bluuebunny/crossref_metadata_2025 huggingface dataset:
Hole-assisted multicore optical fiber for next generation telecom transmission systems
Authors: Ziolowicz A. , Szymanski M. , Szostkiewicz L. , Tenderenda T. , Napierala M. , Murawski M. , Holdynski Z. , Ostrowski L. , Mergo P. , Poturaj K. , Makara M. , Slowikowski M. , Pawlik K. , Stanczyk T. , Stepien K. , Wysokinski K. , Broczkowska M. , Nasilowski T.
Published: August 2014

We present a multicore fiber dedicated for next generation transmission systems. To overcome the issue of multicore fibers' integration with existing transmission systems, the fiber is designed in such a way that the transmission parameters for each core (i.e., chromatic dispersion, attenuation, bending loss, etc.) are in total accordance with the obligatory standards for telecommunication single core fibers (i.e., ITU-T G.652 and G.657). We show the results of numerical investigations and measurements carried out for the fabricated fiber, which confirm low core-to-core crosstalk and compatibility with standard single-core single-mode transmission links making the fiber ready for implementation in the near future.
The influence of Nd dopants on spin and orbital moments in Nd-doped permalloy thin films
Authors: Luo Chen , Zhang Wen , Wong P. K. J. , Zhai Ya , You Biao , Du Jun , Zhai Hongru
Published: August 2014

Magnetic properties of NdX-Ni80Fe20(1−X) thin films have been investigated using x-ray absorption spectroscopy and x-ray magnetic circular dichroism (XMCD) at room temperature. With the Nd concentration increasing, the ratio of orbital-to-spin moment of Ni and Fe increases significantly, indicating that the spin-orbit coupling in permalloy thin films is enhanced due to the Nd impurities. The spin and orbital moments have been obtained by the sum rules analysis, which shows that the Nd impurities lead to a strong dispersion of spin moments of Fe and Ni while have no effect on orbital moments in Nd-doped permalloy thin films. Element-specific XMCD hysteresis loops suggest an antiferromagnetic coupling between the magnetic moments of Nd and permalloy at room temperature. The static magnetic properties have been studied by vibrating sample magnetometer for comparison, which shows a nice agreement with the XMCD results.
Terajets produced by dielectric cuboids
Authors: Pacheco-Peña V. , Beruete M. , Minin I. V. , Minin O. V.
Published: August 2014

The capability of generating terajets using three-dimensional (3D) dielectric cuboids working at terahertz (THZ) frequencies (as analogues of nanojets in the infrared band) is introduced and studied numerically. The focusing performance of the terajets is evaluated in terms of the transversal full width at half maximum (FWHM) along x- and y-directions using different refractive indices for a 3D dielectric cuboid with a fixed geometry, obtaining a quasi-symmetric terajet with a subwavelength resolution of ∼0.46λ0 when the refractive index is n = 1.41. Moreover, the backscattering enhancement produced when metal particles are introduced in the terajet region is demonstrated for a 3D dielectric cuboid and compared with its two-dimensional (2D) counterpart. The results of the jet generated for the 3D case are experimentally validated at sub-THZ waves, demonstrating the ability to produce terajets using 3D cuboids.
Ion-implantation-enhanced chalcogenide-glass resistive-switching devices
Authors: Hughes Mark A. , Fedorenko Yanina , Gwilliam Russell M. , Homewood Kevin P. , Hinder Steven , Gholipour Behrad , Hewak Daniel W. , Lee Tae-Hoon , Elliott Stephen R. , Curry Richard J.
Published: August 2014

We report amorphous GaLaSO-based resistive switching devices, with and without Pb-implantation before deposition of an Al active electrode, which switch due to deposition and dissolution of Al metal filaments. The devices set at 2–3 and 3–4 V with resistance ratios of 6 × 104 and 3 × 109 for the unimplanted and Pb-implanted devices, respectively. The devices reset under positive Al electrode bias, and Al diffused 40 nm further into GaLaSO in the unimplanted device. We attribute the positive reset and higher set bias, compared to devices using Ag or Cu active electrodes, to the greater propensity of Al to oxidise.
The effect of metal-contacts on carbon nanotube for high frequency interconnects and devices
Authors: Chimowa George , Bhattacharyya Somnath
Published: August 2014

High frequency characterisation of platinum and tungsten contacts on individual multi-walled carbon nanotubes (MWNT) is performed from 10 MHz to 50 GHz. By measuring the scattering parameters of aligned individual MWNTs, we show that metal contacts enhance an inductive response due to the improved MWNT-electrode coupling reducing the capacitive effect. This behaviour is pronounced in the frequency below 10 GHz and strong for tungsten contacts. We explain the inductive response as a result of the interaction of stimulus current with the localized (or defects) states present at the contact region resulting in the current lagging behind the voltage. The results are further supported by direct current measurements that show tungsten to significantly increase carbon nanotube-electrode coupling. The immediate consequence is the reduction of the contact resistance, implying a reduction of electron tunnelling barrier from the electrode to the carbon nanotube.
Forces on an attractive surface generated from a thermoresponsive polymer gel
Authors: Konkoli Zoran , Wegrzyn Ilona , Jesorka Aldo
Published: August 2014

