bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a tonometric sensor for measurement and recording of arterial pressure waveform
Authors: Tomczuk K. , Werszko M. , Sasiadek J. Z. , Kosek J. , Berny W. , Weiser A. , Feder-Kubis J.
Published: September 2013

There are many techniques and devices for measurement and recording of arterial blood pressure. Some of them allow (enable) additionally to observe the shape of a wave of arterial pressure, which can be regarded as one of the most important diagnostic parameters of human cardiovascular system. This paper presents a novel design and prototype of a new, non-invasive blood waveform measuring device. It expounds theoretical and experimental (including latest preliminary clinical) results obtained during several years of extensive investigations into blood pressure waveform measuring and monitoring problem. According to investigations performed in the laboratory and preliminary clinical evaluation, the sensor has linear steady-state characteristics and satisfactory dynamic properties. It is an efficient and accurate tool for blood pressure waveform monitoring and assessing the cardiovascular condition of the patients. The novelty of this solution is that the device is equipped with a pneumatic pressure sensor based on the pneumatic nozzle flapper amplifier principle with negative feedback. Due to such a technical solution, the device does not require any cuff, which remains an essential component of the majority of contemporary non-invasive blood pressure measurement devices; therefore, it can be used on the artery where the application of a cuff would be impossible (e.g., carotid artery). This advantage makes possible to obtain an accurate shape of blood pressure waveform with high fidelity, comparable to a direct measurement method. Moreover, during the measurement the device converts directly “pressure into pressure.” Such a principle of operation makes possible to eliminate additional calibration (at the current stage of research we have eliminated the necessity of calibration in laboratory conditions).
Reassessment of structure of smectic phases: Nano-segregation in smectic E phase in 4-n-alkyl-4′-isothiocyanato-1,1′-biphenyls
Authors: Saito Kazuya , Miyazawa Takahito , Fujiwara Akio , Hishida Mafumi , Saitoh Hideki , Massalska-Arodź Maria , Yamamura Yasuhisa
Published: September 2013

Based on new diffraction data from aligned samples of smectic E (SmE) phase of 4-n-alkyl-4′-isothiocyanato-1,1′-biphenyls, systematics against the alkyl chain length n is analyzed. In order to perform the analysis, the molecular form factor approximated by a box-shaped distribution is calculated while taking the rounding of the distribution at corners into account. The analysis clearly shows the nano-segregated layered structure, which does not fit to the traditional structural view of SmE phase but does fit to the model the present authors proposed recently. Some implications of this conclusion are discussed in relation to the importance of the molten state of alkyl chains in most of real mesogens revealed previously through thermodynamic analyses.
Graphene-insulator-graphene active plasmonic terahertz devices
Authors: Sensale-Rodriguez Berardi
Published: September 2013

This work theoretically explores the perspectives of stacked graphene-insulator-graphene layers as active terahertz devices. Out-of-plane resonant tunneling current between the graphene layers is shown to constitute a gain medium for electron-plasma-waves propagating in the plane of the graphene sheets. The interaction between both phenomena can lead to either stable THz amplification (with power gain >7 dB) or very sensitive terahertz detection (with sensitivity >105 V/W) under appropriate device configurations.
Carbon mediated reduction of silicon dioxide and growth of copper silicide particles in uniform width channels
Authors: Pizzocchero Filippo , Bøggild Peter , Booth Timothy J.
Published: September 2013

We show that surface arc-discharge deposited carbon plays a critical intermediary role in the breakdown of thermally grown oxide diffusion barriers of 90 nm on a silicon wafer at 1035  °C in an Ar/H2 atmosphere, resulting in the formation of epitaxial copper silicide particles in ≈ 10 μm wide channels, which are aligned with the intersections of the (100) surface of the wafer and the {110} planes on an oxidized silicon wafer, as well as endotaxial copper silicide nanoparticles within the wafer bulk. We apply energy dispersive x-ray spectroscopy, in combination with scanning and transmission electron microscopy of focused ion beam fabricated lammelas and trenches in the structure to elucidate the process of their formation.
Enhancing quantum efficiency of parallel-like bulk heterojunction solar cells
Authors: Seo Ji-Won , Lee Sang-Hoon , Lee Jung-Yong
Published: September 2013

We report enhanced internal quantum efficiency and absorption of parallel-like bulk heterojunction small molecular organic solar cells by inserting multi-functional layers (MFLs). The inserted MFL has an energy level between main donor and acceptor levels, assisting exciton dissociation of the charge transfer state and charge transport from active layers to electrodes. Furthermore, two donors having complementary absorption spectra yield higher and broader absorption efficiency. When a ClAlPc:C60 layer was inserted as a MFL on CuPc:C60, the short circuit current (Jsc) was improved, leading to an increase of the power conversion efficiency from 2.34% to 2.71%.
Electron affinity of pentacene thin film studied by radiation-damage free inverse photoemission spectroscopy
Authors: Han Weining , Yoshida Hiroyuki , Ueno Nobuo , Kera Satoshi
Published: September 2013

