bluuebunny/crossref_metadata_2025_split huggingface dataset:
MCRS1 associates with cytoplasmic dynein and mediates pericentrosomal material recruitment
Authors: Lee Si-Hyung , Lee Mi-Sun , Choi Tae-Ik , Hong Hyowon , Seo Jun-Young , Kim Cheol-Hee , Kim Joon 
Published: June 2016

AbstractMCRS1 is involved in multiple cellular activities, including mitotic spindle assembly, mTOR signaling and tumorigenesis. Although MCRS1 has been reported to bind to the dynein regulator NDE1, a functional interaction between MCRS1 and cytoplasmic dynein remains unaddressed. Here, we demonstrate that MCRS1 is required for dynein-dependent cargo transport to the centrosome and also plays a role in primary cilium formation. MCRS1 localized to centriolar satellites. Knockdown of MCRS1 resulted in a dispersion of centriolar satellites whose establishment depends on cytoplasmic dynein. By contrast, NDE1 was not necessary for the proper distribution of centriolar satellites, indicating a functional distinction between MCRS1 and NDE1. Unlike NDE1, MCRS1 played a positive role for the initiation of ciliogenesis, possibly through its interaction with TTBK2. Zebrafish with homozygous mcrs1 mutants exhibited a reduction in the size of the brain and the eye due to excessive apoptosis. In addition, mcrs1 mutants failed to develop distinct layers in the retina, and showed a defect in melatonin-induced aggregation of melanosomes in melanophores. These phenotypes are reminiscent of zebrafish dynein mutants. Reduced ciliogenesis was also apparent in the olfactory placode of mcrs1 mutants. Collectively, our findings identify MCRS1 as a dynein-interacting protein critical for centriolar satellite formation and ciliogenesis.
Noise Response Data Reveal Novel Controllability Gramian for Nonlinear Network Dynamics
Authors: Kashima Kenji 
Published: June 2016

AbstractControl of nonlinear large-scale dynamical networks, e.g., collective behavior of agents interacting via a scale-free connection topology, is a central problem in many scientific and engineering fields. For the linear version of this problem, the so-called controllability Gramian has played an important role to quantify how effectively the dynamical states are reachable by a suitable driving input. In this paper, we first extend the notion of the controllability Gramian to nonlinear dynamics in terms of the Gibbs distribution. Next, we show that, when the networks are open to environmental noise, the newly defined Gramian is equal to the covariance matrix associated with randomly excited, but uncontrolled, dynamical state trajectories. This fact theoretically justifies a simple Monte Carlo simulation that can extract effectively controllable subdynamics in nonlinear complex networks. In addition, the result provides a novel insight into the relationship between controllability and statistical mechanics.
Synthetic long non-coding RNAs [SINEUPs] rescue defective gene expression in vivo
Authors: Indrieri Alessia , Grimaldi Claudia , Zucchelli Silvia , Tammaro Roberta , Gustincich Stefano , Franco Brunella 
Published: June 2016

AbstractNon-coding RNAs provide additional regulatory layers to gene expression as well as the potential to being exploited as therapeutic tools. Non-coding RNA-based therapeutic approaches have been attempted in dominant diseases, however their use for treatment of genetic diseases caused by insufficient gene dosage is currently more challenging. SINEUPs are long antisense non-coding RNAs that up-regulate translation in mammalian cells in a gene-specific manner, although, so far evidence of SINEUP efficacy has only been demonstrated in in vitro systems. We now show that synthetic SINEUPs effectively and specifically increase protein levels of a gene of interest in vivo. We demonstrated that SINEUPs rescue haploinsufficient gene dosage in a medakafish model of a human disorder leading to amelioration of the disease phenotype. Our results demonstrate that SINEUPs act through mechanisms conserved among vertebrates and that SINEUP technology can be successfully applied in vivo as a new research and therapeutic tool for gene-specific up-regulation of endogenous functional proteins.
A C-terminally truncated mouse Best3 splice variant targets and alters the ion balance in lysosome-endosome hybrids and the endoplasmic reticulum
Authors: Wu Lichang , Sun Yu , Ma Liqiao , Zhu Jun , Zhang Baoxia , Pan Qingjie , Li Yuyin , Liu Huanqi , Diao Aipo , Li Yinchuan 
Published: June 2016

