bluuebunny/crossref_metadata_2025 huggingface dataset:
Interrogating cellular fate decisions with high-throughput arrays of multiplexed cellular communities
Authors: Chen Sisi , Bremer Andrew W. , Scheideler Olivia J. , Na Yun Suk , Todhunter Michael E. , Hsiao Sonny , Bomdica Prithvi R. , Maharbiz Michel M. , Gartner Zev J. , Schaffer David V.
Published: January 2016

Recreating heterotypic cell–cell interactions in vitro is key to dissecting the role of cellular communication during a variety of biological processes. This is especially relevant for stem cell niches, where neighbouring cells provide instructive inputs that govern cell fate decisions. To investigate the logic and dynamics of cell–cell signalling networks, we prepared heterotypic cell–cell interaction arrays using DNA-programmed adhesion. Our platform specifies the number and initial position of up to four distinct cell types within each array and offers tunable control over cell-contact time during long-term culture. Here, we use the platform to study the dynamics of single adult neural stem cell fate decisions in response to competing juxtacrine signals. Our results suggest a potential signalling hierarchy between Delta-like 1 and ephrin-B2 ligands, as neural stem cells adopt the Delta-like 1 phenotype of stem cell maintenance on simultaneous presentation of both signals.
Impairment of PARK14-dependent Ca2+ signalling is a novel determinant of Parkinson’s disease
Authors: Zhou Qingde , Yen Allen , Rymarczyk Grzegorz , Asai Hirohide , Trengrove Chelsea , Aziz Nadine , Kirber Michael T. , Mostoslavsky Gustavo , Ikezu Tsuneya , Wolozin Benjamin , Bolotina Victoria M.
Published: January 2016

The etiology of idiopathic Parkinson’s disease (idPD) remains enigmatic despite recent successes in identification of genes (PARKs) that underlie familial PD. To find new keys to this incurable neurodegenerative disorder we focused on the poorly understood PARK14 disease locus (Pla2g6 gene) and the store-operated Ca2+ signalling pathway. Analysis of the cells from idPD patients reveals a significant deficiency in store-operated PLA2g6-dependent Ca2+ signalling, which we can mimic in a novel B6.Cg-Pla2g6ΔEx2-VB (PLA2g6 ex2KO) mouse model. Here we demonstrate that genetic or molecular impairment of PLA2g6-dependent Ca2+ signalling is a trigger for autophagic dysfunction, progressive loss of dopaminergic (DA) neurons in substantia nigra pars compacta and age-dependent L-DOPA-sensitive motor dysfunction. Discovery of this previously unknown sequence of pathological events, its association with idPD and our ability to mimic this pathology in a novel genetic mouse model opens new opportunities for finding a cure for this devastating neurodegenerative disease.
Global marine protected areas do not secure the evolutionary history of tropical corals and fishes
Authors: Mouillot D. , Parravicini V. , Bellwood D. R. , Leprieur F. , Huang D. , Cowman P. F. , Albouy C. , Hughes T. P. , Thuiller W. , Guilhaumon F.
Published: January 2016

Although coral reefs support the largest concentrations of marine biodiversity worldwide, the extent to which the global system of marine-protected areas (MPAs) represents individual species and the breadth of evolutionary history across the Tree of Life has never been quantified. Here we show that only 5.7% of scleractinian coral species and 21.7% of labrid fish species reach the minimum protection target of 10% of their geographic ranges within MPAs. We also estimate that the current global MPA system secures only 1.7% of the Tree of Life for corals, and 17.6% for fishes. Regionally, the Atlantic and Eastern Pacific show the greatest deficit of protection for corals while for fishes this deficit is located primarily in the Western Indian Ocean and in the Central Pacific. Our results call for a global coordinated expansion of current conservation efforts to fully secure the Tree of Life on coral reefs.
Quantum algorithms: an overview
Authors: Montanaro Ashley
Published: January 2016

Quantum computers are designed to outperform standard computers by running quantum algorithms. Areas in which quantum algorithms can be applied include cryptography, search and optimisation, simulation of quantum systems and solving large systems of linear equations. Here we briefly survey some known quantum algorithms, with an emphasis on a broad overview of their applications rather than their technical details. We include a discussion of recent developments and near-term applications of quantum algorithms.
Erratum: Term rules for simple metal clusters
Authors: Yoshida Daisuke , Raebiger Hannes
Published: January 2016

Scientific Reports 5: Article number: 15760; published online 26 October 2015; updated on 12 January 2016
Correction: Corrigendum: Tea polyphenols as an antivirulence compound Disrupt Quorum-Sensing Regulated Pathogenicity of Pseudomonas aeruginosa
Authors: Yin Hongping , Deng Yifeng , Wang Huafu , Liu Wugao , Zhuang Xiyi , Chu Weihua
Published: January 2016

Green tea, a water extract of non-fermented leaves of Camellia sinensis L., is one of the nonalcoholic beverages in China. It is becoming increasingly popular worldwide, because of its refreshing, mild stimulant and medicinal properties. Here we examined the quorum sensing inhibitory potentials of tea polyphenols (TP) as antivirulence compounds both in vitro and in vivo. Biosensor assay data suggested minimum inhibitory concentrations (MICs) of TP against selected pathogens were 6.25 ~ 12.5 mg/mL. At sub-MIC, TP can specifically inhibit the production of violacein in Chromobacterium violaceum 12472 with almost 98% reduction at 3.125 mg/mL without affecting its growth rate. Moreover, TP exhibited inhibitory effects on virulence phenotypes regulated by QS in Pseudomonas aeruginosa. The total proteolytic activity, elastase, swarming motility and biofilm formation were reduced in a concentration-dependent manner. In vivo, TP treatment resulted in the reduction of P. aeruginosa pathogenicity in Caenorhabditis elegans. When its concentration was 3.125 mg/mL, the survival rate reached 63.3%. In the excision wound infection model, the wound contraction percentage in treatment groups was relatively increased and the colony-forming units (CFU) in the wound area were significantly decreased. These results suggested that TP could be developed as a novel non-antibiotic QS inhibitor without killing the bacteria but as an antivirulence compound to control bacterial infection.
Functional properties of flagellin as a stimulator of innate immunity
Authors: Lu Yuan , Swartz James R.
Published: January 2016

