bluuebunny/crossref_metadata_2025 huggingface dataset:
Nuclear AURKA acquires kinase-independent transactivating function to enhance breast cancer stem cell phenotype
Authors: Zheng Feimeng , Yue Caifeng , Li Guohui , He Bin , Cheng Wei , Wang Xi , Yan Min , Long Zijie , Qiu Wanshou , Yuan Zhongyu , Xu Jie , Liu Bing , Shi Qian , Lam Eric W.-F. , Hung Mien-Chie , Liu Quentin
Published: January 2016

Centrosome-localized mitotic Aurora kinase A (AURKA) facilitates G2/M events. Here we show that AURKA translocates to the nucleus and causes distinct oncogenic properties in malignant cells by enhancing breast cancer stem cell (BCSC) phenotype. Unexpectedly, this function is independent of its kinase activity. Instead, AURKA preferentially interacts with heterogeneous nuclear ribonucleoprotein K (hnRNP K) in the nucleus and acts as a transcription factor in a complex that induces a shift in MYC promoter usage and activates the MYC promoter. Blocking AURKA nuclear localization inhibits this newly discovered transactivating function of AURKA, sensitizing resistant BCSC to kinase inhibition. These findings identify a previously unknown oncogenic property of the spatially deregulated AURKA in tumorigenesis and provide a potential therapeutic opportunity to overcome kinase inhibitor resistance.
Catch reconstructions reveal that global marine fisheries catches are higher than reported and declining
Authors: Pauly Daniel , Zeller Dirk
Published: January 2016

Fisheries data assembled by the Food and Agriculture Organization (FAO) suggest that global marine fisheries catches increased to 86 million tonnes in 1996, then slightly declined. Here, using a decade-long multinational ‘catch reconstruction’ project covering the Exclusive Economic Zones of the world’s maritime countries and the High Seas from 1950 to 2010, and accounting for all fisheries, we identify catch trajectories differing considerably from the national data submitted to the FAO. We suggest that catch actually peaked at 130 million tonnes, and has been declining much more strongly since. This decline in reconstructed catches reflects declines in industrial catches and to a smaller extent declining discards, despite industrial fishing having expanded from industrialized countries to the waters of developing countries. The differing trajectories documented here suggest a need for improved monitoring of all fisheries, including often neglected small-scale fisheries, and illegal and other problematic fisheries, as well as discarded bycatch.
Magnetic bilayer-skyrmions without skyrmion Hall effect
Authors: Zhang Xichao , Zhou Yan , Ezawa Motohiko
Published: January 2016

Magnetic skyrmions might be used as information carriers in future advanced memories, logic gates and computing devices. However, there exists an obstacle known as the skyrmion Hall effect (SkHE), that is, the skyrmion trajectories bend away from the driving current direction due to the Magnus force. Consequently, the skyrmions in constricted geometries may be destroyed by touching the sample edges. Here we theoretically propose that the SkHE can be suppressed in the antiferromagnetically exchange-coupled bilayer system, since the Magnus forces in the top and bottom layers are exactly cancelled. We show that such a pair of SkHE-free magnetic skyrmions can be nucleated and be driven by the current-induced torque. Our proposal provides a promising means to move magnetic skyrmions in a perfectly straight trajectory in ultra-dense devices with ultra-fast processing speed.
Exceptional preservation of eye structure in arthropod visual predators from the Middle Jurassic
Authors: Vannier Jean , Schoenemann Brigitte , Gillot Thomas , Charbonnier Sylvain , Clarkson Euan
Published: January 2016

Vision has revolutionized the way animals explore their environment and interact with each other and rapidly became a major driving force in animal evolution. However, direct evidence of how ancient animals could perceive their environment is extremely difficult to obtain because internal eye structures are almost never fossilized. Here, we reconstruct with unprecedented resolution the three-dimensional structure of the huge compound eye of a 160-million-year-old thylacocephalan arthropod from the La Voulte exceptional fossil biota in SE France. This arthropod had about 18,000 lenses on each eye, which is a record among extinct and extant arthropods and is surpassed only by modern dragonflies. Combined information about its eyes, internal organs and gut contents obtained by X-ray microtomography lead to the conclusion that this thylacocephalan arthropod was a visual hunter probably adapted to illuminated environments, thus contradicting the hypothesis that La Voulte was a deep-water environment.
Genomic signals of migration and continuity in Britain before the Anglo-Saxons
Authors: Martiniano Rui , Caffell Anwen , Holst Malin , Hunter-Mann Kurt , Montgomery Janet , Müldner Gundula , McLaughlin Russell L. , Teasdale Matthew D. , van Rheenen Wouter , Veldink Jan H. , van den Berg Leonard H. , Hardiman Orla , Carroll Maureen , Roskams Steve , Oxley John , Morgan Colleen , Thomas Mark G. , Barnes Ian , McDonnell Christine , Collins Matthew J. , Bradley Daniel G.
Published: January 2016

