bluuebunny/crossref_metadata_2025 huggingface dataset:
Nanoscale magnetic structure and properties of solution-derived self-assembled La0.7Sr0.3MnO3 islands
Authors: Zabaleta J. , Jaafar M. , Abellán P. , Montón C. , Iglesias-Freire O. , Sandiumenge F. , Ramos C. A. , Zysler R. D. , Puig T. , Asenjo A. , Mestres N. , Obradors X.
Published: January 2012

Strain-induced self-assembled La0.7Sr0.3MnO3 nanoislands of lateral size 50−150 nm and height 10−40 nm have been grown on yttria-stabilized zirconia (001)-substrates from ultradiluted chemical solutions based on metal propionates. The nanoislands grow highly relaxed withstanding the epitaxial relation (001)LSMO[110]//(001)YSZ[010] and show bulk-like average magnetic properties in terms of Curie temperature and saturation magnetization. The interplay of the magnetocrystalline and shape anisotropy within the nanoisland ensemble results in an in-plane magnetic anisotropy with a magnetocrystalline constant K1(150  K)=-(5±1)  kJ/m3 and in-plane easy axis along the [110]-La0.7Sr0.3MnO3 direction as measured, for the first time, through ferromagnetic resonance experiments. Magnetic force microscopy studies reveal the correlation between nanoisland size and its magnetic domain structure in agreement with micromagnetic simulations. In particular, we have established the required geometric conditions for single domain, multidomain, and vortex configurations.
Self-generated electric field suppressing the ferroelectric to antiferroelectric phase transition in ferroelectric ceramics under shock wave compression
Authors: Jiang Dongdong , Du Jinmei , Gu Yan , Feng Yujun
Published: January 2012

Kinetics of the ferroelectric (FE) to antiferroelectric (AFE) phase transformation under shock wave compression is critical to design the shock-activated power supply and can be characterized in terms of both a transition rate and a limiting degree of transition. By measuring the depoling currents under the short-circuit and high-impedance conditions, we investigated the influence of self-generated electric field on the phase transition kinetics of tin-modified lead zirconate titanate ceramics (Pb0.99Nb0.02[(Zr0.90Sn0.10)0.96Ti0.04]0.98O3) in the pressure range from 0.61 to 4.50 GPa. Experimental results indicate that the self-generated electric field does not appear to have a significant effect on the depoling currents at high shock pressures, but has a strong effect at low pressures. At 0.61 and 1.03 GPa, transition rate and degree diminish with increasing the electric field, illustrating that the self-generated electric field suppresses the FE-to-AFE phase transition. These observations are found to be generally consistent with many ferroelectric materials and results under hydrostatic compression. Fundamental issues are discussed from the perspective of the soft mode theory.
Vertical waveguides integrated with silicon photodetectors: Towards high efficiency and low cross-talk image sensors
Authors: Tut Turgut , Dan Yaping , Duane Peter , Yu Young , Wober Munib , Crozier Kenneth B.
Published: January 2012

We describe the experimental realization of vertical silicon nitride waveguides integrated with silicon photodetectors. The waveguides are embedded in a silicon dioxide layer. Scanning photocurrent microscopy is performed on a device containing a waveguide, and on a device containing the silicon dioxide layer, but without the waveguide. The results confirm the waveguide’s ability to guide light onto the photodetector with high efficiency. We anticipate that the use of these structures in image sensors, with one waveguide per pixel, would greatly improve efficiency and significantly reduce inter-pixel crosstalk.
Plasmonic light trapping leads to responsivity increase in colloidal quantum dot photodetectors
Authors: Pelayo García de Arquer F. , Beck Fiona J. , Bernechea María , Konstantatos Gerasimos
Published: January 2012

We report broadband responsivity enhancement in PbS colloidal quantum dot (CQDs) photoconductive photodetectors due to absorption increase offered by a plasmonic scattering layer of Ag metal nanoparticles. Responsivity enhancements are observed in the near infrared with a maximum 2.4-fold increase near the absorption band edge of ∼1 μm for ∼400 nm thick devices. Additionally, we study the effect of the mode structure on the efficiency of light trapping provided by random nanoparticle scattering in CQD films and provide insights for plasmonic scattering enhancement in CQD thin films.
Direct imaging of both ferroelectric and antiferromagnetic domains in multiferroic BiFeO3 single crystal using x-ray photoemission electron microscopy
Authors: Moubah R. , Elzo M. , El Moussaoui S. , Colson D. , Jaouen N. , Belkhou R. , Viret M.
Published: January 2012

In this work, we propose to study the magnetic and ferroelectric configurations in ferroelectric multidomain BiFeO3 single crystals. Using x-ray (magnetic) linear dichroism in a photoemission electron microscope (X-PEEM), we are able to directly image both the antiferromagnetic and ferroelectric domains. We find that inside one single ferroelectric domain several antiferromagnetic domains coexist. This is different from what was observed on epitaxial thin films, where the ferroelectric domains perfectly match the antiferromagnetic ones, but also from previous neutron measurements on ferroelectric monodomain single-crystals for which one single antiferromagnetic domain was identified. This underlines the fundamental differences between thin films, bulk samples, and single versus ferroelectric multidomain samples.
A Monte Carlo study of the low resistance state retention of HfOx based resistive switching memory
Authors: Yu Shimeng , Yin Chen Yang , Guan Ximeng , Philip Wong H.-S. , Kittl Jorge A.
Published: January 2012

