bluuebunny/crossref_metadata_2025 huggingface dataset:
Chaperonin 60 sustains osteoblast autophagy and counteracts glucocorticoid aggravation of osteoporosis by chaperoning RPTOR
Authors: Lian Wei-Shiung , Ko Jih-Yang , Chen Yu-Shan , Ke Huei-Ching , Wu Shin-Long , Kuo Chung-Wen , Wang Feng-Sheng
Published: September 2018

Glucocorticoid excess medication interrupts osteoblast homeostasis and exacerbates bone mass and microstructure loss ramping up the pathogenesis of osteoporotic disorders. Heat shock protein 60 (HSP60) is found to maintain protein function within cellular microenvironment upon encountering detrimental stress. In this study, we revealed that supraphysiological dexamethasone decreased HSP60 expression along with deregulated autophagy in osteoblasts cultures. This chaperonin is required to sustain autophagic markers Atg4, and Atg12 expression, LC3-II conversion, and autophagic puncta formation, and alleviated the glucocorticoid-induced loss of osteogenic gene expression and mineralized matrix accumulation. Regulator-associated protein of mTOR complex 1 (RPTOR) existed in HSP60 immunoprecipitate contributing to the HSP60-promoted autophagy and osteogenesis because knocking down RPTOR impaired autophagic influx and osteogenic activity. HSP60 shielded from RPTOR dysfunction by reducing the glucocorticoid-induced RPTOR de-phosphorylation, aggregation, and ubiquitination. In vivo, forced RPTOR expression attenuated the methylprednisolone-induced loss of osteoblast autophagy, bone mass, and trabecular microstructure in mice. HSP60 transgenic mice displayed increased cortical bone, mineral acquisition, and osteoblast proliferation along with higher osteogenesis of bone marrow mesenchymal cells than those of wild-type mice. HSP60 overexpression retained RPTOR signaling, sustained osteoblast autophagy, and compromised the severity of glucocorticoid-induced bone loss and sparse trabecular histopathology. Taken together, HSP60 is essential to maintain osteoblast autophagy, which facilitates mineralized matrix production. It fends off glucocorticoid-induced osteoblast apoptosis and bone loss by stabilizing RPTOR action to autophagy. This study offers a new insight into the mechanistic by which chaperonin protects against the glucocorticoid-induced osteoblast dysfunction and bone loss.
Reconfiguring surface functions using visible-light-controlled metal-ligand coordination
Authors: Xie Chaoming , Sun Wen , Lu Hao , Kretzschmann Annika , Liu Jiahui , Wagner Manfred , Butt Hans-Jürgen , Deng Xu , Wu Si
Published: September 2018

Most surfaces are either static or switchable only between “on” and “off” states for a specific application. It is a challenge to develop reconfigurable surfaces that can adapt to rapidly changing environments or applications. Here, we demonstrate fabrication of surfaces that can be reconfigured for user-defined functions using visible-light-controlled Ru–thioether coordination chemistry. We modify substrates with Ru complex Ru-H2O. To endow a Ru-H2O-modified substrate with a certain function, a functional thioether ligand is immobilized on the substrate via Ru–thioether coordination. To change the surface function, the immobilized thioether ligand is cleaved from the substrate by visible-light-induced ligand dissociation, and then another thioether ligand with a distinct function is immobilized on the substrate. Different thioethers endow the surface with different functions. Based on this strategy, we rewrite surface patterns, manipulate protein adsorption, and control surface wettability. This strategy enables the fabrication of reconfigurable surfaces with customizable functions on demand.
Positive cardiac inotrope omecamtiv mecarbil activates muscle despite suppressing the myosin working stroke
Authors: Woody Michael S. , Greenberg Michael J. , Barua Bipasha , Winkelmann Donald A. , Goldman Yale E. , Ostap E. Michael
Published: September 2018

Omecamtiv mecarbil (OM) is a positive cardiac inotrope in phase-3 clinical trials for treatment of heart failure. Although initially described as a direct myosin activator, subsequent studies are at odds with this description and do not explain OM-mediated increases in cardiac performance. Here we show, via single-molecule, biophysical experiments on cardiac myosin, that OM suppresses myosin’s working stroke and prolongs actomyosin attachment 5-fold, which explains inhibitory actions of the drug observed in vitro. OM also causes the actin-detachment rate to become independent of both applied load and ATP concentration. Surprisingly, increased myocardial force output in the presence of OM can be explained by cooperative thin-filament activation by OM-inhibited myosin molecules. Selective suppression of myosin is an unanticipated route to muscle activation that may guide future development of therapeutic drugs.
Controlling factor of incoming plate hydration at the north-western Pacific margin
Authors: Fujie Gou , Kodaira Shuichi , Kaiho Yuka , Yamamoto Yojiro , Takahashi Tsutomu , Miura Seiichi , Yamada Tomoaki
Published: September 2018

Hydration of the subducting oceanic plate determines the amount of water transported from Earth’s surface into its interior, and plate bending-related faulting (bend faulting) just prior to subduction is considered to promote hydration. Bend faulting shows significant spatial variation, but its contribution to hydration is still poorly understood. Here we present the results of controlled-source seismic surveys around the junction of the Japan and Kuril trenches. We found structural changes caused by bend faulting before subduction differed distinctly between both trenches and were well correlated with plate hydration after subduction, suggesting the bend faulting controls spatial variations in plate hydration. Differences in bend faulting are closely related to the angle between the current trench and the ancient spreading ridge, and the hydration is more extensive where this trench-ridge angle is oblique in the study area. Thus, we propose this angle is a major factor controlling plate hydration.
Gap junction protein Connexin-43 is a direct transcriptional regulator of N-cadherin in vivo
Authors: Kotini Maria , Barriga Elias H. , Leslie Jonathan , Gentzel Marc , Rauschenberger Verena , Schambony Alexandra , Mayor Roberto
Published: September 2018

