bluuebunny/crossref_metadata_2025 huggingface dataset:
An Empirical Model of Vertical Plasma Drift Over the African Sector
Authors: Dubazane Makhosonke Berthwell , Habarulema John Bosco
Published: May 2018

Daytime vertical E × B drift can be derived from difference of H‐component magnetic field measurements (ΔH) using a pair of low‐latitude and equatorial latitude magnetometer stations. Knowledge of E × B drift is of utmost importance in space weather‐related predictions since it can significantly affect ionospheric density structures and dynamics. For the first time, we developed a quantitative relationship between equatorial electrojet (ΔH) and vertical E × B drift over the African region using magnetometer data and E × B drift observations from the Communication and Navigation Outage Forecasting System (C/NOFS) satellite during local daytime (0700–1800 LT) from 2008 to 2013 when magnetometer data were available. Additionally, we have constructed vertical E × B drift models over the African sector based on C/NOFS vertical E × B drift data and relevant physical and geophysical inputs. Validating using data not included in model development, our model estimated C/NOFS vertical E × B drift with correlation coefficient values of 0.85 and 0.56 during quiet and disturbed conditions, respectively. The daily pattern of the E × B drift velocity is consistent between the developed model based on C/NOFS data and the climatological Scherliess‐Fejer model. However, the Scherliess‐Fejer model generally overestimated C/NOFS vertical E × B drift (in most cases) with a correlation coefficient of 0.54 during quiet conditions.
Recombinant amelogenin regulates the bioactivity of mouse cementoblasts in vitro
Authors: Hakki Sema S. , Bozkurt S. Buket , Türkay Emre , Dard Michel , Purali Nuhan , Götz Werner
Published: May 2018

Amelogenin (AMG) is a cell adhesion molecule that has an important role in the mineralization of enamel and regulates events during dental development and root formation. The purpose of the present study was to investigate the effects of recombinant human AMG (rhAMG) on mineralized tissue-associated genes in cementoblasts. Immortalized mouse cementoblasts (OCCM-30) were treated with different concentrations (0.1, 1, 10, 100, 1000, 10,000, 100,000 ng · mL-1) of recombinant human AMG (rhAMG) and analyzed for proliferation, mineralization and mRNA expression of bone sialoprotein (BSP), osteocalcin (OCN), collagen type I (COL I), osteopontin (OPN), runt-related transcription factor 2 (Runx2), cementum attachment protein (CAP), and alkaline phosphatase (ALP) genes using quantitative RT-PCR. The dose response of rhAMG was evaluated using a real-time cell analyzer. Total RNA was isolated on day 3, and cell mineralization was assessed using von Kossa staining on day 8. COL I, OPN and lysosomal-associated membrane protein-1 (LAMP-1), which is a cell surface binding site for amelogenin, were evaluated using immunocytochemistry. F-actin bundles were imaged using confocal microscopy. rhAMG at a concentration of 100,000 ng · mL-1 increased cell proliferation after 72 h compared to the other concentrations and the untreated control group. rhAMG (100,000 ng · mL-1) upregulated BSP and OCN mRNA expression levels eightfold and fivefold, respectively. rhAMG at a concentration of 100,000 ng · mL-1 remarkably enhanced LAMP-1 staining in cementoblasts. Increased numbers of mineralized nodules were observed at concentrations of 10,000 and 100,000 ng · mL-1 rhAMG. The present data suggest that rhAMG is a potent regulator of gene expression in cementoblasts and support the potential application of rhAMG in therapies aimed at fast regeneration of damaged periodontal tissue.
p53-dependent CD51 expression contributes to characteristics of cancer stem cells in prostate cancer
Authors: Sui Xin , Cai Jianye , Li Hongyu , He Chenchen , Zhou Congya , Dong Yiping , Chen Li , Zhang Bin , Wang Yingnan , Zhang Yanan , Qiu Yuan , Zhang Yuanyuan , Zhao Yang , Huang Yinong , Shen Yutian , Wu Haoxiang , Xiao Jiaqi , Mason Clifford , Zhu Qing , Han Suxia
Published: May 2018

Abstract

Castration-resistant prostate cancer (CRPC), which is considered to contain cancer stem cells (CSCs), leads to a high relapse rate in patients with prostate cancer (PCa). However, the markers of prostate CSCs are controversial. Here we demonstrate that CD51, in part, correlates with the poor prognosis of PCa patients. Further, we find that CD51 is a functional molecule that is able to promote the malignancy of PCa through enhancing tumor initiation, metastatic potential, and chemoresistance. Moreover, we find that elevated CD51 expression in PCa specimens correlates with p53 loss of function. Mechanistically, we demonstrate that p53 acts via Sp1/3 to repress CD51 transcription, and CD51 is required for PCa stemness and metastasis properties, and is downregulated by p53. Taken together, these results indicate that CD51 is a novel functional marker for PCa, which may provide a therapeutic target for the efficiently restricting PCa progression.
E2F1 inhibition mediates cell death of metastatic melanoma
Authors: Rouaud Florian , Hamouda-Tekaya Nedra , Cerezo Michaël , Abbe Patricia , Zangari Joséphine , Hofman Veronique , Ohanna Mickaël , Mograbi Baharia , El-Hachem Najla , Benfodda Zohra , Lebeau Alexandre , Tulic Meri K. , Hofman Paul , Bertolotto Corine , Passeron Thierry , Annicotte Jean-Sébastien , Ballotti Robert , Rocchi Stéphane
Published: May 2018

