bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered temporal correlations in parietal alpha and prefrontal theta oscillations in early-stage Alzheimer disease
Authors: Montez Teresa , Poil Simon-Shlomo , Jones Bethany F. , Manshanden Ilonka , Verbunt Jeroen P. A. , van Dijk Bob W. , Brussaard Arjen B. , van Ooyen Arjen , Stam Cornelis J. , Scheltens Philip , Linkenkaer-Hansen Klaus
Published: January 2009

Encoding and retention of information in memory are associated with a sustained increase in the amplitude of neuronal oscillations for up to several seconds. We reasoned that coordination of oscillatory activity over time might be important for memory and, therefore, that the amplitude modulation of oscillations may be abnormal in Alzheimer disease (AD). To test this hypothesis, we measured magnetoencephalography (MEG) during eyes-closed rest in 19 patients diagnosed with early-stage AD and 16 age-matched control subjects and characterized the autocorrelation structure of ongoing oscillations using detrended fluctuation analysis and an analysis of the life- and waiting-time statistics of oscillation bursts. We found that Alzheimer's patients had a strongly reduced incidence of alpha-band oscillation bursts with long life- or waiting-times (< 1 s) over temporo-parietal regions and markedly weaker autocorrelations on long time scales (1–25 seconds). Interestingly, the life- and waiting-times of theta oscillations over medial prefrontal regions were greatly increased. Whereas both temporo-parietal alpha and medial prefrontal theta oscillations are associated with retrieval and retention of information, metabolic and structural deficits in early-stage AD are observed primarily in temporo-parietal areas, suggesting that the enhanced oscillations in medial prefrontal cortex reflect a compensatory mechanism. Together, our results suggest that amplitude modulation of neuronal oscillations is important for cognition and that indices of amplitude dynamics of oscillations may prove useful as neuroimaging biomarkers of early-stage AD.
Mechanisms of Auger-induced chemistry derived from wave packet dynamics
Authors: Su Julius T. , Goddard William A.
Published: January 2009

To understand how core ionization and subsequent Auger decay lead to bond breaking in large systems, we simulate the wave packet dynamics of electrons in the hydrogenated diamond nanoparticle
C
197
H
112
. We find that surface core ionizations cause emission of carbon fragments and protons through a direct Auger mechanism, whereas deeper core ionizations cause hydrides to be emitted from the surface via remote heating, consistent with results from photon-stimulated desorption experiments [Hoffman A, Laikhtman A, (2006)
J Phys Condens Mater
18:S1517–S1546]. This demonstrates that it is feasible to study the chemistry of highly excited large-scale systems using simulation and analysis tools comparable in simplicity to those used for classical molecular dynamics.
Two amino acid residues determine 2-APB sensitivity of the ion channels TRPV3 and TRPV4
Authors: Hu Hongzhen , Grandl Jörg , Bandell Michael , Petrus Matt , Patapoutian Ardem
Published: January 2009

Temperature-activated transient receptor potential ion channels (thermoTRPs) are polymodal detectors of various stimuli including temperature, voltage, and chemicals. To date, it is not known how TRP channels integrate the action of such disparate stimuli. Identifying specific residues required for channel-activation by distinct stimuli is necessary for understanding overall TRP channel function. TRPV3 is activated by warm temperatures and various chemicals, and is modulated by voltage. One potent activator of TRPV3 is 2-aminoethyl diphenylborinate (2-APB), a synthetic chemical that modulates many TRP channels. In a high-throughput mutagenesis screen of ≈14,000 mutated mouse TRPV3 clones, we found 2 residues (H426 and R696) specifically required for sensitivity of TRPV3 to 2-APB, but not to camphor or voltage. The cytoplasmic N-terminal mutation H426N in human, dog, and frog TRPV3 also effectively abolished 2-APB activation without affecting camphor responses. Interestingly, chicken TRPV3 is weakly sensitive to 2-APB, and the equivalent residue at 426 is an asparagine (N). Mutating this residue to histidine induced 2-APB sensitivity of chicken TRPV3 to levels comparable for other TRPV3 orthologs. The cytoplasmic C-terminal mutation R696K in the TRP box displayed 2-APB specific deficits only in the presence of extracellular calcium, suggesting involvement in gating. TRPV4, a related thermoTRP, is 2-APB insensitive and has variant sequences at both residues identified here. Remarkably, mutating these 2 residues in TRPV4 to TRPV3 sequences (N426H and W737R) was sufficient to induce TRPV3-like 2-APB sensitivity. Therefore, 2-APB activation of TRPV3 is separable from other activation mechanisms, and depends on 2 cytoplasmic residues.
A helix-to-coil transition at the ε-cut site in the transmembrane dimer of the amyloid precursor protein is required for proteolysis
Authors: Sato Takeshi , Tang Tzu-chun , Reubins Gabriella , Fei Jeffrey Z. , Fujimoto Taiki , Kienlen-Campard Pascal , Constantinescu Stefan N. , Octave Jean-Noel , Aimoto Saburo , Smith Steven O.
Published: January 2009