Connexins are the primary components of gap junctions, providing direct links between cells under many physiological processes. Here, we demonstrate that in addition to this canonical role, Connexins act as transcriptional regulators. We show that Connexin 43 (Cx43) controls neural crest cell migration in vivo by directly regulating N-cadherin transcription. This activity requires interaction between Cx43 carboxy tail and the basic transcription factor-3, which drives the translocation of Cx43 tail to the nucleus. Once in the nucleus they form a complex with PolII which directly binds to the N-cadherin promoter. We found that this mechanism is conserved between amphibian and mammalian cells. Given the strong evolutionary conservation of connexins across vertebrates, this may reflect a common mechanism of gene regulation by a protein whose function was previously ascribed only to gap junctional communication.
Androgen receptor expression in normal breast tissue and subsequent breast cancer risk
Authors: Kensler Kevin H. , Beca Francisco , Baker Gabrielle M. , Heng Yujing J. , Beck Andrew H. , Schnitt Stuart J. , Hazra Aditi , Rosner Bernard A. , Eliassen A. Heather , Hankinson Susan E. , Brown Myles , Tamimi Rulla M.
Published: September 2018

Sex steroid hormone signaling is critical in the development of breast cancers, although the role of the androgen receptor remains unclear. This study evaluated androgen receptor (AR) expression in normal breast tissue as a potential marker of breast cancer risk. We conducted a nested case–control study of women with benign breast disease (BBD) within the Nurses’ Health Studies. Epithelial AR expression was assessed by immunohistochemistry in normal tissue from the BBD biopsy and the percent of positive nuclei was estimated in ordinal categories of 10% for 78 breast cancer cases and 276 controls. Logistic regression models adjusting for the matching factors and BBD lesion type were used to calculate odds ratios (ORs) for the association between AR expression (tertiles: ≤10%, 11–30%, and >30%) and breast cancer risk. AR expression in normal breast tissue was not associated with subsequent breast cancer risk (ORT3vsT1 = 0.9, 95% CI = 0.4–1.8, p trend = 0.68). In comparison with low AR/low ER women, ORs of 0.4 (95% CI = 0.1–1.2) for high AR/high ER women, 1.8 (95% CI = 0.4–7.8) for low AR/high ER women, and 0.7 (95% CI = 0.3–1.6) for high AR/low ER women were observed (p interaction = 0.21). Ki67 did not modify the association between AR expression and breast cancer risk (p interaction = 0.75). There was little evidence for an overall association between AR expression in normal breast tissue and breast cancer risk. These findings did not show that the AR association varied by Ki67 expression in normal breast tissue, though there was suggestive heterogeneity by ER expression.
Dvl3 polymorphism interacts with life events and pro-inflammatory cytokines to influence major depressive disorder susceptibility
Authors: Zhang Jian , Yang Jiarun , Han Dong , Zhao Xueyan , Ma Jingsong , Ban Bo , Zhu Xiongzhao , Yang Yanjie , Cao Depin , Qiu Xiaohui
Published: September 2018

The purpose of this study is to explore Dvl3 variants and their interaction with negative life events on MDD susceptibility in a Chinese Han population. Additionally, we also attempted to identify whether there is an association between Dvl3 variants and pro-inflammatory cytokines. A total of 1102 participants, consisting of 550 patients with MDD and 552 healthy subjects, were recruited for genotyping by TaqMan allelic discrimination assay. Pro-inflammatory cytokine mRNA levels in peripheral blood were measured by QPCR. After the assessment of negative life events by the Life Events Scale, the Dvl3 gene–environment interaction (G × E) and risk factors were evaluated using generalized multifactor dimensionality reduction method (GMDR) and logistic regression analysis, respectively. This study is the first to reveal the interaction between Dvl3 allelic variations and negative life events as well as pro-inflammatory cytokines on MDD susceptibility in a Chinese Han population.
Superstatistical distribution of daily precipitation extremes: A worldwide assessment
Authors: De Michele Carlo , Avanzi Francesco
Published: September 2018

Maximum annual daily precipitation is a fundamental hydrologic variable that does not attain asymptotic conditions. Thus the classical extreme value theory (i.e., the Fisher-Tippett’s theorem) does not apply and the recurrent use of the Generalized Extreme Value distribution (GEV) to estimate precipitation quantiles for structural-design purposes could be inappropriate. In order to address this issue, we first determine the exact distribution of maximum annual daily precipitation starting from a Markov chain and in a closed analytical form under the hypothesis of stochastic independence. As a second step, we formulate a superstatistics conjecture of daily precipitation, meaning that we assume that the parameters of this exact distribution vary from a year to another according to probability distributions, which is supported by empirical evidence. We test this conjecture using the world GHCN database to perform a worldwide assessment of this superstatistical distribution of daily precipitation extremes. The performances of the superstatistical distribution and the GEV are tested against data using the Kolmogorov-Smirnov statistic. By considering the issue of model’s extrapolation, that is, the evaluation of the estimated model against data not used in calibration, we show that the superstatistical distribution provides more robust estimations than the GEV, which tends to underestimate (7–13%) the quantile associated to the largest cumulative frequency. The superstatistical distribution, on the other hand, tends to overestimate (10–14%) this quantile, which is a safer option for hydraulic design. The parameters of the proposed superstatistical distribution are made available for all 20,561 worldwide sites considered in this work.
High-Resolution AMS Dating of Architecture, Boulder Artworks and the Transition to Farming at Lepenski Vir
Authors: Borić Dušan , Higham Thomas , Cristiani Emanuela , Dimitrijević Vesna , Nehlich Olaf , Griffiths Seren , Alexander Craig , Mihailović Bojana , Filipović Dragana , Allué Ethel , Buckley Michael
Published: September 2018