A Monte Carlo simulator is developed to investigate the low resistance state (LRS) retention of HfOx based resistive switching memory. The simulator tracks the evolution of oxygen ions and oxygen vacancies by choosing the occurrence of the generation/recombination/migration processes based on their corresponding probability at each simulation step. The current through the resulting conductive filament (CF) configuration is then calculated by a trap-assisted-tunneling solver. The simulation results are corroborated with experimental data. The LRS retention is found to be CF size dependent, and its variability is suggested to be intrinsic due to the stochastic nature of the CF dissolution. The tail bits of the failure time distribution become a limiting factor of the device reliability in a large memory array.
Cholesteric liquid crystal-carbon nanotube hybrid architectures for gas detection
Authors: Chang Chin-Kai , Chiu Shih-Wen , Kuo Hui-Lung , Tang Kea-Tiong
Published: January 2012

The ability of a hybrid material that is based on cholesteric liquid crystal and carbon nanotube to detect acetone vapor is investigated. We find that the phase transition in this cholesteric liquid crystal-carbon nanotube hybrid will enable carbon nanotube to form conducting networks under the higher vapor concentration. This cholesteric liquid crystal-carbon nanotube hybrid exhibits an obvious change in reflected color and electrical resistance in the early and later stages of gas diffusion, respectively. This hybrid architecture has potential application as a gas sensor with a high dynamic range.
Communication: A chemically accurate global potential energy surface for the HO + CO → H + CO2 reaction
Authors: Li Jun , Wang Yimin , Jiang Bin , Ma Jianyi , Dawes Richard , Xie Daiqian , Bowman Joel M. , Guo Hua
Published: January 2012

We report a chemically accurate global potential energy surface for the HOCO system based on high-level ab initio calculations at ∼35 000 points. The potential energy surface is shown to reproduce important stationary points and minimum energy paths. Quasi-classical trajectory calculations indicated a good agreement with experimental data.
Communication: Crystallite nucleation in supercooled glycerol near the glass transition
Authors: Yuan Hai-Feng , Xia Ted , Plazanet Marie , Demé Bruno , Orrit Michel
Published: January 2012

Heterogeneity and solid-like structures found near the glass transition provide a key to a better understanding of supercooled liquids and of the glass transition. However, the formation of solid-like structures and its effect on spatial heterogeneity in supercooled liquids is neither well documented nor well understood. In this work, we reveal the crystalline nature of the solid-like structures in supercooled glycerol by means of neutron scattering. The results indicate that inhomogeneous nucleation happens at temperatures near Tg. Nevertheless, the thermal history of the sample is essential for crystallization. This implies such structures in supercooled liquids strongly depend on thermal history. Our work suggests that different thermal histories may lead to different structures and therefore to different length and time scales of heterogeneity near the glass transition.
An economic case for providing free access to antiretroviral therapy for HIV-positive people in South Australia
Authors: Heymer Kelly-Jean , Wentzlaff-Eggebert Matthias , Mortimer Elissa , Wilson David P.
Published: January 2012

Background
As financial constraints can be a barrier to accessing HIV antiretroviral therapy (ART), we argue for the removal of copayment requirements from HIV medications in South Australia. Methods: Using a simple mathematical model informed by available behavioural and biological data and reflecting the HIV epidemiology in South Australia, we calculated the expected number of new HIV transmissions caused by persons who are not currently on ART compared with transmissions for people on ART. The extra financial investment required to cover the copayments to prevent an HIV infection was compared with the treatment costs saved due to averting HIV infections. Results: It was estimated that one HIV infection is prevented per year for every 31.4 persons (median, 24.0–42.7 interquartile range (IQR)) who receive treatment. By considering the incremental change in costs and outcomes of a change in program from the current status quo, it would cost the health sector $17 860 per infection averted (median, $13 651–24 287 IQR) if ART is provided as a three-dose, three-drug combination without requirements for user-pay copayments. Conclusions: The costs of removing copayment fees for ART are less than the costs of treating extra HIV infections that would result under current conditions. Removing the copayment requirement for HIV medication would be cost-effective from a governmental perspective.
Highly localized sensitivity to climate forcing drives endemic cholera in a megacity
Authors: Reiner Robert C. , King Aaron A. , Emch Michael , Yunus Mohammad , Faruque A. S. G. , Pascual Mercedes
Published: January 2012

The population dynamics of endemic cholera in urban environments—in particular interannual variation in the size and distribution of seasonal outbreaks—remain poorly understood and highly unpredictable. In part, this situation is due to the considerable demographic, socioeconomic, and environmental heterogeneity of large and growing urban centers. Despite this heterogeneity, the influence of climate variability on the population dynamics of infectious diseases is considered a large-scale, regional, phenomenon, and as such has been previously addressed for cholera only with temporal models that do not incorporate spatial structure. Here we show that a probabilistic spatial model can explain cholera dynamics in the megacity of Dhaka, Bangladesh, and afford a basis for cholera forecasts at lead times of 11 mo. Critically, we find that the action of climate variability (El Niño southern oscillation and flooding) is quite localized: There is a climate-sensitive urban core that acts to propagate risk to the rest of the city. The modeling framework presented here should be applicable to cholera in other cities, as well as to other infectious diseases in urban settings and other biological systems with spatiotemporal interactions.
Modulation of value representation by social context in the primate orbitofrontal cortex
Authors: Azzi João C. B. , Sirigu Angela , Duhamel Jean-René
Published: January 2012