Processing of amyloid precursor protein (APP) by γ-secretase is the last step in the formation of the Aβ peptides associated Alzheimer's disease. Solid-state NMR spectroscopy is used to establish the structural features of the transmembrane (TM) and juxtamembrane (JM) domains of APP that facilitate proteolysis. Using peptides corresponding to the APP TM and JM regions (residues 618–660), we show that the TM domain forms an α-helical homodimer mediated by consecutive GxxxG motifs. We find that the APP TM helix is disrupted at the intracellular membrane boundary near the ε-cleavage site. This helix-to-coil transition is required for γ-secretase processing; mutations that extend the TM α-helix inhibit ε cleavage, leading to a low production of Aβ peptides and an accumulation of the α- and β-C-terminal fragments. Our data support a progressive cleavage mechanism for APP proteolysis that depends on the helix-to-coil transition at the TM-JM boundary and unraveling of the TM α-helix.
Nitric oxide and TNF-α trigger colonic inflammation and carcinogenesis inHelicobacter hepaticus-infected,Rag2-deficient mice
Authors: Erdman S. E. , Rao V. P. , Poutahidis T. , Rogers A. B. , Taylor C. L. , Jackson E. A. , Ge Z. , Lee C. W. , Schauer D. B. , Wogan G. N. , Tannenbaum S. R. , Fox J. G.
Published: January 2009

Recombinase-activating gene-2-deficient (Rag2−/−) mice lacking functional lymphocytes provide a useful model of chronic inflammatory bowel disease-emulating events in human colon cancer. Infection ofRag2−/−mice withHelicobacter hepaticusled to accumulation of macrophages and neutrophils in the colon, a process temporally related to up-regulation of tissue inducible nitric oxide synthase (iNOS) expression at the site of infection and increased nitric oxide (NO) production, as evidenced by urinary excretion of nitrate. Progressive development of increasingly severe inflammation, hyperplasia, dysplasia, and cancer accompanied these changes. Concurrent administration of an iNOS inhibitor prevented NO production and abrogated epithelial pathology and inhibited the onset of cancer. The presence of Gr-1+neutrophils and elevated tumor necrosis factor-α (TNF-α) expression in colon were required for increased iNOS expression and cancer, whereas interleukin-10 (IL-10) down-regulated TNF-α and iNOS expression and suppressed cancer. Anti-inflammatory CD4+regulatory lymphocytes also down-regulated iNOS and reduced cancer formation. Collectively, these results confirm essential roles for inflammation, increased TNF-α expression, and elevated NO production in colon carcinogenesis.
Effects of linker sequences on vesicle fusion mediated by lipid-anchored DNA oligonucleotides
Authors: Chan Yee-Hung M. , van Lengerich Bettina , Boxer Steven G.
Published: January 2009

Synthetic lipid–oligonucleotide conjugates inserted into lipid vesicles mediate fusion when one population of vesicles displays the 5′-coupled conjugate and the other the 3′-coupled conjugate, so that anti-parallel hybridization allows the membrane surfaces to come into close proximity. Improved assays show that lipid mixing proceeds more quickly and to a much greater extent than content mixing, suggesting the latter is rate limiting. To test the effect of membrane–membrane spacing on fusion, a series of conjugates was constructed by adding 2–24 noncomplementary bases at the membrane-proximal ends of two complementary sequences. Increasing linker lengths generally resulted in progressively reduced rates and extents of lipid and content mixing, in contrast to higher vesicle docking rates. The relatively flexible, single-stranded DNA linker facilitates docking but allows greater spacing between the vesicles after docking, thus making the transition into fusion less probable, but not preventing it altogether. These experiments demonstrate the utility of DNA as a model system for fusion proteins, where sequence can easily be modified to systematically probe the effect of distance between bilayers in the fusion reaction.
KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients
Authors: Gajiwala Ketan S. , Wu Joe C. , Christensen James , Deshmukh Gayatri D. , Diehl Wade , DiNitto Jonathan P. , English Jessie M. , Greig Michael J. , He You-Ai , Jacques Suzanne L. , Lunney Elizabeth A. , McTigue Michele , Molina David , Quenzer Terri , Wells Peter A. , Yu Xiu , Zhang Yan , Zou Aihua , Emmett Mark R. , Marshall Alan G. , Zhang Hui-Min , Demetri George D.
Published: January 2009

Most gastrointestinal stromal tumors (GISTs) exhibit aberrant activation of the receptor tyrosine kinase (RTK) KIT. The efficacy of the inhibitors imatinib mesylate and sunitinib malate in GIST patients has been linked to their inhibition of these mutant KIT proteins. However, patients on imatinib can acquire secondary KIT mutations that render the protein insensitive to the inhibitor. Sunitinib has shown efficacy against certain imatinib-resistant mutants, although a subset that resides in the activation loop, including D816H/V, remains resistant. Biochemical and structural studies were undertaken to determine the molecular basis of sunitinib resistance. Our results show that sunitinib targets the autoinhibited conformation of WT KIT and that the D816H mutant undergoes a shift in conformational equilibrium toward the active state. These findings provide a structural and enzymologic explanation for the resistance profile observed with the KIT inhibitors. Prospectively, they have implications for understanding oncogenic kinase mutants and for circumventing drug resistance.
Anthropogenic enhancement of Egypt's Mediterranean fishery
Authors: Oczkowski Autumn J. , Nixon Scott W. , Granger Stephen L. , El-Sayed Abdel-Fattah M. , McKinney Richard A.
Published: January 2009

