bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of metal gates on remote phonon scattering in titanium nitride/hafnium dioxide n-channel metal–oxide–semiconductor field effect transistors–low temperature electron mobility study
Authors: Maitra Kingsuk , Frank Martin M. , Narayanan Vijay , Misra Veena , Cartier Eduard A.
Published: December 2007

We report low temperature (40–300 K) electron mobility measurements on aggressively scaled [equivalent oxide thickness (EOT)=1 nm] n-channel metal–oxide–semiconductor field effect transistors (nMOSFETs) with HfO2 gate dielectrics and metal gate electrodes (TiN). A comparison is made with conventional nMOSFETs containing HfO2 with polycrystalline Si (poly-Si) gate electrodes. No substantial change in the temperature acceleration factor is observed when poly-Si is replaced with a metal gate, showing that soft optical phonons are not significantly screened by metal gates. A qualitative argument based on an analogy between remote phonon scattering and high-resolution electron energy-loss spectroscopy (HREELS) is provided to explain the underlying physics of the observed phenomenon. It is also shown that soft optical phonon scattering is strongly damped by thin SiO2 interface layers, such that room temperature electron mobility values at EOT=1 nm become competitive with values measured in nMOSFETs with SiON gate dielectrics used in current high performance processors.
Laboratory detection of the elusive HSCO+ isomer
Authors: McCarthy M. C. , Thaddeus P.
Published: December 2007

The rotational spectrum of protonated carbonyl sulfide, HSCO+, has now been detected in the centimeter-wave band in a molecular beam by Fourier transform microwave spectroscopy. Rotational and centrifugal distortion constants have been determined from transitions in the Ka=0 ladder of the normal isotopic species, and DSCO+ and H34SCO+. HSCO+ is systematically more abundant by a factor of three than HOCS+, the isomer obtained by attaching the H+ to the other end of the molecule, which ab initio calculations long predicted to be higher in energy by 4–5kcal∕mol. Because HSCO+ is comparable in polarity to HOCS+ and is apparently more stable and because OCS is widely distributed in astronomical sources, HSCO+ is a good candidate for detection with radio telescopes.
Compositional dependence of phase structure and electrical properties in (K0.42Na0.58)NbO3-LiSbO3 lead-free ceramics
Authors: Wu Jiagang , Xiao Dingquan , Wang Yuanyu , Zhu Jianguo , Yu Ping , Jiang Yihang
Published: December 2007

( 1 − x ) ( K 0.42 Na 0.58 ) NbO 3 - x LiSbO 3  [(1−x)KNN-xLS] lead-free piezoelectric ceramics were prepared by the conventional mixed oxide method. The compositional dependence of the phase structure and the electrical properties of the ceramics were studied. A morphotropic phase boundary (MPB) between the orthorhombic and tetragonal phases was identified in the composition range of 0.04<x<0.06. The ceramics near the MPB exhibit a strong compositional dependence and enhanced piezoelectric properties. The ceramics with 5 mol. % LS exhibit enhanced electrical properties (d33∼270 pC/N, kp∼47.2%, Tc∼364 °C , To-t=35 °C, εr∼1412, tan δ∼2.8%, and Pr∼25.7 μC/cm2; Ec∼11.1 kV/cm) and possess low dielectric loss (<2%) at 10 and 100 kHz at high temperature (250–400 °C). The low dielectric loss at high temperature is very important for high-temperature application of the ceramics. The related mechanism of the enhanced electrical properties of the ceramics was also discussed. These results show that (1−x)KNN-xLS (x=0.05) ceramic is a promising lead-free piezoelectric material.
Analysis of relaxor mechanism and structural distortion for SrBi1.6Nd0.4Nb2O9 bismuth-layer-structured ceramics
Authors: Sun Lin , Chu Junhao , Feng Chude , Chen Lidong
Published: December 2007

The 1∕2{h00} and 1∕2{hk0} type superlattice reflections in the electron diffraction patterns indicate the presence of ordered polar regions in SrBi1.6Nd0.4Nb2O9. The research of x-ray Rietveld refinement and synchrotron radiation x-ray absorption fine structure spectroscopy determined that Nd3+ replaced Bi3+ in the Bi2O2 layers for SrBi1.6Nd0.4Nb2O9 and the relaxor behavior could be attributed to the disorder of Nd3+ and Bi3+ in the Bi2O2 layers. The tilting angle of NbO6 is obtained by Rietveld refinement method and the refinement result indicates that the substitution of Nd3+ for Bi3+ remarkably decrease the structural distortion, which leads to the lower transition temperature.
Submicrometer photoresponse mapping of nanowire superconducting single-photon detectors
Authors: Hadfield Robert H. , Dalgarno Paul A. , O’Connor John A. , Ramsay Euan , Warburton Richard J. , Gansen Eric J. , Baek Burm , Stevens Martin J. , Mirin Richard P. , Nam Sae Woo
Published: December 2007

We report on the photoresponse mapping of nanowire superconducting single-photon detectors using a focal spot significantly smaller than the device area (10×10μm2). Using a confocal microscope configuration and solid immersion lens, we achieve a spot size of 320nm full width at half maximum onto the device at 470nm wavelength. We compare the response maps of two devices: The higher detection efficiency device gives a uniform response, whereas the lower detection efficiency device is limited by a single defect or constriction.
Effects of NH3 plasma pretreatment on initial reactions of atomic layer deposition TaN barrier layer on SiOC dielectric
Authors: Sun Liang , Xue Yuan , Ding Shi-Jin , Guo Hao-Wen , Zhang David Wei , Wang Li-Kang
Published: December 2007

