bluuebunny/crossref_metadata_2025 huggingface dataset:
Amplification of USP13 drives ovarian cancer metabolism
Authors: Han Cecil , Yang Lifeng , Choi Hyun Ho , Baddour Joelle , Achreja Abhinav , Liu Yunhua , Li Yujing , Li Jiada , Wan Guohui , Huang Cheng , Ji Guang , Zhang Xinna , Nagrath Deepak , Lu Xiongbin
Published: November 2016

Dysregulated energetic metabolism has been recently identified as a hallmark of cancer. Although mutations in metabolic enzymes hardwire metabolism to tumourigenesis, they are relatively infrequent in ovarian cancer. More often, cancer metabolism is re-engineered by altered abundance and activity of the metabolic enzymes. Here we identify ubiquitin-specific peptidase 13 (USP13) as a master regulator that drives ovarian cancer metabolism. USP13 specifically deubiquitinates and thus upregulates ATP citrate lyase and oxoglutarate dehydrogenase, two key enzymes that determine mitochondrial respiration, glutaminolysis and fatty acid synthesis. The USP13 gene is co-amplified with PIK3CA in 29.3% of high-grade serous ovarian cancers and its overexpression is significantly associated with poor clinical outcome. Inhibiting USP13 remarkably suppresses ovarian tumour progression and sensitizes tumour cells to the treatment of PI3K/AKT inhibitor. Our results reveal an important metabolism-centric role of USP13, which may lead to potential therapeutics targeting USP13 in ovarian cancers.
Modulation of mRNA and lncRNA expression dynamics by the Set2–Rpd3S pathway
Authors: Kim Ji Hyun , Lee Bo Bae , Oh Young Mi , Zhu Chenchen , Steinmetz Lars M. , Lee Yookyeong , Kim Wan Kyu , Lee Sung Bae , Buratowski Stephen , Kim TaeSoo
Published: November 2016

H3K36 methylation by Set2 targets Rpd3S histone deacetylase to transcribed regions of mRNA genes, repressing internal cryptic promoters and slowing elongation. Here we explore the function of this pathway by analysing transcription in yeast undergoing a series of carbon source shifts. Approximately 80 mRNA genes show increased induction upon SET2 deletion. A majority of these promoters have overlapping lncRNA transcription that targets H3K36me3 and deacetylation by Rpd3S to the mRNA promoter. We previously reported a similar mechanism for H3K4me2-mediated repression via recruitment of the Set3C histone deacetylase. Here we show that the distance between an mRNA and overlapping lncRNA promoter determines whether Set2–Rpd3S or Set3C represses. This analysis also reveals many previously unreported cryptic ncRNAs induced by specific carbon sources, showing that cryptic promoters can be environmentally regulated. Therefore, in addition to repression of cryptic transcription and modulation of elongation, H3K36 methylation maintains optimal expression dynamics of many mRNAs and ncRNAs.
Selective suppression of antisense transcription by Set2-mediated H3K36 methylation
Authors: Venkatesh Swaminathan , Li Hua , Gogol Madelaine M. , Workman Jerry L.
Published: November 2016

Maintenance of a regular chromatin structure over the coding regions of genes occurs co-transcriptionally via the ‘chromatin resetting’ pathway. One of the central players in this pathway is the histone methyltransferase Set2. Here we show that the loss of Set2 in yeast, Saccharomyces cerevisiae, results in transcription initiation of antisense RNAs embedded within body of protein-coding genes. These RNAs are distinct from the previously identified non-coding RNAs and cover 11% of the yeast genome. These RNA species have been named Set2-repressed antisense transcripts (SRATs) since the co-transcriptional addition of the H3K36 methyl mark by Set2 over their start sites results in their suppression. Interestingly, loss of chromatin resetting factor Set2 or the subsequent production of SRATs does not affect the abundance of the sense transcripts. This difference in transcriptional outcomes of overlapping transcripts due to a strand-independent addition of H3K36 methylation is a key regulatory feature of interleaved transcriptomes.
Direct evidence for microbial-derived soil organic matter formation and its ecophysiological controls
Authors: Kallenbach Cynthia M. , Frey Serita D. , Grandy A. Stuart
Published: November 2016

Soil organic matter (SOM) and the carbon and nutrients therein drive fundamental submicron- to global-scale biogeochemical processes and influence carbon-climate feedbacks. Consensus is emerging that microbial materials are an important constituent of stable SOM, and new conceptual and quantitative SOM models are rapidly incorporating this view. However, direct evidence demonstrating that microbial residues account for the chemistry, stability and abundance of SOM is still lacking. Further, emerging models emphasize the stabilization of microbial-derived SOM by abiotic mechanisms, while the effects of microbial physiology on microbial residue production remain unclear. Here we provide the first direct evidence that soil microbes produce chemically diverse, stable SOM. We show that SOM accumulation is driven by distinct microbial communities more so than clay mineralogy, where microbial-derived SOM accumulation is greatest in soils with higher fungal abundances and more efficient microbial biomass production.
Wnt5a induces renal AQP2 expression by activating calcineurin signalling pathway
Authors: Ando Fumiaki , Sohara Eisei , Morimoto Tetsuji , Yui Naofumi , Nomura Naohiro , Kikuchi Eriko , Takahashi Daiei , Mori Takayasu , Vandewalle Alain , Rai Tatemitsu , Sasaki Sei , Kondo Yoshiaki , Uchida Shinichi
Published: November 2016

