bluuebunny/crossref_metadata_2025 huggingface dataset:
Lipid transport by mammalian ABC proteins
Authors: Quazi Faraz , Molday Robert S.
Published: September 2011

ABC (ATP-binding cassette) proteins actively transport a wide variety of substrates, including peptides, amino acids, sugars, metals, drugs, vitamins and lipids, across extracellular and intracellular membranes. Of the 49 hum an ABC proteins, a significant number are known to mediate the extrusion of lipids from membranes or the flipping of membrane lipids across the bilayer to generate and maintain membrane lipid asymmetry. Typical lipid substrates include phospholipids, sterols, sphingolipids, bile acids and related lipid conjugates. Members of the ABCA subfamily of ABC transporters and other ABC proteins such as ABCB4, ABCG1 and ABCG5/8 implicated in lipid transport play important roles in diverse biological processes such as cell signalling, membrane lipid asymmetry, removal of potentially toxic compounds and metabolites, and apoptosis. The importance of these ABC lipid transporters in cell physiology is evident from the finding that mutations in the genes encoding many of these proteins are responsible for severe inherited diseases. For example, mutations in ABCA1 cause Tangier disease associated with defective efflux of cholesterol and phosphatidylcholine from the plasma membrane to the lipid acceptor protein apoA1 (apolipoprotein AI), mutations in ABCA3 cause neonatal surfactant deficiency associated with a loss in secretion of the lipid pulmonary surfactants from lungs of newborns, mutations in ABCA4 cause Stargardt macular degeneration, a retinal degenerative disease linked to the reduced clearance of retinoid compounds from photoreceptor cells, mutations in ABCA12 cause harlequin and lamellar ichthyosis, skin diseases associated with defective lipid trafficking in keratinocytes, and mutations in ABCB4 and ABCG5/ABCG8 are responsible for progressive intrafamilial hepatic disease and sitosterolaemia associated with defective phospholipid and sterol transport respectively. This chapter highlights the involvement of various mammalian ABC transporters in lipid transport in the context of their role in cell signalling, cellular homoeostasis, apoptosis and inherited disorders.
Ge clustering effects in Ge doped CdTe: Electrical and structural properties
Authors: Fraboni B. , Boscherini F. , Fochuk P. , Cavallini A.
Published: September 2011

High resistivity CdTe can be achieved by introducing impurities that create deep levels which, in turn, control the electronic transport properties of the material via a compensation process. We have characterized the effects of thermal annealing of high resistivity CdTe:Ge under either Te- or Cd-rich atmosphere to understand how modifications in the structure of Ge-related defective states and their electrical activity affect the material transport properties. We have investigated the transport properties with current-voltage analyses, the electrically active deep traps by photo-induced current transient spectroscopy and the local environment of Ge atoms by x-ray absorption spectroscopy. By correlating the modifications observed, we determined the occurrence of Ge clustering effects and associated them to the formation of electrically active deep donor traps, one located at EC-0.31 eV and the other one at midgap, with an activation energy of 0.82 eV.
Destruction of methane in low-pressure, electrodeless radio frequency plasma on quartz walls
Authors: Mozetic Miran , Vesel Alenka , Alegre Daniel , Tabares Francisco L.
Published: September 2011

The destruction of methane in a low pressure, electrodeless radiofrequency discharge was studied by mass spectrometry. Plasmas were created in a quartz tube with the inner diameter of 3.6 cm. A coil with 6 turns was fixed onto the tube and connected to radio frequency (RF) generator via a matching network. Methane flows between 1.16 and 3.30 mbar.l/s and various RF powers up to 1200 W were used. Depending on gas flow and RF power, the discharge was either in E or H mode. The evolution of different hydrocarbon species versus discharge power was measured systematically by a differentially pumped mass spectrometer. No carbon deposit on the quartz walls was seen during the scans. The results showed that the destruction of methane depended on the flow rate as well as the discharge power and was accomplished already in the E mode. Well-pronounced maxima in the formation of both ethane and acetylene were observed at low gas flow rates. The observed products from radical recombination evolved with plasma conditions, and their contribution to the global carbon balance strongly decreased at high power-per-particle density. The functionality of secondary hydrocarbon formation with respect to the experimental parameters has been analyzed and a simple kinetic model is proposed in order to account for the observed trends.
Effects of external axial magnetic field on fast electron propagation
Authors: Yang X. H. , Borghesi M. , Qiao B. , Geissler M. , Robinson A. P. L.
Published: September 2011

A scheme employing an external axial magnetic field is proposed to diagnose the intrinsic divergence of laser-generated fast electron beams, and this is studied numerically with hybrid simulations. The maximum beam radius of fast electrons increases with the initial divergence and decreases with the amplitude of the axial magnetic field. It is indicated that the intrinsic divergence of fast electrons can be inferred from measurements of the beam radius at different depth under the axial field. The proposed scheme here may be useful for future fast ignition experiments and in other applications of laser-generated fast electron beams.
Hydrodynamic approach to the free electron laser instability
Authors: Tzenov Stephan I. , Marinov Kiril B.
Published: September 2011