Melanoma is one of the most lethal cancers when it reaches a metastatic stage. Despite advancements in targeted therapies (BRAF inhibitors) or immunotherapies (anti-CTLA-4 or anti-PD1), most patients with melanoma will need additional treatment. Thus, there is an urgent need to develop new therapeutical approaches to bypass resistance and achieve more prolonged responses. In this context, we were interested in E2F1, a transcription factor that plays a major role in the control of cell cycle under physiological and pathological conditions. Here we confirmed that E2F1 is highly expressed in melanoma cells. Inhibition of E2F1 activity further increased melanoma cell death and senescence, both in vitro and in vivo. Moreover, blocking E2F1 also induced death of melanoma cells resistant to BRAF inhibitors. In conclusion, our studies suggest that targeting the E2F1 signaling pathway may be therapeutically relevant for melanoma.
Molecular functional analyses revealed essential roles of HSP90 and lamin A/C in growth, migration, and self-aggregation of dermal papilla cells
Authors: Thanomkitti Kanchalit , Fong-ngern Kedsarin , Sueksakit Kanyarat , Thuangtong Rattapon , Thongboonkerd Visith
Published: May 2018

Previous expression study using quantitative proteomics has shown that immune-mediated pathway may not be the main mechanism inducing alopecia areata (AA). Nevertheless, functional impact of such expression data set remained unknown and unexplored. This study thus aimed to define potentially novel mechanisms of the AA pathogenesis by functional investigations of the differentially expressed proteins previously identified from lesional biopsies. From 122 altered proteins, protein–protein interactions network analysis revealed that downregulated heat shock protein 90 (HSP90) and lamin A/C served as the central nodes of protein–protein interactions involving in several crucial biological functions, including cytoskeleton organization, extracellular matrix organization, and tissue development. Interaction between HSP90 and lamin A/C in dermal papilla cells (DPCs) was confirmed by reciprocal immunoprecipitation and immunofluorescence co-staining. Small-interfering RNA (siRNA) targeting to HSP90 (siHSP90) and lamin A/C (siLamin A/C) effectively reduced levels of HSP90 and lamin A/C, respectively and vice versa, comparing to non-transfected and siControl-transfected cells, strengthening their interactive roles in DPCs. Functional investigations revealed that DPCs transfected with siHSP90 and siLamin A/C had defective cell proliferation and growth, prolonged doubling time, cell cycle arrest at G0/G1 phase, and defective self-aggregation formation. Moreover, siHSP90-transfected cells had less spindle index, reduced levels of vimentin (mesenchymal marker) and fibronectin (extracellular matrix), and defective migratory activity. Our data have demonstrated for the first time that HSP90 and lamin A/C physically interact with each other. Moreover, both of them are essential for growth, migration, and self-aggregation of DPCs and can be linked to the disease mechanisms of AA.
Programmable sequential mutagenesis by inducible Cpf1 crRNA array inversion
Authors: Chow Ryan D. , Kim Hyunu Ray , Chen Sidi
Published: May 2018

Mutations and genetic alterations are often sequentially acquired in various biological and pathological processes, such as development, evolution, and cancer. Certain phenotypes only manifest with precise temporal sequences of genetic events. While multiple approaches have been developed to model the effects of mutations in tumorigenesis, few recapitulate the stepwise nature of cancer evolution. Here we describe a flexible sequential mutagenesis system, Cpf1-Flip, with inducible inversion of a single crRNA array (FlipArray), and demonstrate its application in stepwise mutagenesis in murine and human cells. As a proof-of-concept, we further utilize Cpf1-Flip in a pooled-library approach to model the acquisition of diverse resistance mutations to cancer immunotherapy. Cpf1-Flip offers a simple, versatile, and controlled approach for precise mutagenesis of multiple loci in a sequential manner.
Quantifying climate feedbacks in polar regions
Authors: Goosse Hugues , Kay Jennifer E. , Armour Kyle C. , Bodas-Salcedo Alejandro , Chepfer Helene , Docquier David , Jonko Alexandra , Kushner Paul J. , Lecomte Olivier , Massonnet François , Park Hyo-Seok , Pithan Felix , Svensson Gunilla , Vancoppenolle Martin
Published: May 2018

The concept of feedback is key in assessing whether a perturbation to a system is amplified or damped by mechanisms internal to the system. In polar regions, climate dynamics are controlled by both radiative and non-radiative interactions between the atmosphere, ocean, sea ice, ice sheets and land surfaces. Precisely quantifying polar feedbacks is required for a process-oriented evaluation of climate models, a clear understanding of the processes responsible for polar climate changes, and a reduction in uncertainty associated with model projections. This quantification can be performed using a simple and consistent approach that is valid for a wide range of feedbacks, offering the opportunity for more systematic feedback analyses and a better understanding of polar climate changes.
Hematopoietic stem cells can differentiate into restricted myeloid progenitors before cell division in mice
Authors: Grinenko Tatyana , Eugster Anne , Thielecke Lars , Ramasz Beáta , Krüger Anja , Dietz Sevina , Glauche Ingmar , Gerbaulet Alexander , von Bonin Malte , Basak Onur , Clevers Hans , Chavakis Triantafyllos , Wielockx Ben
Published: May 2018

