bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatoma cell‐derived leptin downregulates the immunosuppressive function of regulatory T‐cells to enhance the anti‐tumor activity of CD8+ T‐cells
Authors: Wei Renxiong , Hu Yaoren , Dong Feibo , Xu Xiaozhen , Hu Airong , Gao Guosheng
Published: December 2015

The adaptive immune response against hepatocellular carcinoma (HCC) could be a therapeutic target to restrain HCC initiation and growth. The interactions between hepatoma cells and immune cells modify the anti‐tumor immunity to influence hepatoma cell survival. To explore the potential interplay between hepatoma cells and anti‐HCC T‐cells, we conducted a HCC induction mouse model to analyze the phenotypic and functional alterations of T‐cell subsets. We found that both hepatoma tissues and hepatoma cell lines substantially produced higher leptin, which is an adipokine usually expressed in fat tissue, than normal liver tissue or hepatocytes. We also found that regulatory T‐cells (Tregs), effector CD4+ T‐cells and CD8+ T‐cells upregulated expression of leptin receptor (LEPR) in spleens and livers after HCC induction. In vitro study showed that macrophages and dendritic cells isolated from HCC livers upregulated LEPR expression on T‐cells. Leptin inhibited Treg activation and function in vitro, demonstrated by lower expression of TGF‐β, IL‐10, CTLA4 and GITR in Tregs, as wells weaker suppression of CD8+ T‐cell proliferation and production of cytotoxic mediators. In addition, silencing LEPR in Tregs favored tumor growth in a hepatoma cell line allograft model. Taken together, our study suggests that hepatoma cells could enhance anti‐HCC immunity through secreting leptin to down‐regulate Treg activity and subsequently promote CD8+ T‐cell response.
Resonant magnetoelastic microstructures for wireless actuation of liquid flow on 3D surfaces and use in glaucoma drainage implants
Authors: Pepakayala Venkatram , Stein Joshua , Gianchandani Yogesh
Published: December 2015

Magnetoelastic resonators made from metal alloy foils are widely used for miniature wireless anti-theft tags and have also been explored for use in various sensing applications. Through annealing within three-dimensional (3D) molds, these foils can be formed into curved structures. Consequently, magnetoelastic materials present an opportunity for the development of a new class of wireless, actuators that have small form factors and low surface profiles and that can conform to curved surfaces. This paper describes passive, wireless, resonant magnetoelastic actuators intended for the generation of fluid flow on the surfaces of implantable Ahmed glaucoma drainage devices. The actuators are remotely excited to resonance using a magnetic field generated by external coils. The fluid flow is intended to limit cellular adhesion to the surface of the implant, as this adhesion can ultimately lead to implant encapsulation and failure. The actuators are micromachined from planar 29-μm-thick foils of Metglas 2826MB (Fe40Ni38Mo4B18), an amorphous magnetoelastic alloy, using photochemical machining. Measuring 10.3 × 5.6 mm2, the planar structures are annealed in 3D molds to conform to the surface of the drainage device, which has an aspherical curvature. Six actuator designs are described, with varying shapes and resonant mode shapes. The resonant frequencies for the different designs vary from 520 Hz to 4.7 kHz. Flow velocities of up to 266 μm s−1 are recorded at a wireless activation range of 25–30 mm, with peak actuator vibration amplitudes of 1.5 μm. Integrated actuators such as those described here have the potential to greatly enhance the effectiveness of glaucoma drainage devices at lowering eye pressure and may also be useful in other areas of medicine.
Ultrahigh-throughput discovery of promiscuous enzymes by picodroplet functional metagenomics
Authors: Colin Pierre-Yves , Kintses Balint , Gielen Fabrice , Miton Charlotte M. , Fischer Gerhard , Mohamed Mark F. , Hyvönen Marko , Morgavi Diego P. , Janssen Dick B , Hollfelder Florian
Published: December 2015

Unculturable bacterial communities provide a rich source of biocatalysts, but their experimental discovery by functional metagenomics is difficult, because the odds are stacked against the experimentor. Here we demonstrate functional screening of a million-membered metagenomic library in microfluidic picolitre droplet compartments. Using bait substrates, new hydrolases for sulfate monoesters and phosphotriesters were identified, mostly based on promiscuous activities presumed not to be under selection pressure. Spanning three protein superfamilies, these break new ground in sequence space: promiscuity now connects enzymes with only distantly related sequences. Most hits could not have been predicted by sequence analysis, because the desired activities have never been ascribed to similar sequences, showing how this approach complements bioinformatic harvesting of metagenomic sequencing data. Functional screening of a library of unprecedented size with excellent assay sensitivity has been instrumental in identifying rare genes constituting catalytically versatile hubs in sequence space as potential starting points for the acquisition of new functions.
Recruitment of Pontin/Reptin by E2f1 amplifies E2f transcriptional response during cancer progression
Authors: Tarangelo Amy , Lo Nathanael , Teng Rebecca , Kim Eunsun , Le Linh , Watson Deborah , Furth Emma E. , Raman Pichai , Ehmer Ursula , Viatour Patrick
Published: December 2015

