bluuebunny/crossref_metadata_2025 huggingface dataset:
Expanding Canadian Medicare to include a national pharmaceutical benefit while controlling expenditures: possible lessons from Israel
Authors: Rosen Bruce
Published: February 2018

In Canada, there is an ongoing debate about whether to expand Medicare to include a national pharmaceutical benefit on a universal basis. The potential health benefits are understood to be significant, but there are ongoing concerns about affordability. In Israel, the National Health Insurance benefits package includes a comprehensive pharmaceutical benefit. Nonetheless, per capita pharmaceutical spending is well below that of Canada and the Organization for Economic Co-operation and Development average. This paper highlights seven strategies that Israel has employed to constrain pharmaceutical spending: (1) prioritizing new technologies, subject to a global budget constraint; (2) using regulations and market power to secure fair and reasonable prices; (3) establishing an efficient pharmaceutical distribution system; (4) promoting effective prescribing behavior; (5) avoiding artificial inflation of consumer demand; (6) striking an appropriate balance between respect for IP rights, access and cost containment; and (7) developing a shared societal understanding about the value and limits of pharmaceutical spending. Some of these strategies are already in place in some parts of Canada. Others could be introduced into Canada, and might contribute to the affordability of a national pharmaceutical benefit, but substantial adaptation would be needed. For example, in Israel the health maintenance organizations (HMOs) play a central role in promoting effective prescribing behavior, whereas in HMO-free Canada other mechanisms are needed to advance this important goal.
Value from Ruin? Governing Speculative Conservation in Ruptured Landscapes
Authors: Dressler Wolfram H. , Fletcher Robert , Fabinyi Michael
Published: February 2018

This paper examines how state and non-state actors govern through pursuing speculative conservation among resource-dependent people who must renegotiate altered livelihoods amidst extractivism in ruptured landscapes. As donor aid declines and changes form, bilaterals, state agencies, and civil society now pursue advocacy in overlapping spaces of intensifying extractivism and speculative governance in the ruptured frontiers of Southeast Asia. In these spaces, bilaterals and non-governmental organisations (NGOs) struggle to work with upland farmers who negotiate the contrasting expectations of the abstract, speculative nature of conservation initiatives and the lucrative nature of extractive labour in the face of dramatic transformations of agrarian livelihoods and landscapes. Through a case study of the Philippine uplands, we demonstrate that as speculative conservation unfolds and manifests within and beyond these landscapes, it endeavours to revalue nature monetarily in ways that help reorganise labour and capital in an effort to overcome the exhaustion of capital wrought by rupture. We propose that during moments of rupture speculative conservation coproduces value from ruin by renewing and preserving capital flows.
Insights into the Habitability of Mars
Authors: Rice Melissa
Published: February 2018

NASA’s Curiosity rover explored the Kimberley region of Mars to search for signs that the planet was once habitable.
Earth and Space Science for the Benefit of Humanity
Authors: Hanson Brooks , Lunn Jenny , van der Pluijm Ben , Orcutt John , Colwell Rita , Trumbore Susan , Becker Thorsten , Diffenbaugh Noah , Pincus Robert , Liemohn Mike , ten Brink Uri , Brewer Peter , Zhang Minghua , Hauck II Steven , Hubbard Bryn , Goni Miguel , Thomas Ellen , Wilkinson Phil , Moldwin Mark , Knipp Delores , Geissman John , Clark Martyn
Published: February 2018

A collection of Commentaries published in the journals of the American Geophysical Union illuminate the deep and growing benefits of research in the Earth and space sciences for humanity.
Where and How Can We Find New Sources of Oil and Gas?
Authors: Gaci Said , Hachay Olga
Published: February 2018

The editors of a new book on oil and gas exploration describe developments in methods for identifying oil and gas fields, and for making accurate predictions about their extractive potential.
A Sea Change in Paleoceanography
Authors: Thomas Ellen
Published: February 2018

The Editor-in-Chief of Paleoceanography explains that the journal is changing its name to Paleoceanography and Paleoclimatology to reflect the evolution of science in this field.
Subduction, Stratosphere, Starspots, and Sushi
Authors: Lunn Jenny , Becker Thorsten , Knipp Delores , Yau Andrew , Zhang Minghua
Published: February 2018

Highlights from AGU’s joint meeting with the Japan Geophysical Union.
Short Rains and Long Rains
Authors: Nicholson Sharon
Published: February 2018

A recent paper in Reviews of Geophysics examined the drivers of interannual and regional rainfall variability in eastern Africa.
Small eukaryotic phytoplankton communities in tropical waters off Brazil are dominated by symbioses between Haptophyta and nitrogen-fixing cyanobacteria
Authors: Gérikas Ribeiro Catherine , Lopes dos Santos Adriana , Marie Dominique , Pereira Brandini Frederico , Vaulot Daniel
Published: February 2018

Symbioses between eukaryotic algae and nitrogen-fixing cyanobacteria have been recognized in recent years as a key source of new nitrogen in the oceans. We investigated the composition of the small photosynthetic eukaryote communities associated with nitrogen-fixing cyanobacteria in the Brazilian South Atlantic Bight using a combination of flow cytometry sorting and high throughput sequencing of two genes: the V4 region of 18S rRNA and nifH. Two distinct eukaryotic communities were often encountered, one dominated by the Mamiellophyceae Bathycoccus and Ostreococcus, and one dominated by a prymnesiophyte known to live in symbiosis with the UCYN-A1 nitrogen-fixing cyanobacterium. Among nifH sequences, those from UCYN-A1 were most abundant but three other UCYN-A clades (A2, A3, A4) were also found. Network analysis confirmed the relation between A1 and A2 clades and their hypothesized hosts and pointed out to the potential association between novel clade A4 with Braarudosphaera bigelowii, previously hypothesized to host A2.
The WDR11 complex facilitates the tethering of AP-1-derived vesicles
Authors: Navarro Negredo Paloma , Edgar James R. , Manna Paul T. , Antrobus Robin , Robinson Margaret S.
Published: February 2018

