bluuebunny/crossref_metadata_2025 huggingface dataset:
Optical activity and coupling in twisted dimer meta-atoms
Authors: Liu Mingkai , Powell David A. , Shadrivov Ilya V. , Kivshar Yuri S.
Published: March 2012

We analyse the optical activity in twisted dimers, the meta-atoms of a chiral metamaterial, by introducing a simple yet accurate model for the coupling between them. The near-field interaction coefficients are derived from a Lagrangian model and include the effects of retardation, whereas the far-field radiation is based on a multipole expansion. We show that the optimum twist angle varies with frequency, and near resonance is substantially lower than 45 degrees, which is the lowest symmetry configuration. Our approach is accurate over a wide frequency range, including the resonant regions with the highest optical activity. In contrast to other models of near-field interaction, it requires no fitted parameters or homogenization procedure and is directly applicable to a wide variety of resonant particles.
Electrical characterization of a-InGaZnO thin-film transistors with Cu source/drain electrodes
Authors: Jeong Jaewook , Jun Lee Gwang , Kim Joonwoo , Choi Byeongdae
Published: March 2012

We analyzed the effects of Cu source/drain (S/D) electrodes on the performance of a-InGaZnO (a-IGZO) thin-film transistors (TFTs). Owing to the Cu migration, the parasitic resistance was as low as 10 Ω cm with small current transfer length. Based on the transfer characteristics, we found that VDS dependent Cu migration creates donor-like deep and tail states in the sub-bandgap region. The feasibility of Cu S/D electrodes for a-IGZO TFTs using inverter circuits indicates that fabrication of high performance circuits is possible by controlling the Cu electro-migration.
Physical understanding of cryogenic implant benefits for electrical junction stability
Authors: Adeni Khaja Fareen , Colombeau Benjamin , Thanigaivelan Thirumal , Ramappa Deepak , Henry Todd
Published: March 2012

We investigate the effect of cryogenic temperature implants on electrical junction stability for ultra shallow junction applications for sub-32 nm technology nodes and beyond. A comprehensive study was conducted to gain physical understanding of the impact of cryogenic temperature implants on dopant-defect interactions. Carborane (C2B10H12) molecule, a potential alternative to monomer boron was implanted in carbon preamorphized silicon substrates at cryogenic implant temperatures. Results indicate implants at cryogenic temperatures increase dopant activation with reduced diffusion, resulting in lower sheet resistance for a lower junction depth. Further, this study emphasizes the benefits of co-implants performed at cryogenic temperatures as alternative to traditional preamorphizing implants.
Melting of monatomic glass with free surfaces
Authors: Van Hoang Vo , Quy Dong To
Published: March 2012

Melting of monatomic glass with free surfaces has been studied by molecular dynamics simulations in models with Lennard-Jones-Gauss interatomic potential. Models have been heated up from a glassy state toward a normal liquid state. Atomic mechanism of melting has been analyzed via monitoring spatio-temporal arrangements of liquid-like atoms occurred during heating process. Liquid-like atoms are detected via the Lindemann criterion of melting. It is clear that the transition from glass into supercooled liquid of our “ordinary” glass with free surfaces exhibits a non-heterogeneous behavior, i.e., although liquid-like atoms initiate/grow mainly in the surface shell, significant amount of liquid-like atoms also initiates/grows simultaneously in the interior during heating process. We found three characteristic temperatures of melting of glass with a free surface. Temperature dependence of structure and various thermodynamic quantities of the system upon heating is also presented and discussed.
Eumelanin kinetics and sheet structure
Authors: Sutter J. U. , Bidláková T. , Karolin J. , Birch D. J. S.
Published: March 2012

Melanins are common pigments with a non-repeating primary structure that is generally accepted to be composed of dihydroxyindoles. However, despite intensive research the secondary structure defining the minimum functional unit (protomolecule) remains elusive. We have revisited eumelanin formation in-situ during the non-enzymatic auto-oxidation of 3,4-dihydroxy-L-phenylalanine by using the fluorescence of thioflavin T; an extrinsic probe known to report on sheet structure. This approach obviates the complex intrinsic fluorescence and reveals a sigmoidal temporal dependence of assembly that is consistent with protomolecule formation and assembly into a stacked sheet structure rather than a randomized heteropolymer formed by monomer addition.
Selective killing of ovarian cancer cells through induction of apoptosis by nonequilibrium atmospheric pressure plasma
Authors: Iseki Sachiko , Nakamura Kae , Hayashi Moemi , Tanaka Hiromasa , Kondo Hiroki , Kajiyama Hiroaki , Kano Hiroyuki , Kikkawa Fumitaka , Hori Masaru
Published: March 2012

Two independent ovarian cancer cell lines and fibroblast controls were treated with nonequilibrium atmospheric pressure plasma (NEAPP). Most ovarian cancer cells were detached from the culture dish by continuous plasma treatment to a single spot on the dish. Next, the plasma source was applied over the whole dish using a robot arm. In vitro cell proliferation assays showed that plasma treatments significantly decreased proliferation rates of ovarian cancer cells compared to fibroblast cells. Flow cytometry and western blot analysis showed that plasma treatment of ovarian cancer cells induced apoptosis. NEAPP could be a promising tool for therapy for ovarian cancers.
An over-oxidized form of superoxide dismutase found in sporadic amyotrophic lateral sclerosis with bulbar onset shares a toxic mechanism with mutant SOD1
Authors: Guareschi Stefania , Cova Emanuela , Cereda Cristina , Ceroni Mauro , Donetti Elena , Bosco Daryl A. , Trotti Davide , Pasinelli Piera
Published: March 2012

