bluuebunny/crossref_metadata_2025 huggingface dataset:
An E3 ligase complex regulates SET-domain polycomb group protein activity in
Arabidopsis thaliana
Authors: Jeong Cheol Woong , Roh Hyungmin , Dang Tuong Vi , Choi Yang Do , Fischer Robert L. , Lee Jong Seob , Choi Yeonhee
Published: April 2011

Transcriptional repression via methylation of histone H3 lysine 27 (H3K27) by the polycomb repressive complex 2 (PRC2) is conserved in higher eukaryotes. The
Arabidopsis
PRC2 controls homeotic gene expression, flowering time, and gene imprinting. Although downstream target genes and the regulatory mechanism of PRC2 are well understood, much less is known about the significance of posttranslational regulation of PRC2 protein activity. Here, we show the posttranslational regulation of CURLY LEAF (CLF) SET-domain polycomb group (PcG) protein by the F-box protein, UPWARD CURLY LEAF1 (UCL1). Overexpression of
UCL1
generates mutant phenotypes similar to those observed in plants with a loss-of-function mutation in the
CLF
gene. Leaf curling and early flowering phenotypes of
UCL1
overexpression mutants, like
clf
mutants, are rescued by mutations in the
AGAMOUS
and
FLOWERING LOCUS T
genes, which is consistent with
UCL1
and
CLF
functioning in the same genetic pathway. Overexpression of
UCL1
reduces the level of CLF protein and alters expression and H3K27 methylation of CLF-target genes in transgenic plants, suggesting that UCL1 negatively regulates CLF. Interaction of UCL1 with CLF was detected in plant nuclei and in the yeast two-hybrid system. The UCL1 F-box binds in vivo to components of the E3 ligase complex, which ubiquitylate proteins that are subsequently degraded via the ubiquitin-26S proteasome pathway. Taken together, these results demonstrate the posttranslational regulation of the CLF SET-domain PcG activity by the UCL1 F-box protein in the E3 ligase complex.
Histone chaperone Spt6 is required for class switch recombination but not somatic hypermutation
Authors: Okazaki Il-mi , Okawa Katsuya , Kobayashi Maki , Yoshikawa Kiyotsugu , Kawamoto Shimpei , Nagaoka Hitoshi , Shinkura Reiko , Kitawaki Yoko , Taniguchi Hisaaki , Natsume Tohru , Iemura Shun-Ichiro , Honjo Tasuku
Published: April 2011

Activation-induced cytidine deaminase (AID) is shown to be essential and sufficient to induce two genetic alterations in the Ig loci: class switch recombination (CSR) and somatic hypermutation (SHM). However, it is still unknown how a single-molecule AID differentially regulates CSR and SHM. Here we identified Spt6 as an AID-interacting protein by yeast two-hybrid screening and immunoprecipitation followed by mass spectrometry. Knockdown of Spt6 resulted in severe reduction of CSR in both the endogenous Ig locus in B cells and an artificial substrate in fibroblast cells. Conversely, knockdown of Spt6 did not reduce but slightly enhanced SHM in an artificial substrate in B cells, indicating that Spt6 is required for AID to induce CSR but not SHM. These results suggest that Spt6 is involved in differential regulation of CSR and SHM by AID.
Drinking a hot blood meal elicits a protective heat shock response in mosquitoes
Authors: Benoit Joshua B. , Lopez-Martinez Giancarlo , Patrick Kevin R. , Phillips Zachary P. , Krause Tyler B. , Denlinger David L.
Published: April 2011