The highly productive coastal Mediterranean fishery off the Nile River delta collapsed after the completion of the Aswan High Dam in 1965. But the fishery has been recovering dramatically since the mid-1980s, coincident with large increases in fertilizer application and sewage discharge in Egypt. We use stable isotopes of nitrogen (δ
15
N) to demonstrate that 60%–100% of the current fishery production may be from primary production stimulated by nutrients from fertilizer and sewage runoff. Although the establishment of the dam put Egypt in an ideal position to observe the impact of rapid increases in nutrient loading on coastal productivity in an extremely oligotrophic sea, the Egyptian situation is not unique. Such anthropogenically enhanced fisheries also may occur along the northern rim of the Mediterranean and offshore of some rapidly developing tropical countries, where nutrient concentrations in the coastal waters were previously very low.
Human gut microbiota in obesity and after gastric bypass
Authors: Zhang Husen , DiBaise John K. , Zuccolo Andrea , Kudrna Dave , Braidotti Michele , Yu Yeisoo , Parameswaran Prathap , Crowell Michael D. , Wing Rod , Rittmann Bruce E. , Krajmalnik-Brown Rosa
Published: January 2009

Recent evidence suggests that the microbial community in the human intestine may play an important role in the pathogenesis of obesity. We examined 184,094 sequences of microbial 16S rRNA genes from PCR amplicons by using the 454 pyrosequencing technology to compare the microbial community structures of 9 individuals, 3 in each of the categories of normal weight, morbidly obese, and post-gastric-bypass surgery. Phylogenetic analysis demonstrated that although the
Bacteria
in the human intestinal community were highly diverse, they fell mainly into 6 bacterial divisions that had distinct differences in the 3 study groups. Specifically,
Firmicutes
were dominant in normal-weight and obese individuals but significantly decreased in post-gastric-bypass individuals, who had a proportional increase of
Gammaproteobacteria
. Numbers of the H
2
-producing
Prevotellaceae
were highly enriched in the obese individuals. Unlike the highly diverse
Bacteria
, the
Archaea
comprised mainly members of the order
Methanobacteriales
, which are H
2
-oxidizing methanogens. Using real-time PCR, we detected significantly higher numbers of H
2
-utilizing methanogenic
Archaea
in obese individuals than in normal-weight or post-gastric-bypass individuals. The coexistence of H
2
-producing bacteria with relatively high numbers of H
2
-utilizing methanogenic
Archaea
in the gastrointestinal tract of obese individuals leads to the hypothesis that interspecies H
2
transfer between bacterial and archaeal species is an important mechanism for increasing energy uptake by the human large intestine in obese persons. The large bacterial population shift seen in the post-gastric-bypass individuals may reflect the double impact of the gut alteration caused by the surgical procedure and the consequent changes in food ingestion and digestion.
Hybrid models for sense guessing of Chinese unknown words
Authors: Lu Xiaofei
Published: January 2009

This paper addresses the problem of classifying Chinese unknown words into fine-grained semantic categories defined in a Chinese thesaurus, Cilin (Mei et al. 1984). We present three novel knowledge-based models that capture the relationship between the semantic categories of an unknown word and those of its component characters in three different ways, and combine two of them with a corpus-based model that uses contextual information to classify unknown words. Experiments show that the combined knowledge-based model outperforms previous methods on the same task, but the use of contextual information does not further improve performance.
The classification of 2-compact groups
Authors: Andersen Kasper , Grodal Jesper
Published: January 2009

We prove that any connected22–compact group is classified by its22–adic root datum, and in particular the exotic22–compact groupDI⁡(4)\operatorname {DI}(4), constructed by Dwyer–Wilkerson, is the only simple22–compact group not arising as the22–completion of a compact connected Lie group. Combined with our earlier work with Møller and Viruel forppodd, this establishes the full classification ofpp–compact groups, stating that, up to isomorphism, there is a one-to-one correspondence between connectedpp–compact groups and root data over thepp–adic integers. As a consequence we prove the maximal torus conjecture, giving a one-to-one correspondence between compact Lie groups and finite loop spaces admitting a maximal torus. Our proof is a general induction on the dimension of the group, which works for all primes. It refines the Andersen–Grodal–Møller–Viruel methods by incorporating the theory of root data over thepp–adic integers, as developed by Dwyer–Wilkerson and the authors. Furthermore we devise a different way of dealing with the rigidification problem by utilizing obstruction groups calculated by Jackowski–McClure–Oliver in the early 1990s.
Coilin Is Essential for Cajal Body Organization inDrosophila melanogaster
Authors: Liu Ji-Long , Wu Zheng'an , Nizami Zehra , Deryusheva Svetlana , Rajendra T.K. , Beumer Kelly J. , Gao Hongjuan , Matera A. Gregory , Carroll Dana , Gall Joseph G.
Published: January 2009

Cajal bodies (CBs) are nuclear organelles that occur in a variety of organisms, including vertebrates, insects, and plants. They are most often identified with antibodies against the marker protein coilin. Because the amino acid sequence of coilin is not strongly conserved evolutionarily, coilin orthologues have been difficult to recognize by homology search. Here, we report the identification of Drosophila melanogaster coilin and describe its distribution in tissues of the fly. Surprisingly, we found coilin not only in CBs but also in histone locus bodies (HLBs), calling into question the use of coilin as an exclusive marker for CBs. We analyzed two null mutants in the coilin gene and a piggyBac insertion mutant, which leads to specific loss of coilin from the germline. All three mutants are homozygous viable and fertile. Cells that lack coilin also lack distinct foci of other CB markers, including fibrillarin, the survival motor neuron (SMN) protein, U2 small nuclear RNA (snRNA), U5 snRNA, and the small CB-specific (sca) RNA U85. However, HLBs are not obviously affected in coilin-null flies. Thus, coilin is required for normal CB organization in Drosophila but is not essential for viability or production of functional gametes.
Role of the Tumor Suppressor PTEN in Antioxidant Responsive Element-mediated Transcription and Associated Histone Modifications
Authors: Sakamoto Kensuke , Iwasaki Kenta , Sugiyama Hiroyuki , Tsuji Yoshiaki
Published: January 2009

