bluuebunny/crossref_metadata_2025 huggingface dataset:
Meta-adaptation in the auditory midbrain under cortical influence
Authors: Robinson Benjamin L. , Harper Nicol S. , McAlpine David
Published: November 2016

Neural adaptation is central to sensation. Neurons in auditory midbrain, for example, rapidly adapt their firing rates to enhance coding precision of common sound intensities. However, it remains unknown whether this adaptation is fixed, or dynamic and dependent on experience. Here, using guinea pigs as animal models, we report that adaptation accelerates when an environment is re-encountered—in response to a sound environment that repeatedly switches between quiet and loud, midbrain neurons accrue experience to find an efficient code more rapidly. This phenomenon, which we term meta-adaptation, suggests a top–down influence on the midbrain. To test this, we inactivate auditory cortex and find acceleration of adaptation with experience is attenuated, indicating a role for cortex—and its little-understood projections to the midbrain—in modulating meta-adaptation. Given the prevalence of adaptation across organisms and senses, meta-adaptation might be similarly common, with extensive implications for understanding how neurons encode the rapidly changing environments of the real world.
Interaction of the cotranslational Hsp70 Ssb with ribosomal proteins and rRNA depends on its lid domain
Authors: Gumiero Andrea , Conz Charlotte , Gesé Genís Valentín , Zhang Ying , Weyer Felix Alexander , Lapouge Karine , Kappes Julia , von Plehwe Ulrike , Schermann Géza , Fitzke Edith , Wölfle Tina , Fischer Tamás , Rospert Sabine , Sinning Irmgard
Published: November 2016

Cotranslational chaperones assist in de novo folding of nascent polypeptides in all organisms. In yeast, the heterodimeric ribosome-associated complex (RAC) forms a unique chaperone triad with the Hsp70 homologue Ssb. We report the X-ray structure of full length Ssb in the ATP-bound open conformation at 2.6 Å resolution and identify a positively charged region in the α-helical lid domain (SBDα), which is present in all members of the Ssb-subfamily of Hsp70s. Mutational analysis demonstrates that this region is strictly required for ribosome binding. Crosslinking shows that Ssb binds close to the tunnel exit via contacts with both, ribosomal proteins and rRNA, and that specific contacts can be correlated with switching between the open (ATP-bound) and closed (ADP-bound) conformation. Taken together, our data reveal how Ssb dynamics on the ribosome allows for the efficient interaction with nascent chains upon RAC-mediated activation of ATP hydrolysis.
Soluble IL-33 receptor sST2 inhibits colorectal cancer malignant growth by modifying the tumour microenvironment
Authors: Akimoto Miho , Maruyama Riruke , Takamaru Hiroyuki , Ochiya Takahiro , Takenaga Keizo
Published: November 2016

Interleukin-33 (IL-33) was recently shown to be involved in the inflammatory tumour microenvironment and the progression of colorectal cancer (CRC). We report here that the expression level of sST2, a soluble form of the IL-33 receptor (ST2L), is inversely associated with the malignant growth of CRC. sST2 is downregulated in high-metastatic cells compared with low-metastatic human and mouse CRC cells. Knockdown of sST2 in low-metastatic cells enhances tumour growth, metastasis and tumour angiogenesis, whereas its overexpression in high-metastatic cells suppresses these processes. Circulating and intratumourally administered sST2-Fc fusion protein reduce tumour growth, metastatic spread and tumour angiogenesis in mice bearing high-metastatic CRC. Mechanistically, sST2 suppresses IL-33-induced angiogenesis, Th1- and Th2-responses, macrophage infiltration and macrophage M2a polarization. In conclusion, we show that sST2 negatively regulates tumour growth and the metastatic spread of CRC through modification of the tumour microenvironment. Thus, the IL-33/ST2L axis may be a potential therapeutic target in CRC.
High expression of GNA13 is associated with poor prognosis in hepatocellular carcinoma
Authors: Xu Yi , Rong Jian , Duan Shiyu , Chen Cui , Li Yin , Peng Baogang , Yi Bin , Zheng Zhousan , Gao Ying , Wang Kebing , Yun Miao , Weng Huiwen , Zhang Jiaxing , Ye Sheng
Published: November 2016

Guanine nucleotide binding protein alpha 13 (GNA13) has been found to play critical roles in the development of several human cancers. However, little is known about GNA13 expression and its clinical significance in hepatocellular carcinoma (HCC). In our study, GNA13 was reported to be significantly up-regulated in HCC tissues, and this was correlated with several clinicopathological parameters, including tumor multiplicity (P = 0.004), TNM stage (P = 0.002), and BCLC stage (P = 0.010). Further Cox regression analysis suggested that GNA13 expression was an independent prognostic factor for overall survival (P = 0.014) and disease-free survival (P = 0.005). Moreover, we found that overexpression of GNA13 couldn’t promote cell proliferation in vitro, but could significantly increase the invasion ability of HCC cells. Together, our study demonstrates GNA13 may be served as a prognostic biomarker for HCC patients after curative hepatectomy, in which high expression of GNA13 suggests poor prognosis of HCC patients.
Integrated microRNA and messenger RNA analysis in aortic stenosis
Authors: Coffey Sean , Williams Michael J. A. , Phillips L. Vicky , Galvin Ivor F. , Bunton Richard W. , Jones Gregory T.
Published: November 2016