The mosquito's body temperature increases dramatically when it takes a blood meal from a warm-blooded, vertebrate host. By using the yellow fever mosquito,
Aedes aegypti
, we demonstrate that this boost in temperature following a blood meal prompts the synthesis of heat shock protein 70 (Hsp70). This response, elicited by the temperature of the blood meal, is most robust in the mosquito's midgut. When RNA interference is used to suppress expression of
hsp70
, protein digestion of the blood meal is impaired, leading to production of fewer eggs. We propose that Hsp70 protects the mosquito midgut from the temperature stress incurred by drinking a hot blood meal. Similar increases in
hsp70
were documented immediately after blood feeding in two other mosquitoes (
Culex pipiens
and
Anopheles gambiae
) and the bed bug,
Cimex lectularius
, suggesting that this is a common protective response in blood-feeding arthropods.
FER tyrosine kinase (FER) overexpression mediates resistance to quinacrine through EGF-dependent activation of NF-κB
Authors: Guo Canhui , Stark George R.
Published: April 2011

Quinacrine, a drug with antimalarial and anticancer activities that inhibits NF-κB and activates p53, has progressed into phase II clinical trials in cancer. To further elucidate its mechanism of action and identify pathways of drug resistance, we used an unbiased method for validation-based insertional mutagenesis to isolate a quinacrine-resistant cell line in which an inserted CMV promoter drives overexpression of the FER tyrosine kinase (FER). Overexpression of FER from a cDNA confers quinacrine resistance to several different types of cancer cell lines. We show that quinacrine kills cancer cells primarily by inhibiting the activation of NF-κB and that increased activation of NF-κB through FER overexpression mediates resistance. EGF activates NF-κB and stimulates phosphorylation of FER, EGF receptor (EGFR), and ERK p42/p44, and decreased expression of FER or inhibition of ERK phosphorylation inhibits the EGF-induced activation of NF-κB. FER binds to EGFR, and overexpression of FER in cells untreated with EGF increases this association, leading to increased phosphorylation of EGFR and ERK. We conclude that FER is on a pathway connecting EGFR to NF-κB activation and that this function is responsible for FER-dependent resistance to quinacrine.
PAR proteins cross the boundary
Authors: Leslie Mitch
Published: April 2011

Polarity proteins don't stay on their own side of the membrane.
Cell wound repair in Drosophila occurs through three distinct phases of membrane and cytoskeletal remodeling
Authors: Abreu-Blanco Maria Teresa , Verboon Jeffrey M. , Parkhurst Susan M.
Published: April 2011

When single cells or tissues are injured, the wound must be repaired quickly in order to prevent cell death, loss of tissue integrity, and invasion by microorganisms. We describe Drosophila as a genetically tractable model to dissect the mechanisms of single-cell wound repair. By analyzing the expression and the effects of perturbations of actin, myosin, microtubules, E-cadherin, and the plasma membrane, we define three distinct phases in the repair process—expansion, contraction, and closure—and identify specific components required during each phase. Specifically, plasma membrane mobilization and assembly of a contractile actomyosin ring are required for this process. In addition, E-cadherin accumulates at the wound edge, and wound expansion is excessive in E-cadherin mutants, suggesting a role for E-cadherin in anchoring the actomyosin ring to the plasma membrane. Our results show that single-cell wound repair requires specific spatial and temporal cytoskeleton responses with distinct components and mechanisms required at different stages of the process.
PAR proteins diffuse freely across the anterior–posterior boundary in polarized C. elegans embryos
Authors: Goehring Nathan W. , Hoege Carsten , Grill Stephan W. , Hyman Anthony A.
Published: April 2011