The electron affinity of pentacene thin films has been evaluated during the last decades, but it is still under controversial due to varieties of film quality and radiation damages of the films introduced during inverse photoemission spectroscopy (IPES) experiment together with insufficient energy resolution of the instruments. We employed the near-ultraviolet IPES with a better energy resolution 0.27 ∼ 0.32 eV and using lower energy electron beams (0 eV ≤ Ei ≤ 4.9 eV) to study the unoccupied states of pentacene thin film. Due to a large mean-free-path of the electron in this energy region, the threshold electron affinity of the bulk of pentacene film was precisely determined to be 2.70 ± 0.03 eV. Using the threshold ionization energy of 4.90 ± 0.05 eV determined by ultraviolet photoemission spectroscopy, the band-gap energy of the pentacene film is obtained to be 2.20 ± 0.06 eV.
Defect recombination induced by density-activated carrier diffusion in nonpolar InGaN quantum wells
Authors: Yang Fan , Zhang Chunfeng , Shi Chentian , Joo Park Min , Seop Kwak Joon , Jung Sukkoo , Choi Yoon-Ho , Wu Xuewei , Wang Xiaoyong , Xiao Min
Published: September 2013

We report on the observation of carrier-diffusion-induced defect emission at high excitation density in a-plane InGaN single quantum wells. When increasing excitation density in a relatively high regime, we observed the emergence of defect-related emission together with a significant efficiency reduction of bandedge emission. The experimental results can be well explained with the density-activated carrier diffusion from localized states to defect states. Such a scenario of density-activated defect recombination, as confirmed by the dependences of photoluminescence on the excitation photon energy and temperature, is a plausible origin of efficiency droop in a-plane InGaN quantum-well light-emitting diodes.
In-situ local temperature measurement during three-dimensional direct laser writing
Authors: Mueller Jonathan B. , Fischer Joachim , Mange Yatin J. , Nann Thomas , Wegener Martin
Published: September 2013

We present an approach to measure in situ the local temperature increase in the exposed volume during three-dimensional direct laser writing. The method is based on the detection of luminescence from NaYF4:Yb3+, Er3+ co-doped nanocrystals in a confocal scheme. We found the temperature increase to be below a few K within the normal writing regime. If the photoresist is overexposed, significant temperature changes of several hundred K can be observed.
Photochemical doping of graphene oxide with nitrogen for photoluminescence enhancement
Authors: Liu Fuchi , Tang Nujiang , Tang Tao , Liu Yuan , Feng Qian , Zhong Wei , Du Youwei
Published: September 2013

Nitrogen-doped graphene oxide (NGO) was synthesized by irradiation of graphene oxide (GO) in NH3 atmosphere. NGO obtained by irradiation of GO for 10 min has high N content of 13.62 at. %. The photoluminescence (PL) properties of NGO were investigated. The results showed that compared with GO, NGO exhibits significant PL enhancement with a high enhancement ratio of approximately 1501.57%. It may attribute to the high content of amino-like N, which can effectively enhance PL of GO because of the amino conjugation effect.
Divertor with a third-order null of the poloidal field
Authors: Ryutov D. D. , Umansky M. V.
Published: September 2013

A concept and preliminary feasibility analysis of a divertor with the third-order poloidal field null is presented. The third-order null is the point where not only the field itself but also its first and second spatial derivatives are zero. In this case, the separatrix near the null-point has eight branches, and the number of strike-points increases from 2 (as in the standard divertor) to six. It is shown that this magnetic configuration can be created by a proper adjustment of the currents in a set of three divertor coils. If the currents are somewhat different from the required values, the configuration becomes that of three closely spaced first-order nulls. Analytic approach, suitable for a quick orientation in the problem, is used. Potential advantages and disadvantages of this configuration are briefly discussed.
Collision integrals for charged-charged interaction in two-temperature non-equilibrium plasma
Authors: Ghorui S. , Das A. K.
Published: September 2013

Choice of an appropriate form of shielding distance in the estimation of collision integrals under screened coulomb potential for two-temperature non-equilibrium plasma is addressed. Simple expressions for collision integrals for charged-charged interactions are derived. It is shown that while some of the formalisms used earlier completely ignore the presence of ions, the others incorporating it may result in negative collision integrals for the interactions involving particles at higher charged states. The parametric regimes of concern and impact of different formalisms on the computed transport properties are investigated with specific reference to nitrogen plasma. A revised definition of the shielding distance is proposed, which incorporates both electrons and ions, avoids the problem of negative collision integrals in all practical regimes of interest and results in calculated property values in close agreement with experimentally observed results.
Eulerian simulations of collisional effects on electrostatic plasma waves
Authors: Pezzi Oreste , Valentini Francesco , Perrone Denise , Veltri Pierluigi
Published: September 2013

The problem of collisions in a plasma is a wide subject with a huge historical literature. In fact, the description of realistic plasmas is a tough problem to attack, both from the theoretical and the numerical point of view. In this paper, a Eulerian time-splitting algorithm for the study of the propagation of electrostatic waves in collisional plasmas is presented. Collisions are modeled through one-dimensional operators of the Fokker-Planck type, both in linear and nonlinear forms. The accuracy of the numerical code is discussed by comparing the numerical results to the analytical predictions obtained in some limit cases when trying to evaluate the effects of collisions in the phenomenon of wave plasma echo and collisional dissipation of Bernstein-Greene-Kruskal waves. Particular attention is devoted to the study of the nonlinear Dougherty collisional operator, recently used to describe the collisional dissipation of electron plasma waves in a pure electron plasma column [M. W. Anderson and T. M. O'Neil, Phys. Plasmas 14, 112110 (2007)]. Finally, for the study of collisional plasmas, a recipe to set the simulation parameters in order to prevent the filamentation problem can be provided, by exploiting the property of velocity diffusion operators to smooth out small velocity scales.
Genomic prediction of weight and wool traits in a multi-breed sheep population
Authors: Moghaddar N. , Swan A. A. , van der Werf J. H. J.
Published: September 2013