Primates depend for their survival on their ability to understand their social environment, and their behavior is often shaped by social circumstances. We report that the orbitofrontal cortex, a brain region involved in motivation and reward, is tuned to social information. Macaque monkeys worked to collect rewards for themselves and two monkey partners. Behaviorally, monkeys discriminated between cues signaling small and large rewards, and between cues signaling rewards to self only and reward to both self and another monkey, with a preference for the former over the latter in both instances. Single neurons recorded during this task encoded the meaning of visual cues that predicted the magnitude of future rewards, as well as the motivational value of rewards obtained in a social context. Furthermore, neuronal activity was found to track momentary social preferences and partner's identity and social rank. The orbitofrontal cortex thus contains key neuronal mechanisms for the evaluation of social information.
Class III PI3K Vps34 plays an essential role in autophagy and in heart and liver function
Authors: Jaber Nadia , Dou Zhixun , Chen Juei-Suei , Catanzaro Joseph , Jiang Ya-Ping , Ballou Lisa M. , Selinger Elzbieta , Ouyang Xiaosen , Lin Richard Z. , Zhang Jianhua , Zong Wei-Xing
Published: January 2012

A critical regulator of autophagy is the Class III PI3K Vps34 (also called PIK3C3). Although Vps34 is known to play an essential role in autophagy in yeast, its role in mammals remains elusive. To elucidate the physiological function of Vps34 and to determine its precise role in autophagy, we have generated Vps34
f/f
mice, in which expression of Cre recombinase results in a deletion of exon 4 of Vps34 and a frame shift causing a deletion of 755 of the 887 amino acids of Vps34. Acute ablation of Vps34 in MEFs upon adenoviral Cre infection results in a diminishment of localized generation of phosphatidylinositol 3-phosphate and blockade of both endocytic and autophagic degradation. Starvation-induced autophagosome formation is blocked in both Vps34-null MEFs and liver. Liver-specific Albumin-Cre;Vps34
f/f
mice developed hepatomegaly and hepatic steatosis, and impaired protein turnover. Ablation of Vps34 in the heart of muscle creatine kinase-Cre;Vps34
f/f
mice led to cardiomegaly and decreased contractility. In addition, while amino acid-stimulated mTOR activation was suppressed in the absence of Vps34, the steady-state level of mTOR signaling was not affected in Vps34-null MEFs, liver, or cardiomyocytes. Taken together, our results indicate that Vps34 plays an essential role in regulating functional autophagy and is indispensable for normal liver and heart function.
On achieving high accuracy and reliability in the calculation of relative protein–ligand binding affinities
Authors: Wang Lingle , Berne B. J. , Friesner Richard A.
Published: January 2012

We apply a free energy perturbation simulation method, free energy perturbation/replica exchange with solute tempering, to two modifications of protein–ligand complexes that lead to significant conformational changes, the first in the protein and the second in the ligand. The approach is shown to facilitate sampling in these challenging cases where high free energy barriers separate the initial and final conformations and leads to superior convergence of the free energy as demonstrated both by consistency of the results (independence from the starting conformation) and agreement with experimental binding affinity data. The second case, consisting of two neutral thrombin ligands that are taken from a recent medicinal chemistry program for this interesting pharmaceutical target, is of particular significance in that it demonstrates that good results can be obtained for large, complex ligands, as opposed to relatively simple model systems. To achieve quantitative agreement with experiment in the thrombin case, a next generation force field, Optimized Potentials for Liquid Simulations 2.0, is required, which provides superior charges and torsional parameters as compared to earlier alternatives.
A novel lineage of myoviruses infecting cyanobacteria is widespread in the oceans
Authors: Sabehi Gazalah , Shaulov Lihi , Silver David H. , Yanai Itai , Harel Amnon , Lindell Debbie
Published: January 2012

Viruses infecting bacteria (phages) are thought to greatly impact microbial population dynamics as well as the genome diversity and evolution of their hosts. Here we report on the discovery of a novel lineage of tailed dsDNA phages belonging to the family Myoviridae and describe its first representative, S-TIM5, that infects the ubiquitous marine cyanobacterium,Synechococcus. The genome of this phage encodes an entirely unique set of structural proteins not found in any currently known phage, indicating that it uses lineage-specific genes for virion morphogenesis and represents a previously unknown lineage of myoviruses. Furthermore, among its distinctive collection of replication and DNA metabolism genes, it carries a mitochondrial-like DNA polymerase gene, providing strong evidence for the bacteriophage origin of the mitochondrial DNA polymerase. S-TIM5 also encodes an array of bacterial-like metabolism genes commonly found in phages infecting cyanobacteria including photosynthesis, carbon metabolism and phosphorus acquisition genes. This suggests a common gene pool and gene swapping of cyanophage-specific genes among different phage lineages despite distinct sets of structural and replication genes. All cytosines following purine nucleotides are methylated in the S-TIM5 genome, constituting a unique methylation pattern that likely protects the genome from nuclease degradation. This phage is abundant in the Red Sea and S-TIM5 gene homologs are widespread in the oceans. This unusual phage type is thus likely to be an important player in the oceans, impacting the population dynamics and evolution of their primary producing cyanobacterial hosts.
Task reward structure shapes rapid receptive field plasticity in auditory cortex
Authors: David Stephen V. , Fritz Jonathan B. , Shamma Shihab A.
Published: January 2012

