bluuebunny/crossref_metadata_2025_split huggingface dataset:
Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation
Authors: Cotero Victoria , Fan Ying , Tsaava Tea , Kressel Adam M. , Hancu Ileana , Fitzgerald Paul , Wallace Kirk , Kaanumalle Sireesha , Graf John , Rigby Wayne , Kao Tzu-Jen , Roberts Jeanette , Bhushan Chitresh , Joel Suresh , Coleman Thomas R. , Zanos Stavros , Tracey Kevin J. , Ashe Jeffrey , Chavan Sangeeta S. , Puleo Christopher 
Published: March 2019

AbstractTools for noninvasively modulating neural signaling in peripheral organs will advance the study of nerves and their effect on homeostasis and disease. Herein, we demonstrate a noninvasive method to modulate specific signaling pathways within organs using ultrasound (U/S). U/S is first applied to spleen to modulate the cholinergic anti-inflammatory pathway (CAP), and US stimulation is shown to reduce cytokine response to endotoxin to the same levels as implant-based vagus nerve stimulation (VNS). Next, hepatic U/S stimulation is shown to modulate pathways that regulate blood glucose and is as effective as VNS in suppressing the hyperglycemic effect of endotoxin exposure. This response to hepatic U/S is only found when targeting specific sub-organ locations known to contain glucose sensory neurons, and both molecular (i.e. neurotransmitter concentration and cFOS expression) and neuroimaging results indicate US induced signaling to metabolism-related hypothalamic sub-nuclei. These data demonstrate that U/S stimulation within organs provides a new method for site-selective neuromodulation to regulate specific physiological functions.
Label-free detection of conformational changes in switchable DNA nanostructures with microwave microfluidics
Authors: Stelson Angela C. , Liu Minghui , Little Charles A. E. , Long Christian J. , Orloff Nathan D. , Stephanopoulos Nicholas , Booth James C. 
Published: March 2019

AbstractDetection of conformational changes in biomolecular assemblies provides critical information into biological and self-assembly processes. State-of-the-art in situ biomolecular conformation detection techniques rely on fluorescent labels or protein-specific binding agents to signal conformational changes. Here, we present an on-chip, label-free technique to detect conformational changes in a DNA nanomechanical tweezer structure with microwave microfluidics. We measure the electromagnetic properties of suspended DNA tweezer solutions from 50 kHz to 110 GHz and directly detect two distinct conformations of the structures. We develop a physical model to describe the electrical properties of the tweezers, and correlate model parameters to conformational changes. The strongest indicator for conformational changes in DNA tweezers are the ionic conductivity, while shifts in the magnitude of the cooperative water relaxation indicate the addition of fuel strands used to open the tweezer. Microwave microfluidic detection of conformational changes is a generalizable, non-destructive technique, making it attractive for high-throughput measurements.
Quantifying protein dynamics and stability in a living organism
Authors: Feng Ruopei , Gruebele Martin , Davis Caitlin M. 
Published: March 2019

AbstractAs an integral part of modern cell biology, fluorescence microscopy enables quantification of the stability and dynamics of fluorescence-labeled biomolecules inside cultured cells. However, obtaining time-resolved data from individual cells within a live vertebrate organism remains challenging. Here we demonstrate a customized pipeline that integrates meganuclease-mediated mosaic transformation with fluorescence-detected temperature-jump microscopy to probe dynamics and stability of endogenously expressed proteins in different tissues of living multicellular organisms.
Dynamic marine viral infections and major contribution to photosynthetic processes shown by spatiotemporal picoplankton metatranscriptomes
Authors: Sieradzki Ella T. , Ignacio-Espinoza J. Cesar , Needham David M. , Fichot Erin B. , Fuhrman Jed A. 
Published: March 2019

AbstractViruses provide top-down control on microbial communities, yet their direct study in natural environments was hindered by culture limitations. The advance of bioinformatics enables cultivation-independent study of viruses. Many studies assemble new viral genomes and study viral diversity using marker genes from free viruses. Here we use cellular metatranscriptomics to study active community-wide viral infections. Recruitment to viral contigs allows tracking infection dynamics over time and space. Our assemblies represent viral populations, but appear biased towards low diversity viral taxa. Tracking relatives of published T4-like cyanophages and pelagiphages reveals high genomic continuity. We determine potential hosts by matching dynamics of infection with abundance of particular microbial taxa. Finally, we quantify the relative contribution of cyanobacteria and viruses to photosystem-II psbA (reaction center) expression in our study sites. We show sometimes >50% of all cyanobacterial+viral psbA expression is of viral origin, highlighting the contribution of viruses to photosynthesis and oxygen production.
Intramolecular electron-induced proton transfer and its correlation with excited-state intramolecular proton transfer
Authors: Wang Wei , Marshall Mary , Collins Evan , Marquez Sara , Mu Chaonan , Bowen Kit H. , Zhang Xinxing 
Published: March 2019

