bluuebunny/crossref_metadata_2025 huggingface dataset:
Putative amino acid determinants of the emergence of the 2009 influenza A (H1N1) virus in the human population
Authors: Meroz Daphna , Yoon Sun-Woo , Ducatez Mariette F. , Fabrizio Thomas P. , Webby Richard J. , Hertz Tomer , Ben-Tal Nir
Published: August 2011

The emergence of the unique H1N1 influenza A virus in 2009 resulted in a pandemic that has spread to over 200 countries. The constellation of molecular factors leading to the emergence of this strain is still unclear. Using a computational approach, we identified molecular determinants that may discriminate the hemagglutinin protein of the 2009 human pandemic H1N1 (pH1N1) strain from that of other H1N1 strains. As expected, positions discriminating the pH1N1 from seasonal human strains were located in or near known H1N1 antigenic sites, thus camouflaging the pH1N1 strain from immune recognition. For example, the alteration S145K (an antigenic position) was found as a characteristic of the pH1N1 strain. We also detected positions in the hemagglutinin protein differentiating classical swine viruses from pH1N1. These positions were mostly located in and around the receptor-binding pocket, possibly influencing binding affinity to the human cell. Such alterations may be liable in part for the virus’s efficient infection and adaptation to humans. For instance, 133
A
and 149 were identified as discriminative positions. Significantly, we showed that the substitutions R133
A
K and R149K, predicted to be pH1N1 characteristics, each altered virus binding to erythrocytes and conferred virulence to A/swine/NC/18161/02 in mice, reinforcing the computational findings. Our findings provide a structural explanation for the deficient immunity of humans to the pH1N1 strain. Moreover, our analysis points to unique molecular factors that may have facilitated the emergence of this swine variant in humans, in contrast to other swine variants that failed.
Emergence of potent inhibitors of metastasis in lung cancer via syntheses based on migrastatin
Authors: Lecomte Nicolas , Njardarson Jon T. , Nagorny Pavel , Yang Guangli , Downey Robert , Ouerfelli Ouathek , Moore Malcolm A. S. , Danishefsky Samuel J.
Published: August 2011

Migrastatin is a biologically active natural product isolated from
Streptomyces
that has been shown to inhibit tumor cell migration. Upon completion of the first total synthesis of migrastatin, a number of structurally simplified analogs were prepared. Following extensive in vitro screening, a new generation of analogs was identified that demonstrates substantially higher levels of in vitro inhibitory activity, stability and synthetic accessibility when compared to the parent natural product. Herein, we describe two promising ether-derivative analogs, the migrastatin core ether (ME) and the carboxymethyl-ME (CME), which exhibit high efficacy in blocking tumor cell migration and metastasis in lung cancer. These compounds show an in vitro migration inhibition in the micromolar range (IC
50
: ME 1.5 to 8.2 μM, CME 0.5 to 5 μM). In a human small-cell lung carcinoma (SCLC) primary xenograft model, ME and CME compounds were found to be highly potent in inhibiting overall metastasis even at the lowest dosage used (degree of inhibition: 96.2% and 99.3%, respectively). Together these very encouraging findings suggest that these analogs have promise as potent antimetastatic agents in lung cancer.
Direct and indirect effects of biological factors on extinction risk in fossil bivalves
Authors: Harnik Paul G.
Published: August 2011

Biological factors, such as abundance and body size, may contribute directly to extinction risk and indirectly through their influence on other biological characteristics, such as geographic range size. Paleontological data can be used to explicitly test many of these hypothesized relationships, and general patterns revealed through analysis of the fossil record can help refine predictive models of extinction risk developed for extant species. Here, I use structural equation modeling to tease apart the contributions of three canonical predictors of extinction—abundance, body size, and geographic range size—to the duration of bivalve species in the early Cenozoic marine fossil record of the eastern United States. I find that geographic range size has a strong direct effect on extinction risk and that an apparent direct effect of abundance can be explained entirely by its covariation with geographic range. The influence of geographic range on extinction risk is manifest across three ecologically disparate bivalve clades. Body size also has strong direct effects on extinction risk but operates in opposing directions in different clades, and thus, it seems to be decoupled from extinction risk in bivalves as a whole. Although abundance does not directly predict extinction risk, I reveal weak indirect effects of both abundance and body size through their positive influence on geographic range size. Multivariate models that account for the pervasive covariation between biological factors and extinction are necessary for assessing causality in evolutionary processes and making informed predictions in applied conservation efforts.
Global distribution and conservation of marine mammals
Authors: Pompa Sandra , Ehrlich Paul R. , Ceballos Gerardo
Published: August 2011

We identified 20 global key conservation sites for all marine (123) and freshwater (6) mammal species based on their geographic ranges. We created geographic range maps for all 129 species and a Geographic Information System database for a 46,184 1° x 1° grid-cells, ∼10,000-km2. Patterns of species richness, endemism, and risk were variable among all species and species groups. Interestingly, marine mammal species richness was correlated strongly with areas of human impact across the oceans. Key conservation sites in the global geographic grid were determined either by their species richness or by their irreplaceability or uniqueness, because of the presence of endemic species. Nine key conservation sites, comprising the 2.5% of the grid cells with the highest species richness, were found, mostly in temperate latitudes, and hold 84% of marine mammal species. In addition, we identified 11 irreplaceable key conservation sites, six of which were found in freshwater bodies and five in marine regions. These key conservation sites represent critical areas of conservation value at a global level and can serve as a first step for adopting global strategies with explicit geographic conservation targets for Marine Protected Areas.
Histone H3-variant Cse4-induced positive DNA supercoiling in the yeast plasmid has implications for a plasmid origin of a chromosome centromere
Authors: Huang Chu-Chun , Chang Keng-Ming , Cui Hong , Jayaram Makkuni
Published: August 2011