As sensory stimuli and behavioral demands change, the attentive brain quickly identifies task-relevant stimuli and associates them with appropriate motor responses. The effects of attention on sensory processing vary across task paradigms, suggesting that the brain may use multiple strategies and mechanisms to highlight attended stimuli and link them to motor action. To better understand factors that contribute to these variable effects, we studied sensory representations in primary auditory cortex (A1) during two instrumental tasks that shared the same auditory discrimination but required different behavioral responses, either approach or avoidance. In the approach task, ferrets were rewarded for licking a spout when they heard a target tone amid a sequence of reference noise sounds. In the avoidance task, they were punished unless they inhibited licking to the target. To explore how these changes in task reward structure influenced attention-driven rapid plasticity in A1, we measured changes in sensory neural responses during behavior. Responses to the target changed selectively during both tasks but did so with opposite sign. Despite the differences in sign, both effects were consistent with a general neural coding strategy that maximizes discriminability between sound classes. The dependence of the direction of plasticity on task suggests that representations in A1 change not only to sharpen representations of task-relevant stimuli but also to amplify responses to stimuli that signal aversive outcomes and lead to behavioral inhibition. Thus, top-down control of sensory processing can be shaped by task reward structure in addition to the required sensory discrimination.
Modeling and design by hierarchical natural moves
Authors: Sim Adelene Y. L. , Levitt Michael , Minary Peter
Published: January 2012

We develop a unique algorithm implemented in the program MOSAICS (Methodologies for Optimization and Sampling in Computational Studies) that is capable of nanoscale modeling without compromising the resolution of interest. This is achieved by modeling with customizable hierarchical degrees of freedom, thereby circumventing major limitations of conventional molecular modeling. With the emergence of RNA-based nanotechnology, large RNAs in all-atom representation are used here to benchmark our algorithm. Our method locates all favorable structural states of a model RNA of significant complexity while improving sampling accuracy and increasing speed many fold over existing all-atom RNA modeling methods. We also modeled the effects of sequence mutations on the structural building blocks of tRNA-based nanotechnology. With its flexibility in choosing arbitrary degrees of freedom as well as in allowing different all-atom energy functions, MOSAICS is an ideal tool to model and design biomolecules of the nanoscale.
Asynchronous Ca
2
+
current conducted by voltage-gated Ca
2+
(Ca
V
)-2.1 and Ca
V
2.2 channels and its implications for asynchronous neurotransmitter release
Authors: Few Alexandra P. , Nanou Evanthia , Watari Hirofumi , Sullivan Jane M. , Scheuer Todd , Catterall William A.
Published: January 2012

We have identified an asynchronously activated Ca
2+
current through voltage-gated Ca
2+
(Ca
V
)-2.1 and Ca
V
2.2 channels, which conduct P/Q- and N-type Ca
2+
currents that initiate neurotransmitter release. In nonneuronal cells expressing Ca
V
2.1 or Ca
V
2.2 channels and in hippocampal neurons, prolonged Ca
2+
entry activates a Ca
2+
current, I
Async
, which is observed on repolarization and decays slowly with a half-time of 150–300 ms. I
Async
is not observed after L-type Ca
2+
currents of similar size conducted by Ca
V
1.2 channels. I
Async
is Ca
2+
-selective, and it is unaffected by changes in Na
+
, K
+
, Cl
−
, or H
+
or by inhibitors of a broad range of ion channels. During trains of repetitive depolarizations, I
Async
increases in a pulse-wise manner, providing Ca
2+
entry that persists between depolarizations. In single-cultured hippocampal neurons, trains of depolarizations evoke excitatory postsynaptic currents that show facilitation followed by depression accompanied by asynchronous postsynaptic currents that increase steadily during the train in parallel with I
Async
. I
Async
is much larger for slowly inactivating Ca
V
2.1 channels containing β
2a
-subunits than for rapidly inactivating channels containing β
1b
-subunits. I
Async
requires global rises in intracellular Ca
2+
, because it is blocked when Ca
2+
is chelated by 10 mM EGTA in the patch pipette. Neither mutations that prevent Ca
2+
binding to calmodulin nor mutations that prevent calmodulin regulation of Ca
V
2.1 block I
Async
. The rise of I
Async
during trains of stimuli, its decay after repolarization, its dependence on global increases of Ca
2+
, and its enhancement by β
2a
-subunits all resemble asynchronous release, suggesting that I
Async
is a Ca
2+
source for asynchronous neurotransmission.
Role of histone deacetylases in transcription factor regulation and cell cycle modulation in endothelial cells in response to disturbed flow
Authors: Lee Ding-Yu , Lee Chih-I , Lin Ting-Er , Lim Seh Hong , Zhou Jing , Tseng Ying-Chih , Chien Shu , Chiu Jeng-Jiann
Published: January 2012

Vascular endothelial cells (ECs) are exposed to different flow patterns (i.e., disturbed vs. laminar), and the associated oscillatory shear stress (OSS) or pulsatile shear stress (PSS) lead to differential responses. We investigated the roles of class I and II histone deacetylases (HDAC-1/2/3 and HDAC-5/7, respectively) in regulating NF-E2–related factor-2 (Nrf2) and Krüppel-like factor-2 (KLF2), two transcription factors governing many shear-responsive genes, and the cell cycle in ECs in response to OSS. Application of OSS (0.5 ± 4 dynes/cm
2
) to cultured ECs sustainably up-regulated class I and II HDACs and their nuclear accumulation, whereas PSS (12 ± 4 dynes/cm
2
) induced phosphorylation-dependent nuclear export of class II HDACs.
En face
immunohistochemical examination of rat aortic arch and experimentally stenosed abdominal aorta revealed high HDAC-2/3/5 levels in ECs in areas exposed to disturbed flow. OSS induced the association of HDAC-1/2/3 with Nrf2 and HDAC-3/5/7 with myocyte enhancer factor-2; deacetylation of these factors led to down-regulation of antioxidant gene NAD(P)H quinone oxidoreductase-1 (NQO1) and KLF2. HDAC-1/2/3– and HDAC-3/5/7–specific small interfering RNAs eliminated the OSS-induced down-regulation of NQO1 and KLF2, respectively. OSS up-regulated cyclin A and down-regulated p21
CIP1
in ECs and induced their proliferation; these effects were mediated by HDAC-1/2/3. Intraperitoneal administration of the class I-specific HDAC inhibitor valproic acid into bromodeoxyuridine (BrdU)-infused rats inhibited the increased EC uptake of BrdU at poststenotic sites. The OSS-induced HDAC signaling and EC responses are mediated by phosphatidylinositol 3-kinase/Akt. Our findings demonstrate the important roles of different groups of HDACs in regulating the oxidative, inflammatory, and proliferative responses of ECs to disturbed flow with OSS.
A review of thinking and research about inclusive education policy, with suggestions for a new kind of inclusive thinking
Authors: Thomas Gary
Published: January 2012