Hematopoietic stem cells (HSCs) continuously replenish all blood cell types through a series of differentiation steps and repeated cell divisions that involve the generation of lineage-committed progenitors. However, whether cell division in HSCs precedes differentiation is unclear. To this end, we used an HSC cell-tracing approach and Ki67RFP knock-in mice, in a non-conditioned transplantation model, to assess divisional history, cell cycle progression, and differentiation of adult HSCs. Our results reveal that HSCs are able to differentiate into restricted progenitors, especially common myeloid, megakaryocyte-erythroid and pre-megakaryocyte progenitors, without undergoing cell division and even before entering the S phase of the cell cycle. Additionally, the phenotype of the undivided but differentiated progenitors correlated with the expression of lineage-specific genes and loss of multipotency. Thus HSC fate decisions can be uncoupled from physical cell division. These results facilitate a better understanding of the mechanisms that control fate decisions in hematopoietic cells.
DOT1L inhibition attenuates graft-versus-host disease by allogeneic T cells in adoptive immunotherapy models
Authors: Kagoya Yuki , Nakatsugawa Munehide , Saso Kayoko , Guo Tingxi , Anczurowski Mark , Wang Chung-Hsi , Butler Marcus O. , Arrowsmith Cheryl H. , Hirano Naoto
Published: May 2018

Adoptive T-cell therapy is a promising therapeutic approach for cancer patients. The use of allogeneic T-cell grafts will improve its applicability and versatility provided that inherent allogeneic responses are controlled. T-cell activation is finely regulated by multiple signaling molecules that are transcriptionally controlled by epigenetic mechanisms. Here we report that inhibiting DOT1L, a histone H3-lysine 79 methyltransferase, alleviates allogeneic T-cell responses. DOT1L inhibition reduces miR-181a expression, which in turn increases the ERK phosphatase DUSP6 expression and selectively ameliorates low-avidity T-cell responses through globally suppressing T-cell activation-induced gene expression alterations. The inhibition of DOT1L or DUSP6 overexpression in T cells attenuates the development of graft-versus-host disease, while retaining potent antitumor activity in xenogeneic and allogeneic adoptive immunotherapy models. These results suggest that DOT1L inhibition may enable the safe and effective use of allogeneic antitumor T cells by suppressing unwanted immunological reactions in adoptive immunotherapy.
Early Cambrian origin of the shelf sediment mixed layer
Authors: Gougeon Romain C. , Mángano M. Gabriela , Buatois Luis A. , Narbonne Guy M. , Laing Brittany A.
Published: May 2018

The mixed layer of modern oceans is a zone of fully homogenized sediment resulting from bioturbation. The mixed layer is host to complex biogeochemical cycles that directly impact ecosystem functioning, affecting ocean productivity and marine biodiversity. The timing of origin of the mixed layer has been controversial, with estimates ranging from Cambrian to Silurian, hindering our understanding of biogeochemical cycling and ecosystem dynamics in deep time. Here we report evidence from the Global Stratotype Section and Point (GSSP) of the basal Cambrian in the Burin Peninsula of Newfoundland, Canada, showing that a well-developed mixed layer of similar structure to that of modern marine sediments was established in shallow marine settings by the early Cambrian (approximately 529 million years ago). These findings imply that the benthos significantly contributed to establishing new biogeochemical cycles during the Cambrian explosion.
Hybrid nanostructured particles via surfactant-free double miniemulsion polymerization
Authors: Zhao Yongliang , Liu Junli , Chen Zhi , Zhu Xiaomin , Möller Martin
Published: May 2018

Double emulsions are complex fluid systems, in which droplets of a dispersed liquid phase contain even smaller dispersed liquid droplets. Particularly, water-in-oil-in-water double emulsions provide significant advantages over simple oil-in-water emulsions for microencapsulation, such as carrier of both aqueous and oily payloads and sustained release profile. However, double emulsions are thermodynamically unstable systems consisting typically of relatively large droplets. Here we show that nanoscale water-in-oil-in-water double emulsions can be prepared by adding a silica precursor polymer, hyperbranched polyethoxysiloxane, to the oil phase without any additional surfactants. The resulting double miniemulsions are transformed to robust water@SiO2@polymer@SiO2nanocapsules via conversion of the precursor to silica and polymerization of the oil phase. Other intriguing nanostructures like nanorattles and Janus-like nanomushrooms can also be obtained by changing preparation conditions. This simple surfactant-free double miniemulsion polymerization technique opens a promising avenue for mass production of various complex hybrid nanostructures that are amenable to numerous applications.
Dynamics of a qubit while simultaneously monitoring its relaxation and dephasing
Authors: Ficheux Q. , Jezouin S. , Leghtas Z. , Huard B.
Published: May 2018

Decoherence originates from the leakage of quantum information into external degrees of freedom. For a qubit, the two main decoherence channels are relaxation and dephasing. Here, we report an experiment on a superconducting qubit where we retrieve part of the lost information in both of these channels. We demonstrate that raw averaging the corresponding measurement records provides a full quantum tomography of the qubit state where all three components of the effective spin-1/2 are simultaneously measured. From single realizations of the experiment, it is possible to infer the quantum trajectories followed by the qubit state conditioned on relaxation and/or dephasing channels. The incompatibility between these quantum measurements of the qubit leads to observable consequences in the statistics of quantum states. The high level of controllability of superconducting circuits enables us to explore many regimes from the Zeno effect to underdamped Rabi oscillations depending on the relative strengths of driving, dephasing, and relaxation.
Iron-specific Signal Separation from within Heavy Metal Stained Biological Samples Using X-Ray Microtomography with Polychromatic Source and Energy-Integrating Detectors
Authors: Katchalski Tsvi , Case Tom , Kim Keun-young , Ramachandra Ranjan , Bushong Eric A. , Deerinck Thomas J. , Haberl Matthias G. , Mackey Mason R. , Peltier Steven , Castillon Guillaume A. , Fujikawa Nobuko , Lawrence Albert R. , Ellisman Mark H.
Published: May 2018