Changes in gene expression during tumorigenesis are often considered the consequence of de novo mutations occurring in the tumour. An alternative possibility is that the transcriptional response of oncogenic transcription factors evolves during tumorigenesis. Here we show that aberrant E2f activity, following inactivation of the Rb gene family in a mouse model of liver cancer, initially activates a robust gene expression programme associated with the cell cycle. Slowly accumulating E2f1 progressively recruits a Pontin/Reptin complex to open the chromatin conformation at E2f target genes and amplifies the E2f transcriptional response. This mechanism enhances the E2f-mediated transactivation of cell cycle genes and initiates the activation of low binding affinity E2f target genes that regulate non-cell-cycle functions, such as the Warburg effect. These data indicate that both the physiological and the oncogenic activities of E2f result in distinct transcriptional responses, which could be exploited to target E2f oncogenic activity for therapy.
Quadratic Fermi node in a 3D strongly correlated semimetal
Authors: Kondo Takeshi , Nakayama M. , Chen R. , Ishikawa J. J. , Moon E.-G. , Yamamoto T. , Ota Y. , Malaeb W. , Kanai H. , Nakashima Y. , Ishida Y. , Yoshida R. , Yamamoto H. , Matsunami M. , Kimura S. , Inami N. , Ono K. , Kumigashira H. , Nakatsuji S. , Balents L. , Shin S.
Published: December 2015

Strong spin–orbit coupling fosters exotic electronic states such as topological insulators and superconductors, but the combination of strong spin–orbit and strong electron–electron interactions is just beginning to be understood. Central to this emerging area are the 5d transition metal iridium oxides. Here, in the pyrochlore iridate Pr2Ir2O7, we identify a non-trivial state with a single-point Fermi node protected by cubic and time-reversal symmetries, using a combination of angle-resolved photoemission spectroscopy and first-principles calculations. Owing to its quadratic dispersion, the unique coincidence of four degenerate states at the Fermi energy, and strong Coulomb interactions, non-Fermi liquid behaviour is predicted, for which we observe some evidence. Our discovery implies that Pr2Ir2O7 is a parent state that can be manipulated to produce other strongly correlated topological phases, such as topological Mott insulator, Weyl semimetal, and quantum spin and anomalous Hall states.
Structural basis of DNA gyrase inhibition by antibacterial QPT-1, anticancer drug etoposide and moxifloxacin
Authors: Chan Pan F. , Srikannathasan Velupillai , Huang Jianzhong , Cui Haifeng , Fosberry Andrew P. , Gu Minghua , Hann Michael M. , Hibbs Martin , Homes Paul , Ingraham Karen , Pizzollo Jason , Shen Carol , Shillings Anthony J. , Spitzfaden Claus E. , Tanner Robert , Theobald Andrew J. , Stavenger Robert A. , Bax Benjamin D. , Gwynn Michael N.
Published: December 2015

New antibacterials are needed to tackle antibiotic-resistant bacteria. Type IIA topoisomerases (topo2As), the targets of fluoroquinolones, regulate DNA topology by creating transient double-strand DNA breaks. Here we report the first co-crystal structures of the antibacterial QPT-1 and the anticancer drug etoposide with Staphylococcus aureus DNA gyrase, showing binding at the same sites in the cleaved DNA as the fluoroquinolone moxifloxacin. Unlike moxifloxacin, QPT-1 and etoposide interact with conserved GyrB TOPRIM residues rationalizing why QPT-1 can overcome fluoroquinolone resistance. Our data show etoposide’s antibacterial activity is due to DNA gyrase inhibition and suggests other anticancer agents act similarly. Analysis of multiple DNA gyrase co-crystal structures, including asymmetric cleavage complexes, led to a ‘pair of swing-doors’ hypothesis in which the movement of one DNA segment regulates cleavage and religation of the second DNA duplex. This mechanism can explain QPT-1’s bacterial specificity. Structure-based strategies for developing topo2A antibacterials are suggested.
Corticostriatal pathways contribute to the natural time course of positive mood
Authors: Admon Roee , Pizzagalli Diego A.
Published: December 2015

The natural time course of mood includes both acute responses to stimuli and spontaneous fluctuations. To date, neuroimaging studies have focused on either acute affective responses or spontaneous neural fluctuations at rest but no prior study has concurrently probed both components, or how mood disorders might modulate these processes. Here, using fMRI, we capture the acute affective and neural responses to naturalistic positive mood induction, as well as their spontaneous fluctuations during resting states. In both healthy controls and individuals with a history of depression, our manipulation acutely elevates positive mood and ventral striatum activation. Only controls, however, sustain positive mood over time, and this effect is accompanied by the emergence of a reciprocal relationship between the ventral striatum and medial prefrontal cortex during ensuing rest. Findings suggest that corticostriatal pathways contribute to the natural time course of positive mood fluctuations, while disturbances of those neural interactions may characterize mood disorder.
Hybrid integrated biological–solid-state system powered with adenosine triphosphate
Authors: Roseman Jared M. , Lin Jianxun , Ramakrishnan Siddharth , Rosenstein Jacob K. , Shepard Kenneth L.
Published: December 2015

There is enormous potential in combining the capabilities of the biological and the solid state to create hybrid engineered systems. While there have been recent efforts to harness power from naturally occurring potentials in living systems in plants and animals to power complementary metal-oxide-semiconductor integrated circuits, here we report the first successful effort to isolate the energetics of an electrogenic ion pump in an engineered in vitro environment to power such an artificial system. An integrated circuit is powered by adenosine triphosphate through the action of Na+/K+ adenosine triphosphatases in an integrated in vitro lipid bilayer membrane. The ion pumps (active in the membrane at numbers exceeding 2 × 106 mm−2) are able to sustain a short-circuit current of 32.6 pA mm−2 and an open-circuit voltage of 78 mV, providing for a maximum power transfer of 1.27 pW mm−2 from a single bilayer. Two series-stacked bilayers provide a voltage sufficient to operate an integrated circuit with a conversion efficiency of chemical to electrical energy of 14.9%.
Tank binding kinase 1 is a centrosome-associated kinase necessary for microtubule dynamics and mitosis
Authors: Pillai Smitha , Nguyen Jonathan , Johnson Joseph , Haura Eric , Coppola Domenico , Chellappan Srikumar
Published: December 2015