AbstractThe Bestrophin family has been characterized as Cl− channels in mammals and Na+ channels in bacteria, but their exact physiological roles remian unknown. In this study, a natural C-terminally truncated variant of mouse Bestrophin 3 (Best3V2) expression in myoblasts and muscles is demonstrated. Unlike full-length Best3, Best3V2 targets the two important intracellular Ca stores: the lysosome and the ER. Heterologous overexpression leads to lysosome swelling and renders it less acidic. Best3V2 overexpression also results in compromised Ca2+ release from the ER. Knocking down endogenous Best3 expression in myoblasts makes these cells more excitable in response to Ca2+ mobilizing reagents, such as caffeine. We propose that Best3V2 in myoblasts may work as a tuner to control Ca2+ release from intracellular Ca2+ stores.
Chalcone-based Selective Inhibitors of a C4 Plant Key Enzyme as Novel Potential Herbicides
Authors: Nguyen G. T. T. , Erlenkamp G. , Jäck O. , Küberl A. , Bott M. , Fiorani F. , Gohlke H. , Groth G. 
Published: June 2016

AbstractWeeds are a challenge for global food production due to their rapidly evolving resistance against herbicides. We have identified chalcones as selective inhibitors of phosphoenolpyruvate carboxylase (PEPC), a key enzyme for carbon fixation and biomass increase in the C4 photosynthetic pathway of many of the world’s most damaging weeds. In contrast, many of the most important crop plants use C3 photosynthesis. Here, we show that 2′,3′,4′,3,4-Pentahydroxychalcone (IC50 = 600 nM) and 2′,3′,4′-Trihydroxychalcone (IC50 = 4.2 μM) are potent inhibitors of C4 PEPC but do not affect C3 PEPC at a same concentration range (selectivity factor: 15–45). Binding and modeling studies indicate that the active compounds bind at the same site as malate/aspartate, the natural feedback inhibitors of the C4 pathway. At the whole plant level, both substances showed pronounced growth-inhibitory effects on the C4 weed Amaranthus retroflexus, while there were no measurable effects on oilseed rape, a C3 plant. Growth of selected soil bacteria was not affected by these substances. Our chalcone compounds are the most potent and selective C4 PEPC inhibitors known to date. They offer a novel approach to combat C4 weeds based on a hitherto unexplored mode of allosteric inhibition of a C4 plant key enzyme.
High-resolution biophysical analysis of the dynamics of nucleosome formation
Authors: Hatakeyama Akiko , Hartmann Brigitte , Travers Andrew , Nogues Claude , Buckle Malcolm 
Published: June 2016

AbstractWe describe a biophysical approach that enables changes in the structure of DNA to be followed during nucleosome formation in in vitro reconstitution with either the canonical “Widom” sequence or a judiciously mutated sequence. The rapid non-perturbing photochemical analysis presented here provides ‘snapshots’ of the DNA configuration at any given moment in time during nucleosome formation under a very broad range of reaction conditions. Changes in DNA photochemical reactivity upon protein binding are interpreted as being mainly induced by alterations in individual base pair roll angles. The results strengthen the importance of the role of an initial (H3/H4)2 histone tetramer-DNA interaction and highlight the modulation of this early event by the DNA sequence. (H3/H4)2 binding precedes and dictates subsequent H2A/H2B-DNA interactions, which are less affected by the DNA sequence, leading to the final octameric nucleosome. Overall, our results provide a novel, exciting way to investigate those biophysical properties of DNA that constitute a crucial component in nucleosome formation and stabilization.
Rhomboid intramembrane protease RHBDL4 triggers ER-export and non-canonical secretion of membrane-anchored TGFα
Authors: Wunderle Lina , Knopf Julia D. , Kühnle Nathalie , Morlé Aymeric , Hehn Beate , Adrain Colin , Strisovsky Kvido , Freeman Matthew , Lemberg Marius K. 
Published: June 2016