The objective of this study was to predict the accuracy of genomic prediction for 26 traits, including weight, muscle, fat, and wool quantity and quality traits, in Australian sheep based on a large, multi-breed reference population. The reference population consisted of two research flocks, with the main breeds being Merino, Border Leicester (BL), Poll Dorset (PD), and White Suffolk (WS). The genomic estimated breeding value (GEBV) was based on GBLUP (genomic best linear unbiased prediction), applying a genomic relationship matrix calculated from the 50K Ovine SNP chip marker genotypes. The accuracy of GEBV was evaluated as the Pearson correlation coefficient between GEBV and accurate estimated breeding value based on progeny records in a set of genotyped industry animals. The accuracies of weight traits were relatively low to moderate in PD and WS breeds (0.11–0.27) and moderate to relatively high in BL and Merino (0.25–0.63). The accuracy of muscle and fat traits was moderate to relatively high across all breeds (between 0.21 and 0.55). The accuracy of GEBV of yearling and adult wool traits in Merino was, on average, high (0.33–0.75). The results showed the accuracy of genomic prediction depends on trait heritability and the effective size of the reference population, whereas the observed GEBV accuracies were more related to the breed proportions in the multi-breed reference population. No extra gain in within-breed GEBV accuracy was observed based on across breed information. More investigations are required to determine the precise effect of across-breed information on within-breed genomic prediction.
Influence of processing on the digestibility of amino acids and starch in cereals and legumes in non-ruminants
Authors: Wiseman Julian
Published: September 2013

Non-ruminant livestock diets in most regions of the world are based on cereals and plant proteins that are particularly important in view of the current ban on animal proteins within the European Union, although they are still valuable raw materials elsewhere. The major component of cereals is starch that makes a significant contribution to energy-yielding value. Starch has traditionally been viewed as being very well digested, although, increasingly, this statement is being challenged. Thus, native (raw) starch is, to a varying degree depending on the origin, crystalline which is less well digested than is amorphous starch. Processing (invariably heat treatment) reduces the degree of crystallinity of starch, leading to better digestibility, particularly in young animals. For newly weaned pigs, processing can overcome, to an extent, the post-weaning growth check. Extrusion can improve the coefficient of apparent digestibility of starch in wheat three-quarters along the small intestine, from a range of 0.50 to 0.85 (raw) to 0.95. Plant proteins invariably contain naturally occurring anti-nutritive factors, principally trypsin inhibitors that are particularly important in soya beans but also occasionally in peas. The inhibitors are heat labile and denatured by heat. There are several technologies available for processing plant proteins, but a key message is that equipment operates under variable conditions of temperature, duration and moisture addition. Over-processing risks protein being denatured; for example, a trypsin inhibitor activity of 1.5 mg/g is associated with a reduction in amino acid digestibility. It is crucial that processing conditions are defined accurately rather than simply providing the name of the equipment.
NFAT5 induction by the pre–T-cell receptor serves as a selective survival signal in T-lymphocyte development
Authors: Berga-Bolaños Rosa , Alberdi Maria , Buxadé Maria , Aramburu José , López-Rodríguez Cristina
Published: September 2013

Significance

The pre–T-cell receptor (pre-TCR) marks a functional checkpoint in thymocyte development that controls functions such as survival, proliferation, and differentiation. Despite knowledge accumulated on signaling pathways activated by the pre-TCR, less is known about the specialization of transcription factors downstream from this receptor and the genes they control. The Relish (Rel)-like transcription factors NF-κB and NFATc were previously known to control specific points of thymocyte maturation. Our work now positions the Rel-like protein NFAT5 as a target of the IKKβ pathway in thymocytes and as a downstream effector of the prosurvival role of the pre-TCR through its ability to regulate the expression of the survival-promoting proteins A1 and Bcl2 and attenuate the proapoptotic axis comprised by p53 and Noxa proteins.
Transcription factor ZBED6 affects gene expression, proliferation, and cell death in pancreatic beta cells
Authors: Wang Xuan , Jiang Lin , Wallerman Ola , Engström Ulla , Ameur Adam , Gupta Rajesh Kumar , Qi Yu , Andersson Leif , Welsh Nils
Published: September 2013

We have investigated whether the recently discovered transcription factor, zinc finger BED domain-containing protein 6 (ZBED6), is expressed in insulin-producing cells and, if so, to what extent it affects beta cell function. ZBED6 was translated from a
ZC3H11A
transcript in which the
ZBED6
-containing intron was retained. ZBED6 was present in mouse βTC-6 cells and human islets as a double nuclear band at 115/120 kDa and as a single cytoplasmic band at 95–100 kDa, which lacked N-terminal nuclear localization signals. We propose that ZBED6 supports proliferation and survival of beta cells, possibly at the expense of specialized beta cell function—i.e., insulin production—because (
i
) the nuclear ZBED6 were the predominant forms in rapidly proliferating βTC-6 cells, but not in human islet cells; (
ii
) down-regulation of ZBED6 in βTC-6 cells resulted in altered morphology, decreased proliferation, a partial S/G2 cell-cycle arrest, increased expression of beta cell-specific genes, and higher rates of apoptosis; (
iii
) silencing of ZBED6 in the human PANC-1 duct cell line reduced proliferation rates; and (
iv
) ZBED6 binding was preferentially to genes that control transcription, macromolecule biosynthesis, and apoptosis. Furthermore, it is possible that beta cells, by switching from full length to a truncated form of ZBED6, can decide the subcellular localization of ZBED6, thereby achieving differential ZBED6-mediated transcriptional regulation.
Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves
Authors: English Arthur W. , Liu Kevin , Nicolini Jennifer M. , Mulligan Amanda M. , Ye Keqiang
Published: September 2013