Heritable nephrogenic diabetes insipidus (NDI) is characterized by defective urine concentration mechanisms in the kidney, which are mainly caused by loss-of-function mutations in the vasopressin type 2 receptor. For the treatment of heritable NDI, novel strategies that bypass the defective vasopressin type 2 receptor are required to activate the aquaporin-2 (AQP2) water channel. Here we show that Wnt5a regulates AQP2 protein expression, phosphorylation and trafficking, suggesting that Wnt5a is an endogenous ligand that can regulate AQP2 without the activation of the classic vasopressin/cAMP signalling pathway. Wnt5a successfully increases the apical membrane localization of AQP2 and urine osmolality in an NDI mouse model. We also demonstrate that calcineurin is a key regulator of Wnt5a-induced AQP2 activation without affecting intracellular cAMP level and PKA activity. The importance of calcineurin is further confirmed with its activator, arachidonic acid, which shows vasopressin-like effects underlining that calcineurin activators may be potential therapeutic targets for heritable NDI.
Somatic increase of CCT8 mimics proteostasis of human pluripotent stem cells and extends C. elegans lifespan
Authors: Noormohammadi Alireza , Khodakarami Amirabbas , Gutierrez-Garcia Ricardo , Lee Hyun Ju , Koyuncu Seda , König Tim , Schindler Christina , Saez Isabel , Fatima Azra , Dieterich Christoph , Vilchez David
Published: November 2016

Human embryonic stem cells can replicate indefinitely while maintaining their undifferentiated state and, therefore, are immortal in culture. This capacity may demand avoidance of any imbalance in protein homeostasis (proteostasis) that would otherwise compromise stem cell identity. Here we show that human pluripotent stem cells exhibit enhanced assembly of the TRiC/CCT complex, a chaperonin that facilitates the folding of 10% of the proteome. We find that ectopic expression of a single subunit (CCT8) is sufficient to increase TRiC/CCT assembly. Moreover, increased TRiC/CCT complex is required to avoid aggregation of mutant Huntingtin protein. We further show that increased expression of CCT8 in somatic tissues extendsCaenorhabditis eleganslifespan in a TRiC/CCT-dependent manner. Ectopic expression of CCT8 also ameliorates the age-associated demise of proteostasis and corrects proteostatic deficiencies in worm models of Huntington’s disease. Our results suggest proteostasis is a common principle that links organismal longevity with hESC immortality.
FOXK1 interaction with FHL2 promotes proliferation, invasion and metastasis in colorectal cancer
Authors: Wu M , Wang J , Tang W , Zhan X , Li Y , Peng Y , Huang X , Bai Y , Zhao J , Li A , Chen C , Chen Y , Peng H , Ren Y , Li G , Liu S , Wang J
Published: November 2016

The transcriptional factor Forkhead box k1 (FOXK1) is a member of the FOX family. The abnormal expression of FOXK1 may have an important role in tumour development. Our previous studies showed that four-and-a-half LIM protein 2 (FHL2) is a critical inducer of the epithelial-to-mesenchymal transition (EMT) and invasion. However, the molecular mechanism by which FOXK1 synergizes with FHL2 tumour proliferation, EMT and metastasis is not well defined. We evaluated that messenger RNA (mRNA) and protein expression levels by quantitative RT–PCR, western blot, immunofluorescence and immunohistochemistry (IHC) assays. The migration and invasive abilities of colorectal cancer (CRC) cells were evaluated using short hairpin RNA (shRNA)-mediated inhibition in vitro and in vivo. We showed that FOXK1 expression was upregulated in CRC compared with matched normal tissues. FOXK1 physically interacts with FHL2 in CRC. Moreover, higher expression levels of the two proteins were significantly associated with differentiation, lymph node metastasis, AJCC stage and poorer prognosis. Furthermore, the overexpression of FOXK1 in CRC cells is associated with EMT, invasion and metastasis. However, the siRNA-mediated repression of FHL2 in FOXK1-overexpressing cells reversed EMT and both the proliferative and metastatic phenotypes in vitro and in vivo. These data identified that the co-expression of FOXK1 and FHL2 enhances cell proliferation and metastasis through the induction of EMT. Thus, FOXK1 and FHL2 may serve as putative targets in the combined therapy of CRC.
Combining Multiple Hypothesis Testing with Machine Learning Increases the Statistical Power of Genome-wide Association Studies
Authors: Mieth Bettina , Kloft Marius , Rodríguez Juan Antonio , Sonnenburg Sören , Vobruba Robin , Morcillo-Suárez Carlos , Farré Xavier , Marigorta Urko M. , Fehr Ernst , Dickhaus Thorsten , Blanchard Gilles , Schunk Daniel , Navarro Arcadi , Müller Klaus-Robert
Published: November 2016