Initial reaction mechanisms of atomic layer deposition TaN barrier layer on the different group-terminated SiOC surfaces have been investigated by density functional theory. TaCl5 molecules are hardly absorbed on –CH3 terminated surfaces mostly existing in SiOC dielectrics, which retards a uniform TaN layer growth. After NH3 plasma pretreatment, –NH2 terminated surfaces enhance the chemisorptions of TaCl5 and guarantee ALD TaN reaction sequences to go ahead, thus a uniform TaN barrier layer on SiOC dielectrics can be easily synthesized. In addition, HCl molecules as by-products are easily desorbed to benefit a high quality TaN layer with low Cl contaminations.
Spatial Bloch oscillations of plasmons in nanoscale metal waveguide arrays
Authors: Lin Weihua , Zhou Xiang , Wang Guo Ping , Chan C. T.
Published: December 2007

A kind of metal waveguide array (MWGA) structures designed for observing spatial plasmon Bloch oscillations (BOs) in nanoscale is presented. The gradient of plasmon propagation constants across the MWGAs is realized by gradually changing the dielectric constant of the dielectrics filling in the guides. Plasmon BOs in the MWGAs manifest themselves as periodic breathing and transverse motion under the conditions of initial single and multiple waveguide excitations, respectively. Analytical results from the coupled wave theory are confirmed by finite-difference time-domain numerical simulations.
Habitat complexity and predation risk determine juvenile snapper (Pagrus auratus) and goatfish (Upeneichthys lineatus) behaviour and distribution
Authors: Ross P. M. , Thrush S. F. , Montgomery J. C. , Walker J. W. , Parsons D. M.
Published: December 2007

Early research into the distribution of juvenile snapper (Pagrus auratus) indicated that complex habitats were not important during early life stages. Recent studies in soft-sediment environments, however, have shown juvenile snapper to be more abundant in areas of complex habitat. No previous studies have investigated how and why this species uses both reef and soft-sediment habitats. Therefore, we examined the role of topographic complexity in influencing juvenile snapper distribution and habitat use, providing both field and laboratory evidence for the importance of complex benthic habitats for juvenile snapper and goatfish (Upeneichthys lineatus). Underwater visual censuses showed both species to be most abundant over sand flats adjacent to rocky reef habitats, a distribution that may balance the requirements of food acquisition and predator avoidance. In aquaria experiments, where juvenile snapper were given a choice between habitat with and without shelter, the use of shelter habitat increased significantly in the presence of a predatory threat. This demonstration of the use of complex habitat as shelter highlights the importance of benthic complexity for juvenile snapper and suggests that the management of essential habitats could enhance juvenile survivorship and should have an important role to play in sustainable management of exploited species.
Unusual source of food: impact of dead siblings on encapsulated embryo development of Crepipatella fecunda (Gastropoda : Calyptraeidae)
Authors: Cubillos V. M. , Chaparro O. R. , Montiel Y. A. , Véliz D.
Published: December 2007

Embryonic cannibalism has been identified in directly developing calyptraeid species through observation of the ingestion of encapsulated sibling embryos. The object of the present study was to determine the effects of experimentally induced cannibalism on larval development in encapsulated larvae of Crepipatella fecunda (a species having mixed development). The effects studied included the time of intracapsular development, protoconch size and velar characteristics of the larvae. Mortality was induced during intracapsular development through mechanical disruption (‘treatment’) of embryos. A treatment and control group of embryos from the same female were compared. Encapsulated veligers actively fed on their sacrificed congeners. Larvae hatched in less than 10 days from treated capsules and had mean shell lengths and velum areas significantly lower than those from the control, but no significant differences in cilia length. In treated capsules where the embryos underwent a slow development (>20 days), the larvae produced shells, vela and cilia larger than those of the controls. In an intermediate period of intracapsular development, the differences recorded among larval characters were not statistically significant. The results showed that: (1) the encapsulated veligers were capable of feeding on exogenous food before hatching; (2) the consumption of non-living congeners decreased the time of intracapsular development; and (3) the morphometry of the larvae hatching from treated capsules varied depending on the period of intracapsular development and seems to be adaptively stabilised towards homogeneous larval morphometry.
Mitochondrial DNA variation of the west-coast rock lobster, Jasus lalandii: marked genetic diversity differences among sampling sites
Authors: Matthee Conrad A. , Cockcroft Andrew C. , Gopal Keshni , von der Heyden Sophie
Published: December 2007