Biological samples are frequently stained with heavy metals in preparation for examining the macro, micro and ultra-structure using X-ray microtomography and electron microscopy. A single X-ray microtomography scan reveals detailed 3D structure based on staining density, yet it lacks both material composition and functional information. Using a commercially available polychromatic X-ray source, energy integrating detectors and a two-scan configuration labelled by their energy- “High” and “Low”, we demonstrate how a specific element, here shown with iron, can be detected from a mixture with other heavy metals. With proper selection of scan configuration, achieving strong overlap of source characteristic emission lines and iron K-edge absorption, iron absorption was enhanced enabling K-edge imaging. Specifically, iron images were obtained by scatter plot material analysis, after selecting specific regions within scatter plots generated from the “High” and “Low” scans. Using this method, we identified iron rich regions associated with an iron staining reaction that marks the nodes of Ranvier along nerve axons within mouse spinal roots, also stained with osmium metal commonly used for electron microscopy.
Publisher Correction: Investigating the relationship between Aerosol Optical Depth and Precipitation over Southeast Asia with Relative Humidity as an influencing factor
Authors: Ng Daniel Hui Loong , Li Ruimin , Raghavan Srivatsan V. , Liong Shie-Yui
Published: May 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.
Therapeutic nanoparticles penetrate leaves and deliver nutrients to agricultural crops
Authors: Karny Avishai , Zinger Assaf , Kajal Ashima , Shainsky-Roitman Janna , Schroeder Avi
Published: May 2018

As the world population grows, there is a need for efficient agricultural technologies to provide global food requirements and reduce environmental toll. In medicine, nanoscale drug delivery systems grant improved therapeutic precision by overcoming biological barriers and enhancing drug targeting to diseased tissues. Here, we loaded nanoscale drug-delivery systems with agricultural nutrients, and applied them to the leaves of tomato plants. We show that the nanoparticles – liposomes composed of plant-derived lipids, penetrate the leaf and translocate in a bidirectional manner, distributing to other leaves and to the roots. The liposomes were then internalized by the plant cells, where they released their active ingredient. Up to 33% of the applied nanoparticles penetrated the leaf, compared to less than one percent of free-molecules applied in a similar manner. In our study, tomato plants treated with liposomes loaded with Fe and Mg overcame acute nutrient deficiency which was not treatable using ordinary agricultural nutrients. Furthermore, to address regulatory concerns regarding airborne nanoparticles, we rationally designed liposomes that were stable only over short spraying distances (less than 2 meters), while the liposomes disintegrated into safe molecular building blocks (phospholipids) over longer airborne distances. These findings support expanding the implementation of nanotechnology for delivering micronutrients to agricultural crops for increasing yield.
Anatomy of a fumarolic system inferred from a multiphysics approach
Authors: Gresse Marceau , Vandemeulebrouck Jean , Byrdina Svetlana , Chiodini Giovanni , Roux Philippe , Rinaldi Antonio Pio , Wathelet Marc , Ricci Tullio , Letort Jean , Petrillo Zaccaria , Tuccimei Paola , Lucchetti Carlo , Sciarra Alessandra
Published: May 2018

Fumaroles are a common manifestation of volcanic activity that are associated with large emissions of gases into the atmosphere. These gases originate from the magma, and they can provide indirect and unique insights into magmatic processes. Therefore, they are extensively used to monitor and forecast eruptive activity. During their ascent, the magmatic gases interact with the rock and hydrothermal fluids, which modify their geochemical compositions. These interactions can complicate our understanding of the real volcanic dynamics and remain poorly considered. Here, we present the first complete imagery of a fumarolic plumbing system using three-dimensional electrical resistivity tomography and new acoustic noise localization. We delineate a gas reservoir that feeds the fumaroles through distinct channels. Based on this geometry, a thermodynamic model reveals that near-surface mixing between gas and condensed steam explains the distinct geochemical compositions of fumaroles that originate from the same source. Such modeling of fluid interactions will allow for the simulation of dynamic processes of magmatic degassing, which is crucial to the monitoring of volcanic unrest.
Long non-coding RNA expression patterns in lung tissues of chronic cigarette smoke induced COPD mouse model
Authors: Zhang Haiyun , Sun Dejun , Li Defu , Zheng Zeguang , Xu Jingyi , Liang Xue , Zhang Chenting , Wang Sheng , Wang Jian , Lu Wenju
Published: May 2018

Long non-coding RNAs (lncRNAs) have critical regulatory roles in protein-coding gene expression. Aberrant expression profiles of lncRNAs have been observed in various human diseases. In this study, we investigated transcriptome profiles in lung tissues of chronic cigarette smoke (CS)-induced COPD mouse model. We found that 109 lncRNAs and 260 mRNAs were significantly differential expressed in lungs of chronic CS-induced COPD mouse model compared with control animals. GO and KEGG analyses indicated that differentially expressed lncRNAs associated protein-coding genes were mainly involved in protein processing of endoplasmic reticulum pathway, and taurine and hypotaurine metabolism pathway. The combination of high throughput data analysis and the results of qRT-PCR validation in lungs of chronic CS-induced COPD mouse model, 16HBE cells with CSE treatment and PBMC from patients with COPD revealed that NR_102714 and its associated protein-coding gene UCHL1 might be involved in the development of COPD both in mouse and human. In conclusion, our study demonstrated that aberrant expression profiles of lncRNAs and mRNAs existed in lungs of chronic CS-induced COPD mouse model. From animal models perspective, these results might provide further clues to investigate biological functions of lncRNAs and their potential target protein-coding genes in the pathogenesis of COPD.
TDP-43 regulation of stress granule dynamics in neurodegenerative disease-relevant cell types
Authors: Khalfallah Yousra , Kuta Rachel , Grasmuck Camille , Prat Alexandre , Durham Heather D. , Vande Velde Christine
Published: May 2018

