bluuebunny/crossref_metadata_2025 huggingface dataset:
Conformational pathway provides unique sensitivity to a synaptic mGluR
Authors: Habrian Chris H. , Levitz Joshua , Vyklicky Vojtech , Fu Zhu , Hoagland Adam , McCort-Tranchepain Isabelle , Acher Francine , Isacoff Ehud Y.
Published: December 2019

Metabotropic glutamate receptors (mGluRs) are dimeric G-protein–coupled receptors that operate at synapses. Macroscopic and single molecule FRET to monitor structural rearrangements in the ligand binding domain (LBD) of the mGluR7/7 homodimer revealed it to have an apparent affinity ~4000-fold lower than other mGluRs and a maximal activation of only ~10%, seemingly too low for activation at synapses. However, mGluR7 heterodimerizes, and we find it to associate with mGluR2 in the hippocampus. Strikingly, the mGluR2/7 heterodimer has high affinity and efficacy. mGluR2/7 shows cooperativity in which an unliganded subunit greatly enhances activation by agonist bound to its heteromeric partner, and a unique conformational pathway to activation, in which mGluR2/7 partially activates in the Apo state, even when its LBDs are held open by antagonist. High sensitivity and an unusually broad dynamic range should enable mGluR2/7 to respond to both glutamate transients from nearby release and spillover from distant synapses.
Syngeneic animal models of tobacco-associated oral cancer reveal the activity of in situ anti-CTLA-4
Authors: Wang Zhiyong , Wu Victoria H. , Allevato Michael M. , Gilardi Mara , He Yudou , Luis Callejas-Valera Juan , Vitale-Cross Lynn , Martin Daniel , Amornphimoltham Panomwat , Mcdermott James , Yung Bryan S. , Goto Yusuke , Molinolo Alfredo A. , Sharabi Andrew B. , Cohen Ezra E. W. , Chen Qianming , Lyons J. Guy , Alexandrov Ludmil B. , Gutkind J. Silvio
Published: December 2019

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use is the main risk factor for HNSCC, and tobacco-associated HNSCCs have poor prognosis and response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity (≤20%) in HNSCC, highlighting the need to identify new therapeutic options. For this, mouse models that accurately mimic the complexity of the HNSCC mutational landscape and tumor immune environment are urgently needed. Here, we report a mouse HNSCC model system that recapitulates the human tobacco-related HNSCC mutanome, in which tumors grow when implanted in the tongue of immunocompetent mice. These HNSCC lesions have similar immune infiltration and response rates to anti-PD-1 (≤20%) immunotherapy as human HNSCCs. Remarkably, we find that >70% of HNSCC lesions respond to intratumoral anti-CTLA-4. This syngeneic HNSCC mouse model provides a platform to accelerate the development of immunotherapeutic options for HNSCC.
Aurora-A mediated phosphorylation of LDHB promotes glycolysis and tumor progression by relieving the substrate-inhibition effect
Authors: Cheng Aoxing , Zhang Peng , Wang Bo , Yang Dongdong , Duan Xiaotao , Jiang Yongliang , Xu Tian , Jiang Ya , Shi Jiahui , Ding Chengtao , Wu Gao , Sang Zhihong , Wu Qiang , Wang Hua , Wu Mian , Zhang Zhiyong , Pan Xin , Pan Yue-yin , Gao Ping , Zhang Huafeng , Zhou Cong-zhao , Guo Jing , Yang Zhenye
Published: December 2019

Overexpressed Aurora-A kinase promotes tumor growth through various pathways, but whether Aurora-A is also involved in metabolic reprogramming-mediated cancer progression remains unknown. Here, we report that Aurora-A directly interacts with and phosphorylates lactate dehydrogenase B (LDHB), a subunit of the tetrameric enzyme LDH that catalyzes the interconversion between pyruvate and lactate. Aurora-A-mediated phosphorylation of LDHB serine 162 significantly increases its activity in reducing pyruvate to lactate, which efficiently promotes NAD+ regeneration, glycolytic flux, lactate production and bio-synthesis with glycolytic intermediates. Mechanistically, LDHB serine 162 phosphorylation relieves its substrate inhibition effect by pyruvate, resulting in remarkable elevation in the conversions of pyruvate and NADH to lactate and NAD+. Blocking S162 phosphorylation by expression of a LDHB-S162A mutant inhibited glycolysis and tumor growth in cancer cells and xenograft models. This study uncovers a function of Aurora-A in glycolytic modulation and a mechanism through which LDHB directly contributes to the Warburg effect.
Fast and quantitative 2D and 3D orientation mapping using Raman microscopy
Authors: Ilchenko Oleksii , Pilgun Yuriy , Kutsyk Andrii , Bachmann Florian , Slipets Roman , Todeschini Matteo , Okeyo Peter Ouma , Poulsen Henning Friis , Boisen Anja
Published: December 2019