The purported migrations that have formed the peoples of Britain have been the focus of generations of scholarly controversy. However, this has not benefited from direct analyses of ancient genomes. Here we report nine ancient genomes (∼1 ×) of individuals from northern Britain: seven from a Roman era York cemetery, bookended by earlier Iron-Age and later Anglo-Saxon burials. Six of the Roman genomes show affinity with modern British Celtic populations, particularly Welsh, but significantly diverge from populations from Yorkshire and other eastern English samples. They also show similarity with the earlier Iron-Age genome, suggesting population continuity, but differ from the later Anglo-Saxon genome. This pattern concords with profound impact of migrations in the Anglo-Saxon period. Strikingly, one Roman skeleton shows a clear signal of exogenous origin, with affinities pointing towards the Middle East, confirming the cosmopolitan character of the Empire, even at its northernmost fringes.
Mutational spectrum of Barrett’s stem cells suggests paths to initiation of a precancerous lesion
Authors: Yamamoto Yusuke , Wang Xia , Bertrand Denis , Kern Florian , Zhang Ting , Duleba Marcin , Srivastava Supriya , Khor Chiea Chuen , Hu Yuanyu , Wilson Lane H. , Blaszyk Hagen , Rolshud Daniil , Teh Ming , Liu Jianjun , Howitt Brooke E. , Vincent Matthew , Crum Christopher P. , Nagarajan Niranjan , Ho Khek Yu , McKeon Frank , Xian Wa
Published: January 2016

The precancerous lesion known as Barrett’s oesophagus can evolve to oesophageal adenocarcinoma in decades-long processes of regenerative growth. Here we report the isolation and propagation of distinct, patient-matched stem cells of Barrett’s, gastric and oesophageal epithelia that yield divergent tumour types following in vitro transformation and xenografting. Genomic analyses reveal a broad mutational spectrum unique to Barrett’s stem cells that likely reflects their risk for oncogenesis. Remarkably, 25% of cases show no cancer-related genomic changes, suggesting that Barrett’s initiates without driver mutations. Most cases, however, sustain patterns of deletions almost identical to adenocarcinoma though tumour-associated gene amplifications were absent. Notably, those suspected of low-grade dysplasia have p53 mutations or undergo amplifications of proto-oncogenes and receptor tyrosine kinases, implicating these events in lethal transitions. Our findings suggest paths for the initiation and progression of Barrett’s and define a discrete stem cell underlying its regenerative growth whose eradication could prevent oesophageal adenocarcinoma.
The Shp2-induced epithelial disorganization defect is reversed by HDAC6 inhibition independent of Cdc42
Authors: Tien Sui-Chih , Lee Hsiao-Hui , Yang Ya-Chi , Lin Miao-Hsia , Chen Yu-Ju , Chang Zee-Fen
Published: January 2016

Regulation of Shp2, a tyrosine phosphatase, critically influences the development of various diseases. Its role in epithelial lumenogenesis is not clear. Here we show that oncogenic Shp2 dephosphorylates Tuba to decrease Cdc42 activation, leading to the abnormal multi-lumen formation of epithelial cells. HDAC6 suppression reverses oncogenic Shp2-induced multiple apical domains and spindle mis-orientation during division in cysts to acquire normal lumenogenesis. Intriguingly, Cdc42 activity is not restored in this rescued process. We present evidence that simultaneous reduction in myosin II and ERK1/2 activity by HDAC6 inhibition is responsible for the reversion. In HER2-positive breast cancer cells, Shp2 also mediates Cdc42 repression, and HDAC6 inhibition or co-suppression of ERK/myosin II promotes normal epithelial lumen phenotype without increasing Cdc42 activity. Our data suggest a mechanism of epithelial disorganization by Shp2 deregulation, and reveal the cellular context where HDAC6 suppression is capable of establishing normal epithelial lumenogenesis independent of Cdc42.
New observations on maternal age effect on germline de novo mutations
Authors: Wong Wendy S. W. , Solomon Benjamin D. , Bodian Dale L. , Kothiyal Prachi , Eley Greg , Huddleston Kathi C. , Baker Robin , Thach Dzung C. , Iyer Ramaswamy K. , Vockley Joseph G. , Niederhuber John E.
Published: January 2016

Germline mutations are the source of evolution and contribute substantially to many health-related processes. Here we use whole-genome deep sequencing data from 693 parents–offspring trios to examine the de novo point mutations (DNMs) in the offspring. Our estimate for the mutation rate per base pair per generation is 1.05 × 10−8, well within the range of previous studies. We show that maternal age has a small but significant correlation with the total number of DNMs in the offspring after controlling for paternal age (0.51 additional mutations per year, 95% CI: 0.29, 0.73), which was not detectable in the smaller and younger parental cohorts of earlier studies. Furthermore, while the total number of DNMs increases at a constant rate for paternal age, the contribution from the mother increases at an accelerated rate with age.These observations have implications related to the incidence of de novo mutations relating to maternal age.
Plant traits, productivity, biomass and soil properties from forest sites in the Pacific Northwest, 1999–2014
Authors: Berner Logan T. , Law Beverly E.
Published: January 2016

Plant trait measurements are needed for evaluating ecological responses to environmental conditions and for ecosystem process model development, parameterization, and testing. We present a standardized dataset integrating measurements from projects conducted by the Terrestrial Ecosystem Research and Regional Analysis- Pacific Northwest (TERRA-PNW) research group between 1999 and 2014 across Oregon and Northern California, where measurements were collected for scaling and modeling regional terrestrial carbon processes with models such as Biome-BGC and the Community Land Model. The dataset contains measurements of specific leaf area, leaf longevity, leaf carbon and nitrogen for 35 tree and shrub species derived from more than 1,200 branch samples collected from over 200 forest plots, including several AmeriFlux sites. The dataset also contains plot-level measurements of forest composition, structure (e.g., tree biomass), and productivity, as well as measurements of soil structure (e.g., bulk density) and chemistry (e.g., carbon). Publically-archiving regional datasets of standardized, co-located, and geo-referenced plant trait measurements will advance the ability of earth system models to capture species-level climate sensitivity at regional to global scales.
Characterization of Social Behaviors in caspase-3 deficient mice
Authors: Lo Shih-Ching , Scearce-Levie Kimberly , Sheng Morgan
Published: January 2016