Jasus lalandii (Milne-Edwards 1837), the west-coast rock lobster, occurs in the shallow, cool–temperate waters along the south and west coasts of southern Africa. This species has a long history of intensive exploitation, which has had a significant impact on population numbers in the past. To enhance our current understanding of lobster population structuring, genetic data from the mitochondrial (mt) DNA 16S rRNA gene was generated for 235 adult individuals collected at eight sampling sites. Most individuals (59.6%) share a common haplotype and 35 unique haplotypes were dispersed throughout the range. In total, 97.2% of the variation was found among individuals within sampling sites and 2.8% was among sites. Pairwise ΦST analyses revealed shallow, yet significant structure between Hout Bay individuals and some other sampling sites. The J. lalandii haplotype network indicates a starlike structure with no geographic signal; however, genetic diversity sharply decreases towards the edges of the species distribution. The general lack of phylogeographic structure among J. lalandii populations probably results from the absence of strong barriers to larval dispersal. Based on our mtDNA data there is no justification for the recognition of separate fishing stocks, but the high genetic diversities of populations at Hout Bay and Cape Hangklip, the latter currently outside of marine protected areas, makes these populations critical to conservation efforts.
FoxO transcription factors activate Akt and attenuate insulin signaling in heart by inhibiting protein phosphatases
Authors: Ni Yan G. , Wang Na , Cao Dian J. , Sachan Nita , Morris David J. , Gerard Robert D. , Kuro-o Makoto , Rothermel Beverly A. , Hill Joseph A.
Published: December 2007

Insulin resistance and metabolic syndrome are rapidly expanding public health problems. Acting through the PI3K/Akt pathway, insulin and insulin-like growth factor-1 (IGF-1) inactivate FoxO transcription factors, a class of highly conserved proteins important in numerous physiological functions. However, even as FoxO is a downstream target of insulin, FoxO factors also control upstream signaling elements governing insulin sensitivity and glucose metabolism. Here, we report that sustained activation of either FoxO1 or FoxO3 in cardiac myocytes increases basal levels of Akt phosphorylation and kinase activity. FoxO-activated Akt directly interacts with and phosphorylates FoxO, providing feedback inhibition. We reported previously that FoxO factors attenuate cardiomyocyte calcineurin (PP2B) activity. We now show that calcineurin forms a complex with Akt and inhibition of calcineurin enhances Akt phosphorylation. In addition, FoxO activity suppresses protein phosphatase 2A (PP2A) and disrupts Akt-PP2A and Akt–calcineurin interactions. Repression of Akt–PP2A/B interactions and phosphatase activities contributes, at least in part, to FoxO-dependent increases in Akt phosphorylation and kinase activity. Resveratrol, an activator of Sirt1, increases the transcriptional activity of FoxO1 and triggers Akt phosphorylation in heart. Importantly, FoxO-mediated increases in Akt activity diminish insulin signaling, as manifested by reduced Akt phosphorylation, reduced membrane translocation of Glut4, and decreased insulin-triggered glucose uptake. Also, inactivation of the gene coding for FoxO3 enhances insulin-dependent Akt phosphorylation. Taken together, this study demonstrates that changes in FoxO activity have a dose-responsive repressive effect on insulin signaling in cardiomyocytes through inhibition of protein phosphatases, which leads to altered Akt activation, reduced insulin sensitivity, and impaired glucose metabolism.
The role of Pleistocene refugia and rivers in shaping gorilla genetic diversity in central Africa
Authors: Anthony Nicola M. , Johnson-Bawe Mireille , Jeffery Kathryn , Clifford Stephen L. , Abernethy Kate A. , Tutin Caroline E. , Lahm Sally A. , White Lee J. T. , Utley John F. , Wickings E. Jean , Bruford Michael W.
Published: December 2007

The role of Pleistocene forest refugia and rivers in the evolutionary diversification of tropical biota has been the subject of considerable debate. A range-wide analysis of gorilla mitochondrial and nuclear variation was used to test the potential role of both refugia and rivers in shaping genetic diversity in current populations. Results reveal strong patterns of regional differentiation that are consistent with refugial hypotheses for central Africa. Four major mitochondrial haplogroups are evident with the greatest divergence between eastern (A, B) and western (C, D) gorillas. Coalescent simulations reject a model of recent east–west separation during the last glacial maximum but are consistent with a divergence time within the Pleistocene. Microsatellite data also support a similar regional pattern of population genetic structure. Signatures of demographic expansion were detected in eastern lowland (B) and Gabon/Congo (D3) mitochondrial haplogroups and are consistent with a history of postglacial expansion from formerly isolated refugia. Although most mitochondrial haplogroups are regionally defined, limited admixture is evident between neighboring haplogroups. Mantel tests reveal a significant isolation-by-distance effect among western lowland gorilla populations. However, mitochondrial genetic distances also correlate with the distance required to circumnavigate intervening rivers, indicating a possible role for rivers in partitioning gorilla genetic diversity. Comparative data are needed to evaluate the importance of both mechanisms of vicariance in other African rainforest taxa.
Characterization and engineering of the bifunctional
N
- and
O
-glucosyltransferase involved in xenobiotic metabolism in plants
Authors: Brazier-Hicks Melissa , Offen Wendy A. , Gershater Markus C. , Revett Timothy J. , Lim Eng-Kiat , Bowles Dianna J. , Davies Gideon J. , Edwards Robert
Published: December 2007

