bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of rotational shear on granular discharge rates
Authors: Hilton J. E. , Cleary P. W.
Published: July 2010

The mass flow rate of a packed granular column subject to rotational shear discharging though an aperture is investigated computationally. We show that the flow rate increases in response to the applied shear. This increase obeys a power-law relation based on the rotational Froude number, Fr=Lω2/g, where ω is the angular rotation speed and L is a system length scale. The exponent of this relation is found to be independent of the particle diameter, intergrain friction, and the geometry of the setup.
Graphene field-effect transistors with self-aligned gates
Authors: Farmer Damon B. , Lin Yu-Ming , Avouris Phaedon
Published: July 2010

We present a device fabrication process that produces graphene-based field-effect transistors with self-aligned gates. This process utilizes the inherent nucleation inhibition of atomic-layer-deposited films with the graphene surface to achieve electrical isolation of the gate electrode from the source/drain electrodes while maintaining electrical access to the graphene channel. Self-alignment produces access lengths of 15–20 nm, which allows for improved device stability, performance, and a minimal normalized contact resistance of 540 Ω μm.
Electro-optic measurement of carrier mobility in an organic thin-film transistor
Authors: Bittle E. G. , Brill J. W. , Anthony J. E.
Published: July 2010

We have used an electro-optic technique to measure the position-dependent infrared absorption of holes injected into a thin crystal of the organic semiconductor, 6,13-bis(triisopropylsilylethynyl)-pentacene incorporated in a field-effect transistor. By applying square-wave voltages of variable frequency to the gate or drain, one can measure the time it takes for charges to accumulate on the surface, and therefore, determine their mobility.
Ge quantum dot tunneling diode with room temperature negative differential resistance
Authors: Oehme M. , Karmous A. , Sarlija M. , Werner J. , Kasper E. , Schulze J.
Published: July 2010

We present current density-voltage characteristics of Ge quantum dot p+-i-n+ tunneling diodes. The diode structure with Ge quantum dots embedded in the intrinsic region was grown by low temperature molecular beam epitaxy without any postgrowth annealing steps. The quantum dot diodes were fabricated using a low thermal budget fabrication process which preserves the Ge quantum structure. A negative differential resistance at room temperature of a Ge quantum dot tunneling diode was observed. A maximum peak to valley ratio of 1.6 at room temperature was achieved.
Pseudomonas syringae
hijacks plant stress chaperone machinery for virulence
Authors: Jelenska Joanna , van Hal Jodocus A. , Greenberg Jean T.
Published: July 2010

Plant heat shock protein Hsp70 is the major target of HopI1, a virulence effector of pathogenic
Pseudomonas syringae
. Hsp70 is essential for the virulence function of HopI1. HopI1 directly binds Hsp70 through its C-terminal J domain and stimulates Hsp70 ATP hydrolysis activity in vitro. In plants, HopI1 forms large complexes in association with Hsp70 and induces and recruits cytosolic Hsp70 to chloroplasts, the site of HopI1 localization. Deletion of a central P/Q-rich repeat region disrupts HopI1 virulence but not Hsp70 interactions or association with chloroplasts. Thus, HopI1 must not only bind Hsp70 through its J domain, but likely actively affects Hsp70 activity and/or specificity. At high temperature, HopI1 is dispensable for
P. syringae
pathogenicity, unless excess Hsp70 is provided. A working hypothesis is that Hsp70 has a defense-promoting activity(s) that HopI1 or high temperature can subvert. Enhanced susceptibility of Hsp70-depleted plants to nonpathogenic strains of
P. syringae
supports a defense-promoting role for Hsp70.
Regulatory Factor X (RFX)-mediated transcriptional rewiring of ciliary genes in animals
Authors: Piasecki Brian P. , Burghoorn Jan , Swoboda Peter
Published: July 2010

Cilia were present in the last eukaryotic common ancestor (LECA) and were retained by most organisms spanning all extant eukaryotic lineages, including organisms in the Unikonta (Amoebozoa, fungi, choanoflagellates, and animals), Archaeplastida, Excavata, Chromalveolata, and Rhizaria. In certain animals, including humans, ciliary gene regulation is mediated by Regulatory Factor X (RFX) transcription factors (TFs). RFX TFs bind X-box promoter motifs and thereby positively regulate >50 ciliary genes. Though RFX-mediated ciliary gene regulation has been studied in several bilaterian animals, little is known about the evolutionary conservation of ciliary gene regulation. Here, we explore the evolutionary relationships between RFX TFs and cilia. By sampling the genome sequences of >120 eukaryotic organisms, we show that RFX TFs are exclusively found in unikont organisms (whether ciliated or not), but are completely absent from the genome sequences of all nonunikont organisms (again, whether ciliated or not). Sampling the promoter sequences of 12 highly conserved ciliary genes from 23 diverse unikont and nonunikont organisms further revealed that phylogenetic footprints of X-box promoter motif sequences are found exclusively in ciliary genes of certain animals. Thus, there is no correlation between cilia/ciliary genes and the presence or absence of RFX TFs and X-box promoter motifs in nonanimal unikont and in nonunikont organisms. These data suggest that RFX TFs originated early in the unikont lineage, distinctly after cilia evolved. The evolutionary model that best explains these observations indicates that the transcriptional rewiring of many ciliary genes by RFX TFs occurred early in the animal lineage.
A time-invariant principle of genome evolution
Authors: De Subhajyoti , Babu M. Madan
Published: July 2010