Aortic valve stenosis (AS) is a major cause of morbidity and mortality, with no effective medical therapies. Investigation into the underlying biology of AS in humans is limited by difficulties in obtaining healthy valvular tissue for use as a control group. However, micro-ribonucleic acids (miRNAs) are stable in post-mortem tissue. We compared valve specimens from patients undergoing aortic valve replacement for AS to non-diseased cadaveric valves. We found 106 differentially expressed miRNAs (p < 0.05, adjusted for multiple comparisons) on microarray analysis, with highly correlated expression among up- and down-regulated miRNAs. Integrated miRNA/gene expression analysis validated the microarray results as a whole, while quantitative polymerase chain reaction confirmed downregulation of miR-122-5p, miR-625-5p, miR-30e-5p and upregulation of miR-21-5p and miR-221-3p. Pathway analysis of the integrated miRNA/mRNA network identified pathways predominantly involved in extracellular matrix function. A number of currently available therapies target products of upregulated genes in the integrated miRNA/mRNA network, with these genes being predominantly more peripheral members of the network. The identification of a group of tissue miRNA associated with AS may contribute to the development of new therapeutic approaches to AS. This study highlights the importance of systems biology-based approaches to complex diseases.
Sphingosine 1-phosphate lyase ablation disrupts presynaptic architecture and function via an ubiquitin- proteasome mediated mechanism
Authors: Mitroi Daniel N. , Deutschmann André U. , Raucamp Maren , Karunakaran Indulekha , Glebov Konstantine , Hans Michael , Walter Jochen , Saba Julie , Gräler Markus , Ehninger Dan , Sopova Elena , Shupliakov Oleg , Swandulla Dieter , van Echten-Deckert Gerhild
Published: November 2016

The bioactive lipid sphingosine 1-phosphate (S1P) is a degradation product of sphingolipids that are particularly abundant in neurons. We have shown previously that neuronal S1P accumulation is toxic leading to ER-stress and an increase in intracellular calcium. To clarify the neuronal function of S1P, we generated brain-specific knockout mouse models in which S1P-lyase (SPL), the enzyme responsible for irreversible S1P cleavage was inactivated. Constitutive ablation of SPL in the brain (SPLfl/fl/Nes) but not postnatal neuronal forebrain-restricted SPL deletion (SPLfl/fl/CaMK) caused marked accumulation of S1P. Hence, altered presynaptic architecture including a significant decrease in number and density of synaptic vesicles, decreased expression of several presynaptic proteins, and impaired synaptic short term plasticity were observed in hippocampal neurons from SPLfl/fl/Nes mice. Accordingly, these mice displayed cognitive deficits. At the molecular level, an activation of the ubiquitin-proteasome system (UPS) was detected which resulted in a decreased expression of the deubiquitinating enzyme USP14 and several presynaptic proteins. Upon inhibition of proteasomal activity, USP14 levels, expression of presynaptic proteins and synaptic function were restored. These findings identify S1P metabolism as a novel player in modulating synaptic architecture and plasticity.
Thermally induced magnetic relaxation in square artificial spin ice
Authors: Andersson M. S. , Pappas S. D. , Stopfel H. , Östman E. , Stein A. , Nordblad P. , Mathieu R. , Hjörvarsson B. , Kapaklis V.
Published: November 2016

The properties of natural and artificial assemblies of interacting elements, ranging from Quarks to Galaxies, are at the heart of Physics. The collective response and dynamics of such assemblies are dictated by the intrinsic dynamical properties of the building blocks, the nature of their interactions and topological constraints. Here we report on the relaxation dynamics of the magnetization of artificial assemblies of mesoscopic spins. In our model nano-magnetic system - square artificial spin ice – we are able to control the geometrical arrangement and interaction strength between the magnetically interacting building blocks by means of nano-lithography. Using time resolved magnetometry we show that the relaxation process can be described using the Kohlrausch law and that the extracted temperature dependent relaxation times of the assemblies follow the Vogel-Fulcher law. The results provide insight into the relaxation dynamics of mesoscopic nano-magnetic model systems, with adjustable energy and time scales, and demonstrates that these can serve as an ideal playground for the studies of collective dynamics and relaxations.
Allostasis in health and food addiction
Authors: De Ridder Dirk , Manning Patrick , Leong Sook Ling , Ross Samantha , Vanneste Sven
Published: November 2016

Homeostasis is the basis of modern medicine and allostasis, a further elaboration of homeostasis, has been defined as stability through change, which was later modified to predictive reference resetting. It has been suggested that pleasure is related to salience (behavioral relevance), and withdrawal has been linked to allostasis in addictive types. The question arises how the clinical and neural signatures of pleasure, salience, allostasis and withdrawal relate, both in a non-addicted and addicted state. Resting state EEGs were performed in 66 people, involving a food-addicted obese group, a non-food addicted obese group and a lean control group. Correlation analyses were performed on behavioral data, and correlation, comparative and conjunction analyses were performed to extract electrophysiological relationships between pleasure, salience, allostasis and withdrawal. Pleasure/liking seems to be the phenomenological expression that enough salient stimuli are obtained, and withdrawal can be seen as a motivational incentive because due to allostatic reference resetting, more stimuli are required. In addition, in contrast to non-addiction, a pathological, non-adaptive salience attached to food results in withdrawal mediated through persistent allostatic reference resetting.
Seed sojourn and fast viability loss constrain seedling production of a prominent riparian protection plant Salix variegata Franch
Authors: Ayi Qiaoli , Zeng Bo , Liu Jianhui , Shi Shaohua , Niu Hangang , Lin Feng , Zhang Yeyi
Published: November 2016

