bluuebunny/crossref_metadata_2025 huggingface dataset:
Greenland records of aerosol source and atmospheric lifetime changes from the Eemian to the Holocene
Authors: Schüpbach S. , Fischer H. , Bigler M. , Erhardt T. , Gfeller G. , Leuenberger D. , Mini O. , Mulvaney R. , Abram N. J. , Fleet L. , Frey M. M. , Thomas E. , Svensson A. , Dahl-Jensen D. , Kettner E. , Kjaer H. , Seierstad I. , Steffensen J. P. , Rasmussen S. O. , Vallelonga P. , Winstrup M. , Wegner A. , Twarloh B. , Wolff K. , Schmidt K. , Goto-Azuma K. , Kuramoto T. , Hirabayashi M. , Uetake J. , Zheng J. , Bourgeois J. , Fisher D. , Zhiheng D. , Xiao C. , Legrand M. , Spolaor A. , Gabrieli J. , Barbante C. , Kang J.-H. , Hur S. D. , Hong S. B. , Hwang H. J. , Hong S. , Hansson M. , Iizuka Y. , Oyabu I. , Muscheler R. , Adolphi F. , Maselli O. , McConnell J. , Wolff E. W.
Published: April 2018

The Northern Hemisphere experienced dramatic changes during the last glacial, featuring vast ice sheets and abrupt climate events, while high northern latitudes during the last interglacial (Eemian) were warmer than today. Here we use high-resolution aerosol records from the Greenland NEEM ice core to reconstruct the environmental alterations in aerosol source regions accompanying these changes. Separating source and transport effects, we find strongly reduced terrestrial biogenic emissions during glacial times reflecting net loss of vegetated area in North America. Rapid climate changes during the glacial have little effect on terrestrial biogenic aerosol emissions. A strong increase in terrestrial dust emissions during the coldest intervals indicates higher aridity and dust storm activity in East Asian deserts. Glacial sea salt aerosol emissions in the North Atlantic region increase only moderately (50%), likely due to sea ice expansion. Lower aerosol concentrations in Eemian ice compared to the Holocene are mainly due to shortened atmospheric residence time, while emissions changed little.
Incorporation of bridged nucleic acids into CRISPR RNAs improves Cas9 endonuclease specificity
Authors: Cromwell Christopher R. , Sung Keewon , Park Jinho , Krysler Amanda R. , Jovel Juan , Kim Seong Keun , Hubbard Basil P.
Published: April 2018

Off-target DNA cleavage is a paramount concern when applying CRISPR-Cas9 gene-editing technology to functional genetics and human therapeutic applications. Here, we show that incorporation of next-generation bridged nucleic acids (2′,4′-BNANC[N-Me]) as well as locked nucleic acids (LNA) at specific locations in CRISPR-RNAs (crRNAs) broadly reduces off-target DNA cleavage by Cas9 in vitro and in cells by several orders of magnitude. Using single-molecule FRET experiments we show that BNANC incorporation slows Cas9 kinetics and improves specificity by inducing a highly dynamic crRNA–DNA duplex for off-target sequences, which shortens dwell time in the cleavage-competent, “zipped” conformation. In addition to describing a robust technique for improving the precision of CRISPR/Cas9-based gene editing, this study illuminates an application of synthetic nucleic acids.
Phosphatase activity tunes two-component system sensor detection threshold
Authors: Landry Brian P. , Palanki Rohan , Dyulgyarov Nikola , Hartsough Lucas A. , Tabor Jeffrey J.
Published: April 2018

Two-component systems (TCSs) are the largest family of multi-step signal transduction pathways in biology, and a major source of sensors for biotechnology. However, the input concentrations to which biosensors respond are often mismatched with application requirements. Here, we utilize a mathematical model to show that TCS detection thresholds increase with the phosphatase activity of the sensor histidine kinase. We experimentally validate this result in engineered Bacillus subtilis nitrate and E. coli aspartate TCS sensors by tuning their detection threshold up to two orders of magnitude. We go on to apply our TCS tuning method to recently described tetrathionate and thiosulfate sensors by mutating a widely conserved residue previously shown to impact phosphatase activity. Finally, we apply TCS tuning to engineer B. subtilis to sense and report a wide range of fertilizer concentrations in soil. This work will enable the engineering of tailor-made biosensors for diverse synthetic biology applications.
HATRIC-based identification of receptors for orphan ligands
Authors: Sobotzki Nadine , Schafroth Michael A. , Rudnicka Alina , Koetemann Anika , Marty Florian , Goetze Sandra , Yamauchi Yohei , Carreira Erick M. , Wollscheid Bernd
Published: April 2018

Cellular responses depend on the interactions of extracellular ligands, such as nutrients, growth factors, or drugs, with specific cell-surface receptors. The sensitivity of these interactions to non-physiological conditions, however, makes them challenging to study using in vitro assays. Here we present HATRIC-based ligand receptor capture (HATRIC-LRC), a chemoproteomic technology that successfully identifies target receptors for orphan ligands on living cells ranging from small molecules to intact viruses. HATRIC-LRC combines a click chemistry-based, protein-centric workflow with a water-soluble catalyst to capture ligand-receptor interactions at physiological pH from as few as 1 million cells. We show HATRIC-LRC utility for general antibody target validation within the native nanoscale organization of the surfaceome, as well as receptor identification for a small molecule ligand. HATRIC-LRC further enables the identification of complex extracellular interactomes, such as the host receptor panel for influenza A virus (IAV), the causative agent of the common flu.
Horizontal antimicrobial resistance transfer drives epidemics of multiple Shigella species
Authors: Baker Kate S. , Dallman Timothy J. , Field Nigel , Childs Tristan , Mitchell Holly , Day Martin , Weill François-Xavier , Lefèvre Sophie , Tourdjman Mathieu , Hughes Gwenda , Jenkins Claire , Thomson Nicholas
Published: April 2018

