bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating the Neuroprotective Effects of Turmeric Extract: Structural Interactions of β-Amyloid Peptide with Single Curcuminoids
Authors: Randino Rosario , Grimaldi Manuela , Persico Marco , De Santis Augusta , Cini Elena , Cabri Walter , Riva Antonella , D’Errico Gerardino , Fattorusso Caterina , D’Ursi Anna Maria , Rodriquez Manuela
Published: December 2016

A broad biophysical analysis was performed to investigate the molecular basis of the neuroprotective action of Curcuma longa extracts in Alzheimer’s disease. By combining circular dichroism and electron paramagnetic resonance experiments with molecular modeling calculations, the minor components of Curcuma longa extracts, such as demethoxycurcumin (2, DMC), bisdemethoxycurcumin (3, BDMC) and cyclocurcumin (4, CYC), were analyzed in a membrane environment mimicking the phospholipid bilayer. Our study provides the first evidence on the relative role of single curcuminoids interacting with Aβ-peptide. When the CYC and curcumin metabolite tetrahydrocurcumin (5, THC) were inserted into an anionic lipid solution, a significant modification of the Aβ CD curves was detected. These data were implemented by EPR experiments, demonstrating that CYC reaches the inner part of the bilayer, while the other curcuminoids are localized close to the membrane interface. Computational studies provided a model for the curcuminoid-Aβ interaction, highlighting the importance of a constrained “semi-folded” conformation to interact with Aβ analogously to the pattern observed in α-helical coiled-coil peptide structures. This combined approach led to a better understanding of the intriguing in vitro and in vivo activity of curcuminoids as anti-Alzheimer agents, paving a new path for the rational design of optimized druggable analogues.
Molecular typing and virulence analysis of multidrug resistant Klebsiella pneumoniae clinical isolates recovered from Egyptian hospitals
Authors: Wasfi Reham , Elkhatib Walid F. , Ashour Hossam M.
Published: December 2016

Klebsiella pneumonia infection rates have increased dramatically. Molecular typing and virulence analysis are powerful tools that can shed light on Klebsiella pneumonia infections. Whereas 77.7% (28/36) of clinical isolates indicated multidrug resistant (MDR) patterns, 50% (18/36) indicated carpabenem resistance. Gene prevalence for the AcrAB efflux pump (82.14%) was more than that of the mdtK efflux pump (32.14%) in the MDR isolates. FimH-1 and mrkD genes were prevalent in wound and blood isolates. FimH-1 gene was prevalent in sputum while mrkD gene was prevalent in urine. Serum resistance associated with outer membrane protein coding gene (traT) was found in all blood isolates. IucC, entB, and Irp-1 were detected in 32.14%, 78.5% and 10.7% of MDR isolates, respectively. We used two Polymerase Chain Reaction (PCR) analyses: Enterobacterial Repetitive Intergenic Consensus (ERIC) and Random Amplified Polymorphic DNA (RAPD). ERIC-PCR revealed 21 and RAPD-PCR revealed 18 distinct patterns of isolates with similarity ≥80%. ERIC genotyping significantly correlated with resistance patterns and virulence determinants. RAPD genotyping significantly correlated with resistance patterns but not with virulence determinants. Both RAPD and ERIC genotyping methods had no correlation with the capsule types. These findings can help up better predict MDR Klebsiella pneumoniae outbreaks associated with specific genotyping patterns.
3-D Microwell Array System for Culturing Virus Infected Tumor Cells
Authors: El Assal Rami , Gurkan Umut A. , Chen Pu , Juillard Franceline , Tocchio Alessandro , Chinnasamy Thiruppathiraja , Beauchemin Chantal , Unluisler Sebnem , Canikyan Serli , Holman Alyssa , Srivatsa Srikar , Kaye Kenneth M. , Demirci Utkan
Published: December 2016

Cancer cells have been increasingly grown in pharmaceutical research to understand tumorigenesis and develop new therapeutic drugs. Currently, cells are typically grown using two-dimensional (2-D) cell culture approaches, where the native tumor microenvironment is difficult to recapitulate. Thus, one of the main obstacles in oncology is the lack of proper infection models that recount main features present in tumors. In recent years, microtechnology-based platforms have been employed to generate three-dimensional (3-D) models that better mimic the native microenvironment in cell culture. Here, we present an innovative approach to culture Kaposi’s sarcoma-associated herpesvirus (KSHV) infected human B cells in 3-D using a microwell array system. The results demonstrate that the KSHV-infected B cells can be grown up to 15 days in a 3-D culture. Compared with 2-D, cells grown in 3-D had increased numbers of KSHV latency-associated nuclear antigen (LANA) dots, as detected by immunofluorescence microscopy, indicating a higher viral genome copy number. Cells in 3-D also demonstrated a higher rate of lytic reactivation. The 3-D microwell array system has the potential to improve 3-D cell oncology models and allow for better-controlled studies for drug discovery.
Fixation Probabilities for Any Configuration of Two Strategies on Regular Graphs
Authors: Chen Yu-Ting , McAvoy Alex , Nowak Martin A.
Published: December 2016

Population structure and spatial heterogeneity are integral components of evolutionary dynamics, in general, and of evolution of cooperation, in particular. Structure can promote the emergence of cooperation in some populations and suppress it in others. Here, we provide results for weak selection to favor cooperation on regular graphs for any configuration, meaning any arrangement of cooperators and defectors. Our results extend previous work on fixation probabilities of rare mutants. We find that for any configuration cooperation is never favored for birth-death (BD) updating. In contrast, for death-birth (DB) updating, we derive a simple, computationally tractable formula for weak selection to favor cooperation when starting from any configuration containing any number of cooperators. This formula elucidates two important features: (i) the takeover of cooperation can be enhanced by the strategic placement of cooperators and (ii) adding more cooperators to a configuration can sometimes suppress the evolution of cooperation. These findings give a formal account for how selection acts on all transient states that appear in evolutionary trajectories. They also inform the strategic design of initial states in social networks to maximally promote cooperation. We also derive general results that characterize the interaction of any two strategies, not only cooperation and defection.
Genome-wide analysis of long-term evolutionary domestication in Drosophila melanogaster
Authors: Phillips Mark A. , Long Anthony D. , Greenspan Zachary S. , Greer Lee F. , Burke Molly K. , Villeponteau Bryant , Matsagas Kennedy C. , Rizza Cristina L. , Mueller Laurence D. , Rose Michael R.
Published: December 2016