Salix variegata Franch, a prominent plant applied in riparian shelter vegetation in Three Gorges reservoir region of China, produces many seeds every year but generates only a few or no seedlings. Whether the low seedling production of S. variegata is caused by seed sterility or by rapid loss of seed viability remains unknown. We investigated the sojourn time of mature seeds in capsules produced in early, mid, and late reproductive season and the germinability of mature seeds fresh or stored after different period of time. The sojourn time of seeds in capsules was 2.89, 3.95, and 4.72 days in early, mid, and late reproductive season, respectively. The maximal germination percentage of non-stored fresh seeds produced in early, mid, and late reproductive season was 93.33%, 78.67%, and 40%, respectively, which indicates mature seeds were not sterile. The longest viability-retaining time of seeds produced in early, mid, and late reproductive season was only 8, 16, 16 days, respectively, indicating that mature seeds of S. variegata lost viability very rapidly. Mature seeds possessed good viability, but their rapid viability loss caused the low seedling production and hampered the population growth of S. variegata in the riparian area of Three Gorges reservoir region.
Seep-carbonate lamination controlled by cyclic particle flux
Authors: Himmler Tobias , Bayon Germain , Wangner David , Enzmann Frieder , Peckmann Jörn , Bohrmann Gerhard
Published: November 2016

Authigenic carbonate build-ups develop at seafloor methane-seeps, where microbially mediated sulphate-dependent anaerobic oxidation of methane facilitates carbonate precipitation. Despite being valuable recorders of past methane seepage events, their role as archives of atmospheric processes has not been examined. Here we show that cyclic sedimentation pulses related to the Indian monsoon in concert with authigenic precipitation of methane-derived aragonite gave rise to a well-laminated carbonate build-up within the oxygen minimum zone off Pakistan (northern Arabian Sea). U–Th dating indicates that the build-up grew during past ~1,130 years, creating an exceptional high-resolution archive of the Indian monsoon system. Monsoon-controlled formation of seep-carbonates extends the known environmental processes recorded by seep-carbonates, revealing a new relationship between atmospheric and seafloor processes.
Lower Vitamin D Metabolites Levels Were Associated With Increased Coronary Artery Diseases in Type 2 Diabetes Patients in India
Authors: Adela Ramu , Borkar Roshan M , Bhandi Murali Mohan , Vishwakarma Gayatri , Reddy P. Naveen Chander , Srinivas R. , Banerjee Sanjay K
Published: November 2016

The purpose of the present study was to measure six vitamin D metabolites and to find the association between vitamin D deficiency and coronary artery diseases in diabetes (T2DM_CAD). Four groups [control (n = 50), type 2 diabetes (T2DM, n = 71), coronary artery diseases (CAD, n = 28), T2DM_CAD (n = 38)] of total 187 subjects were included in the study. Six vitamin D metabolites (D2, D3, 25(OH)D2, 25(OH)D3, 1,25(OH)2D2, 1,25(OH)2D3), total 25(OH)D and total 1,25(OH)2D were measured by UPLC/APCI/HRMS method in these subjects. Although all the vitamin D metabolites were significantly decreased in T2DM_CAD as compared to both control and T2DM subjects (p < 0.05), only two metabolites i.e., 25(OH)D3 and total 25(OH)D were significantly (p < 0.05) decreased in the T2DM subjects as compared with the control subjects (p < 0.05). Vitamin D3, 1,25(OH)2D2, 25(OH)D, and 1,25(OH)2D levels were significantly decreased in T2DM_CAD subjects as compared with CAD subjects (p < 0.05). Further, multiple logistic regression analysis revealed that total 25(OH)D and total 1,25(OH)2D can be used to predict T2DM (OR 0.82.95% CI 0.68–0.99; p = 0.0208) and T2DM with CAD (OR 0.460, 95% CI 0.242–0.874; p = 0.0177), respectively. Our data concludes that lower concentration of 1,25(OH)2D is associated with type 2 diabetes coexisting with coronary artery diseases in South Indian subjects.
Radiocaesium partitioning in Japanese cedar forests following the “early” phase of Fukushima fallout redistribution
Authors: Coppin Frederic , Hurtevent Pierre , Loffredo Nicolas , Simonucci Caroline , Julien Anthony , Gonze Marc-Andre , Nanba Kenji , Onda Yuichi , Thiry Yves
Published: November 2016

Our study focused on radiocaesium (137Cs) partitioning in forests, three vegetation periods after the Fukushima Daiichi nuclear power plant accident.137Cs distribution in forest components (organic and mineral soil layers as well as tree compartments: stem, bark, needles, branches and roots) was measured for two Japanese cedar stand ages (17 and 33 years old). The results showed that around 85% of the initial deposit was found in the forest floor and topsoil. For the youngest stand almost 70% of the deposit is present in the forest floor, whereas for the oldest stand 50% is present in the 0–3 cm mineral soil layer. For trees, old and perennial organs (including dead and living needles and branches, litter fall and outer bark) directly exposed to the fallout remained the most contaminated. The crown concentrated 61–69% of the total tree contamination. Surprisingly the dead organs concentrated 25 ± 9% (young cedars) to 36 ± 20% (mature cedar) of the trees’ residual activity, highlighting the importance of that specific compartment in the early post-accident phase for Japanese cedar forests. Although the stem (including bark) represents the highest biomass pool, it only concentrates 3.3% and 4.6% of the initial137Cs deposit for mature and young cedars, respectively.
Brain-inspired speech segmentation for automatic speech recognition using the speech envelope as a temporal reference
Authors: Lee Byeongwook , Cho Kwang-Hyun
Published: November 2016