The glucosylation of pollutant and pesticide metabolites in plants controls their bioactivity and the formation of subsequent chemical residues. The model plant
Arabidopsis thaliana
contains >100 glycosyltransferases (GTs) dedicated to small-molecule conjugation and, whereas 44 of these enzymes catalyze the
O
-glucosylation of chlorinated phenols, only one, UGT72B1, shows appreciable
N
-glucosylating activity toward chloroanilines. UGT72B1 is a bifunctional
O
-glucosyltransferase (OGT) and
N
-glucosyltransferase (NGT). To investigate this unique dual activity, the structure of the protein was solved, at resolutions up to 1.45 Å, in various forms including the Michaelis complex with intact donor analog and trichlorophenol acceptor. The catalytic mechanism and basis for
O/N
specificity was probed by mutagenesis and domain shuffling with an orthologous enzyme from
Brassica napus
(
Bn
UGT), which possesses only OGT activity. Mutation of
Bn
UGT at just two positions (D312N and F315Y) installed high levels of NGT activity. Molecular modeling revealed the connectivity of these residues to H19 on UGT72B1, with its mutagenesis exclusively defining NGT activity in the
Arabidopsis
enzyme. These results shed light on the conjugation of nonnatural substrates by plant GTs, highlighting the catalytic plasticity of this enzyme class and the ability to engineer unusual and desirable transfer to nitrogen-based acceptors.
Fat and Expanded act in parallel to regulate growth through Warts
Authors: Feng Yongqiang , Irvine Kenneth D.
Published: December 2007

The conserved
Drosophila
tumor suppressors Fat and Expanded have both recently been implicated in regulating the activity of the Warts tumor suppressor. However, there has been disagreement as to the nature of the links among Fat, Expanded, and Warts and the significance of these links to growth control. We report here that mutations in either
expanded
or
fat
can be rescued to viability simply by overexpressing Warts, indicating that their essential function is their influence on Warts rather than reported effects on endocytosis or other pathways. These rescue experiments also separate the transcriptional from the planar cell polarity branches of Fat signaling and reveal that Expanded does not directly affect polarity. We also investigate the relationship between
expanded
and
fat
and show, contrary to prior reports, that they have additive effects on imaginal disk growth and development. Although mutation of
fat
can cause partial loss of Expanded protein from the membrane, mutation of
fat
promotes growth even when Expanded is overexpressed and accumulates at its normal subapical location. These observations argue against recent proposals that Fat acts simply as a receptor for the Hippo signaling pathway and instead support the proposal that Fat and Expanded can act in parallel to regulate Warts through distinct mechanisms.
Hemopressin is an inverse agonist of CB
1
cannabinoid receptors
Authors: Heimann Andrea S. , Gomes Ivone , Dale Camila S. , Pagano Rosana L. , Gupta Achla , de Souza Laura L. , Luchessi Augusto D. , Castro Leandro M. , Giorgi Renata , Rioli Vanessa , Ferro Emer S. , Devi Lakshmi A.
Published: December 2007

To date, the endogenous ligands described for cannabinoid receptors have been derived from membrane lipids. To identify a peptide ligand for CB
1
cannabinoid receptors, we used the recently described conformation-state sensitive antibodies and screened a panel of endogenous peptides from rodent brain or adipose tissue. This led to the identification of hemopressin (PVNFKFLSH) as a peptide ligand that selectively binds CB
1
cannabinoid receptors. We find that hemopressin is a CB
1
receptor-selective antagonist, because it is able to efficiently block signaling by CB
1
receptors but not by other members of family A G protein-coupled receptors (including the closely related CB
2
receptors). Hemopressin also behaves as an inverse agonist of CB
1
receptors, because it is able to block the constitutive activity of these receptors to the same extent as its well characterized antagonist, rimonabant. Finally, we examine the activity of hemopressin
in vivo
using different models of pain and find that it exhibits antinociceptive effects when administered by either intrathecal, intraplantar, or oral routes, underscoring hemopressin's therapeutic potential. These results represent a demonstration of a peptide ligand for CB
1
cannabinoid receptors that also exhibits analgesic properties. These findings are likely to have a profound impact on the development of novel therapeutics targeting CB
1
receptors.
Sickle cell vasoocclusion and rescue in a microfluidic device
Authors: Higgins J. M. , Eddington D. T. , Bhatia S. N. , Mahadevan L.
Published: December 2007

The pathophysiology of sickle cell disease is complicated by the multiscale processes that link the molecular genotype to the organismal phenotype: hemoglobin polymerization occurring in milliseconds, microscopic cellular sickling in a few seconds or less [Eaton WA, Hofrichter J (1990)
Adv Protein Chem
40:63–279], and macroscopic vessel occlusion over a time scale of minutes, the last of which is necessary for a crisis [Bunn HF (1997)
N Engl J Med
337:762–769]. Using a minimal but robust artificial microfluidic environment, we show that it is possible to evoke, control, and inhibit the collective vasoocclusive or jamming event in sickle cell disease. We use a combination of geometric, physical, chemical, and biological means to quantify the phase space for the onset of a jamming event, as well as its dissolution, and find that oxygen-dependent sickle hemoglobin polymerization and melting alone are sufficient to recreate jamming and rescue. We further show that a key source of the heterogeneity in occlusion arises from the slow collective jamming of a confined, flowing suspension of soft cells that change their morphology and rheology relatively quickly. Finally, we quantify and investigate the effects of small-molecule inhibitors of polymerization and therapeutic red blood cell exchange on this dynamical process. Our experimental study integrates the dynamics of collective processes associated with occlusion at the molecular, polymer, cellular, and tissue level; lays the foundation for a quantitative understanding of the rate-limiting processes; and provides a potential tool for optimizing and individualizing treatment, and identifying new therapies.
The α10 nicotinic acetylcholine receptor subunit is required for normal synaptic function and integrity of the olivocochlear system
Authors: Vetter Douglas E. , Katz Eleonora , Maison Stéphane F. , Taranda Julián , Turcan Sevin , Ballestero Jimena , Liberman M. Charles , Elgoyhen A. Belén , Boulter Jim
Published: December 2007