Significance

If treatments with small-molecule trkB agonists, especially systemically, proved effective in enhancing axon regeneration in injured peripheral nerves, such a result could form the basis for the development of a unique treatment strategy for peripheral nerve injuries.
Hierarchical excitatory synaptic connectivity in mouse olfactory cortex
Authors: McGinley Matthew J. , Westbrook Gary L.
Published: September 2013

Significance

The dynamics of activity in neural networks form the basis of many brain functions ranging from neural plasticity, memory formation, and sensory perception to consciousness. These dynamics are shaped by immensely complex connectivity patterns of excitatory and inhibitory synapses. Here we used the variance structure of network-wide bursts of excitation to examine connection topology in the olfactory cortex—often viewed as a randomly organized network—and compared it with simulations of several network models. A hierarchical network topology best reproduced the excitatory activity in this cortical region as a result of a subpopulation of neurons (the hierarchy) that generate numerous connections, particularly with members of the same subpopulation. This network organization provides clues to sensory processing in the olfactory cortex.
Predicting the public health benefit of vaccinating cattle against
Escherichia
coli
O157
Authors: Matthews Louise , Reeve Richard , Gally David L. , Low J. Chris , Woolhouse Mark E. J. , McAteer Sean P. , Locking Mary E. , Chase-Topping Margo E. , Haydon Daniel T. , Allison Lesley J. , Hanson Mary F. , Gunn George J. , Reid Stuart W. J.
Published: September 2013

Identifying the major sources of risk in disease transmission is key to designing effective controls. However, understanding of transmission dynamics across species boundaries is typically poor, making the design and evaluation of controls particularly challenging for zoonotic pathogens. One such global pathogen is
Escherichia coli
O157, which causes a serious and sometimes fatal gastrointestinal illness. Cattle are the main reservoir for
E. coli
O157, and vaccines for cattle now exist. However, adoption of vaccines is being delayed by conflicting responsibilities of veterinary and public health agencies, economic drivers, and because clinical trials cannot easily test interventions across species boundaries, lack of information on the public health benefits. Here, we examine transmission risk across the cattle–human species boundary and show three key results. First, supershedding of the pathogen by cattle is associated with the genetic marker
stx2
. Second, by quantifying the link between shedding density in cattle and human risk, we show that only the relatively rare supershedding events contribute significantly to human risk. Third, we show that this finding has profound consequences for the public health benefits of the cattle vaccine. A naïve evaluation based on efficacy in cattle would suggest a 50% reduction in risk; however, because the vaccine targets the major source of human risk, we predict a reduction in human cases of nearly 85%. By accounting for nonlinearities in transmission across the human–animal interface, we show that adoption of these vaccines by the livestock industry could prevent substantial numbers of human
E. coli
O157 cases.
Human and natural influences on the changing thermal structure of the atmosphere
Authors: Santer Benjamin D. , Painter Jeffrey F. , Bonfils Céline , Mears Carl A. , Solomon Susan , Wigley Tom M. L. , Gleckler Peter J. , Schmidt Gavin A. , Doutriaux Charles , Gillett Nathan P. , Taylor Karl E. , Thorne Peter W. , Wentz Frank J.
Published: September 2013

Significance

Observational satellite data and the model-predicted response to human influence have a common latitude/altitude pattern of atmospheric temperature change. The key features of this pattern are global-scale tropospheric warming and stratospheric cooling over the 34-y satellite temperature record. We show that current climate models are highly unlikely to produce this distinctive signal pattern by internal variability alone, or in response to naturally forced changes in solar output and volcanic aerosol loadings. We detect a “human influence” signal in all cases, even if we test against natural variability estimates with much larger fluctuations in solar and volcanic influences than those observed since 1979. These results highlight the very unusual nature of observed changes in atmospheric temperature.
Organellar oligopeptidase (OOP) provides a complementary pathway for targeting peptide degradation in mitochondria and chloroplasts
Authors: Kmiec Beata , Teixeira Pedro F. , Berntsson Ronnie P.-A. , Murcha Monika W. , Branca Rui M. M. , Radomiljac Jordan D. , Regberg Jakob , Svensson Linda M. , Bakali Amin , Langel Ülo , Lehtiö Janne , Whelan James , Stenmark Pål , Glaser Elzbieta
Published: September 2013