Uncovering general principles of genome evolution that are time-invariant and that operate in germ and somatic cells has implications for genome-wide association studies (GWAS), gene therapy, and disease genomics. Here we investigate the relationship between structural alterations (e.g., insertions and deletions) and single-nucleotide substitutions by comparing the following genomes that diverged at different times across germ- and somatic-cell lineages: (
i
) the reference human and chimpanzee genome (in million years), (
ii
) the reference human and personal genomes (in tens of thousands of years), and (
iii
) structurally altered regions in cancer and genetically engineered cells (in days). At the species level, genes with structural alteration in nearby regions show increased single-nucleotide changes and tend to evolve faster. In personal genomes, the single-nucleotide substitution rate is higher near sites of structural alteration and decreases with increasing distance. In human cancer cell populations and in cells genetically engineered using zinc-finger nucleases, single-nucleotide changes occur frequently near sites of structural alterations. We present evidence that structural alteration induces single-nucleotide changes in nearby regions and discuss possible molecular mechanisms that contribute to this phenomenon. We propose that the low fidelity of nonreplicative error-prone repair polymerases, which are used during insertion or deletion, result in break-repair-induced single-nucleotide mutations in the vicinity of structural alteration. Thus, in the mutational landscape, structural alterations are linked to single-nucleotide changes across different time scales in both somatic- and germ-cell lineages. We discuss implications for genome evolution, GWAS, disease genomics, and gene therapy and emphasize the need to investigate both types of mutations within a single framework.
Genetic flexibility of regulatory networks
Authors: Hunziker Alexander , Tuboly Csaba , Horváth Péter , Krishna Sandeep , Semsey Szabolcs
Published: July 2010

Gene regulatory networks are based on simple building blocks such as promoters, transcription factors (TFs) and their binding sites on DNA. But how diverse are the functions that can be obtained by different arrangements of promoters and TF binding sites? In this work we constructed synthetic regulatory regions using promoter elements and binding sites of two noninteracting TFs, each sensing a single environmental input signal. We show that simply by combining these three kinds of elements, we can obtain 11 of the 16 Boolean logic gates that integrate two environmental signals in vivo. Further, we demonstrate how combination of logic gates can result in new logic functions. Our results suggest that simple elements of transcription regulation form a highly flexible toolbox that can generate diverse functions under natural selection.
Quantum size effects on the work function of metallic thin film nanostructures
Authors: Kim Jungdae , Qin Shengyong , Yao Wang , Niu Qian , Chou M. Y. , Shih Chih-Kang
Published: July 2010

In this paper, we present the direct observation of quantum size effects (QSE) on the work function in ultrathin Pb films. By using scanning tunneling microscopy and spectroscopy, we show that the very existence of quantum well states (QWS) in these ultrathin films profoundly affects the measured tunneling decay constant
κ
, resulting in a very rich phenomenon of “quantum oscillations” in
κ
as a function of thickness,
L
, and bias voltage,
V

s

. More specifically, we find that the phase of the quantum oscillations in
κ
vs.
L
depends sensitively upon the bias voltage, which often results in a total phase reversal at different biases. On the other hand, at very low sample bias (|
V

s

| < 0.03 V) the measurement of
κ
vs.
L
accurately reflects the quantum size effect on the work function. In particular, the minima in the quantum oscillations of
κ
vs.
L
occur at the locations where QWS cross the Fermi energy, thus directly unraveling the QSE on the work function in ultrathin films, which was predicted more than three decades ago. This further clarifies several contradictions regarding the relationship between the QWS locations and the work function.
Nonideal Rayleigh–Taylor mixing
Authors: Lim Hyunkyung , Iwerks Justin , Glimm James , Sharp David H.
Published: July 2010

Rayleigh–Taylor mixing is a classical hydrodynamic instability that occurs when a light fluid pushes against a heavy fluid. The two main sources of nonideal behavior in Rayleigh–Taylor (RT) mixing are regularizations (physical and numerical), which produce deviations from a pure Euler equation, scale invariant formulation, and nonideal (i.e., experimental) initial conditions. The Kolmogorov theory of turbulence predicts stirring at all length scales for the Euler fluid equations without regularization. We interpret mathematical theories of existence and nonuniqueness in this context, and we provide numerical evidence for dependence of the RT mixing rate on nonideal regularizations; in other words, indeterminacy when modeled by Euler equations. Operationally, indeterminacy shows up as nonunique solutions for RT mixing, parametrized by Schmidt and Prandtl numbers, in the large Reynolds number (Euler equation) limit. Verification and validation evidence is presented for the large eddy simulation algorithm used here. Mesh convergence depends on breaking the nonuniqueness with explicit use of the laminar Schmidt and Prandtl numbers and their turbulent counterparts, defined in terms of subgrid scale models. The dependence of the mixing rate on the Schmidt and Prandtl numbers and other physical parameters will be illustrated. We demonstrate numerically the influence of initial conditions on the mixing rate. Both the dominant short wavelength initial conditions and long wavelength perturbations are observed to play a role. By examination of two classes of experiments, we observe the absence of a single universal explanation, with long and short wavelength initial conditions, and the various physical and numerical regularizations contributing in different proportions in these two different contexts.
Identification and pharmacological characterization of cholesterol-5,6-epoxide hydrolase as a target for tamoxifen and AEBS ligands
Authors: de Medina Philippe , Paillasse Michael R. , Segala Gregory , Poirot Marc , Silvente-Poirot Sandrine
Published: July 2010