Although homomeric channels assembled from the α9 nicotinic acetylcholine receptor (nAChR) subunit are functional
in vitro
, electrophysiological, anatomical, and molecular data suggest that native cholinergic olivocochlear function is mediated via heteromeric nAChRs composed of both α9 and α10 subunits. To gain insight into α10 subunit function
in vivo
, we examined olivo cochlear innervation and function in α
10
null-mutant mice. Electrophysiological recordings from postnatal (P) days P8–9 inner hair cells revealed ACh-gated currents in α
10
+/+
and α
10
+/−
mice, with no detectable responses to ACh in α
10
−/−
mice. In contrast, a proportion of α
10
−/−
outer hair cells showed small ACh-evoked currents. In α
10
−/−
mutant mice, olivocochlear fiber stimulation failed to suppress distortion products, suggesting that the residual α9 homomeric nAChRs expressed by outer hair cells are unable to transduce efferent signals
in vivo
. Finally, α
10
−/−
mice exhibit both an abnormal olivocochlear morphology and innervation to outer hair cells and a highly disorganized efferent innervation to the inner hair cell region. Our results demonstrate that α
9
−/−
and α
10
−/−
mice have overlapping but nonidentical phenotypes. Moreover, α10 nAChR subunits are required for normal olivocochlear activity because α9 homomeric nAChRs do not support maintenance of normal olivocochlear innervation or function in α
10
−/−
mutant mice.
Melanocortin-2 receptor accessory protein MRAP forms antiparallel homodimers
Authors: Sebag Julien A. , Hinkle Patricia M.
Published: December 2007

The melanocortin-2 (MC2) receptor accessory protein (MRAP) is required for trafficking of the G protein-coupled MC2 receptor to the plasma membrane. The mechanism of action and structure of MRAP, which has a single transmembrane domain, are unknown. Here, we show that MRAP displays a previously uncharacterized topology. Epitopes on both the N- and C-terminal ends of MRAP were localized on the external face of CHO cells at comparable levels. Using antibodies raised against N- and C-terminal MRAP peptides, we demonstrated that both ends of endogenous MRAP face the outside in adrenal cells. Nearly half of MRAP was glycosylated at the single endogenous N-terminal glycosylation site, and over half was glycosylated when the natural glycosylation site was replaced by one in the C-terminal domain. A mutant MRAP with potential glycosylation sites on both sides of the membrane was singly but not doubly glycosylated, suggesting that MRAP is not monotopic. Coimmunoprecipitation of differentially tagged MRAPs established that MRAP is a dimer. By selectively immunoprecipitating cell surface MRAP in one or the other orientation, we showed that MRAP homodimers are antiparallel and form a stable complex with MC2 receptor. In the absence of MRAP, MC2 receptor was trapped in the endoplasmic reticulum, but with MRAP, the MC2 receptor was glycosylated and localized on the plasma membrane, where it signaled in response to ACTH. MRAP acted specifically, because it did not increase surface expression of other melanocortin, β2-adrenergic, or TSH-releasing hormone receptors. MRAP is the first eukaryotic membrane protein identified with an antiparallel homodimeric structure.
A universal driver of macroevolutionary change in the size of marine phytoplankton over the Cenozoic
Authors: Finkel Z. V. , Sebbo J. , Feist-Burkhardt S. , Irwin A. J. , Katz M. E. , Schofield O. M. E. , Young J. R. , Falkowski P. G.
Published: December 2007

The size structure of phytoplankton assemblages strongly influences energy transfer through the food web and carbon cycling in the ocean. We determined the macroevolutionary trajectory in the median size of dinoflagellate cysts to compare with the macroevolutionary size change in other plankton groups. We found the median size of the dinoflagellate cysts generally decreases through the Cenozoic. Diatoms exhibit an extremely similar pattern in their median size over time, even though species diversity of the two groups has opposing trends, indicating that the macroevolutionary size change is an active response to selection pressure rather than a passive response to changes in diversity. The changes in the median size of dinoflagellate cysts are highly correlated with both deep ocean temperatures and the thermal gradient between the surface and deep waters, indicating the magnitude and frequency of nutrient availability may have acted as a selective factor in the macroevolution of cell size in the plankton. Our results suggest that climate, because it affects stratification in the ocean, is a universal abiotic driver that has been responsible for macroevolutionary changes in the size structure of marine planktonic communities over the past 65 million years of Earth's history.
Positive selection at the protein network periphery: Evaluation in terms of structural constraints and cellular context
Authors: Kim Philip M. , Korbel Jan O. , Gerstein Mark B.
Published: December 2007

Because of recent advances in genotyping and sequencing, human genetic variation and adaptive evolution in the primate lineage have become major research foci. Here, we examine the relationship between genetic signatures of adaptive evolution and network topology. We find a striking tendency of proteins that have been under positive selection (as compared with the chimpanzee) to be located at the periphery of the interaction network. Our results are based on the analysis of two types of genome evolution, both in terms of intra- and interspecies variation. First, we looked at single-nucleotide polymorphisms and their fixed variants, single-nucleotide differences in the human genome relative to the chimpanzee. Second, we examine fixed structural variants, specifically large segmental duplications and their polymorphic precursors known as copy number variants. We propose two complementary mechanisms that lead to the observed trends. First, we can rationalize them in terms of constraints imposed by protein structure: We find that positively selected sites are preferentially located on the exposed surface of proteins. Because central network proteins (hubs) are likely to have a larger fraction of their surface involved in interactions, they tend to be constrained and under negative selection. Conversely, we show that the interaction network roughly maps to cellular organization, with the periphery of the network corresponding to the cellular periphery (i.e., extracellular space or cell membrane). This suggests that the observed positive selection at the network periphery may be due to an increase of adaptive events on the cellular periphery responding to changing environments.
Hydrogen sulfide increases thermotolerance and lifespan inCaenorhabditis elegans
Authors: Miller Dana L. , Roth Mark B.
Published: December 2007