Recent studies suggest that Cu/Zn superoxide dismutase (SOD1) could be pathogenic in both familial and sporadic amyotrophic lateral sclerosis (ALS) through either inheritable or nonheritable modifications. The presence of a misfolded WT SOD1 in patients with sporadic ALS, along with the recently reported evidence that reducing SOD1 levels in astrocytes derived from sporadic patients inhibits astrocyte-mediated toxicity on motor neurons, suggest that WT SOD1 may acquire toxic properties similar to familial ALS-linked mutant SOD1, perhaps through posttranslational modifications. Using patients’ lymphoblasts, we show here that indeed WT SOD1 is modified posttranslationally in sporadic ALS and is iper-oxidized (i.e., above baseline oxidation levels) in a subset of patients with bulbar onset. Derivatization analysis of oxidized carbonyl compounds performed on immunoprecipitated SOD1 identified an iper-oxidized SOD1 that recapitulates mutant SOD1-like properties and damages mitochondria by forming a toxic complex with mitochondrial Bcl-2. This study conclusively demonstrates the existence of an iper-oxidized SOD1 with toxic properties in patient-derived cells and identifies a common SOD1-dependent toxicity between mutant SOD1-linked familial ALS and a subset of sporadic ALS, providing an opportunity to develop biomarkers to subclassify ALS and devise SOD1-based therapies that go beyond the small group of patients with mutant SOD1.
Lateral gene transfer as a support for the tree of life
Authors: Abby Sophie S. , Tannier Eric , Gouy Manolo , Daubin Vincent
Published: March 2012

Lateral gene transfer (LGT), the acquisition of genes from other species, is a major evolutionary force. However, its success as an adaptive process makes the reconstruction of the history of life an intricate puzzle: If no gene has remained unaffected during the course of life's evolution, how can one rely on molecular markers to reconstruct the relationships among species? Here, we take a completely different look at LGT and its impact for the reconstruction of the history of life. Rather than trying to remove the effect of LGT in phylogenies, and ignoring as a result most of the information of gene histories, we use an explicit phylogenetic model of gene transfer to reconcile gene histories with the tree of species. We studied 16 bacterial and archaeal phyla, representing a dataset of 12,000 gene families distributed in 336 genomes. Our results show that, in most phyla, LGT provides an abundant phylogenetic signal on the pattern of species diversification and that this signal is robust to the choice of gene families under study. We also find that LGT brings an abundant signal on the location of the root of species trees, which has been previously overlooked. Our results quantify the great variety of gene transfer rates among lineages of the tree of life and provide strong support for the “complexity hypothesis,” which states that genes whose products participate to macromolecular protein complexes are relatively resistant to transfer.
Magnetically sensitive light-induced reactions in cryptochrome are consistent with its proposed role as a magnetoreceptor
Authors: Maeda Kiminori , Robinson Alexander J. , Henbest Kevin B. , Hogben Hannah J. , Biskup Till , Ahmad Margaret , Schleicher Erik , Weber Stefan , Timmel Christiane R. , Hore P. J.
Published: March 2012

Among the biological phenomena that fall within the emerging field of “quantum biology” is the suggestion that magnetically sensitive chemical reactions are responsible for the magnetic compass of migratory birds. It has been proposed that transient radical pairs are formed by photo-induced electron transfer reactions in cryptochrome proteins and that their coherent spin dynamics are influenced by the geomagnetic field leading to changes in the quantum yield of the signaling state of the protein. Despite a variety of supporting evidence, it is still not clear whether cryptochromes have the properties required to respond to magnetic interactions orders of magnitude weaker than the thermal energy,
k
B
T
. Here we demonstrate that the kinetics and quantum yields of photo-induced flavin—tryptophan radical pairs in cryptochrome are indeed magnetically sensitive. The mechanistic origin of the magnetic field effect is clarified, its dependence on the strength of the magnetic field measured, and the rates of relevant spin-dependent, spin-independent, and spin-decoherence processes determined. We argue that cryptochrome is fit for purpose as a chemical magnetoreceptor.
Tomato immune receptor Ve1 recognizes effector of multiple fungal pathogens uncovered by genome and RNA sequencing
Authors: de Jonge Ronnie , Peter van Esse H. , Maruthachalam Karunakaran , Bolton Melvin D. , Santhanam Parthasarathy , Saber Mojtaba Keykha , Zhang Zhao , Usami Toshiyuki , Lievens Bart , Subbarao Krishna V. , Thomma Bart P. H. J.
Published: March 2012

Fungal plant pathogens secrete effector molecules to establish disease on their hosts, and plants in turn use immune receptors to try to intercept these effectors. The tomato immune receptor Ve1 governs resistance to race 1 strains of the soil-borne vascular wilt fungi
Verticillium dahliae
and
Verticillium albo-atrum
, but the corresponding
Verticillium
effector remained unknown thus far. By high-throughput population genome sequencing, a single 50-Kb sequence stretch was identified that only occurs in race 1 strains, and subsequent transcriptome sequencing of
Verticillium
-infected
Nicotiana benthamiana
plants revealed only a single highly expressed ORF in this region, designated
Ave1
(for
A
virulence on Ve1 tomato
). Functional analyses confirmed that Ave1 activates Ve1-mediated resistance and demonstrated that Ave1 markedly contributes to fungal virulence, not only on tomato but also on
Arabidopsis
. Interestingly, Ave1 is homologous to a widespread family of plant natriuretic peptides. Besides plants, homologous proteins were only found in the bacterial plant pathogen
Xanthomonas axonopodis
and the plant pathogenic fungi
Colletotrichum higginsianum
,
Cercospora beticola
, and
Fusarium oxysporum
f. sp.
lycopersici
. The distribution of Ave1 homologs, coincident with the presence of
Ave1
within a flexible genomic region, strongly suggests that
Verticillium
acquired
Ave1
from plants through horizontal gene transfer. Remarkably, by transient expression we show that also the Ave1 homologs from
F. oxysporum
and
C. beticola
can activate
Ve1
-mediated resistance. In line with this observation,
Ve1
was found to mediate resistance toward
F. oxysporum
in tomato, showing that this immune receptor is involved in resistance against multiple fungal pathogens.
Rabbits are not resistant to prion infection
Authors: Chianini Francesca , Fernández-Borges Natalia , Vidal Enric , Gibbard Louise , Pintado Belén , de Castro Jorge , Priola Suzette A. , Hamilton Scott , Eaton Samantha L. , Finlayson Jeanie , Pang Yvonne , Steele Philip , Reid Hugh W. , Dagleish Mark P. , Castilla Joaquín
Published: March 2012