Coordinated regulation of PI3-kinase (PI3K) and the tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) plays a pivotal role in various cell functions. PTEN is deficient in many cancer cells, including Jurkat human leukemia. Here, we demonstrate that the status of PTEN determines cellular susceptibility to oxidative stress through antioxidant-responsive element (ARE)-mediated transcription of detoxification genes. We found that ferritin H transcription was robustly induced in tert-butylhydroquinone (t-BHQ)-treated Jurkat cells via an ARE, and it was due to PTEN deficiency. Chromatin immunoprecipitation assays revealed that p300/CREB-binding protein (CBP) histone acetyltransferases and Nrf2 recruitment to the ARE and Bach1 release were blocked by the PI3K inhibitor LY294002, along with the partial inhibition of Nrf2 nuclear accumulation. Furthermore, acetylations of histone H3 Lys9 and Lys18, and deacetylation of Lys14 were associated with the PI3K-dependent ARE activation. Consistently, PTEN restoration in Jurkat cells inhibited t-BHQ–mediated expression of ferritin H and another ARE-regulated gene NAD(P)H:quinone oxidoreductase 1. Conversely, PTEN knockdown in K562 cells enhanced the response to t-BHQ. The PTEN status under t-BHQ treatment affected hydrogen peroxide-mediated caspase-3 cleavage. The PI3K-dependent ferritin H induction was observed by treatment with other ARE-activating agents ethoxyquin and hemin. Collectively, the status of PTEN determines chromatin modifications leading to ARE activation.
Caveolin-2 Is Required for Apical Lipid Trafficking and Suppresses Basolateral Recycling Defects in the Intestine ofCaenorhabditis elegans
Authors: Parker Scott , Walker Denise S. , Ly Sung , Baylis Howard A.
Published: January 2009

Caveolins are plasma membrane–associated proteins that colocalize with, and stabilize caveolae. Their functions remain unclear although they are known to be involved in specific events in cell signaling and endocytosis. Caenorhabditis elegans encodes two caveolin genes, cav-1 and cav-2. We show that cav-2 is expressed in the intestine where it is localized to the apical membrane and in intracellular bodies. Using the styryl dye FM4-64 and BODIPY-labeled lactosylceramide, we show that the intestinal cells of cav-2 animals are defective in the apical uptake of lipid markers. These results suggest parallels with the function of caveolins in lipid homeostasis in mammals. We also show that CAV-2 depletion suppresses the abnormal accumulation of vacuoles that result from defective basolateral recycling in rme-1 and rab-10 mutants. Analysis of fluorescent markers of basolateral endocytosis and recycling suggest that endocytosis is normal in cav-2 mutants and thus, that the suppression of basolateral recycling defects in cav-2 mutants is due to changes in intracellular trafficking pathways. Finally, cav-2 mutants also have abnormal trafficking of yolk proteins. Taken together, these data indicate that caveolin-2 is an integral component of the trafficking network in the intestinal cells of C. elegans.
The Two SAS-6 Homologs inTetrahymena thermophilaHave Distinct Functions in Basal Body Assembly
Authors: Culver Brady P. , Meehl Janet B. , Giddings Thomas H. , Winey Mark
Published: January 2009

Cilia and flagella are structurally and functionally conserved organelles present in basal as well as higher eukaryotes. The assembly of cilia requires a microtubule based scaffold called a basal body. The ninefold symmetry characteristic of basal bodies and the structurally similar centriole is organized around a hub and spoke structure termed the cartwheel. To date, SAS-6 is one of the two clearly conserved components of the cartwheel. In some organisms, overexpression of SAS-6 causes the formation of supernumerary centrioles. We questioned whether the centriole assembly initiation capacity of SAS-6 is separate from or directly related to its structural role at the cartwheel. To address this question we used Tetrahymena thermophila, which expresses two SAS-6 homologues, TtSAS6a and TtSAS6b. Cells lacking either TtSAS6a or TtSAS6b are defective in new basal body assembly. TtSas6a localizes to all basal bodies equally, whereas TtSas6b is enriched at unciliated and assembling basal bodies. Interestingly, overexpression of TtSAS6b but not TtSAS6a, led to the assembly of clusters of new basal bodies in abnormal locations. Our data suggest a model where TtSAS6a and TtSAS6b have diverged such that TtSAS6a acts as a structural component of basal bodies, whereas TtSAS6b influences the location of new basal body assembly.
Esc2 and Sgs1 Act in Functionally Distinct Branches of the Homologous Recombination Repair Pathway inSaccharomyces cerevisiae
Authors: Mankouri Hocine W. , Ngo Hien-Ping , Hickson Ian D.
Published: January 2009