Starting from the Vlasov-Maxwell system, an exact relativistic hydrodynamic closure for a special type water bag distributions satisfying the Vlasov equation has been derived. It has been shown that the hydrodynamic equations are fully equivalent to the original Vlasov-Maxwell equations. The linear stability of the exact hydrodynamic closure has been studied as well. It has been shown that all basic features of the small signal gain can be derived from the fluid dynamic description developed here. Satisfactory agreement with previously reported results has been also found.
A study of the role of various reactions on the density distribution of hydrogen, silylene, and silyl in SiH4/H2 plasma discharges
Authors: Aman-ur-Rehman  , Kwon H. C. , Park W. T. , Lee J. K.
Published: September 2011

Fluid model has been used to study the effect of pressure on the distribution of hydrogen (H), silylene (SiH2), and silyl (SiH3) in hydrogen silane plasma discharges used for deposition of hydrogenated microcrystalline silicon (μc-Si:H) or hydrogenated amorphous silicon (a-Si:H) thin films for solar cells. Time averaged reaction rates have been calculated to study the influence of various reactions on the density distributions of hydrogen, silylene, and silyl. Change in the distributions of hydrogen and silylene from bell shaped distribution at low pressure (1 Torr) to double humped distribution at high pressure (5 Torr) is explained with the help of time averaged reaction rates. Important reactions have been identified that contribute to the production and consumption of hydrogen (H), silylene (SiH2), and silyl (SiH3). The hydrogen consumption reactions SiH4 + H → SiH3 + H2 and SiH3 + H → SiH2 + H2 are found to play a central role in deciding the distribution of hydrogen. On the other hand, silylene consumption reaction SiH2 + H2 → SiH4 is found to play a central role in determining the distribution of silylene. The distribution of these species at high pressure has been explained by using time averaged continuity equation. The code has been optimized by identifying 33 reactions (out of 53 reactions which contribute in the production and consumption of H, SiH2, and SiH3) that have no net effect on the density and distribution of these species. It is observed that dropping of 33 reactions has insignificant effect on the density of all the thin film deposition precursors such as Si, SiH, SiH2, SiH3, and Si2H5. This reduced set of 20 reactions can be used instead of 53 reactions to calculate the density and distribution of H, SiH2, and SiH3 in the fluid simulation of SiH4/H2 plasma discharges.
Amorphous interface layer in thin graphite films grown on the carbon face of SiC
Authors: Colby R. , Bolen M. L. , Capano M. A. , Stach E. A.
Published: September 2011

Cross-sectional transmission electron microscopy (TEM) is used to characterize an amorphous layer observed at the interface in graphite and graphene films grown via thermal decomposition of C-face 4H-SiC. The amorphous layer does not cover the entire interface, but uniform contiguous regions span microns of cross-sectional interface. Scanning transmission electron microscopy (STEM) images and electron energy loss spectroscopy (EELS) demonstrate that the amorphous layer is a carbon-rich composition of Si/C. The amorphous layer is clearly observed in samples grown at 1600 °C for a range of growth pressures in argon, but not at 1500 °C, suggesting a temperature-dependent formation mechanism.
Determination of long time discharge current in microelectromechanical system capacitive switches
Authors: Koutsoureli M. , Papaioannou G.
Published: September 2011

An improved method to study the long term discharge current through the dielectric film in microelectromechanical system capacitive switches is presented. The method allows the detection of currents in the sub-fempto-Ampere range by monitoring the decay of the bias for minimum capacitance in the pull-up state. The method has been applied for time interval in excess of 10 000 s. Finally, it is shown that in carefully designed devices the method allows the calculation of the current that arises from the charge fluctuation decay.
A unifying approach for food webs, phylogeny, social networks, and statistics
Authors: Chiu Grace S. , Westveld Anton H.
Published: September 2011

A food web consists of nodes, each consisting of one or more species. The role of each node as predator or prey determines the trophic relations that weave the web. Much effort in trophic food web research is given to understand the connectivity structure, or the nature and degree of dependence among nodes. Social network analysis (SNA) techniques—quantitative methods commonly used in the social sciences to understand network relational structure—have been used for this purpose, although postanalysis effort or biological theory is still required to determine what natural factors contribute to the feeding behavior. Thus, a conventional SNA alone provides limited insight into trophic structure. Here we show that by using novel statistical modeling methodologies to express network links as the random response of within- and internode characteristics (predictors), we gain a much deeper understanding of food web structure and its contributing factors through a unified statistical SNA. We do so for eight empirical food webs: Phylogeny is shown to have nontrivial influence on trophic relations in many webs, and for each web trophic clustering based on feeding activity and on feeding preference can differ substantially. These and other conclusions about network features are purely empirical, based entirely on observed network attributes while accounting for biological information built directly into the model. Thus, statistical SNA techniques, through statistical inference for feeding activity and preference, provide an alternative perspective of trophic clustering to yield comprehensive insight into food web structure.
Transcription factor TFIIF is not required for initiation by RNA polymerase II, but it is essential to stabilize transcription factor TFIIB in early elongation complexes
Authors: Čabart Pavel , Újvári Andrea , Pal Mahadeb , Luse Donal S.
Published: September 2011