AbstractRhomboid intramembrane proteases are the enzymes that release active epidermal growth factor receptor (EGFR) ligands in Drosophila and C. elegans, but little is known about their functions in mammals. Here we show that the mammalian rhomboid protease RHBDL4 (also known as Rhbdd1) promotes trafficking of several membrane proteins, including the EGFR ligand TGFα, from the endoplasmic reticulum (ER) to the Golgi apparatus, thereby triggering their secretion by extracellular microvesicles. Our data also demonstrate that RHBDL4-dependent trafficking control is regulated by G-protein coupled receptors, suggesting a role for this rhomboid protease in pathological conditions, including EGFR signaling. We propose that RHBDL4 reorganizes trafficking events within the early secretory pathway in response to GPCR signaling. Our work identifies RHBDL4 as a rheostat that tunes secretion dynamics and abundance of specific membrane protein cargoes.
Selective Expression of Osteopontin in ALS-resistant Motor Neurons is a Critical Determinant of Late Phase Neurodegeneration Mediated by Matrix Metalloproteinase-9
Authors: Morisaki Yuta , Niikura Mamiko , Watanabe Mizuho , Onishi Kosuke , Tanabe Shogo , Moriwaki Yasuhiro , Okuda Takashi , Ohara Shinji , Murayama Shigeo , Takao Masaki , Uchida Sae , Yamanaka Koji , Misawa Hidemi 
Published: June 2016

AbstractDifferential vulnerability among motor neuron (MN) subtypes is a fundamental feature of amyotrophic lateral sclerosis (ALS): fast-fatigable (FF) MNs are more vulnerable than fast fatigue-resistant (FR) or slow (S) MNs. The reason for this selective vulnerability remains enigmatic. We report here that the extracellular matrix (ECM) protein osteopontin (OPN) is selectively expressed by FR and S MNs and ALS-resistant motor pools, whereas matrix metalloproteinase-9 (MMP-9) is selectively expressed by FF MNs. OPN is secreted and accumulated as extracellular granules in ECM in three ALS mouse models and a human ALS patient. In SOD1G93A mice, OPN/MMP-9 double positivity marks remodeled FR and S MNs destined to compensate for lost FF MNs before ultimately dying. Genetic ablation of OPN in SOD1G93A mice delayed disease onset but then accelerated disease progression. OPN induced MMP-9 up-regulation via αvβ3 integrin in ChAT-expressing Neuro2a cells and also induced CD44-mediated astrocyte migration and microglial phagocytosis in a non-cell-autonomous manner. Our results demonstrate that OPN expressed by FR/S MNs is involved in the second-wave neurodegeneration by up-regulating MMP-9 through αvβ3 integrin in the mouse model of ALS. The differences in OPN/MMP-9 expression profiles in MN subsets partially explain the selective MN vulnerability in ALS.
Identification of differentially expressed genes from multipotent epithelia at the onset of an asexual development
Authors: Ricci Lorenzo , Chaurasia Ankita , Lapébie Pascal , Dru Philippe , Helm Rebecca R. , Copley Richard R. , Tiozzo Stefano 
Published: June 2016

AbstractOrganisms that have evolved alternative modes of reproduction, complementary to the sexual mode, are found across metazoans. The chordate Botryllus schlosseri is an emerging model for asexual development studies. Botryllus can rebuild its entire body from a portion of adult epithelia in a continuous and stereotyped process called blastogenesis. Anatomy and ontogenies of blastogenesis are well described, however molecular signatures triggering this developmental process are entirely unknown. We isolated tissues at the site of blastogenesis onset and from the same epithelia where this process is never triggered. We linearly amplified an ultra-low amount of mRNA (<10ng) and generated three transcriptome datasets. To provide a conservative landscape of transcripts differentially expressed between blastogenic vs. non-blastogenic epithelia we compared three different mapping and analysis strategies with a de novo assembled transcriptome and partially assembled genome as references, additionally a self-mapping strategy on the dataset. A subset of differentially expressed genes were analyzed and validated by in situ hybridization. The comparison of different analyses allowed us to isolate stringent sets of target genes, including transcripts with potential involvement in the onset of a non-embryonic developmental pathway. The results provide a good entry point to approach regenerative event in a basal chordate.
Three dimensional Graphene aerogels as binder-less, freestanding, elastic and high-performance electrodes for lithium-ion batteries
Authors: Chen Zhihang , Li Hua , Tian Ran , Duan Huanan , Guo Yiping , Chen Yujie , Zhou Jie , Zhang Chunmei , DUGNANI Roberto , Liu Hezhou 
Published: June 2016

