bluuebunny/crossref_metadata_2025 huggingface dataset:
The power of a critical heat engine
Authors: Campisi Michele , Fazio Rosario
Published: June 2016

Since its inception about two centuries ago thermodynamics has sparkled continuous interest and fundamental questions. According to the second law no heat engine can have an efficiency larger than Carnot’s efficiency. The latter can be achieved by the Carnot engine, which however ideally operates in infinite time, hence delivers null power. A currently open question is whether the Carnot efficiency can be achieved at finite power. Most of the previous works addressed this question within the Onsager matrix formalism of linear response theory. Here we pursue a different route based on finite-size-scaling theory. We focus on quantum Otto engines and show that when the working substance is at the verge of a second order phase transition diverging energy fluctuations can enable approaching the Carnot point without sacrificing power. The rate of such approach is dictated by the critical indices, thus showing the universal character of our analysis.
Oncogenic PIK3CA mutations reprogram glutamine metabolism in colorectal cancer
Authors: Hao Yujun , Samuels Yardena , Li Qingling , Krokowski Dawid , Guan Bo-Jhih , Wang Chao , Jin Zhicheng , Dong Bohan , Cao Bo , Feng Xiujing , Xiang Min , Xu Claire , Fink Stephen , Meropol Neal J. , Xu Yan , Conlon Ronald A. , Markowitz Sanford , Kinzler Kenneth W. , Velculescu Victor E. , Brunengraber Henri , Willis Joseph E. , LaFramboise Thomas , Hatzoglou Maria , Zhang Guo-Fang , Vogelstein Bert , Wang Zhenghe
Published: June 2016

Cancer cells often require glutamine for growth, thereby distinguishing them from most normal cells. Here we show that PIK3CA mutations reprogram glutamine metabolism by upregulating glutamate pyruvate transaminase 2 (GPT2) in colorectal cancer (CRC) cells, making them more dependent on glutamine. Compared with isogenic wild-type (WT) cells, PIK3CA mutant CRCs convert substantially more glutamine to α-ketoglutarate to replenish the tricarboxylic acid cycle and generate ATP. Mutant p110α upregulates GPT2 gene expression through an AKT-independent, PDK1–RSK2–ATF4 signalling axis. Moreover, aminooxyacetate, which inhibits the enzymatic activity of aminotransferases including GPT2, suppresses xenograft tumour growth of CRCs with PIK3CA mutations, but not with WT PIK3CA. Together, these data establish oncogenic PIK3CA mutations as a cause of glutamine dependency in CRCs and suggest that targeting glutamine metabolism may be an effective approach to treat CRC patients harbouring PIK3CA mutations.
Structural insights of ZIP4 extracellular domain critical for optimal zinc transport
Authors: Zhang Tuo , Sui Dexin , Hu Jian
Published: June 2016

The ZIP zinc transporter family is responsible for zinc uptake from the extracellular milieu or intracellular vesicles. The LIV-1 subfamily, containing nine out of the 14 human ZIP proteins, is featured with a large extracellular domain (ECD). The critical role of the ECD is manifested by disease-causing mutations on ZIP4, a representative LIV-1 protein. Here we report the first crystal structure of a mammalian ZIP4-ECD, which reveals two structurally independent subdomains and an unprecedented dimer centred at the signature PAL motif. Structure-guided mutagenesis, cell-based zinc uptake assays and mapping of the disease-causing mutations indicate that the two subdomains play pivotal but distinct roles and that the bridging region connecting them is particularly important for ZIP4 function. These findings lead to working hypotheses on how ZIP4-ECD exerts critical functions in zinc transport. The conserved dimeric architecture in ZIP4-ECD is also demonstrated to be a common structural feature among the LIV-1 proteins.
Specific frontal neural dynamics contribute to decisions to check
Authors: Stoll Frederic M. , Fontanier Vincent , Procyk Emmanuel
Published: June 2016

Curiosity and information seeking potently shapes our behaviour and are thought to rely on the frontal cortex. Yet, the frontal regions and neural dynamics that control the drive to check for information remain unknown. Here we trained monkeys in a task where they had the opportunity to gain information about the potential delivery of a large bonus reward or continue with a default instructed decision task. Single-unit recordings in behaving monkeys reveal that decisions to check for additional information first engage midcingulate cortex and then lateral prefrontal cortex. The opposite is true for instructed decisions. Importantly, deciding to check engages neurons also involved in performance monitoring. Further, specific midcingulate activity could be discerned several trials before the monkeys actually choose to check the environment. Our data show that deciding to seek information on the current state of the environment is characterized by specific dynamics of neural activity within the prefrontal cortex.
Correction: Corrigendum: High Color-Purity Green, Orange, and Red Light-Emitting Diodes Based on Chemically Functionalized Graphene Quantum Dots
Authors: Kwon Woosung , Kim Young-Hoon , Kim Ji-Hee , Lee Taehyung , Do Sungan , Park Yoonsang , Jeong Mun Seok , Lee Tae-Woo , Rhee Shi-Woo
Published: June 2016

Scientific Reports 6: Article number: 24205; published online: 06 April 2016; updated: 20 June 2016 The original version of this Article contained an error in the title of the paper, where the word “Diodes” was incorrectly given as “Didoes”. This error has now been corrected in the PDF and HTML versions of the Article.
Correction: Corrigendum: New Insight into the Role of the Calvin Cycle: Reutilization of CO2 Emitted through Sugar Degradation
Authors: Shimizu Rie , Dempo Yudai , Nakayama Yasumune , Nakamura Satoshi , Bamba Takeshi , Fukusaki Eiichiro , Fukui Toshiaki
Published: June 2016