Vesicluar transport of proteins from endosomes to the trans-Golgi network (TGN) is an essential cellular pathway, but much of its machinery is still unknown. A screen for genes involved in endosome-to-TGN trafficking produced two hits, the adaptor protein-1 (AP-1 complex), which facilitates vesicle budding, and WDR11. Here we demonstrate that WDR11 forms a stable complex with two other proteins, which localises to the TGN region and does not appear to be associated with AP-1, suggesting it may act downstream from budding. In a vesicle tethering assay, capture of vesicles by golgin-245 was substantially reduced in WDR11-knockout cells. Moreover, structured illumination microscopy and relocation assays indicate that the WDR11 complex is initially recruited onto vesicles rather than the TGN, where it may in turn recruit the golgin binding partner TBC1D23. We propose that the complex acts together with TBC1D23 to facilitate the golgin-mediated capture of vesicles that were generated using AP-1.
Visualizing catalyst heterogeneity by a multifrequential oscillating reaction
Authors: Suchorski Yuri , Datler Martin , Bespalov Ivan , Zeininger Johannes , Stöger-Pollach Michael , Bernardi Johannes , Grönbeck Henrik , Rupprechter Günther
Published: February 2018

It is well documented that different surface structures of catalytically active metals may exhibit different catalytic properties. This is typically examined by comparing the catalytic activities and/or selectivities of various well-defined smooth and stepped/kinked single crystal surfaces. Here we report the direct observation of the heterogeneity of active polycrystalline surfaces under reaction conditions, which is manifested by multifrequential oscillations during hydrogen oxidation over rhodium, imaged in situ by photoemission electron microscopy. Each specific surface structure, i.e. the crystallographically different µm-sized domains of rhodium, exhibits an individual spiral pattern and oscillation frequency, despite the global diffusional coupling of the surface reaction. This reaction behavior is attributed to the ability of stepped surfaces of high-Miller-index domains to facilitate the formation of subsurface oxygen, serving as feedback mechanism of the observed oscillations. The current experimental findings, backed by microkinetic modeling, may open an alternative approach towards addressing the structure-sensitivity of heterogeneous surfaces.
Ultraconserved element uc.372 drives hepatic lipid accumulation by suppressing miR-195/miR4668 maturation
Authors: Guo Jun , Fang Weiwei , Sun Libo , Lu Yonggang , Dou Lin , Huang Xiuqing , Tang Weiqing , Yu Liqing , Li Jian
Published: February 2018

Ultraconserved (uc) RNAs, a class of long non-coding RNAs (lncRNAs), are conserved across humans, mice, and rats, but the physiological significance and pathological role of ucRNAs is largely unknown. Here we show that uc.372 is upregulated in the livers of db/db mice, HFD-fed mice, and NAFLD patients. Gain-of-function and loss-of-function studies indicate that uc.372 drives hepatic lipid accumulation in mice by promoting lipogenesis. We further demonstrate that uc.372 binds to pri-miR-195/pri-miR-4668 and suppresses maturation of miR-195/miR-4668 to regulate expression of genes related to lipid synthesis and uptake, including ACC, FAS, SCD1, and CD36. Finally, we identify that uc.372 is located downstream of the insulinoma-associated 2 (INSM2) gene that is transcriptionally activated by upstream transcription factor 1 (USF1). Our findings reveal a novel mechanism by which uc.372 drives hepatic steatosis through inhibition of miR-195/miR-4668 maturation to relieve miR-195/miR-4668-mediated suppression of functional target gene expression.
Hedgehog spin-vortex crystal stabilized in a hole-doped iron-based superconductor
Authors: Meier William R. , Ding Qing-Ping , Kreyssig Andreas , Bud’ko Sergey L. , Sapkota Aashish , Kothapalli Karunakar , Borisov Vladislav , Valentí Roser , Batista Cristian D. , Orth Peter P. , Fernandes Rafael M. , Goldman Alan I. , Furukawa Yuji , Böhmer Anna E. , Canfield Paul C.
Published: February 2018

Magnetism is widely considered to be a key ingredient of unconventional superconductivity. In contrast to cuprate high-temperature superconductors, antiferromagnetism in most Fe-based superconductors (FeSCs) is characterized by a pair of magnetic propagation vectors, (π,0) and (0,π). Consequently, three different types of magnetic order are possible. Of these, only stripe-type spin-density wave (SSDW) and spin-charge-density wave (SCDW) orders have been observed. A realization of the proposed spin-vortex crystal (SVC) order is noticeably absent. We report a magnetic phase consistent with the hedgehog variation of SVC order in Ni-doped and Co-doped CaKFe4As4 based on thermodynamic, transport, structural and local magnetic probes combined with symmetry analysis. The exotic SVC phase is stabilized by the reduced symmetry of the CaKFe4As4 structure. Our results suggest that the possible magnetic ground states in FeSCs have very similar energies, providing an enlarged configuration space for magnetic fluctuations to promote high-temperature superconductivity.
SeagrassDB: An open-source transcriptomics landscape for phylogenetically profiled seagrasses and aquatic plants
Authors: Sablok Gaurav , Hayward Regan J. , Davey Peter A. , Santos Rosiane P. , Schliep Martin , Larkum Anthony , Pernice Mathieu , Dolferus Rudy , Ralph Peter J.
Published: February 2018