Interaction between polymers and soft-matter surfaces in the biological cell is a common yet incompletely understood phenomenon. This work investigates a generic situation where a thermoresponsive polymer gel is placed in the vicinity of an adsorbing surface, and starts contracting. The force is mediated by polymer chains that partially attach to the surface and partially to the contracting gel. The main goal was to understand how the force generated by the transforming polymer gel depends on key parameters that describe the system, most importantly, the concentration of the polymer, the length of the force-mediating polymer, and the the distance between the surface and the outer border of the contracting polymer gel. The key result of the paper is the Laplace transform (with regard to the polymer length) of the pulling force expression. Analytical approximations for the force have been obtained, and the exact expression for the pulling force is presented for the situation when the gel starts contracting. In depth analysis of the force behavior revealed several phases adopted by the polymer during the gel contraction.
Operation of ohmic Ti/Al/Pt/Au multilayer contacts to GaN at 600 °C in air
Authors: Hou Minmin , Senesky Debbie G.
Published: August 2014

The high-temperature characteristics (at 600 °C) of Ti/Al/Pt/Au multilayer contacts to gallium nitride (GaN) in air are reported. Microfabricated circular-transfer-line-method test structures were subject to 10 h of thermal storage at 600 °C. Intermittent electrical characterization during thermal storage showed minimal variation in the contact resistance after 2 h and that the specific contact resistivity remained on the order of 10−5 Ω-cm2. In addition, the thermally stored multilayer contacts to GaN showed ohmic I-V characteristics when electrically probed at 600 °C. The microstructural analysis with atomic force microscopy showed minimal changes in surface roughness after thermal storage. Observations of the thermochemical reactions after thermal storage using Auger electron spectroscopy chemical depth profiling showed diffusion of Pt and minimal additional Al oxidation. The results support the use of Ti/Al/Pt/Au multilayer metallization for GaN-based sensors and electronic devices that will operate within a high-temperature and oxidizing ambient.
A polystyrene-based microfluidic device with three-dimensional interconnected microporous walls for perfusion cell culture
Authors: Chan Chung Yu , Goral Vasiliy N. , DeRosa Michael E. , Huang Tony Jun , Yuen Po Ki
Published: August 2014

In this article, we present a simple, rapid prototyped polystyrene-based microfluidic device with three-dimensional (3D) interconnected microporous walls for long term perfusion cell culture. Patterned 3D interconnected microporous structures were created by a chemical treatment together with a protective mask and the native hydrophobic nature of the microporous structures were selectively made hydrophilic using oxygen plasma treatment together with a protective mask. Using this polystyrene-based cell culture microfluidic device, we successfully demonstrated the support of four days perfusion cell culture of hepatocytes (C3A cells).
The Biopolitical Border in Practice: Surveillance and Death at the Greece-Turkey Borderzones
Authors: Topak Özgün E
Published: August 2014

This paper examines biopolitical control practices at the Greece—Turkey borders and addresses current debates in the study of borders and biopolitics. The Greek and Frontex authorities have established diverse surveillance mechanisms to control the borderzone space and to monitor, intercept, apprehend, and push back migrants or to block their passage. The location of contemporary borders has been much debated in the literature. This paper provides a nuanced understanding of borders by demonstrating that while borders are diffusing beyond and inside state territories, their practices and effects are concentrated at the edges of state territories—ie, borderzones. Borderzones are biopolitical spaces in which surveillance is most intense and migrants suffer the direct threat of injury and death. Applying biopolitics in the context of borderzones also prompts us to revisit the concept. While Foucault posits that biopolitics is the product of the historical transition away from sovereign powers controlling territory and imposing practices of death towards governmental powers managing population mainly through pastoral, productive, and deterritorialized techniques, the case of the Greece—Turkey borderzones demonstrates that biopolitics operates through sovereign territorial controls and surveillance, practices of death and exclusion, and suspension of rights. This study also highlights the fact that, despite the biopolitical realities, migrants continue to cross the borders.
On the Peripheries of Planetary Urbanization: Globalizing Manaus and its Expanding Impact
Authors: Kanai Juan Miguel
Published: August 2014

In this paper I argue that global urbanism produces peripherality in ways that cannot be adequately problematized without taking into account its actual extent and geographically uneven development. Therefore, planetary urbanization needs to engage scholarly traditions attuned to regional urbanization if the discourse is to move past limitations in the urban globalization canon and its narrow focus on cities. To that end, I examine research on extensive urbanization in the Amazon region. Illustrative case studies show how attempts to globalize Manaus precipitated territorial restructuring and sociospatial change far beyond the city's boundaries. Manaus is now a more unequal city. Selective metropolitan expansion to the Rio Negro's south bank has led to the simultaneous upgrading and peripheralization of Iranduba. Yet, the building of a city-centric regional network of roadways also shaped Roraima State's transformation from isolated borderland to bypassed periphery. Moreover, financial and symbolic appropriations of standing rainforests by metropolitan conservationism marginalize remote communities even in the absence of exploitative deforestation and resource extraction. Final remarks emphasize the need for further research on the hybrid (urban—rural) conditions and functional articulations of distant-yet-impacted peripheries. Such efforts may broaden the political horizons of planetary urbanization by informing extensive contestations of entrepreneurial urbanism.
Trends in Australian government health expenditure by age: a fiscal incidence analysis
Authors: Tapper Alan , Phillimore John
Published: August 2014

Objective
Australian government health expenditure per capita has grown steadily across the past few decades, but little is known about trends in the age distribution of health expenditure.