A range of changes, in politics and economics internationally as well as in thought about learning and society, now make the time right for a re‐think of inclusive education, a re‐think that ceases to employ the constructs and clichés of the past in explaining students' difficulties at school. There exists new discourse on difference, which throws fresh light on the ways that students at school are disadvantaged—there is a new psychology of difference emerging from work in varied social scientific fields that gives insights into the mechanisms by which inequality, relative poverty and contrastive judgment construct difficulty and closure on learning. In this review, both a history and a hope, I argue that no time has been better for such understandings to make themselves realized in policy and practice.
Inhibiting the HSP90 chaperone destabilizes macrophage migration inhibitory factor and thereby inhibits breast tumor progression
Authors: Schulz Ramona , Marchenko Natalia D. , Holembowski Lena , Fingerle-Rowson Günter , Pesic Marina , Zender Lars , Dobbelstein Matthias , Moll Ute M.
Published: January 2012

Intracellular macrophage migration inhibitory factor (MIF) often becomes stabilized in human cancer cells. MIF can promote tumor cell survival, and elevated MIF protein correlates with tumor aggressiveness and poor prognosis. However, the molecular mechanism facilitating MIF stabilization in tumors is not understood. We show that the tumor-activated HSP90 chaperone complex protects MIF from degradation. Pharmacological inhibition of HSP90 activity, or siRNA-mediated knockdown of HSP90 or HDAC6, destabilizes MIF in a variety of human cancer cells. The HSP90-associated E3 ubiquitin ligase CHIP mediates the ensuing proteasome-dependent MIF degradation. Cancer cells contain constitutive endogenous MIF–HSP90 complexes. siRNA-mediated MIF knockdown inhibits proliferation and triggers apoptosis of cultured human cancer cells, whereas HSP90 inhibitor-induced apoptosis is overridden by ectopic MIF expression. In the ErbB2 transgenic model of human HER2-positive breast cancer, genetic ablation of MIF delays tumor progression and prolongs overall survival of mice. Systemic treatment with the HSP90 inhibitor 17AAG reduces MIF expression and blocks growth of MIF-expressing, but not MIF-deficient, tumors. Together, these findings identify MIF as a novel HSP90 client and suggest that HSP90 inhibitors inhibit ErbB2-driven breast tumor growth at least in part by destabilizing MIF.
Genetic resistance to JAK2 enzymatic inhibitors is overcome by HSP90 inhibition
Authors: Weigert Oliver , Lane Andrew A. , Bird Liat , Kopp Nadja , Chapuy Bjoern , van Bodegom Diederik , Toms Angela V. , Marubayashi Sachie , Christie Amanda L. , McKeown Michael , Paranal Ronald M. , Bradner James E. , Yoda Akinori , Gaul Christoph , Vangrevelinghe Eric , Romanet Vincent , Murakami Masato , Tiedt Ralph , Ebel Nicolas , Evrot Emeline , De Pover Alain , Régnier Catherine H. , Erdmann Dirk , Hofmann Francesco , Eck Michael J. , Sallan Stephen E. , Levine Ross L. , Kung Andrew L. , Baffert Fabienne , Radimerski Thomas , Weinstock David M.
Published: January 2012

Enzymatic inhibitors of Janus kinase 2 (JAK2) are in clinical development for the treatment of myeloproliferative neoplasms (MPNs), B cell acute lymphoblastic leukemia (B-ALL) with rearrangements of the cytokine receptor subunit cytokine receptor–like factor 2 (CRLF2), and other tumors with constitutive JAK2 signaling. In this study, we identify G935R, Y931C, and E864K mutations within the JAK2 kinase domain that confer resistance across a panel of JAK inhibitors, whether present in cis with JAK2 V617F (observed in MPNs) or JAK2 R683G (observed in B-ALL). G935R, Y931C, and E864K do not reduce the sensitivity of JAK2-dependent cells to inhibitors of heat shock protein 90 (HSP90), which promote the degradation of both wild-type and mutant JAK2. HSP90 inhibitors were 100–1,000-fold more potent against CRLF2-rearranged B-ALL cells, which correlated with JAK2 degradation and more extensive blockade of JAK2/STAT5, MAP kinase, and AKT signaling. In addition, the HSP90 inhibitor AUY922 prolonged survival of mice xenografted with primary human CRLF2-rearranged B-ALL further than an enzymatic JAK2 inhibitor. Thus, HSP90 is a promising therapeutic target in JAK2-driven cancers, including those with genetic resistance to JAK enzymatic inhibitors.
First Report of Hop stunt viroid Infecting Hop in Slovenia
Authors: Radisek S. , Majer A. , Jakse J. , Javornik B. , Matoušek J.
Published: January 2012