Speech segmentation is a crucial step in automatic speech recognition because additional speech analyses are performed for each framed speech segment. Conventional segmentation techniques primarily segment speech using a fixed frame size for computational simplicity. However, this approach is insufficient for capturing the quasi-regular structure of speech, which causes substantial recognition failure in noisy environments. How does the brain handle quasi-regular structured speech and maintain high recognition performance under any circumstance? Recent neurophysiological studies have suggested that the phase of neuronal oscillations in the auditory cortex contributes to accurate speech recognition by guiding speech segmentation into smaller units at different timescales. A phase-locked relationship between neuronal oscillation and the speech envelope has recently been obtained, which suggests that the speech envelope provides a foundation for multi-timescale speech segmental information. In this study, we quantitatively investigated the role of the speech envelope as a potential temporal reference to segment speech using its instantaneous phase information. We evaluated the proposed approach by the achieved information gain and recognition performance in various noisy environments. The results indicate that the proposed segmentation scheme not only extracts more information from speech but also provides greater robustness in a recognition test.
Inter-annual maintenance of the fine-scale genetic structure in a biennial plant
Authors: Valverde Javier , Gómez José María , García Cristina , Sharbel Timothy F. , Jiménez María Noelia , Perfectti Francisco
Published: November 2016

Within plant populations, space-restricted gene movement, together with environmental heterogeneity, can result in a spatial variation in gene frequencies. In biennial plants, inter-annual flowering migrants can homogenize gene frequencies between consecutive cohorts. However, the actual impact of these migrants on spatial genetic variation remains unexplored. Here, we used 10 nuclear microsatellite and one plastid genetic marker to characterize the spatial genetic structure within two consecutive cohorts in a population of the biennial plantErysimum mediohispanicum(Brassicaceae). We explored the maintenance of this structure between consecutive flowering cohorts at different levels of complexity, and investigated landscape effects on gene flow. We found that cohorts were not genetically differentiated and showed a spatial genetic structure defined by a negative genetic-spatial correlation at fine scale that varied in intensity with compass directions. This spatial genetic structure was maintained when comparing plants from different cohorts. Additionally, genotypes were consistently associated with environmental factors such as light availability and soil composition, but to a lesser extent compared with the spatial autocorrelation. We conclude that inter-annual migrants, in combination with limited seed dispersal and environmental heterogeneity, play a major role in shaping and maintaining the spatial genetic structure among cohorts in this biennial plant.
Reduction of randomness in seismic noise as a short-term precursor to a volcanic eruption
Authors: Glynn C. C. , Konstantinou K. I.
Published: November 2016

Ambient seismic noise is characterized by randomness incurred by the random position and strength of the noise sources as well as the heterogeneous properties of the medium through which it propagates. Here we use ambient noise data recorded prior to the 1996 Gjálp eruption in Iceland in order to show that a reduction of noise randomness can be a clear short-term precursor to volcanic activity. The eruption was preceded on 29 September 1996 by a Mw ~5.6 earthquake that occurred in the caldera rim of the Bárdarbunga volcano. A significant reduction of randomness started occurring 8 days before the earthquake and 10 days before the onset of the eruption. This reduction was observed even at stations more than 100 km away from the eruption site. Randomness increased to its previous levels 160 minutes after the Bárdarbunga earthquake, during which time aftershocks migrated from the Bárdarbunga caldera to a site near the Gjálp eruption fissure. We attribute this precursory reduction of randomness to the lack of higher frequencies (>1 Hz) in the noise wavefield caused by high absorption losses as hot magma ascended in the upper crust.
Phenotypic and functional characterization of the major lymphocyte populations in the fruit-eating bat Pteropus alecto
Authors: Martínez Gómez Julia María , Periasamy Pravin , Dutertre Charles-Antoine , Irving Aaron Trent , Ng Justin Han Jia , Crameri Gary , Baker Michelle L. , Ginhoux Florent , Wang Lin-Fa , Alonso Sylvie
Published: November 2016

The unique ability of bats to act as reservoir for viruses that are highly pathogenic to humans suggests unique properties and functional characteristics of their immune system. However, the lack of bat specific reagents, in particular antibodies, has limited our knowledge of bat’s immunity. Using cross-reactive antibodies, we report the phenotypic and functional characterization of T cell subsets, B and NK cells in the fruit-eating bat Pteropus alecto. Our findings indicate the predominance of CD8+ T cells in the spleen from wild-caught bats that may reflect either the presence of viruses in this organ or predominance of this cell subset at steady state. Instead majority of T cells in circulation, lymph nodes and bone marrow (BM) were CD4+ subsets. Interestingly, 40% of spleen T cells expressed constitutively IL-17, IL-22 and TGF-β mRNA, which may indicate a strong bias towards the Th17 and regulatory T cell subsets. Furthermore, the unexpected high number of T cells in bats BM could suggest an important role in T cell development. Finally, mitogenic stimulation induced proliferation and production of effector molecules by bats immune cells. This work contributes to a better understanding of bat’s immunity, opening up new perspectives of therapeutic interventions for humans.
Non-RVD mutations that enhance the dynamics of the TAL repeat array along the superhelical axis improve TALEN genome editing efficacy
Authors: Tochio Naoya , Umehara Kohei , Uewaki Jun-ichi , Flechsig Holger , Kondo Masaharu , Dewa Takehisa , Sakuma Tetsushi , Yamamoto Takashi , Saitoh Takashi , Togashi Yuichi , Tate Shin-ichi
Published: November 2016