The ability of prions to infect some species and not others is determined by the transmission barrier. This unexplained phenomenon has led to the belief that certain species were not susceptible to transmissible spongiform encephalopathies (TSEs) and therefore represented negligible risk to human health if consumed. Using the protein misfolding cyclic amplification (PMCA) technique, we were able to overcome the species barrier in rabbits, which have been classified as TSE resistant for four decades. Rabbit brain homogenate, either unseeded or seeded in vitro with disease-related prions obtained from different species, was subjected to serial rounds of PMCA. De novo rabbit prions produced in vitro from unseeded material were tested for infectivity in rabbits, with one of three intracerebrally challenged animals succumbing to disease at 766 d and displaying all of the characteristics of a TSE, thereby demonstrating that leporids are not resistant to prion infection. Material from the brain of the clinically affected rabbit containing abnormal prion protein resulted in a 100% attack rate after its inoculation in transgenic mice overexpressing rabbit PrP. Transmissibility to rabbits (>470 d) has been confirmed in 2 of 10 rabbits after intracerebral challenge. Despite rabbits no longer being able to be classified as resistant to TSEs, an outbreak of “mad rabbit disease” is unlikely.
Mitochondrial pathway of apoptosis is ancestral in metazoans
Authors: Bender Cheryl E. , Fitzgerald Patrick , Tait Stephen W. G. , Llambi Fabien , McStay Gavin P. , Tupper Douglas O. , Pellettieri Jason , Alvarado Alejandro Sánchez , Salvesen Guy S. , Green Douglas R.
Published: March 2012

The mitochondrial pathway of apoptosis is the major mechanism of physiological cell death in vertebrates. In this pathway, proapoptotic members of the Bcl-2 family cause mitochondrial outer membrane permeabilization (MOMP), allowing the release of cytochrome
c
, which interacts with Apaf-1 to trigger caspase activation and apoptosis. Despite conservation of Bcl-2, Apaf-1, and caspases in invertebrate phyla, the existence of the mitochondrial pathway in any invertebrate is, at best, controversial. Here we show that apoptosis in a lophotrochozoan, planaria (phylum Platyhelminthes), is associated with MOMP and that cytochrome
c
triggers caspase activation in cytosolic extracts from these animals. Further, planarian Bcl-2 family proteins can induce and/or regulate cell death in yeast and can replace Bcl-2 proteins in mammalian cells to regulate MOMP. These results suggest that the mitochondrial pathway of apoptosis in animals predates the emergence of the vertebrates but was lost in some lineages (e.g., nematodes). In further support of this hypothesis, we surveyed the ability of cytochrome
c
to trigger caspase activation in cytosolic extracts from a variety of organisms and found this effect in cytosolic extracts from invertebrate deuterostomes (phylum Echinodermata).
Antigen-specific memory in B-1a and its relationship to natural immunity
Authors: Yang Yang , Ghosn Eliver Eid Bou , Cole Leah E. , Obukhanych Tetyana V. , Sadate-Ngatchou Patricia , Vogel Stefanie N. , Herzenberg Leonard A. , Herzenberg Leonore A.
Published: March 2012

In the companion article by Yang and colleagues [Yang Y, et al. (2012)
Proc Natl Acad Sci USA
, 109, 10.1073/pnas.1121631109], we have shown that priming with glycolipid (FtL) from
Francisella tularensis
live-vaccine strain (
i
) induces FtL-specific B-1a to produce robust primary responses (IgM >>IgG); (
ii
) establishes persistent long-term production of serum IgM and IgG anti-FtL at natural antibody levels; and (
iii
) elicits FtL-specific B-1a memory cells that arise in spleen but rapidly migrate to the peritoneal cavity, where they persist indefinitely but divide only rarely. Here, we show that FtL rechallenge alone induces these PerC B-1a memory cells to divide extensively and to express a unique activation signature. However, FtL rechallenge in the context of a Toll-like receptor 4 agonist-stimulated inflammatory response readily induces these memory cells to migrate to spleen and initiate production of dominant IgM anti-FtL secondary responses. Thus, studies here reveal unique mechanisms that govern B-1a memory development and expression, and introduce B-1a memory as an active participant in immune defenses. In addition, at a practical level, these studies suggest previously unexplored vaccination strategies for pathogen-associated antigens that target the B-1a repertoire.
Antigen-specific antibody responses in B-1a and their relationship to natural immunity
Authors: Yang Yang , Ghosn Eliver Eid Bou , Cole Leah E. , Obukhanych Tetyana V. , Sadate-Ngatchou Patricia , Vogel Stefanie N. , Herzenberg Leonard A. , Herzenberg Leonore A.
Published: March 2012

