bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of osteoblastic Smurf1 promotes bone formation in mouse models of distinctive age-related osteoporosis
Authors: Liang Chao , Peng Songlin , Li Jie , Lu Jun , Guan Daogang , Jiang Feng , Lu Cheng , Li Fangfei , He Xiaojuan , Zhu Hailong , Au D. W. T. , Yang Dazhi , Zhang Bao-Ting , Lu Aiping , Zhang Ge
Published: August 2018

Bone morphogenetic protein (BMP) signaling is essential for osteogenesis. However, recombinant human BMPs (rhBMPs) exhibit large inter-individual variations in local bone formation during clinical spinal fusion. Smurf1 ubiquitinates BMP downstream molecules for degradation. Here, we classify age-related osteoporosis based on distinct intraosseous BMP-2 levels and Smurf1 activity. One major subgroup with a normal BMP-2 level and elevated Smurf1 activity (BMP-2n/Smurf1e) shows poor response to rhBMP-2 during spinal fusion, when compared to another major subgroup with a decreased BMP-2 level and normal Smurf1 activity (BMP-2d/Smurf1n). We screen a chalcone derivative, i.e., 2-(4-cinnamoylphenoxy)acetic acid, which effectively inhibits Smurf1 activity and increases BMP signaling. For BMP-2n/Smurf1e mice, the chalcone derivative enhances local bone formation during spinal fusion. After conjugating to an osteoblast-targeting and penetrating oligopeptide (DSS)6, the chalcone derivative promotes systemic bone formation in BMP-2n/Smurf1e mice. This study demonstrates a precision medicine-based bone anabolic strategy for age-related osteoporosis.
Treatment with mRNA coding for the necroptosis mediator MLKL induces antitumor immunity directed against neo-epitopes
Authors: Van Hoecke Lien , Van Lint Sandra , Roose Kenny , Van Parys Alexander , Vandenabeele Peter , Grooten Johan , Tavernier Jan , De Koker Stefaan , Saelens Xavier
Published: August 2018

Cancer immunotherapy can induce durable antitumor responses. However, many patients poorly respond to such therapies. Here we describe a generic antitumor therapy that is based on the intratumor delivery of mRNA that codes for the necroptosis executioner mixed lineage kinase domain-like (MLKL) protein. This intervention stalls primary tumor growth and protects against distal and disseminated tumor formation in syngeneic mouse melanoma and colon carcinoma models. Moreover, MLKL-mRNA treatment combined with immune checkpoint blockade further improves the antitumor activity. MLKL-mRNA treatment rapidly induces T cell responses directed against tumor neo-antigens and requires CD4+ and CD8+ T cells to prevent tumor growth. Type I interferon signaling and Batf3-dependent dendritic cells are essential for this mRNA treatment to elicit tumor antigen-specific T cell responses. Moreover, MLKL-mRNA treatment blunts the growth of human lymphoma in mice with a reconstituted human adaptive immune system. MLKL-based treatment can thus be exploited as an effective antitumor immunotherapy.
Impact ionization by hot carriers in a black phosphorus field effect transistor
Authors: Ahmed Faisal , Kim Young Duck , Yang Zheng , He Pan , Hwang Euyheon , Yang Hyunsoo , Hone James , Yoo Won Jong
Published: August 2018

The strong Coulombic interactions in miniaturized structures can lead to efficient carrier multiplication, which is essential for many-body physics and design of efficient photonic devices beyond thermodynamic conversion limits. However, carrier multiplication has rarely been realized in layered semiconducting materials despite strong electronic interactions. Here, we report the experimental observation of unusual carrier multiplication in a multilayer black phosphorus device. Electric field-dependent Hall measurements confirm a substantial increase of carrier density in multilayer black phosphorus channel, which is attributed to the impact ionization by energetic carriers. This mechanism relies on the generation of self-heating induced charge carriers under the large electric field due to competition between electron–electron and electron–phonon interactions in the direct and narrow band gap (0.3 eV) of the multilayer black phosphorus. These findings point the way toward utilization of carrier multiplication to enhance the performance of electronics and optoelectronics devices based on two-dimensional materials.
In-built thermo-mechanical cooperative feedback mechanism for self-propelled multimodal locomotion and electricity generation
Authors: Wang Xiao-Qiao , Tan Chuan Fu , Chan Kwok Hoe , Lu Xin , Zhu Liangliang , Kim Sang-Woo , Ho Ghim Wei
Published: August 2018

Utilization of ubiquitous low-grade waste heat constitutes a possible avenue towards soft matter actuation and energy recovery opportunities. While most soft materials are not all that smart relying on power input of some kind for continuous response, we conceptualize a self-locked thermo-mechano feedback for autonomous motility and energy generation functions. Here, the low-grade heat usually dismissed as ‘not useful’ is used to fuel a soft thermo-mechano-electrical system to perform perpetual and untethered multimodal locomotions. The innately resilient locomotion synchronizes self-governed and auto-sustained temperature fluctuations and mechanical mobility without external stimulus change, enabling simultaneous harvesting of thermo-mechanical energy at the pyro/piezoelectric mechanistic intersection. The untethered soft material showcases deterministic motions (translational oscillation, directional rolling, and clockwise/anticlockwise rotation), rapid transitions and dynamic responses without needing power input, on the contrary extracting power from ambient. This work may open opportunities for thermo-mechano-electrical transduction, multigait soft energy robotics and waste heat harvesting technologies.
Giant spin-valley polarization and multiple Hall effect in functionalized bismuth monolayers
Authors: Zhou Tong , Zhang Jiayong , Jiang Hua , Žutić Igor , Yang Zhongqin
Published: August 2018

