bluuebunny/crossref_metadata_2025 huggingface dataset:
Persistent two-dimensional growth of (110) manganite films
Authors: Bachelet R. , Pesquera D. , Herranz G. , Sánchez F. , Fontcuberta J.
Published: September 2010

We have deposited La2/3Sr1/3MnO3(110) thin films by pulsed laser deposition, changing the ratio of surface diffusivity to deposition flux (D/F) by adjusting substrate temperature and laser repetition rate. We show that persistent two-dimensional layer-by-layer growth, at least up to 30 nm, can be achieved by exploiting diffusion-limited growth (small D/F ratio), giving rise to atomically-flat epitaxial films. The results are of interest in spintronic applications such as tunnel magnetoresistance devices, and the approach presented here can be extended to other functional films of high surface energy.
The effect of N-polar GaN domains as Ohmic contacts
Authors: Xie J. , Mita S. , Collazo R. , Rice A. , Tweedie J. , Sitar Z.
Published: September 2010

Transfer line method measurements revealed that if the Ohmic contact regions were replaced by N-polar GaN, the contact resistance could be reduced from 0.71 Ω mm (or ρc=4×10−6 Ω cm2) to 0.24 Ω mm for a ∼200 nm thick Si-doped GaN layer. The reduction in contact resistance was largely due to the ∼1019 cm−3 free carriers in N-polar source/drain regions as measured by Hall effect. Secondary ion mass spectroscopy confirmed that oxygen doping in the N-polar region was more than three orders of magnitude greater than that in the Ga-polar region that was explained by the large difference in the adsorption energy for oxygen (∼1.3 eV/atom) between the N- and Ga-polar surfaces during the metalorganic chemical vapor deposition.
Response of Colorado River runoff to dust radiative forcing in snow
Authors: Painter Thomas H. , Deems Jeffrey S. , Belnap Jayne , Hamlet Alan F. , Landry Christopher C. , Udall Bradley
Published: September 2010

The waters of the Colorado River serve 27 million people in seven states and two countries but are overallocated by more than 10% of the river’s historical mean. Climate models project runoff losses of 7–20% from the basin in this century due to human-induced climate change. Recent work has shown however that by the late 1800s, decades prior to allocation of the river’s runoff in the 1920s, a fivefold increase in dust loading from anthropogenically disturbed soils in the southwest United States was already decreasing snow albedo and shortening the duration of snow cover by several weeks. The degree to which this increase in radiative forcing by dust in snow has affected timing and magnitude of runoff from the Upper Colorado River Basin (UCRB) is unknown. Here we use the Variable Infiltration Capacity model with postdisturbance and predisturbance impacts of dust on albedo to estimate the impact on runoff from the UCRB across 1916–2003. We find that peak runoff at Lees Ferry, Arizona has occurred on average 3 wk earlier under heavier dust loading and that increases in evapotranspiration from earlier exposure of vegetation and soils decreases annual runoff by more than 1.0 billion cubic meters or ∼5% of the annual average. The potential to reduce dust loading through surface stabilization in the deserts and restore more persistent snow cover, slow runoff, and increase water resources in the UCRB may represent an important mitigation opportunity to reduce system management tensions and regional impacts of climate change.
Behavioral dimensions of food security
Authors: Timmer C. Peter
Published: September 2010

The empirical regularities of behavioral economics, especially loss aversion, time inconsistency, other-regarding preferences, herd behavior, and framing of decisions, present significant challenges to traditional approaches to food security. The formation of price expectations, hoarding behavior, and welfare losses from highly unstable food prices all depends on these behavioral regularities. At least when they are driven by speculative bubbles, market prices for food staples (and especially for rice, the staple food of over 2 billion people) often lose their efficiency properties and the normative implications assigned by trade theory. Theoretical objections to government efforts to stabilize food prices, thus, have reduced saliency, although operational, financing, and implementation problems remain important, even critical. The experience of many Asian governments in stabilizing their rice prices over the past half century is drawn on in this paper to illuminate both the political mandates stemming from behavioral responses of citizens and operational problems facing efforts to stabilize food prices. Despite the theoretical problems with free markets, the institutional role of markets in economic development remains. All policy instruments must operate compatibly with prices in markets. During policy design, especially for policies designed to alter market prices, incentive structures need to be compatible with respect to both government capacity (bureaucratic and budgetary) and empirical behavior on the part of market participants who will respond to planned policy changes. A new theoretical underpinning to political economy analysis is needed that incorporates this behavioral perspective, with psychology, sociology, and anthropology all likely to make significant contributions.
The G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) facilitates tumor development by serving as an extracellular pH sensor
Authors: Ihara Yuichiro , Kihara Yasuyuki , Hamano Fumie , Yanagida Keisuke , Morishita Yasuyuki , Kunita Akiko , Yamori Takao , Fukayama Masashi , Aburatani Hiroyuki , Shimizu Takao , Ishii Satoshi
Published: September 2010