Scientific Reports 5: Article number: 11617; published online: 01 July 2015; updated: 20 June 2016 In this Article, there is an error in Figure 3 where the formation of the ATP molecule between the reaction steps 3PGA and 2 Pyruvate should be omitted. The correct Figure 3 appears below as Figure 1.
Correction: Corrigendum: TiO2-catalyzed synthesis of sugars from formaldehyde in extraterrestrial impacts on the early Earth
Authors: Civiš Svatopluk , Szabla Rafał , Szyja Bartłomiej M. , Smykowski Daniel , Ivanek Ondřej , Knížek Antonín , Kubelík Petr , Šponer Jiří , Ferus Martin , Šponer Judit E.
Published: June 2016

Scientific Reports 6: Article number: 23199; published online: 16 March 2016; updated: 20 June 2016 The Acknowledgements section in this Article is incomplete. “We thank professor Rutger van Santen for helpful discussions. This research has been financially supported by the Ministry of Education, Youth and Sports of the Czech Republic under the project CEITEC 2020 (LQ1601).
Role of dimensionality in complex networks
Authors: Brito Samuraí , da Silva L. R. , Tsallis Constantino
Published: June 2016

Deep connections are known to exist between scale-free networks and non-Gibbsian statistics. For example, typical degree distributions at the thermodynamical limit are of the form "Equation missing", where the q-exponential form "Equation missing" optimizes the nonadditive entropy Sq (which, for q → 1, recovers the Boltzmann-Gibbs entropy). We introduce and study here d-dimensional geographically-located networks which grow with preferential attachment involving Euclidean distances through "Equation missing". Revealing the connection with q-statistics, we numerically verify (for d = 1, 2, 3 and 4) that the q-exponential degree distributions exhibit, for both q and k, universal dependences on the ratio αA/d. Moreover, the q = 1 limit is rapidly achieved by increasing αA/d to infinity.
The histone deacetylase inhibiting drug Entinostat induces lipid accumulation in differentiated HepaRG cells
Authors: Nunn Abigail D. G. , Scopigno Tullio , Pediconi Natalia , Levrero Massimo , Hagman Henning , Kiskis Juris , Enejder Annika
Published: June 2016

Dietary overload of toxic, free metabolic intermediates leads to disrupted insulin signalling and fatty liver disease. However, it was recently reported that this pathway might not be universal: depletion of histone deacetylase (HDAC) enhances insulin sensitivity alongside hepatic lipid accumulation in mice, but the mechanistic role of microscopic lipid structure in this effect remains unclear. Here we study the effect of Entinostat, a synthetic HDAC inhibitor undergoing clinical trials, on hepatic lipid metabolism in the paradigmatic HepaRG liver cell line. Specifically, we statistically quantify lipid droplet morphology at single cell level utilizing label-free microscopy, coherent anti-Stokes Raman scattering, supported by gene expression. We observe Entinostat efficiently rerouting carbohydrates and free-fatty acids into lipid droplets, upregulating lipid coat protein gene Plin4, and relocating droplets nearer to the nucleus. Our results demonstrate the power of Entinostat to promote lipid synthesis and storage, allowing reduced systemic sugar levels and sequestration of toxic metabolites within protected protein-coated droplets, suggesting a potential therapeutic strategy for diseases such as diabetes and metabolic syndrome.
Nucleus downscaling in mouse embryos is regulated by cooperative developmental and geometric programs
Authors: Tsichlaki Elina , FitzHarris Greg
Published: June 2016

Maintaining appropriate nucleus size is important for cell health, but the mechanisms by which this is achieved are poorly understood. Controlling nucleus size is a particular challenge in early development, where the nucleus must downscale in size with progressive reductive cell divisions. Here we use live and fixed imaging, micromanipulation approaches and small molecule analyses during preimplantation mouse development to probe the mechanisms by which nucleus size is determined. We find a close correlation between cell and nuclear size at any given developmental stage and show that experimental cytoplasmic reduction can alter nuclear size, together indicating that cell size helps dictate nuclear proportions. Additionally, however, by creating embryos with over-sized blastomeres we present evidence of a developmental program that drives nuclear downscaling independently of cell size. We show that this developmental program does not correspond with nuclear import rates, but provide evidence that PKC activity may contribute to this mechanism. We propose a model in which nuclear size regulation during early development is a multi-mode process wherein nucleus size is set by cytoplasmic factors and fine-tuned on a cell-by-cell basis according to cell size.
Phosphodiesterase 3B (PDE3B) regulates NLRP3 inflammasome in adipose tissue
Authors: Ahmad Faiyaz , Chung Youn Wook , Tang Yan , Hockman Steven C. , Liu Shiwei , Khan Yusuf , Huo Kevin , Billings Eric , Amar Marcelo J. , Remaley Alan T. , Manganiello Vincent C.
Published: June 2016