AbstractElectron-induced proton transfer depicts the proton motion coupled with the attachment of a low-energy electron to a molecule, which helps to understand copious fundamental chemical processes. Intramolecular electron-induced proton transfer is a similar process that occurs within a single molecule. To date, there is only one known intramolecular example, to the best of our knowledge. By studying the 10-hydroxybenzo[h]quinoline and 8-hydroxyquinoline molecules using anion photoelectron spectroscopy and density functional theory, and by theoretical screening of six other molecules, here we show the intramolecular electron-induced proton transfer capability of a long list of molecules that meanwhile have the excited-state intramolecular proton transfer property. Careful examination of the intrinsic electronic signatures of these molecules reveals that these two distinct processes should occur to the same category of molecules. Intramolecular electron-induced proton transfer could have potential applications such as molecular devices that are responsive to electrons or current.
Photo-induced ultrafast active ion transport through graphene oxide membranes
Authors: Yang Jinlei , Hu Xiaoyu , Kong Xian , Jia Pan , Ji Danyan , Quan Di , Wang Lili , Wen Qi , Lu Diannan , Wu Jianzhong , Jiang Lei , Guo Wei 
Published: March 2019

AbstractLayered graphene oxide membranes (GOM) with densely packed sub-nanometer-wide lamellar channels show exceptional ionic and molecular transport properties. Mass and charge transport in existing materials follows their concentration gradient, whereas attaining anti-gradient transport, also called active transport, remains a great challenge. Here, we demonstrate a coupled photon-electron-ion transport phenomenon through the GOM. Upon asymmetric light illumination, cations are able to move thermodynamically uphill over a broad range of concentrations, at rates much faster than that via simple diffusion. We propose, as a plausible mechanism, that light irradiation reduces the local electric potential on the GOM following a carrier diffusion mechanism. When the illumination is applied to an off-center position, an electric potential difference is built that can drive the transport of ionic species. We further develop photonic ion switches, photonic ion diodes, and photonic ion transistors as the fundamental elements for active ion sieving and artificial photosynthesis on synthetic nanofluidic circuits.
CryoEM structure of adenovirus type 3 fibre with desmoglein 2 shows an unusual mode of receptor engagement
Authors: Vassal-Stermann Emilie , Effantin Gregory , Zubieta Chloe , Burmeister Wim , Iseni Frédéric , Wang Hongjie , Lieber André , Schoehn Guy , Fender Pascal 
Published: March 2019

AbstractAttachment of human adenovirus (HAd) to the host cell is a critical step of infection. Initial attachment occurs via the adenoviral fibre knob protein and a cellular receptor. Here we report the cryo-electron microscopy (cryo-EM) structure of a <100 kDa non-symmetrical complex comprising the trimeric HAd type 3 fibre knob (HAd3K) and human desmoglein 2 (DSG2). The structure reveals a unique stoichiometry of 1:1 and 2:1 (DSG2: knob trimer) not previously observed for other HAd-receptor complexes. We demonstrate that mutating Asp261 in the fibre knob is sufficient to totally abolish receptor binding. These data shed new light on adenovirus infection strategies and provide insights for adenoviral vector development and structure-based design.
Semaphorin 3A Inhibits Nerve Regeneration During Early Stage after Inferior Alveolar Nerve Transection
Authors: Kanemaru Hiroko , Yamada Yurie , Ohazama Atsushi , Maeda Takeyasu , Seo Kenji 
Published: March 2019