TANK Binding Kinase 1 (TBK1) is a non-canonical IκB kinase that contributes to KRAS-driven lung cancer. Here we report that TBK1 plays essential roles in mammalian cell division. Specifically, levels of active phospho-TBK1 increase during mitosis and localize to centrosomes, mitotic spindles and midbody, and selective inhibition or silencing of TBK1 triggers defects in spindle assembly and prevents mitotic progression. TBK1 binds to the centrosomal protein CEP170 and to the mitotic apparatus protein NuMA, and both CEP170 and NuMA are TBK1 substrates. Further, TBK1 is necessary for CEP170 centrosomal localization and binding to the microtubule depolymerase Kif2b, and for NuMA binding to dynein. Finally, selective disruption of the TBK1–CEP170 complex augments microtubule stability and triggers defects in mitosis, suggesting that TBK1 functions as a mitotic kinase necessary for microtubule dynamics and mitosis.
Left–right asymmetric cell intercalation drives directional collective cell movement in epithelial morphogenesis
Authors: Sato Katsuhiko , Hiraiwa Tetsuya , Maekawa Emi , Isomura Ayako , Shibata Tatsuo , Kuranaga Erina
Published: December 2015

Morphogenetic epithelial movement occurs during embryogenesis and drives complex tissue formation. However, how epithelial cells coordinate their unidirectional movement while maintaining epithelial integrity is unclear. Here we propose a novel mechanism for collective epithelial cell movement based on Drosophila genitalia rotation, in which epithelial tissue rotates clockwise around the genitalia. We found that this cell movement occurs autonomously and requires myosin II. The moving cells exhibit repeated left–right-biased junction remodelling, while maintaining adhesion with their neighbours, in association with a polarized myosin II distribution. Reducing myosinID, known to cause counter-clockwise epithelial-tissue movement, reverses the myosin II distribution. Numerical simulations revealed that a left–right asymmetry in cell intercalation is sufficient to induce unidirectional cellular movement. The cellular movement direction is also associated with planar cell-shape chirality. These findings support a model in which left–right asymmetric cell intercalation within an epithelial sheet drives collective cellular movement in the same direction.
Arp2/3-mediated F-actin formation controls regulated exocytosis in vivo
Authors: Tran Duy T. , Masedunskas Andrius , Weigert Roberto , Ten Hagen Kelly G.
Published: December 2015

The actin cytoskeleton plays crucial roles in many cellular processes, including regulated secretion. However, the mechanisms controlling F-actin dynamics in this process are largely unknown. Through 3D time-lapse imaging in a secreting organ, we show that F-actin is actively disassembled along the apical plasma membrane at the site of secretory vesicle fusion and re-assembled directionally on vesicle membranes. Moreover, we show that fusion pore formation and PIP2 redistribution precedes actin and myosin recruitment to secretory vesicle membranes. Finally, we show essential roles for the branched actin nucleators Arp2/3- and WASp in the process of secretory cargo expulsion and integration of vesicular membranes with the apical plasma membrane. Our results highlight previously unknown roles for branched actin in exocytosis and provide a genetically tractable system to image the temporal and spatial dynamics of polarized secretion in vivo.
DARPP-32 interaction with adducin may mediate rapid environmental effects on striatal neurons
Authors: Engmann Olivia , Giralt Albert , Gervasi Nicolas , Marion-Poll Lucile , Gasmi Laila , Filhol Odile , Picciotto Marina R. , Gilligan Diana , Greengard Paul , Nairn Angus C. , Hervé Denis , Girault Jean-Antoine
Published: December 2015

Environmental enrichment has multiple effects on behaviour, including modification of responses to psychostimulant drugs mediated by striatal neurons. However, the underlying molecular and cellular mechanisms are not known. Here we show that DARPP-32, a hub signalling protein in striatal neurons, interacts with adducins, which are cytoskeletal proteins that cap actin filaments’ fast-growing ends and regulate synaptic stability. DARPP-32 binds to adducin MARCKS domain and this interaction is modulated by DARPP-32 Ser97 phosphorylation. Phospho-Thr75-DARPP-32 facilitates β-adducin Ser713 phosphorylation through inhibition of a cAMP-dependent protein kinase/phosphatase-2A cascade. Caffeine or 24-h exposure to a novel enriched environment increases adducin phosphorylation in WT, but not T75A mutant mice. This cascade is implicated in the effects of brief exposure to novel enriched environment on dendritic spines in nucleus accumbens and cocaine locomotor response. Our results suggest a molecular pathway by which environmental changes may rapidly alter responsiveness of striatal neurons involved in the reward system.
Cell cycle and p53 gate the direct conversion of human fibroblasts to dopaminergic neurons
Authors: Jiang Houbo , Xu Zhimin , Zhong Ping , Ren Yong , Liang Gaoyang , Schilling Haley A. , Hu Zihua , Zhang Yi , Wang Xiaomin , Chen Shengdi , Yan Zhen , Feng Jian
Published: December 2015