Methods
In this paper, the Australian Bureau of Statistics (ABS) fiscal incidence studies, which track expenditure at the household level between 1984 and 2010, are used to shed light on this topic.

Results
The main finding was that spending has shifted focus from the younger half to the older half of the population. This shift is evident in three areas: (1) acute care (hospitals); (2) community health services (doctors); and (3) pharmaceuticals. Together, these areas account for approximately 88% of expenditure. The trend is independent of demographic aging. It is unlikely to reflect changes in population health. Its explanation is open to debate.

Conclusions
Growth in expenditure per household has been more than threefold faster for elderly than young households. Across this period, expenditure per household per week has increased by 51% for the young, by 79% for the middle aged and by 179% for the elderly. This age-related growth is most prominent in expenditure on acute care, community health services and pharmaceuticals.

What is known about the topic?
The Productivity Commission has published figures that relate age and Australian heath expenditure. However, there has been no published study of age-related trends in Australian health expenditure.

What does this paper add?
In addition to tracking age-related trends across 26 years, this paper adds a breakdown of those trends into four categories of expenditure, namely acute care, community health services, pharmaceutical benefits, and other. This breakdown shows that the trends vary by expenditure type.

What are the implications for practitioners?
The paper shows that forward projections in health expenditure need to take into account age-related trends as well as demographic trends.
Stress preconditioning of semen before cryopreservation improves fertility and increases the number of offspring born: a prospective randomised study using a porcine model
Authors: Horváth A. , Szenci O. , Nagy K. , Végh L. , Pribenszky Cs.
Published: August 2014

The aim of the present study was to investigate the effect of applying sublethal stress treatment at room temperature, before cryopreservation (hydrostatic pressure (HP): 40 MPa, 80 min) of 34 boar ejaculate samples, on post-thawed motility and sow fertility. Sows (n = 102) were randomly allocated into equal groups inseminated with HP-treated or untreated frozen–thawed semen. Sows were inseminated twice, 10 h apart, with 6 × 109 spermatozoa per dose without oestrus synchronisation. Rates of non-return of oestrus and pregnancy, and total numbers of piglets and live piglets were significantly higher (P < 0.05) in the HP-treated group. There was also a numerical, albeit non-significant (P > 0.05), improvement in the farrowing rate in the HP-treated group. Although the number of live piglets per litter decreased approximately 15% in both groups by 42 days after farrowing, but this remained significantly higher in the HP-treated group. Although total and progressive sperm motility were significantly (P < 0.001) higher in the HP-treated group, there were no significant differences (P > 0.05) in these parameters between pregnant and non-pregnant sows in either group; thus motility can indicate, but not predict, improved fertility. In conclusion, HP treatment, with sperm cryopreservation, increases in vitro sperm motility and improves reproductive performance without adversely affecting the health of the piglets.
Human extravillous trophoblast invasion: intrinsic and extrinsic regulation
Authors: Menkhorst E. , Winship A. , Van Sinderen M. , Dimitriadis E.
Published: August 2014

During the establishment of pregnancy, a human blastocyst implants into the uterine endometrium to facilitate the formation of a functional placenta. Implantation involves the blastocyst adhering to the uterine luminal epithelium before the primitive syncytiotrophoblast and subsequently specialised cells, the extravillous trophoblast (EVT), invade into the decidua in order to engraft and remodel uterine spiral arteries, creating the placental blood supply at the end of the first trimester. Defects in EVT invasion lead to abnormal placentation and thus adverse pregnancy outcomes. The local decidual environment is thought to play a key role in regulating trophoblast invasion. Here we describe the major cell types present in the decidua during the first trimester of pregnancy and review what is known about their regulation of EVT invasion. Overall, the evidence suggests that in a healthy pregnancy almost all cell types in the decidua actively promote EVT invasion and, further, that reduced EVT invasion towards the end of the first trimester is regulated, in part, by the reduced invasive capacity of EVTs shown at this time.
A nation's parks: failure and success in Fascist nature conservation
Authors: von Hardenberg Wilko Graf
Published: August 2014

Nature conservation is a complex venture, with a great impact, among other things, on local and national power relationships. Nature conservation also depends on a wide set of variables to determine any one planned initiative's long-term success or failure. This article explores what made the difference between success and failure in the history of nature conservation under Mussolini's regime. Many parks were planned in those years in Italy, but only a handful were effectively instituted. This essay will address the following questions: What were the reasons behind the planning and creation of these national parks? What was the role of Fascist ideology in determining the long-term success of a park proposal? Was there anything specifically Fascist in Italian nature conservation in the 1920s and 1930s? Which other variables impacted on the involved decision-making processes?
Where did that come from?—Identifying the source of a sample
Authors: Lindskog Marcus
Published: August 2014