Activation of inflammation in white adipose tissue (WAT), includes infiltration/expansion of WAT macrophages, contributes pathogenesis of obesity, insulin resistance and metabolic syndrome. The inflammasome comprises an intracellular sensor (NLR), caspase-1 and the adaptor ASC. Inflammasome activation leads to maturation of caspase-1 and processing of IL1β, contributing to many metabolic disorders and directing adipocytes to a more insulin-resistant phenotype. Ablation of PDE3B in WAT prevents inflammasome activation by reducing expression of NLRP3, caspase-1, ASC, AIM2, TNFα, IL1β and proinflammatory genes. Following IP injection of lipopolysaccharide (LPS), serum levels of IL1β and TNFα were reduced in PDE3B−/−mice compared to WT. Activation of signaling cascades, which mediate inflammasome responses, were modulated in PDE3B−/−mice WAT, including smad, NFAT, NFkB and MAP kinases. Moreover, expression of chemokine CCL2, MCP-1 and its receptor CCR2, which play an important role in macrophage chemotaxis, were reduced in WAT of PDE3B−/−mice. In addition, atherosclerotic plaque formation was significantly reduced in the aorta of apoE−/−/PDE3B−/−and LDL-R−/−/PDE3B−/−mice compared to apoE−/−and LDL-R−/−mice, respectively. Obesity-induced changes in serum-cholesterol were blocked in PDE3B−/−mice. Collectively, these data establish a role for PDE3B in modulating inflammatory response, which may contribute to a reduced inflammatory state in adipose tissue.
Newly-formed emotional memories guide selective attention processes: Evidence from event-related potentials
Authors: Schupp Harald T. , Kirmse Ursula , Schmälzle Ralf , Flaisch Tobias , Renner Britta
Published: June 2016

Emotional cues can guide selective attention processes. However, emotional stimuli can both activate long-term memory representations reflecting general world knowledge and engage newly formed memory representations representing specific knowledge from the immediate past. Here, the self-completion feature of associative memory was utilized to assess the regulation of attention processes by newly-formed emotional memory. First, new memory representations were formed by presenting pictures depicting a person either in an erotic pose or as a portrait. Afterwards, to activate newly-built memory traces, edited pictures were presented showing only the head region of the person. ERP recordings revealed the emotional regulation of attention by newly-formed memories. Specifically, edited pictures from the erotic compared to the portrait category elicited an early posterior negativity and late positive potential, similar to the findings observed for the original pictures. A control condition showed that the effect was dependent on newly-formed memory traces. Given the large number of new memories formed each day, they presumably make an important contribution to the regulation of attention in everyday life.
Dynamic Behavior of Engineered Lattice Materials
Authors: Hawreliak J. A. , Lind J. , Maddox B. , Barham M. , Messner M. , Barton N. , Jensen B. J. , Kumar M.
Published: June 2016

Additive manufacturing (AM) is enabling the fabrication of materials with engineered lattice structures at the micron scale. These mesoscopic structures fall between the length scale associated with the organization of atoms and the scale at which macroscopic structures are constructed. Dynamic compression experiments were performed to study the emergence of behavior owing to the lattice periodicity in AM materials on length scales that approach a single unit cell. For the lattice structures, both bend and stretch dominated, elastic deflection of the structure was observed ahead of the compaction of the lattice, while no elastic deformation was observed to precede the compaction in a stochastic, random structure. The material showed lattice characteristics in the elastic response of the material, while the compaction was consistent with a model for compression of porous media. The experimental observations made on arrays of 4 × 4 × 6 lattice unit cells show excellent agreement with elastic wave velocity calculations for an infinite periodic lattice, as determined by Bloch wave analysis and finite element simulations.
OncoScape: Exploring the cancer aberration landscape by genomic data fusion
Authors: Schlicker Andreas , Michaut Magali , Rahman Rubayte , Wessels Lodewyk F. A.
Published: June 2016

Although large-scale efforts for molecular profiling of cancer samples provide multiple data types for many samples, most approaches for finding candidate cancer genes rely on somatic mutations and DNA copy number only. We present a new method, OncoScape, which exploits five complementary data types across 11 cancer types to identify new candidate cancer genes. We find many rarely mutated genes that are strongly affected by other aberrations. We retrieve the majority of known cancer genes but also new candidates such as STK31 and MSRA with very high confidence. Several genes show a dual oncogene- and tumor suppressor-like behavior depending on the tumor type. Most notably, the well-known tumor suppressor RB1 shows strong oncogene-like signal in colon cancer. We applied OncoScape to cell lines representing ten cancer types, providing the most comprehensive comparison of aberrations in cell lines and tumor samples to date. This revealed that glioblastoma, breast and colon cancer show strong similarity between cell lines and tumors, while head and neck squamous cell carcinoma and bladder cancer, exhibit very little similarity between cell lines and tumors. To facilitate exploration of the cancer aberration landscape, we created a web portal enabling interactive analysis of OncoScape results (http://ccb.nki.nl/software/oncoscape).
Correction: Corrigendum: Robust Type-specific Hemisynapses Induced by Artificial Dendrites
Authors: Kim Eun Joong , Jeon Chang Su , Lee Soo Youn , Hwang Inseong , Chung Taek Dong
Published: June 2016

Scientific Reports 6: Article number: 24210; published online: 13 April 2016; updated: 20 June 2016 In the original version of this Article, an additional affiliation for Taek Dong Chung was omitted. The correct affiliation is listed below: Advanced Institutes of Convergence Technology, Suwon-Si, Gyeonggi-do 16229, Korea.
Improved oil recovery in nanopores: NanoIOR
Authors: de Almeida James Moraes , Miranda Caetano Rodrigues
Published: June 2016