Stress granules (SGs) are cytoplasmic foci that form in response to various external stimuli and are essential to cell survival following stress. SGs are studied in several diseases, including ALS and FTD, which involve the degeneration of motor and cortical neurons, respectively, and are now realized to be linked pathogenically by TDP-43, originally discovered as a component of ubiquitin-positive aggregates within patients’ neurons and some glial cells. So far, studies to undercover the role of TDP-43 in SGs have used primarily transformed cell lines, and thus rely on the extrapolation of the mechanisms to cell types affected in ALS/FTD, potentially masking cell specific effects. Here, we investigate SG dynamics in primary motor and cortical neurons as well as astrocytes. Our data suggest a cell and stress specificity and demonstrate a requirement for TDP-43 for efficient SG dynamics. In addition, based on our in vitro approach, our data suggest that aging may be an important modifier of SG dynamics which could have relevance to the initiation and/or progression of age-related neurodegenerative diseases.
Performance boost for primary magnesium cells using iron complexing agents as electrolyte additives
Authors: Höche Daniel , Lamaka Sviatlana V. , Vaghefinazari Bahram , Braun Tobias , Petrauskas Rokas P. , Fichtner Maximilian , Zheludkevich Mikhail L.
Published: May 2018

Aqueous Mg battery technology holds significant appeal, owing to the availability of raw materials, high power densities and the possibility of fast mechanical recharge. However, Mg batteries have so far been prone to decreased capacity due to self-corrosion of the anodes from the electrochemical redeposition of impurities, such as Fe, which results in parasitic cathodically active sites on the discharging anode. This work demonstrates that by adding Fe3+-complexing agents like Tiron or salicylate to the aqueous electrolyte of an Mg battery, it was possible to prevent the redeposition of Fe impurities and subsequent self-corrosion of the anode surface, thereby boosting battery performance. To prevent detrimental fouling of anode surface by Mg(OH)2, employed Fe3+-complexing agents must also form soluble complexes with Mg2+ of moderate stability. The interplay of these requirements predetermines the improvement of operating voltage and utilization efficiency.
Two-fluid, hydrodynamic model for spherical electrolyte systems
Authors: David Christin
Published: May 2018

Spatial interaction effects between charge carriers in ionic systems play a sizable role beyond a classical Maxwellian description. We develop a nonlocal, two-fluid, hydrodynamic theory of charges and study ionic plasmon effects, i.e. collective charge oscillations in electrolytes. Ionic spatial dispersion arises from both positive and negative charge dynamics with an impact in the (far-)infrared. Despite highly classical parameters, nonlocal quenching of up to 90% is observed for particle sizes spanning orders of magnitude. Notably, the ionic system is widely tunable via ion concentration, mass and charge, in contrast to solid metal nanoparticles. A nonlocal soft plasmonic theory for ions is relevant for biological and chemical systems bridging hard and soft matter theory and allowing the investigation of non-classical effects in electrolytes in full analogy to solid metal particles. The presented semi-classical approach allows studying plasmonic photo-catalysis introducing nonlocal aspects into electrolyte-metal interactions.
Fabrication and characterization of a scalable surface textured with pico-liter oil drops for mechanistic studies of bacteria-oil interactions
Authors: Jalali Maryam , White Andrew R. , Marti James , Sheng Jian
Published: May 2018

Texturing a large surface with oily micro-drops with controlled size, shape and volume provides an unprecedented capability in investigating complex interactions of bacteria, cells and interfaces. It has particular implications in understanding key microbial processes involved in remediation of environmental disasters, such as Deepwater Horizon oil spill. This work presents a development of scalable micro-transfer molding to functionalize a substrate with oily drop array to generate a microcosm mimicking bacteria encountering a rising droplet cloud. The volume of each drop within a large “printed” surface can be tuned by varying base geometry and area with characteristic scales from 5 to 50 μm. Contrary to macroscopic counterparts, drops with non-Laplacian shapes, i.e. sharp corners, that appears to violate Young-Laplacian relationship locally, are produced. Although the drop relaxes into a spherical cap with constant mean curvature, the contact line with sharp corners remains pinned. Relaxation times from initial to asymptotic shape require extraordinarily long time (>7 days). We demonstrate that non-Laplacian drops are the direct results of self-pinning of contact line by nanoparticles in the oil. This technique has been applied to study biofilm formation at the oil-water interface and can be readily extended to other colloidal fluids.
The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers
Authors: Hindocha C. , Freeman T. P. , Grabski M. , Crudgington H. , Davies A. C. , Stroud J. B. , Das R. K. , Lawn W. , Morgan C. J. A. , Curran H. V.
Published: May 2018

Acute nicotine abstinence in cigarette smokers results in deficits in performance on specific cognitive processes, including working memory and impulsivity which are important in relapse. Cannabidiol (CBD), the non-intoxicating cannabinoid found in cannabis, has shown pro-cognitive effects and preliminary evidence has indicated it can reduce the number of cigarettes smoked in dependent smokers. However, the effects of CBD on cognition have never been tested during acute nicotine withdrawal. The present study therefore aimed to investigate if CBD can improve memory and reduce impulsivity during acute tobacco abstinence. Thirty, non-treatment seeking, dependent, cigarette smokers attended two laboratory-based sessions after overnight abstinence, in which they received either 800 mg oral CBD or placebo (PBO), in a randomised order. Abstinence was biologically verified. Participants were assessed on go/no-go, delay discounting, prose recall and N-back (0-back, 1-back, 2-back) tasks. The effects of CBD on delay discounting, prose recall and the N-back (correct responses, maintenance or manipulation) were null, confirmed by a Bayesian analysis, which found evidence for the null hypothesis. Contrary to our predictions, CBD increased commission errors on the go/no-go task. In conclusion, a single 800 mg dose of CBD does not improve verbal or spatial working memory, or impulsivity during tobacco abstinence.
Wildfire smoke impacts activity and energetics of wild Bornean orangutans
Authors: Erb W. M. , Barrow E. J. , Hofner A. N. , Utami-Atmoko S. S. , Vogel E. R.
Published: May 2018