Tumors often are associated with a low extracellular pH, which induces a variety of cellular events. However, the mechanisms by which tumor cells recognize and react to the acidic environment have not been fully elucidated. T-cell death-associated gene 8 (TDAG8) is an extracellular pH-sensing G protein-coupled receptor that is overexpressed in various tumors and tumor cell lines. In this report, we show that TDAG8 on the surface of tumor cells facilitates tumor development by sensing the acidic environment. Overexpression of TDAG8 in mouse Lewis lung carcinoma (LLC) cells enhanced tumor development in animal models and rendered LLC cells resistant to acidic culture conditions by increasing activation of protein kinase A and extracellular signal-regulated kinase in vitro. Moreover, shRNA-mediated knockdown of endogenous TDAG8 in NCI-H460 human non-small cell lung cancer cells reduced cell survival in an acidic environment in vitro as well as tumor development in vivo. Microarray analyses of tumor-containing lung tissues of mice injected with TDAG8-expressing LLC cells revealed up-regulation of genes related to cell growth and glycolysis. These results support the hypothesis that TDAG8 enhances tumor development by promoting adaptation to the acidic environment to enhance cell survival/proliferation. TDAG8 may represent a therapeutic target for arresting tumor growth.
Membrane sphingolipids as essential molecular signals for
Bacteroides
survival in the intestine
Authors: An Dingding , Na Chongzheng , Bielawski Jacek , Hannun Yusuf A. , Kasper Dennis L.
Published: September 2010

As predominant intestinal symbiotic bacteria,
Bacteroides
are essential in maintaining the health of the normal mammalian host; in return, the host provides a niche with plentiful nutrients for the symbionts. However, the intestinal environment is replete with chemical, physical, and biological challenges that require mechanisms for prompt and adept sensing of and responses to stress if the bacteria are to survive. Herein we propose that to persist in the intestine
Bacteroides
take advantage of their unusual bacterial sphingolipids to mediate signaling pathways previously known to be available only to higher organisms. Sphingolipids convey diverse signal transduction and stress response pathways and have profound physiological impacts demonstrated in a variety of eukaryotic cell types. We propose a mechanism by which the formation of specific sphingolipid membrane microdomains initiates signaling cascades that facilitate survival strategies within the bacteria. Our preliminary data suggest that sphingolipid signaling plays an important role in
Bacteroides
physiology, enabling these bacteria to persist in the intestine and to perform other functions related to symbiosis.
Stealth predation and the predatory success of the invasive ctenophore
Mnemiopsis leidyi
Authors: Colin Sean P. , Costello John H. , Hansson Lars J. , Titelman Josefin , Dabiri John O.
Published: September 2010

In contrast to higher metazoans such as copepods and fish, ctenophores are a basal metazoan lineage possessing a relatively narrow set of sensory-motor capabilities. Yet lobate ctenophores can capture prey at rates comparable to sophisticated predatory copepods and fish, and they are capable of altering the composition of coastal planktonic communities. Here, we demonstrate that the predatory success of the lobate ctenophore
Mnemiopsis leidyi
lies in its use of cilia to generate a feeding current that continuously entrains large volumes of fluid, yet is virtually undetectable to its prey. This form of stealth predation enables
M. leidyi
to feed as a generalist predator capturing prey, including microplankton (approximately 50 μm), copepods (approximately 1 mm), and fish larvae (>3 mm). The efficacy and versatility of this stealth feeding mechanism has enabled
M. leidyi
to be notoriously destructive as a predator and successful as an invasive species.
Animal cells connected by nanotubes can be electrically coupled through interposed gap-junction channels
Authors: Wang Xiang , Veruki Margaret Lin , Bukoreshtliev Nickolay V. , Hartveit Espen , Gerdes Hans-Hermann
Published: September 2010

Tunneling nanotubes (TNTs) are recently discovered conduits for a previously unrecognized form of cell-to-cell communication. These nanoscale, F-actin–containing membrane tubes connect cells over long distances and facilitate the intercellular exchange of small molecules and organelles. Using optical membrane-potential measurements combined with mechanical stimulation and whole-cell patch-clamp recording, we demonstrate that TNTs mediate the bidirectional spread of electrical signals between TNT-connected normal rat kidney cells over distances of 10 to 70 μm. Similar results were obtained for other cell types, suggesting that electrical coupling via TNTs may be a widespread characteristic of animal cells. Strength of electrical coupling depended on the length and number of TNT connections. Several lines of evidence implicate a role for gap junctions in this long-distance electrical coupling: punctate connexin 43 immunoreactivity was frequently detected at one end of TNTs, and electrical coupling was voltage-sensitive and inhibited by meclofenamic acid, a gap-junction blocker. Cell types lacking gap junctions did not show TNT-dependent electrical coupling, which suggests that TNT-mediated electrical signals are transmitted through gap junctions at a membrane interface between the TNT and one cell of the connected pair. Measurements of the fluorescent calcium indicator X-rhod-1 revealed that TNT-mediated depolarization elicited threshold-dependent, transient calcium signals in HEK293 cells. These signals were inhibited by the voltage-gated Ca2+channel blocker mibefradil, suggesting they were generated via influx of calcium through low voltage-gated Ca2+channels. Taken together, our data suggest a unique role for TNTs, whereby electrical synchronization between distant cells leads to activation of downstream target signaling.
Competition–defense tradeoffs and the maintenance of plant diversity
Authors: Viola David V. , Mordecai Erin A. , Jaramillo Alejandra G. , Sistla Seeta A. , Albertson Lindsey K. , Gosnell J. Stephen , Cardinale Bradley J. , Levine Jonathan M.
Published: September 2010