AbstractNeuroma formation at sites of injury can impair peripheral nerve regeneration. Although the involvement of semaphorin 3A has been suggested in neuroma formation, this detailed process after injury is not fully understood. This study was therefore undertaken to examine the effects of semaphorin 3A on peripheral nerve regeneration during the early stage after injury. Immunohistochemistry for semaphorin 3A and PGP9.5, a general neuronal marker, was carried out for clarify chronological changes in their expressions after transection of the mouse inferior alveolar nerve thorough postoperative days 1 to 7. At postoperative day 1, the proximal stump of the damaged IAN exhibited semaphorin 3A, while the distal stump lacked any immunoreactivity. From this day on, its expression lessened, ultimately disappearing completely in all regions of the transected inferior alveolar nerve. A local administration of an antibody to semaphorin 3A into the nerve transection site at postoperative day 3 inhibited axon sprouting at the injury site. This antibody injection increased the number of trigeminal ganglion neurons labeled with DiI (paired t-test, p < 0.05). Immunoreactivity of the semaphorin 3A receptor, neuropilin-1, was also detected at the proximal stump at postoperative day 1. These results suggest that nerve injury initiates semaphorin 3A production in ganglion neurons, which is then delivered through the nerve fibers to the proximal end, thereby contributes to the inhibition of axonal sprouting from the proximal region of injured nerves in the distal direction. To our knowledge, this is the first report to reveal the involvement of Sema3A in the nerve regeneration process at its early stage.
Talbot-Lau x-ray phase-contrast setup for fast scanning of large samples
Authors: Seifert Maria , Ludwig Veronika , Kaeppler Sebastian , Horn Florian , Meyer Pascal , Pelzer Georg , Rieger Jens , Sand Daniel , Michel Thilo , Mohr Jürgen , Riess Christian , Anton Gisela 
Published: March 2019

AbstractCompared to conventional attenuation x-ray radiographic imaging, the x-ray Talbot-Lau technique provides further information about the scattering and the refractive properties of the object in the beam path. Hence, this additional information should improve the diagnostic process concerning medical applications and non-destructive testing. Nevertheless, until now, due to grating fabrication process, Talbot-Lau imaging suffers from small grating sizes (70 mm diameter). This leads to long acquisition times for imaging large objects. Stitching the gratings is one solution. Another one consists of scanning Talbot-Lau setups. In this publication, we present a compact and very fast scanning setup which enables imaging of large samples. With this setup a maximal scanning velocity of 71.7 mm/s is possible. A resolution of 4.1 lines/mm can be achieved. No complex alignment procedures are necessary while the field of view comprises 17.5 × 150 cm2. An improved reconstruction algorithm concerning the scanning approach, which increases robustness with respect to mechanical instabilities, has been developed and is presented. The resolution of the setup in dependence of the scanning velocity is evaluated. The setup imaging qualities are demonstrated using a human knee ex-vivo as an example for a high absorbing human sample.
Strong correlation of novel sleep electroencephalography coherence markers with diagnosis and severity of posttraumatic stress disorder
Authors: Modarres Mo H. , Opel Ryan A. , Weymann Kristianna B. , Lim Miranda M. 
Published: March 2019

AbstractObjective biomarkers of the presence and severity of posttraumatic stress disorder (PTSD) are elusive, yet badly needed. Electroencephalographic (EEG) coherence represents a promising approach to identifying and understanding brain biomarker activity in PTSD. Overnight polysomnography data containing EEG across sleep and wake states was collected in n = 76 Veterans with and without PTSD from a single site under IRB approval. Brain coherence markers (BCM) were calculated from EEG signals using a novel approach to produce one index for PTSD diagnosis (PTSDdx), and another index for PTSD severity (PTSDsev). PTSDdx showed strong sensitivity to the presence of PTSD in the awake state, during non-rapid eye movement (NREM) stage N2 sleep, and in a hybrid BCM incorporating both awake and NREM sleep states. PTSDsev showed a strong correlation with PTSD symptom severity (using the PTSD Checklist 5, or PCL5 survey) in the awake state, during N2 sleep, and in a hybrid BCM incorporating both awake and NREM sleep states. Thus, sleep EEG-based brain coherence markers can be utilized as an objective means for determining the presence and severity of PTSD. This portable, inexpensive, and non-invasive tool holds promise for better understanding the physiological mechanisms underlying PTSD and for tracking objective responses to treatment.
Predicting protein-peptide interaction sites using distant protein complexes as structural templates
Authors: Johansson-Åkhe Isak , Mirabello Claudio , Wallner Björn 
Published: March 2019