Transcription factors TFIIB and TFIIF are both required for RNA polymerase II preinitiation complex (PIC) assembly, but their roles at and downstream of initiation are not clear. We now show that TFIIF phosphorylated by casein kinase 2 remains competent to support PIC assembly but is not stably retained in the PIC. PICs completely lacking TFIIF are not defective in initiation or subsequent promoter clearance, demonstrating that TFIIF is not required for initiation or clearance. Lack of TFIIF in the PIC reduces transcription levels at some promoters, coincident with reduced retention of TFIIB. TFIIB is normally associated with the early elongation complex and is only destabilized at +12 to +13. However, if TFIIF is not retained in the PIC, TFIIB can be lost immediately after initiation. TFIIF therefore has an important role in stabilizing TFIIB within the PIC and after transcription initiates.
Recovery of stereopsis through perceptual learning in human adults with abnormal binocular vision
Authors: Ding Jian , Levi Dennis M.
Published: September 2011

Stereopsis, the perception of depth based on the disparity of the images projected to the retinas of the two eyes, is an important process in our three-dimensional world; however, 3–5% of the population is stereoblind or has seriously impaired stereovision. Here we provide evidence for the recovery of stereopsis through perceptual learning, the repetitive practice of a demanding visual task, in human adults long deprived of normal binocular vision. We used a training paradigm that combines monocular cues that were correlated perfectly with the disparity cues. Following perceptual learning (thousands of trials) with stereoscopic gratings, five adults who initially were stereoblind or stereoanomalous showed substantial recovery of stereopsis, both on psychophysical tests with stimuli that contained no monocular cues and on clinical testing. They reported that depth “popped out” in daily life, and enjoyed 3D movies for the first time. After training, stereo tests with dynamic random-dot stereograms and band-pass noise revealed the properties of the recovered stereopsis: It has reduced resolution and precision, although it is based on perceiving depth by detecting binocular disparity. We conclude that some human adults deprived of normal binocular vision can recover stereopsis at least partially.
In situ engineering of the lymph node microenvironment via intranodal injection of adjuvant-releasing polymer particles
Authors: Jewell Christopher M. , Bustamante López Sandra C. , Irvine Darrell J.
Published: September 2011

Recent studies have demonstrated a simple, potentially universal strategy to enhance vaccine potency, via intralymph node (i.LN) injection. To date, intranodal immunization studies have focused on the delivery of unadjuvanted vaccines (e.g., naked DNA, peptide, or protein). We hypothesized that combining i.LN vaccination with controlled release biomaterials permitting sustained dosing of molecular adjuvants to the local tissue microenvironment would further enhance this promising vaccination strategy. To test this idea, we encapsulated the Toll-like receptor-3 ligand poly(inosinic:cytidylic acid) (polyIC) in biodegradable poly(lactide-
co
-glycolide) microparticles (MPs) designed to remain extracellular and release polyIC in the LN over several days. Intranodal injection of MPs increased persistence of polyIC in LNs compared to the same dose of soluble polyIC or polyIC formulated in nanoparticles, leading to increased accumulation of Toll-like receptor agonist in LN-resident antigen presenting cells and more enduring dendritic cell activation. Intralymph node injection of ovalbumin mixed with polyIC-releasing MPs enhanced the humoral response and expanded ovalbumin-specific T cells to frequencies as high as 18% among all CD8
+
cells following a single injection (8.2-fold greater than the same vaccine given i.m.), a response that could not be matched by antigen mixed with polyIC-loaded nanoparticles or a 10-fold greater dose of soluble polyIC. Thus, i.LN immunization with slow release-formulated adjuvants may be a broadly applicable strategy to enhance therapeutic or prophylactic vaccines.
In vivo protein-interaction mapping of a mitochondrial translocator protein Tom22 at work
Authors: Shiota Takuya , Mabuchi Hide , Tanaka-Yamano Sachiko , Yamano Koji , Endo Toshiya
Published: September 2011

Mitochondrial protein import requires cooperation of the machineries called translocators in the outer and inner mitochondrial membranes. Here we analyze the interactions of Tom22, a multifunctional subunit of the outer membrane translocator TOM40 complex, with other translocator subunits such as Tom20, Tom40, and Tim50 and with substrate precursor proteins at a spatial resolution of the amino acid residue by in vivo and in organello site-specific photocross-linking. Changes in cross-linking patterns caused by excess substrate precursor proteins or presequence peptides indicate how the cytosolic receptor domain of Tom22 accepts substrate proteins and how the intermembrane space domain of Tom22 transfers them to Tim50 of the inner-membrane translocator.
Genetic evidence for a protective role of the peritrophic matrix against intestinal bacterial infection in
Drosophila melanogaster
Authors: Kuraishi Takayuki , Binggeli Olivier , Opota Onya , Buchon Nicolas , Lemaitre Bruno
Published: September 2011

