bluuebunny/crossref_metadata_2025 huggingface dataset:
Atomic mechanism of electric dipole formed at high-K: SiO2 interface
Authors: Lin L. , Robertson J.
Published: May 2011

The mechanism of flat-band voltage shifts in La- and Al-based, etc., oxide capping layers in high-K (dielectric constant) metal gate stacks is investigated by ab initio calculations on atomic models. The capping layer dopants are calculated to segregate to the high-K:SiO2 interface in most cases. An interfacial dipole is observed at both the pure HfO2:SiO2 interface and at oxide doped HfO2:SiO2 interfaces by plotting electrostatic potentials perpendicular to the interfaces. Substitutional La, Sr, Al, Nb, and Ti atoms are calculated to induce potential shifts at the HfO2: SiO2 interface which shift the valence band offset in the experimentally observed directions. The shift does not correlate with the metal’s valence, being the opposite for La and Al, which rules out the oxygen vacancy model. The shift does correlate with the metal’s group-electronegativity or metal work function. The potential shift due to A-O and O-A bond dipoles cancels out, on average, in the ‘bulk’ parts of the gate oxide film, and it is only finite where there is a change in the dielectric constant and screening across this buried interface. The net dipole potential shift only comes from those dopant atoms located at the interface itself, not those that diffused away from this interface.
Lead silicate glass microsphere resonators with absorption-limited Q
Authors: Wang Pengfei , Murugan Ganapathy Senthil , Lee Timothy , Feng Xian , Semenova Yuliya , Wu Qiang , Loh Wei , Brambilla Gilberto , Wilkinson James S. , Farrell Gerald
Published: May 2011

We report the fabrication and characterization of a lead-silicate glass microsphere resonator. We show that at the wavelengths near 1555 nm high Q modes can be efficiently excited from a 109 μm diameter lead-silicate glass microsphere via evanescent coupling using a tapered silica fiber with a waist diameter of 2 μm. Resonances with Q-factors as high as 0.9×107 were observed. This is very close to the theoretical material-limited Q-factor and is the highest Q-factor reported so far from a nonlinear glass microsphere.
Surface roughness reduction in nanocrystalline Cu thin films by electrical stressing treatment
Authors: Chan Tsung-Cheng , Chen Kuan-Chia , Liao Chien-Neng
Published: May 2011

Electromigration-induced surface morphological evolution of nanocrystalline Cu thin films is reported. When applying a high-density current (106 A/cm2), the Cu films showed reduced surface roughness from 7.5 to 1.4 nm after electrical stressing at the temperature below 100 °C. It is suggested that preferential surface diffusion on Cu(111) planes leads to thinning of extruded grains in the electrically stressed Cu film, as evidenced by the weakening (111) texture of the Cu film after electrical stressing. The electrical stressing process shall help reduce roughness of Cu metallization after post thermal treatment.
Slab melting versus slab dehydration in subduction-zone magmatism
Authors: Mibe Kenji , Kawamoto Tatsuhiko , Matsukage Kyoko N. , Fei Yingwei , Ono Shigeaki
Published: May 2011

The second critical endpoint in the basalt-H
2
O system was directly determined by a high-pressure and high-temperature X-ray radiography technique. We found that the second critical endpoint occurs at around 3.4 GPa and 770 °C (corresponding to a depth of approximately 100 km in a subducting slab), which is much shallower than the previously estimated conditions. Our results indicate that the melting temperature of the subducting oceanic crust can no longer be defined beyond this critical condition and that the fluid released from subducting oceanic crust at depths greater than 100 km under volcanic arcs is supercritical fluid rather than aqueous fluid and/or hydrous melts. The position of the second critical endpoint explains why there is a limitation to the slab depth at which adakitic magmas are produced, as well as the origin of across-arc geochemical variations of trace elements in volcanic rocks in subduction zones.
Broad disorder and the allosteric mechanism of myosin II regulation by phosphorylation
Authors: Vileno Bertrand , Chamoun Jean , Liang Hua , Brewer Paul , Haldeman Brian D. , Facemyer Kevin C. , Salzameda Bridget , Song Likai , Li Hui-Chun , Cremo Christine R. , Fajer Piotr G.
Published: May 2011

Double electron electron resonance EPR methods was used to measure the effects of the allosteric modulators, phosphorylation, and ATP, on the distances and distance distributions between the two regulatory light chain of myosin (RLC). Three different states of smooth muscle myosin (SMM) were studied: monomers, the short-tailed subfragment heavy meromyosin, and SMM filaments. We reconstituted myosin with nine single cysteine spin-labeled RLC. For all mutants we found a broad distribution of distances that could not be explained by spin-label rotamer diversity. For SMM and heavy meromyosin, several sites showed two heterogeneous populations in the unphosphorylated samples, whereas only one was observed after phosphorylation. The data were consistent with the presence of two coexisting heterogeneous populations of structures in the unphosphorylated samples. The two populations were attributed to an on and off state by comparing data from unphosphorylated and phosphorylated samples. Models of these two states were generated using a rigid body docking approach derived from EM [Wendt T, Taylor D, Trybus KM, Taylor K (2001)
Proc Natl Acad Sci USA
98:4361–4366] (PNAS, 2001, 98:4361–4366), but our data revealed a new feature of the off-state, which is heterogeneity in the orientation of the two RLC. Our average off-state structure was very similar to the Wendt model reveal a new feature of the off state, which is heterogeneity in the orientations of the two RLC. As found previously in the EM study, our on-state structure was completely different from the off-state structure. The heads are splayed out and there is even more heterogeneity in the orientations of the two RLC.
Astroglial networks scale synaptic activity and plasticity
Authors: Pannasch Ulrike , Vargová Lydia , Reingruber Jürgen , Ezan Pascal , Holcman David , Giaume Christian , Syková Eva , Rouach Nathalie
Published: May 2011