The standard approach to the analysis of genome-wide association studies (GWAS) is based on testing each position in the genome individually for statistical significance of its association with the phenotype under investigation. To improve the analysis of GWAS, we propose a combination of machine learning and statistical testing that takes correlation structures within the set of SNPs under investigation in a mathematically well-controlled manner into account. The novel two-step algorithm, COMBI, first trains a support vector machine to determine a subset of candidate SNPs and then performs hypothesis tests for these SNPs together with an adequate threshold correction. Applying COMBI to data from a WTCCC study (2007) and measuring performance as replication by independent GWAS published within the 2008–2015 period, we show that our method outperforms ordinary raw p-value thresholding as well as other state-of-the-art methods. COMBI presents higher power and precision than the examined alternatives while yielding fewer false (i.e. non-replicated) and more true (i.e. replicated) discoveries when its results are validated on later GWAS studies. More than 80% of the discoveries made by COMBI upon WTCCC data have been validated by independent studies. Implementations of the COMBI method are available as a part of the GWASpi toolbox 2.0.
The Perfect Glass Paradigm: Disordered Hyperuniform Glasses Down to Absolute Zero
Authors: Zhang G. , Stillinger F. H. , Torquato S.
Published: November 2016

Rapid cooling of liquids below a certain temperature range can result in a transition to glassy states. The traditional understanding of glasses includes their thermodynamic metastability with respect to crystals. However, here we present specific examples of interactions that eliminate the possibilities of crystalline and quasicrystalline phases, while creating mechanically stable amorphous glasses down to absolute zero temperature. We show that this can be accomplished by introducing a new ideal state of matter called a “perfect glass”. A perfect glass represents a soft-interaction analog of the maximally random jammed (MRJ) packings of hard particles. These latter states can be regarded as the epitome of a glass since they are out of equilibrium, maximally disordered, hyperuniform, mechanically rigid with infinite bulk and shear moduli, and can never crystallize due to configuration-space trapping. Our model perfect glass utilizes two-, three-, and four-body soft interactions while simultaneously retaining the salient attributes of the MRJ state. These models constitute a theoretical proof of concept for perfect glasses and broaden our fundamental understanding of glass physics. A novel feature of equilibrium systems of identical particles interacting with the perfect-glass potential at positive temperature is that they have a non-relativistic speed of sound that is infinite.
Vectorized magnetometer for space applications using electrical readout of atomic scale defects in silicon carbide
Authors: Cochrane Corey J. , Blacksberg Jordana , Anders Mark A. , Lenahan Patrick M.
Published: November 2016

Magnetometers are essential for scientific investigation of planetary bodies and are therefore ubiquitous on missions in space. Fluxgate and optically pumped atomic gas based magnetometers are typically flown because of their proven performance, reliability, and ability to adhere to the strict requirements associated with space missions. However, their complexity, size, and cost prevent their applicability in smaller missions involving cubesats. Conventional solid-state based magnetometers pose a viable solution, though many are prone to radiation damage and plagued with temperature instabilities. In this work, we report on the development of a new self-calibrating, solid-state based magnetometer which measures magnetic field induced changes in current within a SiC pn junction caused by the interaction of external magnetic fields with the atomic scale defects intrinsic to the semiconductor. Unlike heritage designs, the magnetometer does not require inductive sensing elements, high frequency radio, and/or optical circuitry and can be made significantly more compact and lightweight, thus enabling missions leveraging swarms of cubesats capable of science returns not possible with a single large-scale satellite. Additionally, the robustness of the SiC semiconductor allows for operation in extreme conditions such as the hot Venusian surface and the high radiation environment of the Jovian system.
SARS-CoV fusion peptides induce membrane surface ordering and curvature
Authors: Basso Luis G. M. , Vicente Eduardo F. , Crusca Edson , Cilli Eduardo M. , Costa-Filho Antonio J.
Published: November 2016

Viral membrane fusion is an orchestrated process triggered by membrane-anchored viral fusion glycoproteins. The S2 subunit of the spike glycoprotein from severe acute respiratory syndrome (SARS) coronavirus (CoV) contains internal domains called fusion peptides (FP) that play essential roles in virus entry. Although membrane fusion has been broadly studied, there are still major gaps in the molecular details of lipid rearrangements in the bilayer during fusion peptide-membrane interactions. Here we employed differential scanning calorimetry (DSC) and electron spin resonance (ESR) to gather information on the membrane fusion mechanism promoted by two putative SARS FPs. DSC data showed the peptides strongly perturb the structural integrity of anionic vesicles and support the hypothesis that the peptides generate opposing curvature stresses on phosphatidylethanolamine membranes. ESR showed that both FPs increase lipid packing and head group ordering as well as reduce the intramembrane water content for anionic membranes. Therefore, bending moment in the bilayer could be generated, promoting negative curvature. The significance of the ordering effect, membrane dehydration, changes in the curvature properties and the possible role of negatively charged phospholipids in helping to overcome the high kinetic barrier involved in the different stages of the SARS-CoV-mediated membrane fusion are discussed.
Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis
Authors: Branton W. G. , Lu J. Q. , Surette M. G. , Holt R. A. , Lind J. , Laman J. D. , Power C.
Published: November 2016

