bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical unfolding of proteins L and G with constant force: Similarities and differences
Authors: Glyakina A. V. , Balabaev N. K. , Galzitskaya O. V.
Published: July 2009

Mechanical unfolding of proteins L and G, which have similar structures, is considered in this work, and the question arises what changes happen in the unfolding pathways under the action of mechanical force. Molecular dynamics simulations with explicit water (134 trajectories) demonstrate that the mechanical unfolding with constant force occurs through at least two pathways in both proteins. These pathways practically coincide for both proteins and under different constant extensional forces (600, 700, 800, 900, and 1050 pN) and at different temperatures (320, 350, and 400 K at F=1050 pN). Go-like modeling of forced unfolding of proteins L and G does not agree with experimental results that protein G is more mechanically resistant than protein L. At the same time, molecular dynamics simulations of forced unfolding of proteins L and G with explicit water demonstrate that protein G is more mechanically resistant than protein L. Our investigation demonstrates that mechanical stable elements are the same for both proteins, namely, the N-terminal β-hairpin. This result agrees with experimental data on denaturant unfolding for protein L but not for protein G.
Strain distribution and interface modulation of highly lattice-mismatched InN/GaN heterostructure nanowires
Authors: Kim Y. H. , Park H. J. , Kim K. , Kim C. S. , Yun W. S. , Lee J. W. , Kim M. D.
Published: July 2009

The structural properties of InN/GaN heterostructure nanowires (NWs) were studied using transmission electron microscope techniques to determine strain behavior. A great quantity of the misfit strain between InN and GaN was relaxed through the introduction of misfit dislocations along the interface. Geometric phase analysis revealed a strain-concentration phenomenon in the strain map of the out-of-plane components and a gradual lattice recovery in that of the in-plane components over the InN/GaN interface. Interface structures that were modulated at the atomic-scale were observed in several InN/GaN heterostructure NWs. Complex strain distributions were identified in both InN and GaN.
Interdiffusion in liquid Al–Cu and Ni–Cu alloys
Authors: Cheng H. , Lü Y. J. , Chen M.
Published: July 2009

The interdiffusion processes in liquid Al–Cu and Ni–Cu alloys are studied by using molecular dynamics simulation method. The Maxwell–Stefan (MS) diffusivities are calculated over a wide composition range with both the Green–Kubo method and the Darken relation. Comparisons show that the Darken relation predicts well the MS diffusivity for Ni–Cu alloy, while overestimates the value for Al–Cu alloy, especially in the medium concentration region. Based on the calculated MS diffusivities and the activities of the alloys, the Fickian interdiffusivities are predicted. The results show strong dependences on the compositions of the alloys. In addition, the Fickian interdiffusivities of Al60Cu40 and Ni50Cu50 melts as a function of undercooling are estimated, which is proved to be beneficial in improving the quantitative predictions of dendrite growth velocity in solidification.
Fourier transform microwave spectra of a “new” isomer of OCS-CO2
Authors: Sedo Galen , van Wijngaarden Jennifer
Published: July 2009

The rotational spectrum of a “new” isomer of OCS-CO2 has been measured between 5 and 18 GHz using Fourier transform microwave spectroscopy. Both a- and b-type transitions of the parent dimer and the C13O2-containing isotopologue were fit and the resulting spectroscopic constants confirm that this is the planar O-interior, not-quite-as-parallel isomer that was experimentally observed for the first time in the recent infrared investigation of Dehghany et al. [J. Chem. Phys. 130, 224310 (2009)]. As in the infrared study, the microwave transitions of this isomer appear stronger than those of the previously reported lower energy isomer of OCS-CO2 when helium is used as the backing gas for the supersonic expansion.
Controlled free-form fabrication of nanowires by dielectrophoretic dispension of colloids
Authors: Schirmer Niklas C. , Schwamb Timo , Burg Brian R. , Hotz Nico , Poulikakos Dimos
Published: July 2009

The vertical growth of conductive gold nanowires in ambient atmosphere through on-demand dielectrophoretically guided deposition of nanoparticle-laden colloids is demonstrated. Accelerated by dielectrophoresis, rapidly evaporating colloidal droplets leave a capillary nozzle (diameter of 500 nm) and are guided through an inhomogeneous electrostatic field. The nanoparticles in the colloidal droplets combine under the action of van der Waals attraction forces on the substrate to form highly flexible vertical nanowires with easily controllable lengths and diameters, here in the range of 150–800 nm. After bending to bridge an electrode pair and after annealing at 300 °C, the sample gold nanowires demonstrate excellent electrical conductivity considering their size.
Optical and magnetic properties of CuMnO2 epitaxial thin films with a delafossite-derivative structure
Authors: Hiraga H. , Fukumura T. , Ohtomo A. , Makino T. , Ohkubo A. , Kimura H. , Kawasaki M.
Published: July 2009

A distorted delafossite CuMnO2, called crednerite, was formed into epitaxial thin films on MgAl2O4 (111) substrates by pulsed laser deposition method. X-ray diffraction revealed that the films had high crystalline quality with epitaxial relationship of CuMnO2 (001)//MgAl2O4 (111) and CuMnO2 [100]//MgAl2O4 ⟨11-2⟩. The ultraviolet-visible optical response revealed a distinct absorption peak at 4.5 eV presumably with excitonic nature and broad peaks at 3.0 and 3.7 eV assignable to O 2p–Mn 3d charge transfer excitation. Small magnetic hysteresis with remanent magnetization of 0.04μB/Mn was observed below 20 K, representing canted antiferromagnetic spin ordering.
Physical and chemical characterization of Pt12−nCun clusters via ab initio calculations
Authors: Mejía-López José , García Griselda , Romero Aldo H.
Published: July 2009