Astrocytes dynamically interact with neurons to regulate synaptic transmission. Although the gap junction proteins connexin 30 (Cx30) and connexin 43 (Cx43) mediate the extensive network organization of astrocytes, their role in synaptic physiology is unknown. Here we show, by inactivating Cx30 and Cx43 genes, that astroglial networks tone down hippocampal synaptic transmission in CA1 pyramidal neurons. Gap junctional networking facilitates extracellular glutamate and potassium removal during synaptic activity through modulation of astroglial clearance rate and extracellular space volume. This regulation limits neuronal excitability, release probability, and insertion of postsynaptic AMPA receptors, silencing synapses. By controlling synaptic strength, connexins play an important role in synaptic plasticity. Altogether, these results establish connexins as critical proteins for extracellular homeostasis, important for the formation of functional synapses.
General rules for managing and surveying networks of pests, diseases, and endangered species
Authors: Chadès Iadine , Martin Tara G. , Nicol Samuel , Burgman Mark A. , Possingham Hugh P. , Buckley Yvonne M.
Published: May 2011

The efficient management of diseases, pests, or endangered species is an important global issue faced by agencies constrained by limited resources. The management challenge is even greater when organisms are difficult to detect. We show how to prioritize management and survey effort across time and space for networks of susceptible–infected–susceptible subpopulations. We present simple and robust rules of thumb for protecting desirable, or eradicating undesirable, subpopulations connected in typical network patterns (motifs). We further demonstrate that these rules can be generalized to larger networks when motifs are combined in more complex formations. Results show that the best location to manage or survey a pest or a disease on a network is also the best location to protect or survey an endangered species. The optimal starting point in a network is the fastest motif to manage, where line, star, island, and cluster motifs range from fast to slow. Managing the most connected node at the right time and maintaining the same management direction provide advantages over previously recommended outside–in strategies. When a species or disease is not detected and our belief in persistence decreases, our results recommend shifting resources toward management or surveillance of the most connected nodes. Our analytic approximation provides guidance on how long we should manage or survey networks for hard-to-detect organisms. Our rules take into account management success, dispersal, economic cost, and imperfect detection and offer managers a practical basis for managing networks relevant to many significant environmental, biosecurity, and human health issues.
Synchronized arousal between performers and related spectators in a fire-walking ritual
Authors: Konvalinka Ivana , Xygalatas Dimitris , Bulbulia Joseph , Schjødt Uffe , Jegindø Else-Marie , Wallot Sebastian , Van Orden Guy , Roepstorff Andreas
Published: May 2011

Collective rituals are present in all known societies, but their function is a matter of long-standing debates. Field observations suggest that they may enhance social cohesion and that their effects are not limited to those actively performing but affect the audience as well. Here we show physiological effects of synchronized arousal in a Spanish fire-walking ritual, between active participants and related spectators, but not participants and other members of the audience. We assessed arousal by heart rate dynamics and applied nonlinear mathematical analysis to heart rate data obtained from 38 participants. We compared synchronized arousal between fire-walkers and spectators. For this comparison, we used recurrence quantification analysis on individual data and cross-recurrence quantification analysis on pairs of participants' data. These methods identified fine-grained commonalities of arousal during the 30-min ritual between fire-walkers and related spectators but not unrelated spectators. This indicates that the mediating mechanism may be informational, because participants and related observers had very different bodily behavior. This study demonstrates that a collective ritual may evoke synchronized arousal over time between active participants and bystanders. It links field observations to a physiological basis and offers a unique approach for the quantification of social effects on human physiology during real-world interactions.
Thyroxine is a potential endogenous antagonist of macrophage migration inhibitory factor (MIF) activity
Authors: Al-Abed Yousef , Metz Christine N. , Cheng Kai Fan , Aljabari Bayan , VanPatten Sonya , Blau Steven , Lee Hans , Ochani Mahendar , Pavlov Valentin A. , Coleman Thomas , Meurice Nathalie , Tracey Kevin J. , Miller Edmund J.
Published: May 2011

Abnormally low plasma concentrations of thyroid hormones during sepsis often occur in the absence of thyroidal illness; however, the mechanisms involved in the “euthyroid sick syndrome” remain poorly understood. Here, we describe a previously unrecognized interaction between the thyroid hormone thyroxine (T
4
) and the proinflammatory cytokine macrophage migration inhibitory factor (MIF), together with its clinical relevance in sepsis. We found that in both patients with severe sepsis, and our rodent model, low plasma T
4
concentrations were inversely correlated with plasma MIF concentrations. The MIF molecule contains a hydrophobic pocket that is important for many of its proinflammatory activities. Binding of L-T
4
(or its hormonally inert isomer D-T
4
) significantly, and dose-dependently, inhibited the catalytic activity of this pocket. Moreover, administration of exogenous D-T
4
significantly improved survival in mice with severe sepsis. To examine the specificity of the MIF∶T
4
interaction, wild-type and MIF knockout mice were subjected to the carrageenan-air pouch model of inflammation and then treated with D-T
4
or vehicle. D-T
4
significantly inhibited leukocyte infiltration in wild-type mice but not in MIF knockout mice, providing evidence that in vivo T
4
may influence MIF-mediated inflammatory responses via inhibition of its hydrophobic proinflammatory pocket. These findings demonstrate a new physiological role for T
4
as a natural inhibitor of MIF proinflammatory activity. The data may also, in part, explain the low plasma T
4
concentrations in critically ill, euthyroid patients and suggest that targeting the imbalance between MIF and T
4
may be beneficial in improving outcome from sepsis.
Targeting zebrafish and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitor
Authors: Liu Ning-Ai , Jiang Hong , Ben-Shlomo Anat , Wawrowsky Kolja , Fan Xue-Mo , Lin Shuo , Melmed Shlomo
Published: May 2011