Seagrasses and aquatic plants are important clades of higher plants, significant for carbon sequestration and marine ecological restoration. They are valuable in the sense that they allow us to understand how plants have developed traits to adapt to high salinity and photosynthetically challenged environments. Here, we present a large-scale phylogenetically profiled transcriptomics repository covering seagrasses and aquatic plants. SeagrassDB encompasses a total of 1,052,262 unigenes with a minimum and maximum contig length of 8,831 bp and 16,705 bp respectively. SeagrassDB provides access to 34,455 transcription factors, 470,568 PFAM domains, 382,528 prosite models and 482,121 InterPro domains across 9 species. SeagrassDB allows for the comparative gene mining using BLAST-based approaches and subsequent unigenes sequence retrieval with associated features such as expression (FPKM values), gene ontologies, functional assignments, family level classification, Interpro domains, KEGG orthology (KO), transcription factors and prosite information. SeagrassDB is available to the scientific community for exploring the functional genic landscape of seagrass and aquatic plants at: http://115.146.91.129/index.php.
Publisher Correction: Upregulation of prefrontal metabotropic glutamate receptor 5 mediates neuropathic pain and negative mood symptoms after spinal nerve injury in rats
Authors: Chung Geehoon , Kim Chae Young , Yun Yeong-Chan , Yoon Sang Ho , Kim Myoung-Hwan , Kim Yu Kyeong , Kim Sang Jeong
Published: February 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has not been fixed in the paper.
Offenders become the victim in virtual reality: impact of changing perspective in domestic violence
Authors: Seinfeld S. , Arroyo-Palacios J. , Iruretagoyena G. , Hortensius R. , Zapata L. E. , Borland D. , de Gelder B. , Slater M. , Sanchez-Vives M. V.
Published: February 2018

The role of empathy and perspective-taking in preventing aggressive behaviors has been highlighted in several theoretical models. In this study, we used immersive virtual reality to induce a full body ownership illusion that allows offenders to be in the body of a victim of domestic abuse. A group of male domestic violence offenders and a control group without a history of violence experienced a virtual scene of abuse in first-person perspective. During the virtual encounter, the participants’ real bodies were replaced with a life-sized virtual female body that moved synchronously with their own real movements. Participants' emotion recognition skills were assessed before and after the virtual experience. Our results revealed that offenders have a significantly lower ability to recognize fear in female faces compared to controls, with a bias towards classifying fearful faces as happy. After being embodied in a female victim, offenders improved their ability to recognize fearful female faces and reduced their bias towards recognizing fearful faces as happy. For the first time, we demonstrate that changing the perspective of an aggressive population through immersive virtual reality can modify socio-perceptual processes such as emotion recognition, thought to underlie this specific form of aggressive behaviors.
A biopotential optrode array: operation principles and simulations
Authors: Al Abed Amr , Srinivas Hrishikesh , Firth Josiah , Ladouceur François , Lovell Nigel H. , Silvestri Leonardo
Published: February 2018

We propose an optical electrode ’optrode’ sensor array for biopotential measurements. The transduction mechanism is based on deformed helix ferroelectric liquid crystals which realign, altering the optrode’s light reflectance properties, relative to applied potential fields of biological cells and tissue. A computational model of extracellular potential recording by the optrode including the electro-optical transduction mechanism is presented, using a combination of time-domain and frequency-domain finite element analysis. Simulations indicate that the device has appropriate temporal response to faithfully transduce neuronal spikes, and spatial resolution to capture impulse propagation along a single neuron. These simulations contribute to the development of multi-channel optrode arrays for spatio-temporal mapping of electric events in excitable biological tissue.
Water mediated dielectric polarizability and electron charge transport properties of high resistance natural fibers
Authors: Kumar Ankit , Jash Amit , Dubey Amarish , Bajpai Alok , Philip Deepu , Bhargava Kalpana , Singh Sushil K. , Das Mainak , Banerjee S. S.
Published: February 2018

Recent studies showed that silk and human hair fibers develop thermoelectric properties at optimal water, temperature and light conditions. The nature of charge carriers and the role of water in mediating charge conduction in these fibers is an unexplored issue. By studying four different classes of natural fibers, viz., silk cocoon, human hair, jute and corn silk, we uncover their common electrical transport properties and its dependence on water concentration and temperature. All these fibers uniformly exhibit nonlinear, hysteretic current - voltage characteristics, which scale with water concentration. The optimal electrical conductivity shows thermally activated hopping transport mechanism. Scanning tunneling microscope (STM) and dielectric measurements of silk cocoon fibers showed the electronic density of states and dielectric properties of the hydrated medium enhances with water concentration. Electron paramagnetic resonance (EPR) study reveals that the charge carriers in these membranes are electronic in nature. Our results are explained through the mechanism of hopping of a Polaron, which is an electron surrounded by positive charge fluctuations created by water molecules. The mechanism unravels the peculiar role water plays in mediating electrical activity in these membranes and also opens the possibility for exploring such charge transport mechanism in other biological membranes.
Flash-induced nanowelding of silver nanowire networks for transparent stretchable electrochromic devices
Authors: Lee Chihak , Oh Youngsu , Yoon In Seon , Kim Sun Hong , Ju Byeong-Kwon , Hong Jae-Min
Published: February 2018