The physical, structural, and chemical properties of bimetallic Pt12−nCun clusters, where n goes from 0 to 12, have been investigated within density functional theory. We find that the electronic and magnetic properties depend a lot on the atomic fraction of Cu atoms, mainly as the number of Cu atoms changes from even to odd. The chemical potential increases monotonically as a function of the Cu concentration, whereas other chemical properties such as electrophilicity depend on local changes and decreases monotonically, as well as the ionization potential. The hardness has an oscillatory behavior, which depends on the total number of electrons. The reactivity has been spatially analyzed by studying the highest occupied molecular orbital and lowest unoccupied molecular orbital. Charge delocalization is largely increased by the number of copper atoms, whereas for largely Pt concentrations, the charge is more atomiclike. That charge dependence gives another cluster outside view, which shows a rich spatial reactivity. The magnetic dependence of the cluster on the Cu atom concentration opens the door to potential chemistry applications on bimetallic magnetic nanostructures in the field of spintronics.
The determination of the bulk residual doping in indium nitride films using photoluminescence
Authors: Moret M. , Ruffenach S. , Briot O. , Gil B.
Published: July 2009

We extend to any temperature, the sophisticated calculation of the evolution of the 2 K photoluminescence energy of InN proposed by Arnaudov et al. [Phys. Rev. B 69, 115216 (2004)], in view of determining the residual doping of thin films. From the detailed line shape modeling, we extract the full width at half maximum of the photoluminescence line which, in the first order, varies like n0.51 at low temperature. This allows us to propose a handy tool for rapid residual doping evaluation. Last, temperature and inhomogeneous broadening effects are analyzed. Ignoring the latter is shown to lead to an overestimation of the residual doping.
Analysis of accommodation coefficients of noble gases on aluminum surface with an experimental/computational method
Authors: Selden Nathaniel , Gimelshein Natalia , Gimelshein Sergey , Ketsdever Andrew
Published: July 2009

A method that connects measurements of radiometric forces on a heated vane in the transitional flow regime with the kinetic modeling of the flow, and derives the accommodation coefficients through the successive analysis of measured and computed results, is proposed. The method utilizes the fact that radiometric forces exerted on heated objects immersed in rarefied gases are governed by the interaction of gas molecules with the surface. Experimental results on radiometric forces on a 0.11 m diameter circular vane are obtained on a nano-Newton thrust stand in a 3 m long vacuum chamber for pressures ranging from approximately 0.01 to 1 Pa. The vane was heated to 419 K on the hot side and 396 K on the cold side. The numerical modeling is conducted using a combined ellipsoidal statistical Bhatnagar–Gross–Krook/direct simulation Monte Carlo approach that allows accurate and time efficient analysis of radiometric forces on a vane in large vacuum chambers filled with rarefied gas. Accommodation coefficients for the Maxwell model are estimated for argon, xenon, and helium on a machined aluminum surface, and found to be 0.81, 0.86, and 0.53, respectively.
Nanoscale mapping of temperature and defect evolution inside operating AlGaN/GaN high electron mobility transistors
Authors: Lin Chung-Han , Merz T. A. , Doutt D. R. , Hetzer M. J. , Joh Jungwoo , del Alamo Jesús A. , Mishra U. K. , Brillson L. J.
Published: July 2009

We used depth-resolved microcathodoluminescence spectroscopy (DRCLS) and Kelvin probe force microscopy (KPFM) to measure and map the temperature distribution and defect generation inside state-of-the-art AlGaN/GaN-based high electron mobility transistors (HEMTs) on a scale of tens of nanometers during device operation. DRCLS measurements of near band edge energies across the HEMT’s source-gate-drain regions reveal monotonic temperature increases across the submicron gate-drain channel, peaking under the drain side of the gate. DRCLS defect emissions mapped laterally and localized depthwise near the two-dimensional electron gas interface increase with device operation under the drain-side gate and correlate with higher KPFM surface potential maps.
Dust as a tipping element: The Bodélé Depression, Chad
Authors: Washington Richard , Bouet Christel , Cautenet Guy , Mackenzie Elisabeth , Ashpole Ian , Engelstaedter Sebastian , Lizcano Gil , Henderson Gideon M. , Schepanski Kerstin , Tegen Ina
Published: July 2009

Dust plays a vital role in climate and biophysical feedbacks in the Earth system. One source of dust, the Bodélé Depression in Chad, is estimated to produce about half the mineral aerosols emitted from the Sahara, which is the world's largest source. By using a variety of new remote sensing data, regional modeling, trajectory models, chemical analyses of dust, and future climate simulations, we investigate the current and past sensitivity of the Bodélé. We show that minor adjustments to small features of the atmospheric circulation, such as the Bodélé Low-Level Jet, could profoundly alter the behavior of this feature. Dust production during the mid-Holocene ceased completely from this key source region. Although subject to a great deal of uncertainty, some simulations of the 21st century indicate the potential for a substantial increase in dust production by the end of the century in comparison with current values.
Population increase and environmental deterioration correspond with microlithic innovations in South Asia ca. 35,000 years ago
Authors: Petraglia Michael , Clarkson Christopher , Boivin Nicole , Haslam Michael , Korisettar Ravi , Chaubey Gyaneshwer , Ditchfield Peter , Fuller Dorian , James Hannah , Jones Sacha , Kivisild Toomas , Koshy Jinu , Lahr Marta Mirazón , Metspalu Mait , Roberts Richard , Arnold Lee
Published: July 2009