Fluid flow through minerals pores occurs in underground aquifers, oil and shale gas reservoirs. In this work, we explore water and oil flow through silica nanopores. Our objective is to model the displacement of water and oil through a nanopore to mimic the fluid infiltration on geological nanoporous media and the displacement of oil with and without previous contact with water by water flooding to emulate an improved oil recovery process at nanoscale (NanoIOR). We have observed a barrier-less infiltration of water and oil on the empty (vacuum) simulated 4 nm diameter nanopores. For the water displacement with oil, we have obtained a critical pressure of 600 atm for the oil infiltration, and after the flow was steady, a water layer was still adsorbed to the surface, thus, hindering the direct contact of the oil with the surface. In addition, oil displacement with water was assessed, with and without an adsorbed water layer (AWL). Without the AWL, the pressure needed for oil infiltration was 5000 atm, whereas, with the AWL the infiltration was observed for pressures as low as 10 atm. Hence, the infiltration is greatly affected by the AWL, significantly lowering the critical pressure for oil displacement.
Postnatal development of the electrophysiological properties of somatostatin interneurons in the anterior cingulate cortex of mice
Authors: Pan Geng , Yang Jian-Ming , Hu Xing-Yue , Li Xiao-Ming
Published: June 2016

Somatostatin (SST)-positive interneurons in the anterior cingulate cortex (ACC) play important roles in neuronal diseases, memory and cognitive functions. However, their development in the ACC remains unclear. Using postnatal day 3 (P3) to P45 GIN mice, we found that most of the intrinsic membrane properties of SST interneurons in the ACC were developmentally mature after the second postnatal week and that the development of these neurons differed from that of parvalbumin (PV) interneurons in the prefrontal cortex. In addition, electrical coupling between SST interneurons appeared primarily between P12–14. The coupling probability plateaued at approximately P21–30, with a non-age-dependent development of coupling strength. The development of excitatory chemical afferents to SST interneurons occurred earlier than the development of inhibitory chemical afferents. Furthermore, eye closure attenuated the development of electrical coupling probability at P21–30 but had no effect on coupling strength. Eye closure also delayed the development of inhibitory chemical afferent frequency but had no effect on the excitatory chemical afferent amplitude, frequency or rise time. Our data suggest that SST interneurons in the ACC exhibit inherent developmental characteristics distinct from other interneuron subtypes, such as PV interneurons and that some of these characteristics are subject to environmental regulation.
Direct acceleration of electrons by a CO2 laser in a curved plasma waveguide
Authors: Yi Longqing , Pukhov Alexander , Shen Baifei
Published: June 2016

Laser plasma interaction with micro-engineered targets at relativistic intensities has been greatly promoted by recent progress in the high contrast lasers and the manufacture of advanced micro- and nano-structures. This opens new possibilities for the physics of laser-matter interaction. Here we propose a novel approach that leverages the advantages of high-pressure CO2 laser, laser-waveguide interaction, as well as micro-engineered plasma structure to accelerate electrons to peak energy greater than 1 GeV with narrow slice energy spread (~1%) and high overall efficiency. The acceleration gradient is 26 GV/m for a 1.3 TW CO2 laser system. The micro-bunching of a long electron beam leads to the generation of a chain of ultrashort electron bunches with the duration roughly equal to half-laser-cycle. These results open a way for developing a compact and economic electron source for diverse applications.
Key diffusion mechanisms involved in regulating bidirectional water permeation across E. coli outer membrane lectin
Authors: Sachdeva Shivangi , Kolimi Narendar , Nair Sanjana Anilkumar , Rathinavelan Thenmalarchelvi
Published: June 2016

Capsular polysaccharides (CPSs) are major bacterial virulent determinants that facilitate host immune evasion. E. coli group1 K30CPS is noncovalently attached to bacterial surface by Wzi, a lectin. Intriguingly, structure based phylogenetic analysis indicates that Wzi falls into porin superfamily. Molecular dynamics (MD) simulations further shed light on dual role of Wzi as it also functions as a bidirectional passive water specific porin. Such a functional role of Wzi was not realized earlier, due to the occluded pore. While five water specific entry points distributed across extracellular & periplasmic faces regulate the water diffusion involving different mechanisms, a luminal hydrophobic plug governs water permeation across the channel. Coincidently, MD observed open state structure of “YQF” triad is seen in sugar-binding site of sodium-galactose cotransporters, implicating its involvement in K30CPS surface anchorage. Importance of Loop 5 (L5) in membrane insertion is yet another highlight. Change in water diffusion pattern of periplasmic substitution mutants suggests Wzi’s role in osmoregulation by aiding in K30CPS hydration, corroborating earlier functional studies. Water molecules located inside β-barrel of Wzi crystal structure further strengthens the role of Wzi in osmoregulation. Thus, interrupting water diffusion or L5 insertion may reduce bacterial virulence.
Ultrasensitive proteomic quantitation of cellular signaling by digitized nanoparticle-protein counting
Authors: Jacob Thomas , Agarwal Anupriya , Ramunno-Johnson Damien , O’Hare Thomas , Gönen Mehmet , Tyner Jeffrey W. , Druker Brian J. , Vu Tania Q.
Published: June 2016

