bluuebunny/crossref_metadata_2025 huggingface dataset:
Nucleosomes determine their own patch size in base excision repair
Authors: Meas Rithy , Smerdon Michael J.
Published: June 2016

Base excision repair (BER) processes non-helix distorting lesions (e.g., uracils and gaps) and is composed of two subpathways that differ in the number of nucleotides (nts) incorporated during the DNA synthesis step: short patch (SP) repair incorporates 1 nt and long patch (LP) repair incorporates 2–12 nts. This choice for either LP or SP repair has not been analyzed in the context of nucleosomes. Initial studies with uracil located in nucleosome core DNA showed a distinct DNA polymerase extension profile in cell-free extracts that specifically limits extension to 1 nt, suggesting a preference for SP BER. Therefore, we developed an assay to differentiate long and short repair patches in ‘designed’ nucleosomes containing a single-nucleotide gap at specific locations relative to the dyad center. Using cell-free extracts or purified enzymes, we found that DNA lesions in the nucleosome core are preferentially repaired by DNA polymerase β and there is a significant reduction in BER polymerase extension beyond 1 nt, creating a striking bias for incorporation of short patches into nucleosomal DNA. These results show that nucleosomes control the patch size used by BER.
Imprinting superconducting vortex footsteps in a magnetic layer
Authors: Brisbois Jérémy , Motta Maycon , Avila Jonathan I. , Shaw Gorky , Devillers Thibaut , Dempsey Nora M. , Veerapandian Savita K. P. , Colson Pierre , Vanderheyden Benoît , Vanderbemden Philippe , Ortiz Wilson A. , Nguyen Ngoc Duy , Kramer Roman B. G. , Silhanek Alejandro V.
Published: June 2016

Local polarization of a magnetic layer, a well-known method for storing information, has found its place in numerous applications such as the popular magnetic drawing board toy or the widespread credit cards and computer hard drives. Here we experimentally show that a similar principle can be applied for imprinting the trajectory of quantum units of flux (vortices), travelling in a superconducting film (Nb), into a soft magnetic layer of permalloy (Py). In full analogy with the magnetic drawing board, vortices act as tiny magnetic scribers leaving a wake of polarized magnetic media in the Py board. The mutual interaction between superconducting vortices and ferromagnetic domains has been investigated by the magneto-optical imaging technique. For thick Py layers, the stripe magnetic domain pattern guides both the smooth magnetic flux penetration as well as the abrupt vortex avalanches in the Nb film. It is however in thin Py layers without stripe domains where superconducting vortices leave the clearest imprints of locally polarized magnetic moment along their paths. In all cases, we observe that the flux is delayed at the border of the magnetic layer. Our findings open the quest for optimizing magnetic recording of superconducting vortex trajectories.
Comb-locked Lamb-dip spectrometer
Authors: Gatti Davide , Gotti Riccardo , Gambetta Alessio , Belmonte Michele , Galzerano Gianluca , Laporta Paolo , Marangoni Marco
Published: June 2016

Overcoming the Doppler broadening limit is a cornerstone of precision spectroscopy. Nevertheless, the achievement of a Doppler-free regime is severely hampered by the need of high field intensities to saturate absorption transitions and of a high signal-to-noise ratio to detect tiny Lamb-dip features. Here we present a novel comb-assisted spectrometer ensuring over a broad range from 1.5 to 1.63 μm intra-cavity field enhancement up to 1.5 kW/cm2, which is suitable for saturation of transitions with extremely weak electric dipole moments. Referencing to an optical frequency comb allows the spectrometer to operate with kHz-level frequency accuracy, while an extremely tight locking of the probe laser to the enhancement cavity enables a 10−11 cm−1 absorption sensitivity to be reached over 200 s in a purely dc direct-detection-mode at the cavity output. The particularly simple and robust detection and operating scheme, together with the wide tunability available, makes the system suitable to explore thousands of lines of several molecules never observed so far in a Doppler-free regime. As a demonstration, Lamb-dip spectroscopy is performed on the P(15) line of the 01120-00000 band of acetylene, featuring a line-strength below 10−23 cm/mol and an Einstein coefficient of 5 mHz, among the weakest ever observed.
Critical behavior in a stochastic model of vector mediated epidemics
Authors: Alfinito E. , Beccaria M. , Macorini G.
Published: June 2016