Electrochromic devices (ECDs) are emerging as a novel technology for various applications like commercialized smart window glasses, and auto-dimming rear-view mirrors. Recently, the development of low-power, lightweight, flexible, and stretchable devices has been accelerated to meet the growing demand in the new wearable devices market. Silver nanowires (AgNWs) can become new primary transparent conducting electrode (TCE) materials to replace indium tin oxide (ITO) for ECDs. However, issues such as substrate adhesion, delamination, and higher resistance still exist with AgNWs. Herein, we report a high-performance stretchable flash-induced AgNW-network-based TCE on surface-treated polydimethylsiloxane (PDMS) substrates. A Xe flash light method was used to create nanowelded networks of AgNWs. Surface silane treatments increased the adhesion and durability of the films as well. Finally, ECDs were fabricated under the optimal conditions and examined under strained conditions to demonstrate the resistance and mechanical behaviours of the devices. Results showed a flexible and durable film maintaining a high level of conductivity and reversible resistance behaviour, beyond those currently achievable with standard ITO/PET flexible TCEs.
2-Methoxyestradiol protects against pressure overload-induced left ventricular hypertrophy
Authors: Maayah Zaid H. , Levasseur Jody , Siva Piragasam Ramanaguru , Abdelhamid Ghada , Dyck Jason R. B. , Fahlman Richard P. , Siraki Arno G. , El-Kadi Ayman O. S.
Published: February 2018

Numerous experimental studies have supported the evidence that 2-methoxyestradiol (2 ME) is a biologically active metabolite that mediates multiple effects on the cardiovascular system, largely independent of the estrogen receptor. 2 ME is a major cytochrome P450 1B1 (CYP1B1) metabolite and has been reported to have vasoprotective and anti-inflammatory actions. However, whether 2 ME would prevent cardiac hypertrophy induced by abdominal aortic constriction (AAC) has not been investigated yet. Therefore, the overall objectives of the present study were to elucidate the potential antihypertrophic effect of 2 ME and explore the mechanism(s) involved. Our results showed that 2 ME significantly inhibited AAC-induced left ventricular hypertrophy using echocardiography. The antihypertrophic effect of 2 ME was associated with a significant inhibition of CYP1B1 and mid-chain hydroxyeicosatetraenoic acids. Based on proteomics data, the protective effect of 2 ME is linked to the induction of antioxidant and anti-inflammatory proteins in addition to the modulation of proteins involved in myocardial energy metabolism. In vitro, 2 ME has shown a direct antihypertrophic effect through mitogen-activated protein kinases- and nuclear factor-κB-dependent mechanisms. The present work shows a strong evidence that 2 ME protects against left ventricular hypertrophy. Our data suggest the potential of repurposing 2 ME as a selective CYP1B1 inhibitor for the treatment of heart failure.
Author Correction: Conjugation of wildtype and hypoallergenic mugwort allergen Art v 1 to flagellin induces IL-10-DC and suppresses allergen-specific TH2-responses in vivo
Authors: Schülke Stefan , Kuttich Kirsten , Wolfheimer Sonja , Duschek Nadine , Wangorsch Andrea , Reuter Andreas , Briza Peter , Pablos Isabel , Gadermaier Gabriele , Ferreira Fatima , Vieths Stefan , Toda Masako , Scheurer Stephan
Published: February 2018

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
Association of CD14 rs2569190 polymorphism with mortality in shock septic patients who underwent major cardiac or abdominal surgery: A retrospective study
Authors: Jiménez-Sousa María Ángeles , Liu Pilar , Medrano Luz María , Fernández-Rodríguez Amanda , Almansa Raquel , Gómez-Sánchez Esther , Rico Lucía , Lorenzo Mario , Fadrique Alejandra , Tamayo Eduardo , Resino Salvador
Published: February 2018

The aim of this study was to investigate the relationship between the CD14 rs2569190 polymorphism and death related to septic shock in white European patients who underwent major cardiac or abdominal surgery. We carried out a retrospective study in 205 septic shock patients. The septic shock diagnosis was established by international consensus definitions. The outcome variable was the death within 28, 60 and 90 days after septic shock diagnosis. The CD14 rs2569190 polymorphism was analyzed by Agena Bioscience’s MassARRAY platform. For the genetic association analysis with survival was selected a recessive inheritance model (GG vs. AA/AG). One hundred thirteen out of 205 patients (55.1%) died with a survival median of 39 days (95%CI = 30.6; 47.4). Patients with rs2569190 GG genotype had shorter survival probability than rs2569190 AA/AG genotype at 60 days (62.3% vs 50%; p = 0.035), and 90 days (62.3% vs 52.6%; p = 0.046). The rs2569190 GG genotype was associated with increased risk of septic shock-related death in the first 60 days (adjusted hazard ratio (aHR) = 1.67; p = 0.016) and 90 days (aHR = 1.64; p = 0.020) compared to rs2569190 AA/AG genotype. In conclusion, the presence of CD14 rs2569190 GG genotype was associated with death in shock septic patients who underwent major surgery. Further studies with bigger sample size are required to verify this relationship.
Spatiotemporal regulation of liver development by the Wnt/β-catenin pathway
Authors: Burke Zoë D. , Reed Karen R. , Yeh Sheng-Wen , Meniel Valerie , Sansom Owen J. , Clarke Alan R. , Tosh David
Published: February 2018