The archaeological site of Lepenski Vir is widely known after its remarkable stone art sculptures that represent a unique and unprecedented case of Holocene hunter-gatherer creativity. These artworks were found largely associated with equally unique trapezoidal limestone building floors around their centrally located rectangular stone-lined hearths. A debate has raged since the discovery of the site about the chronological place of various discovered features. While over years different views from that of the excavator about the stratigraphy and chronology of the site have been put forward, some major disagreements about the chronological position of the features that make this site a key point of reference in European Prehistory persist. Despite challenges of re-analyzing the site’s stratigraphy from the original excavation records, taphonomic problems, and issues of reservoir offsets when providing radiocarbon measurements on human and dog bones, our targeted AMS (Accelerator Mass Spectrometry) dating of various contexts from this site with the application of Bayesian statistical modelling allows us to propose with confidence a new and sound chronological framework and provide formal estimates for several key developments represented in the archaeological record of Lepenski Vir that help us in understanding the transition of last foragers to first farmers in southeast Europe as a whole.
Comparative Analysis of TM and Cytoplasmic β-barrel Conformations Using Joint Descriptor
Authors: Thangappan Jayaraman , Wu Sangwook , Lee Sun-Gu
Published: September 2018

Macroscopic descriptors have become valuable as coarse-grained features of complex proteins and are complementary to microscopic descriptors. Proteins macroscopic geometric features provide effective clues in the quantification of distant similarity and close dissimilarity searches for structural comparisons. In this study, we performed a systematic comparison of β-barrels, one of the important classes of protein folds in various transmembrane (TM) proteins against cytoplasmic barrels to estimate the conformational features using a joint-based descriptor. The approach uses joint coordinates and dihedral angles (β and γ) based on the β-strand joints and loops to determine the arrangements and propensities at the local and global levels. We then confirmed that there is a clear preference in the overall β and γ distribution, arrangements of β-strands and loops, signature patterns, and the number of strand effects between TM and cytoplasmic β-barrel geometries. As a robust and simple approach, we determine that the joint-based descriptor could provide a reliable static structural comparison aimed at macroscopic level between complex protein conformations.
A Microfluidic Fluorescent Flow Cytometry Capable of Quantifying Cell Sizes and Numbers of Specific Cytosolic Proteins
Authors: Li Xiufeng , Fan Beiyuan , Liu Lixing , Chen Deyong , Cao Shanshan , Men Dong , Wang Junbo , Chen Jian
Published: September 2018

This study presents a microfluidics based cytometry capable of characterizing cell sizes and counting numbers of specific cytosolic proteins where cells were first bound by antibodies labelled with fluorescence and then aspirated into a constriction microchannel in which fluorescent levels were measured. These raw fluorescent pulses were further divided into a rising domain, a stable domain and a declining domain. In addition, antibody solutions with labelled fluorescence were aspirated through the constriction microchannel, yielding curves to translate raw fluorescent levels to protein concentrations. By using key parameters of three domains as well as the calibration curves, cell diameters and the absolute number of β-actins at the single-cell level were quantified as 14.2 ± 1.7 μm and 9.62 ± 4.29 × 105 (A549, ncell = 14 242), 13.0 ± 2.0 μm and 6.46 ± 3.34 × 105 (Hep G2, ncell = 35 932), 13.8 ± 1.9 μm and 1.58 ± 0.90 × 106 (MCF 10 A, ncell = 16 650), and 12.7 ± 1.5 μm and 1.09 ± 0.49 × 106 (HeLa, ncell = 26 246). This platform could be further adopted to measure numbers of various cytosolic proteins, providing key insights in proteomics at the single-cell level.
Acoustic properties of vowel production in Mandarin-speaking patients with post-stroke dysarthria
Authors: Mou Zhiwei , Chen Zhuoming , Yang Jing , Xu Li
Published: September 2018

This study investigated the acoustic features of vowel production in Mandarin-speaking patients with post-stroke dysarthria (PSD). The subjects included 31 native Mandarin-speaking patients with PSD (age: 25–83 years old) and 38 neurologically normal adults in a similar age range (age: 21–76 years old). Each subject was recorded producing a list of Mandarin monosyllables that included six monophthong vowels (i.e., /a, i, u, ɤ, y, o/) embedded in the /CV/ context. The patients’ speech samples were evaluated by two native Mandarin speakers. The evaluation scores were then used to classify all patients into two levels of severity: mild or moderate-to-severe. Formants (F1 and F2) were extracted from each vowel token. Results showed that all vowel categories in the patients with PSD were produced with more variability than in the healthy speakers. Great overlaps between vowel categories and reduced vowel space were observed in the patients. The magnitude of the vowel dispersion and overlap between vowel categories increased as a function of the severity of the disorder. The deviations of the vowel acoustic features in the patients in comparison to the healthy speakers may provide guidance for clinical rehabilitation to improve the speech intelligibility of patients with PSD.
Stationary Computed Tomography for Space and other Resource-constrained Environments
Authors: Cramer Avilash , Hecla Jake , Wu Dufan , Lai Xiaochun , Boers Tim , Yang Kai , Moulton Tim , Kenyon Steven , Arzoumanian Zaven , Krull Wolfgang , Gendreau Keith , Gupta Rajiv
Published: September 2018

