bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diet-induced adaptive thermogenesis requires neuropeptide FF receptor-2 signalling
Authors: Zhang Lei , Ip Chi Kin , Lee I-Chieh J. , Qi Yue , Reed Felicia , Karl Tim , Low Jac Kee , Enriquez Ronaldo F. , Lee Nicola J. , Baldock Paul A. , Herzog Herbert 
Published: November 2018

AbstractExcess caloric intake results in increased fat accumulation and an increase in energy expenditure via diet-induced adaptive thermogenesis; however, the underlying mechanisms controlling these processes are unclear. Here we identify the neuropeptide FF receptor-2 (NPFFR2) as a critical regulator of diet-induced thermogenesis and bone homoeostasis. Npffr2−/− mice exhibit a stronger bone phenotype and when fed a HFD display exacerbated obesity associated with a failure in activating brown adipose tissue (BAT) thermogenic response to energy excess, whereas the activation of cold-induced BAT thermogenesis is unaffected. NPFFR2 signalling is required to maintain basal arcuate nucleus NPY mRNA expression. Lack of NPFFR2 signalling leads to a decrease in BAT thermogenesis under HFD conditions with significantly lower UCP-1 and PGC-1α levels in the BAT. Together, these data demonstrate that NPFFR2 signalling promotes diet-induced thermogenesis via a novel hypothalamic NPY-dependent circuitry thereby coupling energy homoeostasis with energy partitioning to adipose and bone tissue.
Diffusion-limited association of disordered protein by non-native electrostatic interactions
Authors: Kim Jae-Yeol , Meng Fanjie , Yoo Janghyun , Chung Hoi Sung 
Published: November 2018

AbstractIntrinsically disordered proteins (IDPs) usually fold during binding to target proteins. In contrast to interactions between folded proteins, this additional folding step makes the binding process more complex. Understanding the mechanism of coupled binding and folding of IDPs requires analysis of binding pathways that involve formation of the transient complex (TC). However, experimental characterization of TC is challenging because it only appears for a very brief period during binding. Here, we use single-molecule fluorescence spectroscopy to investigate the mechanism of diffusion-limited association of an IDP. A large enhancement of the association rate is observed due to the stabilization of TC by non-native electrostatic interactions. Moreover, photon-by-photon analysis reveals that the lifetime of TC for IDP binding is at least two orders of magnitude longer than that for binding of two folded proteins. This result suggests the long lifetime of TC is generally required for folding of IDPs during binding processes.
Chemical bonding origin of the unexpected isotropic physical properties in thermoelectric Mg3Sb2 and related materials
Authors: Zhang Jiawei , Song Lirong , Sist Mattia , Tolborg Kasper , Iversen Bo Brummerstedt 
Published: November 2018

AbstractThe Mg3Sb2structure is currently being intensely scrutinized due to its outstanding thermoelectric properties. Usually, it is described as a layered Zintl phase with a clear distinction between covalent [Mg2Sb2]2−layers and ionic Mg2+layers. Based on the quantitative chemical bonding analysis, we unravel instead that Mg3Sb2exhibits a nearly isotropic three-dimensional bonding network with the interlayer and intralayer bonds being mostly ionic and surprisingly similar, which results in the nearly isotropic structural and thermal properties. The isotropic three-dimensional bonding network is found to be broadly applicable to many Mg-containing compounds with the CaAl2Si2-type structure. Intriguingly, a parameter based on the electron density can be used as an indicator measuring the anisotropy of lattice thermal conductivity in Mg3Sb2-related structures. This work extends our understanding of structure and properties based on chemical bonding analysis, and it will guide the search for and design of materials with tailored anisotropic properties.
Thermal transport crossover from crystalline to partial-crystalline partial-liquid state
Authors: Zhou Yanguang , Xiong Shiyun , Zhang Xiaoliang , Volz Sebastian , Hu Ming 
Published: November 2018

AbstractPhase-change materials (crystalline at low temperatures and partial-crystalline partial-liquid state at high temperatures) are widely used as thermoelectric converters and battery electrodes. Here, we report the underlying mechanisms driving the thermal transport of the liquid component, and the thermal conductivity contributions from phonons, vibrations with extremely short mean free path, liquid and lattice-liquid interactions in phase-changed Li2S. In the crystalline state (T ≤ 1000 K), the temperature dependent thermal conductivity manifests two different behaviors, i.e., a typical trend of 1/T below 800 K and an even faster decrease between 800 and 1000 K. For the partial-crystalline partial-liquid Li2S when T ≥ 1100 K, the contributions of liquid and lattice-liquid interactions increase significantly due to the fluidization of Li ions, and the vibrations with extremely short mean free path, presumably assimilated to diffusons, can contribute up to 46% of the total thermal conductivity at T = 1300 K.
Broadband highly directive 3D nanophotonic lenses
Authors: Johlin Eric , Mann Sander A. , Kasture Sachin , Koenderink A. Femius , Garnett Erik C. 
Published: November 2018