The direct conversion of fibroblasts to induced dopaminergic (iDA) neurons and other cell types demonstrates the plasticity of cell fate. The low efficiency of these relatively fast conversions suggests that kinetic barriers exist to safeguard cell-type identity. Here we show that suppression of p53, in conjunction with cell cycle arrest at G1 and appropriate extracellular environment, markedly increase the efficiency in the transdifferentiation of human fibroblasts to iDA neurons by Ascl1, Nurr1, Lmx1a and miR124. The conversion is dependent on Tet1, as G1 arrest, p53 knockdown or expression of the reprogramming factors induces Tet1 synergistically. Tet1 knockdown abolishes the transdifferentiation while its overexpression enhances the conversion. The iDA neurons express markers for midbrain DA neurons and have active dopaminergic transmission. Our results suggest that overcoming these kinetic barriers may enable highly efficient epigenetic reprogramming in general and will generate patient-specific midbrain DA neurons for Parkinson’s disease research and therapy.
Engulfment pathways promote programmed cell death by enhancing the unequal segregation of apoptotic potential
Authors: Chakraborty Sayantan , Lambie Eric J. , Bindu Samik , Mikeladze-Dvali Tamara , Conradt Barbara
Published: December 2015

Components of the conserved engulfment pathways promote programmed cell death in Caenorhabditis elegans (C. elegans) through an unknown mechanism. Here we report that the phagocytic receptor CED-1 mEGF10 is required for the formation of a dorsal–ventral gradient of CED-3 caspase activity within the mother of a cell programmed to die and an increase in the level of CED-3 protein within its dying daughter. Furthermore, CED-1 becomes enriched on plasma membrane regions of neighbouring cells that appose the dorsal side of the mother, which later forms the dying daughter. Therefore, we propose that components of the engulfment pathways promote programmed cell death by enhancing the polar localization of apoptotic factors in mothers of cells programmed to die and the unequal segregation of apoptotic potential into dying and surviving daughters. Our findings reveal a novel function of the engulfment pathways and provide a better understanding of how apoptosis is initiated during C. elegans development.
Correction: Corrigendum: Resistive switching and its suppression in Pt/Nb:SrTiO3 junctions
Authors: Mikheev Evgeny , Hoskins Brian D. , Strukov Dmitri B. , Stemmer Susanne
Published: December 2015

Nature Communications 5: Article number: 3990 (2014); Published 2 June 2014; Updated 7 December 2015 In Fig. 2a of the main manuscript and in Supplementary Fig. 3, the unit label for C−2 (on the vertical axis) should read (cm4/μF2) instead of (m4/μF2). This correction only applies to the labels in these two figures and does not affect any of the calculations or conclusions in the paper.
Elevated levels of TRF2 induce telomeric ultrafine anaphase bridges and rapid telomere deletions
Authors: Nera Bernadette , Huang Hui-Shun , Lai Thao , Xu Lifeng
Published: December 2015

The shelterin protein TRF2 is essential for chromosome-end protection. Depletion of TRF2 causes chromosome end-to-end fusions, initiating genomic instability that can be cancer promoting. Paradoxically, significant increased levels of TRF2 are observed in a subset of human cancers. Experimental overexpression of TRF2 has also been shown to induce telomere shortening, through an unknown mechanism. Here we report that TRF2 overexpression results in replication stalling in duplex telomeric repeat tracts and the subsequent formation of telomeric ultrafine anaphase bridges (UFBs), ultimately leading to stochastic loss of telomeric sequences. These TRF2 overexpression-induced telomere deletions generate chromosome fusions resembling those detected in human cancers and in mammalian cells containing critically shortened telomeres. Therefore, our findings have uncovered a second pathway by which altered TRF2 protein levels can induce end-to-end fusions. The observations also provide mechanistic insight into the molecular basis of genomic instability in tumour cells containing significantly increased TRF2 levels.
Whole-genome sequencing reveals activation-induced cytidine deaminase signatures during indolent chronic lymphocytic leukaemia evolution
Authors: Kasar S. , Kim J. , Improgo R. , Tiao G. , Polak P. , Haradhvala N. , Lawrence M. S. , Kiezun A. , Fernandes S. M. , Bahl S. , Sougnez C. , Gabriel S. , Lander E. S. , Kim H. T. , Getz G. , Brown J. R.
Published: December 2015

Patients with chromosome 13q deletion or normal cytogenetics represent the majority of chronic lymphocytic leukaemia (CLL) cases, yet have relatively few driver mutations. To better understand their genomic landscape, here we perform whole-genome sequencing on a cohort of patients enriched with these cytogenetic characteristics. Mutations in known CLL drivers are seen in only 33% of this cohort, and associated with normal cytogenetics and unmutated IGHV. The most commonly mutated gene in our cohort, IGLL5, shows a mutational pattern suggestive of activation-induced cytidine deaminase (AID) activity. Unsupervised analysis of mutational signatures demonstrates the activities of canonical AID (c-AID), leading to clustered mutations near active transcriptional start sites; non-canonical AID (nc-AID), leading to genome-wide non-clustered mutations, and an ageing signature responsible for most mutations. Using mutation clonality to infer time of onset, we find that while ageing and c-AID activities are ongoing, nc-AID-associated mutations likely occur earlier in tumour evolution.
Rapid RNA–ligand interaction analysis through high-information content conformational and stability landscapes
Authors: Baird Nathan J. , Inglese James , Ferré-D’Amaré Adrian R.
Published: December 2015