People's ability to summarize their knowledge of an observed numerical variable has been extensively studied. However, many real-life situations require people to go beyond summary statistics and infer which process or distribution has generated a sample. The present study investigates the extent to which people can make such inferences when the experienced variable is continuous and when they have had previous experience with instances of the variable. It also tests specific predictions derived from three possible cognitive processes of how inferences about a generating distribution are made. The results indicate that participants are efficient and flexible intuitive statisticians, requiring only as little as four observations in a sample to successfully infer which distribution it came from. Further, the results indicate that the cognitive process supporting the inference uses statistical properties of both an experienced distribution and a presented test sample, as suggested by the Naïve Sampling Model (NSM).
Interplay between phosphorylation and palmitoylation mediates plasma membrane targeting and sorting of GAP43
Authors: Gauthier-Kemper Anne , Igaev Maxim , Sündermann Frederik , Janning Dennis , Brühmann Jörg , Moschner Katharina , Reyher Hans-Jürgen , Junge Wolfgang , Glebov Konstantin , Walter Jochen , Bakota Lidia , Brandt Roland
Published: August 2014

Phosphorylation and lipidation provide posttranslational mechanisms that contribute to the distribution of cytosolic proteins in growing nerve cells. The growth-associated protein GAP43 is susceptible to both phosphorylation and S-palmitoylation and is enriched in the tips of extending neurites. However, how phosphorylation and lipidation interplay to mediate sorting of GAP43 is unclear. Using a combination of biochemical, genetic, and imaging approaches, we show that palmitoylation is required for membrane association and that phosphorylation at Ser-41 directs palmitoylated GAP43 to the plasma membrane. Plasma membrane association decreased the diffusion constant fourfold in neuritic shafts. Sorting to the neuritic tip required palmitoylation and active transport and was increased by phosphorylation-mediated plasma membrane interaction. Vesicle tracking revealed transient association of a fraction of GAP43 with exocytic vesicles and motion at a fast axonal transport rate. Simulations confirmed that a combination of diffusion, dynamic plasma membrane interaction and active transport of a small fraction of GAP43 suffices for efficient sorting to growth cones. Our data demonstrate a complex interplay between phosphorylation and lipidation in mediating the localization of GAP43 in neuronal cells. Palmitoylation tags GAP43 for global sorting by piggybacking on exocytic vesicles, whereas phosphorylation locally regulates protein mobility and plasma membrane targeting of palmitoylated GAP43.
So you think you can edit?
Authors: Budde Priya Prakash
Published: August 2014

This article presents one scientist's perspective on the transition from life at the bench to an editorial career.
RNA-binding protein HuR promotes growth of small intestinal mucosa by activating the Wnt signaling pathway
Authors: Liu Lan , Christodoulou-Vafeiadou Eleni , Rao Jaladanki N. , Zou Tongtong , Xiao Lan , Kyoung Chung Hee , Yang Hong , Gorospe Myriam , Kontoyiannis Dimitris , Wang Jian-Ying
Published: August 2014

Inhibition of growth of the intestinal epithelium, a rapidly self-renewing tissue, is commonly found in various critical disorders. The RNA-binding protein HuR is highly expressed in the gut mucosa and modulates the stability and translation of target mRNAs, but its exact biological function in the intestinal epithelium remains unclear. Here, we investigated the role of HuR in intestinal homeostasis using a genetic model and further defined its target mRNAs. Targeted deletion of HuR in intestinal epithelial cells caused significant mucosal atrophy in the small intestine, as indicated by decreased cell proliferation within the crypts and subsequent shrinkages of crypts and villi. In addition, the HuR-deficient intestinal epithelium also displayed decreased regenerative potential of crypt progenitors after exposure to irradiation. HuR deficiency decreased expression of the Wnt coreceptor LDL receptor–related protein 6 (LRP6) in the mucosal tissues. At the molecular level, HuR was found to bind the Lrp6 mRNA via its 3′-untranslated region and enhanced LRP6 expression by stabilizing Lrp6 mRNA and stimulating its translation. These results indicate that HuR is essential for normal mucosal growth in the small intestine by altering Wnt signals through up-regulation of LRP6 expression and highlight a novel role of HuR deficiency in the pathogenesis of intestinal mucosal atrophy under pathological conditions.
Type II transmembrane domain hydrophobicity dictates the cotranslational dependence for inversion
Authors: Dou Dan , da Silva Diogo V. , Nordholm Johan , Wang Hao , Daniels Robert
Published: August 2014

Membrane insertion by the Sec61 translocon in the endoplasmic reticulum (ER) is highly dependent on hydrophobicity. This places stringent hydrophobicity requirements on transmembrane domains (TMDs) from single-spanning membrane proteins. On examining the single-spanning influenza A membrane proteins, we found that the strict hydrophobicity requirement applies to the Nout-CinHA and M2 TMDs but not the Nin-CoutTMDs from the type II membrane protein neuraminidase (NA). To investigate this discrepancy, we analyzed NA TMDs of varying hydrophobicity, followed by increasing polypeptide lengths, in mammalian cells and ER microsomes. Our results show that the marginally hydrophobic NA TMDs (ΔGapp> 0 kcal/mol) require the cotranslational insertion process for facilitating their inversion during translocation and a positively charged N-terminal flanking residue and that NA inversion enhances its plasma membrane localization. Overall the cotranslational inversion of marginally hydrophobic NA TMDs initiates once ∼70 amino acids past the TMD are synthesized, and the efficiency reaches 50% by ∼100 amino acids, consistent with the positioning of this TMD class in type II human membrane proteins. Inversion of the M2 TMD, achieved by elongating its C-terminus, underscores the contribution of cotranslational synthesis to TMD inversion.
Osh4p is needed to reduce the level of phosphatidylinositol-4-phosphate on secretory vesicles as they mature
Authors: Ling Yading , Hayano Scott , Novick Peter
Published: August 2014