Hydrogen sulfide (H2S) is naturally produced in animal cells. Exogenous H2S has been shown to effect physiological changes that improve the capacity of mammals to survive in otherwise lethal conditions. However, the mechanisms required for such alterations are unknown. We investigated the physiological response ofCaenorhabditis elegansto H2S to elucidate the molecular mechanisms of H2S action. Here we show that nematodes exposed to H2S are apparently healthy and do not exhibit phenotypes consistent with metabolic inhibition. Instead, animals exposed to H2S are thermotolerant and long-lived. These phenotypes require SIR-2.1 activity but are genetically independent of the insulin signaling pathway, mitochondrial dysfunction, and caloric restriction. These studies suggest that SIR-2.1 activity may translate environmental change into physiological alterations that improve survival. It is interesting to consider the possibility that the mechanisms by which H2S increases thermotolerance and lifespan in nematodes are conserved and that studies usingC. elegansmay help explain the beneficial effects observed in mammals exposed to H2S.
Mechanisms for segregating T cell receptor and adhesion molecules during immunological synapse formation in Jurkat T cells
Authors: Kaizuka Yoshihisa , Douglass Adam D. , Varma Rajat , Dustin Michael L. , Vale Ronald D.
Published: December 2007

T cells interacting with antigen-presenting cells (APCs) form an “immunological synapse” (IS), a bull's-eye pattern composed of a central supramolecular activation cluster enriched with T cell receptors (TCRs) surrounded by a ring of adhesion molecules (a peripheral supramolecular activation cluster). The mechanism responsible for segregating TCR and adhesion molecules remains poorly understood. Here, we show that immortalized Jurkat T cells interacting with a planar lipid bilayer (mimicking an APC) will form an IS, thereby providing an accessible model system for studying the cell biological processes underlying IS formation. We found that an actin-dependent process caused TCR and adhesion proteins to cluster at the cell periphery, but these molecules appeared to segregate from one another at the earliest stages of microdomain formation. The TCR and adhesion microdomains attached to actin and were carried centripetally by retrograde flow. However, only the TCR microdomains penetrated into the actin-depleted cell center, whereas the adhesion microdomains appeared to be unstable without an underlying actin cytoskeleton. Our results reveal that TCR and adhesion molecules spatially partition from one another well before the formation of a mature IS and that differential actin interactions help to shape and maintain the final bull's-eye pattern of the IS.
Mapping dynamic protein interactions in MAP kinase signaling using live-cell fluorescence fluctuation spectroscopy and imaging
Authors: Slaughter Brian D. , Schwartz Joel W. , Li Rong
Published: December 2007

Fluorescence correlation spectroscopy (FCS), fluorescence cross-correlation spectroscopy (FCCS), and photon counting histograms (PCH) are fluctuation methods that emerged recently as potentially useful tools for obtaining parameters of molecular dynamics, interactions, and oligomerization
in vivo
. Here, we report the successful implementation of FCS, FCCS, and PCH in live yeast cells using fluorescent protein-tagged proteins expressed from their native chromosomal loci, examining cytosolic dynamics and interactions among components of the mitogen activated protein kinase (MAPK) cascade, a widely occurring signaling motif, in response to mating pheromone. FCS analysis detailed the diffusion characteristics and mobile concentrations of MAPK proteins. FCCS analysis using EGFP and mCherry-tagged protein pairs observed the interactions of Ste7 (MAPK kinase) with the MAPKs, Fus3 or Kss1, and of the scaffold protein, Ste5, with Ste7 and Ste11 (MAPK kinase kinase) in the cytosol, providing
in vivo
constants of their binding equilibrium. The interaction of Ste5 with Fus3 in the cytosol was below the limit of detection, suggesting a weak interaction, if it exists, with
K
d
>400–500 nM. Using PCH, we show that cytosolic Ste5 were mostly monomers. Artificial dimerization of Ste5, as confirmed by PCH, using a dimerizing tag, stimulated the interaction between Ste5 and Fus3. Native Ste5 was found to bind Fus3 preferentially at the cortex in pheromone-treated cells, as detected by fluorescence resonance energy transfer (FRET). These results provide a quantitative spatial map of MAPK complexes
in vivo
and directly support the model that membrane association and regulation of the Ste5 scaffold are critical steps in MAPK activation.
Activation Outcomes Induced in Naïve CD8 T-Cells by Macrophages Primed via “Phagocytic” and Nonphagocytic Pathways
Authors: Olazabal Isabel María , Martín-Cofreces Noa Beatriz , Mittelbrunn María , Martínez del Hoyo Gloria , Alarcón Balbino , Sánchez-Madrid Francisco
Published: December 2007