The extreme vulnerability of humans to new and old pathogens is constantly highlighted by unbound outbreaks of epidemics. This vulnerability is both direct, producing illness in humans (dengue, malaria), and also indirect, affecting its supplies (bird and swine flu, Pierce disease, and olive quick decline syndrome). In most cases, the pathogens responsible for an illness spread through vectors. In general, disease evolution may be an uncontrollable propagation or a transient outbreak with limited diffusion. This depends on the physiological parameters of hosts and vectors (susceptibility to the illness, virulence, chronicity of the disease, lifetime of the vectors,etc.). In this perspective and with these motivations, we analyzed a stochastic lattice model able to capture the critical behavior of such epidemics over a limited time horizon and with a finite amount of resources. The model exhibits a critical line of transition that separates spreading and non-spreading phases. The critical line is studied with new analytical methods and direct simulations. Critical exponents are found to be the same as those of dynamical percolation.
Social apoptosis in honey bee superorganisms
Authors: Page Paul , Lin Zheguang , Buawangpong Ninat , Zheng Huoqing , Hu Fuliang , Neumann Peter , Chantawannakul Panuwan , Dietemann Vincent
Published: June 2016

Eusocial insect colonies form superorganisms, in which nestmates cooperate and use social immunity to combat parasites. However, social immunity may fail in case of emerging diseases. This is the case for the ectoparasitic mite Varroa destructor, which switched hosts from the Eastern honeybee, Apis cerana, to the Western honey bee, Apis mellifera and currently is the greatest threat to A. mellifera apiculture globally. Here, we show that immature workers of the mite’s original host, A. cerana, are more susceptible to V. destructor infestations than those of its new host, thereby enabling more efficient social immunity and contributing to colony survival. This counterintuitive result shows that susceptible individuals can foster superorganism survival, offering empirical support to theoretical arguments about the adaptive value of worker suicide in social insects. Altruistic suicide of immature bees constitutes a social analogue of apoptosis, as it prevents the spread of infections by sacrificing parts of the whole organism and unveils a novel form of transgenerational social immunity in honey bees. Taking into account the key role of susceptible immature bees in social immunity will improve breeding efforts to mitigate the unsustainably high colony losses of Western honey bees due to V. destructor infestations worldwide.
Range expansion of the Bluetongue vector, Culicoides imicola, in continental France likely due to rare wind-transport events
Authors: Jacquet Stéphanie , Huber Karine , Pagès Nonito , Talavera Sandra , Burgin Laura E. , Carpenter Simon , Sanders Christopher , Dicko Ahmadou H. , Djerbal Mouloud , Goffredo Maria , Lhor Youssef , Lucientes Javier , Miranda-Chueca Miguel A. , Pereira Da Fonseca Isabel , Ramilo David W. , Setier-Rio Marie-Laure , Bouyer Jérémy , Chevillon Christine , Balenghien Thomas , Guis Hélène , Garros Claire
Published: June 2016

The role of the northward expansion of Culicoides imicola Kieffer in recent and unprecedented outbreaks of Culicoides-borne arboviruses in southern Europe has been a significant point of contention. We combined entomological surveys, movement simulations of air-borne particles, and population genetics to reconstruct the chain of events that led to a newly colonized French area nestled at the northern foot of the Pyrenees. Simulating the movement of air-borne particles evidenced frequent wind-transport events allowing, within at most 36 hours, the immigration of midges from north-eastern Spain and Balearic Islands, and, as rare events, their immigration from Corsica. Completing the puzzle, population genetic analyses discriminated Corsica as the origin of the new population and identified two successive colonization events within west-Mediterranean basin. Our findings are of considerable importance when trying to understand the invasion of new territories by expanding species.
Metabolic rates of giant pandas inform conservation strategies
Authors: Fei Yuxiang , Hou Rong , Spotila James R. , Paladino Frank V. , Qi Dunwu , Zhang Zhihe
Published: June 2016