Polarization of cells by PAR proteins requires the segregation of antagonistic sets of proteins into two mutually exclusive membrane-associated domains. Understanding how nanometer scale interactions between individual PAR proteins allow spatial organization across cellular length scales requires determining the kinetic properties of PAR proteins and how they are modified in space. We find that PAR-2 and PAR-6, which localize to opposing PAR domains, undergo exchange between well mixed cytoplasmic populations and laterally diffusing membrane-associated states. Domain maintenance does not involve diffusion barriers, lateral sorting, or active transport. Rather, both PAR proteins are free to diffuse between domains, giving rise to a continuous boundary flux because of lateral diffusion of molecules down the concentration gradients that exist across the embryo. Our results suggest that the equalizing effects of lateral diffusion are countered by actin-independent differences in the effective membrane affinities of PAR proteins between the two domains, which likely depend on the ability of each PAR species to locally modulate the membrane affinity of opposing PAR species within its domain. We propose that the stably polarized embryo reflects a dynamic steady state in which molecules undergo continuous diffusion between regions of net association and dissociation.
Platelet-derived serotonin links vascular disease and tissue fibrosis
Authors: Dees Clara , Akhmetshina Alfiya , Zerr Pawel , Reich Nicole , Palumbo Katrin , Horn Angelika , Jüngel Astrid , Beyer Christian , Krönke Gerhard , Zwerina Jochen , Reiter Rudolf , Alenina Natalia , Maroteaux Luc , Gay Steffen , Schett Georg , Distler Oliver , Distler Jörg H.W.
Published: April 2011

Vascular damage and platelet activation are associated with tissue remodeling in diseases such as systemic sclerosis, but the molecular mechanisms underlying this association have not been identified. In this study, we show that serotonin (5-hydroxytryptamine [5-HT]) stored in platelets strongly induces extracellular matrix synthesis in interstitial fibroblasts via activation of 5-HT2B receptors (5-HT2B) in a transforming growth factor β (TGF-β)–dependent manner. Dermal fibrosis was reduced in 5-HT2B−/− mice using both inducible and genetic models of fibrosis. Pharmacologic inactivation of 5-HT2B also effectively prevented the onset of experimental fibrosis and ameliorated established fibrosis. Moreover, inhibition of platelet activation prevented fibrosis in different models of skin fibrosis. Consistently, mice deficient for TPH1, the rate-limiting enzyme for 5-HT production outside the central nervous system, showed reduced experimental skin fibrosis. These findings suggest that 5-HT/5-HT2B signaling links vascular damage and platelet activation to tissue remodeling and identify 5-HT2B as a novel therapeutic target to treat fibrotic diseases.
Memory/effector (CD45RBlo) CD4 T cells are controlled directly by IL-10 and cause IL-22–dependent intestinal pathology
Authors: Kamanaka Masahito , Huber Samuel , Zenewicz Lauren A. , Gagliani Nicola , Rathinam Chozhavendan , O'Connor William , Wan Yisong Y. , Nakae Susumu , Iwakura Yoichiro , Hao Liming , Flavell Richard A.
Published: April 2011

The role of direct IL-10 signaling in different T cell subsets is not well understood. To address this, we generated transgenic mice expressing a dominant-negative IL-10 receptor specifically in T cells (CD4dnIL-10Rα). We found that Foxp3-depleted CD45RBlo (regulatory T cell [Treg cell]–depleted CD45RBlo) but not CD45RBhi CD4+ T cells are controlled directly by IL-10 upon transfer into Rag1 knockout (KO) mice. Furthermore, the colitis induced by transfer of Treg cell–depleted CD45RBlo CD4+ T cells into Rag1 KO mice was characterized by reduced Th1 and increased Th17 cytokine messenger RNA levels in the colon as compared with the colitis induced by transfer of CD45RBhi T cells. In contrast to the CD45RBhi transfer colitis model, in which IL-22 is protective, we found that T cell–derived IL-22 was pathogenic upon transfer of Treg cell–depleted CD45RBlo T cells into Rag1 KO mice. Our results highlight characteristic differences between colitis induced by naive (CD45RBhi) and memory/effector (Treg cell–depleted CD45RBlo) cells and different ways that IL-22 impacts inflammatory bowel disease.
A characterisation of anti-Löwner functions
Authors: Audenaert Koenraad
Published: April 2011