The structure and biological properties of RNAs are a function of changing cellular conditions, but comprehensive, simultaneous investigation of the effect of multiple interacting environmental variables is not easily achieved. We have developed an efficient, high-throughput method to characterize RNA structure and thermodynamic stability as a function of multiplexed solution conditions using Förster resonance energy transfer (FRET). In a single FRET experiment using conventional quantitative PCR instrumentation, 19,400 conditions of MgCl2, ligand and temperature are analysed to generate detailed empirical conformational and stability landscapes of the cyclic diguanylate (c-di-GMP) riboswitch. The method allows rapid comparison of RNA structure modulation by cognate and non-cognate ligands. Landscape analysis reveals that kanamycin B stabilizes a non-native, idiosyncratic conformation of the riboswitch that inhibits c-di-GMP binding. This demonstrates that allosteric control of folding, rather than direct competition with cognate effectors, is a viable approach for pharmacologically targeting riboswitches and other structured RNA molecules.
Room-temperature in situ nuclear spin hyperpolarization from optically pumped nitrogen vacancy centres in diamond
Authors: King Jonathan P. , Jeong Keunhong , Vassiliou Christophoros C. , Shin Chang S. , Page Ralph H. , Avalos Claudia E. , Wang Hai-Jing , Pines Alexander
Published: December 2015

Low detection sensitivity stemming from the weak polarization of nuclear spins is a primary limitation of magnetic resonance spectroscopy and imaging. Methods have been developed to enhance nuclear spin polarization but they typically require high magnetic fields, cryogenic temperatures or sample transfer between magnets. Here we report bulk, room-temperature hyperpolarization of 13C nuclear spins observed via high-field magnetic resonance. The technique harnesses the high optically induced spin polarization of diamond nitrogen vacancy centres at room temperature in combination with dynamic nuclear polarization. We observe bulk nuclear spin polarization of 6%, an enhancement of ∼170,000 over thermal equilibrium. The signal of the hyperpolarized spins was detected in situ with a standard nuclear magnetic resonance probe without the need for sample shuttling or precise crystal orientation. Hyperpolarization via optical pumping/dynamic nuclear polarization should function at arbitrary magnetic fields enabling orders of magnitude sensitivity enhancement for nuclear magnetic resonance of solids and liquids under ambient conditions.
The climate hazards infrared precipitation with stations—a new environmental record for monitoring extremes
Authors: Funk Chris , Peterson Pete , Landsfeld Martin , Pedreros Diego , Verdin James , Shukla Shraddhanand , Husak Gregory , Rowland James , Harrison Laura , Hoell Andrew , Michaelsen Joel
Published: December 2015

The Climate Hazards group Infrared Precipitation with Stations (CHIRPS) dataset builds on previous approaches to ‘smart’ interpolation techniques and high resolution, long period of record precipitation estimates based on infrared Cold Cloud Duration (CCD) observations. The algorithm i) is built around a 0.05° climatology that incorporates satellite information to represent sparsely gauged locations, ii) incorporates daily, pentadal, and monthly 1981-present 0.05° CCD-based precipitation estimates, iii) blends station data to produce a preliminary information product with a latency of about 2 days and a final product with an average latency of about 3 weeks, and iv) uses a novel blending procedure incorporating the spatial correlation structure of CCD-estimates to assign interpolation weights. We present the CHIRPS algorithm, global and regional validation results, and show how CHIRPS can be used to quantify the hydrologic impacts of decreasing precipitation and rising air temperatures in the Greater Horn of Africa. Using the Variable Infiltration Capacity model, we show that CHIRPS can support effective hydrologic forecasts and trend analyses in southeastern Ethiopia.
Multi-omic profiles of human non-alcoholic fatty liver disease tissue highlight heterogenic phenotypes
Authors: Wruck Wasco , Kashofer Karl , Rehman Samrina , Daskalaki Andriani , Berg Daniela , Gralka Ewa , Jozefczuk Justyna , Drews Katharina , Pandey Vikash , Regenbrecht Christian , Wierling Christoph , Turano Paola , Korf Ulrike , Zatloukal Kurt , Lehrach Hans , Westerhoff Hans V. , Adjaye James
Published: December 2015

Non-alcoholic fatty liver disease (NAFLD) is a consequence of sedentary life style and high fat diets with an estimated prevalence of about 30% in western countries. It is associated with insulin resistance, obesity, glucose intolerance and drug toxicity. Additionally, polymorphisms within, e.g., APOC3, PNPLA3, NCAN, TM6SF2 and PPP1R3B, correlate with NAFLD. Several studies have already investigated later stages of the disease. This study explores the early steatosis stage of NAFLD with the aim of identifying molecular mechanisms underlying the etiology of NAFLD. We analyzed liver biopsies and serum samples from patients with high- and low-grade steatosis (also pre-disease states) employing transcriptomics, ELISA-based serum protein analyses and metabolomics. Here, we provide a detailed description of the various related datasets produced in the course of this study. These datasets may help other researchers find new clues for the etiology of NAFLD and the mechanisms underlying its progression to more severe disease states.
Long-term monitoring dataset of fish assemblages impinged at nuclear power plants in northern Taiwan
Authors: Chen Hungyen , Liao Yun-Chih , Chen Ching-Yi , Tsai Jeng-I , Chen Lee-Sea , Shao Kwang-Tsao
Published: December 2015