Indonesia’s peatlands experience frequent and intense wildfires, producing hazardous smoke with consequences for human health, yet there is a lack of research into adverse effects on wildlife. We evaluated the effects of smoke on the activity and energy balance of Bornean orangutans (Pongo pygmaeus wurmbii) in a peat swamp forest at the Tuanan Research Station, Central Kalimantan. We collected behavioural data and urine samples from four adult flanged males before, during, and after wildfires between March 2015 and January 2016. During fires, particulate matter (PM10) concentrations were hazardous. Orangutans increased rest time during and after the smoke period, and decreased travel time and distance and increased fat catabolism post-smoke. The increase in post-smoke ketones was not related to changes in caloric intake and was likely due to an increase in energy expenditure, possibly related to immune response. Results show that wildfire smoke negatively affects orangutan condition, and sustained research is needed to assess the magnitude of the threat to the long-term viability of this Critically Endangered species.
Structure-guided Discovery of Dual-recognition Chemibodies
Authors: Cheng Alan C. , Doherty Elizabeth M. , Johnstone Sheree , DiMauro Erin F. , Dao Jennifer , Luthra Abhinav , Ye Jay , Tang Jie , Nixey Thomas , Min Xiaoshan , Tagari Philip , Miranda Les P. , Wang Zhulun
Published: May 2018

Small molecules and antibodies each have advantages and limitations as therapeutics. Here, we present for the first time to our knowledge, the structure-guided design of “chemibodies” as small molecule-antibody hybrids that offer dual recognition of a single target by both a small molecule and an antibody, using DPP-IV enzyme as a proof of concept study. Biochemical characterization demonstrates that the chemibodies present superior DPP-IV inhibition compared to either small molecule or antibody component alone. We validated our design by successfully solving a co-crystal structure of a chemibody in complex with DPP-IV, confirming specific binding of the small molecule portion at the interior catalytic site and the Fab portion at the protein surface. The discovery of chemibodies presents considerable potential for novel therapeutics that harness the power of both small molecule and antibody modalities to achieve superior specificity, potency, and pharmacokinetic properties.
Adeno-associated Virus Vector-mediated Interleukin-10 Induction Prevents Vascular Inflammation in a Murine Model of Kawasaki Disease
Authors: Nakamura Jun , Watanabe Sachiko , Kimura Hiroaki , Kobayashi Motoi , Karasawa Tadayoshi , Kamata Ryo , Usui-Kawanishi Fumitake , Sadatomo Ai , Mizukami Hiroaki , Nagi-Miura Noriko , Ohno Naohito , Kasahara Tadashi , Minota Seiji , Takahashi Masafumi
Published: May 2018

Kawasaki disease (KD), which is the leading cause of pediatric heart disease, is characterized by coronary vasculitis and subsequent aneurysm formation. Although intravenous immunoglobulin therapy is effective for reducing aneurysm formation, a certain number of patients are resistant to this therapy. Because interleukin-10 (IL-10) was identified as a negative regulator of cardiac inflammation in a murine model of KD induced by Candida albicans water-soluble fraction (CAWS), we investigated the effect of IL-10 supplementation in CAWS-induced vasculitis. Mice were injected intramuscularly with adeno-associated virus (AAV) vector encoding IL-10, then treated with CAWS. The induction of AAV-mediated IL-10 (AAV-IL-10) significantly attenuated the vascular inflammation and fibrosis in the aortic root and coronary artery, resulting in the improvement of cardiac dysfunction and lethality. The predominant infiltrating inflammatory cells in the vascular walls were Dectin-2+CD11b+ macrophages. In vitro experiments revealed that granulocyte/macrophage colony-stimulating factor (GM-CSF) induced Dectin-2 expression in bone marrow-derived macrophages and enhanced the CAWS-induced production of tumor necrosis factor-α (TNF-α) and IL-6. IL-10 had no effect on the Dectin-2 expression but significantly inhibited the production of cytokines. IL-10 also inhibited CAWS-induced phosphorylation of ERK1/2, but not Syk. Furthermore, the induction of AAV-IL-10 prevented the expression of TNF-α and IL-6, but not GM-CSF and Dectin-2 at the early phase of CAWS-induced vasculitis. These findings demonstrate that AAV-IL-10 may have therapeutic application in the prevention of coronary vasculitis and aneurysm formation, and provide new insights into the mechanism underlying the pathogenesis of KD.
Oncotically Driven Control over Glycocalyx Dimension for Cell Surface Engineering and Protein Binding in the Longitudinal Direction
Authors: Siren Erika M. J. , Chapanian Rafi , Constantinescu Iren , Brooks Donald E. , Kizhakkedathu Jayachandran N.
Published: May 2018