According to a celebrated result by Löwner, a real-valued function

f
f

is operator monotone if and only if its Löwner matrix, which is the matrix of divided differences
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper L Subscript f Baseline equals left-parenthesis StartFraction f left-parenthesis x Subscript i Baseline right-parenthesis minus f left-parenthesis x Subscript j Baseline right-parenthesis Over x Subscript i Baseline minus x Subscript j Baseline EndFraction right-parenthesis Subscript i comma j equals 1 Superscript upper N">

L
f

=

(

f
(

x
i

)
−
f
(

x
j

)

x
i

−

x
j

)

i
,
j
=
1

N

L_f=\left (\frac {f(x_i)-f(x_j)}{x_i-x_j}\right )_{i,j=1}^N

, is positive semidefinite for every integer

N
>
0

N>0

and any choice of

x
1

,

x
2

,
…
,

x
N

x_1,x_2,\ldots ,x_N

. In this paper we answer a question of R. Bhatia, who asked for a characterisation of real-valued functions

g
g

defined on

(
0
,
+
∞
)

(0,+\infty )

for which the matrix of divided sums
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper K Subscript g Baseline equals left-parenthesis StartFraction g left-parenthesis x Subscript i Baseline right-parenthesis plus g left-parenthesis x Subscript j Baseline right-parenthesis Over x Subscript i Baseline plus x Subscript j Baseline EndFraction right-parenthesis Subscript i comma j equals 1 Superscript upper N">

K
g

=

(

g
(

x
i

)
+
g
(

x
j

)

x
i

+

x
j

)

i
,
j
=
1

N

K_g=\left (\frac {g(x_i)+g(x_j)}{x_i+x_j}\right )_{i,j=1}^N

, which we call its anti-Löwner matrix, is positive semidefinite for every integer

N
>
0

N>0

and any choice of

x
1

,

x
2

,
…
,

x
N

∈
(
0
,
+
∞
)

x_1,x_2,\ldots ,x_N\in (0,+\infty )

. Such functions, which we call anti-Löwner functions, have applications in the theory of Lyapunov-type equations.
Zero-sum free sets with small sum-set
Authors: Bhowmik Gautami , Halupczok Immanuel , Schlage-Puchta Jan-Christoph
Published: April 2011

Let

A
A

be a zero-sum free subset of

Z

n

\mathbb {Z}_n

with

|

A

|

=
k

|A|=k

. We compute for

k
≤
7

k\leq 7

the least possible size of the set of all subset-sums of

A
A

.
The infrastructure of a global field of arbitrary unit rank
Authors: Fontein Felix
Published: April 2011

In this paper, we show a general way to interpret the infrastructure of a global field of arbitrary unit rank. This interpretation generalizes the prior concepts of the giant-step operation and

f
f

-representations, and makes it possible to relate the infrastructure to the (Arakelov) divisor class group of the global field. In the case of global function fields, we present results that establish that effective implementation of the presented methods is indeed possible, and we show how Shanks’ baby-step giant-step method can be generalized to this situation.
High Levels of a Fungal Superoxide Dismutase and Increased Concentration of a PR-10 Plant Protein in Associations Between the Endophytic Fungus Neotyphodium lolii and Ryegrass
Authors: Zhang Ningxin , Zhang Shuguang , Borchert Sophie , Richardson Kim , Schmid Jan
Published: April 2011

Neotyphodium lolii is a fungal endosymbiont of the ryegrass Lolium perenne. Its growth is tightly controlled and synchronized with that of the plant. How the symbionts communicate is largely unknown but failure of the endophyte to elicit a defense response is considered crucial for successful symbiosis. In silver-stained two-dimensional gels of protein extracts from endophyte-infected ryegrass, a fungal Cu/Zn superoxide dismutase was detectable, even though the fungus accounts for only [Formula: see text] of the biomass, indicating that it is an abundant fungal protein and that the fungus needs protection against reactive oxygen species. The plant increased levels of a pathogenesis-related class 10 (PR-10) protein; when equal amounts of protein from infected and uninfected plants were loaded, PR-10 was only detectable in extracts from infected plants. Presence of the endophyte did not lead to a significant increase in PR10 transcript levels. In protein extracts from a symbiosis containing an N. lolii variant with an abnormal in planta growth pattern, the fungal Cu/Zn superoxide dismutase but not PR-10 protein was detectable. The correlation between increased PR-10 levels and presence of a normally growing endophyte is suggestive of a role of a very limited host defense in the interaction between grass and endophyte.
Development of a Bio-PCR Protocol for the Detection of Xanthomonas arboricola pv. pruni
Authors: Ballard E. L. , Dietzgen R. G. , Sly L. I. , Gouk C. , Horlock C. , Fegan M.
Published: April 2011