AbstractControlling the directivity of emission and absorption at the nanoscale holds great promise for improving the performance of optoelectronic devices. Previously, directive structures have largely been centered in two categories—nanoscale antennas, and classical lenses. Herein, we utilize an evolutionary algorithm to design 3D dielectric nanophotonic lens structures leveraging both the interference-based control of antennas and the broadband operation of lenses. By sculpting the dielectric environment around an emitter, these nanolenses achieve directivities of 101 for point-sources, and 67 for finite-source nanowire emitters; 3× greater than that of a traditional spherical lens with nearly constant performance over a 200 nm wavelength range. The nanolenses are experimentally fabricated on GaAs nanowires, and characterized via photoluminescence Fourier microscopy, with an observed beaming half-angle of 3.5° and a measured directivity of 22. Simulations attribute the main limitation in the obtained directivity to imperfect alignment of the nanolens to the nanowire beneath.
Early childhood investment impacts social decision-making four decades later
Authors: Luo Yi , Hétu Sébastien , Lohrenz Terry , Hula Andreas , Dayan Peter , Ramey Sharon Landesman , Sonnier-Netto Libbie , Lisinski Jonathan , LaConte Stephen , Nolte Tobias , Fonagy Peter , Rahmani Elham , Montague P. Read , Ramey Craig 
Published: November 2018

AbstractEarly childhood educational investment produces positive effects on cognitive and non-cognitive skills, health, and socio-economic success. However, the effects of such interventions on social decision-making later in life are unknown. We recalled participants from one of the oldest randomized controlled studies of early childhood investment—the Abecedarian Project (ABC)—to participate in well-validated interactive economic games that probe social norm enforcement and planning. We show that in a repeated-play ultimatum game, ABC participants who received high-quality early interventions strongly reject unequal division of money across players (disadvantageous or advantageous) even at significant cost to themselves. Using a multi-round trust game and computational modeling of social exchange, we show that the same intervention participants also plan further into the future. These findings suggest that high quality early childhood investment can result in long-term changes in social decision-making and promote social norm enforcement in order to reap future benefits.
A model of temporal scaling correctly predicts that motor timing improves with speed
Authors: Hardy Nicholas F. , Goudar Vishwa , Romero-Sosa Juan L. , Buonomano Dean V. 
Published: November 2018

AbstractTiming is fundamental to complex motor behaviors: from tying a knot to playing the piano. A general feature of motor timing is temporal scaling: the ability to produce motor patterns at different speeds. One theory of temporal processing proposes that the brain encodes time in dynamic patterns of neural activity (population clocks), here we first examine whether recurrent neural network (RNN) models can account for temporal scaling. Appropriately trained RNNs exhibit temporal scaling over a range similar to that of humans and capture a signature of motor timing, Weber’s law, but predict that temporal precision improves at faster speeds. Human psychophysics experiments confirm this prediction: the variability of responses in absolute time are lower at faster speeds. These results establish that RNNs can account for temporal scaling and suggest a novel psychophysical principle: the Weber-Speed effect.
Oestrogen receptor α AF-1 and AF-2 domains have cell population-specific functions in the mammary epithelium
Authors: Cagnet Stéphanie , Ataca Dalya , Sflomos George , Aouad Patrick , Schuepbach-Mallepell Sonia , Hugues Henry , Krust Andrée , Ayyanan Ayyakkannu , Scabia Valentina , Brisken Cathrin 
Published: November 2018