Computed tomography (CT) is used to diagnose many emergent medical conditions, including stroke and traumatic brain injuries. Unfortunately, the size, weight, and expense of CT systems make them largely inaccessible for patients outside of major hospitals. We have designed a module containing multiple miniature x-ray sources that could allow for CT systems to be significantly lighter, smaller, and cheaper, and to operate without any moving parts. We have developed a novel photocathode-based x-ray source, created by depositing a thin film of magnesium on an electron multiplier. When illuminated by a UV LED, this photocathode emits a beam of electrons, with a beam current of up to 1 mA. The produced electrons are accelerated through a high voltage to a tungsten target. These sources are individually addressable and can be pulsed rapidly, through electronic control of the LEDs. Seven of these sources are housed together in a 17.5 degree arc within a custom vacuum manifold. A full ring of these modules could be used for CT imaging. By pulsing the sources in series, we are able to demonstrate x-ray tomosynthesis without any moving parts. With a clinical flat-panel detector, we demonstrate 3D acquisition and reconstructions of a cadaver swine lung.
Site-directed mutagenesis of Campylobacter concisus respiratory genes provides insight into the pathogen’s growth requirements
Authors: Benoit Stéphane L. , Maier Robert J.
Published: September 2018

Campylobacter concisus is an emerging human pathogen found throughout the entire human oral-gastrointestinal tract. The ability of C. concisus to colonize diverse niches of the human body indicates the pathogen is metabolically versatile. C. concisus is able to grow under both anaerobic conditions and microaerophilic conditions. Hydrogen (H2) has been shown to enhance growth and may even be required. Analysis of several C. concisus genome sequences reveals the presence of two sets of genes encoding for distinct hydrogenases: a H2-uptake-type (“Hyd”) complex and a H2-evolving hydrogenase (“Hyf”). Whole cells hydrogenase assays indicate that the former (H2-uptake) activity is predominant in C. concisus, with activity among the highest we have found for pathogenic bacteria. Attempts to generate site-directed chromosomal mutants were partially successful, as we could disrupt hyfB, but not hydB, suggesting that H2-uptake, but not H2-evolving activity, is an essential respiratory pathway in C. concisus. Furthermore, the tetrathionate reductase ttrA gene was inactivated in various C. concisus genomospecies. Addition of tetrathionate to the medium resulted in a ten-fold increase in cell yield for the WT, while it had no effect on the ttrA mutant growth. To our knowledge, this is the first report of mutants in C. concisus.
Dose-dependent behavioural fever responses in desert locusts challenged with the entomopathogenic fungus Metarhizium acridum
Authors: Clancy Lisa M. , Jones Rory , Cooper Amy L. , Griffith Gareth W. , Santer Roger D.
Published: September 2018

Behavioural fever is a common response to immune challenge in ectotherms and confers survival benefits. However, costs accrue rapidly as body temperature rises. Thus, the magnitude of adaptive fever responses might reflect the balance of costs and benefits. We investigated behavioural fever in desert locusts, Schistocerca gregaria, infected with the entomopathogenic fungus Metarhizium acridum. We first tracked the time course of behavioural fever in infected locusts, demonstrating that body temperatures rose on the day following inoculation (day 1), and reached peak intensity on the day after that (day 2). Subsequently, the magnitude of fever responses varied during a day, and locusts tended to exhibit high-intensity fever responses in the mornings when basking was first possible. We speculate that this may have resulted from increased fungal load caused by unimpeded growth overnight when locusts could not fever. We next inoculated locusts with different M. acridum doses ranging from 0 to ca. 75,000 conidia. The magnitude of their behavioural fever responses on day 2 post-inoculation was positively related to fungal dose. Thus, we demonstrate dose-dependency in the behavioural fever responses of desert locusts and suggest that this may reflect the adaptive deployment of behavioural fever to minimize costs relative to benefits.
In-vivo shift of the microbiota in oral biofilm in response to frequent sucrose consumption
Authors: Anderson Annette Carola , Rothballer Michael , Altenburger Markus Jörg , Woelber Johan Peter , Karygianni Lamprini , Lagkouvardos Ilias , Hellwig Elmar , Al-Ahmad Ali
Published: September 2018

Caries is associated with shifts of microbiota in dental biofilms and primarily driven by frequent sucrose consumption. Data on environmentally induced in vivo microbiota shifts are scarce therefore we investigated the influence of frequent sucrose consumption on the oral biofilm. Splint systems containing enamel slabs were worn for 3 × 7 days with 7-day intervals to obtain oral biofilm samples. After a three-month dietary change of sucking 10 g of sucrose per day in addition to the regular diet, biofilm was obtained again at the end of the second phase. The microbiota was analysed using Illumina MiSeq amplicon sequencing (v1-v2 region). In addition, roughness of the enamel surface was measured with laser scanning microscopy. The sucrose phase resulted in significant differences in beta-diversity and significantly decreased species richness. It was marked by a significant increase in abundance of streptococci, specifically Streptococcus gordonii, Streptococcus parasanguinis and Streptococcus sanguinis. Enamel surface roughness began to increase, reflecting initial impairment of dental enamel surface. The results showed that frequent sucrose consumption provoked compositional changes in the microbiota, leading to an increase of non-mutans streptococci, hence supporting the extended ecological plaque hypothesis and emphasizing the synergy of multiple bacterial species in the development of caries.
Parkin-dependent regulation of the MCU complex component MICU1
Authors: Matteucci Alessandra , Patron Maria , Vecellio Reane Denis , Gastaldello Stefano , Amoroso Salvatore , Rizzuto Rosario , Brini Marisa , Raffaello Anna , Calì Tito
Published: September 2018