Cushing disease caused by adrenocorticotropin (ACTH)-secreting pituitary adenomas leads to hypercortisolemia predisposing to diabetes, hypertension, osteoporosis, central obesity, cardiovascular morbidity, and increased mortality. There is no effective pituitary targeted pharmacotherapy for Cushing disease. Here, we generated germline transgenic zebrafish with overexpression of pituitary tumor transforming gene (
PTTG/securin
) targeted to the adenohypophyseal proopiomelanocortin (POMC) lineage, which recapitulated early features pathognomonic of corticotroph adenomas, including corticotroph expansion and partial glucocorticoid resistance. Adult Tg:Pomc-Pttg fish develop neoplastic coticotrophs and pituitary cyclin E up-regulation, as well as metabolic disturbances mimicking hypercortisolism caused by Cushing disease. Early development of corticotroph pathologies in Tg:Pomc-Pttg embryos facilitated drug testing in vivo. We identified a pharmacologic CDK2/cyclin E inhibitor, R-roscovitine (seliciclib; CYC202), which specifically reversed corticotroph expansion in live Tg:Pomc-Pttg embryos. We further validated that orally administered R-roscovitine suppresses ACTH and corticosterone levels, and also restrained tumor growth in a mouse model of ACTH-secreting pituitary adenomas. Molecular analyses in vitro and in vivo showed that R-roscovitine suppresses ACTH expression, induces corticotroph tumor cell senescence and cell cycle exit by up-regulating p27, p21 and p57, and downregulates cyclin E expression. The results suggest that use of selective CDK inhibitors could effectively target corticotroph tumor growth and hormone secretion.
Loss of nuclear factor E2-related factor 1 in the brain leads to dysregulation of proteasome gene expression and neurodegeneration
Authors: Lee Candy S. , Lee Chiashan , Hu Terry , Nguyen Janice M. , Zhang Jiasheng , Martin Maureen V. , Vawter Marquis P. , Huang Eric J. , Chan Jefferson Y.
Published: May 2011

The ubiquitin–proteasome pathway plays an important role in the pathogenesis of neurodegeneration, but mechanisms controlling expression of components in this pathway remain poorly understood. Nuclear factor E2-related factor 1 (Nrf1) transcription factor has been shown to regulate expression of antioxidant and cytoprotective genes. To determine the function of Nrf1 in the brain, mice with a late-stage deletion of
Nrf1
in neuronal cells were generated. Loss of Nrf1 leads to impaired proteasome function and neurodegeneration. Gene expression profiling and RT-PCR analysis revealed a coordinate down-regulation of various proteasomal genes including
PsmB6
, which encodes a catalytic subunit of the proteasome. Transcriptional analysis and chromatin immunoprecipitation experiments demonstrated that PsmB6 is an Nrf1 target gene. These findings reveal Nrf1 as a key transcriptional regulator required for the expression of proteasomal genes in neurons and suggest that perturbations of Nrf1 function may contribute to the pathogenesis of neurodegenerative diseases.
Cadherin-11 regulates fibroblast inflammation
Authors: Chang Sook Kyung , Noss Erika H. , Chen Mei , Gu Zhizhan , Townsend Kirk , Grenha Rosa , Leon Luis , Lee Soo Young , Lee David M. , Brenner Michael B.
Published: May 2011

Fibroblasts are important participants in inflammation. Although not leukocytes, their capacity to produce cytokines, chemokines, and other inflammatory factors locally in tissues suggests that they can contribute to inflammatory diseases. For example, fibroblasts in a rheumatoid arthritis (RA) joint are a dominant source of IL-6 and RANKL in the synovium, both of which are therapeutic targets for inflammation and bone erosion. Previously, we found that fibroblasts can be targeted by mAb directed against cadherin-11 (cad-11), a mesenchymal cadherin that fibroblasts selectively express. Targeting cad-11 significantly reduced inflammation as assessed by joint swelling and clinical inflammation scores. However, the mechanism by which anti–cad-11 reduced inflammation was not known. Here, we show that cad-11 engagement induces synovial fibroblasts to secret proinflammatory cytokines including IL-6. Cad-11 engagement strongly synergized with TNF-α and IL-1β in the induction of IL-6. Importantly, cad-11 activated MAP kinases and NF-κB for IL-6 induction. IL-6 levels in ankles of inflamed joints were reduced in cad-11 mutant mice compared to wild-type mice with inflammatory arthritis. Thus, we suggest that cad-11 modulates synovial fibroblasts to evoke inflammatory factors that may contribute to the inflammatory process in RA.
The dominantly expressed class I molecule of the chicken MHC is explained by coevolution with the polymorphic peptide transporter (TAP) genes
Authors: Walker Brian A. , Hunt Lawrence G. , Sowa Anna K. , Skjødt Karsten , Göbel Thomas W. , Lehner Paul J. , Kaufman Jim
Published: May 2011