Experimental evolutionary genomics now allows biologists to test fundamental theories concerning the genetic basis of adaptation. We have conducted one of the longest laboratory evolution experiments with any sexually-reproducing metazoan, Drosophila melanogaster. We used next-generation resequencing data from this experiment to examine genome-wide patterns of genetic variation over an evolutionary time-scale that approaches 1,000 generations. We also compared measures of variation within and differentiation between our populations to simulations based on a variety of evolutionary scenarios. Our analysis yielded no clear evidence of hard selective sweeps, whereby natural selection acts to increase the frequency of a newly-arising mutation in a population until it becomes fixed. We do find evidence for selection acting on standing genetic variation, as independent replicate populations exhibit similar population-genetic dynamics, without obvious fixation of candidate alleles under selection. A hidden-Markov model test for selection also found widespread evidence for selection. We found more genetic variation genome-wide, and less differentiation between replicate populations genome-wide, than arose in any of our simulated evolutionary scenarios.
Correction: Corrigendum: A ruthenium polypyridyl intercalator stalls DNA replication forks, radiosensitizes human cancer cells and is enhanced by Chk1 inhibition
Authors: Gill Martin R. , Harun Siti Norain , Halder Swagata , Boghozian Ramon A. , Ramadan Kristijan , Ahmad Haslina , Vallis Katherine A.
Published: December 2016

Scientific Reports 6: Article number: 31973; published online: 25 August 2016; updated: 22 December 2016
Deep sequencing of wheat sRNA transcriptome reveals distinct temporal expression pattern of miRNAs in response to heat, light and UV
Authors: Ragupathy Raja , Ravichandran Sridhar , Mahdi Md. Safiur Rahman , Huang Douglas , Reimer Elsa , Domaratzki Michael , Cloutier Sylvie
Published: December 2016

Understanding of plant adaptation to abiotic stresses has implications in plant breeding, especially in the context of climate change. MicroRNAs (miRNAs) and short interfering RNAs play a crucial role in gene regulation. Here, wheat plants were exposed to one of the following stresses: continuous light, heat or ultraviolet radiations over five consecutive days and leaf tissues from three biological replicates were harvested at 0, 1, 2, 3, 7 and 10 days after treatment (DAT). A total of 72 small RNA libraries were sequenced on the Illumina platform generating ~524 million reads corresponding to ~129 million distinct tags from which 232 conserved miRNAs were identified. The expression levels of 1, 2 and 79 miRNAs were affected by ultraviolet radiation, continuous light and heat, respectively. Approximately 55% of the differentially expressed miRNAs were downregulated at 0 and 1 DAT including miR398, miR528 and miR156 that control mRNAs involved in activation of signal transduction pathways and flowering. Other putative targets included histone variants and methyltransferases. These results suggest a temporal miRNA-guided post-transcriptional regulation that enables wheat to respond to abiotic stresses, particularly heat. Designing novel wheat breeding strategies such as regulatory gene-based marker assisted selection depends on accurate identification of stress induced miRNAs.
A new formulation of Bacillus thuringiensis: UV protection and sustained release mosquito larvae studies
Authors: Zhang Lingling , Zhang Xiaojuan , Zhang Yi , Wu Songqin , Gelbič Ivan , Xu Lei , Guan Xiong
Published: December 2016

Persistence of Bacillus thuringiensis is an important factor in determining the success of this product as a pest control agent. In this report we present the development of a highly active mosquitocidal formulation with high resistance to UV. LLP29-M19 strain of Bt, selected by repeated exposure to UV was found to be highly resistant to UV. The product was optimized and the methods used were statistically analyzed. Using single-factor experiments it was determined that the optimal concentration of sodium alginate, CaCl2 and hollow glass beads in the formulation were 1.0%, 2.0% and 3.5%, respectively. Plackett-Burman design was used to screen the interaction of the three factors, CaCl2, sodium alginate and hollow glass beads in the sustained-release formulation. The best combined concentration and mutual effects of the three factors were optimized by response surface methodology. The results showed that the most favorable composition was sodium alginate 0.78%, CaCl2 4.52%, hollow glass bead 3.12%, bacterial powder 3.0%, melanin 0.015%, sodium benzoate 0.2%, and mouse feed 0.5%, resulting in the immobilization time of 4.5 h, at which time the corrected sustained-release virulence rose 2391.67 fold, which was 6.07-fold higher than the basic formulation and deviated only 5.0% from the value predicted by RSM.
Tyrosine Hydroxylase Binding to Phospholipid Membranes Prompts Its Amyloid Aggregation and Compromises Bilayer Integrity
Authors: Baumann Anne , Jorge-Finnigan Ana , Jung-KC Kunwar , Sauter Alexander , Horvath Istvan , Morozova-Roche Ludmilla A. , Martinez Aurora
Published: December 2016