Horizontal gene transfer has played a role in developing the global public health crisis of antimicrobial resistance (AMR). However, the dynamics of AMR transfer through bacterial populations and its direct impact on human disease is poorly elucidated. Here, we study parallel epidemic emergences of multiple Shigella species, a priority AMR organism, in men who have sex with men to gain insight into AMR emergence and spread. Using genomic epidemiology, we show that repeated horizontal transfer of a single AMR plasmid among Shigella enhanced existing and facilitated new epidemics. These epidemic patterns contrasted with slighter, slower increases in disease caused by organisms with vertically inherited (chromosomally encoded) AMR. This demonstrates that horizontal transfer of AMR directly affects epidemiological outcomes of globally important AMR pathogens and highlights the need for integration of genomic analyses into all areas of AMR research, surveillance and management.
Cell-free prediction of protein expression costs for growing cells
Authors: Borkowski Olivier , Bricio Carlos , Murgiano Michela , Rothschild-Mancinelli Brooke , Stan Guy-Bart , Ellis Tom
Published: April 2018

Translating heterologous proteins places significant burden on host cells, consuming expression resources leading to slower cell growth and productivity. Yet predicting the cost of protein production for any given gene is a major challenge, as multiple processes and factors combine to determine translation efficiency. To enable prediction of the cost of gene expression in bacteria, we describe here a standard cell-free lysate assay that provides a relative measure of resource consumption when a protein coding sequence is expressed. These lysate measurements can then be used with a computational model of translation to predict the in vivo burden placed on growing E. coli cells for a variety of proteins of different functions and lengths. Using this approach, we can predict the burden of expressing multigene operons of different designs and differentiate between the fraction of burden related to gene expression compared to action of a metabolic pathway.
Microfabricated electrodes unravel the role of interfaces in multicomponent copper-based CO2 reduction catalysts
Authors: Larrazábal Gastón O. , Shinagawa Tatsuya , Martín Antonio J. , Pérez-Ramírez Javier
Published: April 2018

The emergence of synergistic effects in multicomponent catalysts can result in breakthrough advances in the electrochemical reduction of carbon dioxide. Copper-indium catalysts show high performance toward carbon monoxide production but also extensive structural and compositional changes under operation. The origin of the synergistic effect and the nature of the active phase are not well understood, thus hindering optimization efforts. Here we develop a platform that sheds light into these aspects, based on microfabricated model electrodes that are evaluated under conventional experimental conditions. The relationship among the electrode performance, geometry and composition associates the high carbon monoxide evolution activity of copper-indium catalysts to indium-poor bimetallic phases, which are formed upon exposure to reaction conditions in the vicinity of the interfaces between copper oxide and an indium source. The exploratory extension of this approach to the copper-tin system demonstrates its versatility and potential for the study of complex multicomponent electrocatalysts.
Micro-CT X-ray imaging exposes structured diffusion barriers within biofilms
Authors: Keren-Paz Alona , Brumfeld Vlad , Oppenheimer-Shaanan Yaara , Kolodkin-Gal Ilana
Published: April 2018

In nature, bacteria predominantly exist as highly structured biofilms, which are held together by extracellular polymeric substance and protect their residents from environmental insults, such as antibiotics. The mechanisms supporting this phenotypic resistance are poorly understood. Recently, we identified a new mechanism maintaining biofilms - an active production of calcite minerals. In this work, a high-resolution and robust µCT technique is used to study the mineralized areas within intact bacterial biofilms. µCT is a vital tool for visualizing bacterial communities that can provide insights into the relationship between bacterial biofilm structure and function. Our results imply that dense and structured calcium carbonate lamina forms a diffusion barrier sheltering the inner cell mass of the biofilm colony. Therefore, µCT can be employed in clinical settings to predict the permeability of the biofilms. It is demonstrated that chemical interference with urease, a key enzyme in biomineralization, inhibits the assembly of complex bacterial structures, prevents the formation of mineral diffusion barriers and increases biofilm permeability. Therefore, biomineralization enzymes emerge as novel therapeutic targets for highly resistant infections.
Caregiver burden and caregiver appraisal of psychiatric symptoms are not modulated by subthalamic deep brain stimulation for Parkinson’s disease
Authors: Mosley Philip E. , Breakspear Michael , Coyne Terry , Silburn Peter , Smith David
Published: April 2018