Phosphatidylinositol-4-phosphate (PI4P) is produced on both the Golgi and the plasma membrane. Despite extensive vesicular traffic between these compartments, genetic analysis suggests that the two pools of PI4P do not efficiently mix with one another. Several lines of evidence indicate that the PI4P produced on the Golgi is normally incorporated into secretory vesicles, but the fate of that pool has been unclear. We show here that in yeast the oxysterol-binding proteins Osh1–Osh7 are collectively needed to maintain the normal distribution of PI4P and that Osh4p is critical in this function. Osh4p associates with secretory vesicles at least in part through its interaction with PI4P and is needed, together with lipid phosphatases, to reduce the level of PI4P as vesicles approach sites of exocytosis. This reduction in PI4P is necessary for a switch in the regulation of the Sec4p exchange protein, Sec2p, from an interaction with the upstream Rab, Ypt31/32, to an interaction with a downstream Sec4p effector, Sec15p. Spatial regulation of PI4P levels thereby plays an important role in vesicle maturation.
Quantitative analysis of APP axonal transport in neurons: role of JIP1 in enhanced APP anterograde transport
Authors: Chiba Kyoko , Araseki Masahiko , Nozawa Keisuke , Furukori Keiko , Araki Yoichi , Matsushima Takahide , Nakaya Tadashi , Hata Saori , Saito Yuhki , Uchida Seiichi , Okada Yasushi , Nairn Angus C. , Davis Roger J. , Yamamoto Tohru , Kinjo Masataka , Taru Hidenori , Suzuki Toshiharu
Published: August 2014

Alzheimer's β-amyloid precursor protein (APP) associates with kinesin-1 via JNK-interacting protein 1 (JIP1); however, the role of JIP1 in APP transport by kinesin-1 in neurons remains unclear. We performed a quantitative analysis to understand the role of JIP1 in APP axonal transport. In JIP1-deficient neurons, we find that both the fast velocity (∼2.7 μm/s) and high frequency (66%) of anterograde transport of APP cargo are impaired to a reduced velocity (∼1.83 μm/s) and a lower frequency (45%). We identified two novel elements linked to JIP1 function, located in the central region of JIP1b, that interact with the coiled-coil domain of kinesin light chain 1 (KLC1), in addition to the conventional interaction of the JIP1b 11–amino acid C-terminal (C11) region with the tetratricopeptide repeat of KLC1. High frequency of APP anterograde transport is dependent on one of the novel elements in JIP1b. Fast velocity of APP cargo transport requires the C11 domain, which is regulated by the second novel region of JIP1b. Furthermore, efficient APP axonal transport is not influenced by phosphorylation of APP at Thr-668, a site known to be phosphorylated by JNK. Our quantitative analysis indicates that enhanced fast-velocity and efficient high-frequency APP anterograde transport observed in neurons are mediated by novel roles of JIP1b.
Flat clathrin lattices: stable features of the plasma membrane
Authors: Grove Joe , Metcalf Daniel J. , Knight Alex E. , Wavre-Shapton Silène T. , Sun Tony , Protonotarios Emmanouil D. , Griffin Lewis D. , Lippincott-Schwartz Jennifer , Marsh Mark
Published: August 2014

Clathrin-mediated endocytosis (CME) is a fundamental property of eukaryotic cells. Classical CME proceeds via the formation of clathrin-coated pits (CCPs) at the plasma membrane, which invaginate to form clathrin-coated vesicles, a process that is well understood. However, clathrin also assembles into flat clathrin lattices (FCLs); these structures remain poorly described, and their contribution to cell biology is unclear. We used quantitative imaging to provide the first comprehensive description of FCLs and explore their influence on plasma membrane organization. Ultrastructural analysis by electron and superresolution microscopy revealed two discrete populations of clathrin structures. CCPs were typified by their sphericity, small size, and homogeneity. FCLs were planar, large, and heterogeneous and present on both the dorsal and ventral surfaces of cells. Live microscopy demonstrated that CCPs are short lived and culminate in a peak of dynamin recruitment, consistent with classical CME. In contrast, FCLs were long lived, with sustained association with dynamin. We investigated the biological relevance of FCLs using the chemokine receptor CCR5 as a model system. Agonist activation leads to sustained recruitment of CCR5 to FCLs. Quantitative molecular imaging indicated that FCLs partitioned receptors at the cell surface. Our observations suggest that FCLs provide stable platforms for the recruitment of endocytic cargo.
The novel component Kgd4 recruits the E3 subunit to the mitochondrial α-ketoglutarate dehydrogenase
Authors: Heublein Manfred , Burguillos Miguel A. , Vögtle F. Nora , Teixeira Pedro F. , Imhof Axel , Meisinger Chris , Ott Martin
Published: August 2014