Genetic studies of South Asia's population history have led to postulations of a significant and early population expansion in the subcontinent, dating to sometime in the Late Pleistocene. We evaluate this argument, based on new mtDNA analyses, and find evidence for significant demographic transition in the subcontinent, dating to 35–28 ka. We then examine the paleoenvironmental and, particularly, archaeological records for this time period and note that this putative demographic event coincides with a period of ecological and technological change in South Asia. We document the development of a new diminutive stone blade (microlithic) technology beginning at 35–30 ka, the first time that the precocity of this transition has been recognized across the subcontinent. We argue that the transition to microlithic technology may relate to changes in subsistence practices, as increasingly large and probably fragmented populations exploited resources in contracting favorable ecological zones just before the onset of full glacial conditions.
Structural transitions within human Rad51 nucleoprotein filaments
Authors: Robertson Ragan B. , Moses Dana N. , Kwon YoungHo , Chan Pamela , Chi Peter , Klein Hannah , Sung Patrick , Greene Eric C.
Published: July 2009

Rad51 is a core component of the eukaryotic homologous recombination machinery and is responsible for key mechanistic steps during strand invasion. Higher order oligomers of Rad51 display a remarkable degree of structural variation, forming rings, compressed filaments, and elongated filaments. It is unclear whether Rad51 can transition directly between these different oligomeric structures without disassembling first into monomers. We have used single-molecule microscopy to investigate the behavior of human Rad51 assembled on double-stranded DNA. Our results show that human Rad51 can form elongated nucleoprotein filaments on DNA, but ATP hydrolysis causes a decrease in their length without concomitant dissociation of protein. Compressed Rad51 filaments can re-elongate when presented with either ATP or the non-hydrolyzable analog AMP-PNP, and these cycles of elongation and compression are reversible. A Rad51 mutant deficient in ATP hydrolysis is locked into an extended conformation that is incapable of transitioning to a compressed filament. Similarly, wild-type Rad51 bound to DNA in the presence of AMP-PNP was trapped in the elongated state. Proteins incapable of transitioning to the compressed state were also highly resistant to dissociation from the DNA. Taken together, our results indicate that nucleotide hydrolysis by human Rad51 triggers a reversible structural transition leading to filaments with reduced helical pitch.
Patterns of neural activity associated with honest and dishonest moral decisions
Authors: Greene Joshua D. , Paxton Joseph M.
Published: July 2009

What makes people behave honestly when confronted with opportunities for dishonest gain? Research on the interplay between controlled and automatic processes in decision making suggests 2 hypotheses: According to the “Will” hypothesis, honesty results from the active resistance of temptation, comparable to the controlled cognitive processes that enable the delay of reward. According to the “Grace” hypothesis, honesty results from the absence of temptation, consistent with research emphasizing the determination of behavior by the presence or absence of automatic processes. To test these hypotheses, we examined neural activity in individuals confronted with opportunities for dishonest gain. Subjects undergoing functional magnetic resonance imaging (fMRI) gained money by accurately predicting the outcomes of computerized coin-flips. In some trials, subjects recorded their predictions in advance. In other trials, subjects were rewarded based on self-reported accuracy, allowing them to gain money dishonestly by lying about the accuracy of their predictions. Many subjects behaved dishonestly, as indicated by improbable levels of “accuracy.” Our findings support the Grace hypothesis. Individuals who behaved honestly exhibited no additional control-related activity (or other kind of activity) when choosing to behave honestly, as compared with a control condition in which there was no opportunity for dishonest gain. In contrast, individuals who behaved dishonestly exhibited increased activity in control-related regions of prefrontal cortex, both when choosing to behave dishonestly and on occasions when they refrained from dishonesty. Levels of activity in these regions correlated with the frequency of dishonesty in individuals.
Impaired defense mechanism against inflammation, hyperalgesia, and airway hyperreactivity in somatostatin 4 receptor gene-deleted mice
Authors: Helyes Zsuzsanna , Pintér Erika , Sándor Katalin , Elekes Krisztián , Bánvölgyi Ágnes , Keszthelyi Dániel , Szőke Éva , Tóth Dániel M. , Sándor Zoltán , Kereskai László , Pozsgai Gábor , Allen Jeremy P. , Emson Piers C. , Markovics Adrienn , Szolcsányi János
Published: July 2009

We have shown that somatostatin released from activated capsaicin-sensitive nociceptive nerve endings during inflammatory processes elicits systemic anti-inflammatory and analgesic effects. With the help of somatostatin receptor subtype 4 gene–deleted mice (sst
4
−/−
), we provide here several lines of evidence that this receptor has a protective role in a variety of inflammatory disease models; several symptoms are more severe in the sst
4
knockout animals than in their wild-type counterparts. Acute carrageenan-induced paw edema and mechanical hyperalgesia, inflammatory pain in the early phase of adjuvant-evoked chronic arthritis, and oxazolone-induced delayed-type hypersensitivity reaction in the skin are much greater in mice lacking the sst
4
receptor. Airway inflammation and consequent bronchial hyperreactivity elicited by intranasal lipopolysaccharide administration are also markedly enhanced in sst
4
knockouts, including increased perivascular/peribronchial edema, neutrophil/macrophage infiltration, mucus-producing goblet cell hyperplasia, myeloperoxidase activity, and IL-1β, TNF-α, and IFN-γ expression in the inflamed lung. It is concluded that during these inflammatory conditions the released somatostatin has pronounced counterregulatory effects through sst
4
receptor activation. Thus, this receptor is a promising novel target for developing anti-inflammatory, analgesic, and anti-asthmatic drugs.
Identification of genes conferring resistance to 5-fluorouracil
Authors: Yoo Byoung Kwon , Gredler Rachel , Vozhilla Nicollaq , Su Zao-zhong , Chen Dong , Forcier Talitha , Shah Khalid , Saxena Utsav , Hansen Ulla , Fisher Paul B. , Sarkar Devanand
Published: July 2009