Transcription activator-like effector (TALE) nuclease (TALEN) is widely used as a tool in genome editing. The DNA binding part of TALEN consists of a tandem array of TAL-repeats that form a right-handed superhelix. Each TAL-repeat recognises a specific base by the repeat variable diresidue (RVD) at positions 12 and 13. TALEN comprising the TAL-repeats with periodic mutations to residues at positions 4 and 32 (non-RVD sites) in each repeat (VT-TALE) exhibits increased efficacy in genome editing compared with a counterpart without the mutations (CT-TALE). The molecular basis for the elevated efficacy is unknown. In this report, comparison of the physicochemical properties between CT- and VT-TALEs revealed that VT-TALE has a larger amplitude motion along the superhelical axis (superhelical motion) compared with CT-TALE. The greater superhelical motion in VT-TALE enabled more TAL-repeats to engage in the target sequence recognition compared with CT-TALE. The extended sequence recognition by the TAL-repeats improves site specificity with limiting the spatial distribution of FokI domains to facilitate their dimerization at the desired site. Molecular dynamics simulations revealed that the non-RVD mutations alter inter-repeat hydrogen bonding to amplify the superhelical motion of VT-TALE. The TALEN activity is associated with the inter-repeat hydrogen bonding among the TAL repeats.
pH-responsive Virus-like Nanoparticles with Enhanced Tumour-targeting Ligands for Cancer Drug Delivery
Authors: Biabanikhankahdani Roya , Alitheen Noorjahan Banu Mohamed , Ho Kok Lian , Tan Wen Siang
Published: November 2016

Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery. FA was conjugated to a pentadecapeptide containing nanoglue bound on tHBcAg nanoparticles to increase the specificity and efficacy of the drug delivery system. The tHBcAg nanoparticles loaded with doxorubicin (DOX) and polyacrylic acid (PAA) demonstrated a sustained drug release profile in vitro under tumour tissue conditions in a controlled manner and improved the uptake of DOX in colorectal cancer cells, leading to enhanced antitumour effects. This study demonstrated that DOX-PAA can be packaged into VLNPs without any modification of the DOX molecules, preserving the pharmacological activity of the loaded DOX. The nanoglue can easily be used to display a tumour-targeting molecule on the exterior surface of VLNPs and can bypass the laborious and time-consuming genetic engineering approaches.
Fibrillar Attapulgite–Rubber Nanocomposites
Authors: Ning Nanying , Chu Guangyu , Feng Yuxing , Zhen Xiuchun , Tian Ming , Chan Tung W.
Published: November 2016

Rubber, as a special polymer material with high elasticity at room temperature, has been widely used in industries. However, rubber has to be reinforced by using nanofillers to meet the needs of industrial applications because of its low mechanical strength. Fibrillar attapulgite (AT) with a unique structure and low cost, has attracted massive interests as a good filler for reinforcing rubber. In this chapter, the composition, morphology, physical and chemical characteristic of AT will be introduced. Then, the preparation methods, interfacial design, dispersion and filler network, structure-properties relationship of AT/rubber composites will be summarized. The synergistic effect of fibrillar attapulgite and other microfibers on the mechanical properties of rubber will be summarized.
A NASBA on microgel-tethered molecular-beacon microarray for real-time microbial molecular diagnostics
Authors: Ma Y. , Dai X. , Hong T. , Munk G. B. , Libera M.
Published: November 2016

Gel-tethered molecular beacons coupled with NASBA RNA amplification enable real-time microbial detection and differentiation in a bloodstream infection model.
The first water-soluble pillar[5]arene dimer: synthesis and construction of a reversible fluorescent supramolecular polymer network in water
Authors: Sun Yan , Wang Jin , Yao Yong
Published: November 2016

The first water-soluble pillar[5]arene dimer was successfully designed and synthesized. It can complex with carboxylate anion functionalized tetraphenyl ethylene to form a reversible fluorescent supramolecular polymer network in water.
A DNA kinetics competition strategy of hybridization chain reaction for molecular information processing circuit construction
Authors: Tang Weiyang , Huang Qichen , Yang Zhenjie , Zheng Qiwei , Wang Lihong , Zhang Junmin , Chen Liang , Zhou Xuechang , Liu Yizhen , Hu Jiming
Published: November 2016

A DNA kinetics competition strategy of HCR for recognizing input combinations and input sequences has been proposed.
Direct conjugation of antibodies to the ZnS shell of quantum dots for FRET immunoassays with low picomolar detection limits
Authors: Bhuckory S. , Mattera L. , Wegner K. D. , Qiu X. , Wu Y.-T. , Charbonnière L. J. , Reiss P. , Hildebrandt N.
Published: November 2016

Direct conjugation of IgG, F(ab′)2, and Fab antibodies to the ZnS shells of penicillamine-coated quantum dots for high-sensitivity FRET biosensing.
A unified ligand electronic parameter based on 13C NMR spectroscopy of N-heterocyclic carbene complexes
Authors: Teng Qiaoqiao , Huynh Han Vinh
Published: November 2016