Subthalamic deep brain stimulation is an advanced therapy that typically improves quality of life for persons with Parkinson’s disease (PD). However, the effect on caregiver burden is unclear. We recruited 64 persons with PD and their caregivers from a movement disorders clinic during the assessment of eligibility for subthalamic DBS. We used clinician-, patient- and caregiver-rated instruments to follow the patient–caregiver dyad from pre- to postoperative status, sampling repeatedly in the postoperative period to ascertain fluctuations in phenotypic variables. We employed multivariate models to identify key drivers of burden. We clustered caregiver-rated variables into ‘high’ and ‘low’ symptom groups and examined whether postoperative cluster assignment could be predicted from baseline values. Psychiatric symptoms in the postoperative period made a substantial contribution to longitudinal caregiver burden. The development of stimulation-dependent mood changes was also associated with increased burden. However, caregiver burden and caregiver-rated psychiatric symptom clusters were temporally stable and thus predicted only by their baseline values. We confirmed this finding using frequentist and Bayesian statistics, concluding that in our sample, subthalamic DBS for PD did not significantly influence caregiver burden or caregiver-rated psychiatric symptoms. Specifically, patient–caregiver dyads with high burden and high levels of psychiatric symptoms at baseline were likely to maintain this profile during follow-up. These findings support the importance of assessing caregiver burden prior to functional neurosurgery. Furthermore, they suggest that interventions addressing caregiver burden in this population should target those with greater symptomatology at baseline and may usefully prioritise psychiatric symptoms reported by the caregiver.
Translation of remote control regenerative technologies for bone repair
Authors: Markides Hareklea , McLaren Jane S. , Telling Neil D. , Alom Noura , Al-Mutheffer E’atelaf A. , Oreffo Richard O. C. , Zannettino Andrew , Scammell Brigitte E. , White Lisa J. , El Haj Alicia J.
Published: April 2018

The role of biomechanical stimuli, or mechanotransduction, in normal bone homeostasis and repair is understood to facilitate effective osteogenesis of mesenchymal stem cells (MSCs) in vitro. Mechanotransduction has been integrated into a multitude of in vitro bone tissue engineering strategies and provides an effective means of controlling cell behaviour towards therapeutic outcomes. However, the delivery of mechanical stimuli to exogenous MSC populations, post implantation, poses a significant translational hurdle. Here, we describe an innovative bio-magnetic strategy, MICA, where magnetic nanoparticles (MNPs) are used to remotely deliver mechanical stimuli to the mechano-receptor, TREK-1, resulting in activation and downstream signalling via an external magnetic array. In these studies, we have translated MICA to a pre-clinical ovine model of bone injury to evaluate functional bone repair. We describe the development of a magnetic array capable of in vivo MNP manipulation and subsequent osteogenesis at equivalent field strengths in vitro. We further demonstrate that the viability of MICA-activated MSCs in vivo is unaffected 48 h post implantation. We present evidence to support early accelerated repair and preliminary enhanced bone growth in MICA-activated defects within individuals compared to internal controls. The variability in donor responses to MICA-activation was evaluated in vitro revealing that donors with poor osteogenic potential were most improved by MICA-activation. Our results demonstrate a clear relationship between responders to MICA in vitro and in vivo. These unique experiments offer exciting clinical applications for cell-based therapies as a practical in vivo source of dynamic loading, in real-time, in the absence of pharmacological agents.
Author Correction: Diphenyleneiodonium chloride (DPIC) displays broad-spectrum bactericidal activity
Authors: Pandey Manitosh , Singh Alok Kumar , Thakare Ritesh , Talwar Sakshi , Karaulia Pratiksha , Dasgupta Arunava , Chopra Sidharth , Pandey Amit Kumar
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Striking diflubenzuron resistance in Culex pipiens, the prime vector of West Nile Virus
Authors: Grigoraki Linda , Puggioli Arianna , Mavridis Konstantinos , Douris Vassilis , Montanari Mario , Bellini Romeo , Vontas John
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Electrical and optical properties of epitaxial binary and ternary GeTe-Sb2Te3 alloys
Authors: Boschker Jos E. , Lü Xiang , Bragaglia Valeria , Wang Ruining , Grahn Holger T. , Calarco Raffaella
Published: April 2018

Phase change materials such as pseudobinary GeTe-Sb2Te3 (GST) alloys are an essential part of existing and emerging technologies. Here, we investigate the electrical and optical properties of epitaxial phase change materials: α-GeTe, Ge2Sb2Te5 (GST225), and Sb2Te3. Temperature-dependent Hall measurements reveal a reduction of the hole concentration with increasing temperature in Sb2Te3 that is attributed to lattice expansion, resulting in a non-linear increase of the resistivity that is also observed in GST225. Fourier transform infrared spectroscopy at room temperature demonstrates the presence of electronic states within the energy gap for α-GeTe and GST225. We conclude that these electronic states are due to vacancy clusters inside these two materials. The obtained results shed new light on the fundamental properties of phase change materials such as the high dielectric constant and persistent photoconductivity and have the potential to be included in device simulations.
Author Correction: Potential impacts of climate change on habitat suitability for the Queensland fruit fly
Authors: Sultana Sabira , Baumgartner John B. , Dominiak Bernard C. , Royer Jane E. , Beaumont Linda J.
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Essential role of mitochondrial Stat3 in p38MAPK mediated apoptosis under oxidative stress
Authors: Cheng Xinlai , Peuckert Christiane , Wölfl Stefan
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Intrinsically-disordered N-termini in human parechovirus 1 capsid proteins bind encapsidated RNA
Authors: Shakeel Shabih , Evans James D. , Hazelbaker Mark , Kao C. Cheng , Vaughan Robert C. , Butcher Sarah J.
Published: April 2018