The
Saccharomyces cerevisiae
2-μm plasmid is a multicopy selfish genome that resides in the nucleus. The genetic organization of the plasmid is optimized for stable, high-copy propagation in host-cell populations. The plasmid's partitioning system poaches host factors, including the centromere-specific histone H3-variant Cse4 and the cohesin complex, enabling replicated plasmid copies to segregate equally in a chromosome-coupled fashion. We have characterized the in vivo chromatin topology of the plasmid partitioning locus
STB
in its Cse4-associated and Cse4-nonassociated states. We find that the occupancy of Cse4 at
STB
induces positive DNA supercoiling, with a linking difference (ΔLk) contribution estimated between +1 and +2 units. One plausible explanation for this contrary topology is the presence of a specialized Cse4-containing nucleosome with a right-handed DNA writhe at a functional
STB
, contrasted by a standard histone H3-containing nucleosome with a left-handed DNA writhe at a nonfunctional
STB
. The similarities between
STB
and centromere in their nucleosome signature and DNA topology would be consistent with the potential origin of the unusual point centromere of budding yeast chromosomes from the partitioning locus of an ancestral plasmid.
Hu proteins regulate alternative splicing by inducing localized histone hyperacetylation in an RNA-dependent manner
Authors: Zhou Hua-Lin , Hinman Melissa N. , Barron Victoria A. , Geng Cuiyu , Zhou Guangjin , Luo Guangbin , Siegel Ruth E. , Lou Hua
Published: August 2011

Recent studies have provided strong evidence for a regulatory link among chromatin structure, histone modification, and splicing regulation. However, it is largely unknown how local histone modification patterns surrounding alternative exons are connected to differential alternative splicing outcomes. Here we show that splicing regulator Hu proteins can induce local histone hyperacetylation by association with their target sequences on the pre-mRNA surrounding alternative exons of two different genes. In both primary and mouse embryonic stem cell-derived neurons, histone hyperacetylation leads to an increased local transcriptional elongation rate and decreased inclusion of these exons. Furthermore, we demonstrate that Hu proteins interact with histone deacetylase 2 and inhibit its deacetylation activity. We propose that splicing regulators may actively modulate chromatin structure when recruited to their target RNA sequences cotranscriptionally. This “reaching back” interaction with chromatin provides a means to ensure accurate and efficient regulation of alternative splicing.
C terminus of Hsc70-interacting protein (CHIP)-mediated degradation of hippocampal estrogen receptor-α and the critical period hypothesis of estrogen neuroprotection
Authors: Zhang Quan-guang , Han Dong , Wang Rui-min , Dong Yan , Yang Fang , Vadlamudi Ratna K. , Brann Darrell W.
Published: August 2011

Recent work suggests that timing of 17β-estradiol (E2) therapy may be critical for observing a beneficial neural effect. Along these lines, E2 neuroprotection, but not its uterotropic effect, was shown to be lost following long-term E2 deprivation (LTED), and this effect was associated with a significant decrease of estrogen receptor-α (ERα) in the hippocampus but not the uterus. The purpose of the current study was to determine the mechanism underlying the ERα decrease and to determine whether aging leads to a similar loss of hippocampal ERα and E2 sensitivity. The results of the study show that ERα in the rat hippocampal CA1 region but not the uterus undergoes enhanced interaction with the E3 ubiquitin ligase C terminus of heat shock cognate protein 70 (Hsc70)-interacting protein (CHIP) that leads to its ubiquitination/proteasomal degradation following LTED (10-wk ovariectomy). E2 treatment initiated before but not after LTED prevented the enhanced ERα-CHIP interaction and ERα ubiquitination/degradation and was fully neuroprotective against global cerebral ischemia. Administration of a proteasomal inhibitor or CHIP antisense oligonucleotides to knock down CHIP reversed the LTED-induced down-regulation of ERα. Further work showed that these observations extended to natural aging, because aged rats showed enhanced CHIP interaction; ubiquitination and degradation of both hippocampal ERα and ERβ; and, importantly, a correlated loss of E2 neuroprotection against global cerebral ischemia. In contrast, E2 administration to middle-aged rats was still capable of exerting neuroprotection. As a whole, the study provides support for a “critical period” for E2 neuroprotection of the hippocampus and provides important insight into the mechanism underlying the critical period.
Impact of a stress-inducible switch to mutagenic repair of DNA breaks on mutation in
Escherichia coli
Authors: Shee Chandan , Gibson Janet L. , Darrow Michele C. , Gonzalez Caleb , Rosenberg Susan M.
Published: August 2011