In most mammals, the MHC class I molecules are polymorphic and determine the specificity of peptide presentation, whereas the transporter associated with antigen presentation (TAP) heterodimers are functionally monomorphic. In chickens, there are two classical class I genes but only one is expressed at a high level, which can result in strong MHC associations with resistance to particular infectious pathogens. However, the basis for having a single dominantly expressed class I molecule has been unclear. Here we report TAP1 and TAP2 sequences from 16 chicken lines, and show that both genes have high allelic polymorphism and moderate sequence diversity, with variation in positions expected for peptide binding. We analyze peptide translocation in two MHC haplotypes, showing that chicken TAPs specify translocation at three peptide positions, matching the peptide motif of the single dominantly expressed class I molecule. These results show that coevolution between class I and TAP genes can explain the presence of a single dominantly expressed class I molecule in common chicken MHC haplotypes. Moreover, such coevolution in the primordial MHC may have been responsible for the appearance of the antigen presentation pathways at the birth of the adaptive immune system.
Overt attention toward oriented objects in free-viewing barn owls
Authors: Harmening Wolf Maximilian , Orlowski Julius , Ben-Shahar Ohad , Wagner Hermann
Published: May 2011

Visual saliency based on orientation contrast is a perceptual product attributed to the functional organization of the mammalian brain. We examined this visual phenomenon in barn owls by mounting a wireless video microcamera on the owls’ heads and confronting them with visual scenes that contained one differently oriented target among similarly oriented distracters. Without being confined by any particular task, the owls looked significantly longer, more often, and earlier at the target, thus exhibiting visual search strategies so far demonstrated in similar conditions only in primates. Given the considerable differences in phylogeny and the structure of visual pathways between owls and humans, these findings suggest that orientation saliency has computational optimality in a wide variety of ecological contexts, and thus constitutes a universal building block for efficient visual information processing in general.
Enhanced synaptic plasticity in mice with phosphomimetic mutation of the GluA1 AMPA receptor
Authors: Makino Yuichi , Johnson Richard C. , Yu Yilin , Takamiya Kogo , Huganir Richard L.
Published: May 2011

Phosphorylation of the GluA1 subunit of AMPA receptors has been proposed to regulate receptor trafficking and synaptic transmission and plasticity. However, it remains unclear whether GluA1 phosphorylation is permissive or sufficient for enacting these functional changes. Here we investigate the role of GluA1 phosphorylation at S831 and S845 residues in the hippocampus through the analyses of GluA1 S831D/S845D phosphomimetic knock-in mice. S831D/S845D mice showed normal total and surface expression and subcellular localization of GluA1 as well as intact basal synaptic transmission. In addition, theta-burst stimulation, a protocol that was sufficient to induce robust long-term potentiation (LTP) in WT mice, resulted in LTP of similar magnitude in S831D/S845D mice. However, S831D/S845D mice showed LTP induced with 10-Hz stimulation, a protocol that is weaker than theta-burst stimulation and was not sufficient to induce LTP in WT mice. Moreover, S831D/S845D mice exhibited LTP induced with spike-timing–dependent plasticity (STDP) protocol at a long pre-post interval that was subthreshold for WT mice, although a suprathreshold STDP protocol at a short pre-post interval resulted in similarly robust LTP for WT and S831D/S845D mice. These results indicate that phosphorylation of GluA1 at S831 and S845 is sufficient to lower the threshold for LTP induction, increasing the probability of synaptic plasticity.
RNA 3′ processing functions of
Arabidopsis
FCA and FPA limit intergenic transcription
Authors: Sonmez Cagla , Bäurle Isabel , Magusin Andreas , Dreos Rene , Laubinger Sascha , Weigel Detlef , Dean Caroline
Published: May 2011

The RNA-binding proteins FCA and FPA were identified based on their repression of the flowering time regulator
FLC
but have since been shown to have widespread roles in the
Arabidopsis thaliana
genome. Here, we use whole-genome tiling arrays to show that a wide spectrum of genes and transposable elements are misexpressed in the
fca-9 fpa-7 (fcafpa)
double mutant at two stages of seedling development. There was a significant bias for misregulated genomic segments mapping to the 3′ region of genes. In addition, the double mutant misexpressed a large number of previously unannotated genomic segments corresponding to intergenic regions. We characterized a subset of these misexpressed unannotated segments and established that they resulted from extensive transcriptional read-through, use of downstream polyadenylation sites, and alternative splicing. In some cases, the transcriptional read-through significantly reduced expression of the associated genes. FCA/FPA-dependent changes in DNA methylation were found at several loci, supporting previous associations of FCA/FPA function with chromatin modifications. Our data suggest that FCA and FPA play important roles in the
A. thaliana
genome in RNA 3′ processing and transcription termination, thus limiting intergenic transcription.
Posttranscriptional activation of gene expression in
Xenopus laevis
oocytes by microRNA–protein complexes (microRNPs)
Authors: Mortensen Richard D. , Serra Maria , Steitz Joan A. , Vasudevan Shobha
Published: May 2011