Ecologists have long observed that consumers can maintain species diversity in communities of their prey. Many theories of how consumers mediate diversity invoke a tradeoff between species’ competitive ability and their ability to withstand predation. Under this constraint, the best competitors are also most susceptible to consumers, preventing them from excluding other species. However, empirical evidence for competition–defense tradeoffs is limited and, as such, the mechanisms by which consumers regulate diversity remain uncertain. We performed a meta-analysis of 36 studies to evaluate the prevalence of the competition–defense tradeoff and its role in maintaining diversity in plant communities. We quantified species’ responses to experimental resource addition and consumer removal as estimates of competitive ability and resistance to consumers, respectively. With this analysis, we found mixed empirical evidence for a competition–defense tradeoff; in fact, competitive ability tended to be weakly positively correlated with defense overall. However, when present, negative relationships between competitive ability and defense influenced species diversity in the manner predicted by theory. In the minority of communities for which a tradeoff was detected, species evenness was higher, and resource addition and consumer removal reduced diversity. Our analysis reframes the commonly held notion that consumers structure plant communities through a competition–defense tradeoff. Such a tradeoff can maintain diversity when present, but negative correlations between competitive ability and defense were less common than is often assumed. In this respect, this study supports an emerging theoretical paradigm in which predation interacts with competition to both enhance and reduce species diversity.
Leptin therapy improves insulin-deficient type 1 diabetes by CNS-dependent mechanisms in mice
Authors: Fujikawa Teppei , Chuang Jen-Chieh , Sakata Ichiro , Ramadori Giorgio , Coppari Roberto
Published: September 2010

Leptin monotherapy reverses the deadly consequences and improves several of the metabolic imbalances caused by insulin-deficient type 1 diabetes (T1D) in rodents. However, the mechanism(s) underlying these effects is totally unknown. Here, we report that intracerebroventricular (icv) infusion of leptin reverses lethality and greatly improves hyperglycemia, hyperglucagonemia, hyperketonemia, and polyuria caused by insulin deficiency in mice. Notably, icv leptin administration leads to increased body weight while suppressing food intake, thus correcting the catabolic consequences of T1D. Also, icv leptin delivery improves expression of the metabolically relevant hypothalamic neuropeptides proopiomelanocortin, neuropeptide Y, and agouti-related peptide in T1D mice. Furthermore, this treatment normalizes phosphoenolpyruvate carboxykinase 1 contents without affecting glycogen levels in the liver. Pancreatic β-cell regeneration does not underlie these beneficial effects of leptin, because circulating insulin levels were undetectable at basal levels and following a glucose overload. Also, pancreatic
preproinsulin
mRNA was completely absent in these icv leptin-treated T1D mice. Furthermore, the antidiabetic effects of icv leptin administration rapidly vanished (i.e., within 48 h) after leptin treatment was interrupted. Collectively, these results unveil a key role for the brain in mediating the antidiabetic actions of leptin in the context of T1D.
Complement receptor 1 is the host erythrocyte receptor forPlasmodium falciparumPfRh4 invasion ligand
Authors: Tham Wai-Hong , Wilson Danny W. , Lopaticki Sash , Schmidt Christoph Q. , Tetteh-Quarcoo Patience B. , Barlow Paul N. , Richard Dave , Corbin Jason E. , Beeson James G. , Cowman Alan F.
Published: September 2010

Plasmodium falciparumis responsible for the most severe form of malaria disease in humans, causing more than 1 million deaths each year. As an obligate intracellular parasite,P. falciparum’s ability to invade erythrocytes is essential for its survival within the human host.P. falciparuminvades erythrocytes using multiple host receptor–parasite ligand interactions known as invasion pathways. Here we show that CR1 is the host erythrocyte receptor for PfRh4, a majorP. falciparumligand essential for sialic acid–independent invasion. PfRh4 and CR1 interact directly, with aKdof 2.9 μM. PfRh4 binding is strongly correlated with the CR1 level on the erythrocyte surface. Parasite invasion via sialic acid–independent pathways is reduced in low-CR1 erythrocytes due to limited availability of this receptor on the surface. Furthermore, soluble CR1 can competitively block binding of PfRh4 to the erythrocyte surface and specifically inhibit sialic acid–independent parasite invasion. These results demonstrate that CR1 is an erythrocyte receptor used by the parasite ligand PfRh4 forP. falciparuminvasion.
PGE2-regulated wnt signaling andN-acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury
Authors: North Trista E. , Babu I. Ramesh , Vedder Lea M. , Lord Allegra M. , Wishnok John S. , Tannenbaum Steven R. , Zon Leonard I. , Goessling Wolfram
Published: September 2010

Acetaminophen (APAP) toxicity is the most common drug-induced cause of acute liver failure in the United States. The only available treatment,N-acetylcysteine (NAC), has a limited time window of efficacy, indicating a need for additional therapeutic options. Zebrafish have emerged as a powerful tool for drug discovery. Here, we developed a clinically relevant zebrafish model of APAP toxicity. APAP depleted glutathione stores, elevated aminotransferase levels, increased apoptosis, and caused dose-dependent hepatocyte necrosis. These outcomes were limited by NAC and conserved in zebrafish embryos. In a targeted embryonic chemical screen, prostaglandin E2 (PGE2) was identified as a potential therapeutic agent; in the adult, PGE2 similarly decreased APAP-associated toxicity. Significantly, when combined with NAC, PGE2 extended the time window for a successful intervention, synergistically reducing apoptosis, improving liver enzymes, and preventing death. Use of a wnt reporter zebrafish line and chemical genetic epistasis showed that the effects of PGE2 are mediated through the wnt signaling pathway. Zebrafish can be used as a clinically relevant toxicological model amenable to the identification of additional therapeutics and biomarkers of APAP injury; our data suggest combinatorial PGE2 and NAC treatment would be beneficial for patients with APAP-induced liver damage.
Oscillatory phase coupling coordinates anatomically dispersed functional cell assemblies
Authors: Canolty Ryan T. , Ganguly Karunesh , Kennerley Steven W. , Cadieu Charles F. , Koepsell Kilian , Wallis Jonathan D. , Carmena Jose M.
Published: September 2010