A real-time SYBR Green I assay was developed and evaluated as a biological and enzymatic polymerase chain reaction (Bio-PCR) protocol for the detection of Xanthomonas arboricola pv. pruni. Suppression subtractive hybridization was used to generate a X. arboricola pv. pruni-specific subtracted DNA library, using X. arboricola pv. corylina as the driver strain. Primer pair 29F/R, designed from cloned sequence, showed no homology to GenBank sequences and amplified a 344-bp product in all X. arboricola pv. pruni isolates. Compared with other published X. arboricola pv. pruni primers, this primer pair was shown to be the only one capable of differentiating X. arboricola pv. pruni from all other X. arboricola pathovars. A real-time assay was developed and shown to be capable of detecting less than 10 CFU and 0.1 pg of DNA. Epiphytic bacteria isolated from plum tissue was used to further evaluate the specificity of the assay. A Bio-PCR protocol, developed for field evaluation, confirmed X. arboricola pv. pruni isolation from asymptomatic and symptomatic plum tissue over a 9-week period between host flowering and the first appearance of leaf and fruit symptoms in an orchard. Dilution plating enabled X. arboricola pv. pruni numbers to be quantified, providing supportive evidence for the usefulness of the Bio-PCR protocol in plant pathology and quarantine surveillance.
Tryptophan Regulates Thaxtomin A and Indole-3-Acetic Acid Production in Streptomyces scabiei and Modifies Its Interactions with Radish Seedlings
Authors: Legault Geneviève S. , Lerat Sylvain , Nicolas Philippe , Beaulieu Carole
Published: April 2011

The virulence of Streptomyces scabiei, the causal agent of common scab, depends mainly on the production of the toxin thaxtomin A. S. scabiei also produces indole-3-acetic acid (IAA) but the role of this hormone in the interaction between pathogenic streptomycetes and plants has not yet been elucidated. Tryptophan is a biosynthetic precursor of both IAA and thaxtomin A. In this study, the effect of tryptophan on thaxtomin A and IAA production as well as its effect on the transcription of the corresponding biosynthetic genes in S. scabiei has been analyzed. In vitro IAA production depended on the availability of tryptophan. However, addition of this amino acid to the culture medium inhibited the biosynthesis of thaxtomin A. Expression of thaxtomin A biosynthetic genes nos and txtA were strongly repressed in the presence of tryptophan; however, modulation of the expression was not observed for the IAA biosynthetic genes iaaM and iaaH. The effects of an exogenous tryptophan supply on S. scabiei virulence were assessed on radish seedlings. Addition of tryptophan reduced symptoms on inoculated radish roots compared with seedlings grown in the absence of the bacterium, by way of inhibition of thaxtomin A production and increase of IAA biosynthesis.
Effect of Wetness Duration and Temperature on the Development of Anthracnose on Selected Almond Tissues and Comparison of Cultivar Susceptibility
Authors: Diéguez-Uribeondo J. , Förster H. , Adaskaveg J. E.
Published: April 2011