Valleytronic materials, characterized by local extrema (valleys) in their bands, and topological insulators have separately attracted great interest recently. However, the interplay between valleytronic and topological properties in one single system, likely to enable important unexplored phenomena and applications, has been largely overlooked so far. Here, by combining a tight-binding model with first-principles calculations, we find the large-band-gap quantum spin Hall effects (QSHEs) and valley Hall effects appear simultaneously in the bismuth monolayers decorated with hydrogen/halogen elements, denoted as Bi2XY (X, Y = H, F, Cl, Br, or I). A staggered exchange field is introduced into the Bi2XY monolayers by transition-metal atom (Cr, Mo, or W) doping or LaFeO3 magnetic substrates, which together with the strong spin-orbit coupling of bismuth atoms generates a time-reversal-symmetry-broken QSHE and a huge valley splitting (up to 513 meV) in the system. With gate control, QSHE and anomalous charge, spin, valley Hall effects can be observed in the single system. These predicted multiple and exotic Hall effects, associated with various degrees of freedom of electrons, could enable applications of the functionalized bismuth monolayers in electronics, spintronics, and valleytronics.
The E3 SUMO ligase PIASγ is a novel interaction partner regulating the activity of diabetes associated hepatocyte nuclear factor-1α
Authors: Kaci Alba , Keindl Magdalena , Solheim Marie H. , Njølstad Pål R. , Bjørkhaug Lise , Aukrust Ingvild
Published: August 2018

The transcription factor hepatocyte nuclear factor-1α (HNF-1A) is involved in normal pancreas development and function. Rare variants in the HNF1A gene can cause monogenic diabetes, while common variants confer type 2 diabetes risk. The precise mechanisms for regulation of HNF-1A, including the role and function of post-translational modifications, are still largely unknown. Here, we present the first evidence for HNF-1A being a substrate of SUMOylation in cellulo and identify two lysine (K) residues (K205 and K273) as SUMOylation sites. Overexpression of protein inhibitor of activated STAT (PIASγ) represses the transcriptional activity of HNF-1A and is dependent on simultaneous HNF-1A SUMOylation at K205 and K273. Moreover, PIASγ is a novel HNF-1A interaction partner whose expression leads to translocation of HNF-1A to the nuclear periphery. Thus, our findings support that the E3 SUMO ligase PIASγ regulates HNF-1A SUMOylation with functional implications, representing new targets for drug development and precision medicine in diabetes.
Zircon U-Pb geochronology of crystal tuff on Lingshan Island and its geological implications for magmatism, stratigraphic age and geological events
Authors: Gao Jindong , Feng Qiao , Zhang Xiaoli , Zhou Lifa , Jiao Zunsheng , Qin Yu
Published: August 2018

Due to the unique location in the Ludong region, geochronological study of this area is essential for the understanding of the Cretaceous tectonic evolution of Eastern China. Sedimentary sequences interbedded with tuff layers unconformably overlay metamorphic rocks in the Sulu Orogen. This research presents a more reliable geochronological dataset of a tuff layer on Lingshan Island in Qingdao. A total of 103 valid age values from 216 zircon grains were obtained in three fresh tuff samples. Approximately 87% of these zircon ages are dated as the Early Cretaceous, and their peak ages shift from the Aptian stage to the Albian stage. The spatial-temporal relationship between the tuff and the Mesozoic igneous rocks of Eastern China indicate the impact of the Pacific Plate subduction beneath the Asian continent. Six Albian single detrital zircons have a weighted average age of 103.8 ± 1.4 Ma, with the youngest age (103.4 ± 1.4 Ma) constraining the maximum depositional age of the tuff layer. The age sequence of four sections on Lingshan Island is defined in this study: sections A and B belong to the Laiyang Group, and sections C and D are considered the Qingshan Group and were deposited in the Late Cretaceous. Two pre-Cretaceous zircon age peaks were also observed. These age peaks coincide with the magmatic and metamorphic ages preserved in the Sulu Orogen; thus, the Sulu Orogen is the provenance of the sedimentary rocks on Lingshan Island.
Complete sequence of kenaf (Hibiscus cannabinus) mitochondrial genome and comparative analysis with the mitochondrial genomes of other plants
Authors: Liao Xiaofang , Zhao Yanhong , Kong Xiangjun , Khan Aziz , Zhou Bujin , Liu Dongmei , Kashif Muhammad Haneef , Chen Peng , Wang Hong , Zhou Ruiyang
Published: August 2018

Plant mitochondrial (mt) genomes are species specific due to the vast of foreign DNA migration and frequent recombination of repeated sequences. Sequencing of the mt genome of kenaf (Hibiscus cannabinus) is essential for elucidating its evolutionary characteristics. In the present study, single-molecule real-time sequencing technology (SMRT) was used to sequence the complete mt genome of kenaf. Results showed that the complete kenaf mt genome was 569,915 bp long and consisted of 62 genes, including 36 protein-coding, 3 rRNA and 23 tRNA genes. Twenty-five introns were found among nine of the 36 protein-coding genes, and five introns were trans-spliced. A comparative analysis with other plant mt genomes showed that four syntenic gene clusters were conserved in all plant mtDNAs. Fifteen chloroplast-derived fragments were strongly associated with mt genes, including the intact sequences of the chloroplast genes psaA, ndhB and rps7. According to the plant mt genome evolution analysis, some ribosomal protein genes and succinate dehydrogenase genes were frequently lost during the evolution of angiosperms. Our data suggest that the kenaf mt genome retained evolutionarily conserved characteristics. Overall, the complete sequencing of the kenaf mt genome provides additional information and enhances our better understanding of mt genomic evolution across angiosperms.
A detailed investigation of the porcine skin and nose microbiome using universal and Staphylococcus specific primers
Authors: Strube Mikael Lenz , Hansen Julie Elvekjær , Rasmussen Sophia , Pedersen Karl
Published: August 2018