We report the development of a well-defined flagellin-based nanoparticle stimulator and also provide a new mechanism of action model explaining how flagellin-triggered innate immunity has evolved to favor localized rather than potentially debilitating systemic immune stimulation. Cell-free protein synthesis (CFPS) was used to facilitate mutational analysis and precisely orientated display of flagellin on Hepatitis B core (HBc) protein virus-like particles (VLPs). The need for product stability and an understanding of mechanism of action motivated investigations indicating that the D0 domain of flagellin is sensitive to amino acid sequence independent hydrolysis – apparently due to the need for structural flexibility during natural flagellin polymerization. When D0-stabilized flagellin was attached to HBc VLPs with the D0 domain facing outward, flagellin’s tendency to polymerize caused the VLPs to precipitate. However, attaching the D0 domain to the VLP surface produced a stable nanoparticle adjuvant. Surprisingly, attaching only 2 flagellins per VLP provided the same 1 pM potency as did VLPs with about 33 attached flagellins suggesting that the TLR5 receptor is highly effective in delivering its intracellular signal. These observations suggest that flagellin’s protease sensitivity, tendency to aggregate and very high affinity for TLR5 receptors limit its systemic distribution to favor localized immune stimulation.
Ammonia-induced miRNA expression changes in cultured rat astrocytes
Authors: Oenarto Jessica , Karababa Ayse , Castoldi Mirco , Bidmon Hans J. , Görg Boris , Häussinger Dieter
Published: January 2016

Hepatic encephalopathy is a neuropsychiatric syndrome evolving from cerebral osmotic disturbances and oxidative/nitrosative stress. Ammonia, the main toxin of hepatic encephalopathy, triggers astrocyte senescence in an oxidative stress-dependent way. As miRNAs are critically involved in cell cycle regulation and their expression may be regulated by oxidative stress, we analysed, whether astrocyte senescence is a consequence of ammonia-induced miRNA expression changes. Using a combined miRNA and gene microarray approach, 43 miRNA species which were downregulated and 142 genes which were upregulated by NH4Cl (5 mmol/l, 48 h) in cultured rat astrocytes were found. Ammonia-induced miRNA and gene expression changes were validated by qPCR and 43 potential miRNA target genes, including HO-1, were identified by matching upregulated mRNA species with predicted targets of miRNA species downregulated by ammonia. Inhibition of HO-1 targeting miRNAs which were downregulated by NH4Cl strongly upregulated HO-1 mRNA and protein levels and inhibited astrocyte proliferation in a HO-1-dependent way. Preventing ammonia-induced upregulation of HO-1 by taurine (5 mmol/l) as well as blocking HO-1 activity by tin-protoporphyrine IX fully prevented ammonia-induced proliferation inhibition and senescence. The data suggest that ammonia induces astrocyte senescence through NADPH oxidase-dependent downregulation of HO-1 targeting miRNAs and concomitant upregulation of HO-1 at both mRNA and protein level.
Correction: Corrigendum: Robustness and period sensitivity analysis of minimal models for biochemical oscillators
Authors: Caicedo-Casso Angélica , Kang Hye-Won , Lim Sookkyung , Hong Christian I.
Published: January 2016

Biological systems exhibit numerous oscillatory behaviors from calcium oscillations to circadian rhythms that recur daily. These autonomous oscillators contain complex feedbacks with nonlinear dynamics that enable spontaneous oscillations. The detailed nonlinear dynamics of such systems remains largely unknown. In this paper, we investigate robustness and dynamical differences of five minimal systems that may underlie fundamental molecular processes in biological oscillatory systems. Bifurcation analyses of these five models demonstrate an increase of oscillatory domains with a positive feedback mechanism that incorporates a reversible reaction, and dramatic changes in dynamics with small modifications in the wiring. Furthermore, our parameter sensitivity analysis and stochastic simulations reveal different rankings of hierarchy of period robustness that are determined by the number of sensitive parameters or network topology. In addition, systems with autocatalytic positive feedback loop are shown to be more robust than those with positive feedback via inhibitory degradation regardless of noise type. We demonstrate that robustness has to be comprehensively assessed with both parameter sensitivity analysis and stochastic simulations.
Erratum: Dynamic creation of a topologically-ordered Hamiltonian using spin-pulse control in the Heisenberg model
Authors: Tanamoto Tetsufumi , Ono Keiji , Liu Yu-xi , Nori Franco
Published: January 2016

Hamiltonian engineering is an important approach for quantum information processing, when appropriate materials do not exist in nature or are unstable. So far there is no stable material for the Kitaev spin Hamiltonian with anisotropic interactions on a honeycomb lattice, which plays a crucial role in the realization of both Abelian and non-Abelian anyons. Here, we show two methods to dynamically realize the Kitaev spin Hamiltonian from the conventional Heisenberg spin Hamiltonian using pulse-control techniques based on the Baker-Campbell-Hausdorff (BCH) formula. In the first method, the Heisenberg interaction is changed into Ising interactions in the first process of the pulse sequence. In the next process of the first method, we transform them to a desirable anisotropic Kitaev spin Hamiltonian. In the second more efficient method, we show that if we carefully design two-dimensional pulses that vary depending on the qubit location, we can obtain the desired Hamiltonian in only one step of applying the BCH formula. As an example, we apply our methods to spin qubits based on quantum dots, in which the effects of both the spin-orbit interaction and the hyperfine interaction are estimated.
Cryopreservation of the gorgonian endosymbiont Symbiodinium
Authors: Chong Gabriella , Tsai Sujune , Wang Li-Hsueh , Huang Chih-Yang , Lin Chiahsin
Published: January 2016