The microsomal antiestrogen binding site (AEBS) is a high-affinity target for the antitumor drug tamoxifen and its cognate ligands that mediate breast cancer cell differentiation and apoptosis. The AEBS, a hetero-oligomeric complex composed of 3β-hydroxysterol-Δ
8
-Δ
7
-isomerase (D8D7I) and 3β-hydroxysterol-Δ
7
-reductase (DHCR7), binds different structural classes of ligands, including ring B oxysterols. These oxysterols are inhibitors of cholesterol-5,6-epoxide hydrolase (ChEH), a microsomal epoxide hydrolase that has yet to be molecularly identified. We hypothesized that the AEBS and ChEH might be related entities. We show that the substrates of ChEH, cholestan-5α,6α-epoxy-3β-ol (α-CE) and cholestan-5β,6β-epoxy-3β-ol (β-CE), and its product, cholestane-3β,5α,6β-triol (CT), are competitive ligands of tamoxifen binding to the AEBS. Conversely, we show that each AEBS ligand is an inhibitor of ChEH activity, and that there is a positive correlation between these ligands’ affinity for the AEBS and their potency to inhibit ChEH (
r
2
= 0.95;
n
= 39;
P
< 0.0001). The single expression of D8D7I or DHCR7 in COS-7 cells slightly increased ChEH activity (1.8- and 2.6-fold), whereas their coexpression fully reconstituted ChEH, suggesting that the formation of a dimer is required for ChEH activity. Similarly, the single knockdown of D8D7I or DHCR7 using siRNA partially inhibited ChEH in MCF-7 cells, whereas the knockdown of both D8D7I and DHCR7 abolished ChEH activity by 92%. Taken together, our findings strongly suggest that the AEBS carries out ChEH activity and establish that ChEH is a new target for drugs of clinical interest, polyunsaturated fatty acids and ring B oxysterols.
Efficacy of bortezomib in a direct xenograft model of primary effusion lymphoma
Authors: Sarosiek Kristopher A. , Cavallin Lucas E. , Bhatt Shruti , Toomey Ngoc L. , Natkunam Yasodha , Blasini Wilfredo , Gentles Andrew J. , Ramos Juan Carlos , Mesri Enrique A. , Lossos Izidore S.
Published: July 2010

Primary effusion lymphoma (PEL) is an aggressive B-cell lymphoma most commonly diagnosed in HIV-positive patients and universally associated with Kaposi's sarcoma-associated herpesvirus (KSHV). Chemotherapy treatment of PEL yields only short-term remissions in the vast majority of patients, but efforts to develop superior therapeutic approaches have been impeded by lack of animal models that accurately mimic human disease. To address this issue, we developed a direct xenograft model, UM-PEL-1, by transferring freshly isolated human PEL cells into the peritoneal cavities of NOD/SCID mice without in vitro cell growth to avoid the changes in KSHV gene expression evident in cultured cells. We used this model to show that bortezomib induces PEL remission and extends overall survival of mice bearing lymphomatous effusions. The proapoptotic effects of bortezomib are not mediated by inhibition of the prosurvival NF-κB pathway or by induction of a terminal unfolded protein response. Transcriptome analysis by genomic arrays revealed that bortezomib down-regulated cell-cycle progression, DNA replication, and Myc-target genes. Furthermore, we demonstrate that in vivo treatment with either bortezomib or doxorubicin induces KSHV lytic reactivation. These reactivations were temporally distinct, and this difference may help elucidate the therapeutic window for use of antivirals concurrently with chemotherapy. Our findings show that this direct xenograft model can be used for testing novel PEL therapeutic strategies and also can provide a rational basis for evaluation of bortezomib in clinical trials.
The 3-4 loop of an archaeal glutamate transporter homolog experiences ligand-induced structural changes and is essential for transport
Authors: Compton Emma L. R. , Taylor Erin M. , Mindell Joseph A.
Published: July 2010

Glutamatergic synaptic transmission is terminated by members of the excitatory amino acid transporter (EAAT) family of proteins that remove glutamate from the synaptic cleft by transporting it into surrounding glial cells. Recent structures of a bacterial homolog suggest that major motions within the transmembrane domain translocate the substrate across the membrane. However, the events leading to this large structural rearrangement are much less clear. Two reentrant loops have been proposed to act as extracellular and intracellular gates, but whether other regions of these proteins play a role in the transport process is unknown. We hypothesized that transport-related conformational changes could change the solvent accessibilities of affected residues, as reflected in protease sensitivity or small-molecule reactivity. In the model system Glt
Ph
, an archaeal EAAT homologue from
Pyrococcus horikoshii
, limited trypsin proteolysis experiments initially identified a site in the long extracellular loop that stretches between helices 3 and 4 that becomes protected from proteolysis in the presence of a substrate, L-aspartate, or an inhibitor, DL-TBOA in the presence of Na
+
, the cotransported ion. Using a combination of site-directed cysteine-scanning mutagenesis and fluorescein-5-maleimide labeling we found that positions throughout the loop experience these ligand-induced conformational changes. By selectively cleaving the 3-4 loop (via introduced Factor Xa sites) we demonstrate that it plays a vital role in the transport process; though structurally intact, the cleaved proteins are unable to transport aspartate. These results inculcate the 3-4 loop as an important player in the transport process, a finding not predicted by any of the available crystal structures of Glt
Ph
.
Genetic inhibition of PKA phosphorylation of RyR2 prevents dystrophic cardiomyopathy
Authors: Sarma Satyam , Li Na , van Oort Ralph J. , Reynolds Corey , Skapura Darlene G. , Wehrens Xander H. T.
Published: July 2010