Impaired social interaction is a defining feature of autism spectrum disorder, a neurodevelopmental disorder that shows a strong male preponderance in prevalence. Studies have identified neural circuits, neuromodulators and genetic factors involved in social behaviors, but mechanistic understanding of gender-specific social deficits is lacking. We report that deletion of the caspase-3 gene, encoding a protease with functions in apoptosis and neural plasticity, alters specific social behaviors in male mice, while leaving females unaffected. Casp3−/− mice showed normal behavioral responses to olfactory cues from food, neutral chemical and biological sources. Both Casp3−/− males and females displayed robust social exploration, sociability, recognition and preference for an enclosed novel mouse in the three-chamber test. However, Casp3−/− males showed significantly reduced social interaction behaviors when exposed to a freely moving novel mouse, including decreased interaction time and diminished mounting. Thus caspase-3 is essential for a subset of social behaviors, but despite similar hyper-locomotion in both sexes, only male Casp3−/− mice exhibited social interaction deficits, which is interesting given the male bias of autism.
Determination and correction of persistent biases in quantum annealers
Authors: Perdomo-Ortiz Alejandro , O’Gorman Bryan , Fluegemann Joseph , Biswas Rupak , Smelyanskiy Vadim N.
Published: January 2016

Calibration of quantum computers is essential to the effective utilisation of their quantum resources. Specifically, the performance of quantum annealers is likely to be significantly impaired by noise in their programmable parameters, effectively misspecification of the computational problem to be solved, often resulting in spurious suboptimal solutions. We developed a strategy to determine and correct persistent, systematic biases between the actual values of the programmable parameters and their user-specified values. We applied the recalibration strategy to two D-Wave Two quantum annealers, one at NASA Ames Research Center in Moffett Field, California and another at D-Wave Systems in Burnaby, Canada. We show that the recalibration procedure not only reduces the magnitudes of the biases in the programmable parameters but also enhances the performance of the device on a set of random benchmark instances.
Combined Labelled and Label-free SERS Probes for Triplex Three-dimensional Cellular Imaging
Authors: Chen Yong , Bai Xiangru , Su Le , Du Zhanwei , Shen Aiguo , Materny Arnulf , Hu Jiming
Published: January 2016

Cells are complex chemical systems, where the molecular composition at different cellular locations and specific intracellular chemical interactions determine the biological function. An in-situ nondestructive characterization of the complicated chemical processes (like e.g. apoptosis) is the goal of our study. Here, we present the results of simultaneous and three-dimensional imaging of double organelles (nucleus and membrane) in single HeLa cells by means of either labelled or label-free surface-enhanced Raman spectroscopy (SERS). This combination of imaging with and without labels is not possible when using fluorescence microscopy. The SERS technique is used for a stereoscopic description of the intrinsic chemical nature of nuclei and the precise localization of folate (FA) and luteinizing hormone-releasing hormone (LHRH) on the membrane under highly confocal conditions. We also report on the time-dependent changes of cell nuclei as well as membrane receptor proteins during apoptosis analyzed by statistical multivariate methods. The multiplex three-dimensional SERS imaging technique allows for both temporal (real time) and spatial (multiple organelles and molecules in three-dimensional space) live-cell imaging and therefore provides a new and attractive 2D/3D tracing method in biomedicine on subcellular level.
Controllable electrical and physical breakdown of poly-crystalline silicon nanowires by thermally assisted electromigration
Authors: Park Jun-Young , Moon Dong-Il , Seol Myeong-Lok , Jeon Chang-Hoon , Jeon Gwang-Jae , Han Jin-Woo , Kim Choong-Ki , Park Sang-Jae , Lee Hee Chul , Choi Yang-Kyu
Published: January 2016

The importance of poly-crystalline silicon (poly-Si) in semiconductor manufacturing is rapidly increasing due to its highly controllable conductivity and excellent, uniform deposition quality. With the continuing miniaturization of electronic components, low dimensional structures such as 1-dimensional nanowires (NWs) have attracted a great deal of attention. But such components have a much higher current density than 2- or 3- dimensional films and high current can degrade device lifetime and lead to breakdown problems. Here, we report on the electrical and thermal characteristics of poly-Si NWs, which can also be used to control electrical and physical breakdown under high current density. This work reports a controllable catastrophic change of poly-Si NWs by thermally-assisted electromigration and underlying mechanisms. It also reports the direct and real time observation of these catastrophic changes of poly-Si nanowires for the first time, using scanning electron microscopy.
A Combination of Chemometrics and Quantum Mechanics Methods Applied to Analysis of Femtosecond Transient Absorption Spectrum of Ortho-Nitroaniline
Authors: Yi Jing , Xiong Ying , Cheng Kemei , Li Menglong , Chu Genbai , Pu Xuemei , Xu Tao
Published: January 2016