Human parechoviruses (HPeV) are picornaviruses with a highly-ordered RNA genome contained within icosahedrally-symmetric capsids. Ordered RNA structures have recently been shown to interact with capsid proteins VP1 and VP3 and facilitate virus assembly in HPeV1. Using an assay that combines reversible cross-linking, RNA affinity purification and peptide mass fingerprinting (RCAP), we mapped the RNA-interacting regions of the capsid proteins from the whole HPeV1 virion in solution. The intrinsically-disordered N-termini of capsid proteins VP1 and VP3, and unexpectedly, VP0, were identified to interact with RNA. Comparing these results to those obtained using recombinantly-expressed VP0 and VP1 confirmed the virion binding regions, and revealed unique RNA binding regions in the isolated VP0 not previously observed in the crystal structure of HPeV1. We used RNA fluorescence anisotropy to confirm the RNA-binding competency of each of the capsid proteins’ N-termini. These findings suggests that dynamic interactions between the viral RNA and the capsid proteins modulate virus assembly, and suggest a novel role for VP0.
Publisher Correction: Identification and characterization of the novel colonization factor CS30 based on whole genome sequencing in enterotoxigenic Escherichia coli (ETEC)
Authors: von Mentzer Astrid , Tobias Joshua , Wiklund Gudrun , Nordqvist Stefan , Aslett Martin , Dougan Gordon , Sjöling Åsa , Svennerholm Ann-Mari
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Publisher Correction: Selective Tropism of Dengue Virus for Human Glycoprotein Ib
Authors: Attatippaholkun Nattapol , Kosaisawe Nont , U-Pratya Yaowalak , Supraditaporn Panthipa , Lorthongpanich Chanchao , Pattanapanyasat Kovit , Issaragrisil Surapol
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: The Oncogenic Role of COL23A1 in Clear Cell Renal Cell Carcinoma
Authors: Xu Fujiang , Chang Kun , Ma Jian , Qu Yuanyuan , Xie Huyang , Dai Bo , Gan Hualei , Zhang Hailiang , Shi Guohai , Zhu Yao , Zhu Yiping , Shen Yijun , Ye Dingwei
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Glomerulocapillary miRNA response to HLA-class I antibody in vitro and in vivo
Authors: Heinemann Falko M. , Jindra Peter T. , Bockmeyer Clemens L. , Zeuschner Philip , Wittig Juliane , Höflich Heike , Eßer Marc , Abbas Mahmoud , Dieplinger Georg , Stolle Katharina , Vester Udo , Hoyer Peter F. , Immenschuh Stephan , Heinold Andreas , Horn Peter A. , Li Wentian , Eisenberger Ute , Becker Jan U.
Published: April 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
On the contributing role of the transmembrane domain for subunit-specific sensitivity of integrin activation
Authors: Pagani Giulia , Gohlke Holger
Published: April 2018

Integrins are α/β heterodimeric transmembrane adhesion receptors. Evidence exists that their transmembrane domain (TMD) separates upon activation. Subunit-specific differences in activation sensitivity of integrins were reported. However, whether sequence variations in the TMD lead to differential TMD association has remained elusive. Here, we show by molecular dynamics simulations and association free energy calculations on TMDs of integrin αIIbβ3, αvβ3, and α5β1 that αIIbβ3 TMD is most stably associated; this difference is related to interaction differences across the TMDs. The order of TMD association stability is paralleled by the basal activity of these integrins, which suggests that TMD differences can have a decisive effect on integrin conformational free energies. We also identified a specific order of clasp disintegration upon TMD dissociation, which suggests that the closed state of integrins may comprise several microstates. Our results provide unprecedented insights into a possibly contributing role of TMD towards subunit-specific sensitivity of integrin activation.
An estradiol-independent BDNF-NPY cascade is involved in the antidepressant effect of mechanical acupuncture instruments in ovariectomized rats
Authors: Seo Su Yeon , Moon Ji-Young , Kang Suk-Yun , Kwon O. Sang , Kwon Sunoh , Bang Se kyun , Kim Soo Phil , Choi Kwang-Ho , Ryu Yeonhee
Published: April 2018

Menopause-related depression devastates women’s quality of life after middle age. Previous research has shown that estrogen hormone therapy has serious adverse effects; thus, complementary and integrative therapies have been considered clinically. The present study investigates whether stimulation of an acupoint using a mechanical acupuncture instrument (MAI) can mitigate depression-like behavior caused by estrogen deficiency in ovariectomized (OVX) rats. The animals were divided into Sham OVX, OVX, OVX + Sameumgyo (SP6) and OVX + NonAcu (non-acupuncture point) groups. MAI stimulation significantly increased the total distance traveled in the open-field test and the number of open-arm entries in the elevated plus maze and decreased the duration of immobility in the forced swim test. In addition to this decrease in depression-like behavior, brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY) release increased in the hippocampus in response to MAI treatment, but estradiol levels did not recover. Furthermore, microinjection of the BDNF receptor antagonist ANA-12 (0.1 pmol/1 μl) into the hippocampus before MAI stimulation significantly suppressed the recovery of NPY levels. Taken together, these findings indicate that MAI stimulation at SP6 facilitates an estradiol-independent BDNF-NPY cascade, which may contribute to its antidepressant effects in OVX rats, an animal model of menopausal disorders.
Bayesian-Driven First-Principles Calculations for Accelerating Exploration of Fast Ion Conductors for Rechargeable Battery Application
Authors: Jalem Randy , Kanamori Kenta , Takeuchi Ichiro , Nakayama Masanobu , Yamasaki Hisatsugu , Saito Toshiya
Published: April 2018