Microbial communities reside in healthy tissues but are often disrupted during disease. Bacterial genomes and proteins are detected in brains from humans, nonhuman primates, rodents and other species in the absence of neurological disease. We investigated the composition and abundance of microbiota in frozen and fixed autopsied brain samples from patients with multiple sclerosis (MS) and age- and sex-matched nonMS patients as controls, using neuropathological, molecular and bioinformatics tools. 16s rRNA sequencing revealed Proteobacteria to be the dominant phylum with restricted diversity in cerebral white matter (WM) from MS compared to nonMS patients. Both clinical groups displayed 1,200–1,400 bacterial genomes/cm3 and low bacterial rRNA:rDNA ratios in WM. RNAseq analyses showed a predominance of Proteobacteria in progressive MS patients’ WM, associated with increased inflammatory gene expression, relative to a broader range of bacterial phyla in relapsing-remitting MS patients’ WM. Although bacterial peptidoglycan (PGN) and RNA polymerase beta subunit immunoreactivities were observed in all patients, PGN immunodetection was correlated with demyelination and neuroinflammation in MS brains. Principal component analysis revealed that demyelination, PGN and inflammatory gene expression accounted for 86% of the observed variance. Thus, inflammatory demyelination is linked to an organ-specific dysbiosis in MS that could contribute to underlying disease mechanisms.
A novel bio-engineering approach to generate an eminent surface-functionalized template for selective detection of female sex pheromone of Helicoverpa armigera
Authors: Moitra Parikshit , Bhagat Deepa , Pratap Rudra , Bhattacharya Santanu
Published: November 2016

Plant pests exert serious effects on food production due to which the global crop yields are reduced by ~20–40 percent per year. Hence to meet the world’s food needs, loses of food due to crop pests must be reduced. Herein the silicon dioxide based MEMS devices are covalently functionalized for robust and efficient optical sensing of the female sex pheromones of the pests like Helicoverpa armigera for the first time in literature. The functionalized devices are also capable of selectively measuring the concentration of this pheromone at femtogram level which is much below the concentration of pheromone at the time of pest infestation in an agricultural field. Experiments are also performed in a confined region in the presence of male and female pests and tomato plants which directly mimics the real environmental conditions. Again the reversible use and absolutely trouble free transportation of these pheromone nanosensors heightens their potentials for commercial use. Overall, a novel and unique approach for the selective and reversible sensing of female sex pheromones of certain hazardous pests is reported herein which may be efficiently and economically carried forward from the research laboratory to the agricultural field.
Evolution of cooperation under indirect reciprocity and arbitrary exploration rates
Authors: Santos Fernando P. , Pacheco Jorge M. , Santos Francisco C.
Published: November 2016

Cooperation has been recognized as an evolutionary puzzle since Darwin, and remains identified as one of the biggest challenges of the XXIst century. Indirect Reciprocity (IR), a key mechanism that humans employ to cooperate with each other, establishes that individual behaviour depends on reputations, which in turn evolve depending on social norms that classify behaviours as good or bad. While it is well known that different social norms give rise to distinct cooperation levels, it remains unclear how the performance of each norm is influenced by the random exploration of new behaviours, often a key component of social dynamics where a plethora of stimuli may compel individuals to deviate from pre-defined behaviours. Here we study, for the first time, the impact of varying degrees of exploration rates – the likelihood of spontaneously adopting another strategy, akin to a mutation probability in evolutionary dynamics – in the emergence of cooperation under IR. We show that high exploration rates may either improve or harm cooperation, depending on the underlying social norm at work. Regarding some of the most popular social norms studied to date, we find that cooperation under Simple-standing and Image-score is enhanced by high exploration rates, whereas the opposite occurs for Stern-judging and Shunning.
Narrowing the spread in CMIP5 model projections of air-sea CO2 fluxes
Authors: Wang Lei , Huang Jianbin , Luo Yong , Zhao Zongci
Published: November 2016

Large spread appears in the projection of air-sea CO2 fluxes using the latest simulations from the Coupled Model Intercomparison Project Phase 5 (CMIP5). Here, two methods are applied to narrow this spread in 13 CMIP5 models. One method involves model selection based on the ability of models to reproduce the observed air-sea CO2 fluxes from 1980 to 2005. The other method involves constrained estimation based on the strong relationship between the historical and future air-sea CO2 fluxes. The estimated spread of the projected air-sea CO2 fluxes is effectively reduced by using these two approaches. These two approaches also show great agreement in the global ocean and three regional oceans of the equatorial Pacific Ocean, the North Atlantic Ocean and the Southern Ocean, including the average state and evolution characteristics. Based on the projections of the two approaches, the global ocean carbon uptake will increase in the first half of the 21st century then remain relatively stable and is projected to be 3.68–4.57 PgC/yr at the end of 21st century. The projections indicate that the increase in the CO2 uptake by the oceans will cease at the year of approximately 2070.
Evaluation of the Effects of Conjunctivochalasis Excision on Tear Stability and Contrast Sensitivity
Authors: Qiu Weiqiang , Zhang Mingzhou , Xu Ting , Liu Ziyuan , Lv Huibin , Wang Wei , Li Xuemin
Published: November 2016

Conjunctivochalasis (CCh) disrupts tear flow and damages tear film stability. This study sought to evaluate the tear stability and contrast sensitivity of patients with CCh on whom CCh excision was performed. The study included 39 eyes from 39 patients; all patients had eyes with grade 2 or 3 CCh, underwent CCh excision, and were evaluated before and three months after the surgery. The evaluated variables included the ocular surface disease index (OSDI), the tear break-up time (TBUT), corneal fluorescein staining, corneal surface irregularity, Schirmer’s I test, the tear meniscus area (TMA), and contrast sensitivity. A follow-up of three months was achieved in 36 eyes for 36 patients. All parameters improved significantly after surgery (p < 0.05), except Schirmer’s I test, thus suggesting that CCh excision is an effective method for reconstructing the lower tear meniscus and improving both tear film stability and corneal surface irregularity. The results further demonstrated a simultaneous increase in contrast sensitivity after surgery.
Isotope effect in superconducting n-doped SrTiO3
Authors: Stucky A. , Scheerer G. W. , Ren Z. , Jaccard D. , Poumirol J.-M. , Barreteau C. , Giannini E. , van der Marel D.
Published: November 2016