B-1a cells are primarily thought of as natural antibody-producing cells. However, we now show that appropriate antigenic stimulation induces IgM and IgG B-1a antibody responses and long-lived T-independent antigen-specific B-1a memory that differs markedly from canonical B-2 humoral immunity. Thus, we show here that in the absence of inflammation, priming with glycolipid (FtL) from
Francisella tularensis
live vaccine strain induces splenic FtL-specific B-1a to mount dominant IgM and activation-induced cytidine deaminase-dependent IgG anti-FtL responses that occur within 3–5 d of FtL priming and fade within 1 wk to natural antibody levels that persist indefinitely in the absence of secondary FtL immunization. Equally surprising, FtL priming elicits long-term FtL-specific B-1a memory cells (IgM>>IgG) that migrate rapidly to the peritoneal cavity and persist there indefinitely, ready to respond to appropriately administrated secondary antigenic stimulation. Unlike B-2 responses, primary FtL-specific B-1a responses and establishment of persistent FtL-specific B-1a memory occur readily in the absence of adjuvants, IL-7, T cells, or germinal center support. However, in another marked departure from the mechanisms controlling B-2 memory responses, rechallenge with FtL in an inflammatory context is required to induce B-1a secondary antibody responses. These findings introduce previously unexplored vaccination strategies for pathogens that target the B-1a repertoire.
Effects of Exposure on Discrimination of Similar Stimuli and on Memory for Their Unique and Common Features
Authors: de Zilva Daniel , Mitchell Chris J.
Published: March 2012

Human participants received exposure to similar visual stimuli (AW and BW) that shared a common feature (W). Experiment 1 demonstrated that subsequent discrimination between AW and BW was more accurate when the two stimuli were preexposed on an intermixed schedule (AW, BW, AW, BW…) than when they were preexposed on a blocked schedule (AW, AW…BW, BW…): the intermixed–blocked effect. Furthermore, memory for the unique features of the stimuli (A and B) was better when the stimuli were preexposed on an intermixed schedule than when they were preexposed on a blocked schedule. Conversely, memory for the common features of the stimuli (W) was better when the stimuli were preexposed on a blocked schedule than when they were preexposed on an intermixed schedule. Experiment 2 again demonstrated the intermixed–blocked effect, but participants were preexposed to the stimuli in such a way that the temporal spacing between exposures to the unique features was equated between schedules. Memory for the unique and common features was similar to that found in Experiment 1. These findings support the proposal that perceptual learning depends on a mechanism that enhances memory for the unique features and reduces memory for common features.
Sensitivity to probabilistic orthographic cues to lexical stress in adolescent speakers with autism spectrum disorder and typical peers
Authors: Arciuli Joanne , Paul Rhea
Published: March 2012

Lexical stress refers to the opposition of strong and weak syllables within polysyllabic words and is a core feature of the English prosodic system. There are probabilistic cues to lexical stress present in English orthography. For example, most disyllabic English words ending with the letters “-ure” have first-syllable stress (e.g., “pasture”, but note words such as “endure”), whereas most ending with “-ose” have second-syllable stress (e.g., “propose”, but note examples such as “glucose”). Adult native speakers of English are sensitive to these probabilities during silent reading. During testing, they tend to assign first-syllable stress when reading a nonword such as “lenture” but second-syllable stress when reading “fostpose” (Arciuli & Cupples, 2006). Difficulties with prosody, including problems processing lexical stress, are a notable feature of autism spectrum disorder (ASD). The current study investigated the ability of adolescents with ASD (13–17 years of age) to show this sensitivity compared with a group of typically developing peers. Results indicated reduced sensitivity to probabilistic cues to lexical stress in the group with ASD. The implications of these findings are discussed.
Modelling of pulsed RF corona discharges in high-pressure air
Authors: Auzas F , Makarov M , Naidis G V
Published: March 2012

An approach to description of pulsed RF corona discharges in high-pressure air is developed, based on the model of a filamentary discharge sustained by an electromagnetic wave guided along the plasma filament. Results of numerical simulation of spatial-temporal discharge dynamics at the quasi-stationary stage are obtained for various values of gas pressure and wave frequency. Experimental data on the discharge length versus the power absorbed by the discharge are presented. Their comparison with simulation results is given.
Fulcrum: condensing redundant reads from high-throughput sequencing studies
Authors: Burriesci Matthew S. , Lehnert Erik M. , Pringle John R.
Published: March 2012

Motivation: Ultra-high-throughput sequencing produces duplicate and near-duplicate reads, which can consume computational resources in downstream applications. A tool that collapses such reads should reduce storage and assembly complications and costs.

Results: We developed Fulcrum to collapse identical and near-identical Illumina and 454 reads (such as those from PCR clones) into single error-corrected sequences; it can process paired-end as well as single-end reads. Fulcrum is customizable and can be deployed on a single machine, a local network or a commercially available MapReduce cluster, and it has been optimized to maximize ease-of-use, cross-platform compatibility and future scalability. Sequence datasets have been collapsed by up to 71%, and the reduced number and improved quality of the resulting sequences allow assemblers to produce longer contigs while using less memory.

Availability and implementation: Source code and a tutorial are available at http://pringlelab.stanford.edu/protocols.html under a BSD-like license. Fulcrum was written and tested in Python 2.6, and the single-machine and local-network modes depend on a modified version of the Parallel Python library (provided).