The giant panda is an icon of conservation and survived a large-scale bamboo die off in the 1980s in China. Captive breeding programs have produced a large population in zoos and efforts continue to reintroduce those animals into the wild. However, we lack sufficient knowledge of their physiological ecology to determine requirements for survival now and in the face of climate change. We measured resting and active metabolic rates of giant pandas in order to determine if current bamboo resources were sufficient for adding additional animals to populations in natural reserves. Resting metabolic rates were somewhat below average for a panda sized mammal and active metabolic rates were in the normal range. Pandas do not have exceptionally low metabolic rates. Nevertheless, there is enough bamboo in natural reserves to support both natural populations and large numbers of reintroduced pandas. Bamboo will not be the limiting factor in successful reintroduction.
Synchrotron X-ray microtransections: a non invasive approach for epileptic seizures arising from eloquent cortical areas
Authors: Pouyatos B. , Nemoz C. , Chabrol T. , Potez M. , Bräuer E. , Renaud L. , Pernet-Gallay K. , Estève F. , David O. , Kahane P. , Laissue J. A. , Depaulis A. , Serduc R.
Published: June 2016

Synchrotron-generated X-ray (SRX) microbeams deposit high radiation doses to submillimetric targets whilst minimizing irradiation of neighboring healthy tissue. We developed a new radiosurgical method which demonstrably transects cortical brain tissue without affecting adjacent regions. We made such image-guided SRX microtransections in the left somatosensory cortex in a rat model of generalized epilepsy using high radiation doses (820 Gy) in thin (200 μm) parallel slices of tissue. This procedure, targeting the brain volume from which seizures arose, altered the abnormal neuronal activities for at least 9 weeks, as evidenced by a decrease of seizure power and coherence between tissue slices in comparison to the contralateral cortex. The brain tissue located between transections stayed histologically normal, while the irradiated micro-slices remained devoid of myelin and neurons two months after irradiation. This pre-clinical proof of concept highlights the translational potential of non-invasive SRX transections for treating epilepsies that are not eligible for resective surgery.
Induction of Germ Cell-like Cells from Porcine Induced Pluripotent Stem Cells
Authors: Wang Hanning , Xiang Jinzhu , Zhang Wei , Li Junhong , Wei Qingqing , Zhong Liang , Ouyang Hongsheng , Han Jianyong
Published: June 2016

The ability to generate germ cells from pluripotent stem cells (PSCs) is valuable for human regenerative medicine and animal breeding. Germ cell-like cells (GCLCs) have been differentiated from mouse and human PSCs, but not from porcine PSCs, which are considered an ideal model for stem cell applications. Here, we developed a defined culture system for the induction of primordial germ cell-like cells (PGCLCs) from porcine induced PSCs (piPSCs). The identity of the PGCLCs was characterized by observing cell morphology, detecting germ cell marker gene expression and evaluating epigenetic properties. PGCLCs could further differentiate into spermatogonial stem cell-like cells (SSCLCs)in vitro. Importantly, meiosis occurred during SSCLC induction. Xenotransplantation of GCLCs into seminiferous tubules of infertile immunodeficient mice resulted in immunohistochemically identifiable germ cellsin vivo. Overall, our study provides a feasible strategy for directing piPSCs to the germ cell fate and lays a foundation for exploring germ cell development mechanisms.
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

MCRS1 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

Control 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

Non-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

The 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

Weeds 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

We 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

Rhomboid 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

Differential 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

Organisms 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

In 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

HIF-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

Superiorly 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

Contemporary 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

Synaptic 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

Integrated 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

We 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.
IRESPred: Web Server for Prediction of Cellular and Viral Internal Ribosome Entry Site (IRES)
Authors: Kolekar Pandurang , Pataskar Abhijeet , Kulkarni-Kale Urmila , Pal Jayanta , Kulkarni Abhijeet
Published: June 2016