MRSA is an increasing problem in humans as well as livestock. The bacterial co-colonization of the skin in MRSA carriers has been poorly investigated and moreover, there have been no methods for high resolution investigations of the Staphylococcus genus apart from tediously culturing or doing multiple PCRs. On 120 samples from pig ear, skin and nose, we generated amplicons from the V1-V2 region of the 16S rRNA gene to gather an overview of the genus-level microbiome, along with using MRSA specific plates to count MRSA. In parallel with this, amplicons of the tuf gene were generated, targeting only a region of the tuf gene found only in the Staphylococcus genus. Using these methods, we determined a core microbiota across the healthy pig and determined the Staphylococcus genus to be dominated by S. equorum. Moreover, we found Streptococcus to be inversely associated with Staphylococcus and MRSA, suggesting a role for this genus in combating MRSA. In this work, we have thoroughly investigated the skin and nose microbiome of the pig and developed a high throughput method for profiling the Staphylococcus genus which we believe will be useful for further investigations.
Coupling Energy Capture and Storage – Endeavoring to make a solar battery
Authors: Arora Yukti , Battu Shateesh , Haram Santosh , Khushalani Deepa
Published: August 2018

Storage of solar radiation is currently accomplished by coupling two separate devices, one that captures and converts the energy into an electrical impulse (a photovoltaic cell) and another that stores this electrical output (a battery or a supercapacitor electrochemical cell). This configuration however has several challenges that stem from a complex coupled-device architecture and multiple interfaces through which charge transfer has to occur. As such presented here is a scheme whereby solar energy capture and storage have been coupled using a single bi-functional material. Two electroactive semiconductors BiVO4 (n-type) and Co3O4 (p-type) have been separately evaluated for their energy storage capability in the presence and absence of visible radiation. Each of these have the capability to function as a light harvester and also they have faradaic capability. An unprecedented aspect has been observed in that upon photo-illumination of either of these semiconductors, in situ charge carriers being generated play a pivotal role in perturbing the electroactivity of the redox species such that the majority charge carriers, viz. electrons in BiVO4 and holes in Co3O4, influence the redox response in a disproportionate manner. More importantly, there is an enhancement of ca. 30% in the discharge capacity of BiVO4 in the presence of light and this directly provides a unique route to augment charge storage during illumination.
The UV/Visible Radiation Boundary Region (385–405 nm) Damages Skin Cells and Induces “dark” Cyclobutane Pyrimidine Dimers in Human Skin in vivo
Authors: Lawrence Karl P. , Douki Thierry , Sarkany Robert P. E. , Acker Stephanie , Herzog Bernd , Young Antony R.
Published: August 2018

The adverse effects of terrestrial solar ultraviolet radiation (UVR) (~295–400 nm) on the skin are well documented, especially in the UVB region (~295–320 nm). The effects of very long-wave UVA (>380 nm) and visible radiation (≥400 nm) are much less known. Sunscreens have been beneficial in inhibiting a wide range of photodamage, however most formulations provide very little protection in the long wave UVA region (380–400 nm) and almost none from shortwave visible wavelengths (400–420 nm). We demonstrate photodamage in this region for a number of different endpoints including cell viability, DNA damage (delayed cyclobutane pyrimidine dimers), differential gene expression (for genes associated with inflammation, oxidative stress and photoageing) and induction of oxidizing species in vitro in HaCaT keratinocytes and in vivo in human volunteers. This work has implications for phototherapy and photoprotection.
Bolometric photodetection using plasmon-assisted resistivity change in vanadium dioxide
Authors: Takeya Hironobu , Frame James , Tanaka Takuo , Urade Yoshiro , Fang Xu , Kubo Wakana
Published: August 2018

Vanadium oxide is a key sensing material for bolometric photodetection, thanks to its strong temperature dependence of resistivity close to room temperature. Here we demonstrate the photodetection of a stoichiometric vanadium dioxide thin film integrated with silver nanorods. The nanorods convert light into heat, consequently suppressing the resistivity of vanadium dioxide via localised surface plasmon resonance. Incorporation of this thermo-plasmonic effect into bolometric photodetection allows for wavelength and polarisation sensitivity. This work opens the path to a broad family of photodetection functionalities for vanadium dioxide-based microbolometers.
Mapping discontinuous epitopes for MRK-16, UIC2 and 4E3 antibodies to extracellular loops 1 and 4 of human P-glycoprotein
Authors: Vahedi Shahrooz , Lusvarghi Sabrina , Pluchino Kristen , Shafrir Yinon , Durell Stewart R. , Gottesman Michael M. , Ambudkar Suresh V.
Published: August 2018

P-glycoprotein (P-gp), an ATP-dependent efflux pump, is associated with the development of multidrug resistance in cancer cells. Antibody-mediated blockade of human P-gp activity has been shown to overcome drug resistance by re-sensitizing resistant cancer cells to anticancer drugs. Despite the potential clinical application of this finding, the epitopes of the three human P-gp-specific monoclonal antibodies MRK-16, UIC2 and 4E3, which bind to the extracellular loops (ECLs) have not yet been mapped. By generating human-mouse P-gp chimeras, we mapped the epitopes of these antibodies to ECLs 1 and 4. We then identified key amino acids in these regions by replacing mouse residues with homologous human P-gp residues to recover binding of antibodies to the mouse P-gp. We found that changing a total of ten residues, five each in ECL1 and ECL4, was sufficient to recover binding of both MRK-16 and 4E3 antibodies, suggesting a common epitope. However, recovery of the conformation-sensitive UIC2 epitope required replacement of thirteen residues in ECL1 and the same five residues replaced in the ECL4 for MRK-16 and 4E3 binding. These results demonstrate that discontinuous epitopes for MRK-16, UIC2 and 4E3 are located in the same regions of ECL1 and 4 of the multidrug transporter.
Alteration of β-Adrenoceptor Signaling in Left Ventricle of Acute Phase Takotsubo Syndrome: a Human Study
Authors: Nakano Tomoya , Onoue Kenji , Nakada Yasuki , Nakagawa Hitoshi , Kumazawa Takuya , Ueda Tomoya , Nishida Taku , Soeda Tsunenari , Okayama Satoshi , Watanabe Makoto , Kawata Hiroyuki , Kawakami Rika , Horii Manabu , Okura Hiroyuki , Uemura Shiro , Hatakeyama Kinta , Sakaguchi Yasuhiro , Saito Yoshihiko
Published: August 2018