We report the influence on the superconducting critical temperature Tc in doped SrTiO3 of the substitution of the natural 16O atoms by the heavier isotope 18O. We observe that for a wide range of doping this substitution causes a strong (~50%) enhancement of Tc. Also the magnetic critical field Hc2 is increased by a factor ~2. Such a strong impact on Tc and Hc2, with a sign opposite to conventional superconductors, is unprecedented. The observed effect could be the consequence of strong coupling of the doped electrons to lattice vibrations (phonons), a notion which finds support in numerous optical and photo-emission studies. The unusually large size of the observed isotope effect supports a recent model for superconductivity in these materials based on strong coupling to the ferroelectric soft modes of SrTiO3.
Autophagy is required for PDAC glutamine metabolism
Authors: Seo Ju-Won , Choi Jungwon , Lee So-Yeon , Sung Suhyun , Yoo Hyun Ju , Kang Min-Ji , Cheong Heesun , Son Jaekyoung
Published: November 2016

Macroautophagy (autophagy) is believed to maintain energy homeostasis by degrading unnecessary cellular components and molecules. Its implication in regulating cancer metabolism recently started to be uncovered. However, the precise roles of autophagy in cancer metabolism are still unclear. Here, we show that autophagy plays a critical role in glutamine metabolism, which is required for tumor survival. Pancreatic ductal adenocarcinoma (PDAC) cells require both autophagy and typical glutamine transporters to maintain intracellular glutamine levels. Glutamine deprivation, but not that of glucose, led to the activation of macropinocytosis-associated autophagy through TFEB induction and translocation into the nucleus. In contrast, glutamine uptake increased as a compensatory response to decreased intracellular glutamine levels upon autophagy inhibition. Moreover, autophagy inhibition and glutamine deprivation did not induce cell death, while glutamine deprivation dramatically activated apoptotic cell death upon autophagy inhibition. Interestingly, the addition of α-ketoglutarate significantly rescued the apoptotic cell death caused by the combination of the inhibition of autophagy with glutamine deprivation. Our data suggest that macropinocytosis-associated autophagy is a critical process providing glutamine for anaplerosis of the TCA cycle in PDAC. Thus, targeting both autophagy and glutamine metabolism to completely block glutamine supply may provide new therapeutic approaches to treat refractory tumors.
Transition steps in peroxide reduction and a molecular switch for peroxide robustness of prokaryotic peroxiredoxins
Authors: Kamariah Neelagandan , Sek Mun Foong , Eisenhaber Birgit , Eisenhaber Frank , Grüber Gerhard
Published: November 2016

In addition to their antioxidant function, the eukaryotic peroxiredoxins (Prxs) facilitate peroxide-mediated signaling by undergoing controlled inactivation by peroxide-driven over-oxidation. In general, the bacterial enzyme lacks this controlled inactivation mechanism, making it more resistant to high H2O2 concentrations. During peroxide reduction, the active site alternates between reduced, fully folded (FF), and oxidized, locally unfolded (LU) conformations. Here we present novel insights into the divergence of bacterial and human Prxs in robustness and sensitivity to inactivation, respectively. Structural details provide new insights into sub-steps during the catalysis of peroxide reduction, enabling the transition from an FF to a LU conformation. Complementary to mutational and enzymatic results, these data unravel the essential role of the C-terminal tail of bacterial Prxs to act as a molecular switch, mediating the transition from an FF to a LU state. In addition, we propose that the C-terminal tail has influence on the propensity of the disulphide bond formation, indicating that as a consequence on the robustness and sensitivity to over-oxidation. Finally, a physical linkage between the catalytic site, the C-terminal tail and the oligomer interface is described.
Lévy random walks on multiplex networks
Authors: Guo Quantong , Cozzo Emanuele , Zheng Zhiming , Moreno Yamir
Published: November 2016

Random walks constitute a fundamental mechanism for many dynamics taking place on complex networks. Besides, as a more realistic description of our society, multiplex networks have been receiving a growing interest, as well as the dynamical processes that occur on top of them. Here, inspired by one specific model of random walks that seems to be ubiquitous across many scientific fields, the Lévy flight, we study a new navigation strategy on top of multiplex networks. Capitalizing on spectral graph and stochastic matrix theories, we derive analytical expressions for the mean first passage time and the average time to reach a node on these networks. Moreover, we also explore the efficiency of Lévy random walks, which we found to be very different as compared to the single layer scenario, accounting for the structure and dynamics inherent to the multiplex network. Finally, by comparing with some other important random walk processes defined on multiplex networks, we find that in some region of the parameters, a Lévy random walk is the most efficient strategy. Our results give us a deeper understanding of Lévy random walks and show the importance of considering the topological structure of multiplex networks when trying to find efficient navigation strategies.
Droplet Merging on a Lab-on-a-Chip Platform by Uniform Magnetic Fields
Authors: Varma V. B. , Ray A. , Wang Z. M. , Wang Z. P. , Ramanujan R. V.
Published: November 2016