Significance

Import of proteins to mitochondria and chloroplasts is essential for organelle biogenesis and organism survival. Proteins to be imported contain an N-terminal peptide targeting the protein to the correct organelle. The targeting peptides are cleaved off after the completed import. Because the free targeting peptides are potentially toxic to organellar activities, they must be removed. Here we report the identification and characterization of a unique mitochondrial and chloroplastic oligopeptidase, organellar oligopeptidase, that provides a complementary pathway for the degradation of targeting peptides and also participates in general organellar quality control mechanisms degrading the peptides produced from complete protein degradation.
Reactivation of stalled polyribosomes in synaptic plasticity
Authors: Graber Tyson E. , Hébert-Seropian Sarah , Khoutorsky Arkady , David Alexandre , Yewdell Jonathan W. , Lacaille Jean-Claude , Sossin Wayne S.
Published: September 2013

Significance

In neurons, many mRNAs are transported to synapses in a translationally repressed state, allowing for the spatial and temporal regulation of protein synthesis required for synaptic plasticity. It has been assumed that these mRNAs are repressed at the initiation step of translation. Here we provide evidence for a second mechanism whereby these mRNAs are instead repressed at elongation/termination awaiting translational reactivation upon appropriate synaptic signals. Our results establish that a form of translation-dependent synaptic plasticity, which is dysregulated in neurodevelopmental and psychiatric pathologies, occurs independently of translation initiation. Elucidating the upstream pathways that lead to repression and reactivation of elongation/termination on these mRNAs may provide new avenues for the design of therapies targeting neurodevelopmental disorders.
Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and
NEK2
as a new disease gene
Authors: Nishiguchi Koji M. , Tearle Richard G. , Liu Yangfan P. , Oh Edwin C. , Miyake Noriko , Benaglio Paola , Harper Shyana , Koskiniemi-Kuendig Hanna , Venturini Giulia , Sharon Dror , Koenekoop Robert K. , Nakamura Makoto , Kondo Mineo , Ueno Shinji , Yasuma Tetsuhiro R. , Beckmann Jacques S. , Ikegawa Shiro , Matsumoto Naomichi , Terasaki Hiroko , Berson Eliot L. , Katsanis Nicholas , Rivolta Carlo
Published: September 2013

Significance

Retinitis pigmentosa (RP) is a genetic disease that causes progressive blindness and that is caused by mutations in more than 50 genes. Conventional methods for identification of both RP mutations and novel RP genes involve the screening of DNA sequences spanning coding exons. In our work, we conversely test the use of whole genome sequencing, a technique that takes into account all variants from both the coding and noncoding regions of the human genome. In our approach, we identify a number of unique RP mutations, a previously undescribed disease gene, as well as pathogenic structural DNA rearrangements originating in introns.
Multiscaled exploration of coupled folding and binding of an intrinsically disordered molecular recognition element in measles virus nucleoprotein
Authors: Wang Yong , Chu Xiakun , Longhi Sonia , Roche Philippe , Han Wei , Wang Erkang , Wang Jin
Published: September 2013

Significance

Quantitative understanding of how coupled binding and folding occurs for intrinsically disordered molecular recognition element (MoRE) critical for function is still challenging. By developing an integrated approach, we provided physical quantification of folding and binding energy landscapes of a MoRE at atomistic level. Our predictions are in remarkable agreements with the experiments, and lead to the recognition mechanism via conformational selection, followed by induced folding. We provided an explanation for the underlying connections among “downhill folding,” “molten globule,” and “intrinsic disorder.” We proposed a “kinetic divide-and-conquer” mechanism to understand the high specificity without high affinity in intrinsic disordered protein binding.
Critical role of segment-specific packaging signals in genetic reassortment of influenza A viruses
Authors: Essere Boris , Yver Matthieu , Gavazzi Cyrille , Terrier Olivier , Isel Catherine , Fournier Emilie , Giroux Fabienne , Textoris Julien , Julien Thomas , Socratous Clio , Rosa-Calatrava Manuel , Lina Bruno , Marquet Roland , Moules Vincent
Published: September 2013

Significance

Genetic reassortment is one of the main mechanisms by which pandemic viruses emerge during influenza A coinfection, but little is known about the molecular mechanisms affecting this process. Here, we studied genetic reassortment between a human and an avian influenza A strain, focusing on the generation of reassortant viruses containing the avian HA gene, which have pandemic potential. We found that this genetic process was strongly biased, and we show that packaging signals are crucial for genetic reassortment and that suboptimal compatibility between the segment-specific packaging signals of the two parental viruses limits the emergence of reassortant viruses.
Evidence for a rapid release of carbon at the Paleocene-Eocene thermal maximum
Authors: Wright James D. , Schaller Morgan F.
Published: September 2013

Significance

Calcium carbonate and carbon isotope records from the rhythmically bedded Marlboro Clay, deposited during the onset of the PETM CIE, show that the massive release of isotopically light carbon was instantaneous, providing important constraints for the magnitude of carbon released and potential mechanisms.
Structural basis for discriminatory recognition of
Plasmodium
lactate dehydrogenase by a DNA aptamer
Authors: Cheung Yee-Wai , Kwok Jane , Law Alan W. L. , Watt Rory M. , Kotaka Masayo , Tanner Julian A.
Published: September 2013