AbstractProtein-peptide interactions play an important role in major cellular processes, and are associated with several human diseases. To understand and potentially regulate these cellular function and diseases it is important to know the molecular details of the interactions. However, because of peptide flexibility and the transient nature of protein-peptide interactions, peptides are difficult to study experimentally. Thus, computational methods for predicting structural information about protein-peptide interactions are needed. Here we present InterPep, a pipeline for predicting protein-peptide interaction sites. It is a novel pipeline that, given a protein structure and a peptide sequence, utilizes structural template matches, sequence information, random forest machine learning, and hierarchical clustering to predict what region of the protein structure the peptide is most likely to bind. When tested on its ability to predict binding sites, InterPep successfully pinpointed 255 of 502 (50.7%) binding sites in experimentally determined structures at rank 1 and 348 of 502 (69.3%) among the top five predictions using only structures with no significant sequence similarity as templates. InterPep is a powerful tool for identifying peptide-binding sites; with a precision of 80% at a recall of 20% it should be an excellent starting point for docking protocols or experiments investigating peptide interactions. The source code for InterPred is available at http://wallnerlab.org/InterPep/.
Increased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the Avy obesity-associated gene
Authors: Yong Jing , Tian Jide , Dang Hoa , Wu Ting-Ting , Atkinson Mark A. , Sun Ren , Kaufman Daniel L. 
Published: March 2019

AbstractThere has been considerable debate as to whether obesity can act as an accelerator of type 1 diabetes (T1D). We assessed this possibility using transgenic mice (MIP-TF mice) whose ß-cells express enhanced green fluorescent protein (EGFP). Infecting these mice with EGFP-expressing murine herpes virus-68 (MHV68-EGFP) caused occasional transient elevation in their blood glucose, peri-insulitis, and Th1 responses to EGFP which did not spread to other ß-cell antigens. We hypothesized that obesity-related systemic inflammation and ß-cell stress could exacerbate the MHV68-EGFP-induced ß-cell autoreactivity. We crossed MIP-TF mice with Avymice which develop obesity and provide models of metabolic disease alongside early stage T2D. Unlike their MIP-TF littermates, MHV68-EGFP–infected Avy/MIP-TF mice developed moderate intra-insulitis and transient hyperglycemia. MHV68-EGFP infection induced a more pronounced intra-insulitis in older, more obese, Avy/MIP-TF mice. Moreover, in MHV68-EGFP-infected Avy/MIP-TF mice, Th1 reactivity spread from EGFP to other ß-cell antigens. Thus, the spreading of autoreactivity among ß-cell antigens corresponded with the transition from peri-insulitis to intra-insulitis and occurred in obese Avy/MIP-TF mice but not lean MIP-TF mice. These observations are consistent with the notion that obesity-associated systemic inflammation and ß-cell stress lowers the threshold necessary for T cell autoreactivity to spread from EGFP to other ß-cell autoantigens.
Salvage Carbon-Ion Radiation Therapy For Locoregionally Recurrent Head and Neck Malignancies
Authors: Gao Jing , Hu Jiyi , Guan Xiyin , Yang Jing , Hu Weixu , Kong Lin , Lu Jiade J. 
Published: March 2019

AbstractTo investigate the safety and efficacy of salvage carbon-ion radiation therapy (CIRT) in patients with locoregionally recurrent head and neck malignancies. One hundred and forty-one patients with locally recurrent head and neck malignancies previously treated with radiotherapy were salvaged using intensity-modulated carbon-ion radiation therapy (CIRT). The median dose was 60 Gray-Equivalent (GyE) (range 50–69 GyE, 2.0~3.5 GyE/daily fraction). All patients completed planned CIRT except for one. With a median follow-up time of 14.7 (range 1.6–36.4) months, the 1-year overall survival rate was 95.9%. Local, regional, and distant progression free survival rates were 84.9% and 97.7%, and 96%, respectively. Grade 3 or higher acute and late toxicities were observed in 7.1% of the patients. Ten patients developed mucosal necrosis and 4 of these patients deceased. Due to its physical and biological characteristics, CIRT appeared to be an acceptable treatment option for patients with locoregionally recurrent head and neck malignancies after previous radiotherapy. Treatment-induced adverse effects and early response to CIRT were both favorable. Longer follow-up is needed to evaluate the long-term outcome in terms of disease control, survival, as well as potential late effects.
Manipulation of cell migration by laserporation-induced local wounding
Authors: Pervin Mst. Shaela , Yumura Shigehiko 
Published: March 2019