Blossoms, leaves, fruit, and woody tissues of almond can be affected by anthracnose caused by Colletotrichum acutatum. Because the disease occurs throughout rainy spring seasons, the effect of temperature and wetness duration on disease development was evaluated in controlled studies. The lowest inoculum concentration where disease developed on leaves was 104 conidia/ml. Longer wetness durations were needed for leaves than for blossoms and disease increased linearly with increasing wetness durations. Inoculation temperature mainly affected final disease levels. Temperature during incubation affected the rate of disease development, while final disease levels were very similar at 10, 15, or 20°C. An analysis of covariance was performed to compare regressions of the effects of wetness and temperature on disease development for several almond cultivars. For blossom inoculations at 15°C in growth-chamber studies, a common slope model was statistically sufficient to describe all four cultivars. Cultivar Nonpareil (NP) had a significantly (P < 0.05) lower adjusted means at the midpoint than cultivars Carmel (CA), NePlus Ultra (NU), and Wood Colony (WC). For blossom inoculations at 20°C and for leaf inoculations at all temperatures evaluated, an unequal slope model was statistically justified for comparing regression lines. For blossoms, the slopes were significantly different (P < 0.05) for pair-wise comparisons of CA-NU, NU-WC, and NP-WC. For leaves, most of the cultivars responded differently to infection at different temperatures. Two of the pair-wise comparisons demonstrated unequal slopes at all three temperatures evaluated (i.e., NU-NP and NU-WC). Overall, for blossoms and leaves, NP was the least susceptible, NU was the most susceptible, and WC and CA showed an intermediate susceptibility. In field blossom and fruit studies, a common slope model was statistically sufficient to describe all four cultivars. NP had a significantly lower midpoint (i.e., was less susceptible) than CA or WC, whereas no significant difference (P > 0.1) occurred in comparisons between CA and WC.
Comparative analysis of the primate X-inactivation center region and reconstruction of the ancestral primate XIST locus
Authors: Horvath Julie E. , Sheedy Christina B. , Merrett Stephanie L. , Diallo Abdoulaye Banire , Swofford David L. , NISC Comparative Sequencing Program  , Green Eric D. , Willard Huntington F.
Published: April 2011

Here we provide a detailed comparative analysis across the candidate X-Inactivation Center (XIC) region and the XIST locus in the genomes of six primates and three mammalian outgroup species. Since lemurs and other strepsirrhine primates represent the sister lineage to all other primates, this analysis focuses on lemurs to reconstruct the ancestral primate sequences and to gain insight into the evolution of this region and the genes within it. This comparative evolutionary genomics approach reveals significant expansion in genomic size across the XIC region in higher primates, with minimal size alterations across the XIST locus itself. Reconstructed primate ancestral XIC sequences show that the most dramatic changes during the past 80 million years occurred between the ancestral primate and the lineage leading to Old World monkeys. In contrast, the XIST locus compared between human and the primate ancestor does not indicate any dramatic changes to exons or XIST-specific repeats; rather, evolution of this locus reflects small incremental changes in overall sequence identity and short repeat insertions. While this comparative analysis reinforces that the region around XIST has been subject to significant genomic change, even among primates, our data suggest that evolution of the XIST sequences themselves represents only small lineage-specific changes across the past 80 million years.
Human population dispersal “Out of Africa” estimated from linkage disequilibrium and allele frequencies of SNPs
Authors: McEvoy Brian P. , Powell Joseph E. , Goddard Michael E. , Visscher Peter M.
Published: April 2011