AbstractIn this work it is shown how porous graphene aerogels fabricated by an eco-friendly and simple technological process, could be used as electrodes in lithium- ion batteries. The proposed graphene framework exhibited excellent performance including high reversible capacities, superior cycling stability and rate capability. A significantly lower temperature (75 °C) than the one currently utilized in battery manufacturing was utilized for self-assembly hence providing potential significant savings to the industrial production. After annealing at 600 °C, the formation of Sn-C-O bonds between the SnO2 nanoparticles and the reduced graphene sheets will initiate synergistic effect and improve the electrochemical performance. The XPS patterns revealed the formation of Sn-C-O bonds. Both SEM and TEM imaging of the electrode material showed that the three dimensional network of graphene aerogels and the SnO2 particles were distributed homogeneously on graphene sheets. Finally, the electrochemical properties of the samples as active anode materials for lithium-ion batteries were tested and examined by constant current charge–discharge cycling and the finding fully described in this manuscript.
Docetaxel induced-JNK2/PHD1 signaling pathway increases degradation of HIF-1α and causes cancer cell death under hypoxia
Authors: Oh Eun-Taex , Kim Chan Woo , Kim Soo Jung , Lee Jae-Seon , Hong Soon-Sun , Park Heon Joo 
Published: June 2016

AbstractHIF-1 (hypoxia-inducible factor-1) regulates the expression of more than 70 genes involved in angiogenesis, tumor growth, metastasis, chemoresistance, and radioresistance. Thus, there is growing interest in using HIF-1 inhibitors as anticancer drugs. Docetaxel, a Food and Drug Administration-approved anticancer drug, is reported to enhance HIF-1α degradation. Here, we investigated the molecular mechanism underlying docetaxel-induced HIF-1α degradation and cancer cell death under hypoxic conditions. Docetaxel pretreatment enhanced the polyubiquitination and proteasome-mediated degradation of HIF-1α, and increased cancer cell death under hypoxic conditions. Docetaxel also activated the prolyl hydroxylase, PHD1, in hypoxia, and pharmacological inhibition or siRNA-mediated knockdown of PHD1 prevented docetaxel-induced HIF-1α degradation and cancer cell death. Additionally, siRNA-mediated JNK2 knockdown blocked docetaxel-induced HIF-1α degradation and cancer cell death by inhibiting PHD1 activation. A luciferase reporter assay revealed that inhibition of the JNK2/PHD1 signaling pathway significantly increased the transcriptional activity of HIF-1 in docetaxel-treated cancer cells under hypoxia. Consistent with these results, docetaxel-treated JNK2-knockdown tumors grew much faster than control tumors through inhibition of docetaxel-induced PHD1 activation and degradation of HIF-1α. Our results collectively show that, under hypoxic conditions, docetaxel induces apoptotic cell death through JNK2/PHD1 signaling-mediated HIF-1α degradation.
Ultrahigh photoconductivity of bandgap-graded CdSxSe1−x nanowires probed by terahertz spectroscopy
Authors: Liu Hongwei , Lu Junpeng , Yang Zongyin , Teng Jinghua , Ke Lin , Zhang Xinhai , Tong Limin , Sow Chorng Haur 
Published: June 2016

AbstractSuperiorly high photoconductivity is desirable in optoelectronic materials and devices for information transmission and processing. Achieving high photoconductivity via bandgap engineering in a bandgap-graded semiconductor nanowire has been proposed as a potential strategy. In this work, we report the ultrahigh photoconductivity of bandgap-graded CdSxSe1−x nanowires and its detailed analysis by means of ultrafast optical-pump terahertz-probe (OPTP) spectroscopy. The recombination rates and carrier mobility are quantitatively obtained via investigation of the transient carrier dynamics in the nanowires. By analysis of the terahertz (THz) spectra, we obtain an insight into the bandgap gradient and band alignment to carrier transport along the nanowires. The demonstration of the ultrahigh photoconductivity makes bandgap-graded CdSxSe1−x nanowires a promising candidate as building blocks for nanoscale electronic and photonic devices.
Stroke and thromboembolic event rates in atrial fibrillation according to different guideline treatment thresholds: A nationwide cohort study
Authors: Nielsen Peter Brønnum , Larsen Torben Bjerregaard , Skjøth Flemming , Overvad Thure Filskov , Lip Gregory Y. H. 
Published: June 2016