Tyrosine hydroxylase (TH), a rate-limiting enzyme in the synthesis of catecholamine neurotransmitters and hormones, binds to negatively charged phospholipid membranes. Binding to both large and giant unilamellar vesicles causes membrane permeabilization, as observed by efflux and influx of fluorescence dyes. Whereas the initial protein-membrane interaction involves the N-terminal tail that constitutes an extension of the regulatory ACT-domain, prolonged membrane binding induces misfolding and self-oligomerization of TH over time as shown by circular dichroism and Thioflavin T fluorescence. The gradual amyloid-like aggregation likely occurs through cross-β interactions involving aggregation-prone motives in the catalytic domains, consistent with the formation of chain and ring-like protofilaments observed by atomic force microscopy in monolayer-bound TH. PC12 cells treated with the neurotoxin 6-hydroxydopamine displayed increased TH levels in the mitochondrial fraction, while incubation of isolated mitochondria with TH led to a decrease in the mitochondrial membrane potential. Furthermore, cell-substrate impedance and viability assays showed that supplementing the culture media with TH compromises cell viability over time. Our results revealed that the disruptive effect of TH on cell membranes may be a cytotoxic and pathogenic factor if the regulation and intracellular stability of TH is compromised.
Composition of the Hemagglutinin Polybasic Proteolytic Cleavage Motif Mediates Variable Virulence of H7N7 Avian Influenza Viruses
Authors: Abdelwhab E. M. , Veits Jutta , Ulrich Reiner , Kasbohm Elisa , Teifke Jens P. , Mettenleiter Thomas C.
Published: December 2016

Acquisition of a polybasic cleavage site (pCS) in the hemagglutinin (HA) is a prerequisite for the shift of low pathogenic (LP) avian influenza virus (AIV) to the highly pathogenic (HP) form in chickens. Whereas presence of a pCS is required for high pathogenicity, less is known about the effect of composition of pCS on virulence of AIV particularly H7N7. Here, we investigated the virulence of four avian H7N7 viruses after insertion of different naturally occurring pCS from two HPAIV H7N7 (designated pCSGE and pCSUK) or from H7N1 (pCSIT). In vitro, the different pCS motifs modulated viral replication and the HA cleavability independent on the HA background. However, in vivo, the level of virulence conferred by the different pCS varied significantly. Within the respective viral backgrounds viruses with pCSIT and pCSGE were more virulent than those coding for pCSUK. The latter showed also the most restricted spread in inoculated birds. Besides the pCS, other gene segments modulated virulence of these H7N7 viruses. Together, the specific composition of the pCS significantly influences virulence of H7N7 viruses. Eurasian LPAIV H7N7 may shift to high pathogenicity after acquisition of “specific” pCS motifs and/or other gene segments from HPAIV.
STAT3 Undergoes Acetylation-dependent Mitochondrial Translocation to Regulate Pyruvate Metabolism
Authors: Xu Yan S. , Liang Jinyuan J. , Wang Yumei , Zhao Xiang-zhong J. , Xu Li , Xu Ye-yang , Zou Quanli C. , Zhang Junxun M. , Tu Cheng-e , Cui Yan-ge , Sun Wei-hong , Huang Chao , Yang Jing-hua , Chin Y. Eugene
Published: December 2016

Cytoplasmic STAT3, after activation by growth factors, translocates to different subcellular compartments, including nuclei and mitochondria, where it carries out different biological functions. However, the precise mechanism by which STAT3 undergoes mitochondrial translocation and subsequently regulates the tricarboxylic acid (TCA) cycle-electron transport chain (ETC) remains poorly understood. Here, we clarify this process by visualizing STAT3 acetylation in starved cells after serum reintroduction or insulin stimulation. CBP-acetylated STAT3 undergoes mitochondrial translocation in response to serum introduction or insulin stimulation. In mitochondria, STAT3 associates with the pyruvate dehydrogenase complex E1 (PDC-E1) and subsequently accelerates the conversion of pyruvate to acetyl-CoA, elevates the mitochondrial membrane potential, and promotes ATP synthesis. SIRT5 deacetylates STAT3, thereby inhibiting its function in mitochondrial pyruvate metabolism. In the A549 lung cancer cell line, constitutively acetylated STAT3 localizes to mitochondria, where it maintains the mitochondrial membrane potential and ATP synthesis in an active state.
Olaparib significantly delays photoreceptor loss in a model for hereditary retinal degeneration
Authors: Sahaboglu Ayse , Barth Melanie , Secer Enver , Amo Eva M. del , Urtti Arto , Arsenijevic Yvan , Zrenner Eberhart , Paquet-Durand François
Published: December 2016

The enzyme poly-ADP-ribose-polymerase (PARP) mediates DNA-repair and rearrangements of the nuclear chromatin. Generally, PARP activity is thought to promote cell survival and in recent years a number of PARP inhibitors have been clinically developed for cancer treatment. Paradoxically, PARP activity is also connected to many diseases including the untreatable blinding disease Retinitis Pigmentosa (RP), where PARP activity appears to drive the pathogenesis of photoreceptor loss. We tested the efficacy of three different PARP inhibitors to prevent photoreceptor loss in the rd1 mouse model for RP. In retinal explant cultures in vitro, olaparib had strong and long-lasting photoreceptor neuroprotective capacities. We demonstrated target engagement by showing that olaparib reduced photoreceptor accumulation of poly-ADP-ribosylated proteins. Remarkably, olaparib also reduced accumulation of cyclic-guanosine-monophosphate (cGMP), a characteristic marker for photoreceptor degeneration. Moreover, intravitreal injection of olaparib in rd1 animals diminished PARP activity and increased photoreceptor survival, confirming in vivo neuroprotection. This study affirms the role of PARP in inherited retinal degeneration and for the first time shows that a clinically approved PARP inhibitor can prevent photoreceptor degeneration in an RP model. The wealth of human clinical data available for olaparib highlights its strong potential for a rapid clinical translation into a novel RP treatment.
Tunable Spin dependent beam shift by simultaneously tailoring geometric and dynamical phases of light in inhomogeneous anisotropic medium
Authors: Pal Mandira , Banerjee Chitram , Chandel Shubham , Bag Ankan , Majumder Shovan K. , Ghosh Nirmalya
Published: December 2016