Hebb proposed that neuronal cell assemblies are critical for effective perception, cognition, and action. However, evidence for brain mechanisms that coordinate multiple coactive assemblies remains lacking. Neuronal oscillations have been suggested as one possible mechanism for cell assembly coordination. Prior studies have shown that spike timing depends upon local field potential (LFP) phase proximal to the cell body, but few studies have examined the dependence of spiking on distal LFP phases in other brain areas far from the neuron or the influence of LFP–LFP phase coupling between distal areas on spiking. We investigated these interactions by recording LFPs and single-unit activity using multiple microelectrode arrays in several brain areas and then used a unique probabilistic multivariate phase distribution to model the dependence of spike timing on the full pattern of proximal LFP phases, distal LFP phases, and LFP–LFP phase coupling between electrodes. Here we show that spiking activity in single neurons and neuronal ensembles depends on dynamic patterns of oscillatory phase coupling between multiple brain areas, in addition to the effects of proximal LFP phase. Neurons that prefer similar patterns of phase coupling exhibit similar changes in spike rates, whereas neurons with different preferences show divergent responses, providing a basic mechanism to bind different neurons together into coordinated cell assemblies. Surprisingly, phase-coupling–based rate correlations are independent of interneuron distance. Phase-coupling preferences correlate with behavior and neural function and remain stable over multiple days. These findings suggest that neuronal oscillations enable selective and dynamic control of distributed functional cell assemblies.
Melanopsin-dependent light avoidance in neonatal mice
Authors: Johnson Juliette , Wu Vincent , Donovan Michael , Majumdar Sriparna , Rentería René C. , Porco Travis , Van Gelder Russell N. , Copenhagen David R.
Published: September 2010

Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) form a light-sensitive system separate from rods and cones. Direct light stimulation of ipRGCs can regulate many nonimage-forming visual functions such as photoentrainment of circadian rhythms and pupil responses, and can intensify migraine headache in adults. In mice, ipRGCs are light responsive as early as the day of birth. In contrast, their eyelids do not open until 12–13 d after birth (P12–13), and light signaling from rods and cones does not begin until approximately P10. No physiological or behavioral function is established for ipRGCs in neonates before the onset of rod and cone signaling. Here we report that mouse pups as young as P6 will completely turn away from a light. Light-induced responses of ipRGCs could be readily recorded in retinas of pups younger than P9, and we found no evidence for rod- and cone-mediated visual signaling to the RGCs of these younger mice. These results confirm that negative phototaxis is evident before the onset of rod- and cone-mediated visual signaling, and well before the onset of image-forming vision. Negative phototaxis was absent in mice lacking melanopsin. We conclude that light activation of melanopsin ipRGCs is necessary and sufficient for negative phototaxis. These results strongly suggest that light activation of ipRGCs may regulate physiological functions such as sleep/wake cycles in preterm and neonatal infants.
Evidence for the prepattern/cooption model of vertebrate jaw evolution
Authors: Cerny Robert , Cattell Maria , Sauka-Spengler Tatjana , Bronner-Fraser Marianne , Yu Feiqiao , Medeiros Daniel Meulemans
Published: September 2010

The appearance of jaws was a turning point in vertebrate evolution because it allowed primitive vertebrates to capture and process large, motile prey. The vertebrate jaw consists of separate dorsal and ventral skeletal elements connected by a joint. How this structure evolved from the unjointed gill bar of a jawless ancestor is an unresolved question in vertebrate evolution. To understand the developmental bases of this evolutionary transition, we examined the expression of 12 genes involved in vertebrate pharyngeal patterning in the modern jawless fish lamprey. We find nested expression of
Dlx
genes, as well as combinatorial expression of
Msx, Hand
and
Gsc
genes along the dorso-ventral (DV) axis of the lamprey pharynx, indicating gnathostome-type pharyngeal patterning evolved before the appearance of the jaw. In addition, we find that
Bapx
and
Gdf5/6/7
, key regulators of joint formation in gnathostomes, are not expressed in the lamprey first arch, whereas
Barx
, which is absent from the intermediate first arch in gnathostomes, marks this domain in lamprey. Taken together, these data support a new scenario for jaw evolution in which incorporation of
Bapx
and
Gdf5/6/7
into a preexisting DV patterning program drove the evolution of the jaw by altering the identity of intermediate first-arch chondrocytes. We present this “Pre-pattern/Cooption” model as an alternative to current models linking the evolution of the jaw to the de novo appearance of sophisticated pharyngeal DV patterning.
Cardiomyopathy-linked myosin regulatory light chain mutations disrupt myosin strain-dependent biochemistry
Authors: Greenberg Michael J. , Kazmierczak Katarzyna , Szczesna-Cordary Danuta , Moore Jeffrey R.
Published: September 2010