Hop (Humulus lupulus), of the Cannabaceae family, is a dioecious perennial climbing plant that is native to Asia, North America, and Europe and is commercially grown in many countries for its use in brewing and the pharmaceutical industry. Slovenia has a more than 100-year-old hop-growing tradition and it is an important national agricultural business, with 90% of production exported to foreign markets. Since 2007, symptoms similar to Hop stunt viroid (HSVd) infection have been observed in several hop gardens with cvs. Celeia, Bobek, and Aurora in the Savinja Valley and Koroška Region. Symptoms include stunting, leaf curl, small cone formation, and dry root rot. In the first year of finding the disease, the incidence varied from 1 to 30% and increased rapidly (by as much as 10%) each subsequent year, predominantly along plant rows. For molecular identification of the pathogen, RNA was extracted from leaves and cones of symptomatic and asymptomatic plants from two different hop gardens with cv. Celeia using Tri Reagent (T9424; Sigma-Aldrich, St Louis, MO). Reverse transcription-PCR was carried out using two pairs of specific HSVd primers, HSVdI/HSVdII and HSVdeI/HSVdeII (3,4). Both primer pairs gave a single PCR product from tissue from symptomatic plants, with expected lengths of ~300 bp, but no amplicons were produced using samples from asymptomatic plants. PCR products from HSVdI/HSVdII were subjected to direct sequencing and HSVdeI/HSVdeII products were cloned in PCR Script SK (+) (Stratagene, La Jolla, CA) vector and sequenced. Five sequences (EMBL Accession Nos. HE575344, HE575345, HE575346, HE575347, and HE575348) were obtained, which revealed 96 to 99% sequence identity with various HSVd variants (grapevine, citrus, and cucumber) reported in GenBank of the National Centre for Biotechnology Information (NCBI). HSVd belonging to the Hostuviroid genus, Pospiviroidae family, has been previously reported in hop in Japan, South Korea, North America, and China (1,2). To our knowledge, this is the first report of the detection of HSVd on hop in Europe. Strict phytosanitary measures have been taken to prevent further spread and to eradicate HSVd infections.

References: (1) K. C. Eastwell and T. Sano. Hop Stunt. Page 48 in: Compendium of Hop Diseases and Pests. W. F. Mahaffee et al., eds. The American Phytopathological Society, St. Paul, MN, 2009. (2) L. Guo et al. Plant Pathol. 57:764, 2008. (3) J. Matoušek et al. Plant Soil Environ. 49:168, 2003. (4) J. Matoušek et al. J. Virol. Methods 122:153, 2004.
Biometrical, Biochemical, and Molecular Diagnosis of Portuguese Meloidogyne hispanica Isolates
Authors: Maleita Carla M. , Simões Maria José , Egas Conceição , Curtis Rosane H. C. , de O. Abrantes Isabel M.
Published: January 2012

Meloidogyne hispanica infects many economically important crops worldwide. The accurate identification of this pathogen is essential for the establishment of efficient and sustainable integrated pest management programs. Portuguese M. hispanica isolates were studied by biometrical, biochemical, and molecular characteristics. Biometrical characteristics of M. hispanica females, males, and second-stage juveniles were similar to the original description. Biochemical studies revealed a unique enzyme pattern (Hi4) for M. hispanica esterases that allowed for species differentiation. Molecular analysis of the mtDNA region from COII and 16S rRNA genes resulted in amplification products (1,800 bp) similar to M. hispanica, M. ethiopica, and M. javanica, and the described HinfI was unable to discriminate M. hispanica from the other two species. Analysis of the mtDNA sequences revealed altered nucleotides among the isolates that created new restriction sites for AluI and DraIII. The resulting restriction patterns successfully discriminated between the three species, providing a new tool for Meloidogyne identification. Finally, the phylogenetic relationship between M. hispanica and several Meloidogyne spp. sequences was analyzed using mtDNA, confirming the divergence between meiotic and mitotic species and revealing the proximity of M. hispanica to closely related species. Based on the studies conducted, the application of isozyme or polymerase chain reaction restriction fragment length polymorphism analysis would be a useful and efficient methodology for M. hispanica identification.
First Report of Lavender Wilt Caused by Fusarium sporotrichioides in Croatia
Authors: Cosic J. , Vrandecic K. , Jurkovic D. , Postic J. , Orzali L. , Riccioni L.
Published: January 2012

In May 2011, samples of lavender plants (Lavandula × intermedia) showing wilt symptoms were collected from two commercial plantings in Slavonia County. Disease was observed on 20 to 30% of the plants. Symptoms of the disease consisted of chlorosis, stunting, wilting, and death. Vascular tissue of stems and roots exhibited brown discoloration. Isolations of the pathogen were made from the discolored tissues on potato dextrose agar (PDA). Colonies were initially white, but with age became red, and red pigments were produced in agar. Microconidia were pear shaped, oval, and fusoid, and ranged from 4.5 to 14.0 × 2.8 to 4.7 μm. Macroconidia were curved, mostly three septate, and ranged from 21.8 to 24.3 × 2.9 to 3.9 μm. Morphology of colonies and conidia matched the description of Fusarium sporotrichioides Sherb. (1). Identity of the fungus was confirmed by examining a portion of the EF1-α gene using the degenerated primers EF1 and EF2 (2). BLAST searches of the obtained sequences showed a 100% homology with several isolates of F. sporotrichioides from GenBank. Pathogenicity tests were conducted on 20 4-month-old rooted cuttings under greenhouse conditions. Each plant was planted in a separate pot containing 0.7 liter of sterile soil. Inoculum for artificial infection was prepared with sterilized mixtures of wheat and barley seeds (10 g of each). Seeds were inoculated with a F. sporotrichioides spore suspension (106 conidia/ml) and incubated at 22°C for 10 days. Noninoculated seeds served as controls. Ten seeds were placed under the soil surface around the root of each plant. Plants were irrigated and placed in a greenhouse (22°C and a 12-h day/night photoperiod). Sixteen days after inoculation, 80% of inoculated plants were wilted. Symptoms on infected plants were similar to those observed in the field. The pathogen was reisolated and confirmed from the infected vascular tissue, thus fulfilling Koch's postulates. A previous paper reported lavender as host of F. solani in China (4) and F. oxysporum in Saudi Arabia (3). To our knowledge, this is the first report of Fusarium wilt of lavender caused by F. sporotrichioides.