Astrocyte elevated gene-1 (AEG-1) is overexpressed in >90% of human hepatocellular carcinoma (HCC) patients and plays a significant role in mediating aggressive progression of HCC. AEG-1 is known to augment invasion, metastasis, and angiogenesis, and we now demonstrate that AEG-1 directly contributes to another important hallmark of aggressive cancers, that is, resistance to chemotherapeutic drugs, such as 5-fluorouracil (5-FU). AEG-1 augments expression of the transcription factor LSF that regulates the expression of thymidylate synthase (TS), a target of 5-FU. In addition, AEG-1 enhances the expression of dihydropyrimidine dehydrogenase (DPYD) that catalyzes the initial and rate-limiting step in the catabolism of 5-FU. siRNA-mediated inhibition of AEG-1, LSF, or DPYD significantly increased the sensitivity of HCC cells to 5-FU in vitro and a lentivirus delivering AEG-1 siRNA in combination with 5-FU markedly inhibited growth of HCC cells xenotransplanted in athymic nude mice when compared to either agent alone. The present studies highlight 2 previously unidentified genes, AEG-1 and LSF, contributing to chemoresistance. Inhibition of AEG-1 might be exploited as a therapeutic strategy along with 5-FU-based combinatorial chemotherapy for HCC, a highly fatal cancer with currently very limited therapeutic options.
De novo synthesis of estrogen in pregnant uterus is critical for stromal decidualization and angiogenesis
Authors: Das Amrita , Mantena Srinivasa Raju , Kannan Athilakshmi , Evans Dean B. , Bagchi Milan K. , Bagchi Indrani C.
Published: July 2009

Implantation is initiated when the embryo attaches to the uterine luminal epithelium during early pregnancy. Following this event, uterine stromal cells undergo steroid hormone-dependent transformation into morphologically and functionally distinct decidual cells in a unique process known as decidualization. An angiogenic network is also formed in the uterine stromal bed, critically supporting the early development of the embryo. The steroid-induced mechanisms that promote stromal differentiation and endothelial proliferation during decidualization are not fully understood. Although the role of ovarian progesterone as a key regulator of decidualization is well established, the requirement of ovarian estrogen (E) during this process remains unresolved. Here we show that the expression of P450 aromatase, a key enzyme that converts androgens to E, is markedly induced in mouse uterine stromal cells undergoing decidualization. The aromatase then acts in conjunction with other steroid biosynthetic enzymes present in the decidual tissue to support de novo synthesis of E. This locally produced E is able to support the advancement of the stromal differentiation program even in the absence ovarian E in an ovariectomized, progesterone-supplemented pregnant mouse model. Administration of letrozole, a specific aromatase inhibitor, to these mice blocked the stromal differentiation process. Gene expression profiling further revealed that the intrauterine E induces the expression of several stromal factors that promote neovascularization in the decidual tissue. Collectively, these studies identified the decidual uterus as a novel site of E biosynthesis and uncovered E-regulated maternal signaling pathways that critically control uterine differentiation and angiogenesis during early pregnancy.
Nucleotide-dependent conformational states of actin
Authors: Pfaendtner Jim , Branduardi Davide , Parrinello Michele , Pollard Thomas D. , Voth Gregory A.
Published: July 2009

The influence of the state of the bound nucleotide (ATP, ADP-Pi, or ADP) on the conformational free-energy landscape of actin is investigated. Nucleotide-dependent folding of the DNase-I binding (DB) loop in monomeric actin and the actin trimer is carried out using all-atom molecular dynamics (MD) calculations accelerated with a multiscale implementation of the metadynamics algorithm. Additionally, an investigation of the opening and closing of the actin nucleotide binding cleft is performed. Nucleotide-dependent free-energy profiles for all of these conformational changes are calculated within the framework of metadynamics. We find that in ADP-bound monomer, the folded and unfolded states of the DB loop have similar relative free-energy. This result helps explain the experimental difficulty in obtaining an ordered crystal structure for this region of monomeric actin. However, we find that in the ADP-bound actin trimer, the folded DB loop is stable and in a free-energy minimum. It is also demonstrated that the nucleotide binding cleft favors a closed conformation for the bound nucleotide in the ATP and ADP-Pi states, whereas the ADP state favors an open confirmation, both in the monomer and trimer. These results suggest a mechanism of allosteric interactions between the nucleotide binding cleft and the DB loop. This behavior is confirmed by an additional simulation that shows the folding free-energy as a function of the nucleotide cleft width, which demonstrates that the barrier for folding changes significantly depending on the value of the cleft width.
Dynamic sensitivity of area V4 neurons during saccade preparation
Authors: Han Xue , Xian Sherry X. , Moore Tirin
Published: July 2009

