones, 3D7, HB3, and IT4/FCR3 by promoter titration, and then isolated individual IEs binding IgM from malaria-unexposed individuals by fluorescence-activated single-cell sorting. The var gene transcription profiles of sub-clones measured by real-time qPCR were used to identify potential IgM-binding PfEMP1 variants. Recombinant DBL and CIDR domains corresponding to those variants were tested by ELISA and protein arrays to confirm their IgM-binding capacity. Selected DBL domains were used to raise specific rat anti-sera to select IEs with uniform expression of candidate PfEMP1 proteins. Our data document that IgM-binding PfEMP1 proteins are common in each of the three clones studied, and that the binding epitopes are mainly found in DBLε and DBLζ domains near the C-terminus.
Visual short-term memory for coherent motion in video game players: evidence from a memory-masking paradigm
Authors: Pavan Andrea , Hobaek Martine , Blurton Steven P. , Contillo Adriano , Ghin Filippo , Greenlee Mark W. 
Published: April 2019

AbstractIn this study, we investigated visual short-term memory for coherent motion in action video game players (AVGPs), non-action video game players (NAVGPs), and non-gamers (control group: CONs). Participants performed a visual memory-masking paradigm previously used with macaque monkeys and humans. In particular, we tested whether video game players form a more robust visual short-term memory trace for coherent moving stimuli during the encoding phase, and whether such memory traces are less affected by an intervening masking stimulus presented 0.2 s after the offset of the to-be-remembered sample. The results showed that task performance of all groups was affected by the masking stimulus, but video game players were affected to a lesser extent than controls. Modelling of performance values and reaction times revealed that video game players have a lower guessing rate than CONs, and higher drift rates than CONs, indicative of more efficient perceptual decisions. These results suggest that video game players exhibit a more robust VSTM trace for moving objects and this trace is less prone to external interference.
18F-Flortaucipir in TDP-43 associated frontotemporal dementia
Authors: Smith R. , Santillo A. F. , Waldö M. Landqvist , Strandberg O. , Berron D. , Vestberg S. , van Westen D. , van Swieten J. , Honer M. , Hansson O. 
Published: April 2019

AbstractRetention of 18F-Flortaucipir is reportedly increased in the semantic variant of primary progressive aphasia (svPPA), which is dominated by TDP-43 pathology. However, it is unclear if 18F-Flortaucipir is also increased in other TDP-43 diseases, such as bvFTD caused by a C9orf72 gene mutation. We therefore recruited six C9orf72 expansion carriers, six svPPA patients, and 54 healthy controls. All underwent 18F-Flortaucipir PET and MRI scanning. Data from 39 Alzheimer’s Disease patients were used for comparison. PET tracer retention was assessed both at the region-of-interest (ROI) and at the voxel-level. Further, autoradiography using 3H-Flortaucipir was performed. SvPPA patients exhibited higher 18F-Flortaucipir retention in the lateral temporal cortex bilaterally according to ROI- and voxel-based analyses. In C9orf72 patients, 18F-Flortaucipir binding was slightly increased in the inferior frontal lobes in the ROI based analysis, but these results were not replicated in the voxel-based analysis. Autoradiography did not show specific binding in svPPA cases or in C9orf72-mutation carriers. In conclusion, temporal lobe 18F-Flortaucipir retention was observed in some cases of svPPA, but the uptake was of a lower magnitude compared to AD dementia. C9orf72-mutation carriers exhibited none or limited 18F-Flortaucipir retention, indicating that 18F-Flortaucipir binding in TDP-43 proteinopathies is not a general TDP-43 related phenomenon.
Detection of T lymphocyte subsets and related functional molecules in follicular fluid of patients with polycystic ovary syndrome
Authors: Li Zitao , Peng Anping , Feng Yuanfa , Zhang Xiaona , Liu Fenghua , Chen Chuangqi , Ye Xin , Qu Jiale , Jin Chenxi , Wang Mei , Qiu Huaina , Qi Yanwei , Huang Jun , Yang Quan 
Published: April 2019

AbstractImmune responses play an important role in the pathogenesis of polycystic ovary syndrome (PCOS). However, the characteristics of T lymphocyte subsets in PCOS remain insufficiently understood. In this study, lymphocytes of follicular fluid (FF) were obtained from oocyte retrieval before in-vitro fertilization (IVF) in infertile women with or without PCOS. The levels of cluster of differentiation 25 (CD25), CD69, programmed death 1 (PD-1), interferon-γ (IFN-γ), interleukin 17A (IL-17A) and IL-10 in T lymphocytes were determined by flow cytometry. Our results showed that the percentage of FF CD8+ T cells was significantly decreased in infertile patients with PCOS (P < 0.05). Furthermore, the levels of CD69 and IFN-γ were significantly decreased and the level of PD-1 was increased in both CD4+ and CD8+ T cells from infertile patients with PCOS (P < 0.05). Moreover, the expression of PD-1 on CD4+ or CD8+ T cells was positively correlated with the estradiol (E2) levels in the serum and reversely correlated with the expression of IFN-γ in CD4+ or CD8+ T cells in infertile patients with PCOS. These results suggested that T cell dysfunction may be involved in the pathogenesis of PCOS.