MicroRNA–protein complexes (microRNPs) can activate translation of target reporters and specific mRNAs in quiescent (i.e., G0) mammalian cell lines. Induced quiescent cells, like folliculated immature oocytes, have high levels of cAMP that activate protein kinase AII (PKAII) to maintain G0 and immature states. We report microRNA-mediated up-regulated expression of reporters in immature
Xenopus laevis
oocytes, dependent on
Xenopus
AGO or human AGO2 and on FXR1, as in mammalian cells. Importantly, we find that maintenance of cAMP levels and downstream PKAII signaling are required for microRNA-mediated up-regulated expression in oocytes. We identify an important, endogenous cell state regulator, Myt1 kinase, as a natural target of microRNA-mediated up-regulation in response to xlmiR16, ensuring maintenance of oocyte immaturity. Our data reveal the physiological relevance of cAMP/PKAII-controlled posttranscriptional gene expression activation by microRNAs in maintenance of the immature oocyte state.
Gain-of-function mutations in interleukin-7 receptor-α (IL7R) in childhood acute lymphoblastic leukemias
Authors: Shochat Chen , Tal Noa , Bandapalli Obul R. , Palmi Chiara , Ganmore Ithamar , te Kronnie Geertruy , Cario Gunnar , Cazzaniga Giovanni , Kulozik Andreas E. , Stanulla Martin , Schrappe Martin , Biondi Andrea , Basso Giuseppe , Bercovich Dani , Muckenthaler Martina U. , Izraeli Shai
Published: May 2011

Interleukin-7 receptor α (IL7R) is required for normal lymphoid development. Loss-of-function mutations in this gene cause autosomal recessive severe combined immune deficiency. Here, we describe somatic gain-of-function mutations in IL7R in pediatric B and T acute lymphoblastic leukemias. The mutations cause either a serine-to-cysteine substitution at amino acid 185 in the extracellular domain (4 patients) or in-frame insertions and deletions in the transmembrane domain (35 patients). In B cell precursor leukemias, the mutations were associated with the aberrant expression of cytokine receptor-like factor 2 (CRLF2), and the mutant IL-7R proteins formed a functional receptor with CRLF2 for thymic stromal lymphopoietin (TSLP). Biochemical and functional assays reveal that these IL7R mutations are activating mutations conferring cytokine-independent growth of progenitor lymphoid cells. A cysteine, included in all but three of the mutated IL-7R alleles, is essential for the constitutive activation of the receptor. This is the first demonstration of gain-of-function mutations of IL7R. Our current and recent observations of mutations in IL7R and CRLF2, respectively suggest that the addition of cysteine to the juxtamembranous domains is a general mechanism for mutational activation of type I cytokine receptors in leukemia.
First Report of Clover Proliferation Group Phytoplasmas (16SrVI-A) Associated with Purple Top Diseased Potatoes (Solanum tuberosum) in China
Authors: Cheng M. , Dong J. , Laski P. J. , Zhang Z. , McBeath J. H.
Published: May 2011

Phytoplasma diseases on potatoes are not well understood and have gone largely undetected in China. During the growing seasons of 2005 through 2010, potato disease surveys were conducted in seed and commercial fields in Yunnan Province. Samples were also harvested from three seed potato production areas in the Inner Mongolia Autonomous Region in 2007 and 2010. Disease incidence in these fields ranged from 15 to 85%. Plants displayed symptoms of branch proliferation, aerial tuber formation, upward rolling yellowish and purplish apical leaves, and extremely short stolen or chain tubers (irregular-shaped tubers). Total DNA from 250 samples was extracted from the leaves, stems, and roots of symptomatic and asymptomatic plants. A nested PCR was performed by using primer pair P1/P7 followed by R16F2n/R16R2 to detect the presence of phytoplasmas (1,3). An approximate 1.2-kb PCR product was amplified from symptomatic plants but not from asymptomatic plants. Restriction fragment length polymorphism (RFLP) patterns were analyzed by digesting the 1.2-kb amplicon singly with restriction enzymes AluI, BfaI, MseI, HhaI, HinfI, HpaII, KpnI, RsaI, and TaqI. The RFLP patterns of 120 of the 250 samples matched patterns of the clover proliferation (CP) group (16SrVI) subgroup A (16SrVI-A) phytoplasma (1). In addition, the nested PCR product of P1A/P7A (2) following P1/P7 amplification was cloned and sequenced (GenBank Accession No. HQ609490). Nucleotide sequences were analyzed by iPhyClassifier software (4), confirming the relationship of this phytoplasma to ‘Candidatus Phytoplasma trifolii’ with RFLP patterns identical to group 16SrVI-A. To our knowledge, this is the first report of the CP group phytoplasmas associated with purple top diseased potatoes in China.

References: (1) I.-M. Lee et al. Int. J. Syst. Bacteriol. 48:1153, 1998. (2) I.-M. Lee et al. Int. J. Syst. Evol. Microbiol 54:337, 2004. (3) C. D. Smart et al. Appl. Environ. Microbiol. 62:2988, 1996. (4) Y. Zhao et al. Int. J. Syst. Evol. Microbiol. 59:2582, 2009.
Dynamic Imaging of Perfusion and Oxygenation by Functional Magnetic Resonance Imaging
Authors: Ikuhiro Kida , Paul K. Maciejewski , Hyder Fahmeed
Published: May 2011

Cerebral blood flow can be measured with magnetic resonance imaging (MRI) by arterial spin labeling techniques, where magnetic labeling of flowing spins in arterial blood water functions as the endogenous tracer upon mixing with the unlabeled stationary spins of tissue water. The consequence is that the apparent longitudinal relaxation time (T1) of tissue water is attenuated. A modified functional MRI scheme for dynamic CBF measurement is proposed that depends on extraction of T1 weighting from the blood oxygenation level–dependent (BOLD) image contrast, because the functional MRI signal also has an intrinsic T1 weighting that can be altered by variations of the excitation flip angle. In the α-chloralose-anesthetized rat model at 7T, the authors show that the stimulation-induced BOLD signal change measured with two different flip angles can be combined to obtain a T1-weighted MRI signal, reflecting the magnitude of the CBF change, which can be deconvolved to obtain dynamic changes in CBF. The deconvolution of the T1-weighted MRI signal, which is a necessary step for accurate reflection of the dynamic changes in CBF, was made possible by a transfer function obtained from parallel laser-Doppler flowmetry experiments. For all stimulus durations (ranging from 4 to 32 seconds), the peak CBF response measured by MRI after the deconvolution was reached at 4.5 ± 1.0 seconds, which is in good agreement with (present and prior) laser-Doppler measurements. Because the low flip angle data can also provide dynamic changes of the conventional BOLD image contrast, this method can be used for simultaneous imaging of CBF and BOLD dynamics.
Inflammatory Gene Profiling in the Developing Mouse Brain after Hypoxia-Ischemia
Authors: Maj Hedtjärn , Mallard Carina , Hagberg Henrik
Published: May 2011