Contact:  erik.m.lehnert@gmail.com

Supplementary information:  Supplementary information is available at Bioinformatics online.
FT011, a new anti‐fibrotic drug, attenuates fibrosis and chronic heart failure in experimental diabetic cardiomyopathy
Authors: Zhang Yuan , Edgley Amanda J. , Cox Alison J. , Powell Andrew K. , Wang Bing , Kompa Andrew R. , Stapleton David I. , Zammit Steven C. , Williams Spencer J. , Krum Henry , Gilbert Richard E. , Kelly Darren J.
Published: March 2012

Aims

Cardiac remodelling in diabetes includes pathological accumulation of extracellular matrix and myocyte hypertrophy that contribute to heart dysfunction. Attenuation of remodelling represents a potential therapeutic target. We tested this hypothesis using a new anti‐fibrotic drug, FT011 (Fibrotech Therapeutics Pty Ltd), on diabetic Ren‐2 rats, a model which replicates many of the structural and functional manifestations of diabetic cardiomyopathy in humans.

Methods and results

Homozygous Ren‐2 rats were randomized to receive streptozotocin or vehicle then further randomized to FT011 (200 mg/kg/day) or vehicle treatment for 6 weeks. Prior to tissue collection, cardiac function was assessed via echocardiography and cardiac catheterization. Total collagen deposition and cardiomyocyte hypertrophy were assessed by picrosirius red and haematoxylin and eosin staining, respectively. Macrophage interstitial infiltration and type I and III collagen were quantitated by immunostaining. Without affecting blood pressure or hyperglycaemia, treatment of diabetic rats with FT011 significantly attenuated interstitial fibrosis (total collagen, 5.09 ±1.28 vs, 2.42 ±0.43%/area; type I collagen, 4.09 ±1.16 vs. 1.42 ±0.38%/area; type III collagen, 1.52 ±0.33 vs. 0.71 ±0.14 %/area; P < 0.05), cardiomyocyte hypertrophy (882 ±38 vs. 659 ±28 µm2; P < 0.05), and interstitial macrophage influx (66 ±5.3 vs, 44 ±7.9 number/section; P < 0.05). Cardiac myopathic dilatation was normalized, as evidenced by reduced left ventricular inner diameter at diastole (0.642 ±0.016 vs. 0.577 ±0.024 cm), increased ejection fraction (75 ±1.1 vs. 83 ±1.2%) and preload recruitable stroke work relationship (44 ±6.7 vs. 77 ±6.3 slope‐mmHg; P < 0.05), and reduced end‐diastolic pressure–volume relationship (0.059 ±0.011 vs. 0.02 ±0.003 slope‐mmHg/μL; P < 0.05).

Conclusions

A direct anti‐fibrotic agent, FT011, attenuates cardiac remodelling and dysfunction in experimental diabetic cardiomyopathy. This represents a novel therapy for the treatment of diabetic cardiomyopathy associated with cardiac fibrosis and hypertrophy.
Intracranial Self-stimulation of the Paraventricular Nucleus of the Hypothalamus
Authors: Ewan Eric E. , Martin Thomas J.
Published: March 2012

Background

Neuropathic pain attenuates opioid facilitation of rewarding electrical stimulation of limbic dopaminergic pathways originating from the ventral tegmental area. Whether neuropathic pain alters opioid effects of other brain-reward systems is unknown.

Methods

Control and spinal nerve-ligated (SNL) rats had electrodes implanted into the paraventricular nucleus (PVN) of the hypothalamus or medial forebrain bundle. Control and SNL rats were trained to lever-press for intracranial self-stimulation (ICSS), and modulation by morphine or cocaine was assessed.

Results

Control and SNL rats lever-pressed for stimulation of the PVN and medial forebrain bundle. Morphine produced greater reductions in the frequency at which rats emitted 50% of maximal responding for PVN ICSS (maximal effect 24.67 ± 4.60 [mean ± SEM] and 24.11 ± 5.96 in SNL [n = 6] and control [n = 8] rats, respectively, compared with medial forebrain bundle ICSS (12.38 ± 6.77 [n = 8] and 12.69 ± 1.55 [n = 7]). In contrast, cocaine was less efficacious in potentiating PVN ICSS (maximal effect 11.76 ± 2.86 and 12.38 ± 4.01 in SNL [n = 12] and control [n = 8] rats, respectively) compared with medial forebrain bundle ICSS (30.58 ± 3.40 [n = 9] and 27.55 ± 4.51 [n = 7]).

Conclusions

PVN ICSS is facilitated to a greater extent by morphine than cocaine, and the effects of each drug on this behavior are unaltered after spinal nerve ligation. These effects contrast those observed with direct stimulation of limbic dopamine pathways, suggesting that the PVN may have a greater role in the reinforcing effects of opioids than classic limbic regions, particularly in the presence of chronic pain.
Low pathogenic H7 subtype avian influenza viruses isolated from domestic ducks in South Korea and the close association with isolates of wild birds
Authors: Kim Hye-Ryoung , Park Choi-Kyu , Lee Youn-Jeong , Oem Jae-Ku , Kang Hyun-Mi , Choi Jun-Gu , Lee O-Soo , Bae You-Chan
Published: March 2012

We characterized low pathogenic avian influenza (LPAI) viruses of the H7 subtype that were isolated from domestic ducks and wild birds in South Korea from 2008 to 2011. A total of 20 H7 viruses were collected from live-bird markets (LBMs), duck farms and wild-bird habitats using avian influenza (AI) surveillance and epidemiological approaches. A phylogenetic analysis of the H7 viruses that were isolated from domestic ducks and wild birds demonstrated that they were separated into 12 genotypes (A–D and Wb-1–8, respectively), indicating genetic diversity. These H7 viruses were related to the recently isolated Eurasian LPAI H7 viruses and various influenza viruses that are circulating in Asia, including southern China and South Korea. The same genotype was not found between domestic poultry and wild-bird isolates; however, most of the H7 viruses in poultry (genotypes B and C) were closely related to the H7 virus isolated from a wild bird (genotype Wb-3). Animal-challenge studies revealed that certain H7 AI viruses replicated well only in chickens or ducks depending on the genotype, indicating that the pathogenicity of H7 viruses has the potential to be altered due to multiple reassortments, and these viruses can potentially expand their host range. Our results are evidence of abundant and frequent reassortment between H7 viruses in poultry and wild birds and emphasize the continuing need to monitor the evolutionary genetics of the influenza virus in poultry and wild birds.
Rapid and persistent suppression of feeding behavior induced by sensitization training in Aplysia
Authors: Acheampong Ama , Kelly Kathleen , Shields-Johnson Maria , Hajovsky Julie , Wainwright Marcy , Mozzachiodi Riccardo
Published: March 2012