The study focused on finding a suitable cryoprotectant (CPA) and an optimum freezing protocol for the cryopreservation of the endosymbiotic dinoflagellates (Symbiodinium, clade G) of Junceella fragilis wherein the success of experiments is crucial to both scientific and ecology studies. A two-step freezing technique was developed. The viability of the thawed dinoflagellates was assayed using the adenosine triphosphate (ATP) bioassay for the first time and was further confirmed through the culturing of dinoflagellates in vitro. The results suggested that 30 min was the most suitable holding time for the dinoflagellates and the samples produced highest viability when suspended at 5 cm from the surface of LN2. Results also showed that 1 M methanol with 0.4 M sucrose was the most effective CPA, yielding the highest viability (56.93%). Although cell densities of both cryopreserved and control group suffered an initial decline of culture, the cell densities were maintained throughout the remaining duration. In the present study, the cryopreservation of clade G endosymbiont algae was studied for the first time and the method described here could be applied for future studies on symbiotic algae cryopreservation.
Ab initio molecular dynamic study of solid-state transitions of ammonium nitrate
Authors: Yu Hongyu , Duan Defang , Liu Hanyu , Yang Ting , Tian Fubo , Bao Kuo , Li Da , Zhao Zhonglong , Liu Bingbing , Cui Tian
Published: January 2016

High-pressure polymorphism and phase transitions have wide ranging consequences on the basic properties of ammonium nitrate. However, the phase diagram of ammonium nitrate at high pressure and high temperature is still under debate. This study systematically investigates the phase transitions and structural properties of ammonium nitrate at a pressure range of 5–60 GPa and temperature range of 250–400 K by ab initio molecular dynamics simulations. Two new phases are identified: one corresponds to the experimentally observed phase IV’ and the other is named AN-X. Simultaneously, the lattice strains play a significant role in the formation and stabilization of phase IV’, providing a reasonable explanation for experimental observation of phase IV-IV’ transition which only appears under nonhydrostatic pressure. In addition, 12 O atoms neighboring the NH (N atom in ammonium cation) atom are selected as reference system to clearly display the tanglesome rotation of ammonium cation.
Enhanced air pollution via aerosol-boundary layer feedback in China
Authors: Petäjä T. , Järvi L. , Kerminen V.-M. , Ding A.J. , Sun J.N. , Nie W. , Kujansuu J. , Virkkula A. , Yang X. , Fu C.B. , Zilitinkevich S. , Kulmala M.
Published: January 2016

Severe air pollution episodes have been frequent in China during the recent years. While high emissions are the primary reason for increasing pollutant concentrations, the ultimate cause for the most severe pollution episodes has remained unclear. Here we show that a high concentration of particulate matter (PM) will enhance the stability of an urban boundary layer, which in turn decreases the boundary layer height and consequently cause further increases in PM concentrations. We estimate the strength of this positive feedback mechanism by combining a new theoretical framework with ambient observations. We show that the feedback remains moderate at fine PM concentrations lower than about 200 μg m−3, but that it becomes increasingly effective at higher PM loadings resulting from the combined effect of high surface PM emissions and massive secondary PM production within the boundary layer. Our analysis explains why air pollution episodes are particularly serious and severe in megacities and during the days when synoptic weather conditions stay constant.
Characterization of the interactions of PARP-1 with UV-damaged DNA in vivo and in vitro
Authors: Purohit Nupur K. , Robu Mihaela , Shah Rashmi G. , Geacintov Nicholas E. , Shah Girish M.
Published: January 2016

The existing methodologies for studying robust responses of poly (ADP-ribose) polymerase-1 (PARP-1) to DNA damage with strand breaks are often not suitable for examining its subtle responses to altered DNA without strand breaks, such as UV-damaged DNA. Here we describe two novel assays with which we characterized the interaction of PARP-1 with UV-damaged DNA in vivo and in vitro. Using an in situ fractionation technique to selectively remove free PARP-1 while retaining the DNA-bound PARP-1, we demonstrate a direct recruitment of the endogenous or exogenous PARP-1 to the UV-lesion site in vivo after local irradiation. In addition, using the model oligonucleotides with single UV lesion surrounded by multiple restriction enzyme sites, we demonstrate in vitro that DDB2 and PARP-1 can simultaneously bind to UV-damaged DNA and that PARP-1 casts a bilateral asymmetric footprint from −12 to +9 nucleotides on either side of the UV-lesion. These techniques will permit characterization of different roles of PARP-1 in the repair of UV-damaged DNA and also allow the study of normal housekeeping roles of PARP-1 with undamaged DNA.
The Dendrobium catenatum Lindl. genome sequence provides insights into polysaccharide synthase, floral development and adaptive evolution
Authors: Zhang Guo-Qiang , Xu Qing , Bian Chao , Tsai Wen-Chieh , Yeh Chuan-Ming , Liu Ke-Wei , Yoshida Kouki , Zhang Liang-Sheng , Chang Song-Bin , Chen Fei , Shi Yu , Su Yong-Yu , Zhang Yong-Qiang , Chen Li-Jun , Yin Yayi , Lin Min , Huang Huixia , Deng Hua , Wang Zhi-Wen , Zhu Shi-Lin , Zhao Xiang , Deng Cao , Niu Shan-Ce , Huang Jie , Wang Meina , Liu Guo-Hui , Yang Hai-Jun , Xiao Xin-Ju , Hsiao Yu-Yun , Wu Wan-Lin , Chen You-Yi , Mitsuda Nobutaka , Ohme-Takagi Masaru , Luo Yi-Bo , Van de Peer Yves , Liu Zhong-Jian
Published: January 2016