Non-destructive orientation mapping is an important characterization tool in materials science and geoscience for understanding and/or improving material properties based on their grain structure. Confocal Raman microscopy is a powerful non-destructive technique for chemical mapping of organic and inorganic materials. Here we demonstrate orientation mapping by means of Polarized Raman Microscopy (PRM). While the concept that PRM is sensitive to orientation changes is known, to our knowledge, an actual quantitative orientation mapping has never been presented before. Using a concept of ambiguity-free orientation determination analysis, we present fast and quantitative single-acquisition Raman-based orientation mapping by simultaneous registration of multiple Raman scattering spectra obtained at different polarizations. We demonstrate applications of this approach for two- and three-dimensional orientation mapping of a multigrain semiconductor, a pharmaceutical tablet formulation and a polycrystalline sapphire sample. This technique can potentially move traditional X-ray and electron diffraction type experiments into conventional optical laboratories.
A transferable machine-learning framework linking interstice distribution and plastic heterogeneity in metallic glasses
Authors: Wang Qi , Jain Anubhav
Published: December 2019

When metallic glasses (MGs) are subjected to mechanical loads, the plastic response of atoms is non-uniform. However, the extent and manner in which atomic environment signatures present in the undeformed structure determine this plastic heterogeneity remain elusive. Here, we demonstrate that novel site environment features that characterize interstice distributions around atoms combined with machine learning (ML) can reliably identify plastic sites in several Cu-Zr compositions. Using only quenched structural information as input, the ML-based plastic probability estimates (“quench-in softness” metric) can identify plastic sites that could activate at high strains, losing predictive power only upon the formation of shear bands. Moreover, we reveal that a quench-in softness model trained on a single composition and quench rate substantially improves upon previous models in generalizing to different compositions and completely different MG systems (Ni62Nb38, Al90Sm10 and Fe80P20). Our work presents a general, data-centric framework that could potentially be used to address the structural origin of any site-specific property in MGs.
Saline aqueous fluid circulation in mantle wedge inferred from olivine wetting properties
Authors: Huang Yongsheng , Nakatani Takayuki , Nakamura Michihiko , McCammon Catherine
Published: December 2019

Recently, high electrical conductors have been detected beneath some fore-arcs and are believed to store voluminous slab-derived fluids. This implies that the for-arc mantle wedge is permeable for aqueous fluids. Here, we precisely determine the dihedral (wetting) angle in an olivine–NaCl–H2O system at fore-arc mantle conditions to assess the effect of salinity of subduction-zone fluids on the fluid connectivity. We find that NaCl significantly decreases the dihedral angle to below 60° in all investigated conditions at concentrations above 5 wt% and, importantly, even at 1 wt% at 2 GPa. Our results show that slab-released fluid forms an interconnected network at relatively shallow depths of ~80 km and can partly reach the fore-arc crust without causing wet-melting and serpentinization of the mantle. Fluid transport through this permeable window of mantle wedge accounts for the location of the high electrical conductivity anomalies detected in fore-arc regions.
Nonmagnetic single-molecule spin-filter based on quantum interference
Authors: Pal Atindra Nath , Li Dongzhe , Sarkar Soumyajit , Chakrabarti Sudipto , Vilan Ayelet , Kronik Leeor , Smogunov Alexander , Tal Oren
Published: December 2019

Key spin transport phenomena, including magnetoresistance and spin transfer torque, cannot be activated without spin-polarized currents, in which one electron spin is dominant. At the nanoscale, the relevant length-scale for modern spintronics, spin current generation is rather limited due to unwanted contributions from poorly spin-polarized frontier states in ferromagnetic electrodes, or too short length-scales for efficient spin splitting by spin-orbit interaction and magnetic fields. Here, we show that spin-polarized currents can be generated in silver-vanadocene-silver single molecule junctions without magnetic components or magnetic fields. In some cases, the measured spin currents approach the limit of ideal ballistic spin transport. Comparison between conductance and shot-noise measurements to detailed calculations reveals a mechanism based on spin-dependent quantum interference that yields very efficient spin filtering. Our findings pave the way for nanoscale spintronics based on quantum interference, with the advantages of low sensitivity to decoherence effects and the freedom to use non-magnetic materials.
BEN-solo factors partition active chromatin to ensure proper gene activation in Drosophila
Authors: Ueberschär Malin , Wang Huazhen , Zhang Chun , Kondo Shu , Aoki Tsutomu , Schedl Paul , Lai Eric C. , Wen Jiayu , Dai Qi
Published: December 2019

The Drosophila genome encodes three BEN-solo proteins including Insensitive (Insv), Elba1 and Elba2 that possess activities in transcriptional repression and chromatin insulation. A fourth protein—Elba3—bridges Elba1 and Elba2 to form an ELBA complex. Here, we report comprehensive investigation of these proteins in Drosophila embryos. We assess common and distinct binding sites for Insv and ELBA and their genetic interdependencies. While Elba1 and Elba2 binding generally requires the ELBA complex, Elba3 can associate with chromatin independently of Elba1 and Elba2. We further demonstrate that ELBA collaborates with other insulators to regulate developmental patterning. Finally, we find that adjacent gene pairs separated by an ELBA bound sequence become less differentially expressed in ELBA mutants. Transgenic reporters confirm the insulating activity of ELBA- and Insv-bound sites. These findings define ELBA and Insv as general insulator proteins in Drosophila and demonstrate the functional importance of insulators to partition transcription units.
Infectious stimuli promote malignant B-cell acute lymphoblastic leukemia in the absence of AID
Authors: Rodríguez-Hernández Guillermo , Opitz Friederike V. , Delgado Pilar , Walter Carolin , Álvarez-Prado Ángel F. , González-Herrero Inés , Auer Franziska , Fischer Ute , Janssen Stefan , Bartenhagen Christoph , Raboso-Gallego Javier , Casado-García Ana , Orfao Alberto , Blanco Oscar , Alonso-López Diego , Rivas Javier De Las , Tena-Dávila Sara González de , Müschen Markus , Dugas Martin , Criado Francisco Javier García , Cenador María Begoña García , Vicente-Dueñas Carolina , Hauer Julia , Ramiro Almudena R. , Sanchez-Garcia Isidro , Borkhardt Arndt
Published: December 2019