Droplet microfluidics offers a range of Lab-on-a-chip (LoC) applications. However, wireless and programmable manipulation of such droplets is a challenge. We address this challenge by experimental and modelling studies of uniform magnetic field induced merging of ferrofluid based droplets. Control of droplet velocity and merging was achieved through uniform magnetic field and flow rate ratio. Conditions for droplet merging with respect to droplet velocity were studied. Merging and mixing of colour dye + magnetite composite droplets was demonstrated. Our experimental and numerical results are in good agreement. These studies are useful for wireless and programmable droplet merging as well as mixing relevant to biosensing, bioassay, microfluidic-based synthesis, reaction kinetics, and magnetochemistry.
Temporally-coherent terawatt attosecond XFEL synchronized with a few cycle laser
Authors: Kumar Sandeep , Parc Yong Woon , Landsman Alexandra S. , Kim Dong Eon
Published: November 2016

Attosecond metrology using laser-based high-order harmonics has been significantly advanced and applied to various studies of electron dynamics in atoms, molecules and solids. Laser-based high-order harmonics have a limitation of low power and photon energies. There is, however, a great demand for even higher power and photon energy. Here, we propose a scheme for a terawatt attosecond (TW-as) X-ray pulse in X-ray free-electron laser controlled by a few cycle IR pulse, where one dominant current spike in an electron bunch is used repeatedly to amplify a seeded radiation to a terawatt level. This scheme is relatively simple, compact, straightforward, and also produces a temporally and spectrally clean pulse. The viability of this scheme is demonstrated in simulations using Pohang accelerator laboratory (PAL)-XFEL beam parameters.
Scattering of nanowire surface plasmons coupled to quantum dots with azimuthal angle difference
Authors: Kuo Po-Chen , Chen Guang-Yin , Chen Yueh-Nan
Published: November 2016

Coherent scatterings of surface plasmons coupled to quantun dots have attracted great attention in plasmonics. Recently, an experiment has shown that the quantum dots located nearby a nanowire can be separated not only in distance, but also an angle ϕ along the cylindrical direction. Here, by using the real-space Hamiltonian and the transfer matrix method, we analytically obtain the transmission/reflection spectra of nanowire surface plasmons coupled to quantum dots with an azimuthal angle difference. We find that the scattering spectra can show completely different features due to different positions and azimuthal angles of the quantum dots. When additionally coupling a cavity to the dots, we obtain the Fano-like line shape in the transmission and reflection spectra due to the interference between the localized and delocalized modes.
Novel recombinant papillomavirus genomes expressing selectable genes
Authors: Van Doorslaer Koenraad , Porter Samuel , McKinney Caleb , Stepp Wesley H. , McBride Alison A.
Published: November 2016

Papillomaviruses infect and replicate in keratinocytes, but viral proteins are initially expressed at low levels and there is no effective and quantitative method to determine the efficiency of infection on a cell-to-cell basis. Here we describe human papillomavirus (HPV) genomes that express marker proteins (antibiotic resistance genes and Green Fluorescent Protein), and can be used to elucidate early stages in HPV infection of primary keratinocytes. To generate these recombinant genomes, the late region of the oncogenic HPV18 genome was replaced by CpG free marker genes. Insertion of these exogenous genes did not affect early replication, and had only minimal effects on early viral transcription. When introduced into primary keratinocytes, the recombinant marker genomes gave rise to drug-resistant keratinocyte colonies and cell lines, which maintained the extrachromosomal recombinant genome long-term. Furthermore, the HPV18 “marker” genomes could be packaged into viral particles (quasivirions) and used to infect primary human keratinocytes in culture. This resulted in the outgrowth of drug-resistant keratinocyte colonies containing replicating HPV18 genomes. In summary, we describe HPV18 marker genomes that can be used to quantitatively investigate many aspects of the viral life cycle.
Phenology and Growth dynamics of Avicennia marina in the Central Red Sea
Authors: Almahasheer Hanan , Duarte Carlos M. , Irigoien Xabier
Published: November 2016

The formation of nodes, stem elongation and the phenology of stunted Avicennia marina was examined in the Central Red Sea, where Avicennia marina is at the limit of its distribution range and submitted to extremely arid conditions with salinity above 38 psu and water temperature as high as 35° C. The annual node production was rather uniform among locations averaging 9.59 node y−1, which resulted in a plastocron interval, the interval in between production of two consecutive nodes along a stem, of 38 days. However, the internodal length varied significantly between locations, resulting in growth differences possibly reflecting the environmental conditions of locations. The reproductive cycle lasted for approximately 12 months, and was characterized by peak flowering and propagule development in November and January. These phenological observations provide a starting point for research and restoration programs on the ecology of mangroves in the Central Red Sea, while the plastochrone index reported here would allow calculations of the growth and production of the species from simple morphological measurements.
New Genome-Wide Algorithm Identifies Novel In-Vivo Expressed Mycobacterium Tuberculosis Antigens Inducing Human T-Cell Responses with Classical and Unconventional Cytokine Profiles
Authors: Coppola Mariateresa , van Meijgaarden Krista E. , Franken Kees L. M. C. , Commandeur Susanna , Dolganov Gregory , Kramnik Igor , Schoolnik Gary K. , Comas Inaki , Lund Ole , Prins Corine , van den Eeden Susan J. F. , Korsvold Gro E. , Oftung Fredrik , Geluk Annemieke , Ottenhoff Tom H. M.
Published: November 2016