During the preparation of saccadic eye movements, visual attention is confined to the target of intended fixation and there is a corresponding diminution of visual sensitivity at nontarget locations. Neurons within the macaque visual cortex exhibit correlates of these perceptual changes, such as in area V4, where neuronal responses are enhanced during the preparation of saccades to stimuli within the receptive field (RF), and responses are suppressed during the preparation of saccades to other locations. Both the perceptual and neurophysiological effects suggest that the sensitivity of visual cortical neurons to input is dynamic during saccade preparation. We probed the contrast sensitivity of area V4 neurons to nontarget stimuli at varying times during the preparation of saccades to locations outside of the neuron's receptive field. We found that the contrast sensitivity of many neurons is profoundly altered within 50 ms of saccade onset. The luminance or color contrast sensitivity of individual V4 neurons could increase, decrease, or remain unchanged before saccade onset. For luminance contrast sensitivity, decreases in sensitivity were more frequent and larger in magnitude, resulting in an overall decrement in sensitivity across the population. For color contrast, the effects were smaller and more heterogeneous, resulting in little or no overall change in sensitivity across the population. Our results demonstrate the dynamic influence that saccade preparation has on the sensitivity of visual cortical neurons and suggest a basis for the changes in perception known to occur during saccade preparation.
Protein targeting into secondary plastids of chlorarachniophytes
Authors: Hirakawa Yoshihisa , Nagamune Kisaburo , Ishida Ken-ichiro
Published: July 2009

Most plastid proteins are encoded by the nuclear genome, and consequently, need to be transported into plastids across multiple envelope membranes. In diverse organisms possessing secondary plastids, nuclear-encoded plastid precursor proteins (preproteins) commonly have an N-terminal extension that consists of an endoplasmic reticulum (ER)-targeting signal peptide and a transit peptide-like sequence (TPL). This bipartite targeting peptide is believed to be necessary for targeting the preproteins into the secondary plastids. Here, we newly demonstrate the function of the bipartite targeting peptides of an algal group, chlorarachniophytes, and characterize the functional domains of the TPL in the precursor of a plastid protein, ATP synthase delta subunit (AtpD), using a GFP as a reporter molecule. We show that the C-terminal portion of the TPL is important for targeting the AtpD preprotein from the ER into the chlorarachniophyte plastids, and several positively charged amino acids in the TPL are also necessary for transporting the preprotein across the 2 innermost plastid membranes. Compared with other groups with secondary plastids, the TPL functional domains of the chlorarachniophytes are unique, which might be caused by independent acquisition of their plastids.
Cluster size regulates protein sorting in the immunological synapse
Authors: Hartman Niña C. , Nye Jeffrey A. , Groves Jay T.
Published: July 2009

During antigen recognition by T cells, signaling molecules on the T cell engage ligands on the antigen-presenting cell and organize into spatially distinctive patterns. These are collectively known as the immunological synapse (IS). Causal relationships between large-scale spatial organization and signal transduction have previously been established. Although it is known that receptor transport during IS formation is driven by actin polymerization, the mechanisms by which different proteins become spatially sorted remain unclear. These sorting processes contribute a facet of signal regulation; thus their elucidation is important for ultimately understanding signal transduction through the T cell receptor. Here we investigate protein cluster size as a sorting mechanism using the hybrid live T cell−supported membrane system. The clustering state of the co-stimulatory molecule lymphocyte function-associated antigen-1 (LFA-1) is modulated, either by direct antibody crosslinking or by crosslinking its intercellular adhesion molecule-1 ligand on the supported bilayer. In a mature IS, native LFA-1 generally localizes into a peripheral ring surrounding a central T cell receptor cluster. Higher degrees of LFA-1 clustering, induced by either method, result in progressively more central localization, with the most clustered species fully relocated to the central zone. These results demonstrate that cluster size directly influences protein spatial positioning in the T cell IS. We discuss a sorting mechanism, based on frictional coupling to the actin cytoskeleton, that is consistent with these observations and is, in principle, extendable to all cell surface proteins in the synapse.
Singlet oxygen-dependent translational control in the
tigrina-d.12
mutant of barley
Authors: Khandal Dhriti , Samol Iga , Buhr Frank , Pollmann Stephan , Schmidt Holger , Clemens Stephan , Reinbothe Steffen , Reinbothe Christiane
Published: July 2009

The
tigrina
(
tig
)-
d.12
mutant of barley is impaired in the negative control limiting excess protochlorophyllide (Pchlide) accumulation in the dark. Upon illumination, Pchlide operates as photosensitizer and triggers singlet oxygen production and cell death. Here, we show that both Pchlide and singlet oxygen operate as signals that control gene expression and metabolite accumulation in
tig-d.12
plants. In vivo labeling, Northern blotting, polysome profiling, and protein gel blot analyses revealed a selective suppression of synthesis of the small and large subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase (RBCSs and RBCLs), the major light-harvesting chlorophyll
a/b
-binding protein of photosystem II (LHCB2), as well as other chlorophyll-binding proteins, in response to singlet oxygen. In part, these effects were caused by an arrest in translation initiation of photosynthetic transcripts at 80S cytoplasmic ribosomes. The observed changes in translation correlated with a decline in the phosphorylation level of ribosomal protein S6. At later stages, ribosome dissociation occurred. Together, our results identify translation as a major target of singlet oxygen-dependent growth control and cell death in higher plants.
Leptin-mediated changes in hepatic mitochondrial metabolism, structure, and protein levels
Authors: Singh Amandeep , Wirtz Martin , Parker Nadeene , Hogan Matthew , Strahler John , Michailidis George , Schmidt Sarah , Vidal-Puig Antonio , Diano Sabrina , Andrews Philip , Brand Martin D. , Friedman Jeffrey
Published: July 2009