Basic ideas about the constancy and randomness of mutagenesis that drives evolution were challenged by the discovery of mutation pathways activated by stress responses. These pathways could promote evolution specifically when cells are maladapted to their environment (i.e., are stressed). However, the clearest example—a general stress-response–controlled switch to error-prone DNA break (double-strand break, DSB) repair—was suggested to be peculiar to an
Escherichia coli
F′ conjugative plasmid, not generally significant, and to occur by an alternative stress-independent mechanism. Moreover, mechanisms of spontaneous mutation in
E. coli
remain obscure. First, we demonstrate that this same mechanism occurs in chromosomes of starving F
−
E. coli
. I-SceI endonuclease-induced chromosomal DSBs increase mutation 50-fold, dependent upon general/starvation- and DNA-damage-stress responses, DinB error-prone DNA polymerase, and DSB-repair proteins. Second, DSB repair is also mutagenic if the RpoS general-stress-response activator is expressed in unstressed cells, illustrating a stress-response–controlled switch to mutagenic repair. Third, DSB survival is not improved by RpoS or DinB, indicating that mutagenesis is not an inescapable byproduct of repair. Importantly, fourth, fully half of spontaneous frame-shift and base-substitution mutation during starvation also requires the same stress-response, DSB-repair, and DinB proteins. These data indicate that DSB-repair-dependent stress-induced mutation, driven by spontaneous DNA breaks, is a pathway that cells usually use and a major source of spontaneous mutation. These data also rule out major alternative models for the mechanism. Mechanisms that couple mutagenesis to stress responses can allow cells to evolve rapidly and responsively to their environment.
Homogeneous catalytic O
2
reduction to water by a cytochrome
c
oxidase model with trapping of intermediates and mechanistic insights
Authors: Halime Zakaria , Kotani Hiroaki , Li Yuqi , Fukuzumi Shunichi , Karlin Kenneth D.
Published: August 2011

An efficient and selective four-electron plus four-proton (4
e
-
/4H
+
) reduction of O
2
to water by decamethylferrocene and trifluoroacetic acid can be catalyzed by a synthetic analog of the heme
a
3
/Cu

B

site in cytochrome
c
oxidase (
6
LFeCu) or its Cu-free version (
6
LFe) in acetone. A detailed mechanistic-kinetic study on the homogeneous catalytic system reveals spectroscopically detectable intermediates and that the rate-determining step changes from the O
2
-binding process at 25 °C room temperature (RT) to the O-O bond cleavage of a newly observed Fe
III
-OOH species at lower temperature (-60 °C). At RT, the rate of O
2
-binding to
6
LFeCu is significantly faster than that for
6
LFe, whereas the rates of the O-O bond cleavage of the Fe
III
-OOH species observed (-60 °C) with either the
6
LFeCu or
6
LFe catalyst are nearly the same. Thus, the role of the Cu ion is to assist the heme and lead to faster O
2
-binding at RT. However, the proximate Cu ion has no effect on the O-O bond cleavage of the Fe
III
-OOH species at low temperature.
Ice-shelf collapse from subsurface warming as a trigger for Heinrich events
Authors: Marcott Shaun A. , Clark Peter U. , Padman Laurie , Klinkhammer Gary P. , Springer Scott R. , Liu Zhengyu , Otto-Bliesner Bette L. , Carlson Anders E. , Ungerer Andy , Padman June , He Feng , Cheng Jun , Schmittner Andreas
Published: August 2011

Episodic iceberg-discharge events from the Hudson Strait Ice Stream (HSIS) of the Laurentide Ice Sheet, referred to as Heinrich events, are commonly attributed to internal ice-sheet instabilities, but their systematic occurrence at the culmination of a large reduction in the Atlantic meridional overturning circulation (AMOC) indicates a climate control. We report Mg/Ca data on benthic foraminifera from an intermediate-depth site in the northwest Atlantic and results from a climate-model simulation that reveal basin-wide subsurface warming at the same time as large reductions in the AMOC, with temperature increasing by approximately 2 °C over a 1–2 kyr interval prior to a Heinrich event. In simulations with an ocean model coupled to a thermodynamically active ice shelf, the increase in subsurface temperature increases basal melt rate under an ice shelf fronting the HSIS by a factor of approximately 6. By analogy with recent observations in Antarctica, the resulting ice-shelf loss and attendant HSIS acceleration would produce a Heinrich event.
Conformational switching explains the intrinsic multifunctionality of plant light-harvesting complexes
Authors: Krüger Tjaart P. J. , Wientjes Emilie , Croce Roberta , van Grondelle Rienk
Published: August 2011

The light-harvesting complexes of photosystem I and II (Lhcas and Lhcbs) of plants display a high structural homology and similar pigment content and organization. Yet, the spectroscopic properties of these complexes, and accordingly their functionality, differ substantially. This difference is primarily due to the charge-transfer (CT) character of a chlorophyll dimer in all Lhcas, which mixes with the excitonic states of these complexes, whereas this CT character is generally absent in Lhcbs. By means of single-molecule spectroscopy near room temperature, we demonstrate that the presence or absence of such a CT state in Lhcas and Lhcbs can occasionally be reversed; i.e., these complexes are able to interconvert conformationally to quasi-stable spectral states that resemble the Lhcs of the other photosystem. The high structural similarity of all the Lhca and Lhcb proteins suggests that the stable conformational states that give rise to the mixed CT-excitonic state are similar for all these proteins, and similarly for the conformations that involve no CT state. This indicates that the specific functions related to Lhca and Lhcb complexes are realized by different stable conformations of a single generic protein structure. We propose that this functionality is modulated and controlled by the protein environment.
Temporary increase in plasma membrane tension coordinates the activation of exocytosis and contraction during cell spreading
Authors: Gauthier Nils C. , Fardin Marc Antoine , Roca-Cusachs Pere , Sheetz Michael P.
Published: August 2011