Cellular mRNAs are predominantly translated in a cap-dependent manner. However, some viral and a subset of cellular mRNAs initiate their translation in a cap-independent manner. This requires presence of a structured RNA element, known as, Internal Ribosome Entry Site (IRES) in their 5′ untranslated regions (UTRs). Experimental demonstration of IRES in UTR remains a challenging task. Computational prediction of IRES merely based on sequence and structure conservation is also difficult, particularly for cellular IRES. A web server, IRESPred is developed for prediction of both viral and cellular IRES using Support Vector Machine (SVM). The predictive model was built using 35 features that are based on sequence and structural properties of UTRs and the probabilities of interactions between UTR and small subunit ribosomal proteins (SSRPs). The model was found to have 75.51% accuracy, 75.75% sensitivity, 75.25% specificity, 75.75% precision and Matthews Correlation Coefficient (MCC) of 0.51 in blind testing. IRESPred was found to perform better than the only available viral IRES prediction server, VIPS. The IRESPred server is freely available at http://bioinfo.net.in/IRESPred/.
The SDF-1 rs1801157 Polymorphism is Associated with Cancer Risk: An Update Pooled Analysis and FPRP Test of 17,876 Participants
Authors: Tong Xiang , Ma Yao , Deng Huajiang , Wang Xixi , Liu Sitong , Yan Zhipeng , Peng Shifeng , Fan Hong
Published: June 2016

The stromal cell derived factor-1 (SDF-1) rs1801157 gene polymorphism has been implicated in susceptibility to cancer, but the results were inconclusive. The current study was to precisely investigate the association between SDF-1 rs1801157 polymorphism and cancer risk using meta-analysis and the false positive report probability (FPRP) test. All 17,876 participants were included in the study. The meta-analysis results indicated a significant association between the SDF-1 rs1801157 polymorphism and cancer risk. By subgroup analyses, the results detected that the SDF-1 rs1801157 polymorphism was associated with cancer susceptibility among Asians and Caucasians. Additionally, we also found significant associations between the SDF-1 rs1801157 polymorphism and susceptibility to different types of cancer. However, to avoid a “false positive report”, we further investigated the significant associations observed in the present meta-analysis using the FPRP test. Interestingly, the results of the FPRP test indicated that only 4 gene models were truly associated with cancer risk, especially in Asians. Moreover, we confirmed that the SDF-1 rs1801157 gene polymorphism was only associated with lung and urologic cancer risk. In summary, this study suggested that the SDF-1 rs1801157 polymorphism may serve as a risk factor for cancer development among Asians, especially an increased risk of urologic and lung cancers.
High-contrast grating resonators for label-free detection of disease biomarkers
Authors: Sun Tianbo , Kan Shu , Marriott Gerard , Chang-Hasnain Connie
Published: June 2016

A label-free optical biosensor is described that employs a silicon-based high-contrast grating (HCG) resonator with a spectral linewidth of ~500 pm that is sensitive to ligand-induced changes in surface properties. The device is used to generate thermodynamic and kinetic data on surface-attached antibodies with their respective antigens. The device can detect serum cardiac troponin I, a biomarker of cardiac disease to 100 pg/ml within 4 mins, which is faster and as sensitive as current enzyme-linked immuno-assays for cTnI.
The presence of disulfide bonds reveals an evolutionarily conserved mechanism involved in mitochondrial protein translocase assembly
Authors: Wrobel Lidia , Sokol Anna M. , Chojnacka Magdalena , Chacinska Agnieszka
Published: June 2016

Disulfide bond formation is crucial for the biogenesis and structure of many proteins that are localized in the intermembrane space of mitochondria. The importance of disulfide bond formation within mitochondrial proteins was extended beyond soluble intermembrane space proteins. Tim22, a membrane protein and core component of the mitochondrial translocase TIM22, forms an intramolecular disulfide bond in yeast. Tim22 belongs to the Tim17/Tim22/Tim23 family of protein translocases. Here, we present evidence of the high evolutionary conservation of disulfide bond formation in Tim17 and Tim22 among fungi and metazoa. Topological models are proposed that include the location of disulfide bonds relative to the predicted transmembrane regions. Yeast and human Tim22 variants that are not oxidized do not properly integrate into the membrane complex. Moreover, the lack of Tim17 oxidation disrupts the TIM23 translocase complex. This underlines the importance of disulfide bond formation for mature translocase assembly through membrane stabilization of weak transmembrane domains.
Large transverse Hall-like signal in topological Dirac semimetal Cd3As2
Authors: Guo Shih-Ting , Sankar R. , Chien Yung-Yu , Chang Tay-Rong , Jeng Horng-Tay , Guo Guang-Yu , Chou F. C. , Lee Wei-Li
Published: June 2016