Significance

Aptamers are oligonucleotides selected and evolved to bind tightly and specifically to molecular targets. Aptamers have promise as diagnostic tools and therapeutic agents, but little is known about how they recognize or discriminate their targets. In this study, X-ray crystallography together with several other biophysical techniques reveal how a new DNA aptamer recognizes and discriminates
Plasmodium
lactate dehydrogenase, a protein marker that is a diagnostic indicator of infection with the malaria parasite. We also demonstrate application of the aptamer in target detection. This study broadens our understanding of aptamer-mediated molecular recognition and provides a DNA aptamer that could underpin new innovative approaches for point-of-care malaria diagnosis.
Counting molecules in single organelles with superresolution microscopy allows tracking of the endosome maturation trajectory
Authors: Puchner Elias M. , Walter Jessica M. , Kasper Robert , Huang Bo , Lim Wendell A.
Published: September 2013

Significance

We combined molecule counting and superresolution microscopy to observe the size, shape, and biomolecular composition of vesicles in the endocytic pathway. From a large number of steady-state snapshots, we follow the maturation of vesicles to endosomes. First, phosphatidylinositol 3-phosphate (PI3P) is generated on newly formed vesicles, principally after they shed their clathrin coat. Next, PI3P sites increase (∼100-fold) on small vesicles whose size is tightly regulated. Finally, the GTPase Vps21 (Rab5 homolog) is associated with small endosomal structures during the initial phase of PI3P production, whereas Ypt7 (Rab7 homolog) localizes to larger endosomal structures, which exhibit saturating levels of PI3P.This new technique opens up the possibility of accurately measuring molecular stoichiometries across several orders of magnitude while resolving subdiffraction-limit organelles.
Network structure and dynamics of the mental workspace
Authors: Schlegel Alexander , Kohler Peter J. , Fogelson Sergey V. , Alexander Prescott , Konuthula Dedeepya , Tse Peter Ulric
Published: September 2013

Significance

We do not know how the human brain mediates complex and creative behaviors such as artistic, scientific, and mathematical thought. Scholars theorize that these abilities require conscious experience as realized in a widespread neural network, or “mental workspace,” that represents and manipulates images, symbols, and other mental constructs across a variety of domains. Evidence for such a complex, interconnected network has been difficult to produce with current techniques that mainly study brain activity in isolation and are insensitive to distributed informational processes. The present work takes advantage of emerging techniques in network and information analysis to provide empirical support for such a widespread and interconnected information processing network in the brain that supports the manipulation of visual imagery.
Structures of human primase reveal design of nucleotide elongation site and mode of Pol α tethering
Authors: Kilkenny Mairi Louise , Longo Michael Anthony , Perera Rajika L. , Pellegrini Luca
Published: September 2013

Significance

DNA synthesis during duplication of the genome depends on primase, the DNA-dependent RNA polymerase that initiates nucleotide polymerization by assembling short RNA primers on the unwound template DNA. The mechanism of DNA priming remains poorly understood, principally because of lack of high-resolution structural information. Our study begins to fill the gap in our knowledge by reporting crystal structures of human primase in unliganded form and bound to UTP. We exploit the atomic model of primase to map amino acids that are important for the catalytic function of the enzyme. In addition, we describe crystallographically the interaction between primase and DNA polymerase α, which keeps primase tethered to the replication fork.
Blue whale earplug reveals lifetime contaminant exposure and hormone profiles
Authors: Trumble Stephen J. , Robinson Eleanor M. , Berman-Kowalewski Michelle , Potter Charles W. , Usenko Sascha
Published: September 2013

Significance

Currently, obtaining lifetime chemical profiles (i.e., from birth to death) is extremely rare and difficult for most of Earth’s animals. We have developed a unique approach to quantify hormone and contaminant lifetime profiles for an individual blue whale with a 6-mo resolution using the wax earplug as a natural matrix capable of archiving and preserving these temporal profiles. Using a male blue whale earplug, chemical analysis reveals lifetime patterns of mercury and organic pollutant exposure as well as fluctuating hormone levels. Specifically, we quantified contaminant maternal transfer, time to sexual maturity, and the doubling of stress over the animal’s lifespan. We anticipate that this technique will fundamentally transform our ability to assess human impact on these environmental sentinels and their ecosystems.
Probing the protein-folding mechanism using denaturant and temperature effects on rate constants
Authors: Guinn Emily J. , Kontur Wayne S. , Tsodikov Oleg V. , Shkel Irina , Record M. Thomas
Published: September 2013

Significance

Analysis of effects of denaturants and temperature on folding and unfolding rate constants of 13 globular proteins yields the amount and composition of the surface buried in folding to and from the high–free-energy transition state (TS), and thereby provides information about folding mechanisms and early unstable folding intermediates. All 13 proteins preferentially bury amide surface in folding to TS; amounts of amide and hydrocarbon surface buried in folding to TS generally exceed those buried in forming the native secondary structure. From this, we conclude that most native secondary structure forms in early unstable folding intermediates and that conversion of these intermediates to TS involves nucleation of tertiary interactions, allowing preferential burial of hydrocarbon surface as TS folds.
Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways
Authors: Garland Alaina L. , Walton William G. , Coakley Raymond D. , Tan Chong D. , Gilmore Rodney C. , Hobbs Carey A. , Tripathy Ashutosh , Clunes Lucy A. , Bencharit Sompop , Stutts M. Jackson , Betts Laurie , Redinbo Matthew R. , Tarran Robert
Published: September 2013