Many important signaling and regulatory proteins are expressed at low abundance and are difficult to measure in single cells. We report a molecular imaging approach to quantitate protein levels by digitized, discrete counting of nanoparticle-tagged proteins. Digitized protein counting provides ultrasensitive molecular detection of proteins in single cells that surpasses conventional methods of quantitating total diffuse fluorescence, and offers a substantial improvement in protein quantitation. We implement this digitized proteomic approach in an integrated imaging platform, the single cell-quantum dot platform (SC-QDP), to execute sensitive single cell phosphoquantitation in response to multiple drug treatment conditions and using limited primary patient material. The SC-QDP: 1) identified pAKT and pERK phospho-heterogeneity and insensitivity in individual leukemia cells treated with a multi-drug panel of FDA-approved kinase inhibitors, and 2) revealed subpopulations of drug-insensitive CD34+ stem cells with high pCRKL and pSTAT5 signaling in chronic myeloid leukemia patient blood samples. This ultrasensitive digitized protein detection approach is valuable for uncovering subtle but important differences in signaling, drug insensitivity, and other key cellular processes amongst single cells.
GeLC-MS-based proteomics of Chromobacterium violaceum: comparison of proteome changes elicited by hydrogen peroxide
Authors: Lima D. C. , Duarte F. T. , Medeiros V. K. S. , Carvalho P. C. , Nogueira F. C. S. , Araujo G. D. T. , Domont G. B. , Batistuzzo de Medeiros S. R.
Published: June 2016

Chromobacterium violaceumis a free-living bacillus with several genes that enables it survival under different harsh environments such as oxidative and temperature stresses. Here we performed a label-free quantitative proteomic study to unravel the molecular mechanisms that enableC. violaceumto survive oxidative stress. To achieve this, total proteins extracted from control andC. violaceumcultures exposed during two hours with 8 mM hydrogen peroxide were analyzed using GeLC-MS proteomics. Analysis revealed that under the stress condition, the bacterium expressed proteins that protected it from the damage caused by reactive oxygen condition and decreasing the abundance of proteins responsible for bacterial growth and catabolism. GeLC-MS proteomics analysis provided an overview of the metabolic pathways involved in the response ofC. violaceumto oxidative stress ultimately aggregating knowledge of the response of this organism to environmental stress. This study identified approximately 1500 proteins, generating the largest proteomic coverage ofC. violaceumso far. We also detected proteins with unknown function that we hypothesize to be part of new mechanisms related to oxidative stress defense. Finally, we identified the mechanism of clustered regularly interspaced short palindromic repeats (CRISPR), which has not yet been reported for this organism.
F1 rotary motor of ATP synthase is driven by the torsionally-asymmetric drive shaft
Authors: Kulish O. , Wright A. D. , Terentjev E. M.
Published: June 2016

F1F0 ATP synthase (ATPase) either facilitates the synthesis of ATP in a process driven by the proton moving force (pmf), or uses the energy from ATP hydrolysis to pump protons against the concentration gradient across the membrane. ATPase is composed of two rotary motors, F0 and F1, which compete for control of their shared γ -shaft. We present a self-consistent physical model of F1 motor as a simplified two-state Brownian ratchet using the asymmetry of torsional elastic energy of the coiled-coil γ -shaft. This stochastic model unifies the physical concepts of linear and rotary motors and explains the stepped unidirectional rotary motion. Substituting the model parameters, all independently known from recent experiments, our model quantitatively reproduces the ATPase operation, e.g. the ‘no-load’ angular velocity is ca. 400 rad/s anticlockwise at 4 mM ATP. Increasing the pmf torque exerted by F0 can slow, stop and overcome the torque generated by F1, switching from ATP hydrolysis to synthesis at a very low value of ‘stall torque’. We discuss the motor efficiency, which is very low if calculated from the useful mechanical work it produces - but is quite high when the ‘useful outcome’ is measured in the number of H+ pushed against the chemical gradient.
Elucidating the contributions of multiple aldehyde/alcohol dehydrogenases to butanol and ethanol production in Clostridium acetobutylicum
Authors: Dai Zongjie , Dong Hongjun , Zhang Yanping , Li Yin
Published: June 2016

Ethanol and butanol biosynthesis in Clostridium acetobutylicum share common aldehyde/alcohol dehydrogenases. However, little is known about the relative contributions of these multiple dehydrogenases to ethanol and butanol production respectively. The contributions of six aldehyde/alcohol dehydrogenases of C. acetobutylicum on butanol and ethanol production were evaluated through inactivation of the corresponding genes respectively. For butanol production, the relative contributions from these enzymes were: AdhE1 > BdhB > BdhA ≈ YqhD > SMB_P058 > AdhE2. For ethanol production, the contributions were: AdhE1 > BdhB > YqhD > SMB_P058 > AdhE2 > BdhA. AdhE1 and BdhB are two essential enzymes for butanol and ethanol production. AdhE1 was relatively specific for butanol production over ethanol, while BdhB, YqhD, and SMB_P058 favor ethanol production over butanol. Butanol synthesis was increased in the adhE2 mutant, which had a higher butanol/ethanol ratio (8.15:1) compared with wild type strain (6.65:1). Both the SMB_P058 mutant and yqhD mutant produced less ethanol without loss of butanol formation, which led to higher butanol/ethanol ratio, 10.12:1 and 10.17:1, respectively. To engineer a more efficient butanol-producing strain, adhE1 could be overexpressed, furthermore, adhE2, SMB_P058, yqhD are promising gene inactivation targets. This work provides useful information guiding future strain improvement for butanol production.
Serum Concentrations of Ubiquitin C-Terminal Hydrolase-L1 and Glial Fibrillary Acidic Protein after Pediatric Traumatic Brain Injury
Authors: Mondello Stefania , Kobeissy Firas , Vestri Annarita , Hayes Ronald L. , Kochanek Patrick M. , Berger Rachel P.
Published: June 2016