A combination of the advanced chemometrics method with quantum mechanics calculation was for the first time applied to explore a facile yet efficient analysis strategy to thoroughly resolve femtosecond transient absorption spectroscopy of ortho-nitroaniline (ONA), served as a model compound of important nitroaromatics and explosives. The result revealed that the ONA molecule is primarily excited to S3 excited state from the ground state and then ultrafast relaxes to S2 state. The internal conversion from S2 to S1 occurs within 0.9 ps. One intermediate state S* was identified in the intersystem crossing (ISC) process, which is different from the specific upper triplet receiver state proposed in some other nitroaromatics systems. The S1 state decays to the S* one within 6.4 ps and then intersystem crossing to the lowest triplet state within 19.6 ps. T1 was estimated to have a lifetime up to 2 ns. The relatively long S* state and very long-lived T1 one should play a vital role as precursors to various nitroaromatic and explosive photoproducts.
Quantum coherence of steered states
Authors: Hu Xueyuan , Milne Antony , Zhang Boyang , Fan Heng
Published: January 2016

Lying at the heart of quantum mechanics, coherence has recently been studied as a key resource in quantum information theory. Quantum steering, a fundamental notion originally considered by Schödinger, has also recently received much attention. When Alice and Bob share a correlated quantum system, Alice can perform a local measurement to ‘steer’ Bob’s reduced state. We introduce the maximal steered coherence as a measure describing the extent to which steering can remotely create coherence; more precisely, we find the maximal coherence of Bob’s steered state in the eigenbasis of his original reduced state, where maximization is performed over all positive-operator valued measurements for Alice. We prove that maximal steered coherence vanishes for quantum-classical states whilst reaching a maximum for pure entangled states with full Schmidt rank. Although invariant under local unitary operations, maximal steered coherence may be increased when Bob performs a channel. For a two-qubit state we find that Bob’s channel can increase maximal steered coherence if and only if it is neither unital nor semi-classical, which coincides with the condition for increasing discord. Our results show that the power of steering for coherence generation, though related to discord, is distinct from existing measures of quantum correlation.
Energy-efficient population coding constrains network size of a neuronal array system
Authors: Yu Lianchun , Zhang Chi , Liu Liwei , Yu Yuguo
Published: January 2016

We consider the open issue of how the energy efficiency of the neural information transmission process, in a general neuronal array, constrains the network size and how well this network size ensures the reliable transmission of neural information in a noisy environment. By direct mathematical analysis, we have obtained general solutions proving that there exists an optimal number of neurons in the network, where the average coding energy cost (defined as energy consumption divided by mutual information) per neuron passes through a global minimum for both subthreshold and superthreshold signals. With increases in background noise intensity, the optimal neuronal number decreases for subthreshold signals and increases for suprathreshold signals. The existence of an optimal number of neurons in an array network reveals a general rule for population coding that states that the neuronal number should be large enough to ensure reliable information transmission that is robust to the noisy environment but small enough to minimize energy cost.
The Role of mGluR Copy Number Variation in Genetic and Environmental Forms of Syndromic Autism Spectrum Disorder
Authors: Wenger Tara L. , Kao Charlly , McDonald-McGinn Donna M. , Zackai Elaine H. , Bailey Alice , Schultz Robert T. , Morrow Bernice E. , Emanuel Beverly S. , Hakonarson Hakon
Published: January 2016

While abnormal signaling mediated through metabotropic glutamate receptor 5 (mGluR5) is involved in the pathophysiology of Autism Spectrum Disorder (ASD), Fragile X Syndrome and Tuberous Sclerosis, the role of other mGluRs and their associated signaling network genes in syndromic ASD is unknown. This study sought to determine whether mGluR Copy Number Variants (CNV’s) were overrepresented in children with syndromic ASD and if mGluR “second hit” confers additional risk for ASD in 22q11.2 Deletion Syndrome (22q11DS). To determine whether mGluR network CNV’S are enriched in syndromic ASD, we examined microarrays from children with ASD (n = 539). Patient categorization (syndromic vs nonsyndromic) was done via blinded medical chart review in mGluR positive and randomly selected mGluR negative cases. 11.5% of ASD had mGluR CNV’s vs. 3.2% in controls (p < 0.001). Syndromic ASD was more prevalent in children with mGluR CNVs (74% vs 16%, p < 0.001). A comparison cohort with 22q11DS (n = 25 with ASD, n = 50 without ASD), all haploinsufficient for mGluR network gene RANBP1, were evaluated for “second mGluR hits”. 20% with 22q11.2DS + ASD had “second hits” in mGluR network genes vs 2% in 22q11.2DS-ASD (p < 0.014). We propose that altered RANBP1 expression may provide a mechanistic link for several seemingly unrelated genetic and environmental forms of ASD.
Ginsenoside Rh2 inhibits hepatocellular carcinoma through β-catenin and autophagy
Authors: Yang Zhiqing , Zhao Tingting , Liu Hongli , Zhang Leida
Published: January 2016

Hepatocellular carcinoma (HCC) is the most common liver cancer, with a very poor prognosis. There is an urgent need for an effective therapy for HCC. Ginsenoside Rh2 (GRh2) has been shown to significantly inhibit growth of some types of cancer, whereas its effects on HCC have not been examined. Here, we treated human HCC cells with different doses of GRh2 and found that GRh2 dose-dependently reduced HCC viability, in either CCK-8 assay or MTT assay. The effects of GRh2 on the cancer stem cells (CSCs)-like cells were determined by aldefluor flow cytometry and by tumor sphere formation, showing that GRh2 dose-dependently decreased the number of these CSCs-like cells in HCC. Autophagy-associated protein and β-catenin level were measured in GRh2-treated HCC cells by Western blot, showing that GRh2 increased autophagy and inhibited β-catenin signaling. Expression of short hairpin small interfering RNA (shRNA) for Atg7 in HCC cells completely abolished the effects of GRh2 on β-catenin and cell viability, while overexpression of β-catenin abolished the effects of GRh2 on autophagy and cell viability. Together, our data suggest that GRh2 may inhibit HCC cell growth, possibly through a coordinated autophagy and β-catenin signaling.
A comprehensive gene expression analysis at sequential stages of in vitro cardiac differentiation from isolated MESP1-expressing-mesoderm progenitors
Authors: den Hartogh Sabine C. , Wolstencroft Katherine , Mummery Christine L. , Passier Robert
Published: January 2016