Cell migration and spreading involve the coordination of membrane trafficking, actomyosin contraction, and modifications to plasma membrane tension and area. The biochemical or biophysical basis for this coordination is however unknown. In this study, we show that during cell spreading, lamellipodia protrusion flattens plasma membrane folds and blebs and, once the plasma membrane area is depleted, there is a temporary increase in membrane tension by over twofold that is followed by activation of exocytosis and myosin contraction. Further, an artificial increase in plasma membrane tension stopped lamellipodia protrusion and activated an exocytotic burst. Subsequent decrease in tension restored spreading with activation of contraction. Conversely, blebbistatin inhibition of actomyosin contraction resulted in an even greater increase in plasma membrane tension and exocytosis activation. This spatiotemporal synchronization indicates that membrane tension is the signal that coordinates membrane trafficking, actomyosin contraction, and plasma membrane area change. We suggest that cells use plasma membrane tension as a global physical parameter to control cell motility.
Spatially heterogeneous wastage of Himalayan glaciers
Authors: Fujita Koji , Nuimura Takayuki
Published: August 2011

We describe volumetric changes in three benchmark glaciers in the Nepal Himalayas on which observations have been made since the 1970s. Compared with the global mean of glacier mass balance, the Himalayan glaciers showed rapid wastage in the 1970s–1990s, but similar wastage in the last decade. In the last decade, a glacier in an arid climate showed negative but suppressed mass balance compared with the period 1970s–1990s, whereas two glaciers in a humid climate showed accelerated wastage. A mass balance model with downscaled gridded datasets depicts the fate of the observed glaciers. We also show a spatially heterogeneous distribution of glacier wastage in the Asian highlands, even under the present-day climate warming.
SNARE motif-mediated sorting of synaptobrevin by the endocytic adaptors clathrin assembly lymphoid myeloid leukemia (CALM) and AP180 at synapses
Authors: Koo Seong Joo , Markovic Stefan , Puchkov Dmytro , Mahrenholz Carsten C. , Beceren-Braun Figen , Maritzen Tanja , Dernedde Jens , Volkmer Rudolf , Oschkinat Hartmut , Haucke Volker
Published: August 2011

Neurotransmission depends on the exo-endocytosis of synaptic vesicles at active zones. Synaptobrevin 2 [also known as vesicle-associated membrane protein 2 (VAMP2)], the most abundant synaptic vesicle protein and a major soluble NSF attachment protein receptor (SNARE) component, is required for fast calcium-triggered synaptic vesicle fusion. In contrast to the extensive knowledge about the mechanism of SNARE-mediated exocytosis, little is known about the endocytic sorting of synaptobrevin 2. Here we show that synaptobrevin 2 sorting involves determinants within its SNARE motif that are recognized by the ANTH domains of the endocytic adaptors AP180 and clathrin assembly lymphoid myeloid leukemia (CALM). Depletion of CALM or AP180 causes selective surface accumulation of synaptobrevin 2 but not vGLUT1 at the neuronal surface. Endocytic sorting of synaptobrevin 2 is mediated by direct interaction of the ANTH domain of the related endocytic adaptors CALM and AP180 with the N-terminal half of the SNARE motif centered around M46, as evidenced by NMR spectroscopy analysis and site-directed mutagenesis. Our data unravel a unique mechanism of SNARE motif-dependent endocytic sorting and identify the ANTH domain proteins AP180 and CALM as cargo-specific adaptors for synaptobrevin endocytosis. Defective SNARE endocytosis may also underlie the association of CALM and AP180 with neurodevelopmental and cognitive defects or neurodegenerative disorders.
Reduced production of B-1–specified common lymphoid progenitors results in diminished potential of adult marrow to generate B-1 cells
Authors: Barber Chad L. , Montecino-Rodriguez Encarnacion , Dorshkind Kenneth
Published: August 2011

B-1 B cells have been proposed to be preferentially generated from fetal progenitors, but this view is challenged by studies concluding that B-1 production is sustained throughout adult life. To address this controversy, we compared the efficiency with which hematopoietic stem cells (HSCs) and common lymphoid progenitors (CLPs) from neonates and adults generated B-1 cells in vivo and developed a clonal in vitro assay to quantify B-1 progenitor production from CLPs. Adult HSCs and CLPs generated fewer B-1 cells in vivo compared with their neonatal counterparts, a finding corroborated by the clonal studies that showed that the CLP compartment includes B-1– and B-2–specified subpopulations and that the former cells decrease in number after birth. Together, these data indicate that B-1 lymphopoiesis is not sustained at constant levels throughout life and define a heretofore unappreciated developmental heterogeneity within the CLP compartment.
Response rescaling in bacterial chemotaxis
Authors: Lazova Milena D. , Ahmed Tanvir , Bellomo Domenico , Stocker Roman , Shimizu Thomas S.
Published: August 2011

Sensory systems rescale their response sensitivity upon adaptation according to simple strategies that recur in processes as diverse as single-cell signaling, neural network responses, and whole-organism perception. Here, we study response rescaling in
Escherichia coli
chemotaxis, where adaptation dynamically tunes the cells’ motile response during searches for nutrients. Using in vivo fluorescence resonance energy transfer (FRET) measurements on immobilized cells, we demonstrate that the design of this prokaryotic signaling network follows the fold-change detection (FCD) strategy, responding faithfully to the shape of the input profile irrespective of its absolute intensity. Using a microfluidics-based assay for free swimming cells, we confirm intensity-independent gradient responses at the behavioral level. By theoretical analysis, we identify a set of sufficient conditions for FCD in
E. coli
chemotaxis, which leads to the prediction that the adaptation timescale is invariant with respect to the background input level. Additional FRET experiments confirm that the adaptation timescale is invariant over an ∼10,000-fold range of background concentrations. These observations in a highly optimized bacterial system support the concept that FCD represents a robust sensing strategy for spatial searches. To our knowledge, these experiments provide a unique demonstration of FCD in any biological sensory system.
Morphological and functional stasis in mycorrhizal root nodules as exhibited by a Triassic conifer
Authors: Schwendemann Andrew B. , Decombeix Anne-Laure , Taylor Thomas N. , Taylor Edith L. , Krings Michael
Published: August 2011