The mitochondrial citric acid cycle is a central hub of cellular metabolism, providing intermediates for biosynthetic pathways and channeling electrons to the respiratory chain complexes. In this study, we elucidated the composition and organization of the multienzyme complex α-ketoglutarate dehydrogenase (α-KGDH). In addition to the three classical E1-E3 subunits, we identified a novel component, Kgd4 (Ymr31/MRPS36), which was previously assigned to be a subunit of the mitochondrial ribosome. Biochemical analyses demonstrate that this protein plays an evolutionarily conserved role in the organization of mitochondrial α-KGDH complexes of fungi and animals. By binding to both the E1-E2 core and the E3 subunit, Kgd4 acts as a molecular adaptor that is necessary to a form a stable α-KGDH enzyme complex. Our work thus reveals a novel subunit of a key citric acid–cycle enzyme and shows how this large complex is organized.
LoRDEC: accurate and efficient long read error correction
Authors: Salmela Leena , Rivals Eric
Published: August 2014

Motivation: PacBio single molecule real-time sequencing is a third-generation sequencing technique producing long reads, with comparatively lower throughput and higher error rate. Errors include numerous indels and complicate downstream analysis like mapping or de novo assembly. A hybrid strategy that takes advantage of the high accuracy of second-generation short reads has been proposed for correcting long reads. Mapping of short reads on long reads provides sufficient coverage to eliminate up to 99% of errors, however, at the expense of prohibitive running times and considerable amounts of disk and memory space.

Results : We present LoRDEC, a hybrid error correction method that builds a succinct de Bruijn graph representing the short reads, and seeks a corrective sequence for each erroneous region in the long reads by traversing chosen paths in the graph. In comparison, LoRDEC is at least six times faster and requires at least 93% less memory or disk space than available tools, while achieving comparable accuracy.

Availability and implementaion : LoRDEC is written in C++, tested on Linux platforms and freely available at http://atgc.lirmm.fr/lordec .

Contact:  lordec@lirmm.fr .

Supplementary information:  Supplementary data are available at Bioinformatics online.
Fixation in finite populations evolving in fluctuating environments
Authors: Ashcroft Peter , Altrock Philipp M. , Galla Tobias
Published: August 2014

The environment in which a population evolves can have a crucial impact on selection. We study evolutionary dynamics in finite populations of fixed size in a changing environment. The population dynamics are driven by birth and death events. The rates of these events may vary in time depending on the state of the environment, which follows an independent Markov process. We develop a general theory for the fixation probability of a mutant in a population of wild-types, and for mean unconditional and conditional fixation times. We apply our theory to evolutionary games for which the payoff structure varies in time. The mutant can exploit the environmental noise; a dynamic environment that switches between two states can lead to a probability of fixation that is higher than in any of the individual environmental states. We provide an intuitive interpretation of this surprising effect. We also investigate stationary distributions when mutations are present in the dynamics. In this regime, we find two approximations of the stationary measure. One works well for rapid switching, the other for slowly fluctuating environments.
Delayed self-regulation and time-dependent chemical drive leads to novel states in epigenetic landscapes
Authors: Mitra Mithun K. , Taylor Paul R. , Hutchison Chris J. , McLeish T. C. B. , Chakrabarti Buddhapriya
Published: August 2014

The epigenetic pathway of a cell as it differentiates from a stem cell state to a mature lineage-committed one has been historically understood in terms of Waddington's landscape, consisting of hills and valleys. The smooth top and valley-strewn bottom of the hill represent their undifferentiated and differentiated states, respectively. Although mathematical ideas rooted in nonlinear dynamics and bifurcation theory have been used to quantify this picture, the importance of time delays arising from multistep chemical reactions or cellular shape transformations have been ignored so far. We argue that this feature is crucial in understanding cell differentiation and explore the role of time delay in a model of a single-gene regulatory circuit. We show that the interplay of time-dependent drive and delay introduces a new regime where the system shows sustained oscillations between the two admissible steady states. We interpret these results in the light of recent perplexing experiments on inducing the pluripotent state in mouse somatic cells. We also comment on how such an oscillatory state can provide a framework for understanding more general feedback circuits in cell development.
Multiple solutions and numerical analysis to the dynamic and stationary models coupling a delayed energy balance model involving latent heat and discontinuous albedo with a deep ocean
Authors: Díaz J. I. , Hidalgo A. , Tello L.
Published: August 2014

We study a climatologically important interaction of two of the main components of the geophysical system by adding an energy balance model for the averaged atmospheric temperature as dynamic boundary condition to a diagnostic ocean model having an additional spatial dimension. In this work, we give deeper insight than previous papers in the literature, mainly with respect to the 1990 pioneering model by Watts and Morantine. We are taking into consideration the latent heat for the two phase ocean as well as a possible delayed term. Non-uniqueness for the initial boundary value problem, uniqueness under a non-degeneracy condition and the existence of multiple stationary solutions are proved here. These multiplicity results suggest that an S-shaped bifurcation diagram should be expected to occur in this class of models generalizing previous energy balance models. The numerical method applied to the model is based on a finite volume scheme with nonlinear weighted essentially non-oscillatory reconstruction and Runge–Kutta total variation diminishing for time integration.
Stenotrophomonas maltophilia in Mexico: antimicrobial resistance, biofilm formation and clonal diversity
Authors: Flores-Treviño Samantha , Gutiérrez-Ferman Jessica Lizzeth , Morfín-Otero Rayo , Rodríguez-Noriega Eduardo , Estrada-Rivadeneyra Diego , Rivas-Morales Catalina , Llaca-Díaz Jorge M. , Camacho-Ortíz Adrián , Mendoza-Olazarán Soraya , Garza-González Elvira
Published: August 2014