Significance

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (
CFTR
) gene, which codes for a chloride/bicarbonate channel whose absence leads to dehydration and acidification of CF airways. A contributing factor to CF lung disease is dysregulation of the epithelial Na
+
channel (ENaC), which exacerbates mucus dehydration. Here, we show that ENaC hyperactivity in CF airways is direct consequence of acidic airway surface liquid (ASL) and that ASL hydration is restored by raising ASL pH. Additionally, we show that short palate lung and nasal epithelial clone 1, the most abundant gene in airway epithelia, is the extracellular pH-sensitive factor that inhibits ENaC in normal but not CF airways. We suggest that future CF therapy be directed toward raising the pH of CF airways.
De novo expression of connexin hemichannels in denervated fast skeletal muscles leads to atrophy
Authors: Cea Luis A. , Cisterna Bruno A. , Puebla Carlos , Frank Marina , Figueroa Xavier F. , Cardozo Christopher , Willecke Klaus , Latorre Ramón , Sáez Juan C.
Published: September 2013

Significance

In this paper two biological findings are described and explain several muscle changes induced by denervation: (
i
) the sarcolemma of fast myofibers are permeabilized to small molecules such as Evans blue via connexin (Cx) hemichannels and (
ii
) the absence of Cx43/Cx45 hemichannels greatly attenuates the inflammasome activation and muscle atrophy. The first finding explains the activation of proteolysis in denervated muscles. The second demonstrates that muscle inflammation can occur without inflammatory cell infiltration, offering an explanation how denervated muscles can alter other tissues. These findings unveil therapeutic targets to reduce atrophy in diverse clinical conditions. Because Cx hemichannels are permeable to Evans blue, the use of this dye as tracer of cell damage should be reevaluated in different systems.
GPR171 is a hypothalamic G protein-coupled receptor for BigLEN, a neuropeptide involved in feeding
Authors: Gomes Ivone , Aryal Dipendra K. , Wardman Jonathan H. , Gupta Achla , Gagnidze Khatuna , Rodriguiz Ramona M. , Kumar Sanjai , Wetsel William C. , Pintar John E. , Fricker Lloyd D. , Devi Lakshmi A.
Published: September 2013

Significance

The mechanism by which vertebrate animals control their body weight is a complex process involving a variety of molecules that regulate feeding and metabolism. Some of these molecules are neuropeptides that bind to specific receptors in feeding centers of the brain. One of the most abundant peptides in brain, LENSSPQAPARRLLPP (named BigLEN), has been proposed to function as a neuropeptide involved in regulating body weight, but the receptor through which this peptide acts had not been identified. We screened candidate receptors and found one, G protein-coupled receptor 171 (GPR171), that is activated by BigLEN. Additional studies showed that the BigLEN–GPR171 system plays an important role in regulating feeding and metabolism in mice. Thus, GPR171 is a potential target for developing antiobesity drugs.
Structural basis of regulation and oligomerization of human cystathionine β-synthase, the central enzyme of transsulfuration
Authors: Ereño-Orbea June , Majtan Tomas , Oyenarte Iker , Kraus Jan P. , Martínez-Cruz Luis Alfonso
Published: September 2013

Significance

Cystathionine β-synthase (CBS), the pivotal enzyme of the transsulfuration pathway, regulates the flux through the pathway to yield compounds such as cysteine, glutathione, taurine, and H
2
S that control the cellular redox status and signaling. Our crystal structures of the full-length wild-type and D444N mutant human CBS enzymes show a unique arrangement of the regulatory CBS motifs, thus making it possible to infer how the enzyme is stimulated by its allosteric activator S-adenosyl-L-methionine and how native tetramers are formed. The structure will allow modeling of numerous mutations causing inherited homocystinuria and the design of compounds modulating CBS activity.
A gating mechanism of pentameric ligand-gated ion channels
Authors: Calimet Nicolas , Simoes Manuel , Changeux Jean-Pierre , Karplus Martin , Taly Antoine , Cecchini Marco
Published: September 2013

Significance

Pentameric ligand-gated ion channels (pLGICs) control membrane conductance in living systems from bacteria to humans. Molecular dynamics simulations based on the structures of the prokaryotic channels fromGloeobacter violaceus(GLIC) andErwinia chrysanthemi(ELIC) and the eukaryotic channel fromCaenorhabditis elegans(GluCl) show that the open-to-closed transition begins with a major quaternary (twisting) transition which is followed by tertiary relaxation of the pore-forming helices. The latter is initiated by the outward tilting of the extracellular β-sandwiches in response to agonist unbinding. The proposed atomic resolution mechanism for channel gating, which is in accord with the Monod–Wyman–Changeux model of allostery, is expected to be generally applicable to pLGICs.
C-terminal processing of reaction center protein D1 is essential for the function and assembly of photosystem II inArabidopsis
Authors: Che Yufen , Fu Aigen , Hou Xin , McDonald Kent , Buchanan Bob B. , Huang Weidong , Luan Sheng
Published: September 2013

Significance

In cyanobacteria, the photosystem II (PSII) core subunit, D1, is synthesized as a precursor and must be processed by a C-terminal peptidase before functional PSII can be assembled. Our work shows that in land plants, D1 maturation is not only required for the assembly of a functional PSII, but also is essential for the formation of supercomplexes—structures that are absent in cyanobacteria. This unexpected link opens an avenue for exploring the mechanism for the association of light harvesting complexes with the PSII core complexes—a final step in the development of the naturally occurring form of PSII in land plants.
Spatiotemporal dynamics in understanding hand—object interactions
Authors: Avanzini Pietro , Fabbri-Destro Maddalena , Campi Cristina , Pascarella Annalisa , Barchiesi Guido , Cattaneo Luigi , Rizzolatti Giacomo
Published: September 2013