The peritrophic matrix (PM) forms a layer composed of chitin and glycoproteins that lines the insect intestinal lumen. This physical barrier plays a role analogous to that of mucous secretions of the vertebrate digestive tract and is thought to protect the midgut epithelium from abrasive food particles and microbes. Almost nothing is known about PM functions in
Drosophila
, and its function as an immune barrier has never been addressed by a genetic approach. Here we show that the Drosocrystallin (Dcy) protein, a putative component of the eye lens of
Drosophila
, contributes to adult PM formation. A loss-of-function mutation in the
dcy
gene results in a reduction of PM width and an increase of its permeability. Upon bacterial ingestion a higher level of expression of antibacterial peptides was observed in
dcy
mutants, pointing to an influence of this matrix on bacteria sensing by the Imd immune pathway. Moreover,
dcy
-deficient flies show an increased susceptibility to oral infections with the entomopathogenic bacteria
Pseudomonas entomophila
and
Serratia marcescens
.
Dcy
mutant flies also succumb faster than wild type upon ingestion of a
P. entomophila
toxic extract. We show that this lethality is due in part to an increased deleterious action of Monalysin, a pore-forming toxin produced by
P. entomophila
. Collectively, our analysis of the
dcy
immune phenotype indicates that the PM plays an important role in
Drosophila
host defense against enteric pathogens, preventing the damaging action of pore-forming toxins on intestinal cells.
Developmental basis of sexually dimorphic digit ratios
Authors: Zheng Zhengui , Cohn Martin J.
Published: September 2011

Males and females generally have different finger proportions. In males, digit 2 is shorter than digit 4, but in females digit 2 is the same length or longer than digit 4. The second- to fourth-digit (2D:4D) ratio correlates with numerous sexually dimorphic behavioral and physiological conditions. Although correlational studies suggest that digit ratios reflect prenatal exposure to androgen, the developmental mechanism underlying sexually dimorphic digit development remains unknown. Here we report that the 2D:4D ratio in mice is controlled by the balance of androgen to estrogen signaling during a narrow window of digit development. Androgen receptor (AR) and estrogen receptor α (ER-α) activity is higher in digit 4 than in digit 2. Inactivation of AR decreases growth of digit 4, which causes a higher 2D:4D ratio, whereas inactivation of ER-α increases growth of digit 4, which leads to a lower 2D:4D ratio. We also show that addition of androgen has the same effect as inactivation of ER and that addition of estrogen mimics the reduction of AR. Androgen and estrogen differentially regulate the network of genes that controls chondrocyte proliferation, leading to differential growth of digit 4 in males and females. These studies identify previously undescribed molecular dimorphisms between male and female limb buds and provide experimental evidence that the digit ratio is a lifelong signature of prenatal hormonal exposure. Our results also suggest that the 2D:4D ratio can serve as an indicator of disrupted endocrine signaling during early development, which may aid in the identification of fetal origins of adult diseases.
Reactibodies
generated by kinetic selection couple chemical reactivity with favorable protein dynamics
Authors: Smirnov Ivan , Carletti Eugénie , Kurkova Inna , Nachon Florian , Nicolet Yvain , Mitkevich Vladimir A. , Débat Hélène , Avalle Bérangère , Belogurov Alexey A. , Kuznetsov Nikita , Reshetnyak Andrey , Masson Patrick , Tonevitsky Alexander G. , Ponomarenko Natalia , Makarov Alexander A. , Friboulet Alain , Tramontano Alfonso , Gabibov Alexander
Published: September 2011

Igs offer a versatile template for combinatorial and rational design approaches to the de novo creation of catalytically active proteins. We have used a covalent capture selection strategy to identify biocatalysts from within a human semisynthetic antibody variable fragment library that uses a nucleophilic mechanism. Specific phosphonylation at a single tyrosine within the variable light-chain framework was confirmed in a recombinant IgG construct. High-resolution crystallographic structures of unmodified and phosphonylated Fabs display a 15-Å-deep two-chamber cavity at the interface of variable light (
V
L
) and variable heavy (
V
H
) fragments having a nucleophilic tyrosine at the base of the site. The depth and structure of the pocket are atypical of antibodies in general but can be compared qualitatively with the catalytic site of cholinesterases. A structurally disordered heavy chain complementary determining region 3 loop, constituting a wall of the cleft, is stabilized after covalent modification by hydrogen bonding to the phosphonate tropinol moiety. These features and presteady state kinetics analysis indicate that an induced fit mechanism operates in this reaction. Mutations of residues located in this stabilized loop do not interfere with direct contacts to the organophosphate ligand but can interrogate second shell interactions, because the H3 loop has a conformation adjusted for binding. Kinetic and thermodynamic parameters along with computational docking support the active site model, including plasticity and simple catalytic components. Although relatively uncomplicated, this catalytic machinery displays both stereo- and chemical selectivity. The organophosphate pesticide paraoxon is hydrolyzed by covalent catalysis with rate-limiting dephosphorylation. This
reactibody
is, therefore, a kinetically selected protein template that has enzyme-like catalytic attributes.
Targeted killing of a mammalian cell based upon its specialized metabolic state
Authors: Alexander Peter B. , Wang Jian , McKnight Steven L.
Published: September 2011