Leptin reduces body weight in
ob/ob
mice by decreasing food intake and increasing energy expenditure; however, the mechanisms by which it does the latter are not known. Here we report that 30% of the weight loss induced by leptin treatment of
ob/ob
mice is due to changes in energy expenditure. In assessing leptin's effects on specific tissues, we found that hepatic basal metabolic rate was paradoxically decreased 1.7-fold with leptin treatment, which was the result of a 1.6-fold reduction in mitochondrial volume density and altered substrate oxidation kinetics. The altered kinetics were associated with a decrease in protein levels of 2 mitochondrial respiratory chain components—cytochrome
c
oxidase subunit VIa and cytochrome
c
oxidase subunit IV. In addition to reduced hepatic metabolism, there was reduced long chain fatty acid production and a 2.5-fold increase in hepatic lipid export, both of which explain the reduced steatosis in leptin-treated animals. These data help clarify the role of the liver in leptin-mediated weight loss and define the mechanisms by which leptin alters hepatic metabolism and corrects steatosis.
Structure of the hepatitis E virus-like particle suggests mechanisms for virus assembly and receptor binding
Authors: Guu Tom S. Y. , Liu Zheng , Ye Qiaozhen , Mata Douglas A. , Li Kunpeng , Yin Changcheng , Zhang Jingqiang , Tao Yizhi Jane
Published: July 2009

Hepatitis E virus (HEV), a small, non-enveloped RNA virus in the family
Hepeviridae
, is associated with endemic and epidemic acute viral hepatitis in developing countries. Our 3.5-Å structure of a HEV-like particle (VLP) shows that each capsid protein contains 3 linear domains that form distinct structural elements: S, the continuous capsid; P1, 3-fold protrusions; and P2, 2-fold spikes. The S domain adopts a jelly-roll fold commonly observed in small RNA viruses. The P1 and P2 domains both adopt β-barrel folds. Each domain possesses a potential polysaccharide-binding site that may function in cell-receptor binding. Sugar binding to P1 at the capsid protein interface may lead to capsid disassembly and cell entry. Structural modeling indicates that native T = 3 capsid contains flat dimers, with less curvature than those of T = 1 VLP. Our findings significantly advance the understanding of HEV molecular biology and have application to the development of vaccines and antiviral medications.
Long-term survival following a single treatment of kidney tumors with multiwalled carbon nanotubes and near-infrared radiation
Authors: Burke Andrew , Ding Xuanfeng , Singh Ravi , Kraft Robert A. , Levi-Polyachenko Nicole , Rylander Marissa Nichole , Szot Chris , Buchanan Cara , Whitney Jon , Fisher Jessica , Hatcher Heather C. , D'Agostino Ralph , Kock Nancy D. , Ajayan P. M. , Carroll David L. , Akman Steven , Torti Frank M. , Torti Suzy V.
Published: July 2009

Multiwalled carbon nanotubes (MWCNTs) exhibit physical properties that render them ideal candidates for application as noninvasive mediators of photothermal cancer ablation. Here, we demonstrate that use of MWCNTs to generate heat in response to near-infrared radiation (NIR) results in thermal destruction of kidney cancer in vitro and in vivo. We document the thermal effects of the therapy through magnetic resonance temperature-mapping and heat shock protein-reactive immunohistochemistry. Our results demonstrate that use of MWCNTs enables ablation of tumors with low laser powers (3 W/cm
2
) and very short treatment times (a single 30-sec treatment) with minimal local toxicity and no evident systemic toxicity. These treatment parameters resulted in complete ablation of tumors and a >3.5-month durable remission in 80% of mice treated with 100 μg of MWCNT. Use of MWCNTs with NIR may be effective in anticancer therapy.
Correspondence of the brain's functional architecture during activation and rest
Authors: Smith Stephen M. , Fox Peter T. , Miller Karla L. , Glahn David C. , Fox P. Mickle , Mackay Clare E. , Filippini Nicola , Watkins Kate E. , Toro Roberto , Laird Angela R. , Beckmann Christian F.
Published: July 2009

Neural connections, providing the substrate for functional networks, exist whether or not they are functionally active at any given moment. However, it is not known to what extent brain regions are continuously interacting when the brain is “at rest.” In this work, we identify the major explicit activation networks by carrying out an image-based activation network analysis of thousands of separate activation maps derived from the BrainMap database of functional imaging studies, involving nearly 30,000 human subjects. Independently, we extract the major covarying networks in the resting brain, as imaged with functional magnetic resonance imaging in 36 subjects at rest. The sets of major brain networks, and their decompositions into subnetworks, show close correspondence between the independent analyses of resting and activation brain dynamics. We conclude that the full repertoire of functional networks utilized by the brain in action is continuously and dynamically “active” even when at “rest.”
Extreme diversity in noncalcifying haptophytes explains a major pigment paradox in open oceans
Authors: Liu Hui , Probert Ian , Uitz Julia , Claustre Hervé , Aris-Brosou Stéphane , Frada Miguel , Not Fabrice , de Vargas Colomban
Published: July 2009