Safe and robust batteries are urgently requested today for power sources of electric vehicles. Thus, a growing interest has been noted for fabricating those with solid electrolytes. Materials search by density functional theory (DFT) methods offers great promise for finding new solid electrolytes but the evaluation is known to be computationally expensive, particularly on ion migration property. In this work, we proposed a Bayesian-optimization-driven DFT-based approach to efficiently screen for compounds with low ion migration energies ($${{\boldsymbol{E}}}_{{\boldsymbol{b}}}{\boldsymbol{)}}$$

E

b

)
. We demonstrated this on 318 tavorite-type Li- and Na-containing compounds. We found that the scheme only requires ~30% of the total DFT-$${{\boldsymbol{E}}}_{{\boldsymbol{b}}}$$

E

b

evaluations on the average to recover the optimal compound ~90% of the time. Its recovery performance for desired compounds in the tavorite search space is ~2× more than random search (i.e., for $${{\boldsymbol{E}}}_{{\boldsymbol{b}}}$$

E

b

 < 0.3 eV). Our approach offers a promising way for addressing computational bottlenecks in large-scale material screening for fast ionic conductors.
Stimulation of TLR3 triggers release of lysosomal ATP in astrocytes and epithelial cells that requires TRPML1 channels
Authors: Beckel Jonathan M. , Gómez Néstor Más , Lu Wennan , Campagno Keith E. , Nabet Bardia , Albalawi Farraj , Lim Jason C. , Boesze-Battaglia Kathleen , Mitchell Claire H.
Published: April 2018

Cross-reactions between innate immunity, lysosomal function, and purinergic pathways may link signaling systems in cellular pathologies. We found activation of toll-like receptor 3 (TLR3) triggers lysosomal ATP release from both astrocytes and retinal pigmented epithelial (RPE) cells. ATP efflux was accompanied by lysosomal acid phosphatase and beta hexosaminidase release. Poly(I:C) alkalinized lysosomes, and lysosomal alkalization with bafilomycin or chloroquine triggered ATP release. Lysosomal rupture with glycyl-L-phenylalanine-2-naphthylamide (GPN) eliminated both ATP and acid phosphatase release. Secretory lysosome marker LAMP3 colocalized with VNUT, while MANT-ATP colocalized with LysoTracker. Unmodified membrane-impermeant 21-nt and “non-targeting” scrambled 21-nt siRNA triggered ATP and acid phosphatase release, while smaller 16-nt RNA was ineffective. Poly(I:C)-dependent ATP release was reduced by TBK-1 block and in TRPML1−/− cells, while TRPML activation with ML-SA1 was sufficient to release both ATP and acid phosphatase. The ability of poly(I:C) to raise cytoplasmic Ca2+ was abolished by removing extracellular ATP with apyrase, suggesting ATP release by poly(I:C) increased cellular signaling. Starvation but not rapamycin prevented lysosomal ATP release. In summary, stimulation of TLR3 triggers lysosomal alkalization and release of lysosomal ATP through activation of TRPML1; this links innate immunity to purinergic signaling via lysosomal physiology, and suggests even scrambled siRNA can influence these pathways.
Pannexin 1 sustains the electrophysiological responsiveness of retinal ganglion cells
Authors: Dvoriantchikova Galina , Pronin Alexey , Kurtenbach Sarah , Toychiev Abduqodir , Chou Tsung-Han , Yee Christopher W. , Prindeville Breanne , Tayou Junior , Porciatti Vittorio , Sagdullaev Botir T. , Slepak Vladlen Z. , Shestopalov Valery I.
Published: April 2018

Pannexin 1 (Panx1) forms ATP-permeable membrane channels that play a key role in purinergic signaling in the nervous system in both normal and pathological conditions. In the retina, particularly high levels of Panx1 are found in retinal ganglion cells (RGCs), but the normal physiological function in these cells remains unclear. In this study, we used patch clamp recordings in the intact inner retina to show that evoked currents characteristic of Panx1 channel activity were detected only in RGCs, particularly in the OFF-type cells. The analysis of pattern electroretinogram (PERG) recordings indicated that Panx1 contributes to the electrical output of the retina. Consistently, PERG amplitudes were significantly impaired in the eyes with targeted ablation of the Panx1 gene in RGCs. Under ocular hypertension and ischemic conditions, however, high Panx1 activity permeated cell membranes and facilitated the selective loss of RGCs or stably transfected Neuro2A cells. Our results show that high expression of the Panx1 channel in RGCs is essential for visual function in the inner retina but makes these cells highly sensitive to mechanical and ischemic stresses. These findings are relevant to the pathophysiology of retinal disorders induced by increased intraocular pressure, such as glaucoma.
Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease
Authors: Frejo Lidia , Gallego-Martinez Alvaro , Requena Teresa , Martin-Sanz Eduardo , Amor-Dorado Juan Carlos , Soto-Varela Andres , Santos-Perez Sofia , Espinosa-Sanchez Juan Manuel , Batuecas-Caletrio Angel , Aran Ismael , Fraile Jesus , Rossi-Izquierdo Marcos , Lopez-Escamez Jose Antonio
Published: April 2018