While the Wnt/β-catenin pathway plays a critical role in the maintenance of the zonation of ammonia metabolizing enzymes in the adult liver, the mechanisms responsible for inducing zonation in the embryo are not well understood. Herein we address the spatiotemporal role of the Wnt/β-catenin pathway in the development of zonation in embryonic mouse liver by conditional deletion of Apc and β-catenin at different stages of mouse liver development. In normal development, the ammonia metabolising enzymes carbamoylphosphate synthetase I (CPSI) and Glutamine synthetase (GS) begin to be expressed in separate hepatoblasts from E13.5 and E15.5 respectively and gradually increase in number thereafter. Restriction of GS expression occurs at E18 and becomes increasingly limited to the terminal perivenous hepatocytes postnatally. Expression of nuclear β-catenin coincides with the restriction of GS expression to the terminal perivenous hepatocytes. Conditional loss of Apc resulted in the expression of nuclear β-catenin throughout the developing liver and increased number of cells expressing GS. Conversely, conditional loss of β-catenin resulted in loss of GS expression. These data suggest that the Wnt pathway is critical to the development of zonation as well as maintaining the zonation in the adult liver.
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: February 2018

Since the hemorrhage in severe dengue seems to be primarily related to the defect of the platelet, the possibility that dengue virus (DENV) is selectively tropic for one of its surface receptors was investigated. Flow cytometric data of DENV-infected megakaryocytic cell line superficially expressing human glycoprotein Ib (CD42b) and glycoprotein IIb/IIIa (CD41 and CD41a) were analyzed by our custom-written software in MATLAB. In two-dimensional analyses, intracellular DENV was detected in CD42b+, CD41+ and CD41a+ cells. In three-dimensional analyses, the DENV was exclusively detected in CD42b+ cells but not in CD42b− cells regardless of the other expressions. In single-cell virus-protein analyses, the amount of DENV was directly correlated with those of CD42b at the Pearson correlation coefficient of 0.9. Moreover, RT- PCR and apoptosis assays showed that DENV was able to replicate itself and release its new progeny from the infected CD42b+ cells and eventually killed those cells. These results provide evidence for the involvement of CD42b in DENV infection.
Monolayer PdSe2: A promising two-dimensional thermoelectric material
Authors: Qin Dan , Yan Peng , Ding Guangqian , Ge Xujin , Song Hongyue , Gao Guoying
Published: February 2018

Motivated by the recent experimental synthesis of two-dimensional semiconducting film PdSe2, we investigate the electronic and thermal transport properties of PdSe2 monolayer by using the density functional theory and semiclassical Boltzmann transport equation. The calculated results reveal anisotropic transport properties. Low lattice thermal conductivity about 3 Wm−1 K −1 (300K) along the x direction is obtained, and the dimensionless thermoelectric figure of merit can reach 1.1 along the x direction for p-type doping at room temperature, indicating the promising thermoelectric performance of monolayer PdSe2.
Label-free Raman hyperspectral imaging analysis localizes the cyanogenic glucoside dhurrin to the cytoplasm in sorghum cells
Authors: Heraud Philip , Cowan Max F. , Marzec Katarzyna Maria , Møller Birger Lindberg , Blomstedt Cecilia K. , Gleadow Ros
Published: February 2018

Localisation of metabolites in sorghum coleoptiles using Raman hyperspectral imaging analysis was compared in wild type plants and mutants that lack cyanogenic glucosides. This novel method allows high spatial resolution in situ localization by detecting functional groups associated with cyanogenic glucosides using vibrational spectroscopy. Raman hyperspectral imaging revealed that dhurrin was found mainly surrounding epidermal, cortical and vascular tissue, with the greatest amount in cortical tissue. Numerous “hotspots” demonstrated dhurrin to be located within both cell walls and cytoplasm adpressed towards the plasmamembrane and not in the vacuole as previously reported. The high concentration of dhurrin in the outer cortical and epidermal cell layers is consistent with its role in defence against herbivory. This demonstrates the ability of Raman hyperspectral imaging to locate cyanogenic glucosides in intact tissues, avoiding possible perturbations and imprecision that may accompany methods that rely on bulk tissue extraction methods, such as protoplast isolation.
Microfluidic channel optimization to improve hydrodynamic dissociation of cell aggregates and tissue
Authors: Qiu Xiaolong , Huang Jen-Huang , Westerhof Trisha M. , Lombardo Jeremy A. , Henrikson Katrina M. , Pennell Marissa , Pourfard Pedram P. , Nelson Edward L. , Nath Pulak , Haun Jered B.
Published: February 2018

Maximizing the speed and efficiency at which single cells can be liberated from tissues would dramatically advance cell-based diagnostics and therapies. Conventional methods involve numerous manual processing steps and long enzymatic digestion times, yet are still inefficient. In previous work, we developed a microfluidic device with a network of branching channels to improve the dissociation of cell aggregates into single cells. However, this device was not tested on tissue specimens, and further development was limited by high cost and low feature resolution. In this work, we utilized a single layer, laser micro-machined polyimide film as a rapid prototyping tool to optimize the design of our microfluidic channels to maximize dissociation efficiency. This resulted in a new design with smaller dimensions and a shark fin geometry, which increased recovery of single cells from cancer cell aggregates. We then tested device performance on mouse kidney tissue, and found that optimal results were obtained using two microfluidic devices in series, the larger original design followed by the new shark fin design as a final polishing step. We envision our microfluidic dissociation devices being used in research and clinical settings to generate single cells from various tissue specimens for diagnostic and therapeutic applications.
Characterization of the complete mitogenome of Indian Mouse Deer, Moschiola indica (Artiodactyla: Tragulidae) and its evolutionary significance
Authors: Sarvani Rama K. , Parmar Drashti R. , Tabasum Wajeeda , Thota Neelima , Sreenivas Ara , Gaur Ajay
Published: February 2018