Brain ischemia triggers an inflammatory reaction that progresses for days to weeks and seems to have a role in secondary progression of injury. Inflammation induces a complex pattern of signaling molecules with partly contradictory actions, and the responses may be different in the immature and adult brain. The authors characterized the global inflammatory gene expression in the developing brain as a first step toward understanding the protective and deleterious effects of inflammation after hypoxia-ischemia. Oligonucleotide arrays were used to investigate inflammatory genes in cortex, hippocampus, thalamus, and striatum at 2, 8, 24, and 72 hours after hypoxia-ischemia, which was induced in 9-day-old mice by left carotid artery ligation followed by hypoxia. After hypoxia-ischemia, 148 inflammatory genes were differentially expressed. More than 97% of the genes were upregulated and 93% had not previously been reported after hypoxia-ischemia in the immature brain. The results indicate that microglia/macrophages, T-and B-cells, NK-cells, mast cells, dendritic cells, and polymorphonuclear leukocytes may participate in the response to hypoxia-ischemia. In addition, novel cytokines/chemokines, complement-related, interferon-regulated, components of the TIR/nuclear factor-κB pathway, and a number of immunomodulatory genes were induced. Several of these genes may be of pathophysiologic significance after neonatal hypoxia-ischemia.
Brain Metabolic Alterations in Patients with Type 1 Diabetes–Hyperglycemia-Induced Injury
Authors: Mäkimattila Sari , Malmberg-Cèder Kirsi , Häkkinen Anna-Maija , Vuori Kim , Salonen Oili , Summanen Paula , Yki-Järvinen Hannele , Kaste Markku , Heikkinen Sami , Lundbom Nina , Roine Risto O.
Published: May 2011

Microangiopathic end-organ injury is common in type 1 diabetes. However, the pathophysiology of diabetic encephalopathy is poorly understood. The authors studied 10 normotensive patients with type 1 diabetes with retinopathy, autonomic neuropathy, but without nephropathy, and 10 healthy subjects. Proton magnetic resonance spectroscopy was performed at 1.5 T in the frontal cortex, thalamus, and posterior frontal white matter. There was no change in N-acetyl–containing compounds (NA), but choline-containing compounds (Cho) were increased in the white matter and in the thalamus; myo-inositol was increased in the white matter, glucose excess was found in all brain, and water intensity was increased in the cortical voxel in the patients. Calculated lifetime glycemic exposure correlated inversely with Cho and NA in white matter and with Cho in thalamus. Concentrations of soluble intercellular adhesion molecules and vascular cell adhesion molecules were increased in the patients. In conclusion, in patients with type 1 diabetes, the increase in adhesion molecules and an association between altered brain metabolites and glycemic exposure suggest the presence of a vascularly mediated, progressive metabolic disturbance in the brain.
A Peripheral Adrenoceptor-mediated Sympathetic Mechanism Can Transform Stress-induced Analgesia into Hyperalgesia
Authors: Donello John E. , Guan Yun , Tian Mingting , Cheevers Cynthia V. , Alcantara Miguel , Cabrera Sara , Raja Srinivasa N. , Gil Daniel W.
Published: May 2011

Background

Stress has paradoxical effects on pain, causing stress-induced analgesia but also exacerbating pain via poorly understood mechanisms. Adrenergic neurotransmission is integral in pathways that regulate the response to both pain and stress. Hyperalgesia is often associated with enhanced adrenergic sensitivity of primary afferents, but sympathetic nervous system outflow has not been demonstrated to exacerbate pain perception after stress.

Methods

Rats or C57/BL6 wild-type mice treated with α-2 receptor antagonists or α-2A receptor knockout mice were exposed to ultrasonic noise stress or footshock stress and subsequently tested for hotplate paw withdrawal latencies. The sensory sensitivity of α-2A knockout mice to electrical and chemical stimuli was tested neurophysiologically and behaviorally. The effects of sympatholytic treatments were investigated.

Results

Noise and footshock stressors induced thermal hyperalgesia in rats pretreated systemically with α-2 antagonists. Wild-type mice pretreated with α-2 antagonists and α-2A knockout mice also exhibited thermal hyperalgesia induced by noise stress. Local spinal or intraplantar injection of an α-2 antagonist counteracted stress-induced analgesia without causing hyperalgesia. The α-2A knockout mice had decreased thresholds for peripheral sensitization with sulprostone and for windup of the dorsal horn neuronal response to repetitive electrical stimuli. Stress-induced hyperalgesia was abolished and the sensitization was attenuated by sympathectomy or systemic administration of an α-1-adrenergic antagonist.