The array of phagocytic receptors expressed by macrophages make them very efficient at pathogen clearance, and the phagocytic process links innate with adaptive immunity. Primary macrophages modulate antigen cross-presentation and T-cell activation. We assessed ex vivo the putative role of different phagocytic receptors in immune synapse formation with CD8 naïve T-cells from OT-I transgenic mice and compared this with the administration of antigen as a soluble peptide. Macrophages that have phagocytosed antigen induce T-cell microtubule-organizing center and F-actin cytoskeleton relocalization to the contact site, as well as the recruitment of proximal T-cell receptor signals such as activated Vav1 and PKCθ. At the same doses of loaded antigen (1 μM), “phagocytic” macrophages were more efficient than peptide-antigen–loaded macrophages at forming productive immune synapses with T-cells, as indicated by active T-cell TCR/CD3 conformation, LAT phosphorylation, IL-2 production, and T-cell proliferation. Similar T-cell proliferation efficiency was obtained when low doses of soluble peptide (3–30 nM) were loaded on macrophages. These results suggest that the pathway used for antigen uptake may modulate the antigen density presented on MHC-I, resulting in different signals induced in naïve CD8 T-cells, leading either to CD8 T-cell activation or anergy.
Regulation of Tsg101 Expression by the Steadiness Box: A Role of Tsg101-associated Ligase
Authors: McDonald Bethan , Martin-Serrano Juan
Published: December 2007

As part of the endosomal sorting complex required for transport (ESCRT) machinery, Tsg101 is essential for endosomal sorting, membrane receptor degradation and the final stages of cytokinesis. Depletion or overproduction of the protein can cause disruption of these vital processes and results in severe consequences for the cell. Tsg101 expression is thus controlled posttranslationally within a narrow range and this autoregulation has been mapped to the C-terminus of the protein. Here we elucidate further the mechanisms of this regulation and describe a novel function of Tsg101-associated ligase (Tal) in mediating this control. We show that Tal polyubiquitinates lysine residues in the C-terminus of uncomplexed Tsg101, resulting in proteasomal degradation. However, accessibility to these lysines is prevented by the presence of the other ESCRT-I proteins. We show that VPS28 is a limiting factor, and consequently Tsg101 expression surplus to ESCRT-I function is vulnerable to degradation. The role of Tal in the regulation of Tsg101 steady-state control is highlighted when Tsg101 is overexpressed; however, our data also suggest that additional ligases regulate Tsg101 expression under normal conditions. Lastly, we demonstrate that while the C-terminal lysines are targets for polyubiquitination, they are not required for any additional function necessary for ESCRT activity.
Landscape genetics and the spatial distribution of chronic wasting disease
Authors: Blanchong Julie A , Samuel Michael D , Scribner Kim T , Weckworth Byron V , Langenberg Julia A , Filcek Kristine B
Published: December 2007

Predicting the spread of wildlife disease is critical for identifying populations at risk, targeting surveillance and designing proactive management programmes. We used a landscape genetics approach to identify landscape features that influenced gene flow and the distribution of chronic wasting disease (CWD) in Wisconsin white-tailed deer. CWD prevalence was negatively correlated with genetic differentiation of study area deer from deer in the area of disease origin (core-area). Genetic differentiation was greatest, and CWD prevalence lowest, in areas separated from the core-area by the Wisconsin River, indicating that this river reduced deer gene flow and probably disease spread. Features of the landscape that influence host dispersal and spatial patterns of disease can be identified based on host spatial genetic structure. Landscape genetics may be used to predict high-risk populations based on their genetic connection to infected populations and to target disease surveillance, control and preventative activities.
Rapid facial mimicry in orangutan play
Authors: Davila Ross Marina , Menzler Susanne , Zimmermann Elke
Published: December 2007

Emotional contagion enables individuals to experience emotions of others. This important empathic phenomenon is closely linked to facial mimicry, where facial displays evoke the same facial expressions in social partners. In humans, facial mimicry can be voluntary or involuntary, whereby its latter mode can be processed as rapid as within or at 1 s. Thus far, studies have not provided evidence of rapid involuntary facial mimicry in animals.

This study assessed whether rapid involuntary facial mimicry is present in orangutans (
Pongo pygmaeus; N
=25) for their open-mouth faces (OMFs) during everyday dyadic play. Results clearly indicated that orangutans rapidly mimicked OMFs of their playmates within or at 1 s. Our study revealed the first evidence on rapid involuntary facial mimicry in non-human mammals. This finding suggests that fundamental building blocks of positive emotional contagion and empathy that link to rapid involuntary facial mimicry in humans have homologues in non-human primates.
Social learning of novel route preferences in adult humans
Authors: Reader Simon M , Bruce Matthew J , Rebers Susanne
Published: December 2007

Non-human animals can acquire novel route preferences by following knowledgeable individuals. Such socially learned route preferences can be stably maintained over multiple transmission episodes, sometimes forming long-lived traditions. In humans, preferences for familiar routes or heavily used worn trails over unfamiliar ones have been described in various contexts. However, social learning of route preferences has not been experimentally demonstrated in humans. Here, we demonstrate that social learning and tradition influence route choice. We led adult male and female participants into a room by one of two routes. Participants followed the demonstrated route choices, and later remembered and preferred this choice even when determinably suboptimal (i.e. longer and not preferred by control participants) or when the choice was indicated as arbitrary (the demonstrator took one route to retrieve a poster that had ostensibly fallen). Moreover, route preferences were stably maintained over multiple transmission episodes. We suggest that simple social learning processes, often neglected in human and primate research, can result in long-lived route preferences that may influence a range of additional behaviour patterns.
Number and arrangement of extraocular muscles in primitive gnathostomes: evidence from extinct placoderm fishes
Authors: Young Gavin C
Published: December 2007