Orchids make up about 10% of all seed plant species, have great economical value and are of specific scientific interest because of their renowned flowers and ecological adaptations. Here, we report the first draft genome sequence of a lithophytic orchid, Dendrobium catenatum. We predict 28,910 protein-coding genes and find evidence of a whole genome duplication shared with Phalaenopsis. We observed the expansion of many resistance-related genes, suggesting a powerful immune system responsible for adaptation to a wide range of ecological niches. We also discovered extensive duplication of genes involved in glucomannan synthase activities, likely related to the synthesis of medicinal polysaccharides. Expansion of MADS-box gene clades ANR1, StMADS11, and MIKC*, involved in the regulation of development and growth, suggests that these expansions are associated with the astonishing diversity of plant architecture in the genus Dendrobium. On the contrary, members of the type I MADS box gene family are missing, which might explain the loss of the endospermous seed. The findings reported here will be important for future studies into polysaccharide synthesis, adaptations to diverse environments and flower architecture of Orchidaceae.
Insight into the mechanical, thermodynamics and superconductor properties of NbRuB via first-principles calculation
Authors: Tian Wenyan , Chen Haichuan
Published: January 2016

Using the first-principles calculations, the electronic structure, chemical bonding, mechanical, thermodynamics and superconductor properties of NbRuB are investigated. The optimized lattice parameters were in good agreement with the experimental data. The analysis of the density of states and chemical bonding implies that the metallic behavior of NbRuB originates from the Ru and Nb and the bonding behaviors are a mixture of covalent-ionic bonds. The bulk modulus, shear modulus, Young’s modulus, Poisson’s ratio and hardness of NbRuB were calculated. The results reveal that the NbRuB is ductility and the Vickers hardness is 15.06 GPa. Moreover, the 3D dependences of reciprocals of Young’s modulus is also calculated and discussed, showing strong anisotropic character for NbRuB. Finally, the Debye temperature and superconducting transition temperature are obtained.
Dynamics of the Transcriptome during Human Spermatogenesis: Predicting the Potential Key Genes Regulating Male Gametes Generation
Authors: Zhu Zijue , Li Chong , Yang Shi , Tian Ruhui , Wang Junlong , Yuan Qingqing , Dong Hui , He Zuping , Wang Shengyue , Li Zheng
Published: January 2016

Many infertile men are the victims of spermatogenesis disorder. However, conventional clinical test could not provide efficient information on the causes of spermatogenesis disorder and guide the doctor how to treat it. More effective diagnosis and treating methods could be developed if the key genes that regulate spermatogenesis were determined. Many works have been done on animal models, while there are few works on human beings due to the limited sample resources. In current work, testis tissues were obtained from 27 patients with obstructive azoospermia via surgery. The combination of Fluorescence Activated Cell Sorting and Magnetic Activated Cell Sorting was chosen as the efficient method to sort typical germ cells during spermatogenesis. RNA Sequencing was carried out to screen the change of transcriptomic profile of the germ cells during spermatogenesis. Differential expressed genes were clustered according to their expression patterns. Gene Ontology annotation, pathway analysis and Gene Set Enrichment Analysis were carried out on genes with specific expression patterns and the potential key genes such as HOXs, JUN, SP1 and TCF3 which were involved in the regulation of spermatogenesis, with the potential value serve as molecular tools for clinical purpose, were predicted.
RETRACTED ARTICLE: TRIM25 blockade by RNA interference inhibited migration and invasion of gastric cancer cells through TGF-β signaling
Authors: Zhu Zhenya , Wang Yong , Zhang Chunhui , Yu Shiyong , Zhu Qi , Hou Kun , Yan Bo
Published: January 2016

Tripartite Motif Containing 25 (TRIM25), a member of TRIM proteins, has been found abnormally expressed in cancers of female reproductive system. Here, TRIM25 was conspicuously expressed in human gastric cancer (GC) tissues in which its higher expression generally correlated with the poor prognosis of patients. Small interfering RNA (siRNA)-mediated knockdown of TRIM25 expression in MGC-803 and AGS cells had no effects on cell proliferation, whereas reduced cell migration and invasion. Gene set enrichment analysis on The Cancer Genome Atlas stomach adenocarcinoma (STAD) dataset revealed that several signaling pathways, including the migration, E-cadherin and transforming growth factor-β (TGF-β) pathways, were enriched in TRIM25 higher expression patients. Moreover, ectopic expression of TRIM25 in a GC cell line with lower expression of TRIM25 significantly promoted the migration and invasion. Further experiments with TGF-β inhibitor suggested that TRIM25 may exert its function through TGF-β pathway. In summary, our results indicate that TRIM25 acts as an oncogene in GC and thus presents a novel target for the detection and treatment of GC.
Invariant community structure of soil bacteria in subtropical coniferous and broadleaved forests
Authors: Wang Xiaoli , Wang Xiaoling , Zhang Weixin , Shao Yuanhu , Zou Xiaoming , Liu Tao , Zhou Lixia , Wan Songze , Rao Xingquan , Li Zhian , Fu Shenglei
Published: January 2016