The long-term species diversity patterns in marine fish communities are garnering increasing attention from ecologists and conservation biologists. However, current databases on quantitative abundance information lack consistent long-term time series, which are particularly important in exploring the possible underlying mechanism of community changes and evaluating the effectiveness of biodiversity conservation measures. Here we describe an impinged fish assemblage dataset containing 1, 283, 707 individuals from 439 taxa. Once a month over 19 years (1987–1990 and 2000–2014), we systematically collected the fish killed by impingement upon cooling water intake screens at two nuclear power plants on the northern coast of Taiwan. Because impingement surveys have low sampling errors and can be carried out over many years, they serve as an ideal sampling tool for monitoring how fish diversity and community structure vary over an extended period of time.
Hair-bundle proteomes of avian and mammalian inner-ear utricles
Authors: Wilmarth Phillip A. , Krey Jocelyn F. , Shin Jung-Bum , Choi Dongseok , David Larry L. , Barr-Gillespie Peter G.
Published: December 2015

Examination of multiple proteomics datasets within or between species increases the reliability of protein identification. We report here proteomes of inner-ear hair bundles from three species (chick, mouse, and rat), which were collected on LTQ or LTQ Velos ion-trap mass spectrometers; the constituent proteins were quantified using MS2 intensities, which are the summed intensities of all peptide fragmentation spectra matched to a protein. The data are available via ProteomeXchange with identifiers PXD002410 (chick LTQ), PXD002414 (chick Velos), PXD002415 (mouse Velos), and PXD002416 (rat LTQ). The two chick bundle datasets compared favourably to a third, already-described chick bundle dataset, which was quantified using MS1 peak intensities, the summed intensities of peptides identified by high-resolution mass spectrometry (PXD000104; updated analysis in PXD002445). The mouse bundle dataset described here was comparable to a different mouse bundle dataset quantified using MS1 intensities (PXD002167). These six datasets will be useful for identifying the core proteome of vestibular hair bundles.
A global planktic foraminifer census data set for the Pliocene ocean
Authors: Dowsett Harry , Robinson Marci , Foley Kevin
Published: December 2015

This article presents data derived by the USGS Pliocene Research, Interpretation and Synoptic Mapping (PRISM) Project. PRISM has generated planktic foraminifer census data from core sites and outcrops around the globe since 1988. These data form the basis of a number of paleoceanographic reconstructions focused on the mid-Piacenzian Warm Period (3.264 to 3.025 million years ago). Data are presented as counts of individuals within 64 taxonomic categories for each locality. We describe sample acquisition and processing, age dating, taxonomy and archival storage of material. These data provide a unique, stratigraphically focused opportunity to assess the effects of global warming on marine plankton.
New hope for the survival of the Amur leopard in China
Authors: Jiang Guangshun , Qi Jinzhe , Wang Guiming , Shi Quanhua , Darman Yury , Hebblewhite Mark , Miquelle Dale G. , Li Zhilin , Zhang Xue , Gu Jiayin , Chang Youde , Zhang Minghai , Ma Jianzhang
Published: December 2015

Natural range loss limits the population growth of Asian big cats and may determine their survival. Over the past decade, we collected occurrence data of the critically endangered Amur leopard worldwide and developed a distribution model of the leopard’s historical range in northeastern China over the past decade. We were interested to explore how much current range area exists, learn what factors limit their spatial distribution, determine the population size and estimate the extent of potential habitat. Our results identify 48,252 km2 of current range and 21,173.7 km2 of suitable habitat patches and these patches may support 195.1 individuals. We found that prey presence drives leopard distribution, that leopard density exhibits a negative response to tiger occurrence and that the largest habitat patch connects with 5,200 km2of Russian current range. These insights provide a deeper understanding of the means by which endangered predators might be saved and survival prospects for the Amur leopard not only in China, but also through imperative conservation cooperation internationally.
Ceramides And Stress Signalling Intersect With Autophagic Defects In Neurodegenerative Drosophila blue cheese (bchs) Mutants
Authors: Hebbar Sarita , Sahoo Ishtapran , Matysik Artur , Argudo Garcia Irene , Osborne Kathleen Amy , Papan Cyrus , Torta Federico , Narayanaswamy Pradeep , Fun Xiu Hui , Wenk Markus R , Shevchenko Andrej , Schwudke Dominik , Kraut Rachel
Published: December 2015

Sphingolipid metabolites are involved in the regulation of autophagy, a degradative recycling process that is required to prevent neuronal degeneration. Drosophilablue cheesemutants neurodegenerate due to perturbations in autophagic flux and consequent accumulation of ubiquitinated aggregates. Here, we demonstrate thatblue cheesemutant brains exhibit an elevation in total ceramide levels; surprisingly, however, degeneration is ameliorated when the pool of available ceramides is further increased and exacerbated when ceramide levels are decreased by altering sphingolipid catabolism or blockingde novosynthesis. Exogenous ceramide is seen to accumulate in autophagosomes, which are fewer in number and show less efficient clearance inblue cheesemutant neurons. Sphingolipid metabolism is also shifted away from salvage towardde novopathways, while pro-growth Akt and MAP pathways are down-regulated and ER stress is increased. All these defects are reversed under genetic rescue conditions that increase ceramide generation from salvage pathways. This constellation of effects suggests a possible mechanism whereby the observed deficit in a potentially ceramide-releasing autophagic pathway impedes survival signaling and exacerbates neuronal death.
TLR4 drives the pathogenesis of acquired cholesteatoma by promoting local inflammation and bone destruction
Authors: Si Yu , Chen Yu Bin , Chen Sui Jun , Zheng Yi Qing , Liu Xiang , Liu Yi , Jiang Huai Li , Xu Guo , Li Zhuo Hao , Huang Qiu Hong , Xiong Hao , Zhang Zhi Gang
Published: December 2015