The prerequisite to prevent childhood B-cell acute lymphoblastic leukemia (B-ALL) is to decipher its etiology. The current model suggests that infection triggers B-ALL development through induction of activation-induced cytidine deaminase (AID; also known as AICDA) in precursor B-cells. This evidence has been largely acquired through the use of ex vivo functional studies. However, whether this mechanism governs native non-transplant B-ALL development is unknown. Here we show that, surprisingly, AID genetic deletion does not affect B-ALL development in Pax5-haploinsufficient mice prone to B-ALL upon natural infection exposure. We next test the effect of premature AID expression from earliest pro-B-cell stages in B-cell transformation. The generation of AID off-target mutagenic activity in precursor B-cells does not promote B-ALL. Likewise, known drivers of human B-ALL are not preferentially targeted by AID. Overall these results suggest that infections promote B-ALL through AID-independent mechanisms, providing evidence for a new model of childhood B-ALL development.
Emotionotopy in the human right temporo-parietal cortex
Authors: Lettieri Giada , Handjaras Giacomo , Ricciardi Emiliano , Leo Andrea , Papale Paolo , Betta Monica , Pietrini Pietro , Cecchetti Luca
Published: December 2019

Humans use emotions to decipher complex cascades of internal events. However, which mechanisms link descriptions of affective states to brain activity is unclear, with evidence supporting either local or distributed processing. A biologically favorable alternative is provided by the notion of gradient, which postulates the isomorphism between functional representations of stimulus features and cortical distance. Here, we use fMRI activity evoked by an emotionally charged movie and continuous ratings of the perceived emotion intensity to reveal the topographic organization of affective states. Results show that three orthogonal and spatially overlapping gradients encode the polarity, complexity and intensity of emotional experiences in right temporo-parietal territories. The spatial arrangement of these gradients allows the brain to map a variety of affective states within a single patch of cortex. As this organization resembles how sensory regions represent psychophysical properties (e.g., retinotopy), we propose emotionotopy as a principle of emotion coding.
CO2 hydrogenation to high-value products via heterogeneous catalysis
Authors: Ye Run-Ping , Ding Jie , Gong Weibo , Argyle Morris D. , Zhong Qin , Wang Yujun , Russell Christopher K. , Xu Zhenghe , Russell Armistead G. , Li Qiaohong , Fan Maohong , Yao Yuan-Gen
Published: December 2019

Recently, carbon dioxide capture and conversion, along with hydrogen from renewable resources, provide an alternative approach to synthesis of useful fuels and chemicals. People are increasingly interested in developing innovative carbon dioxide hydrogenation catalysts, and the pace of progress in this area is accelerating. Accordingly, this perspective presents current state of the art and outlook in synthesis of light olefins, dimethyl ether, liquid fuels, and alcohols through two leading hydrogenation mechanisms: methanol reaction and Fischer-Tropsch based carbon dioxide hydrogenation. The future research directions for developing new heterogeneous catalysts with transformational technologies, including 3D printing and artificial intelligence, are provided.
Stress experience and hormone feedback tune distinct components of hypothalamic CRH neuron activity
Authors: Kim Joon S. , Han Su Young , Iremonger Karl J.
Published: December 2019

Stress leaves a lasting impression on an organism and reshapes future responses. However, the influence of past experience and stress hormones on the activity of neural stress circuits remains unclear. Hypothalamic corticotropin-releasing hormone (CRH) neurons orchestrate behavioral and endocrine responses to stress and are themselves highly sensitive to corticosteroid (CORT) stress hormones. Here, using in vivo optical recordings, we find that CRH neurons are rapidly activated in response to stress. CRH neuron activity robustly habituates to repeated presentations of the same, but not novel stressors. CORT feedback has little effect on CRH neuron responses to acute stress, or on habituation to repeated stressors. Rather, CORT preferentially inhibits tonic CRH neuron activity in the absence of stress stimuli. These findings reveal how stress experience and stress hormones modulate distinct components of CRH neuronal activity to mediate stress-induced adaptations.
Computational modeling demonstrates that glioblastoma cells can survive spatial environmental challenges through exploratory adaptation
Authors: Celiku Orieta , Gilbert Mark R. , Lavi Orit
Published: December 2019

Glioblastoma (GBM) is an aggressive type of brain cancer with remarkable cell migration and adaptation capabilities. Exploratory adaptation—utilization of random changes in gene regulation for adaptive benefits—was recently proposed as the process enabling organisms to survive unforeseen conditions. We investigate whether exploratory adaption explains how GBM cells from different anatomic regions of the tumor cope with micro-environmental pressures. We introduce new notions of phenotype and phenotype distance, and determine probable spatial-phenotypic trajectories based on patient data. While some cell phenotypes are inherently plastic, others are intrinsically rigid with respect to phenotypic transitions. We demonstrate that stochastic exploration of the regulatory network structure confers benefits through enhanced adaptive capacity in new environments. Interestingly, even with exploratory capacity, phenotypic paths are constrained to pass through specific, spatial-phenotypic ranges. This work has important implications for understanding how such adaptation contributes to the recurrence dynamics of GBM and other solid tumors.
Differential cardiovascular responses to cutaneous afferent subtypes in a nociceptive intersegmental spinal reflex
Authors: Lee Hyun Joon , White Jason M. , Chung Jumi , Malone Patrick , DeWeerth Stephen P. , Tansey Keith E.
Published: December 2019