New strategies are needed to develop better tools to control TB, including identification of novel antigens for vaccination. Such Mtb antigens must be expressed during Mtb infection in the major target organ, the lung, and must be capable of eliciting human immune responses. Using genome-wide transcriptomics of Mtb infected lungs we developed data sets and methods to identify IVE-TB (in-vivo expressed Mtb) antigens expressed in the lung. Quantitative expression analysis of 2,068 Mtb genes from the predicted first operons identified the most upregulated IVE-TB genes during in-vivo pulmonary infection. By further analysing high-level conservation among whole-genome sequenced Mtb-complex strains (n = 219) and algorithms predicting HLA-class-Ia and II presented epitopes, we selected the most promising IVE-TB candidate antigens. Several of these were recognized by T-cells from in-vitro Mtb-PPD and ESAT6/CFP10-positive donors by proliferation and multi-cytokine production. This was validated in an independent cohort of latently Mtb-infected individuals. Significant T-cell responses were observed in the absence of IFN-γ-production. Collectively, the results underscore the power of our novel antigen discovery approach in identifying Mtb antigens, including those that induce unconventional T-cell responses, which may provide important novel tools for TB vaccination and biomarker profiling. Our generic approach is applicable to other infectious diseases.
A peptidoglycan recognition protein acts in whitefly (Bemisia tabaci) immunity and involves in Begomovirus acquisition
Authors: Wang Zhi-Zhi , Shi Min , Huang Yi-Cun , Wang Xiao-Wei , Stanley David , Chen Xue-Xin
Published: November 2016

Peptidoglycan recognition proteins (PGRPs) are multifunctional pattern recognition proteins. Here, we report that a PGRP gene,BtPGRP, encodes a PGRP from the whiteflyBemisia tabaci(MEAM1) that binds and kills bacteriain vitro. We analyzedBtPGRPtranscriptional profiling, and the distribution of the cognate protein within the midgut. Fungal infection and wasp parasitization induced expression ofBtPGRP. SilencingBtPGRPwith artificial media amended with dsRNA led to reduced expression of a gene encoding an antimicrobial peptide,B. tabaci c-type lysozyme. Begomovirusinfection also led to increased expression ofBtPGRP. We propose that BtPGRP has a potentialTomato yellow leaf curl virus(TYLCV) binding site because we detectedin vitrointeraction between BtPGRP and TYLCV by immunocapture PCR, and recorded the co-localization of TYLCV and BtPGRP in midguts. This work addresses a visible gap in understanding whitefly immunity and provides insight into how the whitefly immunity acts in complex mechanisms ofBegomovirustransmission among plants.
Functional and Structural Signatures of the Anterior Insula are associated with Risk-taking Tendency of Analgesic Decision-making
Authors: Lin Chia-Shu , Lin Hsiao-Han , Wu Shih-Yun
Published: November 2016

In a medical context, decision-making is associated with complicated assessment of gains, losses and uncertainty of outcomes. We here provide novel evidence about the brain mechanisms underlying decision-making of analgesic treatment. Thirty-six healthy participants were recruited and completed the Analgesic Decision-making Task (ADT), which quantified individual tendency of risk-taking (RPI), as the frequency of choosing a riskier option to relieve pain. All the participants received resting-state (rs) functional magnetic resonance imaging (MRI) and structural MRI. On rs-functional connectome, degree centrality (DC) of the bilateral anterior insula (aINS) was positively correlated with the RPI. The functional connectivity between the aINS, the nucleus accumbens and multiple brain regions, predominantly the medial frontal cortex, was positively correlated with the RPI. On structural signatures, the RPI was positively correlated with grey matter volume at the right aINS, and such an association was mediated by DC of the left aINS. Regression analyses revealed that both DC of the left aINS and participants’ imagined pain relief, as the utility of pain reduction, could predict the individual RPI. The findings suggest that the functional and structural brain signature of the aINS is associated with the individual differences of risk-taking tendency in the context of analgesic decision-making.
Improving Estimation of Fiber Orientations in Diffusion MRI Using Inter-Subject Information Sharing
Authors: Chen Geng , Zhang Pei , Li Ke , Wee Chong-Yaw , Wu Yafeng , Shen Dinggang , Yap Pew-Thian
Published: November 2016

Diffusion magnetic resonance imaging is widely used to investigate diffusion patterns of water molecules in the human brain. It provides information that is useful for tracing axonal bundles and inferring brain connectivity. Diffusion axonal tracing, namely tractography, relies on local directional information provided by the orientation distribution functions (ODFs) estimated at each voxel. To accurately estimate ODFs, data of good signal-to-noise ratio and sufficient angular samples are desired. This is however not always available in practice. In this paper, we propose to improve ODF estimation by using inter-subject image correlation. Specifically, we demonstrate that diffusion-weighted images acquired from different subjects can be transformed to the space of a target subject to drastically increase the number of angular samples to improve ODF estimation. This is largely due to the incoherence of the angular samples generated when the diffusion signals are reoriented and warped to the target space. To reorient the diffusion signals, we propose a new spatial normalization method that directly acts on diffusion signals using local affine transforms. Experiments on both synthetic data and real data show that our method can reduce noise-induced artifacts, such as spurious ODF peaks, and yield more coherent orientations.
Autologous temporomandibular joint reconstruction independent of exogenous additives: a proof-of-concept study for guided self-generation
Authors: Wei Jiao , Herrler Tanja , Han Dong , Liu Kai , Huang Rulin , Guba Markus , Dai Chuanchang , Li Qingfeng
Published: November 2016