Aberrant intracellular Ca
2+
regulation is believed to contribute to the development of cardiomyopathy in Duchenne muscular dystrophy. Here, we tested whether inhibition of protein kinase A (PKA) phosphorylation of ryanodine receptor type 2 (RyR2) prevents dystrophic cardiomyopathy by reducing SR Ca
2+
leak in the
mdx
mouse model of Duchenne muscular dystrophy.
mdx
mice were crossed with RyR2-S2808A mice, in which PKA phosphorylation site S2808 on RyR2 is inactivated by alanine substitution. Compared with
mdx
mice that developed age-dependent heart failure,
mdx
-S2808A mice exhibited improved fractional shortening and reduced cardiac dilation. Whereas application of isoproterenol severely depressed cardiac contractility and caused 95% mortality in
mdx
mice, contractility was preserved with only 19% mortality in
mdx
-S2808A mice. SR Ca
2+
leak was greater in ventricular myocytes from
mdx
than
mdx
-S2808A mice. Myocytes from
mdx
mice had a higher incidence of isoproterenol-induced diastolic Ca
2+
release events than myocytes from
mdx
-S2808A mice. Thus, inhibition of PKA phosphorylation of RyR2 reduced SR Ca
2+
leak and attenuated cardiomyopathy in
mdx
mice, suggesting that enhanced PKA phosphorylation of RyR2 at S2808 contributes to abnormal Ca
2+
homeostasis associated with dystrophic cardiomyopathy.
Replenishment of fish populations is threatened by ocean acidification
Authors: Munday Philip L. , Dixson Danielle L. , McCormick Mark I. , Meekan Mark , Ferrari Maud C. O. , Chivers Douglas P.
Published: July 2010

There is increasing concern that ocean acidification, caused by the uptake of additional CO
2
at the ocean surface, could affect the functioning of marine ecosystems; however, the mechanisms by which population declines will occur have not been identified, especially for noncalcifying species such as fishes. Here, we use a combination of laboratory and field-based experiments to show that levels of dissolved CO
2
predicted to occur in the ocean this century alter the behavior of larval fish and dramatically decrease their survival during recruitment to adult populations. Altered behavior of larvae was detected at 700 ppm CO
2
, with many individuals becoming attracted to the smell of predators. At 850 ppm CO
2
, the ability to sense predators was completely impaired. Larvae exposed to elevated CO
2
were more active and exhibited riskier behavior in natural coral-reef habitat. As a result, they had 5–9 times higher mortality from predation than current-day controls, with mortality increasing with CO
2
concentration. Our results show that additional CO
2
absorbed into the ocean will reduce recruitment success and have far-reaching consequences for the sustainability of fish populations.
The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy
Authors: Honigberg Lee A. , Smith Ashley M. , Sirisawad Mint , Verner Erik , Loury David , Chang Betty , Li Shyr , Pan Zhengying , Thamm Douglas H. , Miller Richard A. , Buggy Joseph J.
Published: July 2010

Activation of the B-cell antigen receptor (BCR) signaling pathway contributes to the initiation and maintenance of B-cell malignancies and autoimmune diseases. The Bruton tyrosine kinase (Btk) is specifically required for BCR signaling as demonstrated by human and mouse mutations that disrupt Btk function and prevent B-cell maturation at steps that require a functional BCR pathway. Herein we describe a selective and irreversible Btk inhibitor, PCI-32765, that is currently under clinical development in patients with B-cell non-Hodgkin lymphoma. We have used this inhibitor to investigate the biologic effects of Btk inhibition on mature B-cell function and the progression of B cell-associated diseases in vivo. PCI-32765 blocked BCR signaling in human peripheral B cells at concentrations that did not affect T cell receptor signaling. In mice with collagen-induced arthritis, orally administered PCI-32765 reduced the level of circulating autoantibodies and completely suppressed disease. PCI-32765 also inhibited autoantibody production and the development of kidney disease in the MRL-Fas(lpr) lupus model. Occupancy of the Btk active site by PCI-32765 was monitored in vitro and in vivo using a fluorescent affinity probe for Btk. Active site occupancy of Btk was tightly correlated with the blockade of BCR signaling and in vivo efficacy. Finally, PCI-32765 induced objective clinical responses in dogs with spontaneous B-cell non-Hodgkin lymphoma. These findings support Btk inhibition as a therapeutic approach for the treatment of human diseases associated with activation of the BCR pathway.
Identification of a pheromone regulating caste differentiation in termites
Authors: Matsuura Kenji , Himuro Chihiro , Yokoi Tomoyuki , Yamamoto Yuuka , Vargo Edward L. , Keller Laurent
Published: July 2010

The hallmark of social insects is their caste system: reproduction is primarily monopolized by queens, whereas workers specialize in the other tasks required for colony growth and survival. Pheromones produced by reining queens have long been believed to be the prime factor inhibiting the differentiation of new reproductive individuals. However, there has been very little progress in the chemical identification of such inhibitory pheromones. Here we report the identification of a volatile inhibitory pheromone produced by female neotenics (secondary queens) that acts directly on target individuals to suppress the differentiation of new female neotenics and identify n-butyl-n-butyrate and 2-methyl-1-butanol as the active components of the inhibitory pheromone. An artificial pheromone blend consisting of these two compounds had a strong inhibitory effect similar to live neotenics. Surprisingly, the same two volatiles are also emitted by eggs, playing a role both as an attractant to workers and an inhibitor of reproductive differentiation. This dual production of an inhibitory pheromone by female reproductives and eggs probably reflects the recruitment of an attractant pheromone as an inhibitory pheromone and may provide a mechanism ensuring honest signaling of reproductive status with a tight coupling between fertility and inhibitory power. Identification of a volatile pheromone regulating caste differentiation in a termite provides insights into the functioning of social insect colonies and opens important avenues for elucidating the developmental pathways leading to reproductive and nonreproductive castes.
Biophotonic probing of macromolecular transformations during apoptosis
Authors: Pliss Artem , Kuzmin Andrey N. , Kachynski Aliaksandr V. , Prasad Paras N.
Published: July 2010