Electrical stimulation to segmental dorsal cutaneous nerves (DCNs) activates a nociceptive sensorimotor reflex and the same afferent stimulation also evokes blood pressure (BP) and heart rate (HR) responses in rats. To investigate the relationship between those cardiovascular responses and the activation of nociceptive afferents, we analyzed BP and HR responses to electrical stimulations at each DCN from T6 to L1 at 0.5 mA to activate A-fiber alone or 5 mA to activate both A- and C-fibers at different frequencies. Evoked cardiovascular responses showed a decrease and then an increase in BP and an increase and then a plateau in HR. Segmentally, both cardiovascular responses tended to be larger when evoked from the more rostral DCNs. Stimulation frequency had a larger effect on cardiovascular responses than the rostrocaudal level of the DCN input. Stimulation strength showed a large effect on BP changes dependent on C-fibers whereas HR changes were dependent on A-fibers. Additional A-fiber activation by stimulating up to 4 adjacent DCNs concurrently, but only at 0.5 mA, affected HR but not BP. These data support that cutaneous nociceptive afferent subtypes preferentially contribute to different cardiovascular responses, A-fibers to HR and C-fibers to BP, with temporal (stimulation frequency) and spatial (rostrocaudal level) dynamics.
Collaborating constructively for sustainable biotechnology
Authors: Matthews Nicholas E. , Cizauskas Carrie A. , Layton Donovan S. , Stamford Laurence , Shapira Philip
Published: December 2019

Tackling the pressing sustainability needs of society will require the development and application of new technologies. Biotechnology, emboldened by recent advances in synthetic biology, offers to generate sustainable biologically-based routes to chemicals and materials as alternatives to fossil-derived incumbents. Yet, the sustainability potential of biotechnology is not without trade-offs. Here, we probe this capacity for sustainability for the case of bio-based nylon using both deliberative and analytical approaches within a framework ofConstructive Sustainability Assessment. We highlight the potential for life cycle CO2and N2O savings with bio-based processes, but report mixed results in other environmental and social impact categories. Importantly, we demonstrate how this knowledge can be generated collaboratively and constructively within companies at an early stage to anticipate consequences and to inform the modification of designs and applications. Application of the approach demonstrated here provides an avenue for technological actors to better understand and become responsive to the sustainability implications of their products, systems and actions.
Temporomandibular joint anchorage surgery: a 5-year follow-up study
Authors: Liu Xiuming , Zhou Zhihang , Mao Yi , Chen Xuzhuo , Zheng Jisi , Yang Chi , Zhang Shanyong , Huo Liang
Published: December 2019

The purpose of this study was to confirm the 5-year efficiency of temporomandibular joint (TMJ) anchorage, using clinical evaluation and magnetic resonance imaging (MRI). We also studied the influence of disc length and position on efficiency and postoperative condylar height. Sixty-one patients (76 joints) undergoing TMJ disc anchorage were followed up for >5 years. Visual analogue scale (VAS) score and maximum mouth-opening pre-and postsurgery were analysed and patient satisfaction recorded. Disc length, condyle height and disc position pre- and postsurgery were measured using MRI. Patients were ranked as A, B or C degree according to postoperative disc condyle position. Mean follow-up time was 71.34 months. Maximum mouth-opening improved by 14.34 ± 5.87 mm, and VAS score decreased by 33.44 ± 20.56 (P < 0.05). Clinical evaluation efficiency was 84.21%; patient satisfaction rate was 85.53%. On follow-up MRI, 68 joints were judged A or B degree (89.67%). Disc length was 7.96 ± 1.38 mm, 7.10 ± 1.41 mm and 5.75 ± 1.16 mm in A, B and C groups, respectively. In patients evaluated as C, condylar height decreased by 0.43 ± 1.36 mm, while increasing by 0.67 ± 1.88 mm and 0.51 ± 1.09 mm in A and B groups, respectively (all P < 0.05). We concluded that anchorage surgery improves mouth-opening and eliminates pain, longer disc length is related to better postoperative disc position, and significant condylar reconstruction occurs after disc repositioning. MRI confirmed that TMJ disc anchorage is reliable 5 years postsurgery.
Oral Microbiota Development in Early Childhood
Authors: Kennedy Beatrice , Peura Sari , Hammar Ulf , Vicenzi Silvia , Hedman Anna , Almqvist Catarina , Andolf Ellika , Pershagen Göran , Dicksved Johan , Bertilsson Stefan , Fall Tove
Published: December 2019