Epidemiological studies have found a higher prevalence of allergic symptoms and positive prick tests in patients with Meniere’s disease (MD); however the effect of allergenic extracts in MD has not been established. Thus, this study aims to determine the effect of Aspergillus and Penicillium stimulation in cytokine release and gene expression profile in MD. Patients with MD showed higher basal levels of IL-1β, IL-1RA, IL-6 and TNF-α when compared to healthy controls. We observed that IL-1β levels had a bimodal distribution suggesting two different subgroups of patients, with low and high basal levels of cytokines. Gene expression profile in peripheral blood mononuclear cells (PBMC) showed significant differences in patients with high and low basal levels of IL-1β. We found that both mold extracts triggered a significant release of TNF-α in MD patients, which were not found in controls. Moreover, after mold stimulation, MD patients showed a different gene expression profile in PBMC, according to the basal levels of IL-1β. The results indicate that a subset of MD patients have higher basal levels of proinflammatory cytokines and the exposure to Aspergillus and Penicillium extracts may trigger additional TNF-α release and contribute to exacerbate inflammation.
Structure and co-occurrence patterns in microbial communities under acute environmental stress reveal ecological factors fostering resilience
Authors: Mandakovic Dinka , Rojas Claudia , Maldonado Jonathan , Latorre Mauricio , Travisany Dante , Delage Erwan , Bihouée Audrey , Jean Géraldine , Díaz Francisca P. , Fernández-Gómez Beatriz , Cabrera Pablo , Gaete Alexis , Latorre Claudio , Gutiérrez Rodrigo A. , Maass Alejandro , Cambiazo Verónica , Navarrete Sergio A. , Eveillard Damien , González Mauricio
Published: April 2018

Understanding the factors that modulate bacterial community assembly in natural soils is a longstanding challenge in microbial community ecology. In this work, we compared two microbial co-occurrence networks representing bacterial soil communities from two different sections of a pH, temperature and humidity gradient occurring along a western slope of the Andes in the Atacama Desert. In doing so, a topological graph alignment of co-occurrence networks was used to determine the impact of a shift in environmental variables on OTUs taxonomic composition and their relationships. We observed that a fraction of association patterns identified in the co-occurrence networks are persistent despite large environmental variation. This apparent resilience seems to be due to: (1) a proportion of OTUs that persist across the gradient and maintain similar association patterns within the community and (2) bacterial community ecological rearrangements, where an important fraction of the OTUs come to fill the ecological roles of other OTUs in the other network. Actually, potential functional features suggest a fundamental role of persistent OTUs along the soil gradient involving nitrogen fixation. Our results allow identifying factors that induce changes in microbial assemblage configuration, altering specific bacterial soil functions and interactions within the microbial communities in natural environments.
Canine NAPEPLD-associated models of human myelin disorders
Authors: Minor K. M. , Letko A. , Becker D. , Drögemüller M. , Mandigers P. J. J. , Bellekom S. R. , Leegwater P. A. J. , Stassen Q. E. M. , Putschbach K. , Fischer A. , Flegel T. , Matiasek K. , Ekenstedt K. J. , Furrow E. , Patterson E. E. , Platt S. R. , Kelly P. A. , Cassidy J. P. , Shelton G. D. , Lucot K. , Bannasch D. L. , Martineau H. , Muir C. F. , Priestnall S. L. , Henke D. , Oevermann A. , Jagannathan V. , Mickelson J. R. , Drögemüller C.
Published: April 2018

Canine leukoencephalomyelopathy (LEMP) is a juvenile-onset neurodegenerative disorder of the CNS white matter currently described in Rottweiler and Leonberger dogs. Genome-wide association study (GWAS) allowed us to map LEMP in a Leonberger cohort to dog chromosome 18. Subsequent whole genome re-sequencing of a Leonberger case enabled the identification of a single private homozygous non-synonymous missense variant located in the highly conserved metallo-beta-lactamase domain of theN-acyl phosphatidylethanolamine phospholipase D(NAPEPLD) gene, encoding an enzyme of the endocannabinoid system. We then sequenced this gene in LEMP-affected Rottweilers and identified a different frameshift variant, which is predicted to replace the C-terminal metallo-beta-lactamase domain of the wild type protein. Haplotype analysis of SNP array genotypes revealed that the frameshift variant was present in diverse haplotypes in Rottweilers, and also in Great Danes, indicating an old origin of this secondNAPEPLDvariant. The identification of differentNAPEPLDvariants in dog breeds affected by leukoencephalopathies with heterogeneous pathological features, implicates the NAPEPLD enzyme as important in myelin homeostasis, and suggests a novel candidate gene for myelination disorders in people.
Annealing induced atomic rearrangements on (Ga,In) (N,As) probed by hard X-ray photoelectron spectroscopy and X-ray absorption fine structure
Authors: Ishikawa Fumitaro , Higashi Kotaro , Fuyuno Satoshi , Morifuji Masato , Kondow Masahiko , Trampert Achim
Published: April 2018

We study the effects of annealing on (Ga0.64,In0.36) (N0.045,As0.955) using hard X-ray photoelectron spectroscopy and X-ray absorption fine structure measurements. We observed surface oxidation and termination of the N-As bond defects caused by the annealing process. Specifically, we observed a characteristic chemical shift towards lower binding energies in the photoelectron spectra related to In. This phenomenon appears to be caused by the atomic arrangement, which produces increased In-N bond configurations within the matrix, as indicated by the X-ray absorption fine structure measurements. The reduction in the binding energies of group-III In, which occurs concomitantly with the atomic rearrangements of the matrix, causes the differences in the electronic properties of the system before and after annealing.
The sequence of cortical activity inferred by response latency variability in the human ventral pathway of face processing
Authors: Lin Jo-Fu Lotus , Silva-Pereyra Juan , Chou Chih-Che , Lin Fa-Hsuan
Published: April 2018