Joint defects are complex and difficult to reconstruct. By exploiting the body’s own regenerative capacity, we aimed to individually generate anatomically precise neo-tissue constructs for autologous joint reconstruction without using any exogenous additives. In a goat model, CT scans of the mandibular condyle including articular surface and a large portion of the ascending ramus were processed using computer-aided design and manufacturing. A corresponding hydroxylapatite negative mold was printed in 3D and temporarily embedded into the transition zone of costal periosteum and perichondrium. A demineralized bone matrix scaffold implanted on the contralateral side served as control. Neo-tissue constructs obtained by guided self-generation exhibited accurate configuration, robust vascularization, biomechanical stability, and function. After autologous replacement surgery, the constructs showed stable results with similar anatomical, histological, and functional findings compared to native controls. Further studies are required to assess long-term outcome and possible extensions to other further applications. The absence of exogenous cells, growth factors, and scaffolds may facilitate clinical translation of this approach.
Variations in abundance, diversity and community composition of airborne fungi in swine houses across seasons
Authors: Kumari Priyanka , Woo Cheolwoon , Yamamoto Naomichi , Choi Hong-Lim
Published: November 2016

We examined the abundance, diversity and community composition of airborne fungi in swine houses during winter and summer seasons by using quantitative PCR and Illumina HiSeq sequencing of ITS1 region. The abundance of airborne fungi varied significantly only between seasons, while fungal diversity varied significantly both within and between seasons, with both abundance and diversity peaked in winter. The fungal OTU composition was largely structured by the swine house unit and season as well as by their interactions. Of the measured microclimate variables, relative humidity, particulate matters (PMs), ammonia, and stocking density were significantly correlated with fungal OTU composition. The variation in beta diversity was higher within swine houses during summer, which indicates that the airborne fungal community composition was more heterogeneous in summer compared to winter. We also identified several potential allergen/pathogen related fungal genera in swine houses. The total relative abundance of potential allergen/pathogen related fungal genera varied between swine houses in both seasons, and showed positive correlation with PM2.5. Overall, our findings show that the abundance, diversity and composition of airborne fungi are highly variable in swine houses and to a large extent structured by indoor microclimate variables of swine houses.
Negative feedback regulation of ABA biosynthesis in peanut (Arachis hypogaea): a transcription factor complex inhibits AhNCED1 expression during water stress
Authors: Liu Shuai , Li Meijuan , Su Liangchen , Ge Kui , Li Limei , Li Xiaoyun , Liu Xu , Li Ling
Published: November 2016

Abscisic acid (ABA), a key plant stress-signaling hormone, is produced in response to drought and counteracts the effects of this stress. The accumulation of ABA is controlled by the enzyme 9-cis-epoxycarotenoid dioxygenase (NCED). In Arabidopsis, NCED3 is regulated by a positive feedback mechanism by ABA. In this study in peanut (Arachis hypogaea), we demonstrate that ABA biosynthesis is also controlled by negative feedback regulation, mediated by the inhibitory effect on AhNCED1 transcription of a protein complex between transcription factors AhNAC2 and AhAREB1. AhNCED1 was significantly down-regulated after PEG treatment for 10 h, at which time ABA content reached a peak. A ChIP-qPCR assay confirmed AhAREB1 and AhNAC2 binding to the AhNCED1 promoter in response to ABA. Moreover, the interaction between AhAREB1 and AhNAC2, and a transient expression assay showed that the protein complex could negatively regulate the expression of AhNCED1. The results also demonstrated that AhAREB1 was the key factor in AhNCED1 feedback regulation, while AhNAC2 played a subsidiary role. ABA reduced the rate of AhAREB1 degradation and enhanced both the synthesis and degradation rate of the AhNAC2 protein. In summary, the AhAREB1/AhNAC2 protein complex functions as a negative feedback regulator of drought-induced ABA biosynthesis in peanut.
Quorum Regulated Resistance of Vibrio cholerae against Environmental Bacteriophages
Authors: Hoque M. Mozammel , Naser Iftekhar Bin , Bari S. M. Nayeemul , Zhu Jun , Mekalanos John J. , Faruque Shah M.
Published: November 2016

Predation by bacteriophages can significantly influence the population structure of bacterial communities. Vibrio cholerae the causative agent of cholera epidemics interacts with numerous phages in the aquatic ecosystem, and in the intestine of cholera patients. Seasonal epidemics of cholera reportedly collapse due to predation of the pathogen by phages. However, it is not clear how sufficient number of the bacteria survive to seed the environment in the subsequent epidemic season. We found that bacterial cell density-dependent gene expression termed “quorum sensing” which is regulated by signal molecules called autoinducers (AIs) can protect V. cholerae against predatory phages. V. cholerae mutant strains carrying inactivated AI synthase genes were significantly more susceptible to multiple phages compared to the parent bacteria. Likewise when mixed cultures of phage and bacteria were supplemented with exogenous autoinducers CAI-1 or AI-2 produced by recombinant strains carrying cloned AI synthase genes, increased survival of V. cholerae and a decrease in phage titer was observed. Mutational analyses suggested that the observed effects of autoinducers are mediated in part through the quorum sensing-dependent production of haemaglutinin protease, and partly through downregulation of phage receptors. These results have implication in developing strategies for phage mediated control of cholera.