AbstractOestrogen receptor α (ERα) is a transcription factor with ligand-independent and ligand-dependent activation functions (AF)-1 and -2. Oestrogens control postnatal mammary gland development acting on a subset of mammary epithelial cells (MECs), termed sensor cells, which are ERα-positive by immunohistochemistry (IHC) and secrete paracrine factors, which stimulate ERα-negative responder cells. Here we show that deletion of AF-1 or AF-2 blocks pubertal ductal growth and subsequent development because both are required for expression of essential paracrine mediators. Thirty percent of the luminal cells are ERα-negative by IHC but express Esr1 transcripts. This low level ERα expression through AF-2 is essential for cell expansion during puberty and growth-inhibitory during pregnancy. Cell-intrinsic ERα is not required for cell proliferation nor for secretory differentiation but controls transcript levels of cell motility and cell adhesion genes and a stem cell and epithelial mesenchymal transition (EMT) signature identifying ERα as a key regulator of mammary epithelial cell plasticity.
The critical role of AMPK in driving Akt activation under stress, tumorigenesis and drug resistance
Authors: Han Fei , Li Chien-Feng , Cai Zhen , Zhang Xian , Jin Guoxiang , Zhang Wei-Na , Xu Chuan , Wang Chi-Yun , Morrow John , Zhang Shuxing , Xu Dazhi , Wang Guihua , Lin Hui-Kuan 
Published: November 2018

AbstractPI3K/Akt signaling is activated in cancers and governs tumor initiation and progression, but how Akt is activated under diverse stresses is poorly understood. Here we identify AMPK as an essential regulator for Akt activation by various stresses. Surprisingly, AMPK is also activated by growth factor EGF through Ca2+/Calmodulin-dependent kinase and is essential for EGF-mediated Akt activation and biological functions. AMPK phosphorylates Skp2 at S256 and promotes the integrity and E3 ligase activity of Skp2 SCF complex leading to K63-linked ubiquitination and activation of Akt and subsequent oncogenic processes. Importantly, AMPK-mediated Skp2 S256 phosphorylation promotes breast cancer progression in mouse tumor models, correlates with Akt and AMPK activation in breast cancer patients, and predicts poor survival outcomes. Finally, targeting AMPK-mediated Skp2 S256 phosphorylation sensitizes cells to anti-EGF receptor targeted therapy. Our study sheds light on how stress and EGF induce Akt activation and new mechanisms for AMPK-mediated oncogenesis and drug resistance.
High-resolution ultramicroscopy of the developing and adult nervous system in optically cleared Drosophila melanogaster
Authors: Pende Marko , Becker Klaus , Wanis Martina , Saghafi Saiedeh , Kaur Rashmit , Hahn Christian , Pende Nika , Foroughipour Massih , Hummel Thomas , Dodt Hans-Ulrich 
Published: November 2018

AbstractThe fruit fly, Drosophila melanogaster, is an important experimental model to address central questions in neuroscience at an organismic level. However, imaging of neural circuits in intact fruit flies is limited due to structural properties of the cuticle. Here we present a novel approach combining tissue clearing, ultramicroscopy, and data analysis that enables the visualisation of neuronal networks with single-cell resolution from the larval stage up to the adult Drosophila. FlyClear, the signal preserving clearing technique we developed, stabilises tissue integrity and fluorescence signal intensity for over a month and efficiently removes the overall pigmentation. An aspheric ultramicroscope set-up utilising an improved light-sheet generator allows us to visualise long-range connections of peripheral sensory and central neurons in the visual and olfactory system. High-resolution 3D reconstructions with isotropic resolution from entire GFP-expressing flies are obtained by applying image fusion from orthogonal directions. This methodological integration of novel chemical, optical, and computational techniques allows a major advance in the analysis of global neural circuit organisation.
MAIT cells contribute to protection against lethal influenza infection in vivo
Authors: van Wilgenburg Bonnie , Loh Liyen , Chen Zhenjun , Pediongco Troi J. , Wang Huimeng , Shi Mai , Zhao Zhe , Koutsakos Marios , Nüssing Simone , Sant Sneha , Wang Zhongfang , D’Souza Criselle , Jia Xiaoxiao , Almeida Catarina F. , Kostenko Lyudmila , Eckle Sidonia B. G. , Meehan Bronwyn S. , Kallies Axel , Godfrey Dale I. , Reading Patrick C. , Corbett Alexandra J. , McCluskey James , Klenerman Paul , Kedzierska Katherine , Hinks Timothy S. C. 
Published: November 2018