Accumulating evidence indicates alteration of the β-adrenoceptor (AR), such as desensitization and subtype switching of its coupling G protein, plays a role in the protection against catecholamine toxicity in heart failure. However, in human takotsubo syndrome (TTS), which is associated with a surge of circulating catecholamine in the acute phase, there is no histologic evidence of β-AR alteration. The purpose of this study was to investigate the involvement of alteration of β-AR signaling in the mechanism of TTS development. Left ventricular (LV) biopsied samples from 26 patients with TTS, 19 with normal LV function, and 26 with dilated cardiomyopathy (DCM) were studied. G protein-coupled receptor kinase 2 (GRK2) and β-arrestin2, which initiate the alteration of β-AR signaling, were more abundantly expressed in the myocardium in acute-phase TTS than in those of DCM and normal control as indicated by immunohistochemistry. The percentage of cardiomyocytes that showed positive membrane staining for GRK2 and β-arrestin2 was also significantly higher in acute-phase TTS. Sequential biopsies in the recovery-phase for two patients with TTS revealed that membrane expression of GRK2 and β-arrestin2 faded over time. This study provided the first histologic evidence of the involvement of alteration of β-ARs in the development of TTS.
Lack of cyclin D3 induces skeletal muscle fiber-type shifting, increased endurance performance and hypermetabolism
Authors: Giannattasio Silvia , Giacovazzo Giacomo , Bonato Agnese , Caruso Carla , Luvisetto Siro , Coccurello Roberto , Caruso Maurizia
Published: August 2018

The mitogen-induced D-type cyclins (D1, D2 and D3) are regulatory subunits of the cyclin-dependent kinases CDK4 and CDK6 that drive progression through the G1 phase of the cell cycle. In skeletal muscle, cyclin D3 plays a unique function in controlling the proliferation/differentiation balance of myogenic progenitor cells. Here, we show that cyclin D3 also performs a novel function, regulating muscle fiber type-specific gene expression. Mice lacking cyclin D3 display an increased number of myofibers with higher oxidative capacity in fast-twitch muscle groups, primarily composed of myofibers that utilize glycolytic metabolism. The remodeling of myofibers toward a slower, more oxidative phenotype is accompanied by enhanced running endurance and increased energy expenditure and fatty acid oxidation. In addition, gene expression profiling of cyclin D3−/− muscle reveals the upregulation of genes encoding proteins involved in the regulation of contractile function and metabolic markers specifically expressed in slow-twitch and fast-oxidative myofibers, many of which are targets of MEF2 and/or NFAT transcription factors. Furthermore, cyclin D3 can repress the calcineurin- or MEF2-dependent activation of a slow fiber-specific promoter in cultured muscle cells. These data suggest that cyclin D3 regulates muscle fiber type phenotype, and consequently whole body metabolism, by antagonizing the activity of MEF2 and/or NFAT.
Unexpectedly high Plasmodium sporozoite rate associated with low human blood index in Anopheles coluzzii from a LLIN-protected village in Burkina Faso
Authors: Pombi Marco , Calzetta Maria , Guelbeogo Wamdaogo M. , Manica Mattia , Perugini Eleonora , Pichler Verena , Mancini Emiliano , Sagnon N’Fale , Ranson Hilary , della Torre Alessandra
Published: August 2018

Despite the effectiveness of mass distribution of long-lasting insecticidal nets (LLINs) in reducing malaria transmission in Africa, in hyperendemic areas such as Burkina Faso the burden of malaria remains high. We here report the results of a 4-month survey on the feeding habits andPlasmodiuminfection in malaria vectors from a village in Burkina Faso one year following a national LLIN distribution programme. Low values of human blood index (HBI) observed in the major malaria vectors in the area (Anopheles coluzzii: N = 263, 20.1%;An. arabiensis: 5.8%, N = 103) are consistent with the hypothesis that LLINs reduced the availability of human hosts to mosquitoes. A regression meta-analysis of data from a systematic review of published studies reporting HBI and sporozoite rates (SR) forAn. gambiaecomplex revealed that the observed SR values (An. coluzzii: 7.6%, N = 503;An. arabiensis: 5.3%, N = 225) are out of the ranges expected based on the low HBI observed. We hypothesize that a small fraction of inhabitants unprotected by bednets acts as a “core group” repeatedly exposed to mosquito bites, representing the majorPlasmodiumreservoir for the vectors, able to maintain a high risk of transmission even in a village protected by LLINs.
Mass screening for liver cancer: results from a demonstration screening project in Zhongshan City, China
Authors: Ji Mingfang , Liu Zhiwei , Chang Ellen T. , Yu Xia , Wu Biaohua , Deng Li , Feng Qianjin , Wei Kuangrong , Liang Xuejun , Lian Shifeng , Quan Wen , Wang Panpan , Du Yun , Liang Zhiheng , Xia Shenglin , Lin Hai , Li Fugui , Cheng Weimin , Chen Weiqiang , Yuan Yong , Ye Weimin
Published: August 2018