In Aplysia, noxious stimuli induce sensitization of defensive responses. However, it remains largely unknown whether such stimuli also alter nondefensive behaviors. In this study, we examined the effects of noxious stimuli on feeding. Strong electric shocks, capable of inducing sensitization, also led to the suppression of feeding. The use of multiple training protocols revealed that the time course of the suppression of feeding was analogous to that of sensitization. In addition, the suppression of feeding was present only at the time points in which sensitization was expressed. These results suggest that, in Aplysia, noxious stimuli may produce concurrent changes in neural circuits controlling both defensive and nondefensive behaviors.
NMDA signaling in CA1 mediates selectively the spatial component of episodic memory
Authors: Place Ryan , Lykken Christy , Beer Zachery , Suh Junghyup , McHugh Thomas J. , Tonegawa Susumu , Eichenbaum Howard , Sauvage Magdalena M.
Published: March 2012

Recent studies focusing on the memory for temporal order have reported that CA1 plays a critical role in the memory for the sequences of events, in addition to its well-described role in spatial navigation. In contrast, CA3 was found to principally contribute to the memory for the association of items with spatial or contextual information in tasks focusing on spatial memory. Other studies have shown that NMDA signaling in the hippocampus is critical to memory performance in studies that have investigated spatial and temporal order memory independently. However, the role of NMDA signaling separately in CA1 and CA3 in memory that combines both spatial and temporal processing demands (episodic memory) has not been examined. Here we investigated the effect of the deletion of the NR1 subunit of the NMDA receptor in CA1 or CA3 on the spatial and the temporal aspects of episodic memory, using a behavioral task that allows for these two aspects of memory to be evaluated distinctly within the same task. Under these conditions, NMDA signaling in CA1 specifically contributes to the spatial aspect of memory function and is not required to support the memory for temporal order of events.
Multiple Domains in MtENOD8 Protein Including the Signal Peptide Target It to The Symbiosome
Authors: Meckfessel Matthew H. , Blancaflor Elison B. , Plunkett Michael , Dong Qunfeng , Dickstein Rebecca
Published: March 2012

Symbiotic nitrogen fixation occurs in nodules, specialized organs on the roots of legumes. Within nodules, host plant cells are infected with rhizobia that are encapsulated by a plant-derived membrane forming a novel organelle, the symbiosome. In Medicago truncatula, the symbiosome consists of the symbiosome membrane, a single rhizobium, and the soluble space between them, called the symbiosome space. The symbiosome space is enriched with plant-derived proteins, including the M. truncatula EARLY NODULIN8 (MtENOD8) protein. Here, we present evidence from green fluorescent protein (GFP) fusion experiments that the MtENOD8 protein contains at least three symbiosome targeting domains, including its N-terminal signal peptide (SP). When ectopically expressed in nonnodulated root tissue, the MtENOD8 SP delivers GFP to the vacuole. During the course of nodulation, there is a nodule-specific redirection of MtENOD8-SP-GFP from the vacuole to punctate intermediates and subsequently to symbiosomes, with redirection of MtENOD8-SP-GFP from the vacuole to punctate intermediates preceding intracellular rhizobial infection. Experiments with M. truncatula mutants having defects in rhizobial infection and symbiosome development demonstrated that the MtNIP/LATD gene is required for redirection of the MtENOD8-SP-GFP from the vacuoles to punctate intermediates in nodules. Our evidence shows that MtENOD8 has evolved redundant targeting sequences for symbiosome targeting and that intracellular localization of ectopically expressed MtENOD8-SP-GFP is useful as a marker for monitoring the extent of development in mutant nodules.
The Arabidopsis MicroRNA396-GRF1/GRF3 Regulatory Module Acts as a Developmental Regulator in the Reprogramming of Root Cells during Cyst Nematode Infection
Authors: Hewezi Tarek , Maier Tom R. , Nettleton Dan , Baum Thomas J.
Published: March 2012

The syncytium is a unique plant root organ whose differentiation is induced by plant-parasitic cyst nematodes to create a source of nourishment. Syncytium formation involves the redifferentiation and fusion of hundreds of root cells. The underlying regulatory networks that control this unique change of plant cell fate are not understood. Here, we report that a strong down-regulation of Arabidopsis (Arabidopsis thaliana) microRNA396 (miR396) in cells giving rise to the syncytium coincides with the initiation of the syncytial induction/formation phase and that specific miR396 up-regulation in the developed syncytium marks the beginning of the maintenance phase, when no new cells are incorporated into the syncytium. In addition, our results show that miR396 in fact has a role in the transition from one phase to the other. Expression modulations of miR396 and its Growth-Regulating Factor (GRF) target genes resulted in reduced syncytium size and arrested nematode development. Furthermore, genome-wide expression profiling revealed that the miR396-GRF regulatory system can alter the expression of 44% of the more than 7,000 genes reported to change expression in the Arabidopsis syncytium. Thus, miR396 represents a key regulator for the reprogramming of root cells. As such, this regulatory unit represents a powerful molecular target for the parasitic animal to modulate plant cells and force them into novel developmental pathways.
Statistical quality indicators for electron-density maps
Authors: Tickle Ian J.
Published: March 2012