AbstractLiving organisms employ various mechanisms to escape harm. At the cellular level, mobile cells employ movement to avoid harmful chemicals or repellents. The present study is the first to report that cells move away from the site of injury in response to local wounding. When a migrating Dictyostelium cell was locally wounded at its anterior region by laserporation, the cell retracted its anterior pseudopods, extended a new pseudopod at the posterior region, and migrated in the opposite direction with increasing velocity. When wounded in the posterior region, the cell did not change its polarity and moved away from the site of wounding. Since the cells repair wounds within a short period, we successfully manipulated cell migration by applying multiple wounds. Herein, we discussed the signals that contributed to the wound-induced escape behavior of Dictyostelium cells. Our findings provide important insights into the mechanisms by which cells establish their polarity.
Developing attentional control in naturalistic dynamic road crossing situations
Authors: Nicholls Victoria I. , Jean-Charles Geraldine , Lao Junpeng , de Lissa Peter , Caldara Roberto , Miellet Sebastien 
Published: March 2019

AbstractIn the last 20 years, there has been increasing interest in studying visual attentional processes under more natural conditions. In the present study, we propose to determine the critical age at which children show similar to adult performance and attentional control in a visually guided task; in a naturalistic dynamic and socially relevant context: road crossing. We monitored visual exploration and crossing decisions in adults and children aged between 5 and 15 while they watched road traffic videos containing a range of traffic densities with or without pedestrians. 5–10 year old (y/o) children showed less systematic gaze patterns. More specifically, adults and 11–15 y/o children look mainly at the vehicles’ appearing point, which is an optimal location to sample diagnostic information for the task. In contrast, 5–10 y/os look more at socially relevant stimuli and attend to moving vehicles further down the trajectory when the traffic density is high. Critically, 5-10 y/o children also make an increased number of crossing decisions compared to 11–15 y/os and adults. Our findings reveal a critical shift around 10 y/o in attentional control and crossing decisions in a road crossing task.
Small vessel disease and intracoronary plaque composition: a single centre cross-sectional observational study
Authors: Wightman A. , Barlis P. , MacBain M. , Hodgson L. , Cheng L. , Gocuk S. , Hayat U. , Chow D. , Tacey M. , Hutchinson A. , Colville D. , Lamoureux E. , Savige J. 
Published: March 2019

AbstractCardiac events are commonly triggered by rupture of intracoronary plaque. Many studies have suggested that retinal small vessel abnormalities predict cardiac events. The present study examined retinal microvascular abnormalities associated with intracoronary plaque. This was a single centre cross-sectional observational study of consecutive subjects who underwent coronary angiography and intracoronary optical coherence tomography (OCT) of occlusive coronary artery disease. Subjects’ retinal images were deidentified and graded for microvascular retinopathy (Wong and Mitchell classification), and vessel calibre using a semiautomated method based on Knudtson’s modification of the Parr Hubbard formula. Control subjects had no significant plaque on angiography. Analysis used the Fisher’s exact test or student t-test. Thirty-two subjects with intracoronary plaque including 22 males (79%) had a mean age of 62.6 ± 9.4 years. Twenty-four (86%) had hypertension, 10 (36%) had diabetes, and 21 (75%) were current or former smokers. Their average mean arterial pressure was 90.5 ± 5.8 mm Hg, and mean eGFR was 74 ± 15/min/1.73 m2. On angiography, 23 (82%) had a left anterior descending artery (LAD) stenosis, their mean diseased vessel score was 1.86 ± 1.21, and mean total stent number was 1.04 ± 1.00. Plaque type was mainly (>50%) fibrous (n = 7), lipid (n = 7), calcific (n = 10), or mixed (n = 4). Control subjects had a lower mean diastolic BP (p = 0.01), were less likely to have an LAD stenosis (p < 0.001), a lower mean diseased vessel score (p < 0.001) and fewer stents (p = 0.02). Subjects with plaque were more likely to have a moderate microvascular retinopathy than those with none (p = 0.004). Moderate retinopathy was more common with lipid (p = 0.05) or calcific (p = 0.003) plaque. Individuals with calcific plaque had a larger arteriole calibre (158.4 ± 15.2 µm) than those with no plaque (143.8 ± 10.6 µm, p = 0.02), but calibre was not related to diabetes or smoking. Calibre did not correlate with plaque length, thickness or arc angle. Thus, subjects with intracoronary artery plaque are more likely to have a moderate microvascular retinopathy. Those with calcific plaque have larger retinal arterioles which is consistent with our previous finding of larger vessel calibre in triple coronary artery disease. Retinal microvascular imaging warrants further evaluation in identifying severe coronary artery disease.