Mouse ES cells use a mitochondrial threonine dehydrogenase (TDH) enzyme to catabolize threonine into glycine and acetyl-CoA. Measurements of mRNA abundance have given evidence that ES cells express upwards of 1,000-fold higher levels of TDH mRNA than any of seven other mouse tissues tested. When cell culture medium is deprived of threonine, ES cells rapidly discontinue DNA synthesis, arrest cell division, and eventually die. Such studies led to the conclusion that mouse ES cells exist in a threonine-dependent metabolic state. Proceeding with the assumption that the active TDH enzyme should be essential for the growth and viability of mouse ES cells, we performed a drug screen in search of specific inhibitors of the purified TDH enzyme. Such efforts led to the discovery of a class of quinazolinecarboxamide (Qc) compounds that inhibit the ability of the TDH enzyme to catabolize threonine into glycine and acetyl-CoA. Administration of Qc inhibitors of TDH to mouse ES cells impeded cell growth and resulted in the induction of autophagy. By contrast, the same chemicals failed to affect the growth of HeLa cells at concentrations 300-fold higher than that required to kill mouse ES cells. It was likewise observed that the Qc class of TDH inhibitors failed to affect the growth or viability of ES cell-derived embryoid body cells known to have extinguished TDH expression. These studies demonstrate how it is possible to kill a specific mammalian cell type on the basis of its specialized metabolic state.
Opening the periplasmic cavity in lactose permease is the limiting step for sugar binding
Authors: Smirnova Irina , Kasho Vladimir , Sugihara Junichi , Kaback H. Ronald
Published: September 2011

The lactose permease (LacY) catalyzes galactoside/H
+
symport via an alternating access mechanism in which sugar- and H
+
-binding sites in the middle of the molecule are alternatively exposed to either side of the membrane by opening and closing of inward- and outward-facing cavities. The crystal structures of wild-type LacY, as well as accessibility data for the protein in the membrane, provide strong support for a conformation with a tightly closed periplasmic side and an open cytoplasmic side (an inward-facing conformation). In this study, rates of substrate binding were measured by stopped-flow with purified LacY either in detergent or in reconstituted proteoliposomes. Binding rates are compared with rates of sugar-induced opening of the periplasmic pathway obtained by using a recently developed method based on unquenching of Trp fluorescence. A linear dependence of galactoside-binding rates on sugar concentration is observed in detergent, whereas reconstituted LacY binds substrate at a slower rate that is independent of sugar concentration. Rates of opening of the periplasmic cavity with LacY in detergent are independent of substrate concentration and are essentially the same for different galactosidic sugars. The findings demonstrate clearly that reconstituted LacY is oriented physiologically with a closed periplasmic side that limits access of sugar to the binding site. Moreover, opening of the periplasmic cavity is the limiting factor for sugar binding with reconstituted LacY and may be the limiting step in the overall transport reaction.
General hydrophobic interaction potential for surfactant/lipid bilayers from direct force measurements between light-modulated bilayers
Authors: Donaldson Stephen H. , Lee C. Ted , Chmelka Bradley F. , Israelachvili Jacob N.
Published: September 2011

We establish and quantify correlations among the molecular structures, interaction forces, and physical processes associated with light-responsive self-assembled surfactant monolayers or bilayers at interfaces. Using the surface forces apparatus (SFA), the interaction forces between adsorbed monolayers and bilayers of an azobenzene-functionalized surfactant can be drastically and controllably altered by light-induced conversion of
trans
and
cis
molecular conformations. These reversible conformation changes affect significantly the shape of the molecules, especially in the hydrophobic region, which induces dramatic transformations of molecular packing in self-assembled structures, causing corresponding modulation of electrostatic double layer, steric hydration, and hydrophobic interactions. For bilayers, the isomerization from
trans
to
cis
exposes more hydrophobic groups, making the
cis
bilayers more hydrophobic, which lowers the activation energy barrier for (hemi)fusion. A quantitative and general model is derived for the interaction potential of charged bilayers that includes the electrostatic double-layer force of the Derjaguin–Landau–Verwey–Overbeek theory, attractive hydrophobic interactions, and repulsive steric-hydration forces. The model quantitatively accounts for the elastic strains, deformations, long-range forces, energy maxima, adhesion minima, as well as the instability (when it exists) as two bilayers breakthrough and (hemi)fuse. These results have several important implications, including quantitative and qualitative understanding of the hydrophobic interaction, which is furthermore shown to be a nonadditive interaction.
Fossil evidence of avian crops from the Early Cretaceous of China
Authors: Zheng Xiaoting , Martin Larry D. , Zhou Zhonghe , Burnham David A. , Zhang Fucheng , Miao Desui
Published: September 2011

The crop is characteristic of seed-eating birds today, yet little is known about its early history despite remarkable discoveries of many Mesozoic seed-eating birds in the past decade. Here we report the discovery of some early fossil evidence for the presence of a crop in birds. Two Early Cretaceous birds, the basal ornithurine
Hongshanornis
and a basal avian
Sapeornis
, demonstrate that an essentially modern avian digestive system formed early in avian evolution. The discovery of a crop in two phylogenetically remote lineages of Early Cretaceous birds and its absence in most intervening forms indicates that it was independently acquired as a specialized seed-eating adaptation. Finally, the reduction or loss of teeth in the forms showing seed-filled crops suggests that granivory was possibly one of the factors that resulted in the reduction of teeth in early birds.
Amino acid substitution in NPC1 that abolishes cholesterol binding reproduces phenotype of complete NPC1 deficiency in mice
Authors: Xie Xuefen , Brown Michael S. , Shelton John M. , Richardson James A. , Goldstein Joseph L. , Liang Guosheng
Published: September 2011