Significance

Combining EEG and transcranial magnetic stimulation techniques, we show that reactivation of visual areas plays a fundamental role for understanding conceptual object properties. We suggest that a similar top-down mechanism might also play a role in other higher-order cognitive functions. These results shed a new light on the basic mechanisms underlying perception.
Predicting overfishing and extinction threats in multispecies fisheries
Authors: Burgess Matthew G. , Polasky Stephen , Tilman David
Published: September 2013

Significance

Threats to species from commercial fishing are rarely identified until species have suffered large population declines, by which time recovery can require costly remedial actions, such as fishery closures. We present a mechanistic approach to predicting the threats of future extinction or severe depletion posed by current multispecies fishing practices to a given population. We show that severe depletions recently experienced by four Pacific tuna and billfish populations could have been predicted in the 1950s, using our approach. Our results demonstrate that threatened species can be identified long before they experience severe population declines, providing time for preventative adjustments in fishing practices before consequences become severe and fishery closures or other socioeconomically disruptive interventions are required to protect species.
Inositol polyphosphate multikinase is a transcriptional coactivator required for immediate early gene induction
Authors: Xu Risheng , Paul Bindu D. , Smith Dani R. , Tyagi Richa , Rao Feng , Khan A. Basit , Blech Daniel J. , Vandiver M. Scott , Harraz Maged M. , Guha Prasun , Ahmed Ishrat , Sen Nilkantha , Gallagher Michela , Snyder Solomon H.
Published: September 2013

Significance

The induction of immediate early genes (IEGs) by neural stimuli underlies much of the plasticity of brain function, but regulatory mechanisms have been obscure. Inositol polyphosphate multikinase (IPMK) is a notably pleiotropic enzyme that displays inositol phosphate kinase activity and phosphatidylinositol kinase activity and exhibits physiologically noncatalytic actions such as stabilizing the mammalian target of rapamycin complex 1 complex. We report that IPMK is required for IEG induction by neural activation and neurotrophic stimuli. We have elucidated the molecular mechanisms responsible for IPMK influences; namely, that it enhances the transcriptional coactivation ability of Creb-binding protein (CBP). This epigenetic regulation of IEGs may have both neural and nonneural implications, as IPMK and CBP are broadly expressed in a variety of tissues.
Synthetic polyubiquitinated α-Synuclein reveals important insights into the roles of the ubiquitin chain in regulating its pathophysiology
Authors: Haj-Yahya Mahmood , Fauvet Bruno , Herman-Bachinsky Yifat , Hejjaoui Mirva , Bavikar Sudhir N. , Karthikeyan Subramanian Vedhanarayanan , Ciechanover Aaron , Lashuel Hilal A. , Brik Ashraf
Published: September 2013

Significance

This study describes the nonenzymatic preparation of a protein conjugated to a tetraubiquitin Lys48-based chain made of native isopeptide bonds. We show that certain properties of our model protein, the Parkinson disease-associated protein α-Synuclein (α-Syn), are differentially regulated depending on the length of the conjugated ubiquitin (Ub) chain. In addition, we show that cross-talks between phosphorylation and ubiquitination may play important roles in regulating α-Syn aggregation and pathophysiology. The versatile synthetic strategy described here will enable future studies to further dissect the roles of Ub chain lengths and linkage types, conjugated in a site-specific manner, in regulating the physiological and pathological functions of α-Syn and other proteins.
Atypical mitochondrial fission upon bacterial infection
Authors: Stavru Fabrizia , Palmer Amy E. , Wang Chunxin , Youle Richard J. , Cossart Pascale
Published: September 2013

Significance

Mitochondria are dynamic organelles that constantly fuse and fragment while acting as central hubs of energy production, apoptosis regulation, and Ca
++
signaling, therefore emerging as potential targets of pathogens. We previously showed that the foodborne bacterial pathogen
Listeria monocytogenes
interferes with the dynamics and function of the host cell mitochondrial network via the bacterial toxin listeriolysin O (LLO). In this study, we analyze the effects of LLO on key players known to be involved in mitochondrial dynamics and show that the fission protein dynamin-like protein 1 (Drp1) is not essential for LLO-induced fragmentation of the mitochondrial network, whereas the endoplasmic reticulum (ER) plays an important role, suggesting a unique Drp1-independent and ER-dependent mechanism that is different from the canonical fission machinery.
The secret police and the campaign against Galicians in Soviet Ukraine, 1929–1934
Authors: Bertelsen Olga , Shkandrij Myroslav
Published: September 2013

In 1929–1934 Galician intellectuals who emigrated to Soviet Ukraine from abroad were subject to mass repression. This article demonstrates how the party and the Soviet secret police discredited and eliminated this intelligentsia. Leading party officials perceived Galicians as possessing a strong sense of national identity and internal unity, and therefore an obstacle to plans for homogenizing Soviet Ukraine. The research draws on Ukrainian periodicals published in the early 1930s, on files relating to two major group criminal cases that were conducted in the early 1930s and that are now available to scholars in the Security Service archives of Ukraine (the former Soviet secret police archives), and on recent scholarship in the field. The archival evidence demonstrates that the cases were fabricated and the charges against Galicians were constructed as part of a planned “anti-nationalist” campaign.