The mitochondrial Ca2+ uniporter machinery is a multiprotein complex composed by the Ca2+ selective pore-forming subunit, the mitochondrial uniporter (MCU), and accessory proteins, including MICU1, MICU2 and EMRE. Their concerted action is required to fine-tune the uptake of Ca2+ into the mitochondrial matrix which both sustains cell bioenergetics and regulates the apoptotic response. To adequately fulfil such requirements and avoid impairment in mitochondrial Ca2+ handling, the intracellular turnover of all the MCU components must be tightly regulated. Here we show that the MCU complex regulator MICU1, but not MCU and MICU2, is rapidly and selectively degraded by the Ubiquitin Proteasome System (UPS). Moreover, we show that the multifunctional E3 ubiquitin ligase Parkin (PARK2), whose mutations cause autosomal recessive early-onset Parkinson’s disease (PD), is a potential candidate involved in this process since its upregulation strongly decreases the basal level of MICU1. Parkin was found to interact with MICU1 and, interestingly, Parkin Ubl-domain, but not its E3-ubquitin ligase activity, is required for the degradation of MICU1, suggesting that in addition to the well documented role in the control of Parkin basal auto-inhibition, the Ubl-domain might exert important regulatory functions by acting as scaffold for the proteasome-mediated degradation of selected substrates under basal conditions, i.e. to guarantee their turnover. We have found that also MICU2 stability was affected upon Parkin overexpression, probably as a consequence of increased MICU1 degradation. Our findings support a model in which the PD-related E3 ubiquitin ligase Parkin directly participates in the selective regulation of the MCU complex regulator MICU1 and, indirectly, also of the MICU2 gatekeeper, thus indicating that Parkin loss of function could contribute to the impairment of the ability of mitochondria to handle Ca2+ and consequently to the pathogenesis of PD.
c-Kit+ Cells in Adult Salivary Glands do not Function as Tissue Stem Cells
Authors: Kwak Mingyu , Ninche Ninche , Klein Sabine , Saur Dieter , Ghazizadeh Soosan
Published: September 2018

A rare population of salivary gland cells isolated based on c-Kit immunoreactivity are thought to represent tissue stem cells since they exhibit the most robust proliferative and differentiation capacity ex vivo. Despite their high promise for cell-based therapies aimed at restoring salivary function, the precise location and in vivo function of c-Kit+ stem cells remain unclear. Here, by combining immunostaining with c-KitCreERT2-based genetic labeling and lineage tracing in the adult mouse salivary glands, we show that c-Kit is expressed in a relatively large and heterogeneous cell population that consists mostly of differentiated cells. Moreover, c-Kit does not mark ductal stem cells that are known to express cytokeratin K14. Tracking the fate of in vivo-labeled c-Kit+ or that of K14+ cells in spheroid cultures reveals a limited proliferative potential for c-Kit+ cells and identifies K14+ cells as the major source of salispheres in these cultures. Long-term in vivo lineage tracing studies indicate that although c-Kit marks at least two discrete ductal cell lineages, c-Kit+ cells do not contribute to the normal maintenance of any other cell lineages. Our results indicate that c-Kit is not a reliable marker for salivary gland stem cells, which has important implications for salivary gland regenerative therapies.
The pathogenesis linked to coenzyme Q10 insufficiency in iPSC-derived neurons from patients with multiple-system atrophy
Authors: Nakamoto Fumiko Kusunoki , Okamoto Satoshi , Mitsui Jun , Sone Takefumi , Ishikawa Mitsuru , Yamamoto Yorihiro , Kanegae Yumi , Nakatake Yuhki , Imaizumi Kent , Ishiura Hiroyuki , Tsuji Shoji , Okano Hideyuki
Published: September 2018

Multiple-system atrophy (MSA) is a neurodegenerative disease characterized by autonomic failure with various combinations of parkinsonism, cerebellar ataxia, and pyramidal dysfunction. We previously reported that functionally impaired variants of COQ2, which encodes an essential enzyme in the biosynthetic pathway of coenzyme Q10, are associated with MSA. Here, we report functional deficiencies in mitochondrial respiration and the antioxidative system in induced pluripotent stem cell (iPSC)-derived neurons from an MSA patient with compound heterozygous COQ2 mutations. The functional deficiencies were rescued by site-specific CRISPR/Cas9-mediated gene corrections. We also report an increase in apoptosis of iPSC-derived neurons from MSA patients. Coenzyme Q10 reduced apoptosis of neurons from the MSA patient with compound heterozygous COQ2 mutations. Our results reveal that cellular dysfunctions attributable to decreased coenzyme Q10 levels are related to neuronal death in MSA, particularly in patients with COQ2 variants, and may contribute to the development of therapy using coenzyme Q10 supplementation.
Chemotherapy payload of anti-insoluble fibrin antibody-drug conjugate is released specifically upon binding to fibrin
Authors: Fuchigami Hirobumi , Manabe Shino , Yasunaga Masahiro , Matsumura Yasuhiro
Published: September 2018

Cancer-induced blood coagulation in human tumour generates insoluble fibrin (IF)-rich cancer stroma in which uneven monoclonal antibody (mAb) distribution reduce the potential effectiveness of mAb-mediated treatments. Previously, we developed a mAb that reacts only with IF and not with fibrinogen (FNG) or the fibrin degradation product (FDP). Although IF, FNG and FDP share same amino acid sequences, the mAb is hardly neutralised by FNG and FDP in circulation and accumulates in fibrin clots within tumour tissue. Here, we created an antibody drug conjugate (ADC) using the anti-IF mAb conjugated with a chemotherapy payload (IF-ADC). The conjugate contains a linker severed specifically by plasmin (PLM), which is activated only on binding to IF. Imaging mass spectrometry showed the substantial intratumour distribution of the payload following the IF-ADC injection into mice bearing IF-rich 5–11 xenografts derived from pancreatic tumours of LSL-KrasG12D/+; LSL-Trp53R172H/+; Ptf1a-Cre (KPC) mice. IF-ADC treatment significantly extended the survival of the KPC mice. These data suggest that conjugating chemotherapy drugs to this IF-specific mAb could represent an effective means of treating stroma-rich tumours
Sun-induced fluorescence and gross primary productivity during a heat wave
Authors: Wohlfahrt G. , Gerdel K. , Migliavacca M. , Rotenberg E. , Tatarinov F. , Müller J. , Hammerle A. , Julitta T. , Spielmann F. M. , Yakir D.
Published: September 2018