References: (1) J. F. Leslie and B. A. Summerell. Page 256 in: The Fusarium Laboratory Manual. Blackwell Publishing Professional, Hoboken, NJ, 2006. (2) K. O'Donnell et al. Appl Biol. Sci. 95:2044, 1998. (3) K. Perveen and N. Bokhari. Plant Dis. 94:1163, 2010. (4) Y. Z. Ren et al. New Dis. Rep. 15:55, 2007.
Structure of the interleukin-2 tyrosine kinase Src homology 2 domain; comparison between X-ray and NMR-derived structures
Authors: Joseph Raji E. , Ginder Nathaniel D. , Hoy Julie A. , Nix Jay C. , Fulton D. Bruce , Honzatko Richard B. , Andreotti Amy H.
Published: January 2012

The crystal structure of the interleukin-2 tyrosine kinase Src homology domain (Itk SH2) is described and it is found that unlike in studies of this domain using NMR spectroscopy,cis–trans-prolyl isomerization is not readily detected in the crystal structure. Based on similarities between the Itk SH2 crystal form and thecisform of the Itk SH2 NMR structure, it is concluded that it is likely that the prolyl imide bond at least in part adopts thecisconformation in the crystal form. However, the lack of high-resolution data and the dynamic nature of the proline-containing loop mean that the precise imide-bond conformation cannot be determined and prolylcis–transisomerization in the crystal cannot be ruled out. Given the preponderance of structures that have been solved by X-ray crystallography in the Protein Data Bank, this result supports the notion that prolyl isomerization in folded proteins has been underestimated among known structures. Interestingly, while the precise status of the proline residue is ambiguous, Itk SH2 crystallizes as a domain-swapped dimer. The domain-swapped structure of Itk SH2 is similar to the domain-swapped SH2 domains of Grb2 and Nck, with domain swapping occurring at the β-meander region of all three SH2 domains. Thus, for Itk SH2 structural analysis by NMR spectroscopy and X-ray crystallography revealed very different structural features: proline isomerizationversusdomain-swapped dimerization, respectively.
Lysozyme contamination facilitates crystallization of a heterotrimeric cortactin–Arg–lysozyme complex
Authors: Liu Weizhi , MacGrath Stacey M. , Koleske Anthony J. , Boggon Titus J.
Published: January 2012

Crystallization of contaminating proteins is a frequently encountered problem for macromolecular crystallographers. In this study, an attempt was made to obtain a binary cocrystal structure of the SH3 domain of cortactin and a 17-residue peptide from the Arg nonreceptor tyrosine kinase encompassing a PxxPxxPxxP (PxxP1) motif. However, cocrystals could only be obtained in the presence of trace amounts of a contaminating protein. A structure solution obtained by molecular replacement followed byARP/wARPautomatic model building allowed a `sequence-by-crystallography' approach to discover that the contaminating protein was lysozyme. This 1.65 Å resolution crystal structure determination of a 1:1:1 heterotrimeric complex of Arg, cortactin and lysozyme thus provides an unusual `caveat emptor' warning of the dangers that underpurified proteins harbor for macromolecular crystallographers.
Cytogenetic mapping of the W chromosome in the genus Leporinus (Teleostei, Anostomidae) using a highly repetitive DNA sequence
Authors: Marreta M. E. , Faldoni F. L. C. , Parise‐Maltempi P. P.
Published: January 2012

The distribution of the Leporinus elongatus LeSpeI repetitive sequence in other Leporinus species was studied in an attempt to elucidate the evolutionary history of sex chromosomes in this genus using chromosome fluorescence in situ hybridization. The presence of fluorescent signals only in species that have differentiated sex chromosomes suggests that this sequence is related to the differentiation of sex chromosomes in this genus. Thus, these data will contribute to a better understanding of chromosome evolution, especially for sex chromosomes, in the Leporinus genus.
Role of IGF‐1 and glycaemic control in diabetic retinopathy
Authors: Triebel Jakob
Published: January 2012

Eur J Clin Invest 2012; 42 (7): 804
Richness and composition of plants and birds on land‐bridge islands: effects of island attributes and differential responses of species groups
Authors: Yu Mingjian , Hu Guang , Feeley Kenneth J. , Wu Jianguo , Ding Ping
Published: January 2012

Aim  To test relationships between the richness and composition of vascular plants and birds and attributes of habitat fragments using a model land‐bridge island system, and to investigate whether the effects of fragmentation differ depending on species natural history traits.

Location  Thousand Island Lake, China.