Current Chinese national guidelines recommend routine screening for liver cancer in patients positive for HBsAg, irrespective of fibrosis status, age, or family history of liver cancer. We aim to evaluate whether the recommended screening strategy could reduce liver-cancer-specific mortality. We conducted a liver cancer mass screening trial in Xiaolan Town, Zhongshan City, China, among residents aged 35–64 years in 2012. All volunteers were offered serological testing for hepatitis B virus surface antigen (HBsAg). We proposed biannual screening using serum alpha-fetoprotein (AFP) and ultrasonography examination for subjects positive for HBsAg. Among 17,966 participants (26.2% of 68,510 eligible residents) who were free of liver cancer at baseline in 2012, we identified 57 incident cases of liver cancer within the first 4 years of follow-up (i.e., 43 among 2,848 HBsAg-positive participants and 14 among 15,118 HBsAg-negative participants), compared with 104 cases identified in non-participants (N = 50,544). A total of 207 participants had the recommended number of ultrasonography examinations (every 6 months) during the screening period. Compared with cases identified from non-participants, the cases arising among participants were more likely to be at early stage and had better survival than those among non-participants. However, we did not observe a reduction in liver cancer-specific mortality rate among participants (relative risk = 1.04, 95% confidence interval = 0.68, 1.58, P = 0.856). Our demonstration screening study does not show a reduction in liver cancer mortality within the first 4 years of follow-up according to current guidance in China, although long-term efficacy remains to be evaluated. Targeted surveillance among high-risk individuals as recommended by international guidelines, along with measures to improve compliance, should be evaluated in the Chinese population.
Soluble cMet levels in urine are a significant prognostic biomarker for diabetic nephropathy
Authors: Kim Yong Chul , An Jung Nam , Kim Jin Hyuk , Choi Young-Wook , Oh Sohee , Kwon Sang Ho , Lee Mi-Young , Lee Junghun , Jeong Jae-Gyun , Lim Chun Soo , Kim Yon Su , Yang Seung Hee , Lee Jung Pyo
Published: August 2018

Hepatocyte growth factor and its receptor cMet activate biological pathways necessary for repair and regeneration following kidney injury. Here, we evaluated the clinical role of urinary cMet as a prognostic biomarker in diabetic nephropathy (DN). A total of 218 patients with DN were enrolled in this study. We examined the association of urine cMet levels and long-term outcomes in patients with DN. The levels of urinary cMet were higher in patients with decreased renal function than in patients with relatively preserved renal function (5.25 ± 9.62 ng/ml versus 1.86 ± 4.77 ng/ml, P = 0.001). A fully adjusted model revealed that a urinary cMet cutoff of 2.9 ng/mL was associated with a hazard ratio for end-stage renal disease of 2.33 (95% confidence interval 1.19–4.57, P = 0.014). The addition of urinary cMet to serum creatinine and proteinuria provided the highest net reclassification improvement. We found that in primary cultured human glomerular endothelial cells, TGFβ treatment induced fibrosis, and the protein expression levels of collagen I, collagen IV, fibronectin, and αSMA were decreased after administration of an agonistic cMet antibody. In conclusion, elevated levels of urinary cMet at the time of initial diagnosis could predict renal outcomes in patients with DN.
Translation of metal-phthalocyanines adsorbed on Au(111): from van der Waals interaction to strong electronic correlation
Authors: Buimaga-Iarinca L. , Morari C.
Published: August 2018

Using first-principles calculations, we investigate the binding energy for six transition metal - phthalocyanine molecules adsorbed on Au(111). We focus on the effect of translation on molecule - surface physical properties; van der Waals interactions as well as the strong correlation in d orbitals of transition metals are taken into account in all calculations. We found that dispersion interaction and charge transfer have the dominant role in the molecule-surface interaction, while the interaction between the transition metal and gold has a rather indirect influence over the physics of the molecule-surface system. A detailed analysis of the physical properties of the adsorbates at different geometric configurations allows us to propose qualitative models to account for all values of interface dipole charge transfer and magnetic moment of metal-phthalocyanines adsorbed on Au(111).
Arm swing asymmetry in overground walking
Authors: Killeen Tim , Elshehabi Morad , Filli Linard , Hobert Markus A. , Hansen Clint , Rieger David , Brockmann Kathrin , Nussbaum Susanne , Zörner Björn , Bolliger Marc , Curt Armin , Berg Daniela , Maetzler Walter
Published: August 2018

Treadmill experiments suggest that left-dominant arm swing is common in healthy walking adults and is modulated by cognitive dual-tasking. Little is known about arm swing asymmetry in overground walking. We report directional (dASI) and non-directional arm swing symmetry indices (ndASI) from 334 adults (mean age 68.6 ± 5.9 y) walking overground at comfortable (NW) and fast (FW) speeds and while completing a serial subtraction task (DT). dASI and ndASI were calculated from sagittal shoulder range of motion data generated by inertial measurement units affixed to the wrist. Most (91%) participants were right-handed. Group mean arm swing amplitude was significantly larger on the left in all walking conditions. During NW, ndASI was 39.5 ± 21.8, with a dASI of 21.9 ± 39.5. Distribution of dASI was bimodal with an approximately 2:1 ratio of left:right-dominant arm swing. There were no differences in ndASI between conditions but dASI was smaller during DT compared to FW (15.2 vs 24.6; p = 0.009). Handedness was unrelated to ndASI, dASI or the change in ASI metrics under DT. Left-dominant arm swing is the norm in healthy human walking irrespective of walking condition or handedness. As disease markers, ndASI and dASI may have different and complementary roles.
Collaboration of tRNA modifications and elongation factor eEF1A in decoding and nonsense suppression
Authors: Klassen Roland , Schaffrath Raffael
Published: August 2018