In vitro cardiac differentiation of human pluripotent stem cells (hPSCs) closely recapitulates in vivo embryonic heart development and therefore, provides an excellent model to study human cardiac development. We recently generated the dual cardiac fluorescent reporter MESP1mCherry/wNKX2-5eGFP/w line in human embryonic stem cells (hESCs), allowing the visualization of pre-cardiac MESP1+ mesoderm and their further commitment towards the cardiac lineage, marked by activation of the cardiac transcription factor NKX2-5. Here, we performed a comprehensive whole genome based transcriptome analysis of MESP1-mCherry derived cardiac-committed cells. In addition to previously described cardiac-inducing signalling pathways, we identified novel transcriptional and signalling networks indicated by transient activation and interactive network analysis. Furthermore, we found a highly dynamic regulation of extracellular matrix components, suggesting the importance to create a versatile niche, adjusting to various stages of cardiac differentiation. Finally, we identified cell surface markers for cardiac progenitors, such as the Leucine-rich repeat-containing G-protein coupled receptor 4 (LGR4), belonging to the same subfamily of LGR5 and LGR6, established tissue/cancer stem cells markers. We provide a comprehensive gene expression analysis of cardiac derivatives from pre-cardiac MESP1-progenitors that will contribute to a better understanding of the key regulators, pathways and markers involved in human cardiac differentiation and development.
The Foot’s Arch and the Energetics of Human Locomotion
Authors: Stearne Sarah M. , McDonald Kirsty A. , Alderson Jacqueline A. , North Ian , Oxnard Charles E. , Rubenson Jonas
Published: January 2016

The energy-sparing spring theory of the foot’s arch has become central to interpretations of the foot’s mechanical function and evolution. Using a novel insole technique that restricted compression of the foot’s longitudinal arch, this study provides the first direct evidence that arch compression/recoil during locomotion contributes to lowering energy cost. Restricting arch compression near maximally (~80%) during moderate-speed (2.7 ms−1) level running increased metabolic cost by + 6.0% (p < 0.001, d = 0.67; unaffected by foot strike technique). A simple model shows that the metabolic energy saved by the arch is largely explained by the passive-elastic work it supplies that would otherwise be done by active muscle. Both experimental and model data confirm that it is the end-range of arch compression that dictates the energy-saving role of the arch. Restricting arch compression had no effect on the cost of walking or incline running (3°), commensurate with the smaller role of passive-elastic mechanics in these gaits. These findings substantiate the elastic energy-saving role of the longitudinal arch during running and suggest that arch supports used in some footwear and orthotics may increase the cost of running.
Chemical dampening of Ly6Chi monocytes in the periphery produces anti-depressant effects in mice
Authors: Zheng Xiao , Ma Sijing , Kang An , Wu Mengqiu , Wang Lin , Wang Qiong , Wang Guangji , Hao Haiping
Published: January 2016

The involvement of systemic immunity in depression pathogenesis promises a periphery-targeting paradigm in novel anti-depressant discovery. However, relatively little is known about druggable targets in the periphery for mental and behavioral control. Here we report that targeting Ly6Chi monocytes in blood can serve as a strategy for anti-depressant purpose. A natural compound, ginsenoside Rg1 (Rg1), was firstly validated as a periphery-restricted chemical probe. Rg1 selectively suppressed Ly6Chi monocytes recruitment to the inflamed mice brain. The proinflammatory potential of Ly6Chi monocytes to activate astrocytes was abrogated by Rg1, which led to a blunted feedback release of CCL2 to recruit the peripheral monocytes. In vitro study demonstrated that Rg1 pretreatment on activated THP-1 monocytes retarded their ability to trigger CCL2 secretion from co-cultured U251 MG astrocytes. CCL2-triggered p38/MAPK and PI3K/Akt activation were involved in the action of Rg1. Importantly, in mice models, we found that dampening Ly6Chi monocytes at the periphery ameliorated depression-like behavior induced by neuroinflammation or chronic social defeat stress. Together, our work unravels that blood Ly6Chi monocytes may serve as the target to enable remote intervention on the depressed brain and identifies Rg1 as a lead compound for designing drugs targeting peripheral CCL2 signals.
Towards a fully functional integrated photonic-electronic platform via a single SiGe growth step
Authors: Littlejohns Callum G. , Dominguez Bucio Thalia , Nedeljkovic Milos , Wang Hong , Mashanovich Goran Z. , Reed Graham T. , Gardes Frederic Y.
Published: January 2016