Esc2 is a member of the RENi family of SUMO-like domain proteins and is implicated in gene silencing in Saccharomyces cerevisiae. Here, we identify a dual role for Esc2 during S-phase in mediating both intra-S-phase DNA damage checkpoint signaling and preventing the accumulation of Rad51-dependent homologous recombination repair (HRR) intermediates. These roles are qualitatively similar to those of Sgs1, the yeast ortholog of the human Bloom's syndrome protein, BLM. However, whereas mutation of either ESC2 or SGS1 leads to the accumulation of unprocessed HRR intermediates in the presence of MMS, the accumulation of these structures in esc2 (but not sgs1) mutants is entirely dependent on Mph1, a protein that shows structural similarity to the Fanconi anemia group M protein (FANCM). In the absence of both Esc2 and Sgs1, the intra-S-phase DNA damage checkpoint response is compromised after exposure to MMS, and sgs1esc2 cells attempt to undergo mitosis with unprocessed HRR intermediates. We propose a model whereby Esc2 acts in an Mph1-dependent process, separately from Sgs1, to influence the repair/tolerance of MMS-induced lesions during S-phase.
The Nucleoporin Nup153 Has Separable Roles in Both Early Mitotic Progression and the Resolution of Mitosis
Authors: Mackay Douglas R. , Elgort Suzanne W. , Ullman Katharine S.
Published: January 2009

Accurate inheritance of genomic content during cell division is dependent on synchronized changes in cellular organization and chromosome dynamics. Elucidating how these events are coordinated is necessary for a complete understanding of cell proliferation. Previous in vitro studies have suggested that the nuclear pore protein Nup153 is a good candidate for participating in mitotic coordination. To decipher whether this is the case in mammalian somatic cells, we reduced the levels of Nup153 in HeLa cells and monitored consequences on cell growth. Reduction of Nup153 resulted in a delay during the late stages of mitosis accompanied by an increase in unresolved midbodies. Depletion of Nup153 to an even lower threshold led to a pronounced defect early in mitosis and an accumulation of cells with multilobed nuclei. Although global nucleocytoplasmic transport was not significantly altered under these depletion conditions, the FG-rich region of Nup153 was required to rescue defects in late mitosis. Thus, this motif may play a specialized role as cells exit mitosis. Rescue of the multilobed nuclei phenotype, in contrast, was independent of the FG-domain, revealing two separable roles for Nup153 in the execution of mitosis.
RACK-1 Directs Dynactin-dependent RAB-11 Endosomal Recycling during Mitosis inCaenorhabditis elegans
Authors: Ai Erkang , Poole Daniel S. , Skop Ahna R.
Published: January 2009

Membrane trafficking pathways are necessary for the addition and removal of membrane during cytokinesis. In animal cells, recycling endosomes act as a major source of the additional membranes during furrow progression and abscission. However, the mechanisms and factors that regulate recycling endosomes during the cell cycle remain poorly understood. Here, we show that the Caenorhabditis elegans Receptor of Activated C Kinase 1 (RACK-1) is required for cytokinesis, germline membrane organization, and the recruitment of RAB-11–labeled recycling endosomes to the pericentrosomal region and spindle. RACK-1 is also required for proper chromosome separation and astral microtubule length. RACK-1 localizes to the centrosomes, kinetochores, the midbody, and nuclear envelopes during the cell cycle. We found that RACK-1 directly binds to DNC-2, the C. elegans p50/dynamitin subunit of the dynactin complex. Last, RACK-1 may facilitate the sequestration of recycling endosomes by targeting DNC-2 to centrosomes and the spindle. Our findings suggest a mechanism by which RACK-1 directs the dynactin-dependent redistribution of recycling endosomes during the cell cycle, thus ensuring proper membrane trafficking events during cytokinesis.
The WASP Homologue Las17 Activates the Novel Actin-regulatory Activity of Ysc84 to Promote Endocytosis in Yeast
Authors: Robertson Alastair S. , Allwood Ellen G. , Smith Adam P.C. , Gardiner Fiona C. , Costa Rosaria , Winder Steve J. , Ayscough Kathryn R.
Published: January 2009

Actin plays an essential role in many eukaryotic cellular processes, including motility, generation of polarity, and membrane trafficking. Actin function in these roles is regulated by association with proteins that affect its polymerization state, dynamics, and organization. Numerous proteins have been shown to localize with cortical patches of yeast actin during endocytosis, but the role of many of these proteins remains poorly understood. Here, we reveal that the yeast protein Ysc84 represents a new class of actin-binding proteins, conserved from yeast to humans. It contains a novel N-terminal actin-binding domain termed Ysc84 actin binding (YAB), which can bind and bundle actin filaments. Intriguingly, full-length Ysc84 alone does not bind to actin, but binding can be activated by a specific motif within the polyproline region of the yeast WASP homologue Las17. We also identify a new monomeric actin-binding site on Las17. Together, the polyproline region of Las17 and Ysc84 can promote actin polymerization. Using live cell imaging, kinetics of assembly and disassembly of proteins at the endocytic site were analyzed and reveal that loss of Ysc84 and its homologue Lsb3 decrease inward movement of vesicles consistent with a role in actin polymerization during endocytosis.
Influence of gender of physicians and patients on guideline‐recommended treatment of chronic heart failure in a cross‐sectional study
Authors: Baumhäkel Magnus , Müller Ulrike , Böhm Michael
Published: January 2009

Aims

Clinical outcomes of patients with chronic heart failure (CHF) have improved, but evidence‐based treatment appears to be imbalanced depending on patients' and physicians' gender. We aimed to determine the interactions of gender with medical treatment of CHF.