Substitution mutations in adjacent amino acids of the N-terminal domain of NPC1, a lysosomal membrane protein, abolish its cholesterol binding activity and impair its ability to export cholesterol from lysosomes of cultured cells lacking
npc1
[Kwon HJ, et al. (2009)
Cell
137:1213–1224]. Here, we show that the same two mutations (proline-202 and phenylalanine-203, both changed to alanine) reproduce the phenotype of complete NPC1 deficiency when knocked into the mouse
npc1
gene by homologous recombination. Homozygous

npc1
pf/pf

mice exhibited neurodegeneration beginning at day 49 and died at a median age of 84 d, as previously reported for mice that lack
npc1
. Liver and other organs of the

npc1
pf/pf

mice accumulated excess cholesterol in lysosomes. In liver, mRNAs encoding several lysosomal proteins were elevated, including NPC1 and NPC2 and several digestive enzymes (acid lipase, β-glucuronidase, and cathepsins B and D). Weekly treatment with hydroxypropyl-β-cyclodextrin (HPCD) beginning at 7 wk reduced hepatic cholesterol accumulation and diminished the lysosomal mRNAs. We conclude that the cholesterol binding site in the N-terminal domain of NPC1 is essential for cholesterol export from lysosomes in living animals as it is in cultured cells. The HPCD-mediated reduction of excess lysosomal enzymes may contribute to the ability of this drug to delay the progression of NPC disease in mice.
Drosophila P
elements preferentially transpose to replication origins
Authors: Spradling Allan C. , Bellen Hugo J. , Hoskins Roger A.
Published: September 2011

The
P
transposable element recently invaded wild
Drosophila melanogaster
strains worldwide. A single introduced copy can multiply and spread throughout the fly genome in just a few generations, even though its cut-and-paste transposition mechanism does not inherently increase copy number.
P
element insertions preferentially target the promoters of a subset of genes, but why these sites are hotspots remains unknown. We show that
P
elements selectively target sites that in tissue-culture cells bind origin recognition complex proteins and function as replication origins. The association of origin recognition complex-binding sites with selected promoters and their absence near clustered differentiation genes may dictate
P
element site specificity. Inserting at unfired replication origins during S phase may allow
P
elements to be both repaired and reduplicated, thereby increasing element copy number. The advantage transposons gain by moving from replicated to unreplicated genomic regions may contribute to the association of heterochromatin with late-replicating genomic regions.
Oxytocin receptor gene (
OXTR
) is related to psychological resources
Authors: Saphire-Bernstein Shimon , Way Baldwin M. , Kim Heejung S. , Sherman David K. , Taylor Shelley E.
Published: September 2011

Psychological resources—optimism, mastery, and self-esteem—buffer the deleterious effects of stress and are predictors of neurophysiological and psychological health-related outcomes. These resources have been shown to be highly heritable, yet the genetic basis for this heritability remains unknown. Here, we report a link between the oxytocin receptor (
OXTR
) SNP rs53576 and psychological resources, such that carriers of the “A” allele have lower levels of optimism, mastery, and self-esteem, relative to G/G homozygotes.
OXTR
was also associated with depressive symptomatology. Mediation analysis indicates that the effects of
OXTR
on depressive symptoms may be largely mediated by the influence of
OXTR
on psychological resources.
Recognition of Own- and Other-Race Faces in Autism Spectrum Disorders
Authors: Wilson C. Ellie , Palermo Romina , Burton A. Mike , Brock Jon
Published: September 2011

Empirical data regarding the extent of face recognition abnormalities in autism spectrum disorder (ASD) is inconsistent. Here, 27 ASD and 47 typically developing (TD) children completed an immediate two-alternative forced-choice identity matching task. We contrasted recognition of own- and other-race faces, and, counter to prediction, we found a typical advantage for recognizing own- over other-race faces in both the ASD and TD groups. In addition, ASD and TD groups responded similarly to stimulus manipulations (use of identical or different photographs for identity matching and cropping stimuli to remove hair information). However, age-standardized scores varied widely within the ASD sample, and a subgroup of ASD participants with impaired face recognition did not exhibit a significant own-race recognition advantage. An explanation regarding early experience with faces is considered, and implications for research of individual variation within ASD are discussed.
The Effect of Noun Animacy on the Processing of Unambiguous Sentences: Evidence from French Relative Clauses
Authors: Baudiffier Vanessa , Caplan David , Gaonac'h Daniel , Chesnet David
Published: September 2011

Two experiments, one using self-paced reading and one using eye tracking, investigated the influence of noun animacy on the processing of subject relative (SR) clauses, object relative (OR) clauses, and object relative clauses with stylistic inversion (OR–SI) in French. Each sentence type was presented in two versions: either with an animate relative clause (RC) subject and an inanimate object (AS/IO), or with an inanimate RC subject and an animate object (IS/AO). There was an interaction between the RC structure and noun animacy. The advantage of SR sentences over OR and OR–SI sentences disappeared in AS/IO sentences. The interaction between animacy and structure occurred in self-paced reading times and in total fixation times on the RCs, but not in first-pass reading times. The results are consistent with a late interaction between animacy and structural processing during parsing and provide data relevant to several models of parsing.
Kickback in nematic liquid crystals
Authors: da Costa F. , Grinfeld M. , Langer M. , Mottram N. , Pinto J.
Published: September 2011