We introduce here multiplex nonlinear optical imaging as a powerful tool for studying the molecular organization and its transformation in cellular processes, with the specific example of apoptosis. Apoptosis is a process of self-initiated cell death, critically important for physiological regulation and elimination of genetic disorders. Nonlinear optical microscopy, combining the coherent anti-Stokes Raman scattering (CARS) microscopy and two-photon excited fluorescence (TPEF), has been used for analysis of spatial distribution of major types of biomolecules: proteins, lipids, and nucleic acids in the cells while monitoring their changes during apoptosis. CARS imaging revealed that in the nuclei of proliferating cells, the proteins are distributed nearly uniformly, with local accumulations in several nuclear structures. We have found that this distribution is abruptly disrupted at the onset of apoptosis and is transformed to a progressively irregular pattern. Fluorescence recovery after photobleaching (FRAP) studies indicate that pronounced aggregation of proteins in the nucleoplasm of apoptotic cells coincides with a gradual reduction in their mobility.
Depression of reactivity by the collision energy in the single barrier H + CD
4
→ HD + CD
3
reaction
Authors: Zhang Weiqing , Zhou Yong , Wu Guorong , Lu Yunpeng , Pan Huilin , Fu Bina , Shuai Quan , Liu Lan , Liu Shu , Zhang Liling , Jiang Bo , Dai Dongxu , Lee Soo-Ying , Xie Zhen , Braams Bastiaan J. , Bowman Joel M. , Collins Michael A. , Zhang Dong H. , Yang Xueming
Published: July 2010

Crossed molecular beam experiments and accurate quantum scattering calculations have been carried out for the polyatomic H + CD
4
 → HD + CD
3
reaction. Unprecedented agreement has been achieved between theory and experiments on the energy dependence of the integral cross section in a wide collision energy region that first rises and then falls considerably as the collision energy increases far over the reaction barrier for this simple hydrogen abstraction reaction. Detailed theoretical analysis shows that at collision energies far above the barrier the incoming H-atom moves so quickly that the heavier D-atom on CD
4
cannot concertedly follow it to form the HD product, resulting in the decline of reactivity with the increase of collision energy. We propose that this is also the very mechanism, operating in many abstraction reactions, which causes the differential cross section in the backward direction to decrease substantially or even vanish at collision energies far above the barrier height.
Asymmetry in the clockwise and counterclockwise rotation of the bacterial flagellar motor
Authors: Yuan Junhua , Fahrner Karen A. , Turner Linda , Berg Howard C.
Published: July 2010

Cells of
Escherichia coli
are able to swim up gradients of chemical attractants by modulating the direction of rotation of their flagellar motors, which spin alternately clockwise (CW) and counterclockwise (CCW). Rotation in either direction has been thought to be symmetric and exhibit the same torques and speeds. The relationship between torque and speed is one of the most important measurable characteristics of the motor, used to distinguish specific mechanisms of motor rotation. Previous measurements of the torque–speed relationship have been made with cells lacking the response regulator CheY that spin their motors exclusively CCW. In this case, the torque declines slightly up to an intermediate speed called the “knee speed” after which it falls rapidly to zero. This result is consistent with a “power-stroke” mechanism for torque generation. Here, we measure the torque–speed relationship for cells that express large amounts of CheY and only spin their motors CW. We find that the torque decreases linearly with speed, a result remarkably different from that for CCW rotation. We obtain similar results for wild-type cells by reexamining data collected in previous work. We speculate that CCW rotation might be optimized for runs, with higher speeds increasing the ability of cells to sense spatial gradients, whereas CW rotation might be optimized for tumbles, where the object is to change cell trajectories. But why a linear torque–speed relationship might be optimum for the latter purpose we do not know.
Strong reversible Fe
3+
-mediated bridging between dopa-containing protein films in water
Authors: Zeng Hongbo , Hwang Dong Soo , Israelachvili Jacob N. , Waite J. Herbert
Published: July 2010

Metal-containing polymer networks are widespread in biology, particularly for load-bearing exoskeletal biomaterials.
Mytilus
byssal cuticle is an especially interesting case containing moderate levels of Fe
3+
and cuticle protein—mussel foot protein-1 (mfp-1), which has a peculiar combination of high hardness and high extensibility. Mfp-1, containing 13 mol % of dopa (3, 4-dihydroxyphenylalanine) side-chains, is highly positively charged polyelectrolyte (pI ∼ 10) and didn’t show any cohesive tendencies in previous surface forces apparatus (SFA) studies. Here, we show that Fe
3+
ions can mediate unusually strong interactions between the positively charged proteins. Using an SFA, Fe
3+
was observed to impart robust bridging (
W
ad
 ≈ 4.3 mJ/m
2
) between two noninteracting mfp-1 films in aqueous buffer approaching the ionic strength of seawater. The Fe
3+
bridging between the mfp-1-coated surfaces is fully reversible in water, increasing with contact time and iron concentration up to 10 μM; at 100 μM, Fe
3+
bridging adhesion is abolished. Bridging is apparently due to the formation of multivalent dopa-iron complexes. Similar Fe-mediated bridging (
W
ad
 ≈ 5.7 mJ/m
2
) by a smaller recombinant dopa-containing analogue indicates that bridging is largely independent of molecular weight and posttranslational modifications other than dopa. The results suggest that dopa-metal interactions may provide an energetic new paradigm for engineering strong, self-healing interactions between polymers under water.
Irrelevant events affect voters' evaluations of government performance
Authors: Healy Andrew J. , Malhotra Neil , Mo Cecilia Hyunjung
Published: July 2010