Methods and results

Consecutive patients with CHF (n = 1857) were evaluated regarding co‐morbidities, New York Heart Association classification, current medical treatment, and dosage of angiotensin‐converting enzyme‐inhibitors (ACE‐Is) and beta‐blockers. Gender of patients and treating physicians was recorded. Baseline characteristics of patients and physicians were comparable for males and females. Female patients were less frequently treated with ACE‐Is, angiotensin‐receptor blockers, or beta‐blockers. Achieved doses were lower in female compared with male patients. Guideline‐recommended drug use and achieved target doses tended to be higher in patients treated by female physicians. There was no different treatment for male or female patients by female physicians, whereas male physicians used significantly less medication and lower doses in female patients. In multivariable analysis, female gender of physicians was an independent predictor of use of beta‐blockers.

Conclusion

Treatment of CHF is influenced by patients', but also physicians' gender with regard to evidenced‐based drugs and their dosage. Physicians should be aware of this problem in order to avoid gender‐related treatment imbalances.
Prospective Clinical and Fiberoptic Evaluation of the Supreme Laryngeal Mask Airway ™
Authors: Timmermann Arnd , Cremer Stefan , Eich Christoph , Kazmaier Stephan , Bräuer Anselm , Graf Bernhard M. , Russo Sebastian G.
Published: January 2009

Background

In March 2007, a new disposable laryngeal mask airway (LMA) became available. The LMA Supreme (The Laryngeal Mask Company Limited, St. Helier, Jersey, Channel Islands) aims to combine the LMA Fastrach feature of easy insertion with the gastric access and high oropharyngeal leak pressures of the LMA ProSeal.

Methods

The authors performed an evaluative study with the LMA Supreme, size 4, on 100 women to measure the ease of insertion, determinate the laryngeal fit by fiberoptic classification, evaluate the oropharyngeal leak pressure, and report adverse events.

Results

Insertion of the LMA Supreme was possible in 94 patients (94%) during the first attempt, and in 5 patients (5%) during the second attempt. In one small patient, the LMA Supreme could not be inserted because of limited pharyngeal space. This patient was excluded from further analysis. Insertion of a gastric tube was possible in all patients at the first attempt. The median time for LMA Supreme insertion was 10.0 s (+/-4.7 s; range, 8-30 s). Laryngeal fit, evaluated by fiberscopic view, was rated as optimal in all patients, both immediately after insertion of the LMA Supreme and at the end of surgery. After equalization to room pressure, the mean cuff volume needed to achieve 60 cm H2O cuff pressure was 18.4 ml (+/-3.8 ml; range, 8-31 ml). The mean oropharyngeal leak pressure at the level of 60 cm H2O cuff pressure was 28.1 cm H2O (+/-3.8 cm H2O, range, 21-35 cm H2O). Eight patients (8.1%) complained of a mild sore throat. No patient reported dysphagia or dysphonia.

Conclusions

Clinical evaluation of the LMA Supreme showed easy insertion, optimal laryngeal fit, and low airway morbidity. Oropharyngeal leak pressure results were comparable to earlier data from the LMA ProSeal.
Activation of Sensory Neurons Reduces Ischemia/Reperfusion-induced Acute Renal Injury in Rats
Authors: Mizutani Akio , Okajima Kenji , Murakami Kazunori , Mizutani Sachiko , Kudo Kyosuke , Uchino Tetsuya , Kadoi Yuji , Noguchi Takayuki
Published: January 2009

Background

Prostaglandin I2 (PGI2) produced by endothelial cells improves ischemia/reperfusion-induced acute renal injury by inhibiting leukocyte activation in rats. However, the underlying mechanism(s) of increased PGI2 production is not fully understood. Activation of sensory neurons increases endothelial PGI2 production by releasing calcitonin gene-related peptide (CGRP) in rats with hepatic ischemia or reperfusion. We examined here whether activation of sensory neurons increases PGI2 endothelial production, thereby reducing ischemia/reperfusion-induced acute renal injury.

Methods

Anesthetized rats were subjected to 45 min of renal ischemia/reperfusion. Rats were pretreated with CGRP, capsazepine (a vanilloid receptor-1 antagonist), CGRP(8-37) (a CGRP receptor antagonist), or indomethacin (a cyclooxygenase inhibitor), or subjected to denervation of primary sensory nerves before ischemia/reperfusion.

Results

Renal tissue levels of CGRP and 6-keto-prostaglandin F1alpha, a stable metabolite of PGI2, increased after renal ischemia/reperfusion, peaking at 1 h after reperfusion. Overexpression of CGRP was also noted at 1 h after reperfusion. Increases in renal tissue levels of 6-keto-prostaglandin F1alpha at 1 h after reperfusion were significantly inhibited by pretreatment with capsazepine, CGRP(8-37), and indomethacin. Pretreatment with capsazepine, CGRP(8-37), indomethacin, and denervation of primary sensory nerves significantly increased blood urea nitrogen and serum creatinine levels, renal vascular permeability, renal tissue levels of myeloperoxidase activity, cytokine-induced neutrophil chemoattractant, and tumor necrosis factor-alpha, and decreased renal tissue blood flow. However, pretreatment with CGRP significantly improved these changes.