Early life determinants of the oral microbiota have not been thoroughly elucidated. We studied the association of birth and early childhood characteristics with oral microbiota composition using 16 S ribosomal RNA (rRNA) gene sequencing in a population-based Swedish cohort of 59 children sampled at 6, 12 and 24 months of age. Repeated-measurement regression models adjusted for potential confounders confirmed and expanded previous knowledge about the profound shift of oral microbiota composition in early life. These alterations included increased alpha diversity, decreased beta diversity and alteration of bacterial composition with changes in relative abundance of 14 of the 20 most common operational taxonomic units (OTUs). We also found that birth characteristics, breastfeeding and antibiotic use were associated with overall phyla distribution and/or with the relative abundance of specific OTUs. Further, we detected a novel link between morning salivary cortisol level, a physiological marker of neuroendocrine activity and stress, and overall phyla distribution as well as with decreased abundance of the most common OTU mapped to the Streptococcaceae family. In conclusion, a major part of the maturation of the oral microbiome occurs during the first two years of life, and this development may be influenced by early life circumstances.
The improvement of photocatalysis O2 production over BiVO4 with amorphous FeOOH shell modification
Authors: Zhang Ying , Shi Lei , Geng Zhongxing , Ren Tieqiang , Yang Zhanxu
Published: December 2019

A novel amorphous FeOOH modified BiVO4 photocatalyst (A-FeOOH/BiVO4) was successfully produced and characterized by various techniques. The results showed that amorphous FeOOH with about 2 nm thickness evenly covered on BiVO4 surface, which caused resultant A-FeOOH/BiVO4 exhibiting higher visible light photocatalytic performance for producing O2 from water than BiVO4. When the covered amount of amorphous FeOOH was 8%, the resultant photocatalyst possessed the best photocatalytic performance. To find the reasons for the improvement of photocatalytic property, electrochemical experiments, DRS, PL and BET, were also measured, the experimental results indicated that interface effect between amorphous FeOOH and BiVO4 could conduce to migration of photogenerated charge, and exhibit stronger light responded capacity. These positive factors promoted A-FeOOH/BiVO4 presenting improved the photocatalytic performance. In a word, the combination of amorphous FeOOH with BiVO4 is an effective strategy to conquer important challenges in photocatalysis field.
Hermaphrodites and parasitism: size-specific female reproduction drives infection by an ephemeral parasitic castrator
Authors: Fong Caitlin R. , Kuris Armand M. , Hechinger Ryan F.
Published: December 2019

Sex can influence patterns of parasitism because males and females can differ in encounter with, and susceptibility to, parasites. We investigate an isopod parasite (Hemioniscus balani) that consumes ovarian fluid, blocking female function of its barnacle host, a simultaneous hermaphrodite. As a hermaphrodite, sex is fluid, and individuals may allocate energy differentially to male versus female reproduction. We predicted the relationship between barnacle size and female reproductive function influences the distribution of parasites within barnacle populations. We surveyed 12 populations spanning ~400 km of coastline of southern California and found intermediate-sized barnacles where most likely to be actively functioning as females. While it is unclear why larger individuals are less likely to be actively reproducing as females, we suggest this reduced likelihood is driven by increased investment in male reproductive effort at larger sizes. The female function-size relationship was mirrored by the relationship between size and parasitism. We suggest parasitism by Hemioniscus balani imposes a cost to female function, reinforcing the lack of investment in female function by the largest individuals. Within the subset of suitable (=female) hosts, infection probability increased with size. Hence, the distribution of female function, combined with selection for larger hosts, primarily dictated patterns of infection.
MicroRNA-509-3p inhibits cellular migration, invasion, and proliferation, and sensitizes osteosarcoma to cisplatin
Authors: Patil Sagar L. , Palat Asha , Pan Yinghong , Rajapakshe Kimal , Mirchandani Rachna , Bondesson Maria , Yustein Jason T. , Coarfa Cristian , Gunaratne Preethi H.
Published: December 2019

Osteosarcoma (OS) is the most common primary pediatric malignancy of the bone having poor prognosis and long-term survival rates of less than 30% in patients with metastasis. MicroRNA-509 was reported to be downregulated in OS. We and others previously published that miR-509-3p can strongly attenuate cellular migration/invasion and sensitize ovarian cancer to cisplatin. Here, we show that overexpression of miR-509-3p inhibited migration of primary OS cell lines U2OS, HOS, and SaOS2 as well as metastatic derivatives 143B and LM7. miR-509-3p overexpression also inhibited proliferation and invasion of HOS and 143B cells and sensitized cells to cisplatin. Luciferase reporter assays using 3′-UTRs of predicted miR-509-3p targets associated with metastatic phenotypes revealed ARHGAP1 could be one of the downstream effectors of miR-509-3p in HOS. To find the global impact of miR-509-3p overexpression and cisplatin treatment we performed Reverse Phase Protein Analysis (RPPA). AXL, which has been reported to play a critical role in cisplatin resistance and confirmed as direct target of miR-509-3p was downregulated upon miR-509-3p treatment and further down-regulated upon miR-509-3p + cisplatin treatment. We propose that the miR-509-3p/AXL and miR-509-3p/ARHGAP1 axes have the potential to uncover new druggable targets for the treatment of drug resistant metastatic osteosarcoma.
Microwave magnetic field modulation of spin torque oscillator based on perpendicular magnetic tunnel junctions
Authors: Skowroński Witold , Chęciński Jakub , Ziętek Sławomir , Yakushiji Kay , Yuasa Shinji
Published: December 2019