The donor strengths of various mono- and bidentate ligands can be easily compared on a unified 13C NMR spectroscopic scale.
A liver microphysiological system of tumor cell dormancy and inflammatory responsiveness is affected by scaffold properties
Authors: Clark A. M. , Wheeler S. E. , Young C. L. , Stockdale L. , Shepard Neiman J. , Zhao W. , Stolz D. B. , Venkataramanan R. , Lauffenburger D. , Griffith L. , Wells A.
Published: November 2016

Microphysiological systems fitted with hydrogel scaffolds are critical tools in the assessment and development of therapeutic strategies to target dormant metastases.
Mesoporous template-free gyroid-like nanostructures based on La and Mn co-doped bismuth ferrites with improved photocatalytic activity
Authors: Irfan Syed , Rizwan Syed , Shen Yang , Tomovska Radmila , Zulfiqar Sonia , Sarwar Muhammad Ilyas , Nan Ce-Wen
Published: November 2016

Template-free and gyroid-like mesoporous nanostructures of La and Mn co-doped bismuth ferrites were fabricated using a simple and low-cost double solvent sol–gel technique.
Assessing inter- and intramolecular continuous-flow strategies towards methylphenidate (Ritalin) hydrochloride
Authors: Gérardy Romaric , Winter Marc , Vizza Alessandra , Monbaliu Jean-Christophe M.
Published: November 2016

Development of a scalable continuous-flow process towards enriched threo-methylphenidate (Ritalin) hydrochloride.
Synthesis and Protein Engineering Applications of Cyclotides
Authors: Qu Haiou , Smithies Bronwyn J. , Durek Thomas , Craik David J.
Published: November 2016

Cyclotides are a group of plant-derived peptides with a head-to-tail cyclized backbone that is stabilized by three knotted disulfide bonds. Their exceptional stability and tolerance for residue substitutions have led to interest in their application as drug design scaffolds. To date, chemical synthesis has been the dominant methodology for producing cyclotides and their analogues. Native chemical ligation is the most common strategy to generate the cyclic backbone and has been highly successful at producing a wide range of cyclotides for studies of structure–activity relationships. Both this and other chemical approaches require a specific linker at the C-terminus and typically involve a non-directed folding (disulfide oxidation) regimen, which can sometimes be a limiting factor in final yields. Following the recent discovery of enzymes involved in peptide cyclization in planta, site-specific and highly efficient enzymatic ligations have been used for synthetic cyclotide backbone cyclization. In this review, chemical synthesis strategies and approaches involving cyclization via enzymes for the production of cyclotides are described.
Using fluorescence quenching combined with two-dimensional correlation fluorescence spectroscopy to characterise the binding-site heterogeneity of dissolved organic matter with copper and mercury in lake sediments
Authors: Guo Xu-jing , Li Yun-zhen , Feng Yan-hong , Yuan Dong-hai
Published: November 2016

Environmental contextDissolved organic matter (DOM) plays an important role in influencing the migration and ultimate fate of metals. Different sources of pollution resulted in changes in the structure of sediment DOM in Lake Wuliangsuhai. We investigate the binding properties of DOM with CuII and HgII using fluorescence quenching combined with two-dimensional correlation spectroscopy (2D-COS) in order to demonstrate the influence of different sources of DOM on metals.
AbstractDissolved organic matter (DOM) was collected from three sampling sites (L1, L2 and L3) in Lake Wuliangsuhai. L1 received upstream industrial wastewater and domestic sewage. L2 had suffered from agricultural non-point source pollution. L3 was situated in the lake outlet area. The complexation of DOM with CuII and HgII was investigated based on fluorescence quenching of the synchronous fluorescence spectra on the addition of CuII and on two-dimensional correlation spectroscopy (2D-COS). The synchronous and asynchronous maps derived from 2D-COS provided a clear picture of the heterogeneous distribution of CuII and HgII binding sites, which was not readily detected using only the synchronous fluorescence spectra. CuII and HgII complexation was stronger at shorter wavelengths than at longer wavelengths. Moreover, fluorescence quenching also occurred intensely in the fulvic-like regions (363nm for DOM-Cu in L2 and 365nm for DOM-Hg in L1). The logarithms of the stability constants (log KM) ranged from 4.42 to 6.23, from 4.75 to 4.86, and from 4.80 to 5.73 for DOM-Cu in L1, L2 and L3, respectively, depending on the wavelength. DOM at the longer wavelengths exhibited a higher log KM than that at the shorter wavelengths, and the f values in the protein-like region were clearly high. These results suggest that the influence of the structural and chemical properties of DOM on CuII binding may differ for DOM from different sources. The combined approach of fluorescence quenching and 2D-COS could be applied as a tool for evaluating the metal binding site heterogeneity of DOM.
A high-throughput small molecule screen identifies synergism between DNA methylation and Aurora kinase pathways for X reactivation
Authors: Lessing Derek , Dial Thomas O. , Wei Chunyao , Payer Bernhard , Carrette Lieselot L. G. , Kesner Barry , Szanto Attila , Jadhav Ajit , Maloney David J. , Simeonov Anton , Theriault Jimmy , Hasaka Thomas , Bedalov Antonio , Bartolomei Marisa S. , Lee Jeannie T.
Published: November 2016