The commonly used validation metrics for the local agreement of a structure model with the observed electron density, namely the real-space R (RSR) and the real-space correlation coefficient (RSCC), are reviewed. It is argued that the primary goal of all validation techniques is to verify the accuracy of the model, since precision is an inherent property of the crystal and the data. It is demonstrated that the principal weakness of both of the above metrics is their inability to distinguish the accuracy of the model from its precision. Furthermore, neither of these metrics in their usual implementation indicate the statistical significance of the result. The statistical properties of electron-density maps are reviewed and an improved alternative likelihood-based metric is suggested. This leads naturally to a χ2 significance test of the difference density using the real-space difference density Z score (RSZD). This is a metric purely of the local model accuracy, as required for effective model validation and structure optimization by practising crystallographers prior to submission of a structure model to the PDB. A new real-space observed density Z score (RSZO) is also proposed; this is a metric purely of the model precision, as a substitute for other precision metrics such as the B factor.
Tetartohedral twinning could happen to you too
Authors: Roversi Pietro , Blanc Eric , Johnson Steven , Lea Susan Mary
Published: March 2012

Tetartohedral crystal twinning is discussed as a particular case of (pseudo)merohedral twinning when the number of twinned domains is four. Tetartohedrally twinned crystals often possess pseudosymmetry, with the rotational part of the pseudosymmetry operators coinciding with the twinning operators. Tetartohedrally twinned structures from the literature are reviewed and the recent structure determination of tetartohedrally twinned triclinic crystals of human complement factor I is discussed.
Epstein–Barr virus‐encoded LMP1 triggers regulation of the ERK‐mediated Op18/stathmin signaling pathway in association with cell cycle
Authors: Lin Xuechi , Tang Min , Tao Yongguang , Li Lili , Liu Sufang , Guo Lili , Li Zijian , Ma Xiaoqian , Xu Juan , Cao Ya
Published: March 2012

The MAPKs are activated by a variety of cellular stimuli to participate in a series of signaling cascades and mediate diverse intracellular responses. One potential target of the MAPKs is Op18/stathmin, a molecule that acts as an integrator of diverse cell signaling pathways and regulates the dynamics of microtubules, which are involved in modulating a variety of cellular processes, including cell cycle progression and cell growth. Our study focused on the regulation of the MAPK‐mediated Op18/stathmin signaling pathway, which is triggered by the Epstein–Barr virus‐encoded latent membrane protein 1 (
LMP1
) oncogene in nasopharyngeal carcinoma cells. The results showed that the activity of MAPK, which was induced by LMP1, varied with cell cycle progression; LMP1 upregulated phosphorylation of ERK during the G1/S phase, but negatively regulated phosphorylation of ERK during the G2/M phase. We found that the regulation of Op18/stathmin signaling by LMP1 was mainly mediated through ERK. The inhibition of LMP1 expression attenuated the interaction of ERK with Op18/stathmin and promoted microtubule depolymerization. These findings indicate the existence of a new cell cycle‐associated signaling pathway in which LMP1 regulates ERK‐mediated Op18/stathmin signaling. (Cancer Sci 2012; 103: 993–999)
Expression of TREM‐1 in hepatic stellate cells and prognostic value in hepatitis B‐related hepatocellular carcinoma
Authors: Liao Rui , Sun Tai‐Wei , Yi Yong , Wu Han , Li Yi‐Wei , Wang Jia‐Xing , Zhou Jian , Shi Ying‐Hong , Cheng Yun‐Feng , Qiu Shuang‐Jian , Fan Jia
Published: March 2012

Hepatocellular carcinoma (HCC) is a typical inflammation‐related malignancy characterized by high postoperative recurrence and metastasis. Although several inflammatory cells and inflammatory signatures have been linked to poor prognosis, the inflammation‐associated molecular mechanisms of HCC development and progression are largely unknown. Here we show that triggering receptor expressed in myeloid cells (TREM)‐1, a transmembrane receptor expressing in myeloid cells, was also expressed in tumor‐activated hepatic stellate cells (HSCs) and associated with the aggressive behavior of HCC cells. Enzyme‐linked immunosorbent assay was used to measure the expression levels of soluble TREM‐1 (sTREM‐1) in activated hepatic stellate cells supernatant and 92 preoperative and postoperative plasmas of patients with malignancy and/or benign liver tumor/disease, respectively. Expression levels of TREM‐1 were assessed by immunohistochemistry in tissue microarray from 240 patients with HCC. As a result, increased secretion of sTREM‐1 from activated HSCs was observed after co‐culture with HCC cell lines (P < 0.001), and conditioned medium collected from activated HSCs/cancer associated myofibroblasts (CAMFs) with or without agonist/inhibitor of TREM‐1 significantly changed the migratory ability of HCC cells. The levels of sTREM‐1 were significantly higher in patients with HCC than those with benign liver tumors (P < 0.005). Peritumoral density of TREM‐1 was shown to be an independent prognosis predictor according to univariate (P < 0.001 for both overall survival and time to recurrence) and multivariate analysis (P = 0.008 for overall survival; P = 0.005 for time to recurrence). Thus, these observations suggest that TREM‐1 is related to the aggressive tumor behavior and has potential value as a prognostic factor for HCC. (Cancer Sci 2012; 103: 984–992)
Clinical evaluation of a new tracheal impedance cardiography method
Authors: van der Kleij S. C. J. , Koolen B. B. , Newhall D. A. , Gerritse B. M. , Rosseel P. M. J. , Rijpstra T. A. , Geisler F. E. A. , van der Meer N. J. M.
Published: March 2012