Stenotrophomonas maltophiliais an important multidrug-resistant nosocomial pathogen associated with high mortality. Our aim was to examine antimicrobial susceptibility, biofilm production and clonal relatedness of clinical isolates ofS. maltophilia.S. maltophiliaisolates were collected between 2006 and 2013 from two tertiary care hospitals in Mexico. Antimicrobial susceptibility was evaluated by the broth microdilution method. PCR was used to determine the presence of β-lactamase genes L1 and L2. Biofilm formation was assessed with crystal violet staining. Clonal relatedness was determined by PFGE. Among the 119 collectedS. maltophiliaisolates, 73 (61.3 %) were from the respiratory tract. Resistance levels exceeded 75 % for imipenem, meropenem, ampicillin, aztreonam, gentamicin and tobramycin. Resistance to trimethoprim-sulfamethoxazole was 32.8 %. L1 and L2 genes were detected in 77.1 % (91/118) and 66.9 % (79/118) of isolates, respectively. AllS. maltophiliastrains were able to produce biofilms. Strains were classified as weak (47.9 %, 57/119), moderate (38.7 %, 46/119), or strong (13.4 %, 16/119) biofilm producers. A total of 89 distinct PFGE types were identified and 21.6 % (22/102) of the isolates were distributed in nine clusters. This is the first study in Mexico to reveal characteristics of clinical isolates ofS. maltophilia. Clonal diversity data indicate low cross-transmission ofS. maltophiliain a hospital setting. The high antibiotic resistance underscores the need for continuous surveillance ofS. maltophiliain hospital settings in Mexico.
Indole inhibition of N-acylated homoserine lactone-mediated quorum signalling is widespread in Gram-negative bacteria
Authors: Hidalgo-Romano Benjamin , Gollihar Jimmy , Brown Stacie A. , Whiteley Marvin , Valenzuela Ernesto , Kaplan Heidi B. , Wood Thomas K. , McLean Robert J. C.
Published: August 2014

The LuxI/R quorum-sensing system and its associated N-acylated homoserine lactone (AHL) signal is widespread among Gram-negative bacteria. Although inhibition by indole of AHL quorum signalling in Pseudomonas aeruginosa and Acinetobacter oleivorans has been reported previously, it has not been documented among other species. Here, we show that co-culture with wild-type Escherichia coli, but not with E. coli tnaA mutants that lack tryptophanase and as a result do not produce indole, inhibits AHL-regulated pigmentation in Chromobacterium violaceum (violacein), Pseudomonas chlororaphis (phenazine) and Serratia marcescens (prodigiosin). Loss of pigmentation also occurred during pure culture growth of Chro. violaceum, P. chlororaphis and S. marcescens in the presence of physiologically relevant indole concentrations (0.5–1.0 mM). Inhibition of violacein production by indole was counteracted by the addition of the Chro. violaceum cognate autoinducer, N-decanoyl homoserine lactone (C10-HSL), in a dose-dependent manner. The addition of exogenous indole or co-culture with E. coli also affected Chro. violaceum transcription of vioA (violacein pigment production) and chiA (chitinase production), but had no effect on pykF (pyruvate kinase), which is not quorum regulated. Chro. violaceum AHL-regulated elastase and chitinase activity were inhibited by indole, as was motility. Growth of Chro. violaceum was not affected by indole or C10-HSL supplementation. Using a nematode-feeding virulence assay, we observed that survival of Caenorhabditis elegans exposed to Chro. violaceum, P. chlororaphis and S. marcescens was enhanced during indole supplementation. Overall, these studies suggest that indole represents a general inhibitor of AHL-based quorum signalling in Gram-negative bacteria.
Rational design and adaptive management of combination therapies for Hepatitis C virus infection
Authors: Ke Ruian , Loverdo Claude , Qi Hangfei , Sun Ren , Lloyd-Smith James O.
Published: August 2014

Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky forde novoresistance, and quantifying the number of additional doses needed to compensate when doses are missed. Using data from large-scale resistance assays, we demonstrate that the risk of resistance can be reduced substantially by applying these principles to a combination therapy of daclatasvir and asunaprevir. By providing a mechanistic framework to link patient characteristics to the risk of resistance, these findings show the potential of rational treatment design.
Genomic and transcriptomic insights into the regulation of snake venom production
Authors: Hargreaves Adam D. , Swain Martin T. , Hegarty Matthew J. , Logan Darren W. , Mulley John F.
Published: August 2014

The gene regulatory mechanisms underlying the rapid replenishment of snake venom following expenditure are currently unknown. Using a comparative transcriptomic approach we find that venomous and non-venomous species produce similar numbers of secreted products in their venom or salivary glands and that only one transcription factor (Tbx3) is expressed in venom glands but not salivary glands. We also find evidence for temporal variation in venom production. We have generated a draft genome sequence for the painted saw-scaled viper,Echis coloratus, and identified conserved transcription factor binding sites in the upstream regions of venom genes. We find binding sites to be conserved across members of the same gene family, but not between gene families, indicating that multiple gene regulatory networks are involved in venom production. Finally, we suggest that negative regulation may be important for rapid activation of the venom replenishment cycle.
Sexual dimorphism in epigenomic responses of stem cells to extreme fetal growth
Authors: Delahaye Fabien , Ari Wijetunga N. , Heo Hye J. , Tozour Jessica N. , Zhao Yong Mei , Greally John M. , Einstein Francine H.
Published: August 2014