The mitochondrial genome of Indian mouse deer (Moschiola indica) was sequenced, assembled and characterized for the first time using 22 pairs of polymerase chain reaction (PCR) primers. The mitogenome ofM.indicawhich is 16,444 bp in size was found very similar to most vertebrates in organisation that harbours 13 protein-coding genes, 22 transfer RNA, 2 ribosomal RNA and 1A + T-rich region. Its comparison with over 52 mitogenomes of the order Artiodactyla, showed a conserved nature of gene organisation, codon usage, gene orientation and evolutionary rates of proteins except thatM. indicapossesses an extra copy oftrnF. The complete mitogenome and protein-coding genes ofM. indicawere found to be highly A + T biased. Rate of protein evolution was highest inatp8and lowest incox3. Further, a higher purifying selection pressure was found to be acting on family Tragulidae compared to Bovidae and Cervidae. The phylogenetic analysis ofM.indicaplaced the Tragulidae as sister-group of all other ruminants, similar to previous analyses.Moschiolaforms the sister-group to the other two tragulid generaTragulus(from Asia) andHyemoschus(from Africa), which is unexpected as usually the Asian species are thought to form a monophyletic group.
Conformational states during vinculin unlocking differentially regulate focal adhesion properties
Authors: Chorev Dror S. , Volberg Tova , Livne Ariel , Eisenstein Miriam , Martins Bruno , Kam Zvi , Jockusch Brigitte M. , Medalia Ohad , Sharon Michal , Geiger Benny
Published: February 2018

Focal adhesions (FAs) are multi-protein complexes that connect the actin cytoskeleton to the extracellular matrix, via integrin receptors. The growth, stability and adhesive functionality of these structures are tightly regulated by mechanical stress, yet, despite the extensive characterization of the integrin adhesome, the detailed molecular mechanisms underlying FA mechanosensitivity are still unclear. Besides talin, another key candidate for regulating FA-associated mechanosensing, is vinculin, a prominent FA component, which possesses either closed (“auto-inhibited”) or open (“active”) conformation. A direct experimental demonstration, however, of the conformational transition between the two states is still absent. In this study, we combined multiple structural and biological approaches to probe the transition from the auto-inhibited to the active conformation, and determine its effects on FA structure and dynamics. We further show that the transition from a closed to an open conformation requires two sequential steps that can differentially regulate FA growth and stability.
Challenging human locomotion: stability and modular organisation in unsteady conditions
Authors: Santuz Alessandro , Ekizos Antonis , Eckardt Nils , Kibele Armin , Arampatzis Adamantios
Published: February 2018

The need to move over uneven terrain is a daily challenge. In order to face unexpected perturbations due to changes in the morphology of the terrain, the central nervous system must flexibly modify its control strategies. We analysed the local dynamic stability and the modular organisation of muscle activation (muscle synergies) during walking and running on an even- and an uneven-surface treadmill. We hypothesized a reduced stability during uneven-surface locomotion and a reorganisation of the modular control. We found a decreased stability when switching from even- to uneven-surface locomotion (p < 0.001 in walking, p = 0.001 in running). Moreover, we observed a substantial modification of the time-dependent muscle activation patterns (motor primitives) despite a general conservation of the time-independent coefficients (motor modules). The motor primitives were considerably wider in the uneven-surface condition. Specifically, the widening was significant in both the early (+40.5%, p < 0.001) and late swing (+7.7%, p = 0.040) phase in walking and in the weight acceptance (+13.6%, p = 0.006) and propulsion (+6.0%, p = 0.041) phase in running. This widening highlighted an increased motor output’s robustness (i.e. ability to cope with errors) when dealing with the unexpected perturbations. Our results confirmed the hypothesis that humans adjust their motor control strategies’ timing to deal with unsteady locomotion.
Contributions of Pavlovian incentive motivation to cue-potentiated feeding
Authors: Marshall Andrew T. , Halbout Briac , Liu Angela T. , Ostlund Sean B.
Published: February 2018

Cues signaling the availability of palatable food acquire the ability to potentiate food seeking and consumption. The current study employed a combination of behavioral, pharmacological, and analytical techniques to probe the role of Pavlovian incentive motivation in cue-potentiated feeding. We show that a cue paired with sucrose solution (CS+) can transfer its control over feeding to stimulate sucrose consumption at a new receptacle, and that this effect depends on activation of D1 dopamine receptors, which is known to modulate other forms of cue-motivated behavior but not taste palatability. Microstructural analyses of sucrose-licking behavior revealed that the CS+ tended to increase the frequency with which rats engaged in active bouts of licking behavior without having a reliable effect on the duration of those licking bouts, a measure that was instead associated with sucrose palatability. Furthermore, we found that individual differences in CS+ elicited increases in bout frequency were associated with total sucrose intake at test, supporting the view that this process was related to meaningful dysregulation of eating behavior. The current study, therefore, (1) demonstrates that a dopamine-dependent Pavlovian incentive motivational process can mediate cue-potentiated feeding, and (2) lays out an experimental and analytical approach for parsing this aspect of behavior.
Far-UVC light: A new tool to control the spread of airborne-mediated microbial diseases
Authors: Welch David , Buonanno Manuela , Grilj Veljko , Shuryak Igor , Crickmore Connor , Bigelow Alan W. , Randers-Pehrson Gerhard , Johnson Gary W. , Brenner David J.
Published: February 2018