Variability in neuronal response latency has been typically considered caused by random noise. Previous studies of single cells and large neuronal populations have shown that the temporal variability tends to increase along the visual pathway. Inspired by these previous studies, we hypothesized that functional areas at later stages in the visual pathway of face processing would have larger variability in the response latency. To test this hypothesis, we used magnetoencephalographic data collected when subjects were presented with images of human faces. Faces are known to elicit a sequence of activity from the primary visual cortex to the fusiform gyrus. Our results revealed that the fusiform gyrus showed larger variability in the response latency compared to the calcarine fissure. Dynamic and spectral analyses of the latency variability indicated that the response latency in the fusiform gyrus was more variable than in the calcarine fissure between 70 ms and 200 ms after the stimulus onset and between 4 Hz and 40 Hz, respectively. The sequential processing of face information from the calcarine sulcus to the fusiform sulcus was more reliably detected based on sizes of the response variability than instants of the maximal response peaks. With two areas in the ventral visual pathway, we show that the variability in response latency across brain areas can be used to infer the sequence of cortical activity.
Arousing emoticons edit stream/bounce perception of objects moving past each other
Authors: Gobara Akihiko , Yoshimura Naoto , Yamada Yuki
Published: April 2018

When two identical objects move toward each other, overlap completely, and continue toward opposite ends of a space, observers might perceive them as streaming through or bouncing off each other. This phenomenon is known as ‘stream/bounce perception’. In this study, we investigated the effect of the presentation of emoticons on stream/bounce perception in five experiments. In Experiment 1, we used emoticons representing anger (‘(‘∧’)’), a smile (‘(^_^)’), and a sober face (‘(°_°)’, as a control), and observers were asked to judge whether two objects unrelated to the emoticon had streamed through or bounced off each other. The anger emoticon biased perception toward bouncing when compared with the smile or sober face emoticon. In Experiments 2 and 3, we controlled for the valence and arousal of emoticons, and found that arousal influenced stream/bounce perception but valence did not. Experiments 4 and 5 ruled out the possibility of attentional capture and response bias for the emoticon with higher arousal. Taken together, the findings indicate that emoticons with higher arousal evoke a mental image of a ‘collision’ in observers, thereby eliciting the bounce perception.
Low-intensity repetitive transcranial magnetic stimulation requires concurrent visual system activity to modulate visual evoked potentials in adult mice
Authors: Makowiecki Kalina , Garrett Andrew , Harvey Alan R. , Rodger Jennifer
Published: April 2018

Repetitive transcranial stimulation (rTMS) is an increasingly popular method to non-invasively modulate cortical excitability in research and clinical settings. During rTMS, low-intensity magnetic fields reach areas perifocal to the target brain region, however, effects of these low-intensity (LI-) fields and how they interact with ongoing neural activity remains poorly defined. We evaluated whether coordinated neural activity during electromagnetic stimulation alters LI-rTMS effects on cortical excitability by comparing visually evoked potentials (VEP) and densities of parvalbumin-expressing (PV+) GABAergic interneurons in adult mouse visual cortex after LI-rTMS under different conditions: LI-rTMS applied during visually evoked (strong, coordinated) activity or in darkness (weak, spontaneous activity).We also compared response to LI-rTMS in wildtype and ephrin-A2A5−/− mice, which have visuotopic anomalies thought to disrupt coherence of visually-evoked cortical activity. Demonstrating that LI-rTMS effects in V1 require concurrent sensory-evoked activity, LI-rTMS delivered during visually-evoked activity increased PV+ immunoreactivity in both genotypes; however, VEP peak amplitudes changed only in wildtypes, consistent with intracortical disinhibition. We show, for the first time, that neural activity and the degree of coordination in cortical population activity interact with LI-rTMS to alter excitability in a context-dependent manner.
Association between hedonic hunger and body-mass index versus obesity status
Authors: Ribeiro Gabriela , Camacho Marta , Santos Osvaldo , Pontes Cristina , Torres Sandra , Oliveira-Maia Albino J.
Published: April 2018

Obesity-associated differences in hedonic hunger, while consistently reported, have not been adequately quantified, with most studies failing to demonstrate strong correlations between Body Mass Index (BMI) and hedonic hunger indicators. Here, we quantified and assessed the nature of the relationship between hedonic hunger and BMI, in a cross-sectional study using the Portuguese version of the PFS (P-PFS) to measure hedonic hunger. Data were collected from 1266 participants belonging to non-clinical, clinical (candidates for weight-loss surgery) and population samples. Across samples, significant but weak positive associations were found between P-PFS scores and BMI, in adjusted linear regression models. However, in logistic regression models of data from the clinical and non-clinical samples, the P-PFS Food Available domain score was significantly and robustly associated with belonging to the clinical sample (OR = 1.8, 95%CI: 1.2–2.8; p = 0.008), while in the population sample it was associated to being obese (OR = 2.1, 95%CI: 1.6–2.7; p < 0.001). Thus, hedonic hunger levels are associated with obesity status with the odds of being obese approximately doubling for each unit increase in the P-PFS Food Available score.
High-resolution behavioral mapping of electric fishes in Amazonian habitats
Authors: Madhav Manu S. , Jayakumar Ravikrishnan P. , Demir Alican , Stamper Sarah A. , Fortune Eric S. , Cowan Noah J.
Published: April 2018