Spin orbit interaction and the resulting Spin Hall effect of light are under recent intensive investigations because of their fundamental nature and potential applications. Here, we report an interesting manifestation of spin Hall effect of light and demonstrate its tunability in an inhomogeneous anisotropic medium exhibiting spatially varying retardance level. In our system, the beam shift occurs only for one circular polarization mode keeping the other orthogonal mode unaffected, which is shown to arise due to the combined spatial gradients of the geometric phase and the dynamical phase of light. The constituent two orthogonal circular polarization modes of an input linearly polarized light evolve in different trajectories, eventually manifesting as a large and tunable spin separation. The spin dependent beam shift and the demonstrated principle of simultaneously tailoring space-varying geometric and dynamical phase of light for achieving its tunability (of both magnitude and direction), may provide an attractive route towards development of spin-optical devices.
Alteration of platelet GPVI signaling in ST-elevation myocardial infarction patients demonstrated by a combination of proteomic, biochemical, and functional approaches
Authors: Vélez Paula , Ocaranza-Sánchez Raymundo , López-Otero Diego , Grigorian-Shamagian Lilian , Rosa Isaac , Guitián Esteban , García-Acuña José María , González-Juanatey José Ramón , García Ángel
Published: December 2016

The platelet-specific collagen receptor glycoprotein VI (GPVI) is critical for the formation of arterial thrombosis in vivo. We analyzed GPVI-activated platelets from ST-elevation myocardial infarction (STEMI) patients and matched stable coronary artery disease (SCAD) controls in order to provide novel clues on the degree of involvement of GPVI signaling in the acute event. Firstly, platelets were isolated from systemic venous blood and activated with the GPVI specific agonist CRP (collagen-related peptide). STEMI and SCAD samples were compared by a phosphoproteomics approach. Validations were by immunoblotting in systemic and intracoronary blood from independent cohorts of patients. Twenty-six differentially regulated proteins were identified when comparing CRP-activated systemic platelets from STEMI and SCAD patients, 4 of which were selected for validation studies: PLCɣ2, G6f, SLP-76, and Dok-2. Immunoblot analyses showed these four proteins had higher tyrosine phosphorylation levels in response to CRP in platelets from STEMI patients, being these levels more pronounced at the culprit site of coronary artery occlusion. Moreover, platelet aggregation studies showed a higher response to GPVI agonists in STEMI patients compared to SCAD controls. In conclusion, we show an altered activation state of GPVI signaling in STEMI patients, confirming this receptor as a promising anti-thrombotic target for myocardial infarction.
Fasting plasma glucose variability and all-cause mortality among type 2 diabetes patients: a dynamic cohort study in Shanghai, China
Authors: Xu Dongli , Fang Hong , Xu Wanghong , Yan Yujie , Liu Yinan , Yao Baodong
Published: December 2016

The study aims to examine whether the variation of fasting plasma glucose (FPG), represented by coefficient of variation (CV), independently predicts all-cause mortality among Chinese type 2 diabetes patients. This retrospective cohort study was designed based on a standardized electronic management system of diabetes patients in Shanghai, China. 8871 type 2 diabetes patients were enrolled between 1 January 2007 and 31 December 2007 and were followed-up for all-cause mortality until 31 December 2014. All patients were grouped by the quartiles of CV of FPG. 1136 patients deceased during following-up. After adjusting for other risk factors, CV of FPG was not independently associated with all-cause mortality. Stratified analysis by mean FPG levels (<7 mmol/L and ≥7 mmol/L) observed a significant modifying effect of CV of FPG (P for interact test <0.01). CV of FPG was independently associated with all-cause mortality in patients whose glucose control was poor, with the HRs (95% CI) for the second, third, fourth vs first quartiles of CV of FPG being 1.23(0.94–1.61), 1.23(0.94–1.61), and 1.63(1.25–2.13), respectively. Our results suggest that variability of FPG may be an important predictor of mortality among type 2 diabetes in China, particularly for those with their glycemic status uncontrolled.
Single-cell analysis of differences in transcriptomic profiles of oocytes and cumulus cells at GV, MI, MII stages from PCOS patients
Authors: Liu Qiwei , Li Yumei , Feng Yun , Liu Chaojie , Ma Jieliang , Li Yifei , Xiang Huifen , Ji Yazhong , Cao Yunxia , Tong Xiaowen , Xue Zhigang
Published: December 2016

Polycystic ovary syndrome (PCOS) is a common frequent endocrine disorder among women of reproductive age. Although assisted reproductive techniques (ARTs) are used to address subfertility in PCOS women, their effectiveness is not clear. Our aim was to compare transcriptomic profiles of oocytes and cumulus cells (CCs) between women with and without PCOS, and assess the effectiveness of ARTs in treating PCOS patients. We collected oocytes and CCs from 16 patients with and without PCOS patients to categorize them into 6 groups according to oocyte nuclear maturation. Transcriptional gene expression of oocyte and CCs was determined via single-cell RNA sequencing. The ratio of fertilization and cleavage was higher in PCOS patients than in non-PCOS patients undergoing ARTs, and there was no difference in the number of high-quality embryos between the groups. Differentially expressed genes including PPP2R1A, PDGFRA, EGFR, GJA1, PTGS2, TNFAIP6, TGF-β1, CAV1, INHBB et al. were investigated as potential causes of PCOS oocytes and CCs disorder at early stages, but their expression returned to the normal level at the metaphase II (MII) stage via ARTs. In conclusion, ARTs can improve the quality of cumulus-oocyte complex (COC) and increase the ratio of fertilization and cleavage in PCOS women.
NOD2 dependent neutrophil recruitment is required for early protective immune responses against infectious Litomosoides sigmodontis L3 larvae
Authors: Ajendra Jesuthas , Specht Sabine , Ziewer Sebastian , Schiefer Andrea , Pfarr Kenneth , Parčina Marijo , Kufer Thomas A. , Hoerauf Achim , Hübner Marc P.
Published: December 2016

Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) recognizes muramyl dipeptide (MDP) of bacterial cell walls, triggering NFκB-induced pro-inflammation. As most human pathogenic filariae contain Wolbachia endobacteria that synthesize the MDP-containing cell wall precursor lipid II, NOD2’s role during infection with the rodent filaria Litomosoides sigmodontis was investigated. In NFκB reporter-cells, worm-extract containing Wolbachia induced NOD2 and NOD1. NOD2-deficient mice infected with L. sigmodontis had significantly more worms than wildtype controls early in infection. Increased worm burden was not observed after subcutaneous infection, suggesting that protective NOD2-dependent immune responses occur within the skin. Flow cytometry demonstrated that neutrophil recruitment to the skin was impaired in NOD2−/− mice after intradermal injection of third stage larvae (L3), and blood neutrophil numbers were reduced after L. sigmodontis infection. PCR array supported the requirement of NOD2 for recruitment of neutrophils to the skin, as genes associated with neutrophil recruitment and activation were downregulated in NOD2−/− mice after intradermal L3 injection. Neutrophil depletion before L. sigmodontis infection increased worm recovery in wildtype mice, confirming that neutrophils are essential against invading L3 larvae. This study indicates that NOD-like receptors are implemented in first-line protective immune responses against filarial nematodes.
The differentiated airway epithelium infected by influenza viruses maintains the barrier function despite a dramatic loss of ciliated cells
Authors: Wu Nai-Huei , Yang Wei , Beineke Andreas , Dijkman Ronald , Matrosovich Mikhail , Baumgärtner Wolfgang , Thiel Volker , Valentin-Weigand Peter , Meng Fandan , Herrler Georg
Published: December 2016

Virus-host interactions in the respiratory epithelium during long term influenza virus infection are not well characterized. Therefore, we developed an air-liquid interface culture system for differentiated porcine respiratory epithelial cells to study the effect of virus-induced cellular damage. In our well-differentiated cells, α2,6-linked sialic acid is predominantly expressed on the apical surface and the basal cells mainly express α2,3-linked sialic acid. During the whole infection period, release of infectious virus was maintained at a high titre for more than seven days. The infected epithelial cells were subject to apoptosis resulting in the loss of ciliated cells together with a thinner thickness. Nevertheless, the airway epithelium maintained trans-epithelial electrical resistance and retained its barrier function. The loss of ciliated cells was compensated by the cells which contained the KRT5 basal cell marker but were not yet differentiated into ciliated cells. These specialized cells showed an increase of α2,3-linked sialic acid on the apical surface. In sum, our results help to explain the localized infection of the airway epithelium by influenza viruses. The impairment of mucociliary clearance in the epithelial cells provides an explanation why prior viral infection renders the host more susceptible to secondary co-infection by another pathogen.
Osteoarthritis and the risk of cardiovascular disease: a meta-analysis of observational studies
Authors: Wang Haoran , Bai Jing , He Bing , Hu Xinrong , Liu Dongliang
Published: December 2016

Previous observational studies have suggested a potential relationship between osteoarthritis (OA) and the risk of cardiovascular disease (CVD), with conflicting results. We aimed to provide a systematic and quantitative summary of the association between OA and the risk of CVD. We searched Medline and EMBASE to retrieve prospective and retrospective studies that reported risk estimates of the association between OA status and CVD risk. Pooled estimates were calculated by a random effects model. The search yielded 15 articles including a total of 358,944 participants, including 80,911 OA patients and 29,213 CVD patients. Overall, the risk of CVD was significantly increased by 24% (RR: 1.24, 95% CI: 1.12 to 1.37, P < 0.001) in patients with OA compared with the general population, with no significant publication bias. Furthermore, sensitivity analysis indicated that our results were robust and were not influenced by any one study. In conclusion, this meta-analysis provides strong evidence that OA is a significant risk factor for CVD.
Temperature and microwave near field imaging by thermo-elastic optical indicator microscopy
Authors: Lee Hanju , Arakelyan Shant , Friedman Barry , Lee Kiejin
Published: December 2016

A high resolution imaging of the temperature and microwave near field can be a powerful tool for the non-destructive testing of materials and devices. However, it is presently a very challenging issue due to the lack of a practical measurement pathway. In this work, we propose and demonstrate experimentally a practical method resolving the issue by using a conventional CCD-based optical indicator microscope system. The present method utilizes the heat caused by an interaction between the material and an electromagnetic wave, and visualizes the heat source distribution from the measured photoelastic images. By using a slide glass coated by a metal thin film as the indicator, we obtain optically resolved temperature, electric, and magnetic microwave near field images selectively with a comparable sensitivity, response time, and bandwidth of existing methods. The present method provides a practical way to characterize the thermal and electromagnetic properties of materials and devices under various environments.
Convergent evidence for the molecular basis of musical traits
Authors: Oikkonen Jaana , Onkamo Päivi , Järvelä Irma , Kanduri Chakravarthi
Published: December 2016