Non‐invasive cardiac output measurement by means of impedance cardiography has been evaluated before, and agreement with other methods has been variable. We decided to study a newly developed tracheal impedance device, that is claimed to be more accurate and reliable. This incorporates new software and mathematical formulae, that are designed to reduce signal noise from diathermy, leading to improved accuracy. In 25 cardiothoracic surgery patients, simultaneous measurements were performed using both pulmonary artery thermodilution and the tracheal impedance device, at five peri‐operative time points: before skin incision; after weaning from cardiopulmonary bypass; after sternal closure; and 30 min and 2 h after arrival in the intensive care unit. Mean cardiac output, bias and 95% limits of agreement were 5.3, 0.03 and −2.8 to 2.8 l.min−1, respectively. Tracheal impedance showed good correlation with measurement trends using thermodilution in 88% of measurements, with a mean (95% limit of agreement) angular bias of −9.0° (−83.3 to 65.3°). However, the wide limits of agreement and high percentage error of 53% that were apparent in this study mean that, in its present guise, tracheal impedance is not an acceptable alternative to thermodilution in cardiac surgical patients.
Genome‐wide association study uncovers four QTL predisposing to supernumerary teats in cattle
Authors: Pausch Hubert , Jung Simone , Edel Christian , Emmerling Reiner , Krogmeier Dieter , Götz Kay‐Uwe , Fries Ruedi
Published: March 2012

Supernumerary teats (hyperthelia, SNTs) are a common abnormality of the bovine udder with a medium to high heritability and a postulated oligogenic or polygenic inheritance pattern. SNTs not only negatively affect machine milking ability but also act as a reservoir for bacteria. A genome‐wide association study was carried out to identify genes involved in the development of SNTs in the dual‐purpose Fleckvieh breed. A total of 2467 progeny‐tested bulls were genotyped at 43 698 single nucleotide polymorphisms, and daughter yield deviations (DYDs) for ‘udder clearness' (UC) were used as high‐heritability phenotypes. Massive structuring of the study population was accounted for by principal components analysis‐based and mixed model‐based approaches. Four loci on BTA5, BTA6, BTA11 and BTA17 were significantly associated with the UC DYD. Three associated regions contain genes of the highly conserved Wnt signalling pathway. The four QTL together account for 10.7% of the variance of the UC DYD, whereas the major fraction of the DYD variance is attributable to chromosomes with no identified QTL. Our results support both an oligogenic and a polygenic inheritance pattern of SNTs in cattle. The identified candidate genes permit insights into the genetic architecture of teat malformations in cattle and provide clues to unravel the molecular mechanisms of mammary gland alterations in cattle and other species.
Effects of dehydroepiandrosterone sulphate (DHEAS) replacement on insulin action and quality of life in hypopituitary females: a double‐blind, placebo‐controlled study
Authors: McHenry Claire M. , Bell Patrick M. , Hunter Steven J. , Thompson Christopher J. , Courtney C. H. , Ennis Cieran N. , Sheridan Brian , McCance David R. , Mullan Karen R. , Atkinson A. Brew
Published: March 2012

Objective

Addition of dehydroepiandrosterone sulphate (DHEAS) to standard pituitary replacement may improve quality of life and glucose metabolism. Conflicting results from the previous work probably relate to differences in populations studied and assessment techniques used. We examined the effects of DHEAS on insulin action and the quality of life in female patients with hypopituitary hypoadrenalism.

Design

Randomized, double‐blind, placebo‐controlled, crossover design was used. Patients received either DHEAS 50 mg daily or placebo for 12 weeks.

Patients

Fourteen hypopituitary females on stable standard replacement therapy and with low DHEAS were enrolled.

Measurements

Insulin action by euglycaemic hyperinsulinaemic clamp and extensive quality of life parameters were assessed after each treatment.

Results

Serum DHEAS (DHEAS 5·4 ± 0·8 vs placebo <0·8 ± 0·0 μm; P < 0·001) and androstenedione (DHEAS 4·1 ± 0·8 vs placebo 1·3 ± 0·2 nm; P < 0·05) rose to within the normal range after DHEAS 50 mg daily. There were no differences between treatments in testosterone, sex hormone‐binding globulin (SHBG) or IGF‐1. Quality of life measures were unchanged after DHEAS. There were no differences between treatments in fasting glucose, serum insulin, HbA1c or in insulin action (glucose infusion rates required to maintain euglycaemia; DHEAS 21·9 ± 2·5 vs placebo 24·5 ± 2·1 μmol/kg/min; P = 0·4). Triglyceride concentrations were lower following DHEAS (DHEAS 1·24 ± 0·18 vs placebo 1·41 ± 0·19 mm; P < 0·05) but other lipid parameters remained unchanged.

Conclusion

There were no differences compared with placebo in quality of life or insulin action after DHEAS replacement therapy for 12 weeks. These results do not provide evidence for the addition of DHEAS to standard hypopituitary replacement therapy.
Numerical modelling: a useful tool to simulate collapsing volcanoes
Authors: Pouget Solène , Davies Tim , Kennedy Ben , Kelfoun Karim , Leyrit Hervé
Published: March 2012

Since the nineteenth century scientists have tried to reproduce natural events in order to study and understand them through the technique of modelling. However, technology has evolved rapidly in the past two decades and now sophisticated numerical models are widely used to reproduce past events or simulate new scenarios. These models are particularly useful to reproduce the large scale and complexity of geological events. To illustrate the use and potential of numerical modelling in geological sciences, we describe a simulation of a large debris avalanche caused by the collapse of the north flank of the Taranaki volcano in New Zealand and the value of this information in the context of disaster planning.