Soil bacteria may be influenced by vegetation and play important roles in global carbon efflux and nutrient cycling under global changes. Coniferous and broadleaved forests are two phyletically distinct vegetation types. Soil microbial communities in these forests have been extensively investigated but few studies have presented comparable data regarding the characteristics of bacterial communities in subtropical forests. We investigated soil bacterial biomass and community composition in three pairs of coniferous and broadleaved forests across a subtropical climatic gradient. We found that bacterial biomass differed between the coniferous and broadleaved forests across the subtropical climate gradient; however, this difference disappeared at some individual sites. In contrast, the same 90 bacterial genera were found in both forest types and their relative abundances didn’t differ between the forest types, with the exception of one genus that was more abundant in broadleaved forests. Soil nitrogen or moisture was associated with bacterial groups in the coniferous and broadleaved forests, respectively. Thus, we inferred that these forests can respond differently to future changes in nitrogen deposition or precipitation. This study highlights soil bacterial invariant community composition in contrasting subtropical forests and provides a new perspective on the potential response and feedback of forests to global changes.
Astrocyte-derived adenosine is central to the hypnogenic effect of glucose
Authors: Scharbarg Emeric , Daenens Marion , Lemaître Frédéric , Geoffroy Hélène , Guille-Collignon Manon , Gallopin Thierry , Rancillac Armelle
Published: January 2016

Sleep has been hypothesised to maintain a close relationship with metabolism. Here we focus on the brain structure that triggers slow-wave sleep, the ventrolateral preoptic nucleus (VLPO), to explore the cellular and molecular signalling pathways recruited by an increase in glucose concentration. We used infrared videomicroscopy on ex vivo brain slices to establish that glucose induces vasodilations specifically in the VLPO via the astrocytic release of adenosine. Real-time detection by in situ purine biosensors further revealed that the adenosine level doubles in response to glucose and triples during the wakefulness period. Finally, patch-clamp recordings uncovered the depolarizing effect of adenosine and its A2A receptor agonist, CGS-21680, on sleep-promoting VLPO neurons. Altogether, our results provide new insights into the metabolically driven release of adenosine. We hypothesise that adenosine adjusts the local energy supply to local neuronal activity in response to glucose. This pathway could contribute to sleep-wake transition and sleep intensity.
Systematic Analysis of Sex-Linked Molecular Alterations and Therapies in Cancer
Authors: Ma Jonathan , Malladi Sadhika , Beck Andrew H
Published: January 2016

Though patient sex influences response to cancer treatments, little is known of the molecular causes and cancer therapies are generally given irrespective of patient sex. We assessed transcriptomic differences in tumors from men and women spanning 17 cancer types and we assessed differential expression between tumor and normal samples stratified by sex across 7 cancers. We used the LincsCloud platform to perform Connectivity Map analyses to link transcriptomic signatures identified in male and female tumors with chemical and genetic perturbagens and we performed permutation testing to identify perturbagens that showed significantly differential connectivity with male and female tumors. Our analyses predicted that females are sensitive and males are resistant to tamoxifen treatment of lung adenocarcinoma, a finding which is consistent with known male-female differences in lung cancer. We made several novel predictions, including that CDK1 and PTPN1 knockdown would be more effective in males with hepatocellular carcinoma and SMAD3 and HSPA4 knockdown would be more effective in females with head and neck squamous cell carcinoma. Our results provide a new resource for researchers studying male-female biological and treatment response differences in human cancer. The complete results of our analyses are provided at the website accompanying this manuscript (http://becklab.github.io/SexLinked).
Dissecting the influence of Neolithic demic diffusion on Indian Y-chromosome pool through J2-M172 haplogroup
Authors: Singh Sakshi , Singh Ashish , Rajkumar Raja , Sampath Kumar Katakam , Kadarkarai Samy Subburaj , Nizamuddin Sheikh , Singh Amita , Ahmed Sheikh Shahnawaz , Peddada Vidya , Khanna Vinee , Veeraiah Pandichelvam , Pandit Aridaman , Chaubey Gyaneshwer , Singh Lalji , Thangaraj Kumarasamy
Published: January 2016

The global distribution of J2-M172 sub-haplogroups has been associated with Neolithic demic diffusion. Two branches of J2-M172, J2a-M410 and J2b-M102 make a considerable part of Y chromosome gene pool of the Indian subcontinent. We investigated the Neolithic contribution of demic dispersal from West to Indian paternal lineages, which majorly consists of haplogroups of Late Pleistocene ancestry. To accomplish this, we have analysed 3023 Y-chromosomes from different ethnic populations, of which 355 belonged to J2-M172. Comparison of our data with worldwide data, including Y-STRs of 1157 individuals and haplogroup frequencies of 6966 individuals, suggested a complex scenario that cannot be explained by a single wave of agricultural expansion from Near East to South Asia. Contrary to the widely accepted elite dominance model, we found a substantial presence of J2a-M410 and J2b-M102 haplogroups in both caste and tribal populations of India. Unlike demic spread in Eurasia, our results advocate a unique, complex and ancient arrival of J2a-M410 and J2b-M102 haplogroups into Indian subcontinent.
Construction of a subunit-fusion nitrile hydratase and discovery of an innovative metal ion transfer pattern
Authors: Xia Yuanyuan , Cui Wenjing , Liu Zhongmei , Zhou Li , Cui Youtian , Kobayashi Michihiko , Zhou Zhemin
Published: January 2016