Remote sensing of sun-induced chlorophyll fluorescence (SIF) has been suggested as a promising approach for probing changes in global terrestrial gross primary productivity (GPP). To date, however, most studies were conducted in situations when/where changes in both SIF and GPP were driven by large changes in the absorbed photosynthetically active radiation (APAR) and phenology. Here we quantified SIF and GPP during a short-term intense heat wave at a Mediterranean pine forest, during which changes in APAR were negligible. GPP decreased linearly during the course of the heat wave, while SIF declined slightly initially and then dropped dramatically during the peak of the heat wave, temporally coinciding with a biochemical impairment of photosynthesis inferred from the increase in the uptake ratio of carbonyl sulfide to carbon dioxide. SIF thus accounted for less than 35% of the variability in GPP and, even though it responded to the impairment of photosynthesis, appears to offer limited potential for quantitatively monitoring GPP during heat waves in the absence of large changes in APAR.
Examining the Role of Cone-expressed RPE65 in Mouse Cone Function
Authors: Kolesnikov Alexander V. , Tang Peter H. , Kefalov Vladimir J.
Published: September 2018

Efficient chromophore supply is paramount for the continuous function of vertebrate cone photoreceptors. It is well established that isomerization of all-trans- to 11-cis- retinoid in the retinal pigmented epithelium by RPE65 is a key reaction in this process. Mutations in RPE65 result in a disrupted chromophore supply, retinal degeneration, and blindness. Interestingly, RPE65 has recently been found to also be expressed in cone photoreceptors in several species, including mouse and human. However, the functional role of cone-expressed RPE65 has remained unknown. Here, we used loss and gain of function approaches to investigate this issue. First, we compared the function of cones from control and RPE65-deficient mice. Although we found that deletion of RPE65 partially suppressed cone dark adaptation, the interpretation of this result was complicated by the abnormal cone structure and function caused by the chromophore deficiency in the absence of RPE65 in the pigmented epithelium. As an alternative approach, we generated transgenic mice to express human RPE65 in the cones of mice where RPE65 expression is normally restricted to the pigmented epithelium. Comparison of control (RPE65-deficient) and transgenic (RPE65-expressing) cones revealed no morphological or functional changes, with only a slight delay in dark adaptation, possibly caused by the buffering of retinoids by RPE65. Together, our results do not provide any evidence for a functional role of RPE65 in mouse cones. Future studies will have to determine whether cone-expressed RPE65 plays a role in maintaining the long-term homeostasis of retinoids in cones and their function and survival, particularly in humans.
Digital enzyme assay using attoliter droplet array
Authors: Ono Takao , Ichiki Takanori , Noji Hiroyuki
Published: September 2018

Attoliter-volume and air-sealed reactor array for fast and robust single-molecule enzyme assay.
Monitoring of food spoilage by high resolution THz analysis
Authors: Hindle Francis , Kuuliala Lotta , Mouelhi Meriem , Cuisset Arnaud , Bray Cédric , Vanwolleghem Mathias , Devlieghere Frank , Mouret Gaël , Bocquet Robin
Published: September 2018

High resolution rotational Terahertz (THz) spectroscopy is suited to studies of numerous polar gas phase molecules, and particularly volatile organic compounds (VOCs). Analysis of the headspace gas of packed Salmon fillets indicates the degree of food spoilage.
Analysing single live cells by scanning electrochemical microscopy
Authors: Filice Fraser P. , Ding Zhifeng
Published: September 2018

Scanning electrochemical microscopy (SECM) offers single live cell activities along its topography toward cellular physiology and pathology.
Transition between tangential and co-axial liquid crystalline honeycombs in the self-assembly of Y-shaped bolapolyphiles
Authors: Lehmann Anne , Prehm Marko , Chen Changlong , Liu Feng , Zeng Xiangbing , Ungar Goran , Tschierske Carsten
Published: September 2018

A new liquid crystalline honeycomb with an organization of π-conjugated rods parallel to the honeycomb cells is formed by molecular self-assembly.
In situ growth of copper rhodizonate complexes on reduced graphene oxide for high-performance organic lithium-ion batteries
Authors: Wu Dabei , Li Heng , Li Ruguang , Hu Yulian , Hu Xianluo
Published: September 2018

Copper rhodizonate complexes grown on reduced graphene oxide exhibit outstanding electrochemical lithium-storage performances.
Live imaging of cell membrane-localized MT1-MMP activity on a microfluidic chip
Authors: Li Nan , Zhang Weifei , Lin Ling , He Ziyi , Khan Mashooq , Lin Jin-Ming
Published: September 2018

We designed an enzyme-activatable probe for real time in situ tracking of MT1-MMP activity.
Nonmonotonic thickness-dependence of in-plane thermal conductivity of few-layered MoS2: 2.4 to 37.8 nm
Authors: Yuan Pengyu , Wang Ridong , Wang Tianyu , Wang Xinwei , Xie Yangsu
Published: September 2018