Objective reliable markers to assess traumatic brain injury (TBI) and predict outcome soon after injury are a highly needed tool for optimizing management of pediatric TBI. We assessed serum concentrations of Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-Terminal Hydrolase-L1 (UCH-L1) in a cohort of 45 children with clinical diagnosis of TBI (Glasgow Coma Scale [GCS] 3–15) and 40 healthy subjects, evaluated their associations with clinical characteristics and outcomes, and compared their performance to previously published data on two well-studied blood biomarkers, S100B and MBP. We observed higher serum levels of GFAP and UCH-L1 in brain-injured children compared with controls and also demonstrated a step-wise increase of biomarker concentrations over the continuum of severity from mild to severe TBI. Furthermore, while we found that only the neuronal biomarker UCH-L1 holds potential to detect acute intracranial lesions as assessed by computed tomography (CT), both markers were substantially increased in TBI patients even with a normal CT suggesting the presence of undetected microstructural injuries. Serum UCH-L1 and GFAP concentrations also strongly predicted poor outcome and performed better than S100B and MBP. Our results point to a role of GFAP and UCH-L1 as candidate biomarkers for pediatric TBI. Further studies are warranted.
Ferromagnetic resonance induced large microwave magnetodielectric effect in cerium doped Y3Fe5O12 ferrites
Authors: Chen Fu , Wang Xian , Nie Yan , Li Qifan , Ouyang Jun , Feng Zekun , Chen Yajie , Harris Vincent G.
Published: June 2016

In recent years, multifunctional materials contained simultaneous ferroelectric and ferromagnetic ordering have been realized. Here, a real time room temperature adaptive materials system, which demonstrates an RF magnetodielectric (MD) response, i.e., CexY3−xFe5O12 (x = 0, 0.05, 0.1, 0.15, 0.2), is reported. The magnetic and dielectric properties of Ce-doped YIG microwave ferrites processed by a traditional ceramic route have been measured over a frequency range of 4–8 GHz (C-band). The substitution of Ce not only enhances the microwave electromagnetic properties of the YIG, but also modulates the magnetodielectric response. The maximum magnetodielectric response in Ce-doped YIG sample ranges in magnitude from approximately +5% to −5% under an applied field of 1.78 kOe. This effect was attributed to electron fluctuations on the Fe cation sites. Furthermore, the magnitude of the MD response was shown to be enhanced by the cerium content. It is believed that research of the magnetodielectric effect in YIG ferrites is of great importance to the development of next generation multifunctional adaptive microwave materials, devices and integrated circuits.
Gate Tuning of Förster Resonance Energy Transfer in a Graphene - Quantum Dot FET Photo-Detector
Authors: Li Ruifeng , Schneider Lorenz Maximilian , Heimbrodt Wolfram , Wu Huizhen , Koch Martin , Rahimi-Iman Arash
Published: June 2016

Graphene photo-detectors functionalized by colloidal quantum dots (cQDs) have been demonstrated to show effective photo-detection. Although the transfer of charge carriers or energy from the cQDs to graphene is not sufficiently understood, it is clear that the mechanism and efficiency of the transfer depends on the morphology of the interface between cQDs and graphene, which is determined by the shell of the cQDs in combination with its ligands. Here, we present a study of a graphene field-effect transistor (FET), which is functionalized by long-ligand CdSe/ZnS core/shell cQDs. Time-resolved photo-luminescence from the cQDs as a function of the applied gate voltage has been investigated in order to probe transfer dynamics in this system. Thereby, a clear modification of the photo-luminescence lifetime has been observed, indicating a change of the decay channels. Furthermore, we provide responsivities under a Förster-like energy transfer model as a function of the gate voltage in support of our findings. The model shows that by applying a back-gate voltage to the photo-detector, the absorption can be tuned with respect to the photo-luminescence of the cQDs. This leads to a tunable energy transfer rate across the interface of the photo-detector, which offers an opportunity to optimize the photo-detection.
Predict or classify: The deceptive role of time-locking in brain signal classification
Authors: Rusconi Marco , Valleriani Angelo
Published: June 2016

Several experimental studies claim to be able to predict the outcome of simple decisions from brain signals measured before subjects are aware of their decision. Often, these studies use multivariate pattern recognition methods with the underlying assumption that the ability to classify the brain signal is equivalent to predict the decision itself. Here we show instead that it is possible to correctly classify a signal even if it does not contain any predictive information about the decision. We first define a simple stochastic model that mimics the random decision process between two equivalent alternatives and generate a large number of independent trials that contain no choice-predictive information. The trials are first time-locked to the time point of the final event and then classified using standard machine-learning techniques. The resulting classification accuracy is above chance level long before the time point of time-locking. We then analyze the same trials using information theory. We demonstrate that the high classification accuracy is a consequence of time-locking and that its time behavior is simply related to the large relaxation time of the process. We conclude that when time-locking is a crucial step in the analysis of neural activity patterns, both the emergence and the timing of the classification accuracy are affected by structural properties of the network that generates the signal.
Effects of Long-term Diving Training on Cortical Gyrification
Authors: Zhang Yuanchao , Zhao Lu , Bi Wenwei , Wang Yue , Wei Gaoxia , Evans Alan , Jiang Tianzi
Published: June 2016