Modulation of a microwave signal generated by the spin-torque oscillator (STO) based on a magnetic tunnel junction (MTJ) with perpendicularly magnetized free layer is investigated. Magnetic field inductive loop was created during MTJ fabrication process, which enables microwave field application during STO operation. The frequency modulation by the microwave magnetic field of up to 3 GHz is explored, showing a potential for application in high-data-rate communication technologies. Moreover, an inductive loop is used for self-synchronization of the STO signal, which after field-locking, exhibits significant improvement of the linewidth and oscillation power.
Photonic reservoir computing based on nonlinear wave dynamics at microscale
Authors: Sunada Satoshi , Uchida Atsushi
Published: December 2019

High-dimensional nonlinear dynamical systems, including neural networks, can be utilized as computational resources for information processing. In this sense, nonlinear wave systems are good candidates for such computational resources. Here, we propose and numerically demonstrate information processing based on nonlinear wave dynamics in microcavity lasers, i.e., optical spatiotemporal systems at microscale. A remarkable feature is its ability of high-dimensional and nonlinear mapping of input information to the wave states, enabling efficient and fast information processing at microscale. We show that the computational capability for nonlinear/memory tasks is maximized at the edge of dynamical stability. Moreover, we show that computational capability can be enhanced by applying a time-division multiplexing technique to the wave dynamics. Thus, the computational potential of the wave dynamics can sufficiently be extracted even when the number of detectors to monitor the wave states is limited. In addition, we discuss the merging of optical information processing with optical sensing, revealing a novel method for model-free sensing by using a microcavity reservoir as a sensing element. These results pave a way for on-chip photonic computing with high-dimensional dynamics and a model-free sensing method.
Phylogeographic patterns of intertidal arthropods (Acari, Oribatida) from southern Japanese islands reflect paleoclimatic events
Authors: Pfingstl Tobias , Wagner Maximilian , Hiruta Shimpei F. , Koblmüller Stephan , Hagino Wataru , Shimano Satoshi
Published: December 2019

The Japanese islands represent one of the world’s biodiversity hotspots. Their geological history and present geography resulted in a high number of endemic species in nearly all major metazoan clades. We investigated the phylogeography of three different intertidal mite species from the Ryukyu islands and southern mainland by means of morphometry and molecular genetics. None of the species represents an endemic, nearly all show distributions ranging over at least the southern and central Ryukyus. Two species, Fortuynia shibai and F. churaumi sp. n. clearly represent sister species that are derived from a common Eastern ancestor. Molecular genetic results indicate that these species separated approx. 3 Ma before the opening of the Okinawa trough, whereas F. shibai most likely showed an ancestral distribution stretching from the central Ryukyus across the Tokara strait to Japanese mainland, whereas F. churaumi probably evolved somewhere south of the Tokara strait. Phylogenetic data further indicates that long periods of isolation resulted in heterogeneous genetic structure but subsequent low sea level stands during Pleistocene allowed recent expansion and gene flow between island populations. Comparing these patterns with those of other animals, these tiny wingless mites apparently show better dispersal abilities than partially volant terrestrial organism groups.
Phonetic relevance and phonemic grouping of speech in the automatic detection of Parkinson’s Disease
Authors: Moro-Velazquez Laureano , Gomez-Garcia Jorge A. , Godino-Llorente Juan I. , Grandas-Perez Francisco , Shattuck-Hufnagel Stefanie , Yagüe-Jimenez Virginia , Dehak Najim
Published: December 2019

Literature documents the impact of Parkinson’s Disease (PD) on speech but no study has analyzed in detail the importance of the distinct phonemic groups for the automatic identification of the disease. This study presents new approaches that are evaluated in three different corpora containing speakers suffering from PD with two main objectives: to investigate the influence of the different phonemic groups in the detection of PD and to propose more accurate detection schemes employing speech. The proposed methodology uses GMM-UBM classifiers combined with a technique introduced in this paper called phonemic grouping, that permits observation of the differences in accuracy depending on the manner of articulation. Cross-validation results reach accuracies between 85% and 94% with AUC ranging from 0.91 to 0.98, while cross-corpora trials yield accuracies between 75% and 82% with AUC between 0.84 and 0.95, depending on the corpus. This is the first work analyzing the generalization properties of the proposed approaches employing cross-corpora trials and reaching high accuracies. Among the different phonemic groups, results suggest that plosives, vowels and fricatives are the most relevant acoustic segments for the detection of PD with the proposed schemes. In addition, the use of text-dependent utterances leads to more consistent and accurate models.
Trajectory of vitamin D, micronutrient status and childhood growth in exclusively breastfed children
Authors: Liao Sui-Ling , Yao Tsung-Chieh , Hua Man-Chin , Tsai Ming-Han , Hsu Shih-Yun , Chen Li-Chen , Yeh Kuo-Wei , Chiu Chih-Yung , Lai Shen-Hao , Huang Jing-Long
Published: December 2019