Methods  We compiled presence/absence data of vascular plant and bird species through exhaustive surveys of 41 islands. Plant species were assigned to two categories: shade‐intolerant and shade‐tolerant species; bird species were assigned to three categories: edge, interior, and generalist species. We analysed the relationships between island attributes (area, isolation, elevation, shape complexity, and perimeter to area ratio) and species richness using generalized linear models (GLMs). We also investigated patterns of composition in relation to island attributes using ordination (redundancy analysis).

Results  We found that island area explained a high degree of variation in the species richness of all species groups. The slope of the species–area relationship (z) was 0.16 for all plant species and 0.11 for all bird species. The lowest z‐value was for generalist birds (0.04). The species richness of the three plant species groups was associated with island area per se, while that of all, generalist, and interior birds was explained mainly by elevation, and that of edge bird species was associated primarily with island shape. Patterns of species composition were most strongly related to elevation, island shape complexity, and perimeter to area ratio rather than to island area per se. Species richness had no significant relationship with isolation, but species composition did. We also found differential responses among the species groups to changes in island attributes.

Main conclusions  Within the Thousand Island Lake system, the effects of fragmentation on both bird and plant species appear to be scale‐dependent and taxon‐specific. The number of plant species occurring on an island is strongly correlated with island area, and the richness of birds and the species composition of plants and birds are associated with variables related to habitat heterogeneity. We conclude that the effects of fragmentation on species diversity and composition depend not only on the degree of habitat loss but also on the specific patterns of habitat fragmentation.
Spironolactone diminishes urinary albumin excretion in patients with type 1 diabetes and microalbuminuria: a randomized placebo‐controlled crossover study
Authors: Nielsen S. E. , Persson F. , Frandsen E. , Sugaya T. , Hess G. , Zdunek D. , Shjoedt K. J. , Parving H‐H. , Rossing P.
Published: January 2012

Diabet. Med. 29, e184–e190 (2012)

Aims  Adding aldosterone receptor blockade to standard renoprotective treatment may provide additional renoprotection in patients with overt nephropathy. We expected an impact of spironolactone in early diabetic nephropathy, and for this hypothesis we studied the effect on markers of glomerular and tubular damage in patients with Type 1 diabetes and persistent microalbuminuria.

Methods  A double‐blind, randomized, placebo‐controlled crossover study in 21 patients with Type 1 diabetes and microalbuminuria using spironolactone 25 mg or placebo once daily, for 60 days added to standard antihypertensive treatment. After each treatment period, the primary endpoint were evaluated: urinary(u)‐albumin excretion/24 hour(h) and secondary endpoints; 24 h blood pressure, glomerular filtration rate (GFR) and markers of tubular damage: urinary liver‐type fatty‐acid binding protein (LFABP), neutrophil gelatinase associated lipocalin (NGAL) and kidney injury molecule 1 (KIM1).

Results  All patients completed the study. During spironolactone treatment, urinary albumin excretion rate was reduced by 60% (range 21–80%), from 90 mg/24 h to 35 mg/24 h (P = 0.01). Blood pressure (24 h) did not change during spironolactone treatment (P > 0.2 for all comparisons). The GFR (SD) decreased from 78 (6) mL/min/1.73 m2 to 72 (6) mL/min/1.73 m2 (P = 0.003). Urinary liver‐type fatty‐acid binding protein, neutrophil gelatinase‐associated lipocalin and kidney injury molecule 1 did not change during treatment (P > 0.3 for all comparisons). Treatment was well‐tolerated, but two patients had severe hyperkalaemia (plasma potassium = 5.7 mmol/l), which was sufficiently treated with diuretics and dietary intervention.

Conclusions  Spironolactone treatment in addition to standard renoprotective treatment lowers urinary albumin excretion in microalbuminuric patients with Type 1 diabetes, and thus may offer additional renoprotection independent of blood pressure.
Retinal nerve fibre layer thinning associated with diabetic peripheral neuropathy
Authors: Shahidi A. M. , Sampson G. P. , Pritchard N. , Edwards K. , Vagenas D. , Russell A. W. , Malik R. A. , Efron N.
Published: January 2012

Diabet. Med. 29, e106–e111 (2012)

Aims  To investigate the relationship between retinal nerve fibre layer thickness and peripheral neuropathy in patients with Type 2 diabetes, particularly in those who are at higher risk of foot ulceration.

Methods  Global and sectoral retinal nerve fibre layer thicknesses were measured at 3.45 mm diameter around the optic nerve head using optical coherence tomography (OCT). The level of neuropathy was assessed in 106 participants (82 with Type 2 diabetes and 24 healthy controls) using the 0–10 neuropathy disability score. Participants were stratified into four neuropathy groups: none (0–2), mild (3–5), moderate (6–8), and severe (9–10). A neuropathy disability score ≥ 6 was used to define those at higher risk of foot ulceration. Multivariable regression analysis was performed to assess the effect of neuropathy disability scores, age, disease duration and retinopathy on RNFL thickness.

Results  Inferior (but not global or other sectoral) retinal nerve fibre layer thinning was associated with higher neuropathy disability scores (P = 0.03). The retinal nerve fibre layer was significantly thinner for the group with neuropathy disability scores ≥ 6 in the inferior quadrant (P < 0.005). Age, duration of disease and retinopathy levels did not significantly influence retinal nerve fibre layer thickness. Control participants did not show any significant differences in thickness measurements from the group with diabetes and no neuropathy (P > 0.24 for global and all sectors).

Conclusions  Inferior quadrant retinal nerve fibre layer thinning is associated with peripheral neuropathy in patients with Type 2 diabetes, and is more pronounced in those at higher risk of foot ulceration.