Cadmium arsenide (Cd3As2) is known for its inverted band structure and ultra-high electron mobility. It has been theoretically predicted and also confirmed by ARPES experiments to exhibit a 3D Dirac semimetal phase containing degenerate Weyl nodes. From magneto-transport measurements in high quality single crystals of Cd3As2, a small effective mass m* ≈ 0.05 me is determined from the Shubnikov-de Haas (SdH) oscillations. In certain field orientations, we find a splitting of the SdH oscillation frequency in the FFT spectrum suggesting a possible lifting of the double degeneracy in accord with the helical spin texture at outer and inner Fermi surfaces with opposite chirality predicted by our ab initio calculations. Strikingly, a large antisymmetric magnetoresistance with respect to the applied magnetic fields is uncovered over a wide temperature range in needle crystal of Cd3As2 with its long axis along [112] crystal direction. It reveals a possible contribution of intrinsic anomalous velocity term in the transport equation resulting from a unique 3D Rashba-like spin splitted bands that can be obtained from band calculations with the inclusion of Cd antisite defects.
Accelerated dysbiosis of gut microbiota during aggravation of DSS-induced colitis by a butyrate-producing bacterium
Authors: Zhang Qianpeng , Wu Yanqiu , Wang Jing , Wu Guojun , Long Wenmin , Xue Zhengsheng , Wang Linghua , Zhang Xiaojun , Pang Xiaoyan , Zhao Yufeng , Zhao Liping , Zhang Chenhong
Published: June 2016

Butyrate-producing bacteria (BPB) are potential probiotic candidates for inflammatory bowel diseases as they are often depleted in the diseased gut microbiota. However, here we found that augmentation of a human-derived butyrate-producing strain, Anaerostipes hadrus BPB5, significantly aggravated colitis in dextran sulphate sodium (DSS)-treated mice while exerted no detrimental effect in healthy mice. We explored how the interaction between BPB5 and gut microbiota may contribute to this differential impact on the hosts. Butyrate production and severity of colitis were assessed in both healthy and DSS-treated mice, and gut microbiota structural changes were analysed using high-throughput sequencing. BPB5-inoculated healthy mice showed no signs of colitis, but increased butyrate content in the gut. In DSS-treated mice, BPB5 augmentation did not increase butyrate content, but induced significantly more severe disease activity index and much higher mortality. BPB5 didn’t induce significant changes of gut microbiota in healthy hosts, but expedited the structural shifts 3 days earlier toward the disease phase in BPB5-augmented than DSS-treated animals. The differential response of gut microbiota in healthy and DSS-treated mice to the same potentially beneficial bacterium with drastically different health consequences suggest that animals with dysbiotic gut microbiota should also be employed for the safety assessment of probiotic candidates.
Spatial confinement governs orientational order in patchy particles
Authors: Iwashita Yasutaka , Kimura Yasuyuki
Published: June 2016

Orientational order in condensed matter plays a key role in determining material properties such as ferromagnetism, viscoelasticity or birefringence. We studied purely orientational ordering in closely-packed one-patch colloidal particles confined between flat substrates, where the particles can only rotate and are ordered via the sticky interaction between the patches. For the first time, we experimentally realized a rich variety of mesoscopic patterns through orientational ordering of colloids by controlling patch size and confinement thickness. The combination of experiment and numerical simulation reveals the decisive role of confinement: An ordered state(s) is selected from the (meta)stable options in bulk when it is commensurate with the system geometry and boundary conditions; otherwise, frustration induces a unique order. Our study offers a new means of systematic control over mesoscopic structures via orientational ordering in patchy particles. The system would also possess unique functionalities through the rotational response of the particles to external stimuli.
Novel Fe–Ce–Ti catalyst with remarkable performance for the selective catalytic reduction of NOx by NH3
Authors: Liu Zhiming , Liu Yuxian , Chen Biaohua , Zhu Tianle , Ma Lingling
Published: June 2016