Airborne-mediated microbial diseases such as influenza and tuberculosis represent major public health challenges. A direct approach to prevent airborne transmission is inactivation of airborne pathogens, and the airborne antimicrobial potential of UVC ultraviolet light has long been established; however, its widespread use in public settings is limited because conventional UVC light sources are both carcinogenic and cataractogenic. By contrast, we have previously shown that far-UVC light (207–222 nm) efficiently inactivates bacteria without harm to exposed mammalian skin. This is because, due to its strong absorbance in biological materials, far-UVC light cannot penetrate even the outer (non living) layers of human skin or eye; however, because bacteria and viruses are of micrometer or smaller dimensions, far-UVC can penetrate and inactivate them. We show for the first time that far-UVC efficiently inactivates airborne aerosolized viruses, with a very low dose of 2 mJ/cm2of 222-nm light inactivating >95% of aerosolized H1N1 influenza virus. Continuous very low dose-rate far-UVC light in indoor public locations is a promising, safe and inexpensive tool to reduce the spread of airborne-mediated microbial diseases.
Giant rhyolite lava dome formation after 7.3 ka supereruption at Kikai caldera, SW Japan
Authors: Tatsumi Yoshiyuki , Suzuki-Kamata Keiko , Matsuno Tetsuo , Ichihara Hiroshi , Seama Nobukazu , Kiyosugi Koji , Nakaoka Reina , Nakahigashi Kazuo , Takizawa Hideaki , Hayashi Kazuki , Chiba Tatsuro , Shimizu Satoshi , Sano Mamoru , Iwamaru Hikaru , Morozumi Haruhisa , Sugioka Hiroko , Yamamoto Yojiro
Published: February 2018

Kikai submarine caldera to the south of the Kyushu Island, SW Japan, collapsed at 7.3 ka during the latest supereruption (>500 km3 of magma) in the Japanese Archipelago. Multi functional research surveys of the T/S Fukae Maru in this caldera, including multi-beam echosounder mapping, remotely operated vehicle observation, multi-channel seismic reflection survey, and rock sampling by dredging and diving, provided lines of evidence for creation of a giant rhyolite lava dome (~32 km3) after the caldera collapse. This dome is still active as water column anomalies accompanied by bubbling from its surface are observed. Chemical characteristics of dome-forming rhyolites akin to those of presently active small volcanic cones are different from those of supereruption. The voluminous post-caldera activity is thus not caused simply by squeezing the remnant of syn-caldera magma but may tap a magma system that has evolved both chemically and physically since the 7.3-ka supereruption.
A conserved R type Methionine Sulfoxide Reductase reverses oxidized GrpEL1/Mge1 to regulate Hsp70 chaperone cycle
Authors: Allu Praveen Kumar , Boggula Yerranna , Karri Srinivasu , Marada Adinarayana , Krishnamoorthy Thanuja , Sepuri Naresh Babu V.
Published: February 2018

Cells across evolution employ reversible oxidative modification of methionine and cysteine amino acids within proteins to regulate responses to redox stress. Previously we have shown that mitochondrial localized methionine sulfoxide reductase (Mxr2) reversibly regulates oxidized yeast Mge1 (yMge1), a co-chaperone of Hsp70/Ssc1 to maintain protein homeostasis during oxidative stress. However, the specificity and the conservation of the reversible methionine oxidation mechanism in higher eukaryotes is debatable as human GrpEL1 (hGrpEL1) unlike its homolog yMge1 harbors two methionine residues and multiple cysteines besides the mammalian mitochondria hosting R and S types of Mxrs/Msrs. In this study, using yeast as a surrogate system, we show that hGRPEL1 and R type MSRs but not the S type MSRs complement the deletion of yeast MGE1 or MXR2 respectively. Our investigations show that R type Msrs interact selectively with oxidized hGrpEL1/yMge1 in an oxidative stress dependent manner, reduce the conserved hGrpEL1-Met146-SO and rescue the Hsp70 ATPase activity. In addition, a single point mutation in hGrpEL1-M146L rescues the slow growth phenotype of yeast MXR2 deletion under oxidative duress. Our study illustrates the evolutionarily conserved formation of specific Met-R-SO in hGrpEL1/yMge1 and the essential and canonical role of R type Msrs/Mxrs in mitochondrial redox mechanism.
Asymmetrical ligand-induced cross-regulation of chemokine (C-X-C motif) receptor 4 by α1-adrenergic receptors at the heteromeric receptor complex
Authors: Gao Xianlong , Albee Lauren J. , Volkman Brian F. , Gaponenko Vadim , Majetschak Matthias
Published: February 2018