We describe a nonlocal linear partial differential equation arising in the analysis of dynamics of a nematic liquid crystal. We confirm that it accounts for the kickback phenomenon by decoupling the director dynamics from the flow. We also analyse some of the mathematical properties of the decoupled director equation.
Motivic Poincaré series, toric singularities and logarithmic Jacobian ideals
Authors: Pablos H. , Pérez P.
Published: September 2011

The geometric motivic Poincaré series of a variety, which was introduced by Denef and Loeser, takes into account the classes in the Grothendieck ring of the sequence of jets of arcs in the variety. Denef and Loeser proved that this series has a rational form. We describe it in the case of an affine toric variety of arbitrary dimension. The result, which provides an explicit set of candidate poles, is expressed in terms of the sequence of Newton polyhedra of certain monomial ideals, which we call logarithmic Jacobian ideals, associated to the modules of differential forms with logarithmic poles outside the torus of the toric variety.
The SCAR/WAVE complex is necessary for proper regulation of traction stresses during amoeboid motility
Authors: Bastounis Effie , Meili Ruedi , Alonso-Latorre Baldomero , del Álamo Juan C. , Lasheras Juan C. , Firtel Richard A.
Published: September 2011

Cell migration requires a tightly regulated, spatiotemporal coordination of underlying biochemical pathways. Crucial to cell migration is SCAR/WAVE–mediated dendritic F-actin polymerization at the cell's leading edge. Our goal is to understand the role the SCAR/WAVE complex plays in the mechanics of amoeboid migration. To this aim, we measured and compared the traction stresses exerted by Dictyostelium cells lacking the SCAR/WAVE complex proteins PIR121 (pirA−) and SCAR (scrA−) with those of wild-type cells while they were migrating on flat, elastic substrates. We found that, compared to wild type, both mutant strains exert traction stresses of different strengths that correlate with their F-actin levels. In agreement with previous studies, we found that wild-type cells migrate by repeating a motility cycle in which the cell length and strain energy exerted by the cells on their substrate vary periodically. Our analysis also revealed that scrA− cells display an altered motility cycle with a longer period and a lower migration velocity, whereas pirA− cells migrate in a random manner without implementing a periodic cycle. We present detailed characterization of the traction-stress phenotypes of the various cell lines, providing new insights into the role of F-actin polymerization in regulating cell–substratum interactions and stresses required for motility.
Genetic basis of end‐stage hypertrophic cardiomyopathy
Authors: Garcia‐Pavia Pablo , Vázquez Maria E. , Segovia Javier , Salas Clara , Avellana Patricia , Gómez‐Bueno Manuel , Vilches Carlos , Gallardo M. Esther , Garesse Rafael , Molano Jesús , Bornstein Belén , Alonso‐Pulpon Luis
Published: September 2011

Aims

Hypertrophic cardiomyopathy (HCM) is characterized by a heterogeneous presentation and clinical course. A minority of HCM patients develop end‐stage HCM and require cardiac transplantation. The genetic basis of end‐stage HCM is unknown but small series, isolated case reports and animal models have related the most aggressive heart failure course with the presence of multiple mutations.

Methods and results

Twenty‐six patients (age 40.4 ± 14.5 years; 46% male) transplanted for end‐stage HCM underwent genetic screening of 10 HCM‐related genes (MYH7, MYBPC3, TNNT2, TNNI3, TPM1, TNNC1, MYL3, MYL2, ACTC, LDB3). Additional genetic screening of LAMP2/PRKAG2 and mitochondrial DNA (mtDNA) was performed in four and three cases, respectively. Findings were correlated with clinical and histological features. Pathogenic mutations were identified in 15 patients (58%). Thirteen patients (50%) had mutations in sarcomeric genes (six in MYH7, three in MYBPC3, two in MYL2, one in TNNI3, and one in MYL3) and two patients had mutations in LAMP2. Only three patients (13%) had double mutations and all in homozygosis. Except for a more frequent family history of HCM, patients with mutations in sarcomeric genes did not show any clinical feature that distinguished them from patients without mutations in these genes. Evaluation of 44 relatives from 12 families identified 13 mutation carriers, 9 of whom had an overt HCM phenotype.

Conclusion

Heart transplanted HCM has a heterogeneous genetic background where multiple mutations are uncommon. The clinical course of HCM is not primarily dependent on the presence of multiple sarcomeric mutations. Clinical and genetic evaluation of relatives does not support differential clinical management in HCM based on genetics.
A High Level of Transgenic Viral Small RNA Is Associated with Broad Potyvirus Resistance in Cucurbits
Authors: Leibman Diana , Wolf Dalia , Saharan Vinod , Zelcer Aaron , Arazi Tzahi , Yoel Shiboleth , Gaba Victor , Gal-On Amit
Published: September 2011