Conclusions

Our results suggest activation of sensory neurons in the pathologic process of ischemia/reperfusion-induced acute renal injury. Such activation reduces acute renal injury by attenuating inflammatory responses through enhanced endothelial PGI2 production.
Glutamate, Microdialysis, and Cerebral Ischemia
Authors: Benveniste Helene , Warner David S.
Published: January 2009

Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. By Helene Benveniste, Jørgen Drejer, Arne Schousboe, Nils H. Diemer. J Neurochem 1984; 43:1369-74. Reprinted with permission of Blackwell Publishing. Rats were implanted with 0.3-mm-diameter dialysis tubing through the hippocampus and subsequently perfused with Ringer's solution at a flow rate of 2 ml/min. Samples of the perfusate representing the extracellular fluid were collected over 5-min periods and subsequently analyzed for contents of the amino acids glutamate, aspartate, glutamine, taurine, alanine, and serine. Samples were collected before, during, and after a 10-min period of transient complete cerebral ischemia. The extracellular contents of glutamate and aspartate were increased, respectively, eight- and threefold during the ischemic period; the taurine concentration also was increased 2.6-fold. During the same period the extracellular content of glutamine was significantly decreased (to 68% of the control value), whereas the concentrations of alanine and serine did not change significantly during the ischemic period. The concentrations of gamma-aminobutyric acid (GABA) were too low to be measured reliably. It is suggested that the large increase in the content of extracellular glutamate and aspartate in the hippocampus induced by the ischemia may be one of the causal factors in the damage to certain neurons observed after ischemia.
Predictors Associated with Terminal Renal Function in Deceased Organ Donors in the Intensive Care Unit
Authors: Blasi-Ibanez Annabel , Hirose Ryutaro , Feiner John , Freise Chris , Stock Peter G. , Roberts John P. , Niemann Claus U.
Published: January 2009

Background

Factors determining renal function at organ recovery in deceased kidney donors are not well established.

Methods

The authors studied the prevalence and risk factors associated with elevated prerecovery creatinine and calculated glomerular filtration rate in 458 deceased organ donors identified through the California Donor Transplant Network between January 2005 and December 2006. Data collected retrospectively included demographics, medical history, laboratory values, mechanism of death, and medical treatment in the intensive care unit. Factors were analyzed by both univariate and multivariate analysis.

Results

There were 260 men and 198 women in the study. The age was 43.2 +/- 14.9 yr, and body mass index was 26.9 +/- 6.0 (mean +/- SD). In multivariate analysis, several factors were important determinants of both prerecovery creatinine and glomerular filtration rate. Admission creatinine or glomerular filtration rate were major determinants of respective prerecovery values (P < 0.0001). Higher body mass index was associated with worse renal function (P < 0.01). Higher average glucose values and greater variability in glucose (when included) were associated with worse prerecovery renal function (P < 0.01). Administration of desmopressin acetate was highly associated with preserved renal function (P < 0.001). Lower platelet count (P < 0.0001) and proteinuria (P = 0.005) were also associated with worse renal function.

Conclusion

The data identify several important factors that predict renal function at kidney recovery in deceased donors. In particular, tighter control of blood glucose may improve renal function in potential organ donors, but prospective studies are needed to confirm these findings.
Free amino acids as phagostimulants in cricket nuptial gifts: support for the ‘Candymaker’ hypothesis
Authors: Warwick Stuart , Vahed Karim , Raubenheimer David , Simpson Stephen J
Published: January 2009

Nuptial gifts that are manufactured by the male are found in numerous insect species and some spiders, but there have been very few studies of the composition of such gifts. If, as has been proposed recently, nuptial gifts represent sensory traps, males will be selected to produce gifts that are attractive to females but such gifts will not necessarily provide the female with nutritional benefits (the ‘Candymaker’ hypothesis). We examined the free amino acid content of the spermatophylax of the cricket
Gryllodes sigillatus
(Orthoptera: Gryllidae) using high performance liquid chromatography (HPLC). The spermatophylax (dry weight) consisted of approximately 7 per cent free amino acids. The free amino acid composition was highly imbalanced, with a low proportion of essential amino acids (18.7%) and a high proportion of proline and glycine. The main free amino acids found in the spermatophylax appeared to act as phagostimulants: the duration of feeding on artificial gels by females was positively related to the free amino acid content of the gels. The results therefore suggest that males use free amino acids to ‘sweeten’ a relatively low-value food item. A possible function of glycine in inhibiting female movement is also proposed.
Bioactive ceramic-based materials with designed reactivity for bone tissue regeneration
Authors: Ohtsuki Chikara , Kamitakahara Masanobu , Miyazaki Toshiki
Published: January 2009

Bioactive ceramics have been used clinically to repair bone defects owing to their biological affinity to living bone; i.e. the capability of direct bonding to living bone, their so-called bioactivity. However, currently available bioactive ceramics do not satisfy every clinical application. Therefore, the development of novel design of bioactive materials is necessary. Bioactive ceramics show osteoconduction by formation of biologically active bone-like apatite through chemical reaction of the ceramic surface with surrounding body fluid. Hence, the control of their chemical reactivity in body fluid is essential to developing novel bioactive materials as well as biodegradable materials. This paper reviews novel bioactive materials designed based on chemical reactivity in body fluid.
An overview of biofunctionalization of metals in Japan
Authors: Hanawa Takao
Published: January 2009

Surface modification is an important and predominant technique for obtaining biofunction and biocompatibility in metals for biomedical use. The surface modification technique is a process that changes the surface composition, structure and morphology of a material, leaving the bulk mechanical properties intact. A tremendous number of surface modification techniques using dry and wet processes to improve the hard tissue compatibility of titanium have been developed. Some are now commercially available. Most of these processes have been developed by Japanese institutions since the 1990s. A second approach is the immobilization of biofunctional molecules to the metal surface to control the adsorption of proteins and adhesion of cells, platelets and bacteria. The immobilization of poly(ethylene glycol) to a metal surface with electrodeposition and its effect on biofunction are reviewed. The creation of a metal–polymer composite is another way to obtain metal-based biofunctional materials. The relationship between the shear bonding strength and the chemical structure at the bonding interface of a Ti-segmentated polyurethane composite through a silane coupling agent is explained.
A fast energy-dispersive multi-element detector for X-ray absorption spectroscopy
Authors: Welter Edmund , Hansen Karsten , Reckleben Christian , Diehl Inge
Published: January 2009