To obtain aggregate evidence for the molecular basis of musical abilities and the effects of music, we integrated gene-level data from 105 published studies across multiple species including humans, songbirds and several other animals and used a convergent evidence method to prioritize the top candidate genes. Several of the identified top candidate genes like EGR1, FOS, ARC, BDNF and DUSP1 are known to be activity-dependent immediate early genes that respond to sensory and motor stimuli in the brain. Several other top candidate genes like MAPK10, SNCA, ARHGAP24, TET2, UBE2D3, FAM13A and NUDT9 are located on chromosome 4q21-q24, on the candidate genomic region for music abilities in humans. Functional annotation analyses showed the enrichment of genes involved in functions like cognition, learning, memory, neuronal excitation and apoptosis, long-term potentiation and CDK5 signaling pathway. Interestingly, all these biological functions are known to be essential processes underlying learning and memory that are also fundamental for musical abilities including recognition and production of sound. In summary, our study prioritized top candidate genes related to musical traits.
Detection of timescales in evolving complex systems
Authors: Darst Richard K. , Granell Clara , Arenas Alex , Gómez Sergio , Saramäki Jari , Fortunato Santo
Published: December 2016

Most complex systems are intrinsically dynamic in nature. The evolution of a dynamic complex system is typically represented as a sequence of snapshots, where each snapshot describes the configuration of the system at a particular instant of time. This is often done by using constant intervals but a better approach would be to define dynamic intervals that match the evolution of the system’s configuration. To this end, we propose a method that aims at detecting evolutionary changes in the configuration of a complex system, and generates intervals accordingly. We show that evolutionary timescales can be identified by looking for peaks in the similarity between the sets of events on consecutive time intervals of data. Tests on simple toy models reveal that the technique is able to detect evolutionary timescales of time-varying data both when the evolution is smooth as well as when it changes sharply. This is further corroborated by analyses of several real datasets. Our method is scalable to extremely large datasets and is computationally efficient. This allows a quick, parameter-free detection of multiple timescales in the evolution of a complex system.
An Adaptation To Life In Acid Through A Novel Mevalonate Pathway
Authors: Vinokur Jeffrey M. , Cummins Matthew C. , Korman Tyler P. , Bowie James U.
Published: December 2016

Extreme acidophiles are capable of growth at pH values near zero. Sustaining life in acidic environments requires extensive adaptations of membranes, proton pumps, and DNA repair mechanisms. Here we describe an adaptation of a core biochemical pathway, the mevalonate pathway, in extreme acidophiles. Two previously known mevalonate pathways involve ATP dependent decarboxylation of either mevalonate 5-phosphate or mevalonate 5-pyrophosphate, in which a single enzyme carries out two essential steps: (1) phosphorylation of the mevalonate moiety at the 3-OH position and (2) subsequent decarboxylation. We now demonstrate that in extreme acidophiles, decarboxylation is carried out by two separate steps: previously identified enzymes generate mevalonate 3,5-bisphosphate and a new decarboxylase we describe here, mevalonate 3,5-bisphosphate decarboxylase, produces isopentenyl phosphate. Why use two enzymes in acidophiles when one enzyme provides both functionalities in all other organisms examined to date? We find that at low pH, the dual function enzyme, mevalonate 5-phosphate decarboxylase is unable to carry out the first phosphorylation step, yet retains its ability to perform decarboxylation. We therefore propose that extreme acidophiles had to replace the dual-purpose enzyme with two specialized enzymes to efficiently produce isoprenoids in extremely acidic environments.
Characterization of the relationship between polar and lateral flagellar structural genes in the deep-sea bacterium Shewanella piezotolerans WP3
Authors: Jian Huahua , Wang Han , Zeng Xianping , Xiong Lei , Wang Fengping , Xiao Xiang
Published: December 2016

Bacteria with a dual flagellar system, which consists of a polar flagellum (PF) and several lateral flagella (LF), have been identified in diverse environments. Nevertheless, whether and how these two flagellar systems interact with each other is largely unknown. In the present study, the relationship between the structural genes for the PF and LF of the deep-sea bacterium Shewanella piezotolerans WP3 was investigated by genetic, phenotypic and phylogenetic analyses. The mutation of PF genes induced the expression of LF genes and the production of LF in liquid medium, while the defective LF genes led to a decrease in PF gene transcription. However, the level of PF flagellin remained unchanged in LF gene mutants. Further investigation showed that the flgH2 gene (encoding LF L-ring protein) can compensate for mutations of the flgH1 gene (encoding PF L-ring protein), but this compensation does not occur between the flagellar hook-filament junction proteins (FlgL1, FlgL2). Swarming motility was shown to specifically require LF genes, and PF genes cannot substitute for the LF genes in the lateral flagella synthesis. Considering the importance of flagella-dependent motility for bacterial survival in the abyssal sediment, our study thus provided a better understanding of the adaptation strategy of benthic bacteria.
ADAM17/EGFR axis promotes transglutaminase-dependent skin barrier formation through phospholipase C γ1 and protein kinase C pathways
Authors: Wolf Cristina , Qian Yawen , Brooke Matthew A. , Kelsell David P. , Franzke Claus-Werner
Published: December 2016

The vitally important skin barrier is formed by extensive cross-linking activity of transglutaminases (TGs) during terminal epidermal differentiation. We have previously shown that epidermal deficiency of a disintegrin and metalloproteinase 17 (ADAM17), the principal EGFR ligand sheddase, results in postnatal skin barrier defects in mice due to impeded TG activity. However, the mechanism by which ADAM17/EGFR signalling maintains TG activity during epidermal differentiation remains elusive. Here we demonstrate that ADAM17-dependent EGFR signalling promotes TG activity in keratinocytes committed to terminal differentiation by direct induction of TG1 expression. Restored TG1 expression of EGF-stimulated differentiated Adam17−/− keratinocytes was strongly repressed by inhibitors for PLCγ1 or protein kinase C (PKC) pathways, while treatment with the PKC stimulator 12-O-tetradecanoylphorbol-13-acetate restored TG activity in the epidermis of keratinocyte-specific Adam17−/− (AD17ΔKC) mice. Further investigations emphasized the expression of PKCη, a mediator of TGM1 transcription, to be sensitive to EGFR activation. In agreement, topical skin application of cholesterol sulfate, an activator of PKCη, significantly improved TG activity in epidermis of AD17ΔKC mice. Our results suggest ADAM17/EGFR-driven PLCγ1 and PKC pathways as important promoters of TG1 expression during terminal keratinocyte differentiation. These findings may help to identify new therapeutic targets for inflammatory skin diseases related to epidermal barrier defects.
Chiral determination of 3,4-methylenedioxypyrovalerone enantiomers in rat serum
Authors: Hambuchen Michael D. , Hendrickson Howard P. , Owens S. Michael
Published: December 2016