Does information irrelevant to government performance affect voting behavior? If so, how does this help us understand the mechanisms underlying voters’ retrospective assessments of candidates’ performance in office? To precisely test for the effects of irrelevant information, we explore the electoral impact of local college football games just before an election, irrelevant events that government has nothing to do with and for which no government response would be expected. We find that a win in the 10 d before Election Day causes the incumbent to receive an additional 1.61 percentage points of the vote in Senate, gubernatorial, and presidential elections, with the effect being larger for teams with stronger fan support. In addition to conducting placebo tests based on postelection games, we demonstrate these effects by using the betting market's estimate of a team's probability of winning the game before it occurs to isolate the surprise component of game outcomes. We corroborate these aggregate-level results with a survey that we conducted during the 2009 NCAA men's college basketball tournament, where we find that surprising wins and losses affect presidential approval. An experiment embedded within the survey also indicates that personal well-being may influence voting decisions on a subconscious level. We find that making people more aware of the reasons for their current state of mind reduces the effect that irrelevant events have on their opinions. These findings underscore the subtle power of irrelevant events in shaping important real-world decisions and suggest ways in which decision making can be improved.
Reputation for reciprocity engages the brain reward center
Authors: Phan K. Luan , Sripada Chandra Sekhar , Angstadt Mike , McCabe Kevin
Published: July 2010

Brain reward circuitry, including ventral striatum and orbitofrontal cortex, has been independently implicated in preferences for fair and cooperative outcomes as well as learning of reputations. Using functional MRI (fMRI) and a “trust game” task involving iterative exchanges with fictive partners who acquire different reputations for reciprocity, we measured brain responses in 36 healthy adults when positive actions (entrust investment to partners) yield positive returns (reciprocity) and how these brain responses are modulated by partner reputation for repayment. Here we show that positive reciprocity robustly engages the ventral striatum and orbitofrontal cortex. Moreover, this signal of reciprocity in the ventral striatum appears selectively in response to partners who have consistently returned the investment (e.g., a reputation for reciprocity) and is absent for partners who lack a reputation for reciprocity. These findings elucidate a fundamental brain mechanism, via reward-related neural substrates, by which human cooperative relationships are initiated and sustained.
A generalized Fisher equation and its utility in chemical kinetics
Authors: Ross John , Villaverde Alejandro Fernández , Banga Julio R. , Vázquez Sara , Morán Federico
Published: July 2010

A generalized Fisher equation (GFE) relates the time derivative of the average of the intrinsic rate of growth to its variance. The GFE is an exact mathematical result that has been widely used in population dynamics and genetics, where it originated. Here we demonstrate that the GFE can also be useful in other fields, specifically in chemistry, with models of two chemical reaction systems for which the mechanisms and rate coefficients correspond reasonably well to experiments. A bad fit of the GFE can be a sign of high levels of measurement noise; for low or moderate levels of noise, fulfillment of the GFE is not degraded. Hence, the GFE presents a noise threshold that may be used to test the validity of experimental measurements without requiring any additional information. In a different approach information about the system (model) is included in the calculations. In that case, the discrepancy with the GFE can be used as an optimization criterion for the determination of rate coefficients in a given reaction mechanism.
Coexpression of δ- and μ-opioid receptors in nociceptive sensory neurons
Authors: Wang Hai-Bo , Zhao Bo , Zhong Yan-Qing , Li Kai-Cheng , Li Zi-Yan , Wang Qiong , Lu Yin-Jing , Zhang Zhen-Ning , He Shao-Qiu , Zheng Han-Cheng , Wu Sheng-Xi , Hökfelt Tomas G. M. , Bao Lan , Zhang Xu
Published: July 2010

Morphine-induced analgesia and antinociceptive tolerance are known to be modulated by interaction between δ-opioid receptors (DORs) and μ-opioid receptors (MORs) in the pain pathway. However, evidence for expression of DORs in nociceptive small-diameter neurons in dorsal root ganglia (DRG) and for coexistence of DORs with MORs and neuropeptides has recently been challenged. We now report, using in situ hybridization, single-cell PCR, and immunostaining, that DORs are widely expressed not only in large DRG neurons but in small ones and coexist with MORs in peptidergic small DRG neurons, with protachykinin-dependent localization in large dense-core vesicles. Importantly, both DOR and MOR agonists reduce depolarization-induced Ca2+currents in single small DRG neurons and inhibit afferent C-fiber synaptic transmission in the dorsal spinal cord. Thus, coexistence of DORs and MORs in small DRG neurons is a basis for direct interaction of opioid receptors in modulation of nociceptive afferent transmission and opioid analgesia.
Positive and Negative Mediation as a Function of Whether the Absent Cue was Previously Associated with the Outcome
Authors: Castro Leyre , Matute Helena
Published: July 2010