Exceptional braincase preservation in some Devonian placoderm fishes permits interpretation of muscles and cranial nerves controlling eye movement. Placoderms are the only jawed vertebrates with anterior/posterior obliques as in the jawless lamprey, but with the same function as the superior/inferior obliques of other gnathostomes. Evidence of up to seven extraocular muscles suggests that this may be the primitive number for jawed vertebrates. Two muscles innervated by cranial nerve 6 suggest homologies with lampreys and tetrapods. If the extra muscle acquired by gnathostomes was the internal rectus, Devonian fossils show that it had a similar insertion above and behind the eyestalk in both placoderms and basal osteichthyans.
Growth model for arbuscular mycorrhizal fungi
Authors: Schnepf A , Roose T , Schweiger P
Published: December 2007

In order to quantify the contribution of arbuscular mycorrhizal (AM) fungi to plant phosphorus nutrition, the development and extent of the external fungal mycelium and its nutrient uptake capacity are of particular importance. We develop and analyse a model of the growth of AM fungi associated with plant roots, suitable for describing mechanistically the effects of the fungi on solute uptake by plants. The model describes the development and distribution of the fungal mycelium in soil in terms of the creation and death of hyphae, tip–tip and tip–hypha anastomosis, and the nature of the root–fungus interface. It is calibrated and corroborated using published experimental data for hyphal length densities at different distances away from root surfaces. A good agreement between measured and simulated values was found for three fungal species with different morphologies:Scutellospora calospora(Nicol. & Gerd.) Walker & Sanders;Glomussp.; andAcaulospora laevisGerdemann & Trappe associated withTrifolium subterraneumL. The model and findings are expected to contribute to the quantification of the role of AM fungi in plant mineral nutrition and the interpretation of different foraging strategies among fungal species.
Correlating cell morphology and osteoid mineralization relative to strain profile for bone tissue engineering applications
Authors: Wood M.A , Yang Y , Baas E , Meredith D.O , Richards R.G , Kuiper J.H , El Haj A.J
Published: December 2007

A number of bone tissue engineering strategies use porous three-dimensional scaffolds in combination with bioreactor regimes. The ability to understand cell behaviour relative to strain profile will allow for the effects of mechanical conditioning in bone tissue engineering to be realized and optimized. We have designed a model system to investigate the effects of strain profile on bone cell behaviour. This simplified model has been designed with a view to providing insight into the types of strain distribution occurring across a single pore of a scaffold subjected to perfusion–compression conditioning. Local strains were calculated at the surface of the pore model using finite-element analysis. Scanning electron microscopy was used in secondary electron mode to identify cell morphology within the pore relative to local strains, while backscattered electron detection in combination with X-ray microanalysis was used to identify calcium deposition. Morphology was altered according to the level of strain experienced by bone cells, where cells subjected to compressive strains (up to 0.61%) appeared extremely rounded while those experiencing zero and tensile strain (up to 0.81%) were well spread. Osteoid mineralization was similarly shown to be dose dependent with respect to substrate strain within the pore model, with the highest level of calcium deposition identified in the intermediate zones of tension/compression.
A comparative study of the reported performance of
ab initio
protein structure prediction algorithms
Authors: Helles Glennie
Published: December 2007

Protein structure prediction is one of the major challenges in bioinformatics today. Throughout the past five decades, many different algorithmic approaches have been attempted, and although progress has been made the problem remains unsolvable even for many small proteins. While the general objective is to predict the three-dimensional structure from primary sequence, our current knowledge and computational power are simply insufficient to solve a problem of such high complexity.

Some prediction algorithms do, however, appear to perform better than others, although it is not always obvious which ones they are and it is perhaps even less obvious why that is. In this review, the reported performance results from 18 different recently published prediction algorithms are compared. Furthermore, the general algorithmic settings most likely responsible for the difference in the reported performance are identified, and the specific settings of each of the 18 prediction algorithms are also compared.

The average normalized r.m.s.d. scores reported range from 11.17 to 3.48. With a performance measure including both r.m.s.d. scores and CPU time, the currently best-performing prediction algorithm is identified to be the I-TASSER algorithm. Two of the algorithmic settings—protein representation and fragment assembly—were found to have definite positive influence on the running time and the predicted structures, respectively. There thus appears to be a clear benefit from incorporating this knowledge in the design of new prediction algorithms.
Boltzmann, Lotka and Volterra and spatial structural evolution: an integrated methodology for some dynamical systems
Authors: Wilson Alan
Published: December 2007

It is shown that Boltzmann's methods from statistical physics can be applied to a much wider range of systems, and in a variety of disciplines, than has been commonly recognized. A similar argument can be applied to the ecological models of Lotka and Volterra. Furthermore, it is shown that the two methodologies can be applied in combination to generate the Boltzmann, Lotka and Volterra (BLV) models. These techniques enable both spatial interaction and spatial structural evolution to be modelled, and it is argued that they potentially provide a much richer modelling methodology than that currently used in the analysis of ‘scale-free’ networks.