This study aimed to compare the trajectory of serum 25(OH)D, micronutrient levels, and anthropometric measurements between exclusively breastfed and mixed-fed children. This is a prospective cohort study. Anthropometric measurements of the children were obtained during scheduled clinical visits. Tests for 25(OHD), ferritin, zinc and complete blood count were performed yearly until 3 years of age. Clinical records and questionnaires on dietary habits were obtained. The results showed that despite official recommendations on vitamin D/iron supplements for breastfed children, less than 10% of our exclusively breastfed children received regular supplements. Thus, after 1 year, the odds for having iron deficiency anemia and vitamin D insufficiency were 9 [95% CI, 4–19] and 6 [95% CI, 2–16], respectively. Longitudinal follow-up showed the prevalence of iron deficiency to decrease from 34% at 1 year to 2% at age 3 years. However, the prevalence of vitamin D insufficiency remained persistently high throughout the first three years of life (60% at 1 to 44% at 3 years). Very few children had zinc deficiency. Anthropometric measurements showed exclusively breastfed children to have lower mean z-scores for body weight and height when compared to mixed-fed children after 12 months. In conclusion, children who were exclusively breastfed for longer than 4 months without proper supplement were more likely to have transient iron deficiency anemia and persistent vitamin D insufficiency. Their growth became relatively slower after infancy. Whether this was associated with underlying inadequate serum vitamin D and iron level remains an important issue to be explored.
Cosolvent Analysis Toolkit (CAT): a robust hotspot identification platform for cosolvent simulations of proteins to expand the druggable proteome
Authors: Sabanés Zariquiey Francesc , de Souza João V. , Bronowska Agnieszka K.
Published: December 2019

Cosolvent Molecular Dynamics (MD) simulations are increasingly popular techniques developed for prediction and characterization of allosteric and cryptic binding sites, which can be rendered “druggable” by small molecule ligands. Despite their conceptual simplicity and effectiveness, the analysis of cosolvent MD trajectories relies on pocket volume data, which requires a high level of manual investigation and may introduce a bias. In this work, we present CAT (Cosolvent Analysis Toolkit): an open-source, freely accessible analytical tool, suitable for automated analysis of cosolvent MD trajectories. CAT is compatible with commonly used molecular graphics software packages such as UCSF Chimera and VMD. Using a novel hybrid empirical force field scoring function, CAT accurately ranks the dynamic interactions between the macromolecular target and cosolvent molecules. To benchmark, CAT was used for three validated protein targets with allosteric and orthosteric binding sites, using five chemically distinct cosolvent molecules. For all systems, CAT has accurately identified all known sites. CAT can thus assist in computational studies aiming at identification of protein “hotspots” in a wide range of systems. As an easy-to-use computational tool, we expect that CAT will contribute to an increase in the size of the potentially ‘druggable’ human proteome.
Encoding Temporal Regularities and Information Copying in Hippocampal Circuits
Authors: Roberts Terri P. , Kern Felix B. , Fernando Chrisantha , Szathmáry Eörs , Husbands Phil , Philippides Andrew O. , Staras Kevin
Published: December 2019

Discriminating, extracting and encoding temporal regularities is a critical requirement in the brain, relevant to sensory-motor processing and learning. However, the cellular mechanisms responsible remain enigmatic; for example, whether such abilities require specific, elaborately organized neural networks or arise from more fundamental, inherent properties of neurons. Here, using multi-electrode array technology, and focusing on interval learning, we demonstrate that sparse reconstituted rat hippocampal neural circuits are intrinsically capable of encoding and storing sub-second-order time intervals for over an hour timescale, represented in changes in the spatial-temporal architecture of firing relationships among populations of neurons. This learning is accompanied by increases in mutual information and transfer entropy, formal measures related to information storage and flow. Moreover, temporal relationships derived from previously trained circuits can act as templates for copying intervals into untrained networks, suggesting the possibility of circuit-to-circuit information transfer. Our findings illustrate that dynamic encoding and stable copying of temporal relationships are fundamental properties of simple in vitro networks, with general significance for understanding elemental principles of information processing, storage and replication.
The TreaT-Assay: A Novel Urine-Derived Donor Kidney Cell-Based Assay for Prediction of Kidney Transplantation Outcome
Authors: Thieme Constantin J. , Weist Benjamin J. D. , Mueskes Annemarie , Roch Toralf , Stervbo Ulrik , Rosiewicz Kamil , Wehler Patrizia , Stein Maik , Nickel Peter , Kurtz Andreas , Lachmann Nils , Choi Mira , Schmueck-Henneresse Michael , Westhoff Timm H. , Reinke Petra , Babel Nina
Published: December 2019

Donor-reactive immunity plays a major role in rejection after kidney transplantation, but analysis of donor-reactive T-cells is not applied routinely. However, it has been shown that this could help to identify patients at risk of acute rejection. A major obstacle is the limited quantity or quality of the required allogenic stimulator cells, including a limited availability of donor-splenocytes or an insufficient HLA-matching with HLA-bank cells. To overcome these limitations, we developed a novel assay, termed the TreaT (Transplant reactive T-cells)-assay. We cultivated renal tubular epithelial cells from the urine of kidney transplant patients and used them as stimulators for donor-reactive T-cells, which we analyzed by flow cytometry. We could demonstrate that using the TreaT-assay the quantification and characterization of alloreactive T-cells is superior to other stimulators. In a pilot study, the number of pre-transplant alloreactive T-cells negatively correlated with the post-transplant eGFR. Frequencies of pre-transplant CD161+alloreactive CD4+T-cells and granzyme B producing alloreactive CD8+T-cells were substantially higher in patients with early acute rejection compared to patients without complications. In conclusion, we established a novel assay for the assessment of donor-reactive memory T-cells based on kidney cells with the potential to predict early acute rejection and post-transplant eGFR.
Interactions between sleep disturbances and Alzheimer’s disease on brain function: a preliminary study combining the static and dynamic functional MRI
Authors: Li Kaicheng , Luo Xiao , Zeng Qingze , Jiaerken Yerfan , Wang Shuyue , Xu Xiaopei , Xu Xiaojun , Xu Jingjing , Wang Chao , Zhou Jiong , Huang Peiyu , Zhang Minming
Published: December 2019