After presenting two cues, A and B, together, later pairings of one of the cues alone with an outcome can generate changes in the associative value of the absent cue. These changes can be in the same direction as the present cue (i.e., positive mediation) or in the opposite direction to the present cue (i.e., negative mediation). We found both mediational effects in a human contingency task. In addition, we found that the direction of the change was determined by the existence of a prior association between the absent cue and the outcome. When a prior association exists, the absent cue tends to change its value in the opposite direction to the present cue, whereas when there is no prior association, the absent cue tends to change its value in the same direction as the present cue. Recent associative models (Stout & Miller, 2007) can explain our results.
Tropical R maps and affine geometric crystals
Authors: Kashiwara Masaki , Nakashima Toshiki , Okado Masato
Published: July 2010

By modifying an earlier method of the authors (2008), certain affine geometric crystals are realized in affinization of the fundamental representation

W
(

ϖ
1

)
l

W(\varpi _1)_l

, and the tropical R maps for the affine geometric crystals are described explicitly. We also define prehomogeneous geometric crystals and show that for a positive geometric crystal, the connectedness of the corresponding ultra-discretized crystal is the sufficient condition for prehomogeneity of the positive geometric crystal. Moreover, the uniqueness of tropical R maps is discussed.
CNVineta: a data mining tool for large case–control copy number variation datasets
Authors: Wittig Michael , Helbig Ingo , Schreiber Stefan , Franke Andre
Published: July 2010

Motivation: Copy number variation (CNV), a major contributor to human genetic variation, comprises ≥ 1 kb genomic deletions and insertions. Yet, the identification of CNVs from microarray data is still hampered by high false negative and positive prediction rates due to the noisy nature of the raw data. Here, we present CNVineta, an R package for rapid data mining and visualization of CNVs in large case–control datasets genotyped with single nucleotide polymorphism oligonucleotide arrays. CNVineta is compatible with various established CNV prediction algorithms, can be used for genome-wide association analysis of rare and common CNVs and enables rapid and serial display of log2 of raw data ratios as well as B-allele frequencies for visual quality inspection. In summary, CNVineta aides in the interpretation of large-scale CNV datasets and prioritization of target regions for follow-up experiments.

Availability and Implementation: CNVineta is available as an R package and can be downloaded from http://www.ikmb.uni-kiel.de/CNVineta/; the package contains a tutorial outlining a typical workflow. The CNVineta compatible HapMap dataset can also be downloaded from the link above.

Contact:  m.wittig@mucosa.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
The vitamin D system: a crosstalk between the heart and kidney
Authors: Cozzolino Mario , Ketteler Markus , Zehnder Daniel
Published: July 2010

Chronic kidney disease (CKD) independently increases the rates of cardiovascular disease, whereas the severity of kidney disease correlates with increased cardiovascular morbidity and death. Vitamin D is modified in the liver and the kidney to its active form (1,25‐dihydroxyvitamin D) by the 25‐hydroxy vitamin D 1‐hydroxylase enzyme (CYP27B1). The activated vitamin D brings about its actions through the vitamin D receptor (VDR). The VDRs and CYP27B1 have recently been shown to be expressed in several tissues, not directly involved in mineral homeostasis, including the cardiovascular, immune, and epithelial systems. The action of vitamin D in these tissues is implicated in the regulation of endothelial, vascular smooth muscle, and cardiac cell function, the renin–angiotensin system, inflammatory and fibrotic pathways, and immune response. Impaired VDR activation and signalling results in cellular dysfunction in several organs and biological systems, which leads to reduced bone health, an increased risk for epithelial cancers, metabolic disease, and uncontrolled inflammatory responses. Failure of cardiovascular VDR activation results in hypertension, accelerated atherosclerosis and vascular calcification, cardiac hypertrophy with vascular rarification and fibrosis, and progressive renal dysfunction. An emerging body of evidence has prompted attention to the relationship between CKD, mineral bone disorder (CKD‐MBD), and cardiovascular disease in the new guidelines from Kidney Disease: Improving Global Outcomes. Vitamin D receptor activators, commonly used to treat CKD‐MBD, and an appropriate treatment of vitamin D hormonal system failure in patients with CKD, may help to reduce cardiovascular morbidity and mortality in these patients.
Xenon Pretreatment Attenuates Anesthetic-induced Apoptosis in the Developing Brain in Comparison with Nitrous Oxide and Hypoxia
Authors: Shu Yi , Patel Shivali M. , Pac-Soo Chen , Fidalgo António Rei , Wan Yanjie , Maze Mervyn , Ma Daqing
Published: July 2010

Background

Administration of certain general anesthetics to rodents during the synaptogenic phase of neurodevelopment produces neuronal injury. Preconditioning (pretreatment) can reduce tissue injury caused by a severe insult; the authors investigated whether pretreatment strategies can protect the developing brain from anesthetic-induced neurotoxicity.

Methods

Seven-day-old Sprague-Dawley rats were pretreated with one of the following: 70% xenon, 70% nitrous oxide, or 8% hypoxia for 2 h; 24 h later, rats were exposed to the neurotoxic combination of 70% nitrous oxide and 0.75% isoflurane for 6 h. Cortical and hippocampal neuroapoptosis was assessed using caspase-3 immunostaining. Separate cohorts were maintained for 40 days at which time cognitive function with trace fear conditioning was performed. In other pretreated cohorts, rat cortices were isolated for immunoblotting of caspase-3, Bcl-2, cytochrome C, P53, and mitogen-activated protein kinases. To obviate physiologic influences, organotypic hippocampal slices harvested from postnatal rat pups were cultured for 5 days and exposed to the same conditions as obtained for the in vivo studies, and caspase-3 immunostaining was again the measured outcome.