AbstractContemporary guidelines suggest anticoagulant treatment decisions in atrial fibrillation (AF) patients to be based on risk stratification for stroke. However, guidelines do not agree on the threshold for treatment initiation. We explored the variation in thromboembolic event rates in a non-anticoagulated AF population, according to different guideline threshold and methodological approaches. AF patients between 1998 and 2014 free from anticoagulant treatment were identified. Event rates for ischemic stroke and ischemic stroke/systemic embolism were explored. The overall ischemic stroke rate was 3.20 per 100 person-years (‘formal rate assessment’). For patients with a CHA2DS2-VASc score of 1 the ischemic stroke rate was 0.97 when using a ‘formal rate assessment’, 0.62 when using a ‘conditioning on the future’ approach and 0.93 when using a ‘censoring approach’. Rates for thromboembolism for the ‘European treatment threshold’ (CHA2DS2-VASc score of 1, males only) ranged 1.17 to 1.53. Rates for the ‘U.S. treatment threshold’ (CHA2DS2-VASc of 2) ranged from 1.95 to 2.33. Thromboembolic event rates differed markedly in non-anticoagulated AF patients according to the conflicting European and U.S. guideline treatment thresholds. Second, the choice of methodological approach has implications, thus we recommend using the censoring approach for event rate estimation among AF patients not on treatment.
Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission
Authors: Tokudome Kentaro , Okumura Takahiro , Shimizu Saki , Mashimo Tomoji , Takizawa Akiko , Serikawa Tadao , Terada Ryo , Ishihara Shizuka , Kunisawa Naofumi , Sasa Masashi , Ohno Yukihiro 
Published: June 2016

AbstractSynaptic vesicle glycoprotein 2A (SV2A) is a prototype synaptic vesicle protein regulating action potential-dependent neurotransmitters release. SV2A also serves as a specific binding site for certain antiepileptics and is implicated in the treatment of epilepsy. Here, to elucidate the role of SV2A in modulating epileptogenesis, we generated a novel rat model (Sv2aL174Q rat) carrying a Sv2a-targeted missense mutation (L174Q) and analyzed its susceptibilities to kindling development. Although animals homozygous for the Sv2aL174Q mutation exhibited normal appearance and development, they are susceptible to pentylenetetrazole (PTZ) seizures. In addition, development of kindling associated with repeated PTZ treatments or focal stimulation of the amygdala was markedly facilitated by the Sv2aL174Q mutation. Neurochemical studies revealed that the Sv2aL174Q mutation specifically reduced depolarization-induced GABA, but not glutamate, release in the hippocampus without affecting basal release or the SV2A expression level in GABAergic neurons. In addition, the Sv2aL174Q mutation selectively reduced the synaptotagmin1 (Syt1) level among the exocytosis-related proteins examined. The present results demonstrate that dysfunction of SV2A due to the Sv2aL174Q mutation impairs the synaptic GABA release by reducing the Syt1 level and facilitates the kindling development, illustrating the crucial role of SV2A-GABA system in modulating kindling epileptogenesis.
Integrated ultracompact and broadband wavelength demultiplexer based on multi-component nano-cavities
Authors: Lu Cuicui , Liu Yong-Chun , Hu Xiaoyong , Yang Hong , Gong Qihuang 
Published: June 2016

AbstractIntegrated nanoscale photonic devices have wide applications ranging from optical interconnects and optical computing to optical communications. Wavelength demultiplexer is an essential on-chip optical component which can separate the incident wavelength into different channels; however, the experimental progress is very limited. Here, using a multi-component nano-cavity design, we realize an ultracompact, broadband and high-contrast wavelength demultiplexer, with 2.3 μm feature size, 200 nm operation bandwidth (from 780 nm to 980 nm) and a contrast ratio up to 13.7 dB. The physical mechanism is based on the strong modulation of the surface plasmon polaritons induced by the multi-component nano-cavities and it can be generalized to other nanoscale photonic devices. This provides a strategy for constructing on-chip photon routers and also has applications for chip-integrated optical filter and optical logic gates.
Tensional acoustomechanical soft metamaterials
Authors: Xin Fengxian , Lu Tianjian 
Published: June 2016

AbstractWe create acoustomechanical soft metamaterials whose response to uniaxial tensile stressing can be easily tailored by programming acoustic wave inputs, resulting in force versus stretch curves that exhibit distinct monotonic, s-shape, plateau and non-monotonic snapping behaviors. We theoretically demonstrate this unique metamaterial by considering a thin soft material sheet impinged by two counter-propagating ultrasonic wave inputs across its thickness and stretched by an in-plane uniaxial tensile force. We establish a theoretical acoustomechanical model to describe the programmable mechanics of such soft metamaterial, and introduce the first- and second-order tangential stiffness of its force versus stretch curve to boundary different behaviors that appear during deformation. The proposed phase diagrams for the underlying nonlinear mechanics show promising prospects for designing tunable and switchable photonic/phononic crystals and microfluidic devices that harness snap-through instability.