Mycorrhizal root nodules occur in the conifer families Araucariaceae, Podocarpaceae, and Sciadopityaceae. Although the fossil record of these families can be traced back into the early Mesozoic, the oldest fossil evidence of root nodules previously came from the Cretaceous. Here we report on cellularly preserved root nodules of the early conifer
Notophytum
from Middle Triassic permineralized peat of Antarctica. These fossil root nodules contain fungal arbuscules, hyphal coils, and vesicles in their cortex. Numerous glomoid-type spores are found in the peat matrix surrounding the nodules. This discovery indicates that mutualistic associations between conifer root nodules and arbuscular mycorrhizal fungi date back to at least the early Mesozoic, the period during which most of the modern conifer families first appeared.
Notophytum
root nodules predate the next known appearance of this association by 100 million years, indicating that this specialized form of mycorrhizal symbiosis has ancient origins.
Diagnostic Single‐Nucleotide Polymorphisms Identify Pacific Ocean Perch and Delineate Blackspotted and Rougheye Rockfish
Authors: Garvin Michael R. , Marcotte Robert W. , Palof Katie J. , Riley Rachel J. , Kamin Lisa M. , Gharrett Anthony J.
Published: August 2011

Diagnostic single‐nucleotide polymorphisms (SNPs) that delineate Pacific ocean perchSebastes alutusfrom other rockfish species and distinguish rougheye rockfishS. aleutianusand blackspotted rockfishS. melanostictuswere developed from restriction endonuclease site differences in mitochondrial DNA sequences. The SNP developed for Pacific ocean perch was specific to that species in a panel of adult rockfishes common in Alaskan waters and positively recognized all of 994 adult specimens for reactions in which polymerase chain reaction product was obtained. Species‐specific microsatellite alleles (Sma6) and SNPs were concordant in 113 blackspotted and 26 rougheye rockfish. Five additional individuals were heterozygous for the microsatellite alleles and are presumably hybrids. These SNP markers, which are substantially faster to assay and much less labor‐intensive than restriction site analyses, can be used to identify individuals of any life stage during abundance surveys and provide necessary species identification in ecological and life history studies.
Spatial code recognition in neuronal RNA targeting: Role of RNA–hnRNP A2 interactions
Authors: Muslimov Ilham A. , Patel Mihir V. , Rose Arthur , Tiedge Henri
Published: August 2011

In neurons, regulation of gene expression occurs in part through translational control at the synapse. A fundamental requirement for such local control is the targeted delivery of select neuronal mRNAs and regulatory RNAs to distal dendritic sites. The nature of spatial RNA destination codes, and the mechanism by which they are interpreted for dendritic delivery, remain poorly understood. We find here that in a key dendritic RNA transport pathway (exemplified by BC1 RNA, a dendritic regulatory RNA, and protein kinase M ζ [PKMζ] mRNA, a dendritic mRNA), noncanonical purine•purine nucleotide interactions are functional determinants of RNA targeting motifs. These motifs are specifically recognized by heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2), a trans-acting factor required for dendritic delivery. Binding to hnRNP A2 and ensuing dendritic delivery are effectively competed by RNAs with CGG triplet repeat expansions. CGG repeats, when expanded in the 5′ untranslated region of fragile X mental retardation 1 (FMR1) mRNA, cause fragile X–associated tremor/ataxia syndrome. The data suggest that cellular dysregulation observed in the presence of CGG repeat RNA may result from molecular competition in neuronal RNA transport pathways.
FGF and retinoic acid activity gradients control the timing of neural crest cell emigration in the trunk
Authors: Martínez-Morales Patricia L. , Diez del Corral Ruth , Olivera-Martínez Isabel , Quiroga Alejandra C. , Das Raman M. , Barbas Julio A. , Storey Kate G. , Morales Aixa V.
Published: August 2011

Coordination between functionally related adjacent tissues is essential during development. For example, formation of trunk neural crest cells (NCCs) is highly influenced by the adjacent mesoderm, but the molecular mechanism involved is not well understood. As part of this mechanism, fibroblast growth factor (FGF) and retinoic acid (RA) mesodermal gradients control the onset of neurogenesis in the extending neural tube. In this paper, using gain- and loss-of-function experiments, we show that caudal FGF signaling prevents premature specification of NCCs and, consequently, premature epithelial–mesenchymal transition (EMT) to allow cell emigration. In contrast, rostrally generated RA promotes EMT of NCCs at somitic levels. Furthermore, we show that FGF and RA signaling control EMT in part through the modulation of elements of the bone morphogenetic protein and Wnt signaling pathways. These data establish a clear role for opposition of FGF and RA signaling in control of the timing of NCC EMT and emigration and, consequently, coordination of the development of the central and peripheral nervous system during vertebrate trunk elongation.
Graph braid groups and right-angled Artin groups
Authors: Kim Jee Hyoun , Ko Ki Hyoung , Park Hyo Won
Published: August 2011