Conclusions

Sympathetic postganglionic nerves can enhance pain sensation via a peripheral α-1-adrenoceptor mechanism when sympathetic outflow is disinhibited. The net effect of stress on pain sensation reflects a balance between descending spinal inhibition and sympathetic outflow that can shift toward pain facilitation when central and peripheral α-2-adrenoceptor inhibitory mechanisms are attenuated.
The ontogenetic development of egg‐spots in the haplochromine cichlid fish Astatotilapia burtoni
Authors: Heule C. , Salzburger W.
Published: May 2011

A series of Astatotilapia burtoni photographs were used to investigate the ontogenetic development of male egg‐spots, a putative evolutionary key innovation of haplochromine cichlids. Four stages of egg‐spot development were defined and all males had developed true egg‐spots (stage 4) before reaching a standard length of 25 mm. Raising condition only slightly influenced the timing of the first appearance of true egg‐spots.
Morphological development of larval cobia Rachycentron canadum and the influence of dietary taurine supplementation
Authors: Salze G. , Craig S. R. , Smith B. H. , Smith E. P. , McLean E.
Published: May 2011

The morphological development of larval cobia Rachycentron canadum from 3 days post hatch (dph) until weaning (27 dph) was examined using S.E.M. Two groups of fish were studied: a control group (CF), reared under standard feeding protocol, and a group in which prey items were enriched with supplemental taurine (4 g l−1 day−1; TF). TF fish grew faster (P < 0·001), attained greater size (mean ±s.e. 55·1 ± 1·5 v. 33·9 ± 1·0 mm total length) and had better survival (mean ±s.e. 29·3 ± 0·4 v. 7·1 ± 1·2 %) than CF fish. Canonical variance analysis confirmed findings with respect to differences in growth between the treatment groups with separation being explained by two cranial measurements. S.E.M. revealed that 3 dph larvae of R. canadum (in both groups) possess preopercular spines, superficial neuromasts on the head and body, taste buds in the mouth, an olfactory epithelium which takes the form of simple concave depressions, and primordial gill arches. Gill filaments start to form as early as 6 dph and lamellae buds are visible at 8 dph in both groups. In CF fish, the cephalic lateral line system continues its development at 12–14 dph with invagination of both supra‐ and infraorbital canals. At the same time, a thorn‐like or acanthoid crest forms above the eye. At 14 dph, invaginations of the mandibular and preopercular canals are visible and around 22 dph enclosure of all cranial canals nears completion. In CF larvae, however, completely enclosed cranial canals were not observed within the course of the trial, i.e. 27 dph. In TF larvae, grooves of the cephalic lateral line system form 4 days earlier than observed in CF larvae of R. canadum (i.e. at 8 dph), with enclosure commencing at 16 dph, and completed by 27 dph. Along the flanks of 6 dph larvae of either treatment, four to five equally spaced neuromasts delineate the future position of the trunk lateral line. As myomeres are added to the growing larvae, new neuromasts appear such that at 16 dph a neuromast is associated with each myomere. By 27 dph, the trunk lateral line starts to invaginate in CF larvae, while it initiates closure in TF larvae. These findings elucidate important features of the larval development of R. canadum and show that dietary taurine supplementation benefits larval development, growth and survival in this species. Moreover, they suggest a conditional requirement for taurine in larval R. canadum.
Proteomic analysis of inviable salmonid hybrids between female masu salmon Oncorhynchus masou masou and male rainbow trout Oncorhynchus mykiss during early embryogenesis
Authors: Zheng L. , Tanaka H. , Abe S.
Published: May 2011

Early embryos of inviable hybrids between female masu salmon Oncorhynchus masou masou and male rainbow trout Oncorhynchus mykiss at 9, 12, 15 and 20 days after fertilization were examined for protein expression profiles. A total of 44 proteins, mostly down‐regulated products of house‐keeping genes and those involved in nucleic acid metabolism or chromatin replication, were identified in hybrid embryos by mass spectrometry analysis and protein database searching. The identified down‐regulated proteins may be responsible for the inviability in the hybrids.
Intra‐operative rewarming with Hot Dog® resistive heating and forced‐air heating: a trial of lower‐body warming
Authors: Röder G. , Sessler D. I. , Roth G. , Schopper C. , Mascha E. J. , Plattner O.
Published: May 2011

Resistive heating is an alternative to forced‐air warming which is currently the most commonly used intra‐operative warming system. We therefore tested the hypothesis that rewarming rates are similar with Hot Dog® (Augustine Biomedical) resistive and Bair Hugger® (Arizant) forced‐air heating systems. We evaluated 28 patients having major maxillary tumour surgery. During the establishment of invasive monitoring, patients became hypothermic, dropping their core temperature to about 35 °C. They were then randomly assigned to rewarming with lower‐body resistive (n = 14) or forced‐air (n = 14) heating, with each system set to ‘high’. Our primary outcome was the rewarming rate during active heating over a core temperature range from 35 to 37 °C. Morphometric characteristics were comparable in both groups. Temperature increased at twice the rate in patients assigned to forced‐air warming, with an estimated mean (SE) slope of 0.49 (0.03) °C.h−1 vs 0.24 (0.02) °C.h−1 (p < 0.001). Resistive heating warmed at half the rate of forced air.
Population pharmacokinetic–pharmacodynamic analysis for sugammadex‐mediated reversal of rocuronium‐induced neuromuscular blockade
Authors: Kleijn Huub J. , Zollinger Daniel P. , van den Heuvel Michiel W. , Kerbusch Thomas
Published: May 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Pharmacokinetics and pharmacodynamics of rocuronium are well known.

• A mechanistical pharmacokinetic–pharmacodynamic model based on limited data describing rocuronium and sugammadex pharmacokinetics has been published.