Result

Xenon pretreatment prevented nitrous oxide- and isoflurane-induced neuroapoptosis (in vivo and in vitro) and cognitive deterioration (in vivo). Contrastingly, nitrous oxide- and isoflurane-induced neuroapoptosis was exacerbated by hypoxic pretreatment. Nitrous oxide pretreatment had no effect. Xenon pretreatment increased Bcl-2 expression and decreased both cytochrome C release and P53 expression; conversely, the opposite was evident after hypoxic pretreatment.

Conclusions

Although xenon pretreatment protects against nitrous oxide- and isoflurane-induced neuroapoptosis, hypoxic pretreatment exacerbates anesthetic-induced neonatal neurodegeneration.
Cosyntropin for Prophylaxis against Postdural Puncture Headache after Accidental Dural Puncture
Authors: Hakim Sameh Michel
Published: July 2010

Background

The aim of the current study was to investigate the effect of administration of cosyntropin after accidental dural puncture (ADP) on the incidence of postdural puncture headache (PDPH) and the need for therapeutic epidural blood patch (EBP).

Methods

Ninety parturients who suffered an ADP were studied. After delivery, patients were randomly assigned to one of two equal-sized groups. In group I (cosyntropin group), patients received cosyntropin in a dose of 1 mg intravenously. In group II (control group), patients received an equal volume of normal saline.

Results

Fifteen patients (33%) in the cosyntropin group suffered from PDPH, compared with 31 patients (68.9%) in the control group (P = 0.001). Significantly fewer patients in the cosyntropin group required an EBP, compared with the control group (5 patients [11.1%] vs. 13 patients [28.9%], respectively; P = 0.035). The Kaplan-Meier curves for the occurrence of PDPH showed a hazard ratio of 0.32 (95% CI = 0.16-0.55, P < 0.0001). The time from ADP to occurrence of PDPH was significantly longer in the cosyntropin group (27.2 [7.7] h) in comparison with the control group (17.5 [4.9] h; P < 0.001). However, there were no statistically significant differences among patients who developed PDPH in both groups with regard to the severity or duration of PDPH or with regard to the need for EBP or for repeat EBP (P > 0.05).

Conclusions

Administration of cosyntropin after ADP in parturients was associated with significant reduction in the incidence of PDPH and need for EBP and significant prolongation of the time from ADP to occurrence of PDPH.
Anemia and Patient Blood Management in Hip and Knee Surgery
Authors: Spahn Donat R.
Published: July 2010

A systematic search was conducted to determine the characteristics of perioperative anemia, its association with clinical outcomes, and the effects of patient blood management interventions on these outcomes in patients undergoing major orthopedic surgery. In patients undergoing total hip or knee arthroplasty and hip fracture surgery, preoperative anemia was highly prevalent, ranging from 24 +/- 9% to 44 +/- 9%, respectively. Postoperative anemia was even more prevalent (51% and 87 +/- 10%, respectively). Perioperative anemia was associated with a blood transfusion rate of 45 +/- 25% and 44 +/- 15%, postoperative infections, poorer physical functioning and recovery, and increased length of hospital stay and mortality. Treatment of preoperative anemia with iron, with or without erythropoietin, and perioperative cell salvage decreased the need for blood transfusion and may contribute to improved patient outcomes. High-impact prospective studies are necessary to confirm these findings and establish firm clinical guidelines.
Enhancement of GABAergic Tonic Currents by Midazolam and Noradrenaline in Rat Substantia Gelatinosa Neurons In Vitro
Authors: Maeda Aiko , Katafuchi Toshihiko , Oba Yugo , Shiokawa Hiroaki , Yoshimura Megumu
Published: July 2010

Background

Substantia gelatinosa of the spinal dorsal horn is crucial for transmission and modification of noxious stimuli. Previous studies have demonstrated that intrathecal midazolam, a benzodiazepine agonist, enhanced perioperative analgesia. Not only synaptic but also extrasynaptic inhibitory currents contribute to modification of noxious stimuli. Thus, the effects of midazolam on extrasynaptic gamma-aminobutyric acid (GABA) type A receptors in substantia gelatinosa neurons and interaction with noradrenaline, a transmitter of the descending inhibitory systems, were investigated.

Methods

Using whole cell patch-clamp technique in the adult rat spinal cord slices, extrasynaptic GABAergic currents were recorded in substantia gelatinosa neurons in the presence of gabazine (1 microm), which blocked synaptic GABAergic currents, and then midazolam (5 microm) and noradrenaline (20 microm) were applied.

Results

Bath application of midazolam induced tonic outward currents in the presence of gabazine. Although the decay time of synaptic current was prolonged, neither frequency nor amplitude was affected by midazolam. In contrast, the application of noradrenaline markedly increased both frequency and amplitude of synaptic currents with a slight enhancement of tonic currents. Coapplication of noradrenaline and midazolam markedly increased tonic currents, and the increase was much greater than the sum of currents induced by noradrenaline and midazolam.

Conclusions

Midazolam had much larger effects on extrasynaptic GABA type A receptors than the synaptic receptors, suggesting a role of the enhancement of GABAergic extrasynaptic currents in the midazolam-induced analgesia. Because noradrenaline is shown to increase extrasynaptic GABA concentration, simultaneous administration of noradrenaline and midazolam may enhance the increased GABA action by midazolam, thereby resulting in an increase in tonic extrasynaptic currents.