The thermal conductivity of supported MoS2 is discovered to first decrease with thickness (<9.2 nm), then increase with thickness.
[(H2O)Zn(Imidazole)n]2+: the vital roles of coordination number and geometry in Zn–OH2acidity and catalytic hydrolysis
Authors: Linder Douglas P. , Baker Brett E. , Rodgers Kenton R.
Published: September 2018

The Zn(ii)–(Imidazole(ate))ncoordination motif occurs in numerous biochemical systems, including carbonic anhydrase and the matrix metalloproteinases (MMPs).
Ice-binding site of surface-bound type III antifreeze protein partially decoupled from water
Authors: Verreault Dominique , Alamdari Sarah , Roeters Steven J. , Pandey Ravindra , Pfaendtner Jim , Weidner Tobias
Published: September 2018

Combined SFG/MD analysis together with spectral calculations revealed that type III antifreeze proteins adsorbed at the air–water interface maintains a native state and adopts an orientation that leads to a partial decoupling of its ice-binding site from water.
On the influence of multiple cations on the in-gap states and phototransport properties of iodide-based halide perovskites
Authors: Azulay Doron , Levine Igal , Gupta Satyajit , Barak-Kulbak Einav , Bera Achintya , San Granit , Simha Shir , Cahen David , Millo Oded , Hodes Gary , Balberg Isaac
Published: September 2018

In-gap states in solar cell absorbers that are recombination centers determine the cell's photovoltaic performance.
A honeycomb-like monolayer of HfO2 and the calculation of static dielectric constant eliminating the effect of vacuum spacing
Authors: Weng Junhui , Gao Shang-Peng
Published: September 2018

A novel dielectric material of monolayer 1T-HfO2 has been investigated using first-principles calculations.
Exciton localization in excited-state dynamics of a tetracene trimer: a surface hopping LC-TDDFTB study
Authors: Titov Evgenii , Humeniuk Alexander , Mitrić Roland
Published: September 2018

Ultrafast exciton localization in a tetracene trimer is revealed with long-range corrected DFTB surface hopping simulations.
Sustainable and scalable synthesis of monodisperse carbon nanospheres and their derived superstructures
Authors: Xie Lei , Li Xuefeng , Deng Jiang , Gong Yutong , Wang Haiyan , Mao Shanjun , Wang Yong
Published: September 2018

Carbon nanospheres and their derived superstructures have attracted increasing attention due to their widespread applications ranging from electrochemistry to catalysis.
Synthesis of perfectly ordered mesoporous carbons by water-assisted mechanochemical self-assembly of tannin
Authors: Castro-Gutiérrez Jimena , Sanchez-Sanchez Angela , Ghanbaja Jaafar , Díez Noel , Sevilla Marta , Celzard Alain , Fierro Vanessa
Published: September 2018

Water-assisted mechanosynthesis allows preparing perfectly ordered mesoporous carbons from tannins without crosslinkers or any drying or curing step.
Graphene-based biosensor for on-chip detection of bio-orthogonally labeled proteins to identify the circulating biomarkers of aging during heterochronic parabiosis
Authors: Sadlowski Corinne , Balderston Sarah , Sandhu Mandeep , Hajian Reza , Liu Chao , Tran Thanhtra P. , Conboy Michael J. , Paredes Jacobo , Murthy Niren , Conboy Irina M. , Aran Kiana
Published: September 2018

Click-A+Chip identifies azido modified proteins with a novel graphene linker that performs copper-free-click chemistry on the chip's surface.
An integrated micro-millifluidic processing system
Authors: Zhang Jia Ming , Ji Qinglei , Liu Ying , Huang Jianyong , Duan Huiling
Published: September 2018

An integrated micro-millifluidic processing system based on multimaterial 3D-printing and a maskless lithography system is proposed.
Polycrystalline to preferred-(100) single crystal texture phase transformation of yttrium iron garnet nanoparticles
Authors: Borade Rameshwar B. , Shirsath Sagar E. , Vats Gaurav , Gaikwad Anil S. , Patange S. M. , Kadam S. B. , Kadam R. H. , Kadam A. B.
Published: September 2018

Nanocrystalline Ce-substituted yttrium iron garnet (YIG) powders of different compositions, Y3−xCexFe5O12 (0 ≤ x ≤ 2.0), were synthesized by a combination of sol–gel auto-combustion and solid-state synthesis techniques.
Supramolecular chirality control via self-assembly of oligoaniline in the chemical oxidative polymerization process
Authors: Li Ruiqi , Dai Jijin , Liu Lijia , Wang Jingfeng , Wang Pengli , Li Yufa , Zhou Dan , Han Yushan
Published: September 2018

Chirality control of PANI nanofibers is achieved by selecting the oligomeric species and changing the concentration of CSA and solvents.
Visible-light-activated C–C and C–N bond formation in the synthesis of imidazo[1,2-a]pyridines and imidazo[2,1-b]thiazoles under catalyst and solvent-free conditions
Authors: Shivhare Km Neha , Jaiswal Manish K. , Srivastava Anushree , Tiwari Saurabh K. , Siddiqui I. R.
Published: September 2018

Synthesis of 3-aminoimidazo-fused heterocycles via the Groebke–Blackburn–Bienaymé reaction using a universally available energy source under catalyst and solvent-free conditions.
The chitosan hydrogels: from structure to function
Authors: Fu Jing , Yang Fuchao , Guo Zhiguang
Published: September 2018

This review places an emphasis on chitosan intelligent hydrogels. The fabrication methods and mechanisms are introduced in this review and the interactions of the formation of hydrogels with both physical and chemical bonds are also introduced. The relationship between the structural characteristics and the corresponding functions of stimuli-responsive characteristics, self-healing functions and high mechanical strength properties of the chitosan hydrogels are discussed in detail.
Direct synthesis of diethyl carbonate from ethanol and carbon dioxide over ceria catalysts
Authors: Giram Ganesh G. , Bokade Vijay V. , Darbha Srinivas
Published: September 2018