Though sleep disturbance constitutes the risk factor for Alzheimer’s disease (AD), the underlying mechanism is still unclear. This study aims to explore the interaction between sleep disturbances and AD on brain function. We included 192 normal controls, 111 mild cognitive impairment (MCI), and 30 AD patients, with either poor or normal sleep (PS, NS, respectively). To explore the strength and stability of brain activity, we used static amplitude of low-frequency fluctuation (sALFF) and dynamic ALFF (dALFF) variance. Further, we examined white matter hyperintensities (WMH) and amyloid PET deposition, representing the vascular risk factor and AD-related hallmark, respectively. We observed that sleep disturbance significantly interacted with disease severity, exposing distinct effects on sALFF and dALFF variance. Interestingly, PS groups showed the dALFF variance trajectory of initially increased, then decreased and finally increased along the AD spectrum, while showing the opposite trajectory of sALFF. Further correlation analysis showed that the WMH burden correlates with dALFF variance in PS groups. Conclusively, our study suggested that sleep disturbance interacts with AD severity, expressing as effects of compensatory in MCI and de-compensatory in AD, respectively. Further, vascular impairment might act as important pathogenesis underlying the interaction effect between sleep and AD.
Different level of virtualization of sight and touch produces the uncanny valley of avatar’s hand embodiment
Authors: D’Alonzo M. , Mioli A. , Formica D. , Vollero L. , Di Pino G.
Published: December 2019

Humans increasingly often act through virtual and robotic avatars, which can feed back to their user only virtual sensory information. Since avatar is user’s embodiment and body image is mostly based on senses, how virtualization of sensory inputs affects avatar self-attribution is a key question for understanding nowadays human behavior. By manipulating visual and tactile inputs in a series of experiments fashioned after the rubber hand illusion, we assessed the relative weight of the virtualization of sight (Real, Robotic, Virtual) and of touch (Real, Virtual) on artificial hand embodiment. Virtualization decreased embodiment, but unexpectedly lowest embodiment was found when only one sense was virtual. Discordant levels of virtualization of sight and touch elicited revulsion, extending the concept of the uncanny valley to avatar embodiment. Besides timing, spatial constraints and realism of feedback, a matched degree of virtualization of seen and felt stimuli is a further constraint in building the representation of the body.
Association between anemia and hyperuricemia: results from the Korean National Health and Nutrition Examination Survey
Authors: Eun Yeonghee , Han Kyung-Do , Kim Da Hye , Kim In Young , Park Eun-Jung , Lee Seulkee , Cha Hoon-Suk , Koh Eun-Mi , Lee Jaejoon , Kim Hyungjin
Published: December 2019

Hyperuricemia and anemia share several comorbidities, but the association between the two conditions remains unclear. The purpose of this study was to investigate the association between hyperuricemia and anemia. Data of 10794 subjects from the Korean National Health and Nutrition Examination Survey conducted in 2016–2017 were analyzed using multivariate logistic regression analyses. An association between anemia and hyperuricemia was not evident in subjects without chronic kidney disease (CKD). In patients with CKD, anemia increased the risk of hyperuricemia by 2-fold. This association remained significant when adjusting for the glomerular filtration rate. In subgroup analyses, the association of anemia with hyperuricemia was significant in subjects aged ≥65 years, and in those with diabetes or hypertension. Subgroup analyses of CKD patients showed similar results. In the current study using data from Korean representative samples, anemia in subjects with CKD was associated with a 2-fold increase in the risk of hyperuricemia, which remained significant even after adjustment for renal function.
Correlates of individual variation in the porphyrin-based fluorescence of red-necked nightjars (Caprimulgus ruficollis)
Authors: Camacho Carlos , Negro Juan José , Redondo Iraida , Palacios Sebastián , Sáez-Gómez Pedro
Published: December 2019

Many nocturnal animals, including invertebrates such as scorpions and a variety of vertebrate species, including toadlets, flying squirrels, owls, and nightjars, emit bright fluorescence under ultraviolet light. However, the ecological significance of this unique coloration so attached to nocturnality remains obscure. Here, we used an intensively studied population of migratory red-necked nightjars (Caprimulgus ruficollis) to investigate inter-individual variation in porphyrin-based pink fluorescence according to sex, age, body condition, time of the year, and the extent of white plumage patches known to be involved in sexual communication. Males and females exhibited a similar extent of pink fluorescence on the under-side of the wings in both juvenile and adult birds, but males had larger white patches than females. Body condition predicted the extent of pink fluorescence in juvenile birds, but not in adults. On average, the extent of pink fluorescence in juveniles increased by ca. 20% for every 10-g increase in body mass. For both age classes, there was a slight seasonal increase (1–4% per week) in the amount of fluorescence. Our results suggest that the porphyrin-based coloration of nightjars might signal individual quality, at least in their first potential breeding season, although the ability of these and other nocturnal birds to perceive fluorescence remains to be unequivocally proven.