• However, the available pharmacokinetic–pharmacodynamic model for the effects of sugammadex on rocuronium‐induced neuromuscular blockade has limited predictive power.

WHAT THIS STUDY ADDS

• A pharmacokinetic–pharmacodynamic model is described for rocuronium and sugammadex, based on physiological principles and on data covering a wide range of ages and renal function. From this model, more accurate predictions can be made about sugammadex‐mediated reversal of rocuronium‐induced neuromuscular blockade, in unexplored regimens or populations.

AIMS An integrated population pharmacokinetic–pharmacodynamic model was developed with the following aims: to simultaneously describe pharmacokinetic behaviour of sugammadex and rocuronium; to establish the pharmacokinetic–pharmacodynamic model for rocuronium‐induced neuromuscular blockade and reversal by sugammadex; to evaluate covariate effects; and to explore, by simulation, typical covariate effects on reversal time.

METHODS Data (n= 446) from eight sugammadex clinical studies covering men, women, non‐Asians, Asians, paediatrics, adults and the elderly, with various degrees of renal impairment, were used. Modelling and simulation techniques based on physiological principles were applied to capture rocuronium and sugammadex pharmacokinetics and pharmacodynamics and to identify and quantify covariate effects.

RESULTS Sugammadex pharmacokinetics were affected by renal function, bodyweight and race, and rocuronium pharmacokinetics were affected by age, renal function and race. Sevoflurane potentiated rocuronium‐induced neuromuscular blockade. Posterior predictive checks and bootstrapping illustrated the accuracy and robustness of the model. External validation showed concordance between observed and predicted reversal times, but interindividual variability in reversal time was pronounced. Simulated reversal times in typical adults were 0.8, 1.5 and 1.4 min upon reversal with sugammadex 16 mg kg−1 3 min after rocuronium, sugammadex 4 mg kg−1 during deep neuromuscular blockade and sugammadex 2 mg kg−1 during moderate blockade, respectively. Simulations indicated that reversal times were faster in paediatric patients and slightly slower in elderly patients compared with adults. Renal function did not affect reversal time.

CONCLUSIONS Simulations of the therapeutic dosing regimens demonstrated limited impact of age, renal function and sevoflurane use, as predicted reversal time in typical subjects was always <2 min.
Moving on from voluntary non‐remunerated donors: who is the best blood donor?
Authors: Allain Jean‐Pierre
Published: May 2011

Blood transfusion safety in sub‐Saharan Africa (SSA) is marred by the high prevalence of infectious agents, chronic blood shortage and lack of resources. However, considerable pressure is applied by richer countries and international transfusion bodies to establish voluntary, non‐remunerated blood donors (VNRD) as the only source of blood, excluding the traditional family/replacement donors on the grounds of a higher level of safety. Such a policy increases the cost of a unit of blood by two to fivefold and exacerbates the pre‐existing blood shortage. This review provides compelling evidence that first‐time VNRD are no safer than family/replacement donors and that only repeat donation provides improved blood safety. In order to limit blood shortage and maintain affordability of the blood supply in SSA, both types of donors should be accepted and both should be encouraged to donate regularly.
Assessment of production efficiency, physicochemical properties and storage stability of spray‐dried chlorophyllide, a natural food colourant, using gum Arabic, maltodextrin and soy protein isolate‐based carrier systems
Authors: Comunian Talita A. , Monterrey‐Quintero Ednelí S. , Thomazini Marcelo , Balieiro Julio C. C. , Piccone Pierpaolo , Pittia Paola , Favaro‐Trindade Carmen S.
Published: May 2011

The aim of this research was to study spray drying as potential action to protect chlorophyllide from environmental conditions for shelf‐life extension and characterisation of the powders. Six formulations were prepared with 7.5 and 10 g of carrier agents [gum Arabic (GA), maltodextrin (MA) and soybean protein isolate (SPI)]/100 mL of chlorophyllide solutions. The powders were evaluated for morphological characteristics (SEM), particle size, water activity, moisture, density, hygroscopicity, cold water solubility, sorption isotherms, colour and stability, during 90 days. All the powders were highly soluble, with solubility values around 97%. A significant lower hygroscopicity was observed for GA powders, whilst the lower Xm values obtained by GAB equation fitting of the sorption isotherms was observed for the 7.5 g MA/100 mL samples. All formulations, but the 1 (7.5 g SPI/100 mL of chlorophyllide), provided excellent stability to the chlorophyllide during 90 days of storage even at room temperature.
Comparison of the stability of palm olein and a palm olein/canola oil blend during deep‐fat frying of chicken nuggets and French fries
Authors: Enríquez‐Fernández Blanca Estela , Álvarez de la Cadena y Yañez Liliana , Sosa‐Morales María Elena
Published: May 2011

Stability of palm olein (PO) and a blend 50% palm olein/50% canola oil (POC) during deep‐fat frying at 180 °C of French fries (FF) or chicken nuggets (CN) was studied through the determination of physical and chemical parameters in the fresh and used oils. Degradation at the end of the study resulted in total polar compounds of 12–13.5% for PO and 11.5–14.5% for POC and viscosity of 65–123.3 cP for PO and 63–72.8 cP for POC. Lower peroxide values (5.33–6.32) were obtained for the blend (PO had 5.21–8.55). Food type affected colour parameters and p‐anisidine value of the oils. For CN, the lowest fat content and higher hardness were obtained when they were fried in PO. CN caused a faster deterioration in the oils, in comparison with FF, especially in POC. Gas chromatography allowed to observe differences in fatty acids composition for both used oils.