Silicon-germanium (Si1-xGex) has become a material of great interest to the photonics and electronics industries due to its numerous interesting properties including higher carrier mobilities than Si, a tuneable lattice constant and a tuneable bandgap. In previous work, we have demonstrated the ability to form localised areas of single crystal, uniform composition SiGe-on-insulator. Here we present a method of simultaneously growing several areas of SiGe-on-insulator on a single wafer, with the ability to tune the composition of each localised SiGe area, whilst retaining a uniform composition in that area. We use a rapid melt growth technique that comprises of only a single Ge growth step and a single anneal step. This innovative method is key in working towards a fully integrated photonic-electronic platform, enabling the simultaneous growth of multiple compositions of device grade SiGe for electro-absorption optical modulators operating at a range of wavelengths, photodetectors and bipolar transistors, on the same wafer. This is achieved by modifying the structural design of the SiGe strips, without the need to modify the growth conditions and by using low cost, low thermal-budget methods.
Meta-analysis of lipid-traits in Hispanics identifies novel loci, population-specific effects and tissue-specific enrichment of eQTLs
Authors: Below Jennifer E. , Parra Esteban J. , Gamazon Eric R. , Torres Jason , Krithika S. , Candille Sophie , Lu Yingchang , Manichakul Ani , Peralta-Romero Jesus , Duan Qing , Li Yun , Morris Andrew P. , Gottesman Omri , Bottinger Erwin , Wang Xin-Qun , Taylor Kent D. , Ida Chen Y.-D. , Rotter Jerome I. , Rich Stephen S. , Loos Ruth J. F. , Tang Hua , Cox Nancy J. , Cruz Miguel , Hanis Craig L. , Valladares-Salgado Adan
Published: January 2016

We performed genome-wide meta-analysis of lipid traits on three samples of Mexican and Mexican American ancestry comprising 4,383 individuals and followed up significant and highly suggestive associations in three additional Hispanic samples comprising 7,876 individuals. Genome-wide significant signals were observed in or near CELSR2, ZNF259/APOA5, KANK2/DOCK6 and NCAN/MAU2 for total cholesterol, LPL, ABCA1, ZNF259/APOA5, LIPC and CETP for HDL cholesterol, CELSR2, APOB and NCAN/MAU2 for LDL cholesterol and GCKR, TRIB1, ZNF259/APOA5 and NCAN/MAU2 for triglycerides. Linkage disequilibrium and conditional analyses indicate that signals observed at ABCA1 and LIPC for HDL cholesterol and NCAN/MAU2 for triglycerides are independent of previously reported lead SNP associations. Analyses of lead SNPs from the European Global Lipids Genetics Consortium (GLGC) dataset in our Hispanic samples show remarkable concordance of direction of effects as well as strong correlation in effect sizes. A meta-analysis of the European GLGC and our Hispanic datasets identified five novel regions reaching genome-wide significance: two for total cholesterol (FN1 and SAMM50), two for HDL cholesterol (LOC100996634 and COPB1) and one for LDL cholesterol (LINC00324/CTC1/PFAS). The top meta-analysis signals were found to be enriched for SNPs associated with gene expression in a tissue-specific fashion, suggesting an enrichment of tissue-specific function in lipid-associated loci.
A Matrix Pencil Algorithm Based Multiband Iterative Fusion Imaging Method
Authors: Zou Yong Qiang , Gao Xun Zhang , Li Xiang , Liu Yong Xiang
Published: January 2016

Multiband signal fusion technique is a practicable and efficient way to improve the range resolution of ISAR image. The classical fusion method estimates the poles of each subband signal by the root-MUSIC method and some good results were get in several experiments. However, this method is fragile in noise for the proper poles could not easy to get in low signal to noise ratio (SNR). In order to eliminate the influence of noise, this paper propose a matrix pencil algorithm based method to estimate the multiband signal poles. And to deal with mutual incoherent between subband signals, the incoherent parameters (ICP) are predicted through the relation of corresponding poles of each subband. Then, an iterative algorithm which aimed to minimize the 2-norm of signal difference is introduced to reduce signal fusion error. Applications to simulate dada verify that the proposed method get better fusion results at low SNR.
Design and Fabrication of 3D printed Scaffolds with a Mechanical Strength Comparable to Cortical Bone to Repair Large Bone Defects
Authors: Roohani-Esfahani Seyed-Iman , Newman Peter , Zreiqat Hala
Published: January 2016

A challenge in regenerating large bone defects under load is to create scaffolds with large and interconnected pores while providing a compressive strength comparable to cortical bone (100–150 MPa). Here we design a novel hexagonal architecture for a glass-ceramic scaffold to fabricate an anisotropic, highly porous three dimensional scaffolds with a compressive strength of 110 MPa. Scaffolds with hexagonal design demonstrated a high fatigue resistance (1,000,000 cycles at 1–10 MPa compressive cyclic load), failure reliability and flexural strength (30 MPa) compared with those for conventional architecture. The obtained strength is 150 times greater than values reported for polymeric and composite scaffolds and 5 times greater than reported values for ceramic and glass scaffolds at similar porosity. These scaffolds open avenues for treatment of load bearing bone defects in orthopaedic, dental and maxillofacial applications.
Prediction and characterization of protein-protein interaction network in Bacillus licheniformis WX-02
Authors: Han Yi-Chao , Song Jia-Ming , Wang Long , Shu Cheng-Cheng , Guo Jing , Chen Ling-Ling
Published: January 2016