Gene-silencing has been used to develop resistance against many plant viruses but little is known about the transgenic small-interfering RNA (t-siRNA) that confers this resistance. Transgenic cucumber and melon lines harboring a hairpin construct of the Zucchini yellow mosaic potyvirus (ZYMV) HC-Pro gene accumulated different levels of t-siRNA (6 to 44% of total siRNA) and exhibited resistance to systemic ZYMV infection. Resistance to Watermelon mosaic potyvirus and Papaya ring spot potyvirus-W was also observed in a cucumber line that accumulated high levels of t-siRNA (44% of total siRNA) and displayed significantly increased levels of RNA-dependent RNA (RDR)1 and Argonaute 1, as compared with the other transgenic and nontransformed plants. The majority of the t-siRNA sequences were 21 to 22 nucleotides in length and sense strand biased. The t-siRNA were not uniformly distributed throughout the transgene but concentrated in “hot spots” in a pattern resembling that of the viral siRNA peaks observed in ZYMV-infected cucumber and melon. Mutations in ZYMV at the loci associated with the siRNA peaks did not break this resistance, indicating that hot spot t-siRNA may not be essential for resistance. This study shows that resistance based on gene-silencing can be effective against related viruses and is probably correlated with t-siRNA accumulation and increased expression of RDR1.
Sensitivity of Erysiphe necator to Demethylation Inhibitor Fungicides in Virginia
Authors: Colcol Jeneylyne F. , Rallos Lynn Esther , Baudoin Anton B.
Published: September 2011

Grape powdery mildew (Erysiphe necator) isolates were collected from 2005 to 2007 from vineyards mostly in Virginia but also some in Maryland, North Carolina, and Pennsylvania. Using a leaf disc assay, the isolates were tested against five demethylation inhibitor (DMI) fungicides. Most isolates exhibited reduced sensitivity to the five DMIs when compared with a sensitive group (n = 12) and compared with unexposed populations reported from other areas. The median resistance factor (RF) was highest for tebuconazole (RF = 399) and myclobutanil (RF = 378), followed by triflumizole (RF = 70), triadimefon (RF = 62), and fenarimol (RF = 44). The sensitive group used as the basis for comparison appears to have been more sensitive than unexposed isolates in New York and California. Our finding that the greatest resistance shift occurred with tebuconazole and myclobutanil contrasts with earlier reports from New York and California, where the greatest resistance shift was observed with triadimefon or triadimenol. Sensitivities to all five DMI fungicides were strongly correlated (pairwise r values of 0.70 to 0.87) but our data suggest that some may retain greater utility than others.
Variability in Fusarium Head Blight Epidemics in Relation to Global Climate Fluctuations as Represented by the El Niño-Southern Oscillation and Other Atmospheric Patterns
Authors: Kriss A. B. , Paul P. A. , Madden L. V.
Published: September 2011

Cross-spectral analysis was used to characterize the relationship between climate variability, represented by atmospheric patterns, and annual fluctuations of Fusarium head blight (FHB) disease intensity in wheat. Time series investigated were the Oceanic Niño Index (ONI), which is a measure of the El Niño-Southern Oscillation (ENSO), the Pacific-North American (PNA) pattern and the North Atlantic Oscillation (NAO), which are known to have strong influences on the Northern Hemisphere climate, and FHB disease intensity observations in Ohio from 1965 to 2010 and in Indiana from 1973 to 2008. For each climate variable, mean climate index values for the boreal winter (December to February) and spring (March to May) were utilized. The spectral density of each time series and the (squared) coherency of each pair of FHB–climate-index series were estimated. Significance for coherency was determined by a nonparametric permutation procedure. Results showed that winter and spring ONI were significantly coherent with FHB in Ohio, with a period of about 5.1 years (as well as for some adjacent periods). The estimated phase-shift distribution indicated that there was a generally negative relation between the two series, with high values of FHB (an indication of a major epidemic) estimated to occur about 1 year following low values of ONI (indication of a La Niña); equivalently, low values of FHB were estimated to occur about 1 year after high values of ONI (El Niño). There was also limited evidence that winter ONI had significant coherency with FHB in Indiana. At periods between 2 and 7 years, the PNA and NAO indices were coherent with FHB in both Ohio and Indiana, although results for phase shift and period depended on the specific location, climate index, and time span used in calculating the climate index. Differences in results for Ohio and Indiana were expected because the FHB disease series for the two states were not similar. Results suggest that global climate indices and models could be used to identify potential years with high (or low) risk for FHB development, although the most accurate risk predictions will need to be customized for a region and will also require use of local weather data during key time periods for sporulation and infection by the fungal pathogen.
A stab in the dark: chick killing by brood parasitic honeyguides
Authors: Spottiswoode Claire N. , Koorevaar Jeroen
Published: September 2011

The most virulent avian brood parasites obligately kill host young soon after hatching, thus ensuring their monopoly of host parental care. While the host eviction behaviour of cuckoos (Cuculidae) is well documented, the host killing behaviour of honeyguide (Indicatoridae) chicks has been witnessed only once, 60 years ago, and neverin situin host nests. Here, we report from the Afrotropical greater honeyguide the first detailed observations of honeyguides killing host chicks with their specially adapted bill hooks, based on repeated video recordings (available in the electronic supplementary material). Adult greater honeyguides puncture host eggs when they lay their own, but in about half of host nests at least one host egg survived, precipitating chick killing by the honeyguide hatchling. Hosts always hatched after honeyguide chicks, and were killed within hours. Despite being blind and in total darkness, honeyguides attacked host young with sustained biting, grasping and shaking motions. Attack time of 1–5 min was sufficient to cause host death, which took from 9 min to over 7 h from first attack. Honeyguides also bit unhatched eggs and human hands, but only rarely bit the host parents feeding them.