We give a necessary and sufficient condition for a graph to have a right-angled Artin group as its braid group for braid index

≥
5

\ge 5

. In order to have the necessity part, graphs are organized into small classes so that one of the homological or cohomological characteristics of right-angled Artin groups can be applied. Finally we show that a given graph is planar iff the first homology of its 2-braid group is torsion-free, and we leave the corresponding statement for

n
n

-braid groups as a conjecture along with a few other conjectures about graphs whose braid groups of index

≤
4

\le 4

are right-angled Artin groups.
Semistable locus of a group compactification
Authors: He Xuhua , Starr Jason
Published: August 2011

In this paper, we consider the diagonal action of a connected semisimple group of adjoint type on its wonderful compactification. We show that the semistable locus is a union of the

G
G

-stable pieces and we calculate the geometric quotient.
The Determinants of Internationalization: Evidence from the Wine Industry
Authors: Olmos Marta Fernández
Published: August 2011

Relatively few empirical analyses have attempted to understand the export behavior of small and medium‐sized enterprises, and even fewer have examined the wine industry. The purpose of this research is to apply the resource‐based view to investigate the determinants of international expansion in the wine industry. Using a sample of 177 firms in the qualified appellation of origin (DOC) Rioja wine sector, we have found that process innovations are not a determinant of internationalization. However, the results show a positive and significant link between a firm's marketing activities and its level of internationalization. Our findings provide policy‐makers with some factors to encourage exports in the wine industry.
Hypoalbuminaemia and incident heart failure in older adults
Authors: Filippatos Gerasimos S. , Desai Ravi V. , Ahmed Mustafa I. , Fonarow Gregg C. , Love Thomas E. , Aban Inmaculada B. , Iskandrian Ami E. , Konstam Marvin A. , Ahmed Ali
Published: August 2011

Aims

To test the hypothesis that baseline hypoalbuminaemia is associated with incident heart failure (HF) in community‐dwelling older adults.

Methods and results

Of the 5795 community‐dwelling adults aged ≥65 years in the Cardiovascular Health Study, 5450 were free of centrally adjudicated prevalent HF at baseline, and also had data on baseline serum albumin. Of these, 599 (11%) had hypoalbuminaemia, defined as baseline serum albumin levels ≤3.5 mg/dL. Propensity scores for hypoalbuminaemia were calculated for each patient and used to assemble a matched cohort of 582 pairs of participants with and without hypoalbuminaemia, who were well balanced on 58 baseline characteristics. Using Cox regression models, we estimated the association of hypoalbuminaemia with centrally adjudicated incident HF during 9.6 years of median follow‐up. Matched participants had a mean (±SD) age of 74 (±6) years, 62% were women, and 16% were African Americans. Incident HF occurred in 25 and 20% of matched participants with and without hypoalbuminaemia, respectively [hazard ratio when hypoalbuminaemia was compared with normoalbuminaemia, 1.40; 95% confidence interval, 1.05–1.85; P = 0.020]. Pre‐match unadjusted, multivariable‐adjusted, and propensity‐adjusted hazard ratios (95% confidence intervals) for incident HF associated with hypoalbuminaemia were 1.33 (1.12–1.58; P = 0.001), 1.33 (1.11–1.60; P = 0.002), and 1.25 (1.04–1.50; P= 0.016), respectively. The combined endpoint of incident HF or all‐cause mortality occurred in 59 and 50% of matched participants with and without hypoalbuminaemia, respectively (hazard ratio, 1.33; 95% confidence interval, 1.11–1.61; P= 0.002).

Conclusions

Among community‐dwelling older adults without HF, baseline hypoalbuminaemia was associated with increased risk of incident HF during 10 years of follow‐up.
Exopolysaccharide Production Is Required for Biofilm Formation and Plant Colonization by the Nitrogen-Fixing Endophyte Gluconacetobacter diazotrophicus
Authors: Meneses Carlos H. S. G. , Rouws Luc F. M. , Simões-Araújo Jean L. , Vidal Marcia S. , Baldani José I.
Published: August 2011

The genome of the endophytic diazotrophic bacterial species Gluconacetobacter diazotrophicus PAL5 (PAL5) revealed the presence of a gum gene cluster. In this study, the gumD gene homologue, which is predicted to be responsible for the first step in exopolysaccharide (EPS) production, was insertionally inactivated and the resultant mutant (MGD) was functionally studied. The mutant MGD presented normal growth and nitrogen (N2) fixation levels but did not produce EPS when grown on different carbon sources. MGD presented altered colony morphology on soft agar plates (0.3% agar) and was defective in biofilm formation on glass wool. Most interestingly, MGD was defective in rice root surface attachment and in root surface and endophytic colonization. Genetic complementation reverted all mutant phenotypes. Also, the addition of EPS purified from culture supernatants of the wild-type strain PAL5 to the mutant MGD was effective in partially restoring wild-type biofilm formation and plant colonization. These data provide strong evidence that the PAL5 gumD gene is involved in EPS biosynthesis and that EPS biosynthesis is required for biofilm formation and plant colonization. To our knowledge, this is the first report of a role of EPS in the endophytic colonization of graminaceous plants by a nitrogen-fixing bacterium.
Virulence Dynamics and Regional Structuring of Puccinia striiformis f. sp. tritici in France Between 1984 and 2009
Authors: de Vallavieille-Pope Claude , Ali Sajid , Leconte Marc , Enjalbert Jérôme , Delos Marc , Rouzet Jacques
Published: August 2011