In this study, we constructed a protein-protein interaction (PPI) network of B. licheniformis strain WX-02 with interolog method and domain-based method, which contained 15,864 edges and 2,448 nodes. Although computationally predicted networks have relatively low coverage and high false-positive rate, our prediction was confirmed from three perspectives: local structural features, functional similarities and transcriptional correlations. Further analysis of the COG heat map showed that protein interactions in B. licheniformis WX-02 mainly occurred in the same functional categories. By incorporating the transcriptome data, we found that the topological properties of the PPI network were robust under normal and high salt conditions. In addition, 267 different protein complexes were identified and 117 poorly characterized proteins were annotated with certain functions based on the PPI network. Furthermore, the sub-network showed that a hub protein CcpA jointed directly or indirectly many proteins related to γ-PGA synthesis and regulation, such as PgsB, GltA, GltB, ProB, ProJ, YcgM and two signal transduction systems ComP-ComA and DegS-DegU. Thus, CcpA might play an important role in the regulation of γ-PGA synthesis. This study therefore will facilitate the understanding of the complex cellular behaviors and mechanisms of γ-PGA synthesis in B. licheniformis WX-02.
Below-ground interspecific competition for water in a rubber agroforestry system may enhance water utilization in plants
Authors: Wu Junen , Liu Wenjie , Chen Chunfeng
Published: January 2016

Rubber-based (Hevea brasiliensis) agroforestry systems are regarded as the best way to improve the sustainability of rubber monocultures, but few reports have examined water use in such systems. Accordingly, we tested whether interplanting facilitates water utilization of rubber trees using stable isotope (δD, δ18O and δ13C) methods and by measuring soil water content (SWC), shoot potential and leaf C and N concentrations in aHevea-Flemingiaagroforestry system in Xishuangbanna, southwestern China. We detected a big difference in the utilization of different soil layer water between both species in this agroforestry system, as evidenced by the opposite seasonal fluctuations in both δD and δ18O in stem water. However, similar predawn shoot potential of rubber trees at both sites demonstrating that the interplanted species did not affect the water requirements of rubber trees greatly. Rubber trees with higher δ13C and more stable physiological indexes in this agroforestry system showed higher water use efficiency (WUE) and tolerance ability and the SWC results suggested this agroforestry is conductive to water conservation. Our results clearly indicated that intercropping legume plants with rubber trees can benefit rubber trees own higher N supply, increase their WUE and better utilize soil water of each soil layer.
Factors Affecting Anti-Glycan IgG and IgM Repertoires in Human Serum
Authors: Muthana Saddam M. , Gildersleeve Jeffrey C.
Published: January 2016

Serum anti-glycan antibodies play important roles in many immune processes and are of particular interest as biomarkers for many diseases. Changes in anti-glycan antibodies can occur with the onset of disease or in response to stimuli such as pathogens and vaccination. Understanding relationships between anti-glycan antibody repertoires and genetic and environment factors is critical for basic research and clinical applications, but little information is available. In this study we evaluated the effects of age, race, gender and blood type on anti-glycan antibody profiles in the serum of 135 healthy subjects. As expected, IgG and IgM antibody signals to blood group antigens correlated strongly with blood type. Interestingly, antibodies to other non-ABH glycans, such as the alpha-Gal antigen, also correlated with blood type. A statistically significant decline in IgM signals with age was observed for many antibody subpopulations, but not for IgG. Moreover, statistically significant correlations between race and IgG levels to certain LacNAc-containing glycans were observed. The results have important implications for designing studies and interpreting results in the area of biomarker discovery and for the development of vaccines. The study also highlights the importance of collecting and reporting patient information that could affect serum anti-glycan antibody levels.
Preparation of Pd supported on La(Sr)-Mn-O Perovskite by microwave Irradiation Method and Its Catalytic Performances for the Methane Combustion
Authors: Wang Wei , Yuan Fulong , Niu Xiaoyu , Zhu Yujun
Published: January 2016

In this work, a series of palladium supported on the La0.8Sr0.2MnO3.15 perovskite catalysts (Pd/LSM-x) with different Pd loading were prepared by microwave irradiation processing plus incipient wetness impregnation method and characterized by XRD, TEM, H2-TPR and XPS. These catalysts were evaluated on the lean CH4 combustion. The results show that the Pd/LSM-x samples prepared by microwave irradiation processing possess relative higher surface areas than LSM catalyst. The addition of Pd to the LSM leads to the increase in the oxygen vacancy content and the enhancement in the mobility of lattice oxygen which play an important role on the methane combustion. The Pd/LSM-3 catalysts with 4.2wt% Pd loading exhibited the best performance for CH4 combustion that temperature for 10% and 90% of CH4 conversion is 315 and 520 °C.
Perfect and broadband acoustic absorption by critically coupled sub-wavelength resonators
Authors: Romero-García V. , Theocharis G. , Richoux O. , Merkel A. , Tournat V. , Pagneux V.
Published: January 2016

Perfect absorption is an interdisciplinary topic with a large number of applications, the challenge of which consists of broadening its inherently narrow frequency-band performance. We experimentally and analytically report perfect and broadband absorption for audible sound, by the mechanism of critical coupling, with a sub-wavelength multi-resonant scatterer (SMRS) made of a plate-resonator/closed waveguide structure. In order to introduce the role of the key parameters, we first present the case of a single resonant scatterer (SRS) made of a Helmholtz resonator/closed waveguide structure. In both cases the controlled balance between the energy leakage of the several resonances and the inherent losses of the system leads to perfect absorption peaks. In the case of the SMRS we show that systems with large inherent losses can be critically coupled using resonances with large leakage. In particular, we show that in the SMRS system, with a thickness of λ/12 and diameter of λ/7, several perfect absorption peaks overlap to produce absorption bigger than 93% for frequencies that extend over a factor of 2 in audible frequencies. The reported concepts and methodology provide guidelines for the design of broadband perfect absorbers which could contribute to solve the major issue of noise reduction.
The Epstein-Barr virus encoded LMP1 oncoprotein modulates cell adhesion via regulation of activin A/TGFβ and β1 integrin signalling
Authors: Morris Mhairi A. , Dawson Christopher W. , Laverick Louise , Davis Alexandra M. , Dudman Joe P. R. , Raveenthiraraj Sathuwarman , Ahmad Zeeshan , Yap Lee-Fah , Young Lawrence S.
Published: January 2016