Direct synthesis of diethyl carbonate (DEC) from ethanol and CO2was investigated over “neat” and metal incorporated ceria catalysts. An optimal dependence (“volcanic plot”) of the catalytic activity on the acidity/basicity molar ratio was observed.
Facile one-pot synthesis of a 3-azabicyclo[3.3.1]nonane scaffold by a tandem Mannich reaction
Authors: Yi Xiao , Tang Hongxia , Chen Jing , Xu Xiuling , Ma Yongmin
Published: September 2018

Various 3-azabicyclo[3.3.1]nonane derivatives are readily synthesized directly from aromatic ketones, paraformaldehyde and dimethylamine via a novel one-pot tandem Mannich annulation.
Building bridges between halide perovskite nanocrystals and thin-film solar cells
Authors: Yang Hanjun , Zhang Yi , Hills-Kimball Katie , Zhou Yuanyuan , Chen Ou
Published: September 2018

Perspectives on how halide perovskite nanocrystals are better integrated in perovskite solar cells are provided.
Flow and fracture near the sol–gel transition of silica nanoparticle suspensions
Authors: Gimenes Gustavo E. , Bouchaud Elisabeth
Published: September 2018

Mechanical response to tensile stress, from flow to fracture, as a function of the distance from the sol–gel transition.
Response to comment by Guerra et al.
Authors: Yang Xinyue , Cheng Yan , Su Guanfang
Published: September 2018

This is a response by the authors of the review article ‘A review of the multifunctionality of angiopoietin-like 4 in eye disease’ [Biosci. Rep. (2018) 38, BSR20180557, https://doi.org/10.1042/BSR20180557] to the comment published in this issue by Guerra et al. [Biosci. Rep. (2018) 38, BSR20180557, https://doi.org/10.1042/BSR20181462]
High cadence, linear, and circular polarization monitoring of OJ 287
Authors: Myserlis I. , Komossa S. , Angelakis E. , Gómez J. L. , Karamanavis V. , Krichbaum T. P. , Bach U. , Grupe D.
Published: September 2018

Aims. We present a multifrequency, dense radio monitoring program of the blazar OJ 287 using the 100-m Effelsberg radio telescope. The program aims to test different binary supermassive black hole (SMBH) scenarios and studying the physical conditions in the central region of this bright blazar. Here, we analyze the evolution in total flux density, linear and circular polarization as a means to study the OJ 287 jet structure and its magnetic field geometry.

Methods. We used a recently developed, high-precision data analysis methodology to recover all four Stokes parameters. We measured the total flux density of OJ 287 at nine bands from 2.64 GHz to 43 GHz, the linear polarization parameters at four bands between 2.64 GHz and 10.45 GHz, and the circular polarization at two bands, 4.85 GHz and 8.35 GHz. The mean cadence of our measurements is ten days.

Results. Between December 2015 and January 2017 (MJD 57370–57785), OJ 287 showed flaring activity and complex linear and circular polarization behavior. The radio electric vector position angle (EVPA) showed a large clockwise (CW) rotation by ∼340° with a mean rate of −1.04°/day. Based on concurrent very long baseline interferometric (VLBI) polarization data at 15 GHz and 43 GHz, the rotation seems to originate within the jet core at 43 GHz (projected angular size ≤0.15 mas or 0.67 pc at the redshift of the source). Moreover, optical polarization data show a similar monotonic CW rotation with a rate of about −1.1°/day which is superposed with shorter and faster rotations that exhibit rates of about 7.8°/day, mainly in the CW sense.

Conclusions. The flux density and polarization variability of the single dish, VLBI and optical data is consistent with a polarized emission component propagating on a helical trajectory within a bent jet. We constrained the helix arc length to 0.26 pc and radius to ≤0.04 pc as well as the jet bending arc length projected on the plane of the sky to ≤1.9–7.6 pc. A similar bending has been observed also in high angular resolution VLBI images of the OJ 287 jet at its innermost regions. The helical trajectory covers only a part of the jet width, possibly its spine. In addition, our results indicate the presence of a stable polarized emission component. Its EVPA (−10°) is oriented perpendicular to the large scale jet, suggesting dominance of the poloidal magnetic field component. Finally, the EVPA rotation begins simultaneously with an optical flare and hence the two might be physically connected. That optical flare has been suggested to be linked to the interaction of a secondary SMBH with the inner accretion disk or originating in the jet of the primary.
High frequency saltwater intrusion monitoring using borehole geophysical tools (SMD)
Authors: Baïsset M. , Neyens D.
Published: September 2018

In February 2016, two remote controlled geophysical monitoring tools (SMD) have been installed for the first time in the Reunion Island. Settled into two piezometers drilled into a basaltic coastal aquifer, between the ocean and a production well, they allow the record of groundwater electrical conductivity (ECw) logs on a 30 min basis. Thanks to those two tools, water operator continuously knows the shape and the position of the SWI as data are available online on a secured web application designed especially for SWI data management.

During the observation period a 5,15 m rise of SWI interface has been recorded. Knowing the average porosity, water table elevation and SWI interface position it is possible to estimate available fresh groundwater volume. Along a 1 km band between extraction well and the ocean, available fresh groundwater volume was found to be 1 259 000 m3 in June 2016. In June 2017, due to SWI progression this volume was found to be 777 000 m3, that to say a 480 000 m3 volume of freshwater replaced by brackish water.

SMD network will now be spread in the Reunion Island to improve coastal extraction well management knowing SWI shape and position on a high frequency basis.