The current paradigm holds that cyanobacteria, which evolved oxygenic photosynthesis more than 2 billion years ago, are still the major light harvesters driving primary productivity in open oceans. Here we show that tiny unicellular eukaryotes belonging to the photosynthetic lineage of the Haptophyta are dramatically diverse and ecologically dominant in the planktonic photic realm. The use of Haptophyta-specific primers and PCR conditions adapted for GC-rich genomes circumvented biases inherent in classical genetic approaches to exploring environmental eukaryotic biodiversity and led to the discovery of hundreds of unique haptophyte taxa in 5 clone libraries from subpolar and subtropical oceanic waters. Phylogenetic analyses suggest that this diversity emerged in Paleozoic oceans, thrived and diversified in the permanently oxygenated Mesozoic Panthalassa, and currently comprises thousands of ribotypic species, belonging primarily to low-abundance and ancient lineages of the “rare biosphere.” This extreme biodiversity coincides with the pervasive presence in the photic zone of the world ocean of 19′-hexanoyloxyfucoxanthin (19-Hex), an accessory photosynthetic pigment found exclusively in chloroplasts of haptophyte origin. Our new estimates of depth-integrated relative abundance of 19-Hex indicate that haptophytes dominate the chlorophyll
a
-normalized phytoplankton standing stock in modern oceans. Their ecologic and evolutionary success, arguably based on mixotrophy, may have significantly impacted the oceanic carbon pump. These results add to the growing evidence that the evolution of complex microbial eukaryotic cells is a critical force in the functioning of the biosphere.
Solvation in protein (un)folding of melittin tetramer–monomer transition
Authors: Othon Christina M. , Kwon Oh-Hoon , Lin Milo M. , Zewail Ahmed H.
Published: July 2009

Protein structural integrity and flexibility are intimately tied to solvation. Here, we examine the effect that changes in bulk and local solvent properties have on protein structure and stability. We observe the change in solvation of an unfolding of the protein model, melittin, in the presence of a denaturant, trifluoroethanol. The peptide system displays a well defined transition in that the tetramer unfolds without disrupting the secondary or tertiary structure. In the absence of local structural perturbation, we are able to reveal exclusively the role of solvation dynamics in protein structure stabilization and the (un)folding pathway. A sudden retardation in solvent dynamics, which is coupled to the change in protein structure, is observed at a critical trifluoroethanol concentration. The large amplitude conformational changes are regulated by the local solvent hydrophobicity and bulk solvent viscosity.
Short actin-based mechanism for light-directed chloroplast movement in
Arabidopsis
Authors: Kadota Akeo , Yamada Noboru , Suetsugu Noriyuki , Hirose Mana , Saito Chieko , Shoda Keiko , Ichikawa Satoshi , Kagawa Takatoshi , Nakano Akihiko , Wada Masamitsu
Published: July 2009

Organelle movement is essential for proper function of living cells. In plants, these movements generally depend on actin filaments, but the underlying mechanism is unknown. Here, in
Arabidopsis
, we identify associations of short actin filaments along the chloroplast periphery on the plasma membrane side associated with chloroplast photorelocation and anchoring to the plasma membrane. We have termed these chloroplast-actin filaments (cp-actin filaments). Cp-actin filaments emerge from the chloroplast edge and exhibit rapid turnover. The presence of cp-actin filaments depends on an actin-binding protein, chloroplast unusual positioning1 (CHUP1), localized on the chloroplast envelope.
chup1
mutant lacked cp-actin filaments but showed normal cytoplasmic actin filaments. When irradiated with blue light to induce chloroplast movement, cp-actin filaments relocalize to the leading edge of chloroplasts before and during photorelocation and are regulated by 2 phototropins, phot1 and phot2. Our findings suggest that plants evolved a unique actin-based mechanism for organelle movement.
BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage
Authors: Huang Haiyan , Song Tan-Jing , Li Xi , Hu Lingling , He Qun , Liu Mei , Lane M. Daniel , Tang Qi-Qun
Published: July 2009

Obesity is accompanied by an increase in both adipocyte number and size. The increase in adipocyte number is the result of recruitment to the adipocyte lineage of pluripotent stem cells present in the vascular stroma of adipose tissue. These pluripotent cells have the potential to undergo commitment and then differentiate into adipocytes, as well as myocytes, osteocytes, and chondrocytes. In this article, we show that both bone morphogenetic protein (BMP)2 and BMP4 can induce commitment of C3H10T1/2 pluripotent stem cells into adipocytes. After treatment of C3H10T1/2 stem cells with these BMPs during proliferation followed by exposure to differentiation inducers at growth arrest, nearly all cells enter the adipose development pathway, express specific adipocyte markers, and acquire the adipocyte phenotype. Overexpression of constitutively active BMP receptor (CA)-BMPr1A or CA-BMPr1B induces commitment in the absence of BMP2/4, whereas overexpression of a dominant-negative receptor dominant-negative-BMPr1A suppresses commitment induced by BMP. Also, knockdown of the expression of Smad4 (coregulator in the BMP/Smad signaling pathway) with RNAi disrupts commitment by the BMPs. However, knockdown of expression of p38 MAPK (an intermediary in the BMP/MAPK signaling pathway) with RNAi had little effect on BMP-induced commitment. Together, these findings indicate that the BMP/Smad signaling pathway has a dominant role in adipocyte lineage determination. Proteomic analysis identified lysyl oxidase (LOX), a bona fide downstream target gene of the BMP signaling pathway. Expression of LOX is induced by BMP2/4 during adipocyte lineage commitment, and knockdown of its expression disrupts the commitment process.
Osteochondral defect repair after implantation of biodegradable scaffolds: indirect magnetic resonance arthrography and histopathologic correlation
Authors: Streitparth F. , Schöttle P. , Schlichting K. , Schell H. , Fischbach F. , Denecke T. , Duda G. N. , Schröder R. J.
Published: July 2009

Background: Biodegradable scaffolds have become an important option in the treatment of osteochondral defects. Therefore, accurate and reproducible monitoring of scaffold repair tissue is crucial.