Familial hypertrophic cardiomyopathy (FHC) is caused by mutations in sarcomeric proteins including the myosin regulatory light chain (RLC). Two such FHC mutations, R58Q and N47K, located near the cationic binding site of the RLC, have been identified from population studies. To examine the molecular basis for the observed phenotypes, we exchanged endogenous RLC from native porcine cardiac myosin with recombinant human ventricular wild type (WT) or FHC mutant RLC and examined the ability of the reconstituted myosin to propel actin filament sliding using the in vitro motility assay. We find that, whereas the mutant myosins are indistinguishable from the controls (WT or native myosin) under unloaded conditions, both R58Q- and N47K-exchanged myosins show reductions in force and power output compared with WT or native myosin. We also show that the changes in loaded kinetics are a result of mutation-induced loss of myosin strain sensitivity of ADP affinity. We propose that the R58Q and N47K mutations alter the mechanical properties of the myosin neck region, leading to altered load-dependent kinetics that may explain the observed mutant-induced FHC phenotypes.
Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells
Authors: Stern Joel N. H. , Keskin Derin B. , Kato Zenichiro , Waldner Hanspeter , Schallenberg Sonja , Anderson Ana , von Boehmer Harald , Kretschmer Karsten , Strominger Jack L.
Published: September 2010

In T cell-mediated autoimmune diseases, self-reactive T cells with known antigen specificity appear to be particularly promising targets for antigen-specific induction of tolerance without compromising desired protective host immune responses. Several lines of evidence suggest that delivery of antigens to antigen-presenting dendritic cells (DCs) in the steady state (i.e., to immature DCs) may represent a suitable approach to induce antigen-specific T-cell tolerance peripherally. Here, we report that anti-DEC205–mediated delivery of the self-peptide proteolipid protein (PLP)139–151 to DCs ameliorated clinical symptoms in the PLP-induced SJL model of experimental autoimmune encephalomyelitis. Splenocytes from treated mice were anergized to PLP139–151, and IL-17 secretion was markedly reduced. Moreover, we show directly, using transgenic CD4+Vβ6+TCR T cells specific for PLP139–151, that, under the conditions of the present experiments, these cells also became anergic. In addition, evidence for a CD4+T cell-mediated suppressor mechanism was obtained.
Storage of nuclear magnetization as long-lived singlet order in low magnetic field
Authors: Pileio Giuseppe , Carravetta Marina , Levitt Malcolm H.
Published: September 2010

Hyperpolarized nuclear states provide NMR signals enhanced by many orders of magnitude, with numerous potential applications to analytical NMR, in vivo NMR, and NMR imaging. However, the lifetime of hyperpolarized magnetization is normally limited by the relaxation time constant
T
1
, which lies in the range of milliseconds to minutes, apart from in exceptional cases. In many cases, the lifetime of the hyperpolarized state may be enhanced by converting the magnetization into nuclear singlet order, where it is protected against many common relaxation mechanisms. However, all current methods for converting magnetization into singlet order require the use of a high-field, high-homogeneity NMR magnet, which is incompatible with most hyperpolarization procedures. We demonstrate a new method for converting magnetization into singlet order and back again. The new technique is suitable for magnetically inequivalent spin-pair systems in weak and inhomogeneous magnetic fields, and is compatible with known hyperpolarization technology. The method involves audio-frequency pulsed irradiation at the low-field nuclear Larmor frequency, employing coupling-synchronized trains of 180° pulses to induce singlet–triplet transitions. The echo trains are used as building blocks for a pulse sequence called M2S that transforms longitudinal magnetization into long-lived singlet order. The time-reverse of the pulse sequence, called S2M, converts singlet order back into longitudinal magnetization. The method is demonstrated on a solution of
15
N-labeled nitrous oxide. The magnetization is stored in low magnetic field for over 30 min, even though the
T
1
is less than 3 min under the same conditions.
Reconstructing a solid-solid phase transformation pathway in CdSe nanosheets with associated soft ligands
Authors: Wang Zhongwu , Wen Xiao-Dong , Hoffmann Roald , Son Jae Sung , Li Ruipeng , Fang Chia-Chen , Smilgies Detlef-M. , Hyeon Taeghwan
Published: September 2010

Integrated single-crystal-like small and wide-angle X-ray diffraction images of a CdSe nanosheet under pressure provide direct experimental evidence for the detailed pathway of transformation of the CdSe from a wurtzite to a rock-salt structure. Two consecutive planar atomic slips [(001) 〈110〉 in parallel and (102)

with a distortion angle of ∼40°] convert the wurtzite-based nanosheet into a saw-like rock-salt nanolayer. The transformation pressure is three times that in the bulk CdSe crystal. Theoretical calculations are in accord with the mechanism and the change in transformation pressure, and point to the critical role of the coordinated amines. Soft ligands not only increase the stability of the wurtzite structure, but also improve its elastic strength and fracture toughness. A ligand extension of 2.3 nm appears to be the critical dimension for a turning point in stress distribution, leading to the formation of wurtzite (001)/zinc-blende (111) stacking faults before rock-salt nucleation.
Hydration dynamics at fluorinated protein surfaces
Authors: Kwon Oh-Hoon , Yoo Tae Hyeon , Othon Christina M. , Van Deventer James A. , Tirrell David A. , Zewail Ahmed H.
Published: September 2010