Metallochaperones are metal-binding proteins designed to deliver the appropriate metal to a target protein. The metal is usually transferred between different proteins. In this study, we discovered that metal was transferred between the same subunit of a mutant nitrile hydratase (NHase). Various “activator proteins” mediate the trafficking of metal ions into NHases. We constructed fusion NHases by fusing the β- and α-subunits and/or the “activator proteins” of the NHase from Pseudomonas putida. The fusion NHases exhibited higher thermostability and tolerance to high concentrations of the product amide. The mechanism of the cobalt incorporation changed from a self-subunit swapping pattern to an apoprotein-specific molecular chaperone pattern in vivo and a metallochaperone pattern in vitro. Notably, the cobalt transfer occurred between the same α-subunit in the metallochaperone pattern. These results not only demonstrated the superiority of fusion-type NHases, but also revealed an innovative metal ion transfer pattern in metalloprotein biosynthesis.
Livestock-associated methicillin and multidrug resistant S. aureus in humans is associated with occupational pig contact, not pet contact
Authors: Ye Xiaohua , Fan Yanping , Wang Xiaolin , Liu Weidong , Yu Haifeng , Zhou Junli , Chen Sidong , Yao Zhenjiang
Published: January 2016

This study aimed to explore the association of livestock-associated S. aureus with occupational pig contact and pet contact. In this cross-sectional study, 1,422 participants (including 244 pig workers, 200 pet-owning workers and 978 control workers) responded to a questionnaire and provided a nasal swab for S. aureus analysis. Resulting isolates were tested for antibiotic susceptibility, the immune evasion cluster (IEC) genes and multilocus sequence type. Compared with controls, the pig workers demonstrated a greater prevalence of multidrug-resistant S. aureus (MDRSA) [prevalence ratio (PR) = 3.38; 95% CI: 2.07–5.53] and methicillin-resistant S. aureus (MRSA) (PR = 7.42; 95% CI: 3.71–14.83), but the prevalence of MDRSA and MRSA was similar in pet-owning workers and controls. There was a positive relation of frequency of pig contact with prevalence of MDRSA and MRSA carriage. Only pig workers carried MDRSA CC9 (16 isolates) and MRSA CC9 (16 isolates) and all of these isolates were tetracycline resistant and absent of IEC genes. These findings suggest that livestock-associated MRSA and MDRSA(CC9, IEC-negative, tetracycline-resistant) in humans is associated with occupational pig contact, not pet contact and support growing concern about antibiotics use in pig farms and raising questions about the potential for occupational exposure to opportunistic S. aureus.
Streptomycin treatment alters the intestinal microbiome, pulmonary T cell profile and airway hyperresponsiveness in a cystic fibrosis mouse model
Authors: Bazett Mark , Bergeron Marie-Eve , Haston Christina K.
Published: January 2016

Cystic fibrosis transmembrane conductance regulator deficient mouse models develop phenotypes of relevance to clinical cystic fibrosis (CF) including airway hyperresponsiveness, small intestinal bacterial overgrowth and an altered intestinal microbiome. As dysbiosis of the intestinal microbiota has been recognized as an important contributor to many systemic diseases, herein we investigated whether altering the intestinal microbiome of BALB/c Cftrtm1UNC mice and wild-type littermates, through treatment with the antibiotic streptomycin, affects the CF lung, intestinal and bone disease. We demonstrate that streptomycin treatment reduced the intestinal bacterial overgrowth in Cftrtm1UNC mice and altered the intestinal microbiome similarly in Cftrtm1UNC and wild-type mice, principally by affecting Lactobacillus levels. Airway hyperresponsiveness of Cftrtm1UNC mice was ameliorated with streptomycin and correlated with Lactobacillus abundance in the intestine. Additionally, streptomycin treated Cftrtm1UNC and wild-type mice displayed an increased percentage of pulmonary and mesenteric lymph node Th17, CD8 + IL-17+ and CD8 + IFNγ+ lymphocytes, while the CF-specific increase in respiratory IL-17 producing γδ T cells was decreased in streptomycin treated Cftrtm1UNC mice. Bone disease and intestinal phenotypes were not affected by streptomycin treatment. The airway hyperresponsiveness and lymphocyte profile of BALB/c Cftrtm1UNC mice were affected by streptomycin treatment, revealing a potential intestinal microbiome influence on lung response in BALB/c Cftrtm1UNC mice.
The effect of surface wettability on water vapor condensation in nanoscale
Authors: Niu D. , Tang G. H.
Published: January 2016

The effect of surface wettability on condensation heat transfer in a nanochannel is studied with the molecular dynamics simulations. Different from the conventional size, the results show that the filmwise mode leads to more efficient heat transfer than the dropwise mode, which is attributed to a lower interfacial thermal resistance between the hydrophilic surface and the condensed water compared with the hydrophobic case. The observed temperature jump at the solid-liquid surface confirms that the hydrophilic properties of the solid surface can suppress the interfacial thermal resistance and improve the condensation heat transfer performance effectively.
miR-133 regulates Evi1 expression in AML cells as a potential therapeutic target
Authors: Yamamoto Haruna , Lu Jun , Oba Shigeyoshi , Kawamata Toyotaka , Yoshimi Akihide , Kurosaki Natsumi , Yokoyama Kazuaki , Matsushita Hiromichi , Kurokawa Mineo , Tojo Arinobu , Ando Kiyoshi , Morishita Kazuhiro , Katagiri Koko , Kotani Ai
Published: January 2016