During human brain development, cortical gyrification, which is believed to facilitate compact wiring of neural circuits, has been shown to follow an inverted U-shaped curve, coinciding with the two-stage neurodevelopmental process of initial synaptic overproduction with subsequent pruning. This trajectory allows postnatal experiences to refine the wiring, which may manifest as endophenotypic changes in cortical gyrification. Diving experts, typical elite athletes who commence intensive motor training at a very young age in their early childhood, serve ideal models for examining the gyrification changes related to long-term intensive diving training. Using local gyrification index (LGI), we compared the cortical gyrification between 12 diving experts and 12 controls. Compared with controls, diving experts showed widespread LGI reductions in regions relevant to diving performance. Negative correlations between LGIs and years of diving training were also observed in diving experts. Further exploratory network efficiency analysis of structural cortical networks, inferred from interregional correlation of LGIs, revealed comparable global and local efficiency in diving experts relative to controls. These findings suggest that gyrification reductions in diving experts may be the result of long-term diving training which could refine the neural circuitry (via synaptic pruning) and might be the anatomical substrate underlying their extraordinary diving performance.
A two-year field measurement of methane and nitrous oxide fluxes from rice paddies under contrasting climate conditions
Authors: Sun Huifeng , Zhou Sheng , Fu Zishi , Chen Guifa , Zou Guoyan , Song Xiangfu
Published: June 2016

The effects of three irrigation levels (traditional normal amount of irrigation [NA100%], 70%, and 30% of the normal amount [NA70% and NA30%]) and two rice varieties (Oryza sativa L. Huayou14 and Hanyou8) on CH4 and N2O emissions were investigated over two years under contrasting climate conditions (a ‘warm and dry’ season in 2013 and a normal season in 2014). Hanyou8 was developed as a drought-resistant variety. The mean seasonal air temperature in 2013 was 2.3 °C higher than in 2014, while the amount of precipitation from transplanting to the grain-filling stage in 2013 was only 36% of that in 2014. CH4 emission rose by 93–161%, but rice grain yield fell by 7–13% in 2013, compared to 2014 under the NA100% conditions. Surface standing water depths (SSWD) were higher in Hanyou8 than in Huayou14 due to the lower water demand by Hanyou8. A reduction in the amount of irrigation water applied can effectively reduce the CH4 emissions regardless of the rice variety and climate condition. However, less irrigation during the ‘warm and dry’ season greatly decreased Huayou14 grain yield, but had little impact on Hanyou8. In contrast, N2O emission depended more on fertilization and SSWD than on rice variety.
Multi-targeted metagenetic analysis of the influence of climate and environmental parameters on soil microbial communities along an elevational gradient
Authors: Lanzén Anders , Epelde Lur , Blanco Fernando , Martín Iker , Artetxe Unai , Garbisu Carlos
Published: June 2016

Mountain elevation gradients are invaluable sites for understanding the effects of climate change on ecosystem function, community structure and distribution. However, relatively little is known about the impact on soil microbial communities, in spite of their importance for the functioning of the soil ecosystem. Previous studies of microbial diversity along elevational gradients were often limited by confounding variables such as vegetation, pH, and nutrients. Here, we utilised a transect in the Pyrenees established to minimise variation in such parameters, to examine prokaryotic, fungal, protist and metazoan communities throughout three consecutive years. We aimed to determine the influences of climate and environmental parameters on soil microbial community structure; as well as on the relationships between those microbial communities. Further, functional diversity of heterotrophic bacteria was determined using Biolog. Prokaryotic and fungal community structure, but not alpha-diversity, correlated significantly with elevation. However, carbon-to-nitrogen ratio and pH appeared to affect prokaryotic and protist communities more strongly. Both community structure and physicochemical parameters varied considerably between years, illustrating the value of long-term monitoring of the dynamic processes controlling the soil ecosystem. Our study also illustrates both the challenges and strengths of using microbial communities as indicators of potential impacts of climate change.
Fibroblasts profiling in scarring trachoma identifies IL-6 as a functional component of a fibroblast-macrophage pro-fibrotic and pro-inflammatory feedback loop
Authors: Kechagia Jenny Z. , Ezra Daniel G. , Burton Matthew J. , Bailly Maryse
Published: June 2016

Trachoma is a conjunctiva scarring disease, which is the leading infectious cause of blindness worldwide. Yet, the molecular mechanisms underlying progressive fibrosis in trachoma are unknown. To investigate the contribution of local resident fibroblasts to disease progression, we isolated conjunctival fibroblasts from patients with scarring trachoma and matching control individuals and compared their gene expression profiles and functional properties in vitro. We show that scarring trachoma fibroblasts substantially differ from control counterparts, displaying pro-fibrotic and pro-inflammatory features matched by an altered gene expression profile. This pro-inflammatory signature was exemplified by increased IL-6 expression and secretion and a stronger response to macrophage-mediated stimulation of contraction. We further demonstrate that scarring trachoma fibroblasts can promote Akt phosphorylation in macrophages in an IL-6 –dependent manner. Overall this work has uncovered a distinctive molecular fingerprint for scarring trachoma fibroblasts and identified IL-6- as a potential contributor to the chronic conjunctival fibrosis, mediating reciprocal pro-fibrotic/pro-inflammatory interactions between macrophages and fibroblasts.
Detection of orbital angular momentum using a photonic integrated circuit
Authors: Rui Guanghao , Gu Bing , Cui Yiping , Zhan Qiwen
Published: June 2016