AbstractMucosal associated invariant T (MAIT) cells are evolutionarily-conserved, innate-like lymphocytes which are abundant in human lungs and can contribute to protection against pulmonary bacterial infection. MAIT cells are also activated during human viral infections, yet it remains unknown whether MAIT cells play a significant protective or even detrimental role during viral infections in vivo. Using murine experimental challenge with two strains of influenza A virus, we show that MAIT cells accumulate and are activated early in infection, with upregulation of CD25, CD69 and Granzyme B, peaking at 5 days post-infection. Activation is modulated via cytokines independently of MR1. MAIT cell-deficient MR1−/− mice show enhanced weight loss and mortality to severe (H1N1) influenza. This is ameliorated by prior adoptive transfer of pulmonary MAIT cells in both immunocompetent and immunodeficient RAG2−/−γC−/− mice. Thus, MAIT cells contribute to protection during respiratory viral infections, and constitute a potential target for therapeutic manipulation.
A common genetic mechanism underlies morphological diversity in fruits and other plant organs
Authors: Wu Shan , Zhang Biyao , Keyhaninejad Neda , Rodríguez Gustavo R. , Kim Hyun Jung , Chakrabarti Manohar , Illa-Berenguer Eudald , Taitano Nathan K. , Gonzalo M. J , Díaz Aurora , Pan Yupeng , Leisner Courtney P. , Halterman Dennis , Buell C. Robin , Weng Yiqun , Jansky Shelley H. , van Eck Herman , Willemsen Johan , Monforte Antonio J. , Meulia Tea , van der Knaap Esther 
Published: November 2018

AbstractShapes of edible plant organs vary dramatically among and within crop plants. To explain and ultimately employ this variation towards crop improvement, we determined the genetic, molecular and cellular bases of fruit shape diversity in tomato. Through positional cloning, protein interaction studies, and genome editing, we report that OVATE Family Proteins and TONNEAU1 Recruiting Motif proteins regulate cell division patterns in ovary development to alter final fruit shape. The physical interactions between the members of these two families are necessary for dynamic relocalization of the protein complexes to different cellular compartments when expressed in tobacco leaf cells. Together with data from other domesticated crops and model plant species, the protein interaction studies provide possible mechanistic insights into the regulation of morphological variation in plants and a framework that may apply to organ growth in all plant species.
Mapping knowledge gaps in marine diversity reveals a latitudinal gradient of missing species richness
Authors: Menegotto André , Rangel Thiago F. 
Published: November 2018

AbstractA reliable description of any spatial pattern in species richness requires accurate knowledge about species geographical distribution. However, sampling bias may generate artefactual absences within species range and compromise our capacity to describe biodiversity patterns. Here, we analysed the spatial distribution of 35,000 marine species (varying from copepods to sharks) to identify missing occurrences (gaps) across their latitudinal range. We find a latitudinal gradient of species absence peaking near the equator, a pattern observed in both shallow and deep waters. The tropical gap in species distribution seems a consequence of reduced sampling effort at low latitudes. Overall, our results suggest that spatial gaps in species distribution are the main cause of the bimodal pattern of marine diversity. Therefore, only increasing sampling effort at low latitudes will reveal if the absence of species in the tropics, and the consequent dip in species richness, are artefacts of sampling bias or a natural phenomenon.
Leveraging heterogeneity across multiple datasets increases cell-mixture deconvolution accuracy and reduces biological and technical biases
Authors: Vallania Francesco , Tam Andrew , Lofgren Shane , Schaffert Steven , Azad Tej D. , Bongen Erika , Haynes Winston , Alsup Meia , Alonso Michael , Davis Mark , Engleman Edgar , Khatri Purvesh 
Published: November 2018

AbstractIn silico quantification of cell proportions from mixed-cell transcriptomics data (deconvolution) requires a reference expression matrix, called basis matrix. We hypothesize that matrices created using only healthy samples from a single microarray platform would introduce biological and technical biases in deconvolution. We show presence of such biases in two existing matrices, IRIS and LM22, irrespective of deconvolution method. Here, we present immunoStates, a basis matrix built using 6160 samples with different disease states across 42 microarray platforms. We find that immunoStates significantly reduces biological and technical biases. Importantly, we find that different methods have virtually no or minimal effect once the basis matrix is chosen. We further show that cellular proportion estimates using immunoStates are consistently more correlated with measured proportions than IRIS and LM22, across all methods. Our results demonstrate the need and importance of incorporating biological and technical heterogeneity in a basis matrix for achieving consistently high accuracy.
Inflammation-induced Id2 promotes plasticity in regulatory T cells
Authors: Hwang Sung-Min , Sharma Garima , Verma Ravi , Byun Seohyun , Rudra Dipayan , Im Sin-Hyeog 
Published: November 2018