Recently, we reported that chemokine (C-X-C motif) receptor (CXCR)4 and atypical chemokine receptor 3 regulate α1-adrenergic receptors (α1-AR) through the formation of hetero-oligomeric complexes. Whether α1-ARs also regulate chemokine receptor function within such heteromeric receptor complexes is unknown. We observed that activation of α1b-AR within the α1b-AR:CXCR4 heteromeric complex leads to cross-recruitment of β-arrestin2 to CXCR4, which could not be inhibited with AMD3100. Activation of CXCR4 did not cross-recruit β-arrestin2 to α1b-AR. A peptide analogue of transmembrane domain 2 of CXCR4 interfered with α1b-AR:CXCR4 heteromerization and inhibited α1b-AR-mediated β-arrestin2 cross-recruitment. Phenylephrine (PE) induced internalization of CXCR4 in HEK293 cells co-expressing CXCR4 and α1b-AR and of endogenous CXCR4 in human vascular smooth muscle cells (hVSMC). The latter was detectable despite blockade of CXCR4 with the neutralizing antibody 12G5. hVSMC migrated towards CXCL12 and PE, but not towards a combination of CXCL12 and PE. PE inhibited CXCL12-induced chemotaxis of hVSMC (IC50: 77 ± 30 nM). Phentolamine cross-inhibited CXCL12-induced chemotaxis of hVSMC, whereas AMD3100 did not cross-inhibit PE-induced chemotaxis. These data provide evidence for asymmetrical cross-regulation of CXCR4 by α1-adrenergic receptors within the heteromeric receptor complex. Our findings provide mechanistic insights into the function of α1-AR:CXCR4 heteromers and suggest alternative approaches to modulate CXCR4 in disease conditions.
PP5 (PPP5C) is a phosphatase of Dvl2
Authors: Xie Jianlei , Han Meng , Zhang Miaojun , Deng Haiteng , Wu Wei
Published: February 2018

Dishevelled (Dvl) family proteins are key mediators of Wnt signalling and function in both canonical and noncanonical branches. Dvl2, the most studied Dvl protein, is extensively regulated by phosphorylation. Several kinases were found to be critical for Dvl2 localisation, stability control and functional segregation. For example, S143-phosphorylated Dvl2 was detected, together with CK1δ/ε, at the centrosome and basal body of primary cilia and plays pivotal roles during ciliogenesis. However, relatively less is known about Dvl dephosphorylation and the phosphatases involved. Here, we identified PP5 (PPP5C) as a phosphatase of Dvl2. PP5 interacts with and can directly dephosphorylate Dvl2. Knockdown of PP5 caused elevated Dvl2 phosphorylation both at the basal level and upon Wnt stimulation. In the Dvl2 protein, S143, the 10B5 cluster and other sites were dephosphorylated by PP5. Interestingly, comparison of PP5 with PP2A, another known Dvl2 phosphatase, revealed that PP5 and PP2A are not fully redundant in the regulation of Dvl2 phosphorylation status. In hTERT-RPE1 cells, PP5 was found at the basal body of cilia, where S143-phosphorylated Dvl2 also resides. Functional assays revealed modest effects on ciliogenesis after PP5 depletion or over-expression. Taken together, our results provided evidence to suggest PP5 as a new phosphatase for Dvl2.
Site-specific N-glycosylation analysis of soluble Fcγ receptor IIIb in human serum
Authors: Yagi Hirokazu , Takakura Daisuke , Roumenina Lubka T. , Fridman Wolf Herman , Sautès-Fridman Catherine , Kawasaki Nana , Kato Koichi
Published: February 2018

Fc-receptors for immunoglobulin G (FcγRs) mediate a variety of effector and regulatory mechanisms in the immune system.N-glycosylation of FcγRs critically affects their functions which is well exemplified by antibody-dependent cell-mediated cytotoxicity (ADCC) and phagocytosis mediated by homologous FcγRIIIa and FcγRIIIb, respectively. Although several reports describeN-glycosylation profiles of recombinant FcγRIII glycoproteins, much remains unknown regarding their native glycoforms. Here we performed site-specificN-glycosylation profiling of a soluble form of FcγRIIIb purified from human serum based on mass spectrometric analysis. Our data indicate a distinct and common tendency of the glycoforms exhibited at eachN-glycosylation site between the native and the previously reported recombinant FcγRIII glycoproteins. Among the sixN-glycosylation sites of serum soluble FcγRIIIb, Asn45 was shown to be exclusively occupied by high-mannose-type oligosaccharides, whereas the remaining sites were solely modified by the complex-type oligosaccharides with sialic acid and fucose residues. The results of our endogenous FcγRIII glycoform analyses are important for the optimization of therapeutic antibody efficacy.
Association of muscle mass and fat mass with insulin resistance and the prevalence of metabolic syndrome in Korean adults: a cross-sectional study
Authors: Kim Kyuwoong , Park Sang Min
Published: February 2018

Relationship of muscle mass and fat mass with insulin resistance and metabolic syndrome remains uncertain, especially among Asian population. We performed a cross-sectional study with 14,807 adult participants aged between 18 and 65 in the fourth and fifth Korea National Health and Nutrition Examination Survey with Dual Energy X-ray Absorptiometry (DEXA) data to investigate whether muscle mass and fat mass are associated with insulin resistance and metabolic syndrome. DEXA records were used to categorize the participants into four categories (low muscle/low fat, low muscle/high fat, high muscle/ low fat, and high muscle/high fat). Least square means and incidence rate ratios (IRR) were used to assess the associations of muscle mass and fat mass with insulin resistance and metabolic syndrome. After adjustment for potential confounders, high muscle/low fat was associated with significantly lower insulin resistance (P < 0.001) compared to low muscle/low fat. Low muscle/high fat (IRR: 1.90; 95% confidence interval [CI]:1.44–2.50, P < 0.001) and high muscle/high fat (IRR: 2.30; 95% CI:1.76–3.00, P < 0.001) were significantly associated with the prevalence of metabolic syndrome. Our study suggests that protective association of muscle mass with metabolic syndrome is attenuated by high fat mass in Korean adults.