Significance

In mammalian female cells, nearly all genes are silenced on one of two X chromosomes. Heterozygous females with “dominant” X-linked diseases, such as Rett syndrome, may benefit from pharmacological reactivation of the silent, healthy allele in affected organs. Toward establishing proof of concept, here we carry out a primed screen of a large library of small molecules for compounds that can reactivate expression from the inactive X (Xi). We identify a combination of compounds that inhibits the DNA methylation and Aurora kinase pathways and demonstrate that the two pathways act synergistically to repress genes on the Xi, including genes involved in X-linked disease.
Analysis of de novo sequencing and transcriptome assembly and lignocellulolytic enzymes gene expression of Coriolopsis gallica HTC
Authors: Chen Yuehong , Cao Qinghua , Tao Xiang , Shao Huanhuan , Zhang Kun , Zhang Yizheng , Tan Xuemei
Published: November 2016

White-rot basidiomycete Coriolopsis gallica HTC is one of the main biodegraders of poplar. In our previous study, we have shown the strong capacity of C. gallica HTC to degrade lignocellulose. In this study, equal amounts of total RNA fromC. Gallica HTC cultures grown in different conditions were pooled together. Illumina paired-end RNA sequencing was performed, and 13.2 million 90-bp paired-end reads were generated. We chose the Merged Assembly of Oases data-set for the following blast searches and gene ontology analyses. The reads were assembled de novo into 28,034 transcripts (≥ 100 bp) using combined assembly strategy MAO. The transcripts were annotated using Blast2GO. In all, 18,810 transcripts (≥100 bp) achieved BLASTX hits, of which, 7048 transcripts had GO term and 2074 had ECs. The expression level of 11 lignocellulolytic enzyme genes from the assembled C. gallica HTC transcriptome were detected by real-time quantitative polymerase chain reaction. The results showed that expression levels of these genes were affected by carbon source and nitrogen source at the level of transcription. The current abundant transcriptome data allowed the identification of many new transcripts in C. gallica HTC. Data provided here represent the most comprehensive and integrated genomic resources for cloning and identifying genes of interest from C. gallica HTC. Characterization of C. gallica HTC transcriptome provides an effective tool to understand mechanisms underlying cellular and molecular functions of C. gallica HTC.
Radio transmission characteristics in tunnel environments
Authors: Bedford Michael D. , Kennedy Gareth A. , Foster Patrick J.
Published: November 2016

Radio communication is becoming more widely used in underground mining, although it is still a challenge to achieve good quality and reliable coverage. This research provides information to assist mining professionals in designing voice or data communication systems that operate underground by transmitting along mine tunnels. This has been achieved by presenting a simplified model for predicting the propagation of microwave signals and supplementing this with the results of an extensive experimental study aimed at understanding how the performance predicted by the model differs from real-world performance. The results validate the model under ideal conditions but additional signal attenuation is shown to occur when operating close to a wall, behind a partial obstruction or in a side tunnel. Experimental results indicate the typical magnitude of such additional attenuation. Also, long- and short-range fluctuations to the predicted average is demonstrated and their typical magnitude shown. A system planning approach is outlined.
Lysosomal trafficking regulator Lyst links membrane trafficking to toll-like receptor–mediated inflammatory responses
Authors: Westphal Andreas , Cheng Weijia , Yu Jinbo , Grassl Guntram , Krautkrämer Martina , Holst Otto , Föger Niko , Lee Kyeong-Hee
Published: November 2016

Subcellular compartmentalization of receptor signaling is an emerging principle in innate immunity. However, the functional integration of receptor signaling pathways into membrane trafficking routes and its physiological relevance for immune responses is still largely unclear. In this study, using Lyst-mutant beige mice, we show that lysosomal trafficking regulator Lyst links endolysosomal organization to the selective control of toll-like receptor 3 (TLR3)– and TLR4-mediated proinflammatory responses. Consequently, Lyst-mutant mice showed increased susceptibility to bacterial infection and were largely resistant to endotoxin-induced septic shock. Mechanistic analysis revealed that Lyst specifically controls TLR3- and TLR4-induced endosomal TRIF (TIR domain–containing adapter-inducing interferon β) signaling pathways. Loss of functional Lyst leads to dysregulated phagosomal maturation, resulting in a failure to form an activation-induced Rab7+ endosomal/phagosomal compartment. This specific Rab7+ compartment was further demonstrated to serve as a major site for active TRIF signaling events, thus linking phagosomal maturation to specific TLR signaling pathways. The immunoregulatory role of Lyst on TLR signaling pathways was confirmed in human cells by CRISPR/Cas9-mediated gene inactivation. As mutations in LYST cause human Chédiak-Higashi syndrome, a severe immunodeficiency, our findings also contribute to a better understanding of human disease mechanisms.
Severity of Respiratory Syncytial Virus Lower Respiratory Tract Infection With Viral Coinfection in HIV-Uninfected Children
Authors: Mazur Natalie I. , Bont Louis , Cohen Adam L. , Cohen Cheryl , von Gottberg Anne , Groome Michelle J. , Hellferscee Orienka , Klipstein-Grobusch Kerstin , Mekgoe Omphile , Naby Fathima , Moyes Jocelyn , Tempia Stefano , Treurnicht Florette K. , Venter Marietje , Walaza Sibongile , Wolter Nicole , Madhi Shabir A. ,   for the South African Severe Acute Respiratory Illness (SARI) Surveillance Group
Published: November 2016

Background.

Molecular diagnostics enable sensitive detection of respiratory viruses, but their clinical significance remains unclear in pediatric lower respiratory tract infection (LRTI). We aimed to determine whether viral coinfections increased life-threatening disease in a large cohort.

Methods.