Extreme fetal growth is associated with increased susceptibility to a range of adult diseases through an unknown mechanism of cellular memory. We tested whether heritable epigenetic processes in long-lived CD34+ hematopoietic stem/progenitor cells (HSPCs) showed evidence for re-programming associated with the extremes of fetal growth. Here we show that both fetal growth restriction and over-growth are associated with global shifts towards DNA hypermethylation, targetingcis-regulatory elements in proximity to genes involved in glucose homeostasis and stem cell function. A sexually dimorphic response was found, intrauterine growth restriction (IUGR) associated with substantially greater epigenetic dysregulation in males but large for gestational age (LGA) growth affecting females predominantly. The findings are consistent with extreme fetal growth interacting with variable fetal susceptibility to influence cellular aging and metabolic characteristics through epigenetic mechanisms, potentially generating biomarkers that could identify infants at higher risk for chronic disease later in life.
Hard X-ray nanofocusing at low-emittance synchrotron radiation sources
Authors: Schroer Christian G. , Falkenberg Gerald
Published: August 2014

X-ray scanning microscopy relies on intensive nanobeams generated by imaging a highly brilliant synchrotron radiation source onto the sample with a nanofocusing X-ray optic. Here, using a Gaussian model for the central cone of an undulator source, the nanobeam generated by refractive X-ray lenses is modeled in terms of size, flux and coherence. The beam properties are expressed in terms of the emittances of the storage ring and the lateral sizes of the electron beam. Optimal source parameters are calculated to obtain efficient and diffraction-limited nanofocusing. With decreasing emittance, the usable fraction of the beam for diffraction-limited nanofocusing experiments can be increased by more than two orders of magnitude compared with modern storage ring sources. For a diffraction-limited storage ring, nearly the whole beam can be focused, making these sources highly attractive for X-ray scanning microscopy.
Molecular replacement with a large number of molecules in the asymmetric unit
Authors: Jobichen Chacko , Swaminathan Kunchithapadam
Published: August 2014

The exponential increase in protein structures deposited in the Protein Data Bank (PDB) has resulted in the elucidation of most, if not all, protein folds, thus making molecular replacement (MR) the most frequently used method for structure determination. A survey of the PDB shows that most of the structures determined by molecular replacement contain less than ten molecules in the asymmetric unit and that it is predominantly virus and ribosome structures that contain more than 20 molecules in the asymmetric unit. While the success of the MR method depends on several factors, such as the homology and the size of an input model, it is also a well known fact that this method can become significantly difficult in cases with a large number of molecules in the asymmetric unit, higher crystallographic symmetry and tight packing. In this paper, five representative structures containing 16–18 homomeric molecules in the asymmetric unit and the strategies that have been used to solve these structures are described. The difficulties faced and the lessons learned from these structure-determination efforts will be useful for selected and similar future situations with a large number of molecules in the asymmetric unit.
Cloning, expression, purification, crystallization and preliminary crystallographic analysis of the C-terminal domain of Par-4 (PAWR)
Authors: Tiruttani Subhramanyam Udaya Kumar , Kubicek Jan , Eidhoff Ulf B. , Labahn Joerg
Published: August 2014

Prostate apoptosis response-4 protein is an intrinsically disordered pro-apoptotic protein with tumour suppressor function. Par-4 is known for its selective induction of apoptosis in cancer cells only and its ability to interact with various apoptotic proteinsviaits C-terminus. Par-4, with its unique function and various interacting partners, has gained importance as a potential target for cancer therapy. The C-terminus of the rat homologue of Par-4 was crystallized and a 3.7 Å resolution X-ray diffraction data set was collected. Preliminary data analysis shows the space group to beP41212. The unit-cell parameters area=b= 115.351,c= 123.663 Å, α = β = γ = 90°.
Expression, purification, crystallization and preliminary crystallographic analysis of human myotubularin-related protein 3
Authors: Son Ji Young , Lee Jee Un , Yoo Ki-Young , Shin Woori , Im Dong-Won , Kim Seung Jun , Ryu Seong Eon , Heo Yong-Seok
Published: August 2014

Myotubularin-related proteins are a large family of phosphatases that have the catalytic activity of dephosphorylating the phospholipid molecules phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate. Each of the 14 family members contains a phosphatase catalytic domain, which is inactive in six family members owing to amino-acid changes in a key motif for the activity. All of the members also bear PH-GRAM domains, which have low homologies between them and have roles that are not yet clear. Here, the cloning, expression, purification and crystallization of human myotubularin-related protein 3 encompassing the PH-GRAM and the phosphatase catalytic domain are reported. Preliminary X-ray crystallographic analysis shows that the crystals diffracted to 3.30 Å resolution at a synchrotron X-ray source. The crystals belonged to space groupC2, with unit-cell parametersa= 323.3,b= 263.3,c= 149.4 Å, β = 109.7°.