Purpose: To assess the feasibility of indirect magnetic resonance (MR) arthrography in determining the quality of osteochondral repair after scaffold implantation using an MR imaging (MRI) scoring and grading system with histology as reference.

Material and Methods: Osteochondral defects created at ovine condylar facets were treated with either a commercial poly (DL-lactide-co-glycolide) (PLG) scaffold or a modified softer one ( n=6/group; 87% and 55% of the elastic modulus of ovine subchondral bone, respectively). Empty defects at the contralateral condyle served as control group. A 1.5T MRI scan was performed after 6 months with proton density (PD)-weighted (w) fat-saturated (fs) fast spin-echo (FSE), T1-w two-dimensional (2D), and 3D fs gradient echo (GE) sequences 30min after intravenous Gd-DTPA administration and passive joint movement. Two independent radiologists evaluated the repair tissue. The MR findings were correlated with histological findings.

Results: MRI and histological grading correlated well (10/12 cases). The stiff-scaffold group showed significantly superior repair in comparison to the control group ( P<0.05). The 3D fs GE sequence proved to be most valuable in evaluating morphologic status. Complete defect filling and integration, intact surface and isointense signal to the adjacent native cartilage, subchondral incorporation with bone marrow edema, and graft plug enhancement were associated with a good histological outcome. Histologically, we found a smooth fibrocartilaginous layer and osseous replacement of the scaffold. Incomplete cartilage repair and irregular subchondral structures on the MRI correlated histologically with fibrocartilage-like repair and subchondral sclerosis, due to substantial degradation of the scaffold.

Conclusion: Indirect MR arthrography is an accurate, noninvasive monitoring tool in the follow-up of scaffold implants. The MRI scoring and grading system allows reliable assessment of normal and pathological repair, with high correlation to histological findings.
Extremely rare r-i subtype coronary artery anomaly and accompanying incomplete myocardial bridging on the left anterior descending artery in a symptomatic patient: multidetector computed tomography and coronary angiography findings
Authors: Koksal A. , Canyigit M. , Akgoz A. , Kaya D. , Dincer H. , Akhan O.
Published: July 2009

Myocardial bridging and single coronary artery (SCA) may both lead to myocardial ischemia and related secondary complications. We present multidetector computed tomography (MDCT) and catheter coronary angiography (CCA) findings of R-I subtype SCA, which is a distinctively rare congenital coronary anomaly, and accompanying incomplete myocardial bridging in a case with dyspnea and chest burning. In addition, CCA showed a thin milking effect at the tunneled artery.
Confirmation of t1-bright vein of galen aneurysm spontaneous thrombosis by subtraction magnetic resonance venography: a case report
Authors: Irfan M. , Lohman B. , McKinney A. M.
Published: July 2009

Spontaneous thrombosis of a vein of Galen aneurysmal malformation (VOGM) is rare. We describe a 2-month-old patient with a patent VOGM and hydrocephalus, also confirmed patent at 6 months, but with subsequent lack of filling on preembolization catheter digital subtraction angiography (DSA) at 9 months’ age. Due to the presence of T1- and T2-bright signal, noncontrast T1-weighted images (T1WI), T2-weighted images (T2WI), two-dimensional (2D) time-of-flight (TOF) magnetic resonance venography (MRV), and postcontrast T1WI were ambiguous for patency. However, subtracting the pre- from the postcontrast MRV images confirmed closure compared to subtracted images at 6 months’ age. The factors contributing to thrombosis were likely a combination of a disproportionately small straight sinus, ventriculostomy, and contrast medium from DSA.
Detection of cerebral metastases on magnetic resonance imaging: intraindividual comparison of gadobutrol with gadopentetate dimeglumine
Authors: Anzalone Nicoletta , Gerevini Simonetta , Scotti Roberta , Vezzulli Paolo , Picozzi Piero
Published: July 2009

Background: Contrast-enhanced magnetic resonance (MR) imaging with gadolinium-based contrast agents is widely used for the detection of cerebral metastases with standard contrast agents. Newer developments in MR contrast agents have led to a higher relaxivity and/or concentration for these agents.

Purpose: To assess the effectiveness of a standard dose of 1.0 M gadobutrol compared with a standard dose of gadopentetate dimeglumine for the MR detection of brain metastases.

Material and Methods: 27 patients with at least one cerebral metastasis were examined twice with contrast-enhanced MR imaging, using gadobutrol at 0.1 ml/kg and gadopentetate dimeglumine at 0.2 ml/kg (i.e., identical gadolinium dosage of 0.1 mmol/kg bodyweight). The interval between examinations was 18 hours, and the order of injection was fully randomized. Images were acquired using a three-dimensional (3D) fast gradient echo sequence, and evaluated in blinded fashion by two experienced neuroradiologists in consensus in terms of the total number of lesions detected at each examination in each patient and qualitatively in terms of the lesion conspicuity observed.

Results: A total of 67 lesions were detected after gadobutrol compared with 65 lesions detected after gadopentetate dimeglumine. In two patients, a lesion was seen only after gadobutrol. Qualitative comparison of images revealed improved lesion conspicuity after gadobutrol in 10/27 cases compared with 0/27 cases after gadopentetate dimeglumine, and equivalent conspicuity in 17/27 cases ( P=0.002, gadobutrol vs. gadopentetate dimeglumine).

Conclusion:At equal gadolinium dosage, gadobutrol appears to offer significant advantages over gadopentetate dimeglumine for the visualization of brain metastases, with particular benefit for improving the conspicuity of detected lesions.