The redox cycle (Ce4+ + Fe2+ ↔ Ce3+ + Fe3+) over the Fe–Ce–Ti catalyst contributes to the activation of NOx and NH3 and thus the formation of reaction intermediates, leading to the high catalytic performance for the NH3-SCR of NOx.
Development of a niobium-doped titania inert anode for titanium electrowinning in molten chloride salts
Authors: Snook Graeme A. , McGregor Katherine , Urban Andrew J. , Lanyon Marshall R. , Donelson R. , Pownceby Mark I.
Published: June 2016

The direct electrochemical reduction of solid titanium dioxide in a chloride melt is an attractive method for the production of titanium metal. It has been estimated that this type of electrolytic approach may reduce the costs of producing titanium sponge by more than half, with the additional benefit of a smaller environmental footprint. The process utilises a consumable carbon anode which releases a mixture of CO2and CO gas during electrolysis, but suffers from low current efficiency due to the occurrence of parasitic side reactions involving carbon. The replacement of the carbon anode with a cheap, robust inert anode offers numerous benefits that include: elimination of carbon dioxide emissions, more efficient cell operation, opportunity for three-dimensional electrode configurations and reduced electrode costs. This paper reports a study of Nb-doped titania anode materials for inert anodes in a titanium electrolytic reduction cell. The study examines the effect of niobium content and sintering conditions on the performance of Nb-doped TiO2anodes in laboratory-scale electrolysis tests. Experimental findings, including performance in a 100 h laboratory electrolysis test, are described.
The efficiencies of resonant and nonresonant multiphoton ionization in the femtosecond region
Authors: Kouno Hiroaki , Imasaka Totaro
Published: June 2016

Multiphoton ionization processes studied using a tunable femtosecond laser.
Sensitive fluorescence assay of organophosphorus pesticides based on the fluorescence resonance energy transfer between CdTe quantum dots and porphyrin
Authors: Xue Gao , Yue Zhao , Bing Zhang , Yiwei Tang , Xiuying Liu , Jianrong Li
Published: June 2016

A sensitive and selective quantum dot (QD)-based fluorescence resonance energy transfer (FRET) biosensor was successfully fabricated for the detection of organophosphorus pesticides (OPs).
Monolith dip-it: a bifunctional device for improving the sensitivity of direct analysis in real time mass spectrometry
Authors: Li Xianjiang , Li Ze , Wang Xin , Nie Honggang , Zhang Yiding , Bai Yu , Liu Huwei
Published: June 2016

A bifunctional monolith dip-it was fabricated and applied for improving the sensitivity of direct analysis in real time mass spectrometry (DART-MS).
iSERS microscopy guided by wide field immunofluorescence: analysis of HER2 expression on normal and breast cancer FFPE tissue sections
Authors: Wang Xin-Ping , Zhang Yuying , König Matthias , Papadopoulou Evanthia , Walkenfort Bernd , Kasimir-Bauer Sabine , Bankfalvi Agnes , Schlücker Sebastian
Published: June 2016

Surface-enhanced Raman scattering (SERS) microscopy is an emerging imaging technique for tissue-based cancer diagnostics.
Synthesis of ordered conjugated polycyclic aromatic hydrocarbon polymers through polymerization reaction on Au(111)
Authors: Wang Zhongping , Zhao Huiling , Lu Yan , Xiang Feifei , Leng Xinli , Liu Xiaoqing , Song Xin , Dong Mingdong , Wang Li
Published: June 2016

Synthesis of ordered conjugated polycyclic aromatic hydrocarbon polymers parallel along specific directions within the initial close-packed assembled structure of the precursors.