Acquired cholesteatoma is a chronic inflammatory disease characterized by both hyperkeratinized squamous epithelial overgrowth and bone destruction. Toll-like receptor (TLR) activation and subsequent inflammatory cytokine production are closely associated with inflammatory bone disease. However, the expression and function of TLRs in cholesteatoma remain unclear.We observed inflammatory cell infiltration of the matrix and prematrix of human acquired cholesteatoma, as well as dramatically increased expression of TLR4 and the pro-inflammatory cytokines TNF-α and IL-1β. TLR2 exhibited an up-regulation that was not statistically significant. TLR4 expression in human acquired cholesteatoma correlated with disease severity; the number of TLR4-positive cells increased with an increased degree of cholesteatoma, invasion, bone destruction and hearing loss. Moreover, TLR4 deficiency was protective against experimental acquired cholesteatoma-driven bone destruction and hearing loss, as it reduced local TNF-α and IL-1β expression and impaired osteoclast formation by decreasing expression of the osteoclast effectors receptor activator of nuclear factor (NF)-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP). TLR2 deficiency did not relieve disease severity, inflammatory responses, or osteoclast formation. Moreover, neither TLR2 nor TLR4 deficiency had an effect on antimicrobial peptides, inducible iNOS,BD-2 expression or bacterial clearance. Therefore, TLR4 may promote cholesteatoma-induced bone destruction and deafness by enhancing inflammatory responses and osteoclastogenesis.
Monitoring Network Confirms Land Use Change is a Substantial Component of the Forest Carbon Sink in the eastern United States
Authors: Woodall C. W. , Walters B. F. , Coulston J. W. , D’Amato A. W. , Domke G. M. , Russell M. B. , Sowers P. A.
Published: December 2015

Quantifying forest carbon (C) stocks and stock change within a matrix of land use (LU) and LU change is a central component of large-scale forest C monitoring and reporting practices prescribed by the Intergovernmental Panel on Climate Change (IPCC). Using a region–wide, repeated forest inventory, forest C stocks and stock change by pool were examined by LU categories. In eastern US forests, LU change is a substantial component of C sink strength (~37% of forest sink strength) only secondary to that of C accumulation in forests remaining forest where their comingling with other LUs does not substantially reduce sink strength. The strongest sinks of forest C were study areas not completely dominated by forests, even when there was some loss of forest to agriculture/settlement/other LUs. Long-term LU planning exercises and policy development that seeks to maintain and/or enhance regional C sinks should explicitly recognize the importance of maximizing non-forest to forest LU changes and not overlook management and conservation of forests located in landscapes not currently dominated by forests.
Detection of gene communities in multi-networks reveals cancer drivers
Authors: Cantini Laura , Medico Enzo , Fortunato Santo , Caselle Michele
Published: December 2015

We propose a new multi-network-based strategy to integrate different layers of genomic information and use them in a coordinate way to identify driving cancer genes. The multi-networks that we consider combine transcription factor co-targeting, microRNA co-targeting, protein-protein interaction and gene co-expression networks. The rationale behind this choice is that gene co-expression and protein-protein interactions require a tight coregulation of the partners and that such a fine tuned regulation can be obtained only combining both the transcriptional and post-transcriptional layers of regulation. To extract the relevant biological information from the multi-network we studied its partition into communities. To this end we applied a consensus clustering algorithm based on state of art community detection methods. Even if our procedure is valid in principle for any pathology in this work we concentrate on gastric, lung, pancreas and colorectal cancer and identified from the enrichment analysis of the multi-network communities a set of candidate driver cancer genes. Some of them were already known oncogenes while a few are new. The combination of the different layers of information allowed us to extract from the multi-network indications on the regulatory pattern and functional role of both the already known and the new candidate driver genes.
The Potential of High Resolution Magnetic Resonance Microscopy in the Pathologic Analysis of Resected Breast and Lymph Tissue
Authors: Dashevsky Brittany Z. , D'Alfonso Timothy , Sutton Elizabeth J. , Giambrone Ashley , Aronowitz Eric , Morris Elizabeth A. , Juluru Krishna , Ballon Douglas J.
Published: December 2015

Pathologic evaluation of breast specimens requires a fixation and staining procedure of at least 12 hours duration, delaying diagnosis and post-operative planning. Here we introduce an MRI technique with a custom-designed radiofrequency resonator for imaging breast and lymph tissue with sufficient spatial resolution and speed to guide pathologic interpretation and offer value in clinical decision making. In this study, we demonstrate the ability to image breast and lymphatic tissue using 7.0 Tesla MRI, achieving a spatial resolution of 59 × 59 × 94 μm3 with a signal-to-noise ratio of 15–20, in an imaging time of 56 to 70 minutes. These are the first MR images to reveal characteristic pathologic features of both benign and malignant breast and lymph tissue, some of which were discernible by blinded pathologists who had no prior training in high resolution MRI interpretation.
A highly efficient CMOS nanoplasmonic crystal enhanced slow-wave thermal emitter improves infrared gas-sensing devices
Authors: Pusch Andreas , De Luca Andrea , Oh Sang S. , Wuestner Sebastian , Roschuk Tyler , Chen Yiguo , Boual Sophie , Ali Zeeshan , Phillips Chris C. , Hong Minghui , Maier Stefan A. , Udrea Florin , Hopper Richard H. , Hess Ortwin
Published: December 2015