Transfer RNA (tRNA) from all domains of life contains multiple modified nucleosides, the functions of which remain incompletely understood. Genetic interactions between tRNA modification genes inSaccharomyces cerevisiaesuggest that different tRNA modifications collaborate to maintain translational efficiency. Here we characterize such collaborative functions in the ochre suppressor tRNASUP4. We quantified ochre read-through efficiency in mutants lacking either of the 7 known modifications in the extended anticodon stem loop (G26-C48). Absence of U34, U35, A37, U47 and C48 modifications partially impairedSUP4function. We systematically combined modification defects and scored additive or synergistic negative effects onSUP4performance. Our data reveal different degrees of functional redundancy between specific modifications, the strongest of which was demonstrated for those occurring at positions U34 and A37.SUP4activity in the absence of critical modifications, however, can be rescued in a gene dosage dependent fashion byTEF1which encodes elongation factor eEF1A required for tRNA delivery to the ribosome. Strikingly, the rescue ability of higher-than-normal eEF1A levels extends to tRNA modification defects in natural non-suppressor tRNAs suggesting that elevated eEF1A abundance can partially compensate for functional defects induced by loss of tRNA modifications.
Effects of Khat (Catha edulis) use on catalytic activities of major drug-metabolizing cytochrome P450 enzymes and implication of pharmacogenetic variations
Authors: Bedada Worku , de Andrés Fernando , Engidawork Ephrem , Hussein Jemal , LLerena Adrián , Aklillu Eleni
Published: August 2018

In a one-way cross-over study, we investigated the effect of Khat, a natural amphetamine-like psychostimulant plant, on catalytic activities of five major drug-metabolizing cytochrome P450 (CYP) enzymes. After a one-week Khat abstinence, 63 Ethiopian male volunteers were phenotyped using cocktail probe drugs (caffeine, losartan, dextromethorphan, omeprazole). Phenotyping was repeated after a one-week daily use of 400 g fresh Khat leaves. Genotyping for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A5 were done. Urinary cathinone and phenylpropanolamine, and plasma probe drugs and metabolites concentrations were quantified using LC-MS/MS. Effect of Khat on enzyme activities was evaluated by comparing caffeine/paraxanthine (CYP1A2), losartan/losartan carboxylic acid (CYP2C9), omeprazole/5-hydroxyomeprazole (CYP2C19), dextromethorphan/dextrorphan (CYP2D6) and dextromethorphan/3-methoxymorphinan (CYP3A4) metabolic ratios (MR) before and after Khat use. Wilcoxon-matched-pair-test indicated a significant increase in median CYP2D6 MR (41%, p < 0.0001), and a marginal increase in CYP3A4 and CYP2C19 MR by Khat. Repeated measure ANOVA indicated the impact of CYP1A2 and CYP2C19 genotype on Khat-CYP enzyme interactions. The median MR increased by 35% in CYP1A2*1/*1 (p = 0.07) and by 40% in carriers of defective CYP2C19 alleles (p = 0.03). Urinary log cathinone/phenylpropanolamine ratios significantly correlated with CYP2D6 genotype (p = 0.004) and CYP2D6 MR (P = 0.025). Khat significantly inhibits CYP2D6, marginally inhibits CYP3A4, and genotype-dependently inhibit CYP2C19 and CYP1A2 enzyme activities.
Effects of aspect ratio and metal layer thickness on demoulding of metal/polymer bilayer gratings during nanoimprinting
Authors: Zheng Xu , Wang Qing , Zhang Rui , Ma Lijun , Luan Jinjin
Published: August 2018

During the fabrication of metal/polymer bilayer gratings by nanoimprint lithography, adhesion and friction forces at the interfaces can deform and damage the transferred pattern of the bilayer grating during the demoulding process. To improve the quality of bilayer gratings, the effects of the aspect ratio and metal layer thickness on deformation and stress during the demoulding process in the nanoimprinting of bilayer gratings were investigated. This information was used to determine the optimal grating parameters. The results for the von Mises stress and deformation of bilayer gratings are discussed in detail. The effects of the aspect ratio and metal layer thickness on the grating quality are then considered.
Modulation of Cosmogenic Tritium in Meteoric Precipitation by the 11-year Cycle of Solar Magnetic Field Activity
Authors: Palcsu László , Morgenstern Uwe , Sültenfuss Jürgen , Koltai Gabriella , László Elemér , Temovski Marjan , Major Zoltán , Nagy Judit T. , Papp László , Varlam Carmen , Faurescu Ionut , Túri Marianna , Rinyu László , Czuppon György , Bottyán Emese , Jull A. J. Timothy
Published: August 2018

The relationship between the atmospheric concentration of cosmogenic isotopes, the change of solar activity and hence secondary neutron flux has already been proven. The temporal atmospheric variation of the most studied cosmogenic isotopes shows a significant anti-correlation with solar cycles. However, since artificial tritium input to the atmosphere due to nuclear-weapon tests masked the expected variations of tritium production rate by three orders of magnitude, the natural variation of tritium in meteoric precipitation has not previously been detected. For the first time, we provide clear evidence of the positive correlation between the tritium concentration of meteoric precipitation and neutron flux modulated by solar magnetic activity. We found trends in tritium time series for numerous locations worldwide which are similar to the variation of secondary neutron flux and sun spot numbers. This variability appears to have similar periodicities to that of solar cycle. Frequency analysis, cross correlation analysis, continuous and cross wavelet analysis provide mathematical evidence that the correlation between solar cycle and meteoric tritium does exist. Our results demonstrate that the response of tritium variation in precipitation to the solar cycle can be used to help us understand its role in the water cycle.
Separation and Loss of Centrioles From Primordidal Germ Cells To Mature Oocytes In The Mouse
Authors: Simerly Calvin , Manil-Ségalen Marion , Castro Carlos , Hartnett Carrie , Kong Dong , Verlhac Marie-Hélène , Loncarek Jadranka , Schatten Gerald
Published: August 2018