In this paper results are presented from fluorescence-yield X-ray absorption fine-structure spectroscopy measurements with a new seven-cell silicon drift detector (SDD) module. The complete module, including an integrated circuit for the detector readout, was developed and realised at DESY utilizing a monolithic seven-cell SDD. The new detector module is optimized for applications like XAFS which require an energy resolution of ∼250–300 eV (FWHM Mn Kα) at high count rates. Measurements during the commissioning phase proved the excellent performance for this type of application.
How should we determine length of anticoagulation after proximal deep vein thrombosis of the lower limbs?
Authors: Siragusa Sergio , Caramazza Domenica , Malato Alessandra
Published: January 2009

The current approach for deciding the duration of vitamin K antagonist (VKA) treatment after an episode of venous thrombo‐embolism (VTE) is mainly based on the characteristic of the index event (3 months or longer in case of unknown/persistent risk factors, 3 months or less in case of removable causes). However, the length of anticoagulation should be tailored on the patient’s risk for recurrent thrombosis as well as for bleeding, but such ‘time for decision’ is often unclear and the optimal duration of VKA remains debatable. The presence of persistent residual vein thrombosis and increased d‐dimer levels after stopping therapy are predictors for recurrent deep vein thrombosis (DVT). Management strategies based on these parameters have been demonstrated to optimize the decision for VKA duration, as they establish the patient’s intrinsic risk for recurrent events. This annotation discusses current practice and upcoming approaches regarding the length of VKA treatment after a first episode of DVT.
Food allergy is associated with an increased risk of asthma
Authors: Schroeder A. , Kumar R. , Pongracic J. A. , Sullivan C. L. , Caruso D. M. , Costello J. , Meyer K. E. , Vucic Y. , Gupta R. , Kim J. S. , Fuleihan R. , Wang X.
Published: January 2009

Background
The atopic march is well documented, but the interrelationship of food allergy (FA) and asthma is not well understood.

Objective
The aim of this study was to examine the strength of the association and temporal relationships between FA and asthma.

Methods
This analysis included 271 children 6 years (older group) and 296 children <6 years (younger group) from a family‐based FA cohort in Chicago, IL. Asthma was determined by parental report of physician diagnosis. FA status was determined based on the type and timing of clinical symptoms after ingestion of a specific food, and results of prick skin test (Multi‐Test II) and allergen‐specific IgE (Phadia ImmunoCAP). Analyses were carried out using logistic regression accounting for important covariates and auto‐correlations among siblings. Kaplan–Meier curves were used to compare the time to onset of asthma with the FA status.

Results
Symptomatic FA was associated with asthma in both older [odds ratio (OR)=4.9, 95% confidence interval (CI): 2.5–9.5] and younger children (OR=5.3, 95% CI: 1.7–16.2). The association was stronger among children with multiple or severe food allergies, especially in older children. Children with FA developed asthma earlier and at higher prevalence than children without FA (Cox proportional hazard ratio=3.7, 95% CI: 2.2–6.3 for children 6 years, and hazard ratio=3.3, 95% CI: 1.1–10 for children <6 years of age). No associations were seen between asymptomatic food sensitization and asthma.

Conclusions
Independent of markers of atopy such as aeroallergen sensitization and family history of asthma, there was a significant association between FA and asthma. This association was even stronger in subjects with multiple food allergies or severe FA.
Expression profiling of genes related to asthma exacerbations
Authors: Aoki T. , Matsumoto Y. , Hirata K. , Ochiai K. , Okada M. , Ichikawa K. , Shibasaki M. , Arinami T. , Sumazaki R. , Noguchi E.
Published: January 2009

Background
Asthma is a chronic airway inflammatory disease; however, the molecular mechanisms that underlie asthma exacerbation are only partially understood.

Objective
To identify gene expression signatures that reflect the acute exacerbation of asthma, we examined the differential expression of genes during asthma exacerbation and stable condition by using microarray analysis.

Methods
The subjects were mite‐sensitive asthmatic children and non‐asthmatic control children. The children were divided into four groups (AE: asthma exacerbation, n=12; SA: stable asthma, n=11; IC: infected control, n=6; and NC: non‐infected control, n=5). Total RNA was extracted from peripheral blood mononuclear cells and subjected to microarray analysis with Illumina Human Ref8 BeadChip arrays. Welch's t‐test was performed to identify genes whose expression was altered during asthma exacerbation. Quantitative real‐time RT‐PCR was performed on samples collected from 43 asthmatic children and 11 control children to verify the microarray results.

Results
The expression of 137/16 genes was significantly up/down‐regulated during asthma exacerbation assessed by microarray analysis. Of the genes, 62 were also differentially expressed during upper respiratory infection. Many of the asthma exacerbation related genes were involved in defence responses and responses to external stimuli, but these associations disappeared after excluding the infection‐related genes. Quantitative real‐time RT‐PCR confirmed that the genes related (S100A8 and GAS6) and unrelated to infections (CD200 and RBP7) were differentially expressed during asthma exacerbation (P<0.01).

Conclusions
Previously unidentified immune responses during asthma exacerbation may provide further clarification of the molecular mechanisms underlying asthma.