Understanding of long-term virulence dynamics of pathogen populations in response to host resistance gene deployment is of major importance for disease management and evolutionary biology. We monitored the virulence dynamics of Puccinia striiformis f. sp. tritici, the causal agent of wheat stripe rust, over 25 years in France. Virulence dynamics was explained by estimates of area associated with resistance genes carried by farmers' cultivars. The epidemics assessed through disease severity significantly correlated with the number of P. striiformis f. sp. tritici isolates collected each year, used to describe virulence dynamics. In the south, the dominance of the Mediterranean pathotype 6E16 and the cultivation of a susceptible cultivar were associated with an epidemic from 1997 to 1999. In the north, five epidemics occurred due to successive acquisition of virulence to the resistance genes Yr7, Yr6, Yr9, Yr17, and Yr32, either by acquisition of the virulence in the previous dominant pathotype or by incursion or selection of one or two new pathotypes. Frequency of pathotypes with Vr7 and Vr6 declined with the reduction in the cultivation of corresponding Yr gene cultivars, whereas the virulence Vr9 persisted longer than the cultivation of Yr9 cultivars. Although the first pathotypes carrying Vr9 decreased, this virulence persisted in other pathotypes even in the absence of Yr9 cultivars. At the regional level, Yr9 cultivars in the north caused a shift from high Vr6 frequency to high Vr9 frequency whereas, in the central region, where Yr9 cultivars were rare, Vr6 remained prevalent.
First Report of Leaf Blight of Basella alba Caused by Alternaria alternata in India
Authors: Sankar N. Ravi , Sreeramulu A. , Gopal D. Sai , Bagyanarayana G.
Published: August 2011

Basella alba is a perennial plant of the Basellaceae, native to India, and is distributed widely in the tropics as an ornamental. It is also known as Indian spinach, Ceylon spinach, vine spinach, Malabar spinach or Malabar nightshade and is mostly cultivated as a leafy vegetable or spinach substitute, being rich in vitamin A and C. From 2008 to 2010, severe foliar disease was observed on B. alba in the region of Southern Andhra Pradesh, India. Approximately 75 to 85% of the fields were affected with disease incidence ranging from 70 to 90%. Leaf lesions were elliptical to irregular oval, yellow brown to dark brown, and sometimes concentrically zonate with diffuse margins frequently surrounded by light-colored haloes. Infection often started at the leaf tips and progressed to the base of leaves as symptoms developed. In severe infections, lesions enlarged and coalesced, causing necrosis, wilting, and ultimately death of leaves. Tissues from the margin of infected leaf parts were surface sterilized in 1% sodium hypochlorite for 1 min, plated on potato dextrose agar (PDA), and then incubated at 27°C in the dark for 7 days. Hyphal tips from the margin of each developing colony were subcultured on PDA. Fungal colonies were initially white, becoming olivaceous, and turning brown with age. Conidiophores were brown, short, simple, or sometimes branched. Conidia were obclavate, obpyriform or ellipsoidal with a short conical beak, borne in long chains, branched or unbranched, pale brown to brown, and 18 to 32 μm long and 5 to 14 μm wide at the broadest point. Conidia had three to eight transverse septa and one to two longitudinal septa. On the basis of conidial morphological characteristics, the pathogen was identified as Alternaria alternata (Fr.) Keissler (2). For pathogenicity tests, inoculations were performed on detached, surface sterilized, healthy leaves following the method of Belisario (1). A 5-μl drop of conidial suspension containing 1 × 105 CFU/ml was placed on each leaf and 12 leaves per isolate were used. Leaves were incubated in a growth chamber (90% relative humidity with a 12-h photoperiod). After 7 days, leaf spots that were similar to the original symptoms developed on all inoculated leaves and A. alternata was consistently reisolated from symptomatic leaf tissues on PDA. Control leaves inoculated with sterile distilled water remained asymptomatic. The experiment was performed three times. To our knowledge, this is the first report of A. alternata on B. alba in India.

References: (1) A. Belisario et al. Plant Dis. 83:696, 1999. (2) E. G. Simmons. Alternaria: An Identification Manual. The American Phytopathological Society, St. Paul, MN, 2007.
Use of a Climatic Rule and Fuzzy Sets to Model Geographic Distribution of Climatic Risk for European Canker (Neonectria galligena) of Apple
Authors: Kim Kwang Soo , Beresford Robert M.
Published: August 2011

A rule-based model was developed to assess climatic risk of European canker (Neonectria galligena), which is a major disease of apple in some temperate zones. A descriptive rule was derived from published observations on climatic conditions favorable for European canker development. Fuzzy set theory was used to evaluate the descriptive rule quantitatively. The amount and frequency of rainfall and the average number of hours between 11 and 16°C/day were used as input variables whose values were matched with terms in the rule, e.g., ‘high’ or ‘low’. The degree of a term, e.g., the state of being high or low, to a given input value was determined using a membership function that converts an input value to a number between 0 and 1. The rule was evaluated by combining the degree of the terms associated with monthly climate data. Monthly risk index values derived using the rule were combined for pairs of consecutive months over 12 months. The annual risk of European canker development was represented by the maximum risk index value for 2 months combined. The membership function parameters were adjusted iteratively to achieve a specified level of risk at Talca (Chile), Loughgall (Northern Ireland), East Malling (UK), and Sebastopol (USA), where European canker risk was known. The rule-based model was validated with data collected from Canada, Ecuador, Denmark, Germany, Norway, Poland, Sweden, the Netherlands, New Zealand, and the Pacific Northwest (USA), where European canker has been reported to occur. In these validation areas, the model's risk prediction agreed with reports of disease occurrence. The rule-based model also predicted high risk areas more reliably than the climate matching model, CLIMEX, which relies on correlations between the spatial distribution of a species and climatic conditions. The combination of a climatic rule and fuzzy sets could be used for other applications where prediction of the geographic distribution of organisms is required for climatic risk assessment.
Resistance of Malus domestica Fruit to Botrytis cinerea Depends on Endogenous Ethylene Biosynthesis
Authors: Akagi Aya , Dandekar Abhaya M. , Stotz Henrik U.
Published: August 2011