Oocytes, including from mammals, lack centrioles, but neither the mechanism by which mature eggs lose their centrioles nor the exact stage at which centrioles are destroyed during oogenesis is known. To answer questions raised by centriole disappearance during oogenesis, using a transgenic mouse expressing GFP-centrin-2 (GFP CETN2), we traced their presence from e11.5 primordial germ cells (PGCs) through oogenesis and their ultimate dissolution in mature oocytes. We show tightly coupled CETN2 doublets in PGCs, oogonia, and pre-pubertal oocytes. Beginning with follicular recruitment of incompetent germinal vesicle (GV) oocytes, through full oocyte maturation, the CETN2 doublets separate within the pericentriolar material (PCM) and a rise in single CETN2 pairs is identified, mostly at meiotic metaphase-I and -II spindle poles. Partial CETN2 foci dissolution occurs even as other centriole markers, like Cep135, a protein necessary for centriole duplication, are maintained at the PCM. Furthermore, live imaging demonstrates that the link between the two centrioles breaks as meiosis resumes and that centriole association with the PCM is progressively lost. Microtubule inhibition shows that centriole dissolution is uncoupled from microtubule dynamics. Thus, centriole doublets, present in early G2-arrested meiotic prophase oocytes, begin partial reduction during follicular recruitment and meiotic resumption, later than previously thought.
Intra-individual alterations of serum markers routinely used in forensic pathology depending on increasing post-mortem interval
Authors: Woydt Lina , Bernhard Michael , Kirsten Holger , Burkhardt Ralph , Hammer Niels , Gries André , Dreßler Jan , Ondruschka Benjamin
Published: August 2018

Post-mortem biochemistry of serum markers has been the subject of numerous studies, but in-situ marker stability after death has not been sufficiently evaluated yet. Such laboratory analyses are especially necessary in the cases of functional deaths without morphological evidence of the death causes and also in cardiac death cases with only very short survival times. The aim of the study was to determine the post-mortem stability of commonly-used serum markers at predefined time points. In 20 cases, peripheral venous samples were taken starting immediately after circulatory arrest and ending 48 hours after death. Serum creatinine, urea, 3-β-hydroxybutyrate, tryptase, myoglobin, troponin T, creatin kinase and creatin kinase-MB have been included. For all markers, we observed increasing marker levels for longer post-mortem intervals. Significant marker level changes began two hours after death. Excessive increases were observed for cardiac and muscle markers. Marker levels showed high intra-assay precision. Furthermore, the markers were robust enough to withstand freeze-thaw cycles. Potential contamination of arteriovenous blood did not influence the post-mortem marker levels. Post-mortem blood should be sampled as soon as possible, as increased post-mortem intervals may heavily change marker levels in-situ in individual cases, whereas the markers are mostly unaffected by laboratory conditions.
Short Black Carbon lifetime inferred from a global set of aircraft observations
Authors: Lund Marianne T. , Samset Bjørn H. , Skeie Ragnhild B. , Watson-Parris Duncan , Katich Joseph M. , Schwarz Joshua P. , Weinzierl Bernadett
Published: August 2018

Black Carbon (BC) aerosols substantially affect the global climate. However, accurate simulation of BC atmospheric transport remains elusive, due to shortcomings in modeling and a shortage of constraining measurements. Recently, several studies have compared simulations with observed vertical concentration profiles, and diagnosed a global-mean BC atmospheric residence time of <5 days. These studies have, however, been focused on limited geographical regions, and used temporally and spatially coarse model information. Here we expand on previous results by comparing a wide range of recent aircraft measurements from multiple regions, including the Arctic and the Atlantic and Pacific oceans, to simulated distributions obtained at varying spatial and temporal resolution. By perturbing BC removal processes and using current best-estimate emissions, we confirm a constraint on the global-mean BC lifetime of <5.5 days, shorter than in many current global models, over a broader geographical range than has so far been possible. Sampling resolution influences the results, although generally without introducing major bias. However, we uncover large regional differences in the diagnosed lifetime, in particular in the Arctic. We also find that only a weak constraint can be placed in the African outflow region over the South Atlantic, indicating inaccurate emission sources or model representation of transport and microphysical processes. While our results confirm that BC lifetime is shorter than predicted by most recent climate models, they also cast doubt on the usability of the concept of a “global-mean BC lifetime” for climate impact studies, or as an indicator of model skill.
Frequent mutation of the FOXA1 untranslated region in prostate cancer
Authors: Annala Matti , Taavitsainen Sinja , Vandekerkhove Gillian , Bacon Jack V. W. , Beja Kevin , Chi Kim N. , Nykter Matti , Wyatt Alexander W.
Published: August 2018

Prostate cancer has a low somatic mutation rate but non-coding regions remain underexplored. We sequenced the untranslated regions (UTRs) of 72 established driver genes in 428 patients with metastatic prostate cancer and identified FOXA1 3′-UTR mutations in 12% of patients. The mutations were predominantly insertions or deletions, covered the entire UTR without motif enrichment, and were not detected in other cancers. FOXA1 lies in head-on orientation with the androgen-regulated non-coding gene AL121790.1, resulting in strong prostate lineage-specific bidirectional transcription across the FOXA1 3′-UTR. This suggests transcriptional activity as a cause for the localized hypermutation. The indel-dominant pattern of somatic mutation extends into the FOXA1 coding region, where it is shaped by clonal selection to yield a cluster of non-frameshift indels inside the forkhead domain. Somatic FOXA1 3′-UTR mutations may prove useful for diagnostic and screening approaches, given their high frequency and lineage specificity.
Mobilising ion mobility mass spectrometry for metabolomics
Authors: Sinclair Eleanor , Hollywood Katherine A. , Yan Cunyu , Blankley Richard , Breitling Rainer , Barran Perdita
Published: August 2018