A chiral-selective LC-MS/MS method for determination of MDPV, a drug of abuse with enantiomerically selective pharmacology, was developed and validated.
Targeted combinational therapy inducing mitochondrial dysfunction
Authors: Shin Weon Sup , Park Soon Ki , Verwilst Peter , Koo Seyoung , Lee Joung Hae , Chi Sung-Gil , Kim Jong Seung
Published: December 2016

Mitochondria-directed GSH-activated release of a chlorambucil derivative and an AIE dye induces significantly increased mitochondrial dysfunction and apoptosis.
Dynamics and thermodynamics of the coronene octamer described by coarse-grained potentials
Authors: Hernández-Rojas J. , Calvo F. , Niblett S. , Wales D. J.
Published: December 2016

Coarse-grained models developed for polycyclic aromatic hydrocarbons based on the Paramonov–Yaliraki potential have been employed to investigate the finite temperature thermodynamics, out-of-equilibrium dynamics, energy landscapes, and rearrangement pathways of the coronene octamer.
Cu(i) and Ag(i) complex formation with the hydrophilic phosphine 1,3,5-triaza-7-phosphadamantane in different ionic media. How to estimate the effect of a complexing medium
Authors: Endrizzi Francesco , Di Bernardo Plinio , Zanonato Pier Luigi , Tisato Francesco , Porchia Marina , Ahmed Isse Abdirisak , Melchior Andrea , Tolazzi Marilena
Published: December 2016

Cu(i) and Ag(i) complex formation with the hydrophilic phosphine 1,3,5-triaza-7-phosphadamantane in different ionic media. How to estimate the effect of a complexing medium?
Comparison between the optical properties of aerosols in the fine and coarse fractions over Valladolid, Spain
Authors: Mogo S. , López J. F. , Cachorro V. E. , de Frutos A. , Zocca R. , Barroso A. , Mateos D. , Conceição E.
Published: December 2016

The optical properties of fine and coarse particles allow us to know their contribution for the SSA and radiative forcing.
Mixed-ligand copper(ii) Schiff base complexes: the vital role of co-ligands in DNA/protein interactions and cytotoxicity
Authors: Kathiresan Sellamuthu , Mugesh Subramanian , Annaraj Jamespandi , Murugan Maruthamuthu
Published: December 2016

Four new mixed-ligand copper(ii) complexes display an antibacterial mechanism of cell death via cell-wall rupture and cytotoxicity via apoptotic cell death.
C–F bond activation of perfluorinated arenes by a bioxazoline-derived N-heterocyclic carbene
Authors: Emerson-King Jack , Hauser Simone A. , Chaplin Adrian B.
Published: December 2016

IBioxMe4enacts selective single and double C–F bond activation of octafluorotoluene and hexafluorobenzene, respectively.
Tetraceno[2,1,12,11-opqra]tetracene-extended tetrathiafulvalene – redox-controlled generation of a large PAH core
Authors: Broman Søren Lindbæk , Andersen Cecilie Lindholm , Jousselin-Oba Tanguy , Mansø Mads , Hammerich Ole , Frigoli Michel , Nielsen Mogens Brøndsted
Published: December 2016

The geometry of the tetraceno[2,1,12,11-opqra]tetracene polycyclic aromatic hydrocarbon is controlled by oxidation–reduction of exocyclic dithiafulvene substituents.
Stepwise cyclopropanation on the polycyclopropanated polyketide formation in jawsamycin biosynthesis
Authors: Hiratsuka Tomoshige , Suzuki Hideaki , Minami Atsushi , Oikawa Hideaki
Published: December 2016

Cyclopropane deficient jawsamycin analogs were isolated from transformant harboring jaw genes, enabling us to propose an enzymatic cyclopropanation mechanism.
Recent developments in III–V semiconducting nanowires for high-performance photodetectors
Authors: Shen Lifan , Pun Edwin Y. B. , Ho Johnny C.
Published: December 2016

We present a comprehensive overview of the recent advances in III–V NW-based photodetectors operating in the UV, visible and infrared spectra range.
Understanding the interfacial interactions between dopamine and different graphenes for biomedical materials
Authors: Zhang Hong-ping , Lin Xiao-yan , Lu Xiong , Wang Zhenming , Fang Liming , Tang Youhong
Published: December 2016

A dopamine molecule on the Stone–Wales defective graphene surface.
Aesthetically improved and efficient tannin–metal chelates for the treatment of dentinal hypersensitivity
Authors: Ju Sung-Won , Prajatelistia Ekavianty , Jun Sang Ho , Hwang Dong Soo , Ahn Jin-Soo , Sanandiya Naresh D.
Published: December 2016

Tannin–metal chelates for the efficient nucleation of hydroxyapatite and an aesthetically improved solution for the dentinal hypersensitivity treatment.
Surface and interface structural analysis of W deposited on 6H–SiC substrates annealed in argon
Authors: Thabethe T. T. , Njoroge E. G. , Hlatshwayo T. T. , Ntsoane T. P. , Malherbe J. B.
Published: December 2016

A study of a tungsten (W) thin film deposited on a single crystalline 6H–SiC substrate and annealed in Ar at temperatures of 700 °C, 800 °C, 900 °C and 1000 °C for 1 hour was conducted.
F–Bi4TaO8Cl flower-like hierarchical structures: controlled preparation, formation mechanism and visible photocatalytic hydrogen production
Authors: Nawaz Muhammad , Mou Fangzhi , Xu Leilei , Tu Hao , Guan Jianguo
Published: December 2016