Here we present a simple technique for re-directing reactions on the cell surface to the outermost region of the glycocalyx. Macromolecular crowding with inert polymers was utilized to reversibly alter the accessibility of glycocalyx proteoglycans toward cell-surface reactive probes allowing for reactivity control in the longitudinal direction (‘z’-direction) on the glycocalyx. Studies in HUVECs demonstrated an oncotically driven collapse of the glycocalyx brush structure in the presence of crowders as the mechanism responsible for re-directing reactivity. This phenomenon is consistent across a variety of macromolecular agents including polymers, protein markers and antibodies which all displayed enhanced binding to the outermost surface of multiple cell types. We then demonstrated the biological significance of the technique by increasing the camouflage of red blood cell surface antigens via a crowding-enhanced attachment of voluminous polymers to the exterior of the glycocalyx. The accessibility to Rhesus D (RhD) and CD47 proteins on the cell surface was significantly decreased in crowding-assisted polymer grafting in comparison to non-crowded conditions. This strategy is expected to generate new tools for controlled glycocalyx engineering, probing the glycocalyx structure and function, and improving the development of cell based therapies.
Notoginsenoside R1 inhibits vascular smooth muscle cell proliferation, migration and neointimal hyperplasia through PI3K/Akt signaling
Authors: Fang Haihong , Yang Shilin , Luo Yingying , Zhang Cheng , Rao Yi , Liu Renjing , Feng Yulin , Yu Jun
Published: May 2018

Restenosis caused by neointimal hyperplasia significantly decreases long-term efficacy of percutaneous transluminal angioplasty (PTA), stenting, and by-pass surgery for managing coronary and peripheral arterial diseases. A major cause of pathological neointima formation is abnormal vascular smooth muscle cell (VSMC) proliferation and migration. Notoginsenoside R1 (NGR1) is a novel saponin that is derived from Panax notoginseng and has reported cardioprotective, neuroprotective and anti-inflammatory effects. However, its role in modulating VSMC neointima formation remains unexplored. Herein, we report that NGR1 inhibits serum-induced VSMC proliferation and migration by regulating VSMC actin cytoskeleton dynamics. Using a mouse femoral artery endothelium denudation model, we further demonstrate that systemic administration of NGR1 had a potent therapeutic effect in mice, significantly reducing neointimal hyperplasia following acute vessel injury. Mechanistically, we show that NGR1’s mode of action is through inhibiting the activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Taken together, this study identified NGR1 as a potential therapeutic agent for combating restenosis after PTA in cardiovascular diseases.
Understanding the Connection between Nanoparticle Uptake and Cancer Treatment Efficacy using Mathematical Modeling
Authors: Brocato Terisse A. , Coker Eric N. , Durfee Paul N. , Lin Yu-Shen , Townson Jason , Wyckoff Edward F. , Cristini Vittorio , Brinker C. Jeffrey , Wang Zhihui
Published: May 2018

Nanoparticles have shown great promise in improving cancer treatment efficacy while reducing toxicity and treatment side effects. Predicting the treatment outcome for nanoparticle systems by measuring nanoparticle biodistribution has been challenging due to the commonly unmatched, heterogeneous distribution of nanoparticles relative to free drug distribution. We here present a proof-of-concept study that uses mathematical modeling together with experimentation to address this challenge. Individual mice with 4T1 breast cancer were treated with either nanoparticle-delivered or free doxorubicin, with results demonstrating improved cancer kill efficacy of doxorubicin loaded nanoparticles in comparison to free doxorubicin. We then developed a mathematical theory to render model predictions from measured nanoparticle biodistribution, as determined using graphite furnace atomic absorption. Model analysis finds that treatment efficacy increased exponentially with increased nanoparticle accumulation within the tumor, emphasizing the significance of developing new ways to optimize the delivery efficiency of nanoparticles to the tumor microenvironment.
Linking cervicovaginal immune signatures, HPV and microbiota composition in cervical carcinogenesis in non-Hispanic and Hispanic women
Authors: Łaniewski Paweł , Barnes Dominique , Goulder Alison , Cui Haiyan , Roe Denise J. , Chase Dana M. , Herbst-Kralovetz Melissa M.
Published: May 2018

While high-risk human papillomavirus (HPV) infection is a well-established risk factor for cervical cancer, there are likely other factors within the local microenvironment that contribute to cervical carcinogenesis. Here we investigated relationships between HPV, vaginal pH, vaginal microbiota (VMB) composition, level of genital immune mediators and severity of cervical neoplasm. We enrolled women with low- and high-grade cervical dysplasia (LGD, HGD), invasive cervical carcinoma (ICC), and healthy controls. HPV16, HPV45, HPV58, and HPV31 were the most prevalent in our cohort with HPV16 and HPV31 genotypes more prevalent in Hispanics. Vaginal pH was associated with ethnicity and severity of cervical neoplasm. Lactobacillus dominance decreased with the severity of cervical neoplasm, which correlated with elevated vaginal pH. Hispanic ethnicity was also associated with decreased Lactobacillus dominance. Furthermore, Sneathia was enriched in all precancerous groups, ICC, abnormal pH and Hispanic origin. Patients with ICC, but not LGD and HGD, exhibited increased genital inflammatory scores and elevated specific immune mediators. Notably, IL-36γ was significantly associated with ICC. Our study revealed local, host immune and microbial signatures associated with cervical carcinogenesis and provides an initial step to understanding the complex interplay between mucosal inflammation, HPV persistence and the VMB.
Pretreatment drug resistance in a large countrywide Ethiopian HIV-1C cohort: a comparison of Sanger and high-throughput sequencing
Authors: Telele Nigus Fikrie , Kalu Amare Worku , Gebre-Selassie Solomon , Fekade Daniel , Abdurahman Samir , Marrone Gaetano , Neogi Ujjwal , Tegbaru Belete , Sönnerborg Anders
Published: May 2018