The benefits of adding data from ion mobility measurements to a mass spectrometry based metabolomics workflow are assessed using a panel of small molecules. Data is presented as collision cross section values and distributions.
Efficient preparation of template immobilization-based boronate affinity surface-imprinted silica nanoparticles using poly(4-aminobenzyl alcohol) as an imprinting coating for glycoprotein recognition
Authors: Li Daojin , Tu Tianyong , Wu Xiuyuan
Published: August 2018

Many glycoproteins can be used as disease biomarkers for early clinical diagnostics and treatment of diseases.
Synthesis of highly controlled carbohydrate–polymer based hybrid structures by combining heparin fragments and sialic acid derivatives, and solid phase polymer synthesis
Authors: Baier Mischa , Ruppertz Jana L. , Pfleiderer Moritz M. , Blaum Bärbel S. , Hartmann Laura
Published: August 2018

Heparin fragments have been used in solid phase polymer synthesis to derive biomimetic model compounds.
Activation of C–F bonds α to C–C multiple bonds
Authors: Hamel Jean-Denys , Paquin Jean-François
Published: August 2018

A closer look is given to the successful approaches to the C(sp3)–F activation of benzylic, allylic, propargylic and allenylic fluorides.
Enabling shape memory and healable effects in a conjugated polymer by incorporating siloxane via dynamic imine bond
Authors: Zhang Yaling , Dai Chunhui , Zhou Shiwei , Liu Bin
Published: August 2018

A copolymer of poly(fluorene-co-benzothiadiazole) and poly(dimethylsiloxane) was synthesized via dynamic imine bonds, which showed shape memory, healable and degradable effects.
Diverse catalytic reactivity of a dearomatized PN3P*–nickel hydride pincer complex towards CO2 reduction
Authors: Li Huaifeng , Gonçalves Théo P. , Zhao Qianyi , Gong Dirong , Lai Zhiping , Wang Zhixiang , Zheng Junrong , Huang Kuo-Wei
Published: August 2018

A dearomatized PN3P*–nickel hydride complex catalyzes hydrosilylation of CO2.
Asymmetric total synthesis of pleurospiroketals A and B
Authors: Kobayashi Toyoharu , Tanaka Konomi , Ishida Masako , Yamakita Natsumi , Abe Hideki , Ito Hisanaka
Published: August 2018

The first asymmetric total synthesis of pleurospiroketals A and B has been accomplished in 16 steps from 5-methyl-5-hexenoic acid.
Synthesis of acyl fluorides via photocatalytic fluorination of aldehydic C–H bonds
Authors: Meanwell Michael , Lehmann Johannes , Eichenberger Marc , Martin Rainer E. , Britton Robert
Published: August 2018

Acyl fluorides are produced through the direct fluorination of aldehydic C–H bonds.
An alkynyl-protected Au40 nanocluster featuring PhCC–Au–P^P motifs
Authors: Wang Ting , Zhang Wen-Han , Yuan Shang-Fu , Guan Zong-Jie , Wang Quan-Ming
Published: August 2018

An alkynyl-protected gold nanocluster [Au40(PhCC)20(dppm)4](SbF6)4 (dppm = bis(diphenylphosphino)methane) (1) has been synthesized.
Influence of polaron doping and concentration dependent FRET on luminescence of PAni–PMMA blends for application in PLEDs
Authors: Banerjee Dhritiman , Kar Asit Kumar
Published: August 2018

The role of quantum mechanical phenomena such as polaron–exciton quenching interaction and concentration-dependent FRET in determining the luminescence efficiency of PAni–PMMA polymer blends has been investigated.
Non-phase-separated 2D B–C–N alloys via molecule-like carbon doping in 2D BN: atomic structures and optoelectronic properties
Authors: Ren Xiang-Yang , Xia Sha , Li Xian-Bin , Chen Nian-Ke , Wang Xue-Peng , Wang Dan , Chen Zhan-Guo , Zhang Shengbai , Sun Hong-Bo
Published: August 2018

A new way to overcome the phase-separation problem to fabricate 2D B–C–N via molecule-like carbon doping in 2D BN.
Formation of highly ordered liquid crystalline coatings – an in situ GISAXS study
Authors: Salentinig S. , Zabara Mahsa , Parisse P. , Amenitsch H.
Published: August 2018

In situ GISAXS and AFM reveal the formation of highly geometrically organized glycerol monooleate based liquid crystalline films on silicon wafers.
Predicting structural and energetic changes in Met–aromatic motifs on methionine oxidation to the sulfoxide and sulfone
Authors: Orabi Esam A. , English Ann M.
Published: August 2018

Methionine oxidation increases its affinity for aromatics in the gas phase but lowers it for most complexes in water.
Heat capacities and an updated thermodynamic model for the Li–Sn system
Authors: Reichmann Thomas L. , Li Dajian , Cupid Damian M.
Published: August 2018

Cp was measured using phase-pure Li–Sn compounds, fitted with a new proposed restricted Maier–Kelley equation, and embedded into a thermodynamic description.
A computational study on the tunability of woven covalent organic frameworks for photocatalysis
Authors: Chen Ke , Yang Li , Wu Ziye , Chen Changlun , Jiang Jun , Zhang Guozhen
Published: August 2018

We show that the visible light absorption of COF-505 is tunable via altering central metal ions or the dihedral angle between two adjacent ligand groups by first-principles calculations. We also found that positively charged COF-505 with Pd(ii) exhibits appreciable O–H activation of the adsorbed H2O.
Silver modified barium titanate as a highly efficient piezocatalyst
Authors: Lin Enzhu , Wu Jiang , Qin Ni , Yuan Baowei , Bao Dinghua
Published: August 2018

Surface modification of Ag nanoparticles on BaTiO3 can significantly enhance the piezocatalytic activity of the catalyst.