Hydrothermal method was employed to prepare the flower-like hierarchical structures of F–Bi4TaO8Cl for photocatalytic hydrogen production under visible light irradiation.
Mn(OAc)3 catalyzed intermolecular oxidative peroxycyclization of naphthoquinone
Authors: Biyogo Alex Meye , Curti Christophe , El-Kashef Hussein , Khoumeri Omar , Terme Thierry , Vanelle Patrice
Published: December 2016

Manganese(iii) acetate mediated peroxycyclization between 2-hydroxy-3-methylnaphthoquinone and alkenes allowed the synthesis of more than 50 original dihydronaphtho[2,3-c][1,2]dioxine-5,10(3H,10aH)-diones.
Functionalisation of ligands through click chemistry: long-lived NIR emission from organic Er(iii) complexes with a perfluorinated core and a hydrogen-containing shell
Authors: Peng Y. , Hu J. X. , Lu H. , Wilson R. M. , Motevalli M. , Hernández I. , Gillin W. P. , Wyatt P. B. , Ye H. Q.
Published: December 2016

Erbium complexes with a fluorinated organic core shell linked to a hydrogen-containing shell, have been synthesized using the click reaction between erbium(iii) bis(perfluoro-4-azidophenyl)phosphinate and a series of alkynes.
Enhanced degradation of gaseous benzene by a Fenton reaction
Authors: Liu Gaoyuan , Huang Haibao , Xie Ruijie , Feng Qiuyu , Fang Ruimei , Shu Yajie , Zhan Yujie , Ye Xinguo , Zhong Cheng
Published: December 2016

A wet scrubbing process coupled with advanced oxidation processes (AOP) has raised great interest for the abatement of volatile organic compounds (VOCs) owing to its strong oxidation capacity and few byproducts.
Synthesis of aryl triflones by insertion of arynes into C–SO2CF3 bonds
Authors: Zhao Xian , Huang Yangen , Qing Feng-Ling , Xu Xiu-Hua
Published: December 2016

A new approach toward the synthesis of aryl triflones was achieved by the formal insertion of arynes into C–SO2CF3 bonds.
A liposome-actuated enzyme system and its capability as a self-biomineralized silica nanoreactor
Authors: Municoy S. , Bellino M. G.
Published: December 2016

An assembly to switch enzyme activity and actuate self-biomineralization by changing the liposome permeability through temperature control is reported.
Origin(s) of the apparent colossal permittivity in (In1/2Nb1/2)xTi1−xO2: clarification on the strongly induced Maxwell–Wagner polarization relaxation by DC bias
Authors: Tuichai Wattana , Danwittayakul Supamas , Chanlek Narong , Srepusharawoot Pornjuk , Thongbai Prasit , Maensiri Santi
Published: December 2016

The effects of DC bias on the dielectric and electrical properties of co-doped (In1/2Nb1/2)xTi1−xO2 (IN-T), where x = 0.05 and 0.1, and single-doped Ti0.975Nb0.025O2 ceramics are investigated.
Seeds triggered massive synthesis and multi-step room temperature post-processing of silver nanoink—application for paper electronics
Authors: Zhang Xiao-Yang , Xu Jia-Jia , Wu Jing-Yuan , Shan Feng , Ma Xiao-Dan , Chen Yu-Zhang , Zhang Tong
Published: December 2016

Ink synthesis, room-temperature post-processing and applications for flexible 3D paper electronics.
Piezochromism and hydrochromism through electron transfer: new stories for viologen materials
Authors: Sui Qi , Ren Xiang-Ting , Dai Yu-Xiang , Wang Kai , Li Wen-Tao , Gong Teng , Fang Jia-Jia , Zou Bo , Gao En-Qing , Wang Lin
Published: December 2016

A pyridinium-carboxylate compound undergoes reversible color change under pressure owing to the formation of radicalsviaelectron transfer; dehydration and hydration can also trigger electron transfer.
Highly crosslinked, chlorine tolerant polymer network entwined graphene oxide membrane for water desalination
Authors: Kim Seungju , Lin Xiaocheng , Ou Ranwen , Liu Huiyuan , Zhang Xiwang , Simon George P. , Easton Christopher D. , Wang Huanting
Published: December 2016

A graphene oxide (GO)–polymer nanocomposite membrane was fabricated by integrating GO nanosheets into a highly crosslinked polymer network on a porous polymer substrate for desalination.
Osteogenic and tenogenic induction of hBMSCs by an integrated nanofibrous scaffold with chemical and structural mimicry of the bone–ligament connection
Authors: Lin Zifeng , Zhao Xiujuan , Chen Si , Du Chang
Published: December 2016

A novel electrospinning nanofiber collecting device was designed and utilized to fabricate an integrated PCL nanofibrous scaffold with a “random–aligned–random” structure.
Thermoresponsive hydrogels based on a phosphorylated star-shaped copolymer: mimicking the extracellular matrix for in situ bone repair
Authors: Wu Wei , Lin Zaifu , Liu Yanpeng , Xu Xinyuan , Ding Chunmei , Li Jianshu
Published: December 2016

A bioinspired hydrogel prepared using a star-polymer exhibits sol to gel transition to induce in situ biomineralization and facilitate cell proliferation.
Dielectric elastomers with dual piezo-electrostatic response optimized through chemical design for electromechanical transducers
Authors: Tugui C. , Bele A. , Tiron V. , Hamciuc E. , Varganici C. D. , Cazacu M.
Published: December 2016

Advanced elastomers bearing both dielectric and piezoelectric features within the same material of high interest in the hot topic of electroactive polymers are reported.