AbstractTH17 cells originating from regulatory T (Treg) cells upon loss of the Treg-specific transcription factor Foxp3 accumulate in sites of inflammation and aggravate autoimmune diseases. Whether an active mechanism drives the generation of these pathogenic ‘ex-Foxp3 TH17’ cells, remains unclear. Here we show that pro-inflammatory cytokines enhance the expression of transcription regulator Id2, which mediates cellular plasticity of Treg into ex-Foxp3 TH17 cells. Expression of Id2 in in vitro differentiated iTreg cells reduces the expression of Foxp3 by sequestration of the transcription activator E2A, leading to the induction of TH17-related cytokines. Treg-specific ectopic expression of Id2 in mice significantly reduces the Treg compartment and causes immune dysregulation. Cellular fate-mapping experiments reveal enhanced Treg plasticity compared to wild-type, resulting in exacerbated experimental autoimmune encephalomyelitis pathogenesis or enhanced anti-tumor immunity. Our findings suggest that controlling Id2 expression may provide a novel approach for effective Treg cell immunotherapies for both autoimmunity and cancer.
R430: A potent inhibitor of DNA and RNA viruses
Authors: D’Aiuto Leonardo , McNulty James , Hartline Caroll , Demers Matthew , Kalkeri Raj , Wood Joel , McClain Lora , Chattopadhyay Ansuman , Zhi Yun , Naciri Jennifer , Smith Adam , Yolken Robert , Chowdari Kodavali , Zepeda-Velazquez Carlos , Dokuburra Chanti Babu , Marques Ernesto , Ptak Roger , Kinchington Paul , Watkins Simon , Prichard Mark , Bloom David , Nimgaonkar Vishwajit 
Published: November 2018

AbstractAcyclovir (ACV) is an effective antiviral agent for treating lytic Herpes Simplex virus, type 1 (HSV-1) infections, and it has dramatically reduced the mortality rate of herpes simplex encephalitis. However, HSV-1 resistance to ACV and its derivatives is being increasingly documented, particularly among immunocompromised individuals. The burgeoning drug resistance compels the search for a new generation of more efficacious anti-herpetic drugs. We have previously shown that trans-dihydrolycoricidine (R430), a lycorane-type alkaloid derivative, effectively inhibits HSV-1 infections in cultured cells. We now report that R430 also inhibits ACV-resistant HSV-1 strains, accompanied by global inhibition of viral gene transcription and enrichment of H3K27me3 methylation on viral gene promoters. Furthermore, we demonstrate that R430 prevents HSV-1 reactivation from latency in an ex vivo rodent model. Finally, among a panel of DNA viruses and RNA viruses, R430 inhibited Zika virus with high therapeutic index. Its therapeutic index is comparable to standard antiviral drugs, though it has greater toxicity in non-neuronal cells than in neuronal cells. Synthesis of additional derivatives could enable more efficacious antivirals and the identification of active pharmacophores.
Genetic diversity and distribution dynamics of multidrug-resistant Mycobacterium tuberculosis isolates in Nepal
Authors: Maharjan Bhagwan , Nakajima Chie , Isoda Norikazu , Thapa Jeewan , Poudel Ajay , Shah Yogendra , Yamaguchi Tomoyuki , Shrestha Bhabana , Hoffmann Harald , Avsar Korkut , Shrestha Ashish , Gordon Stephen V. , Suzuki Yasuhiko 
Published: November 2018

AbstractMultidrug-resistant tuberculosis (MDR-TB) is an emerging public health problem in Nepal. Despite the implementation of a successful TB control program in Nepal, notifications of MDR-TB are increasing, yet the reasons are unknown. The objective of this study was to understand the genetic diversity and epidemiological characteristics of MDR-Mycobacterium tuberculosis (MTB) isolates in Nepal. We isolated and genotyped 498 MDR-MTB isolates collected from April 2009 to March 2013 and analyzed the patients’ background information. Our results showed that the lineage 2 (Beijing family) was the most predominant lineage (n = 241; 48.4%), followed by lineage 3 (n = 153, 30.7%). Lineage 4 was the third most prevalent (n = 73, 14.5%) followed by lineage 1 (n = 32, 6.4%). The lineages were significantly associated with geographic region, ethnic group, age and sex of patients. The Beijing genotype was found to have an important role in transmitting MDR-TB in Nepal and was significantly associated with the eastern region, mongoloid ethnic group and younger age group. We conclude that early diagnosis and treatment including molecular-epidemiological surveillance of MDR-TB cases will help to control transmission of MDR-TB in Nepal.