Water-protein interactions dictate many processes crucial to protein function including folding, dynamics, interactions with other biomolecules, and enzymatic catalysis. Here we examine the effect of surface fluorination on water-protein interactions. Modification of designed coiled-coil proteins by incorporation of 5,5,5-trifluoroleucine or (4
S
)-2-amino-4-methylhexanoic acid enables systematic examination of the effects of side-chain volume and fluorination on solvation dynamics. Using ultrafast fluorescence spectroscopy, we find that fluorinated side chains exert electrostatic drag on neighboring water molecules, slowing water motion at the protein surface.
Lateral opening of a translocon upon entry of protein suggests the mechanism of insertion into membranes
Authors: Egea Pascal F. , Stroud Robert M.
Published: September 2010

The structure of the protein-translocating channel SecYEβ from
Pyrococcus furiosus
at 3.1-Å resolution suggests a mechanism for chaperoning transmembrane regions of a protein substrate during its lateral delivery into the lipid bilayer. Cytoplasmic segments of SecY orient the C-terminal α-helical region of another molecule, suggesting a general binding mode and a promiscuous guiding surface capable of accommodating diverse nascent chains at the exit of the ribosomal tunnel. To accommodate this putative nascent chain mimic, the cytoplasmic vestibule widens, and a lateral exit portal is opened throughout its entire length for partition of transmembrane helical segments to the lipid bilayer. In this primed channel, the central plug still occludes the pore while the lateral gate is opened, enabling topological arbitration during early protein insertion. In vivo, a 15 amino acid truncation of the cytoplasmic C-terminal helix of SecY fails to rescue a
secY
-deficient strain, supporting the essential role of this helix as suggested from the structure.
Soluble amyloid precursor protein (APP) regulates
transthyretin
and
Klotho
gene expression without rescuing the essential function of APP
Authors: Li Hongmei , Wang Baiping , Wang Zilai , Guo Qinxi , Tabuchi Katsuhiko , Hammer Robert E. , Südhof Thomas C. , Zheng Hui
Published: September 2010

Amyloidogenic processing of the amyloid precursor protein (APP) generates a large secreted ectodomain fragment (APPsβ), β-amyloid (Aβ) peptides, and an APP intracellular domain (AICD). Whereas Aβ is viewed as critical for Alzheimer's disease pathogenesis, the role of other APP processing products remains enigmatic. Of interest, the AICD has been implicated in transcriptional regulation, and N-terminal cleavage of APPsβ has been suggested to produce an active fragment that may mediate axonal pruning and neuronal cell death. We previously reported that mice deficient in
APP
and APP-like protein 2 (
APLP2
) exhibit early postnatal lethality and neuromuscular synapse defects, whereas mice with neuronal conditional deletion of
APP
and
APLP2
are viable. Using transcriptional profiling, we now identify transthyretin (
TTR
) and
Klotho
as APP/APLP2-dependent genes whose expression is decreased in loss-of-function states but increased in gain-of-function states. Significantly, by creating an
APP
knockin allele that expresses only APPsβ protein, we demonstrate that APPsβ is not normally cleaved in vivo and is fully capable of mediating the APP-dependent regulation of
TTR
and
Klotho
gene expression. Despite being an active regulator of gene expression, APPsβ did not rescue the lethality and neuromuscular synapse defects of
APP
and
APLP2
double-KO animals. Our studies identify
TTR
and
Klotho
as physiological targets of APP that are regulated by soluble APPsβ independent of developmental APP functions. This unexpected APP-mediated signaling pathway may play an important role in maintaining TTR and Klotho levels and their respective functions in Aβ sequestration and aging.
The Ets-1 transcription factor controls the development and function of natural regulatory T cells
Authors: Mouly Enguerran , Chemin Karine , Nguyen Hai Vu , Chopin Martine , Mesnard Laurent , Leite-de-Moraes Maria , Burlen-defranoux Odile , Bandeira Antonio , Bories Jean-Christophe
Published: September 2010

Regulatory T cells (T reg cells) constitute a population of CD4+ T cells that limits immune responses. The transcription factor Foxp3 is important for determining the development and function of T reg cells; however, the molecular mechanisms that trigger and maintain its expression remain incompletely understood. In this study, we show that mice deficient for the Ets-1 transcription factor (Ets-1−/−) developed T cell–mediated splenomegaly and systemic autoimmunity that can be blocked by functional wild-type T reg cells. Spleens of Ets-1−/− mice contained mostly activated T cells, including Th2-polarized CD4+ cells and had reduced percentages of T reg cells. Splenic and thymic Ets-1−/− T reg cells expressed low levels of Foxp3 and displayed the CD103 marker that characterizes antigen-experienced T reg cells. Thymic development of Ets-1−/− T reg cells appeared intrinsically altered as Foxp3-expressing cells differentiate poorly in mixed fetal liver reconstituted chimera and fetal thymic organ culture. Ets-1−/− T reg cells showed decreased in vitro suppression activity and did not protect Rag2−/− hosts from naive T cell–induced inflammatory bowel disease. Furthermore, in T reg cells, Ets-1 interacted with the Foxp3 intronic enhancer and was required for demethylation of this regulatory sequence. These data demonstrate that Ets-1 is required for the development of natural T reg cells and suggest a role for this transcription factor in the regulation of Foxp3 expression.
Conversion of Helicobacter pylori CagA from senescence inducer to oncogenic driver through polarity-dependent regulation of p21
Authors: Saito Yasuhiro , Murata-Kamiya Naoko , Hirayama Toshiya , Ohba Yusuke , Hatakeyama Masanori
Published: September 2010