The study of animal behavior has been revolutionized by sophisticated methodologies that identify and track individuals in video recordings. Video recording of behavior, however, is challenging for many species and habitats including fishes that live in turbid water. Here we present a methodology for identifying and localizing weakly electric fishes on the centimeter scale with subsecond temporal resolution based solely on the electric signals generated by each individual. These signals are recorded with a grid of electrodes and analyzed using a two-part algorithm that identifies the signals from each individual fish and then estimates the position and orientation of each fish using Bayesian inference. Interestingly, because this system involves eavesdropping on electrocommunication signals, it permits monitoring of complex social and physical interactions in the wild. This approach has potential for large-scale non-invasive monitoring of aquatic habitats in the Amazon basin and other tropical freshwater systems.
Dietary supplementation with flaxseed meal and oat hulls modulates intestinal histomorphometric characteristics, digesta- and mucosa-associated microbiota in pigs
Authors: Ndou S. P. , Tun H. M. , Kiarie E. , Walsh M. C. , Khafipour E. , Nyachoti C. M.
Published: April 2018

The establishment of a healthy gastrointestinal milieu may not only offer an opportunity to reduce swine production costs but could also open the way for a lifetime of human health improvement. This study investigates the effects of feeding soluble fibre from flaxseed meal-containing diet (FM) and insoluble fibre from oat hulls-containing diet (OH) on histomorphological characteristics, digesta- and mucosa-associated microbiota and their associations with metabolites in pig intestines. In comparison with the control (CON) and OH diets, the consumption of FM increased (P < 0.001) the jejunal villi height (VH) and the ratio of VH to crypt depths. The PERMANOVA analyses showed distinct (P < 0.05) microbial communities in ileal digesta and mucosa, and caecal mucosa in CON and FM-diets fed pigs compared to the OH diet-fed pigs. The predicted functional metagenomes indicated that amino acids and butanoate metabolism, lysine degradation, bile acids biosynthesis, and apoptosis were selectively enhanced at more than 2.2 log-folds in intestinal microbiota of pigs fed the FM diet. Taken together, flaxseed meal and oat hulls supplementation in growing pigs’ diets altered the gastrointestinal development, as well as the composition and function of microbial communities, depending on the intestinal segment and physicochemical property of the dietary fibre source.
Neurofibromin knockdown in glioma cell lines is associated with changes in cytokine and chemokine secretion in vitro
Authors: Wood Matthew D. , Mukherjee Joydeep , Pieper Russell O.
Published: April 2018

The neurofibromin-1 tumor suppressor gene (NF1) is altered in approximately 20% of sporadic glioblastoma (GBM) cases. NF1 deficient GBM frequently shows a mesenchymal gene expression signature, suggesting a relationship between NF1 status and the tumor microenvironment. To identify changes in the production of secreted cytokines/chemokines in NF1 deficient glioma, we applied cytokine arrays to conditioned media from a panel of three GBM cell lines after siRNA-mediated NF1 knockdown. We identified increased secretion of platelet-derived growth factor AA (PDGF-AA), chitinase-3-like protein 1 (CHI3L1), interleukin-8 (IL-8), and endoglin (ENG) in different subsets of these cell lines. Secretion was associated with induction of the corresponding messenger RNA, suggesting a mechanism involving transcriptional upregulation. By contrast, in non-transformed immortalized normal human astrocytes, PDGF-AA secretion was increased upon NF1 knockdown, while secreted CHI3L1, ENG, and IL-8 were reduced or unchanged. Analysis of The Cancer Genome Atlas confirmed a relationship between glioma NF1 status and ENG and CHI3L1 in tumor samples. Overall, this study identifies candidate changes in secreted proteins from NF1 deficient glioma cells that could influence the tumor microenvironment, and suggests a direct link between NF1 loss and increased tumor cell production of CHI3L1 and endoglin, two factors implicated in mesenchymal identity in glioblastoma.
Comparative analysis of naive, primed and ground state pluripotency in mouse embryonic stem cells originating from the same genetic background
Authors: Ghimire Sabitri , Van der Jeught Margot , Neupane Jitesh , Roost Matthias S. , Anckaert Jasper , Popovic Mina , Van Nieuwerburgh Filip , Mestdagh Pieter , Vandesompele Jo , Deforce Dieter , Menten Björn , Chuva de Sousa Lopes Susana , De Sutter Petra , Heindryckx Björn
Published: April 2018

Mouse embryonic stem cells (mESCs) exist in a naive, primed and ground state of pluripotency. While comparative analyses of these pluripotency states have been reported, the mESCs utilized originated from various genetic backgrounds and were derived in different laboratories. mESC derivation in conventional LIF + serum culture conditions is strain dependent, with different genetic backgrounds potentially affecting subsequent stem cell characteristics. In the present study, we performed a comprehensive characterization of naive, primed and ground state mESCs originating from the same genetic background within our laboratory, by comparing their transcriptional profiles. We showed unique transcriptional profiles for naive, primed and ground state mESCs. While naive and ground state mESCs have more similar but not identical profiles, primed state mESCs show a very distinct profile. We further demonstrate that the differentiation propensity of mESCs to specific germ layers is highly dependent on their respective state of pluripotency.