The plant hormone ethylene regulates fruit ripening, other developmental processes, and a subset of defense responses. Here, we show that 1-aminocyclopropane-1-carboxylic acid synthase (ACS)-silenced apple (Malus domestica) fruit that express a sense construct of ACS were more susceptible to Botrytis cinerea than untransformed apple, demonstrating that ethylene strengthens fruit resistance to B. cinerea infection. Because ethylene response factors (ERFs) are known to contribute to resistance against B. cinerea via the ethylene-signaling pathway, we cloned four ERF cDNAs from fruit of M. domestica: MdERF3, -4, -5, and -6. Expression of all four MdERF mRNAs was ethylene dependent and induced by wounding or by B. cinerea infection. B. cinerea infection suppressed rapid induction of wound-related MdERF expression. MdERF3 was the only mRNA induced by wounding and B. cinerea infection in ACS-suppressed apple fruit, although its induction was reduced compared with wild-type apple. Promoter regions of all four MdERF genes were cloned and putative cis-elements were identified in each promoter. Transient expression of MdERF3 in tobacco increased expression of the GCC-box containing gene chitinase 48.
Low-Fluence Red Light Increases the Transport and Biosynthesis of Auxin
Authors: Liu Xing , Cohen Jerry D. , Gardner Gary
Published: August 2011

In plants, light is an important environmental signal that induces photomorphogenesis and interacts with endogenous signals, including hormones. We found that light increased polar auxin transport in dark-grown Arabidopsis (Arabidopsis thaliana) and tomato (Solanum lycopersicum) hypocotyls. In tomato, this increase was induced by low-fluence red or blue light followed by 1 d of darkness. It was reduced in phyA, phyB1, and phyB2 tomato mutants and was reversed by far-red light applied immediately after the red or blue light exposure, suggesting that phytochrome is involved in this response. We further found that the free indole-3-acetic acid (IAA) level in hypocotyl regions below the hook was increased by red light, while the level of conjugated IAA was unchanged. Analysis of IAA synthesized from [13C]indole or [13C]tryptophan (Trp) revealed that both Trp-dependent and Trp-independent IAA biosynthesis were increased by low-fluence red light in the top section (meristem, cotyledons, and hook), and the Trp-independent pathway appears to become the primary route for IAA biosynthesis after red light exposure. IAA biosynthesis in tissues below the top section was not affected by red light, suggesting that the increase of free IAA in this region was due to increased transport of IAA from above. Our study provides a comprehensive view of light effects on the transport and biosynthesis of IAA, showing that red light increases both IAA biosynthesis in the top section and polar auxin transport in hypocotyls, leading to unchanged free IAA levels in the top section and increased free IAA levels in the lower hypocotyl regions.
Increased Thermostability of Thylakoid Membranes in Isoprene-Emitting Leaves Probed with Three Biophysical Techniques
Authors: Velikova Violeta , Várkonyi Zsuzsanna , Szabó Milán , Maslenkova Liliana , Nogues Isabel , Kovács László , Peeva Violeta , Busheva Mira , Garab Győző , Sharkey Thomas D. , Loreto Francesco
Published: August 2011

Three biophysical approaches were used to get insight into increased thermostability of thylakoid membranes in isoprene-emittingplants.Arabidopsis (Arabidopsis thaliana) plants genetically modified to make isoprene and Platanus orientalis leaves, in which isoprene emission was chemically inhibited, were used. First, in the circular dichroism spectrum the transition temperature of the main band at 694 nm was higher in the presence of isoprene, indicating that the heat stability of chiral macrodomains of chloroplast membranes, and specifically the stability of ordered arrays of light-harvesting complex II-photosystem II in the stacked region of the thylakoid grana, was improved in the presence of isoprene. Second, the decay of electrochromic absorbance changes resulting from the electric field component of the proton motive force (ƊA  515) was evaluated following single-turnover saturating flashes. The decay of ƊA  515 was faster in the absence of isoprene when leaves of Arabidopsis and Platanus were exposed to high temperature, indicating that isoprene protects the thylakoid membranes against leakiness at elevated temperature. Finally, thermoluminescence measurements revealed that S2QB  − charge recombination was shifted to higher temperature in Arabidopsis and Platanus plants in the presence of isoprene, indicating higher activation energy for S2QB  − redox pair, which enables isoprene-emitting plants to perform efficient primary photochemistry of photosystem II even at higher temperatures. The data provide biophysical evidence that isoprene improves the integrity and functionality of the thylakoid membranes at high temperature. These results contribute to our understanding of isoprene mechanism of action in plant protection against environmental stresses.