The Ecotropic viral integration site 1 (Evi1) is a zinc finger transcription factor, which is located on chromosome 3q26, over-expression in some acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Elevated Evi1 expression in AML is associated with unfavorable prognosis. Therefore, Evi1 is one of the strong candidate in molecular target therapy for the leukemia. MicroRNAs (miRNAs) are small non-coding RNAs, vital to many cell functions that negatively regulate gene expression by translation or inducing sequence-specific degradation of target mRNAs. As a novel biologics, miRNAs is a promising therapeutic target due to its low toxicity and low cost. We screened miRNAs which down-regulate Evi1. miR-133 was identified to directly bind to Evi1 to regulate it. miR-133 increases drug sensitivity specifically in Evi1 expressing leukemic cells, but not in Evi1-non-expressing cells The results suggest that miR-133 can be promising therapeutic target for the Evi1 dysregulated poor prognostic leukemia.
In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy
Authors: Jang Won Hyuk , Shim Sehwan , Wang Taejun , Yoon Yeoreum , Jang Won-Suk , Myung Jae Kyung , Park Sunhoo , Kim Ki Hean
Published: January 2016

Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis.
Exogenous avian leukosis virus-induced activation of the ERK/AP1 pathway is required for virus replication and correlates with virus-induced tumorigenesis
Authors: Dai Manman , Feng Min , Ye Yu , Wu Xiaochan , Liu Di , Liao Ming , Cao Weisheng
Published: January 2016

A proteomics approach was used to reveal the up-regulated proteins involved in the targeted mitogen-activated protein kinase (MAPK) signal transduction pathway in DF-1 cells after ALV subgroup J (ALV-J) infection. Next, we found that ALV-J CHN06 strain infection of DF-1 cells correlated with extracellular signal-regulated kinase 2 (ERK2) activation, which was mainly induced within 15 min, a very early stage of infection and at a late infection stage, from 108 h to 132 h post-infection. Infection with other ALV subgroup (A/B) strains also triggered ERK/MAPK activation. Moreover, when activating ERK2, ALV subgroups A, B and J simultaneously induced the phosphorylation of c-Jun, an AP1 family member and p38 activation but had no obvious effect on JNK activation at either 15 min or 120 h. Interestingly, only PD98059 inhibited the ALV-induced c-Jun phosphorylation while SP600125 or SB203580 had no influence on c-Jun activation. Furthermore, the viral gp85 and gag proteins were found to contribute to ERK2/AP1 activation. Additionally, the specific ERK inhibitor, PD980509, significantly suppressed ALV replication, as evidenced by extremely low levels of ALV promoter activity and ALV-J protein expression. In vivo analysis of ERK2 activation in tumor cells derived from ALV-J-infected chicken demonstrated a strong correlation between ERK/MAPK activation and virus-associated tumorigenesis.
Two-phase quasi-equilibrium in β-type Ti-based bulk metallic glass composites
Authors: Zhang L. , Pauly S. , Tang M. Q. , Eckert J. , Zhang H. F.
Published: January 2016

The microstructural evolution of cast Ti/Zr-based bulk metallic glass composites (BMGCs) containing β-Ti still remains ambiguous. This is why to date the strategies and alloys suitable for producing such BMGCs with precisely controllable volume fractions and crystallite sizes are still rather limited. In this work, a Ti-based BMGC containing β-Ti was developed in the Ti-Zr-Cu-Co-Be system. The glassy matrix of this BMGC possesses an exceptional glass-forming ability and as a consequence, the volume fractions as well as the composition of the β-Ti dendrites remain constant over a wide range of cooling rates. This finding can be explained in terms of a two-phase quasi-equilibrium between the supercooled liquid and β-Ti, which the system attains on cooling. The two-phase quasi-equilibrium allows predicting the crystalline and glassy volume fractions by means of the lever rule and we succeeded in reproducing these values by slight variations in the alloy composition at a fixed cooling rate. The two-phase quasi-equilibrium could be of critical importance for understanding and designing the microstructures of BMGCs containing the β-phase. Its implications on the nucleation and growth of the crystalline phase are elaborated.
Prognostic Significance of EZH2 Expression in Non-Small Cell Lung Cancer: A Meta-analysis
Authors: Wang Xinhua , Zhao Hongqing , Lv Lei , Bao Liang , Wang Xun , Han Shuguang
Published: January 2016

Various studies examined the relationship between EZH2 overexpression with the clinical outcome in patients with non-small cell lung cancer (NSCLC), but yielded inconsistent results. Electronic databases updated to Dec 2014 were searched to find relevant studies. A meta-analysis was conducted with eligible studies which quantitatively evaluated the relationship between EZH2 overexpression and survival of patients with NSCLC Survival data were aggregated and quantitatively analyzed. We performed a meta-analysis of 10 studies (n = 1,695 patients) that evaluated the correlation between EZH2 overexpression and survival in patients with lung cancer. Combined hazard ratios suggested that EZH2 overexpression was associated with poor prognosis of overall survival (OS) (HR = 1.68, 95% CI: 1.42–1.93) in patients with lung cancer. In the stratified analysis, significantly risks were found among Asians (HR = 1.33, 95% CI: 1.62–1.70), lung adenocarcinoma patients (HR = 1.75, 95% CI: 1.38–2.52, in stage I NSCLC patients (HR = 2.51, 95% CI: 1.23–3.79), but not among Caucasians. EZH2 overexpression indicates a poor prognosis for patients with NSCLC, this effect appears also significant when the analysis is restricted in Asian population, lung AC and stage I patients, but not among Caucasians.
Flavone synthases from Lonicera japonica and L. macranthoides reveal differential flavone accumulation
Authors: Wu Jie , Wang Xiao-Chen , Liu Yang , Du Hui , Shu Qing-Yan , Su Shang , Wang Li-Jin , Li Shan-Shan , Wang Liang-Sheng
Published: January 2016