Molecular testing was performed for respiratory viruses in nasopharyngeal aspirates collected from children aged <5 years within 24 hours of hospital admission during sentinel surveillance for severe acute respiratory illness (SARI) hospitalization conducted in South Africa during February 2009–December 2013. The primary outcome was life-threatening disease, defined as mechanical ventilation, intensive care unit admission, or death.

Results.

Of 2322 HIV-uninfected children with respiratory syncytial virus (RSV)–associated LRTI, 1330 (57.3%) had RSV monoinfection, 38 (1.6%) had life-threatening disease, 575 (24.8%) had rhinovirus, 347 (14.9%) had adenovirus (ADV), and 30 (1.3%) had influenza virus. RSV and any other viral coinfection was not associated with severe disease (odds ratio [OR], 1.4; 95% confidence interval [CI], OR, 0.74; 95% CI, .39–1.4), ADV coinfection had increased odds of life-threatening disease (adjusted OR, 3.4; 95% CI, 1.6–7.2; P = .001), and influenza coinfection had increased odds of life-threatening disease and prolonged length of stay (adjusted OR, 2.1; 95% CI, 1.0–4.5; P = .05) compared with RSV monoinfection.

Conclusions.

RSV coinfection with any respiratory virus is not associated with more severe disease when compared to RSV alone in this study. However, increased life-threatening disease in RSV-ADV and RSV-influenza coinfection warrants further study.
Collective Bargaining, Equality and Migration: The Journey to and from Brexit
Authors: Novitz Tonia
Published: November 2016

Bob Simpson has documented the evolution of collective labour laws in the UK over several decades and his scholarship reminds us of their intended and unintended consequences. In the highly politically charged context of the 2016 Brexit vote, this article considers how UK and European Union (EU) laws have shaped the nature and scope of collective bargaining in the UK and, thereby, income differentials and equal treatment in the workplace. While it would be possible to provide for equality of treatment between local British and migrant labour in ways that reduce social tensions, instead we have witnessed the imposition of legal frameworks that place workers in a position of competition rather than solidarity. The mistrust of current forms of migration from the EU seems to have been one key part of the journey towards the Brexit vote. An important question is what comes afterwards. If Brexit does not proceed, we should be contemplating reform at both UK and EU levels; but the problems identified here seem unlikely to evaporate in the event of either ‘soft’ or ‘hard’ Brexit. The article concludes that the UK situation offers a salutary reminder to other EU States of the dangers of dismantling systems of sectoral bargaining and mechanisms for extension of collective agreements.
Best Practices for Pressure Ulcer Prevention in the Burn Center
Authors: Warner Julia , Ann Raible Mary , Hajduk Gina , Collavo Jacqueline
Published: November 2016

The State of Pennsylvania Hospital Engagement Network, in collaboration with a hospital system in Southwestern Pennsylvania, established a goal of reducing hospital-acquired pressure ulcers by 20%. A 6-month unfavorable trend of nurse-sensitive clinical indicators called for immediate process improvement. A retrospective chart review resulted in identification of predominant risk factors placing the burn patient at high risk for pressure ulcer formation. Implementations of pressure ulcer prevention measures were inconsistent. Nurses demonstrated varied levels of knowledge about products used for prevention. It became imperative to examine processes within the unit and provide nursing with education, access to skin care supplies, and advanced skin/wound care products for maintaining skin integrity. Creation of evidence-based guidelines was necessary to improve patient outcomes. A collaborative team approach influenced nursing and physician awareness of pressure ulcer risk. Evidence-based prevention guidelines were developed, and consistency in early intervention was achieved, supporting our culture of safety. A change in interprofessional collaborative practice and positive trend in pressure ulcer incidence data supports the success of our program.
Persistent pain after motor vehicle collision: comparative effectiveness of opioids vs nonsteroidal antiinflammatory drugs prescribed from the emergency department—a propensity matched analysis
Authors: Beaudoin Francesca L. , Gutman Roee , Merchant Roland C. , Clark Melissa A. , Swor Robert A. , Jones Jeffrey S. , Lee David C. , Peak David A. , Domeier Robert M. , Rathlev Niels K. , McLean Samuel A.
Published: November 2016

Each year millions of Americans present to the emergency department (ED) for care after a motor vehicle collision (MVC); the majority (>90%) are discharged to home after evaluation. Acute musculoskeletal pain is the norm in this population, and such patients are typically discharged to home with prescriptions for oral opioid analgesics or nonsteroidal antiinflammatory drugs (NSAIDs). The influence of acute pain management on subsequent pain outcomes in this common ED population is unknown. We evaluated the effect of opioid analgesics vs NSAIDs initiated from the ED on the presence of moderate to severe musculoskeletal pain and ongoing opioid use at 6 weeks in a large cohort of adult ED patients presenting to the ED after MVC (n = 948). The effect of opioids vs NSAIDs was evaluated using an innovative quasi-experimental design method using propensity scores to account for covariate imbalances between the 2 treatment groups. No difference in risk for moderate to severe musculoskeletal pain at 6 weeks was observed between those discharged with opioid analgesics vs NSAIDs (risk difference = 7.2% [95% confidence interval: −5.2% to 19.5%]). However, at follow-up participants prescribed opioids were more likely than those prescribed NSAIDs to report use of prescription opioids medications at week 6 (risk difference = 17.5% [95% confidence interval: 5.8%-29.3%]). These results suggest that analgesic choice at ED discharge does not influence the development of persistent moderate to severe musculoskeletal pain 6 weeks after an MVC, but may result in continued use of prescription opioids. Supported by NIAMS R01AR056328 and AHRQ 5K12HS022998.