The Helicobacter pylori CagA bacterial oncoprotein plays a critical role in gastric carcinogenesis. Upon delivery into epithelial cells, CagA causes loss of polarity and activates aberrant Erk signaling. We show that CagA-induced Erk activation results in senescence and mitogenesis in nonpolarized and polarized epithelial cells, respectively. In nonpolarized epithelial cells, Erk activation results in oncogenic stress, up-regulation of the p21Waf1/Cip1 cyclin-dependent kinase inhibitor, and induction of senescence. In polarized epithelial cells, CagA-driven Erk signals prevent p21Waf1/Cip1 expression by activating a guanine nucleotide exchange factor–H1–RhoA–RhoA-associated kinase–c-Myc pathway. The microRNAs miR-17 and miR-20a, induced by c-Myc, are needed to suppress p21Waf1/Cip1 expression. CagA also drives an epithelial-mesenchymal transition in polarized epithelial cells. These findings suggest that CagA exploits a polarity-signaling pathway to induce oncogenesis.
Novel dielectric photonic-band-gap resonant cavity loaded in a gyrotron
Authors: Xiaoan Chen , Gaofeng Liu , Changjian Tang
Published: September 2010

A novel resonant cavity composed of a periodic, multilayer, dielectric photonic crystal is proposed. Using the transfer matrix method and the Bloch theorem for periodic systems, an analysis on the band-gap property of such a structure is made, and the basic electromagnetic property of the photonic-band-gap resonant cavity (PBGC) is preliminarily exhibited. The theoretical studies and the cold cavity simulation results obtained from a high-frequency structure simulator are presented. On the basis of the present research, such a PBGC is quite similar to the two-dimensional PBGC made of triangular lattices of metal rods with a defect at its centre, in which a frequency selectivity is similarly demonstrated. Because of its unique electromagnetic property, the cavity has many promising applications in active and passive devices operating in the millimetre, sub-millimetre, and even THz wave range. As a specific application, the feasibility of substituting the traditional cylindrical resonant cavity loaded in a gyrotron for a dielectric PBGC to achieve a transverse high-order operation is discussed under the consideration of the electromagnetic features of the cavity. The study shows the great potential value of such a cavity for gyrotron devices.
Optimum plasmon hybridization at percolation threshold of silver films near metallic surfaces
Authors: Maaroof A I , Sutherland D S
Published: September 2010

We experimentally demonstrate the strong interaction and plasmonic hybridization from a nanosystem having both localized and delocalized surface plasmon modes simultaneously in the presence of a nearby thin continuous metallic film. In situ dc resistance measurement of silver films and percolation theory were used to accurately determine the systems where the percolation threshold exists by distinguishing the nucleation and growth regions of silver films. We found an optimum plasmon hybridization existing in this percolation threshold region which can be verified from the absorption spectra. We interpret our data in terms of a fitting of the absorption spectra to the Fano-type line shape model.
Simultaneous refractive index and thickness measurement with the transmission interferometric adsorption sensor
Authors: Sannomiya Takumi , Balmer Tobias E , Heuberger Manfred , Vörös Janos
Published: September 2010

Refractive index and thickness of the adlayer are determined simultaneously using the transmission interferometric adsorption sensor (TInAS). Optical biosensors, where both refractive index and thickness of a homogeneous adlayer (thus the adsorbed mass) are determined simultaneously, so-called model-free biosensors, are important tools to investigate the adsorbed mass of biomolecules with unknown conformation. Our proposed calculation method enables model-free biosensing from a single spectrum acquired by a simple TInAS setup, namely using information of peak/dip positions as well as peak/dip intensities. The feasibility of this method was experimentally tested by adsorbing polyelectrolyte multilayer as well as biomolecules. To validate the new method also for the more intricate heterogeneous adlayer, the apparent refractive index and thickness were assessed theoretically by simulating a selection of different adsorbate configurations with the multiple multipole program (MMP). We found that a lateral inhomogeneity of the adsorbate (e.g. islands or adsorbed colloids) results in correct thickness and in reduced refractive index averaged in proportion to their density while vertically inhomogeneous density caused more complex responses. However, the apparent mass was always correct. Measurement errors can lead to significant errors in the apparent refractive index, particularly when the adlayer is very thin (<5 nm). This model-free TInAS technique would be useful not only for the measurement of adsorbed mass but also for the conformational analysis of the adsorbed molecules.
The role of energetic ion bombardment during growth of TiO2 thin films by reactive sputtering
Authors: Amin A , Köhl D , Wuttig M
Published: September 2010