Orbital angular momentum (OAM) state of photons offer an attractive additional degree of freedom that has found a variety of applications. Measurement of OAM state, which is a critical task of these applications, demands photonic integrated devices for improved fidelity, miniaturization, and reconfiguration. Here we report the design of a silicon-integrated OAM receiver that is capable of detecting distinct and variable OAM states. Furthermore, the reconfiguration capability of the detector is achieved by applying voltage to the GeSe film to form gratings with alternate states. The resonant wavelength for arbitrary OAM state is demonstrated to be tunable in a quasi-linear manner through adjusting the duty cycle of the gratings. This work provides a viable approach for the realization of a compact integrated OAM detection device with enhanced functionality that may find important applications in optical communications and information processing with OAM states.
Ultramicroscopy as a novel tool to unravel the tropism of AAV gene therapy vectors in the brain
Authors: Alves Sandro , Bode Julia , Bemelmans Alexis-Pierre , von Kalle Christof , Cartier Nathalie , Tews Björn
Published: June 2016

Recombinant adeno-associated viral (AAV) vectors have advanced to the vanguard of gene therapy. Numerous naturally occurring serotypes have been used to target cells in various tissues. There is a strong need for fast and dynamic methods which efficiently unravel viral tropism in whole organs. Ultramicroscopy (UM) is a novel fluorescence microscopy technique that images optically cleared undissected specimens, achieving good resolutions at high penetration depths while being non-destructive. UM was applied to obtain high-resolution 3D analysis of AAV transduction in adult mouse brains, especially in the hippocampus, a region of interest for Alzheimer’s disease therapy. We separately or simultaneously compared transduction efficacies for commonly used serotypes (AAV9 and AAVrh10) using fluorescent reporter expression. We provide a detailed comparative and quantitative analysis of the transduction profiles. UM allowed a rapid analysis of marker fluorescence expression in neurons with intact projections deep inside the brain, in defined anatomical structures. Major hippocampal neuronal transduction was observed with both vectors, with slightly better efficacy for AAV9 in UM. Glial response and synaptic marker expression did not change post transduction.We propose UM as a novel valuable complementary tool to efficiently and simultaneously unravel tropism of different viruses in a single non-dissected adult rodent brain.
Cosmological flux noise and measured noise power spectra in SQUIDs
Authors: Beck Christian
Published: June 2016

The understanding of the origin of 1/f magnetic flux noise commonly observed in superconducting devices such as SQUIDs and qubits is still a major unsolved puzzle. Here we discuss the possibility that a significant part of the observed low-frequency flux noise measured in these devices is ultimately seeded by cosmological fluctuations. We consider a theory where a primordial flux noise field left over in unchanged form from an early inflationary or quantum gravity epoch of the universe intrinsically influences the phase difference in SQUIDs and qubits. The perturbation seeds generated by this field can explain in a quantitatively correct way the form and amplitude of measured low-frequency flux noise spectra in SQUID devices if one takes as a source of fluctuations the primordial power spectrum of curvature fluctuations as measured by the Planck collaboration. Our theoretical predictions are in excellent agreement with recent low-frequency flux noise measurements of various experimental groups. Magnetic flux noise, so far mainly considered as a nuisance for electronic devices, may thus contain valuable information about fluctuation spectra in the very early universe.
The use of green tea polyphenols for treating residual albuminuria in diabetic nephropathy: A double-blind randomised clinical trial
Authors: Borges Cynthia M. , Papadimitriou Alexandros , Duarte Diego A. , Lopes de Faria Jacqueline M. , Lopes de Faria José B.
Published: June 2016

Prior research has shown that in experimental diabetes mellitus, green tea reduces albuminuria by decreasing podocyte apoptosis through activation of the WNT pathway. We investigated the effect of green tea polyphenols (GTP) on residual albuminuria of diabetic subjects with nephropathy. We conducted a randomised, double-blind study in 42 diabetic subjects with a urinary albumin-creatinine ratio (UACR) >30 mg/g, despite administration of the maximum recommended dose of renin-angiotensin (RAS) inhibition. Patients were randomly assigned to two equal groups to receive either GTP (containing 800 mg of epigallocatechin gallate, 17 with type 2 diabetes and 4 with type 1 diabetes) or placebo (21 with type 2 diabetes) for 12 weeks. Treatment with GTP reduced UACR by 41%, while the placebo group saw a 2% increase in UACR (p = 0.019). Podocyte apoptosis (p = 0.001) and in vitro albumin permeability (p < 0.001) were higher in immortalized human podocytes exposed to plasma from diabetic subjects compared to podocytes treated with plasma from normal individuals. In conclusion, GTP administration reduces albuminuria in diabetic patients receiving the maximum recommended dose of RAS. Reduction in podocyte apoptosis by activation of the WNT pathway may have contributed to this effect.