The application of plasmonics to thermal emitters is generally assisted by absorptive losses in the metal because Kirchhoff’s law prescribes that only good absorbers make good thermal emitters. Based on a designed plasmonic crystal and exploiting a slow-wave lattice resonance and spontaneous thermal plasmon emission, we engineer a tungsten-based thermal emitter, fabricated in an industrial CMOS process and demonstrate its markedly improved practical use in a prototype non-dispersive infrared (NDIR) gas-sensing device. We show that the emission intensity of the thermal emitter at the CO2 absorption wavelength is enhanced almost 4-fold compared to a standard non-plasmonic emitter, which enables a proportionate increase in the signal-to-noise ratio of the CO2 gas sensor.
Developmental exposure to Ethinylestradiol affects transgenerationally sexual behavior and neuroendocrine networks in male mice
Authors: Derouiche Lyes , Keller Matthieu , Duittoz Anne Hélène , Pillon Delphine
Published: December 2015

Reproductive behavior and physiology in adulthood are controlled by hypothalamic sexually dimorphic neuronal networks which are organized under hormonal control during development. These organizing effects may be disturbed by endocrine disrupting chemicals (EDCs). To determine whether developmental exposure to Ethinylestradiol (EE2) may alter reproductive parameters in adult male mice and their progeny, Swiss mice (F1 generation) were exposed from prenatal to peripubertal periods to EE2 (0.1–1 μg/kg/d). Sexual behavior and reproductive physiology were evaluated on F1 males and their F2, F3 and F4 progeny. EE2-exposed F1 males and their F2 to F4 progeny exhibited EE2 dose-dependent increased sexual behavior, with reduced latencies of first mount and intromission and higher frequencies of intromissions with a receptive female. The EE2 1 μg/kg/d exposed animals and their progeny had more calbindin immunoreactive cells in the medial preoptic area, known to be involved in the control of male sexual behavior in rodents. Despite neuroanatomical modifications in the Gonadotropin-Releasing Hormone neuron population of F1 males exposed to both doses of EE2, no major deleterious effects on reproductive physiology were detected. Therefore EE2 exposure during development may induce a hypermasculinization of the brain, illustrating how widespread exposure of animals and humans to EDCs can impact health and behaviors.
Fine-tuned SRF activity controls asymmetrical neuronal outgrowth: implications for cortical migration, neural tissue lamination and circuit assembly
Authors: Scandaglia Marilyn , Benito Eva , Morenilla-Palao Cruz , Fiorenza Anna , del Blanco Beatriz , Coca Yaiza , Herrera Eloísa , Barco Angel
Published: December 2015

The stimulus-regulated transcription factor Serum Response Factor (SRF) plays an important role in diverse neurodevelopmental processes related to structural plasticity and motile functions, although its precise mechanism of action has not yet been established. To further define the role of SRF in neural development and distinguish between cell-autonomous and non cell-autonomous effects, we bidirectionally manipulated SRF activity through gene transduction assays that allow the visualization of individual neurons and their comparison with neighboring control cells. In vitro assays showed that SRF promotes survival and filopodia formation and is required for normal asymmetric neurite outgrowth, indicating that its activation favors dendrite enlargement versus branching. In turn, in vivo experiments demonstrated that SRF-dependent regulation of neuronal morphology has important consequences in the developing cortex and retina, affecting neuronal migration, dendritic and axonal arborization and cell positioning in these laminated tissues. Overall, our results show that the controlled and timely activation of SRF is essential for the coordinated growth of neuronal processes, suggesting that this event regulates the switch between neuronal growth and branching during developmental processes.
Integration of CdSe/CdSexTe1−x Type-II Heterojunction Nanorods into Hierarchically Porous TiO2 Electrode for Efficient Solar Energy Conversion
Authors: Lee Sangheon , Flanagan Joseph C. , Kang Joonhyeon , Kim Jinhyun , Shim Moonsub , Park Byungwoo
Published: December 2015

Semiconductor sensitized solar cells, a promising candidate for next-generation photovoltaics, have seen notable progress using 0-D quantum dots as light harvesting materials. Integration of higher-dimensional nanostructures and their multi-composition variants into sensitized solar cells is, however, still not fully investigated despite their unique features potentially beneficial for improving performance. Herein, CdSe/CdSexTe1−x type-II heterojunction nanorods are utilized as novel light harvesters for sensitized solar cells for the first time. The CdSe/CdSexTe1−x heterojunction-nanorod sensitized solar cell exhibits ~33% improvement in the power conversion efficiency compared to its single-component counterpart, resulting from superior optoelectronic properties of the type-II heterostructure and 1-octanethiol ligands aiding facile electron extraction at the heterojunction nanorod-TiO2 interface. Additional ~31% enhancement in power conversion efficiency is achieved by introducing percolation channels of large pores in the mesoporous TiO2 electrode, which allow 1-D sensitizers to infiltrate the entire depth of electrode. These strategies combined together lead to 3.02% power conversion efficiency, which is one of the highest values among sensitized solar cells utilizing 1-D nanostructures as sensitizer materials.