TiO2 thin films have been deposited by several different sputtering processes: (i) dc magnetron sputtering (dcMS) employing various geometrical conditions, (ii) ion-assisted dc magnetron sputtering where additional ion bombardment of the growing films was performed with an auxiliary ECR ion source and (iii) high power impulse magnetron sputtering (HiPIMS). Films have been investigated mainly by grazing incidence x-ray diffraction and atomic force microscopy. It is shown that the highly energetic oxygen ions inherent in reactive sputtering of metal oxides are the dominant energetic species governing structure formation of TiO2 films by their kinetic impact. The trajectories of these energetic oxygen ions strongly depend on the shape of the erosion trace and hence on the age of the target, which therefore has a strong influence on structure formation. Furthermore, in a HiPIMS discharge the role of this energetic oxygen ion bombardment is strongly intensified due to the increased target voltage and the lower deposition rate compared with a dcMS discharge. It is also demonstrated that films with pure rutile structure which are stable under a post-deposition thermal treatment can be deposited under intense energetic ion bombardment at low temperatures either by HiPIMS at high peak power densities or by ion-assisted dcMS.
Synthesis and characterization of different shaped Sm2O3 nanocrystals
Authors: Ghosh Pushpal , Kundu Simanta , Kar Arik , Ramanujachary K V , Lofland Samuel , Patra Amitava
Published: September 2010

Here, we demonstrate the synthesis of Sm2O3 nanoparticles, nanorods and nanoplates by solution-based techniques. The mechanism related to morphology control is proposed and discussed. The crystal phase of the Sm2O3 nanocrystal is tuned by varying the surfactant in the reaction. It is found that compressive strain is observed for lower temperature (600 °C) heated sample but reversal of strain appears at elevated temperature (900 °C). A chromatic change in photoluminescence (PL) emission with tuning the excitation wavelength has been observed. The PL emission is due to f–f electronic transition from excited states of 4G5/2 of the Sm3+ ion. The PL emission bands at 610 and 656 nm are observed under excitation 370 nm, but bands centred at 545, 610 and 656 nm are observed when the excitation wavelength is tuned to 400 nm. It is seen that the ratio between electric dipole and partially magnetic dipole contributions is maximum for nanorods followed by nanoplates and nanoparticles. Magnetic susceptibility study of the nanocrystals shows that the Sm3+ ion follows the well-known Van Vleck behaviour.
Synthesis, growth mechanism and photoelectrochemical properties of BiVO4 microcrystal electrodes
Authors: Luo Wenjun , Wang Zhiqiang , Wan Lijuan , Li Zhaosheng , Yu Tao , Zou Zhigang
Published: September 2010

BiVO4 films were deposited on fluorine-doped tin oxide substrates by chemical bath deposition. The samples were characterized by an x-ray diffractometer, UV–Vis transmission spectra and a scanning electron microscope. The morphologies of the samples were adjusted by the deposition time, temperature, pH of solution and buffer solution. When the temperature and pH value of the solution were high, the polyhedron microcrystal of BiVO4 exposed fewer less planes on the surface and the films were more compact. On the basis of the experimental results, a possible growth mechanism was proposed. Moreover, the photoelectrochemical properties of the samples with different morphologies were investigated. The results suggested that the compact films with a smaller microcrystal exhibited better performance, which was helpful to understand the relationship between the morphologies of other microcrystal electrodes and their photoelectrochemical properties.
Diplodus spp. on artificial reefs of different ages: influence of the associated macrobenthic community
Authors: Santos Miguel N. , Leitão Francisco , Moura Ana , Cerqueira Marco , Monteiro Carlos C.
Published: September 2010

Santos, M. N., Leitão, F., Moura, A., Cerqueira, M., and Monteiro, C. C. 2011. Diplodus spp. on artificial reefs of different ages: influence of the associated macrobenthic community. – ICES Journal of Marine Science, 68: 87–97. Although artificial reefs (ARs) have been deployed and studied worldwide, few studies have attempted to link the benthic community to fish populations. Three AR fish species (Diplodus bellottii, D. sargus, and D. vulgaris) were tested for the influence of the macrobenthic community at three similar ARs deployed in 1990, 1998, and 2002 off the Algarve (southern Portugal). Diplodus sargus density and biomass differed across ARs, and for D. bellottii and D. vulgaris, higher densities and biomass were observed between the oldest and the youngest ARs. The total available benthic biomass did not differ across habitat age, but the composition of macrofauna differed between older and the most recently deployed AR. The results underscore the importance of within-reef-age benthic composition variability as a determinant factor in structuring local fish populations. As the Algarve AR complex consists of reefs deployed at different times and having different benthic communities, management needs to focus more effort on conserving entire habitats rather than exclusively on maintaining the sustainability of fish resources. Hence, management plans for these areas need to be developed on a site-specific basis, according to the fish and macrobenthic community specificities.
Understanding the Nature and Purpose of Clinical and Educational Supervision
Authors: Kilminster Sue
Published: September 2010

Learning in the workplace is the basis of postgraduate medical education and training. Essentially, you learn to be a doctor by being one. Each training programme has formal educational activities. Doctors in training must undertake independent study, but the most important element of training is the opportunity to undertake medical practice, under appropriate supervision. Although supervision has such a vital role in medical education, it is probably the least investigated and least developed aspect of clinical teaching. This article reviews current understanding and requirements about supervision and concludes that these suggest new directions for developing supervisory practices.
Fitness to Fly
Authors: Patel Yaseen , Simon Chantal
Published: September 2010

It is estimated that 1 billion people travel by air every year, and this is expected to double in 20 years. For the vast majority, commercial flights are safe and comfortable. All flights, short haul or long haul, impose stresses on passengers. GPs are often asked to advise about or certify patients' fitness to fly. This article aims to provide guidance to enable doctors to provide informed and evidence-based advice for their patients.