Baseline plasma samples of 490 randomly selected antiretroviral therapy (ART) naïve patients from seven hospitals participating in the first nationwide Ethiopian HIV-1 cohort were analysed for surveillance drug resistance mutations (sDRM) by population based Sanger sequencing (PBSS). Also next generation sequencing (NGS) was used in a subset of 109 baseline samples of patients. Treatment outcome after 6– and 12–months was assessed by on-treatment (OT) and intention-to-treat (ITT) analyses. Transmitted drug resistance (TDR) was detected in 3.9% (18/461) of successfully sequenced samples by PBSS. However, NGS detected sDRM more often (24%; 26/109) than PBSS (6%; 7/109) (p = 0.0001) and major integrase strand transfer inhibitors (INSTI) DRMs were also found in minor viral variants from five patients. Patients with sDRM had more frequent treatment failure in both OT and ITT analyses. The high rate of TDR by NGS and the identification of preexisting INSTI DRMs in minor wild-type HIV-1 subtype C viral variants infected Ethiopian patients underscores the importance of TDR surveillance in low– and middle–income countries and shows added value of high-throughput NGS in such studies.
Determination of flumequine enantiomers and 7-hydroxyflumequine in water and sediment by chiral HPLC coupled with hybrid quadrupole-time-of-flight mass spectrometer
Authors: Xue Moyong , Qin Yuchang , Gu Xu , Li Junguo , Gao Yunfeng , Yang Xiaowei , Yao Ting , Zhao Zhen
Published: May 2018

A liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for simultaneous enantiomeric analysis of flumequine and its metabolite 7-hydroxyflumequine in water and sediment had been developed based on the separation method. Sediment samples were extracted with ACN and EDTA-Mcllvaine buffer solution (40:60, v/v) then were enriched and cleaned-up by Cleanert PEP solid-phase extraction cartridges. The extract solvent, solid cartridges, mobile phase ratios, and chiral separation column were all optimized to reach high sensitivity and selectivity, good peak shape, and satisfactory resolution. The results showed that the calibration curves of flumequine enantiomers and 7-hydroxyflumequine were linear in the range of 1.0 to 200.0 µg/L with correlation coefficients of 0.9822–0.9988, the mean recoveries for both the enantiomers ranged from 69.9–84.6% with relative standard deviations (RSDs) being 13.1% or below. The limits of detection (LODs) for both flumequine enantiomers were 2.5 µg/L and 5.0 µg/kg in water and sediment samples, whereas the limits of quantification (LOQs) were 8.0 µg/L and 15.0 µg/kg, respectively. While the LODs for 7-hydroxyflumequine were 3.2 µg/L in water samples and 7.0 µg/kg in sediment samples. The proposed method will be extended for studies on the degradation kinetics and environmental behaviors and providing additional information for reliable risk assessment of these chiral antibiotics.
E-cigarettes can emit formaldehyde at high levels under conditions that have been reported to be non-averse to users
Authors: Salamanca James C. , Meehan-Atrash Jiries , Vreeke Shawna , Escobedo Jorge O. , Peyton David H. , Strongin Robert M.
Published: May 2018

E-cigarette aerosol emission studies typically focus on benchmarking toxicant levels versus those of cigarettes. However, such studies do not fully account for the distinct chemical makeup of e-liquids and their unique properties. These approaches often conclude that there are fewer and lower levels of toxins produced by e-cigarettes than by cigarettes. In 2015, we reported the discovery of new hemiacetals derived from the reaction of formaldehyde and the e-liquid solvents. The main finding was that they constituted a significant proportion of potentially undetected formaldehyde. Moreover, unlike gaseous formaldehyde, the hemiacetals reside in the aerosol particulate phase, and thus are capable of delivering formaldehyde more deeply into the lungs. However, the findings were criticized by those claiming that some of the results were obtained under conditions that are averse to vapers. A “reinvestigation” of our study was recently published addressing this latter issue. However, this reinvestigation ignored major details, including no mention of the formaldehyde hemiacetals. Herein, we isolated both gaseous formaldehyde and formaldehyde hemiacetals at an intermediate power level claimed, in the “reinvestigation”, to be relevant to “non-averse,” “normal” usage. The results were that both gaseous formaldehyde and formaldehyde from hemiacetals were produced at levels above OSHA workplace limits.
Evaluation of the utility of a rapid test for syphilis at a sexually transmitted disease clinic in Buenos Aires, Argentina
Authors: Gallo Vaulet Lucía , Morando Nicolás , Casco Ricardo , Melgar Asunta , Nacher Silvia , Rodríguez Fermepin Marcelo , Pando María A.
Published: May 2018

Even though syphilis can be easily diagnosed by simple and low-cost laboratory methods, it continues to be an important health problem. Rapid tests (RT) for the detection of treponemal antibodies can facilitate earlier diagnosis, access to treatment and linkage to care. The aim of this study was to analyse the usefulness of the incorporation of a RT in the detection of patients infected with T. pallidum in a sexually-transmitted disease (STD) clinic. Between March and December 2015, a syphilis RT was offered to patients who spontaneously attended the clinic. Conventional serology testing was additionally indicated to every participant. The RT for syphilis was offered to 1887 patients, of whom 31.1% agreed to get tested. VDRL test was performed in 84.0% of patients that were also tested with syphilis RT, with a significantly higher frequency observed among participants with reactive RT (94.3% vs. 79.8%, p < 0.001). These results showed that 33.7% of the participants were reactive for the RT and 27.0% were reactive for the VDRL test. Both tests were reactive in 24.9% and non-reactive in 64.3%. A high prevalence of active syphilis was detected in patients attending the clinic. The use of a syphilis RT had a positive impact, which in combination with the VDRL test increased the number of patients that were effectively diagnosed.