Flavones are important secondary metabolites found in many plants. InLoniceraspecies, flavones contribute both physiological and pharmaceutical properties. However, flavone synthase (FNS), the key enzyme responsible for flavone biosynthesis, has not yet been characterized inLoniceraspecies. In this study,FNSIIgenes were identified fromLonicera japonicaThunb. andL. macranthoidesHand.-Mazz. In the presence of NADPH, the recombinant cytochrome P450 proteins encoded byLjFNSII-1.1,LjFNSII-2.1andLmFNSII-1.1converted eriodictyol, naringenin and liquiritigenin to the corresponding flavones directly. The different catalytic properties between LjFNSII-2.1 and LjFNSII-1.1 were caused by a single amino acid substitution at position 242 (glutamic acid to lysine). A methionine at position 206 and a leucine at position 381 contributed considerably to the high catalytic activity of LjFNSII-1.1. In addition, LjFNSII-1.1&2.1 and LmFNSII-1.1 also biosynthesize flavones that were further modified byO-glycosylation in transgenic tobacco. The expression levels of theFNSIIgenes were consistent with flavone accumulation patterns in flower buds. Our findings suggested that the weak catalytic activity of LmFNSII-1.1 and the relatively low expression ofLmFNSII-1.1in flowers might be responsible for the low levels of flavone accumulation in flower buds ofL. macranthoides.
Mechanism of 2,3-butanediol stereoisomers formation in a newly isolated Serratia sp. T241
Authors: Zhang Liaoyuan , Guo Zewang , Chen Jiebo , Xu Quanming , Lin Hui , Hu Kaihui , Guan Xiong , Shen Yaling
Published: January 2016

Serratia sp. T241, a newly isolated xylose-utilizing strain, produced three 2,3-butanediol (2,3-BD) stereoisomers. In this study, three 2,3-butanediol dehydrogenases (BDH1-3) and one glycerol dehydrogenase (GDH) involved in 2,3-BD isomers formation by Serratia sp. T241 were identified. In vitro conversion showed BDH1 and BDH2 could catalyzed (3S)-acetoin and (3R)-acetoin into (2S,3S)-2,3-BD and meso-2,3-BD, while BDH3 and GDH exhibited the activities from (3S)-acetoin and (3R)-acetoin to meso-2,3-BD and (2R,3R)-2,3-BD. Four encoding genes were assembled into E. coli with budA (acetolactate decarboxylase) and budB (acetolactate synthase), responsible for converting pyruvate into acetoin. E. coli expressing budAB-bdh1/2 produced meso-2,3-BD and (2S,3S)-2,3-BD. Correspondingly, (2R,3R)-2,3-BD and meso-2,3-BD were obtained by E. coli expressing budAB-bdh3/gdh. These results suggested four enzymes might contribute to 2,3-BD isomers formation. Mutants of four genes were developed in Serratia sp. T241. Δbdh1 led to reduced concentration of meso-2,3-BD and (2S,3S)-2,3-BD by 97.7% and 87.9%. (2R,3R)-2,3-BD with a loss of 73.3% was produced by Δbdh3. Enzyme activity assays showed the decrease of 98.4% and 22.4% by Δbdh1 and Δbdh3 compared with the wild strain. It suggested BDH1 and BDH3 played important roles in 2,3-BD formation, BDH2 and GDH have small effects on 2,3-BD production by Serratia sp. T241.
Large-scale sensor systems based on graphene electrolyte-gated field-effect transistors
Authors: Mackin Charles , Palacios Tomás
Published: January 2016

This work reports a novel graphene electrolyte-gated field-effect transistor (EGFET) array architecture along with a compact, self-contained, and inexpensive measurement system that allows DC characterization of hundreds of graphene EGFETs as a function ofVDSandVGSwithin a matter of minutes.
Novel chromogenic selective sensors for aqueous cyanide ions under high water content and real sample analysis
Authors: Balamurugan Gopal , Velmathi Sivan
Published: January 2016

Novel chromogenic receptors (R1–R2) containing anthraquinone as the signalling unit and imidazole as the binding unit were designed to enhance the sensing action in an aqueous medium.
A narrow amide I vibrational band observed by sum frequency generation spectroscopy reveals highly ordered structures of a biofilm protein at the air/water interface
Authors: Wang Zhuguang , Morales-Acosta M. Daniela , Li Shanghao , Liu Wei , Kanai Tapan , Liu Yuting , Chen Ya-Na , Walker Frederick J. , Ahn Charles H. , Leblanc Roger M. , Yan Elsa C. Y.
Published: January 2016

We observed an unprecedentedly narrow amide I vibrational band from a bacterial biofilm protein at the air/water interface.
Electrically charged selectivity of poly-para-xylylene deposition
Authors: Wu Chih-Yu , Sun Ho-Yi , Liang Wei-Chieh , Hsu Hung-Lun , Ho Hsin-Ying , Chen Yu-Ming , Chen Hsien-Yeh
Published: January 2016

Electrically charged surfaces show inhibited selectivity for the deposition of poly-para-xylylenes, irrespective of their substituted functionalities.
Dimerization of a marginally stable disilenyl germylene to tricyclic systems: evidence for reversible NHC-coordination
Authors: Nieder David , Yildiz Cem B. , Jana Anukul , Zimmer Michael , Huch Volker , Scheschkewitz David
Published: January 2016

Reaction of a base-stabilised silagermenylidene with MeLi yields two tricyclic isomeric Si/Ge species via an unsaturated three-membered ring species that is stabilised by excess N-heterocyclic carbene.
Enhanced performance in gas adsorption and Li ion batteries by docking Li+ in a crown ether-based metal–organic framework
Authors: Bai Linyi , Tu Binbin , Qi Yi , Gao Qiang , Liu Dong , Liu Zhizhou , Zhao Lingzhi , Li Qiaowei , Zhao Yanli
Published: January 2016

Incorporating supramolecular recognition units, crown ether rings, into metal–organic frameworks enables the docking of metal ions through complexation for enhanced performance.