Approximately 20% of global cancer incidence is causally linked to an infectious agent. Epstein-Barr virus (EBV) accounts for around 1% of all virus-associated cancers and is associated with nasopharyngeal carcinoma (NPC). Latent membrane protein 1 (LMP1), the major oncoprotein encoded by EBV, behaves as a constitutively active tumour necrosis factor (TNF) receptor activating a variety of signalling pathways, including the three classic MAPKs (ERK-MAPK, p38 MAPK and JNK/SAPK). The present study identifies novel signalling properties for this integral membrane protein via the induction and secretion of activin A and TGFβ1, which are both required for LMP1’s ability to induce the expression of the extracellular matrix protein, fibronectin. However, it is evident that LMP1 is unable to activate the classic Smad-dependent TGFβ signalling pathway, but rather elicits its effects through the non-Smad arm of TGFβ signalling. In addition, there is a requirement for JNK/SAPK signalling in LMP1-mediated fibronectin induction. LMP1 also induces the expression and activation of the major fibronectin receptor, α5β1 integrin, an effect that is accompanied by increased focal adhesion formation and turnover. Taken together, these findings support the putative role for LMP1 in the pathogenesis of NPC by contributing to the metastatic potential of epithelial cells.
Rspo1-activated signalling molecules are sufficient to induce ovarian differentiation in XY medaka (Oryzias latipes)
Authors: Zhou Linyan , Charkraborty Tapas , Zhou Qian , Mohapatra Sipra , Nagahama Yoshitaka , Zhang Yueguang
Published: January 2016

In contrast to our understanding of testicular differentiation, ovarian differentiation is less well understood in vertebrates. In mammals, R-spondin1 (Rspo1), an activator of Wnt/β-catenin signaling pathway, is located upstream of the female sex determination pathway. However, the functions of Rspo1 in ovarian differentiation remain unclear in non-mammalian species. In order to elucidate the detailed functions of Rspo/Wnt signaling pathway in fish sex determination/differentiation, the ectopic expression of the Rspo1 gene was performed in XY medaka (Oryzias latipes). The results obtained demonstrated that the gain of Rspo1 function induced femininity in XY fish. The overexpression of Rspo1 enhanced Wnt4b and β-catenin transcription and completely suppressed the expression of male-biased genes (Dmy, Gsdf, Sox9a2 and Dmrt1) as well as testicular differentiation. Gonadal reprograming of Rspo1-over-expressed-XY (Rspo1-OV-XY) fish, induced the production of female-biased genes (Cyp19a1a and Foxl2), estradiol-17β production and further female type secondary sexuality. Moreover, Rspo1-OV-XY females were fertile and produced successive generations. Promoter analyses showed that Rspo1 transcription was directly regulated by DM domain genes (Dmy, the sex-determining gene and Dmrt1) and remained unresponsive to Foxl2. Taken together, our results strongly suggest that Rspo1 is sufficient to activate ovarian development and plays a decisive role in the ovarian differentiation in medaka.
Temperature stable mid-infrared GaInAsSb/GaSb Vertical Cavity Surface Emitting Lasers (VCSELs)
Authors: Ikyo A. B. , Marko I. P. , Hild K. , Adams A. R. , Arafin S. , Amann M.-C. , Sweeney S. J.
Published: January 2016

GaInAsSb/GaSb based quantum well vertical cavity surface emitting lasers (VCSELs) operating in mid-infrared spectral range between 2 and 3 micrometres are of great importance for low cost gas monitoring applications. This paper discusses the efficiency and temperature sensitivity of the VCSELs emitting at 2.6 μm and the processes that must be controlled to provide temperature stable operation. We show that non-radiative Auger recombination dominates the threshold current and limits the device performance at room temperature. Critically, we demonstrate that the combined influence of non-radiative recombination and gain peak – cavity mode de-tuning determines the overall temperature sensitivity of the VCSELs. The results show that improved temperature stable operation around room temperature can only be achieved with a larger gain peak – cavity mode de-tuning, offsetting the significant effect of increasing non-radiative recombination with increasing temperature, a physical effect which must be accounted for in mid-infrared VCSEL design.
Molecular Combing of Single DNA Molecules on the 10 Megabase Scale
Authors: Kaykov Atanas , Taillefumier Thibaud , Bensimon Aaron , Nurse Paul
Published: January 2016

DNA combing allows the investigation of DNA replication on genomic single DNA molecules, but the lengths that can be analysed have been restricted to molecules of 200–500 kb. We have improved the DNA combing procedure so that DNA molecules can be analysed up to the length of entire chromosomes in fission yeast and up to 12 Mb fragments in human cells. Combing multi-Mb-scale DNA molecules revealed previously undetected origin clusters in fission yeast and shows that in human cells replication origins fire stochastically forming clusters of fired origins with an average size of 370 kb. We estimate that a single human cell forms around 3200 clusters at mid S-phase and fires approximately 100,000 origins to complete genome duplication. The procedure presented here will be adaptable to other organisms and experimental conditions.