Genetic and fossil evidence supports a single, recent (<200,000 yr) origin of modern Homo sapiens in Africa, followed by later population divergence and dispersal across the globe (the “Out of Africa” model). However, there is less agreement on the exact nature of this migration event and dispersal of populations relative to one another. We use the empirically observed genetic correlation structure (or linkage disequilibrium) between 242,000 genome-wide single nucleotide polymorphisms (SNPs) in 17 global populations to reconstruct two key parameters of human evolution: effective population size (Ne) and population divergence times (T). A linkage disequilibrium (LD)–based approach allows changes in human population size to be traced over time and reveals a substantial reduction in Ne accompanying the “Out of Africa” exodus as well as the dramatic re-expansion of non-Africans as they spread across the globe. Secondly, two parallel estimates of population divergence times provide clear evidence of population dispersal patterns “Out of Africa” and subsequent dispersal of proto-European and proto-East Asian populations. Estimates of divergence times between European–African and East Asian–African populations are inconsistent with its simplest manifestation: a single dispersal from the continent followed by a split into Western and Eastern Eurasian branches. Rather, population divergence times are consistent with substantial ancient gene flow to the proto-European population after its divergence with proto-East Asians, suggesting distinct, early dispersals of modern H. sapiens from Africa. We use simulated genetic polymorphism data to demonstrate the validity of our conclusions against alternative population demographic scenarios.
Cellular site and molecular mode of synapsin action in associative learning
Authors: Michels Birgit , Chen Yi-chun , Saumweber Timo , Mishra Dushyant , Tanimoto Hiromu , Schmid Benjamin , Engmann Olivia , Gerber Bertram
Published: April 2011

Synapsin is an evolutionarily conserved, presynaptic vesicular phosphoprotein. Here, we ask where and how synapsin functions in associative behavioral plasticity. Upon loss or reduction of synapsin in a deletion mutant or via RNAi, respectively, Drosophila larvae are impaired in odor-sugar associative learning. Acute global expression of synapsin and local expression in only the mushroom body, a third-order “cortical” brain region, fully restores associative ability in the mutant. No rescue is found by synapsin expression in mushroom body input neurons or by expression excluding the mushroom bodies. On the molecular level, we find that a transgenically expressed synapsin with dysfunctional PKA-consensus sites cannot rescue the defect of the mutant in associative function, thus assigning synapsin as a behaviorally relevant effector of the AC-cAMP-PKA cascade. We therefore suggest that synapsin acts in associative memory trace formation in the mushroom bodies, as a downstream element of AC-cAMP-PKA signaling. These analyses provide a comprehensive chain of explanation from the molecular level to an associative behavioral change.
The Arabidopsis Transcription FactorLUH/MUM1Is Required for Extrusion of Seed Coat Mucilage
Authors: Huang Jun , DeBowles Danisha , Esfandiari Elahe , Dean Gillian , Carpita Nicholas C. , Haughn George W.
Published: April 2011

During differentiation, the Arabidopsis (Arabidopsis thaliana) seed coat epidermal cells secrete mucilage composed primarily of rhamnogalacturonan I that is extruded from the seed coat upon imbibition. The mucilage of the mucilage modified1 (mum1) mutant contains rhamnogalacturonan I that is more highly branched and lacks the ability to be extruded when exposed to water. Our cloning of the MUM1 gene shows that it encodes a putative transcription factor, LEUNIG_HOMOLOG (LUH). Cellular localization and transcriptional assay results suggest that LUH/MUM1 is a nucleus-localized transcriptional activator. LUH/MUM1 is expressed in all the tissues examined, including the seed coat. Quantitative reverse transcription-polymerase chain reaction data suggest that LUH/MUM1 is expressed throughout seed coat development, reaching peak expression late in differentiation. LUH1/MUM1 expression in plants homozygous for mutations in several genes encoding regulators of seed coat mucilage was unchanged. Thus, LUH/MUM1 expression appears to be independent of other transcription factors known to regulate aspects of seed coat mucilage biology. The expression in the luh/mum1 mutant of three genes encoding enzymes needed for mucilage extrusion, MUM2, SUBSILIN PROTEASE1.7, and β-XYLOSIDASE1, was reduced relative to that of the wild type. Overexpression of MUM2 could partially rescue the mum1 phenotype. These data suggest that LUH/MUM1 is a positive regulator of all three genes.
Synchrotron scanning photoemission microscopy of homogeneous and heterogeneous metal sulfide minerals
Authors: Acres Robert George , Harmer Sarah Louise , Shui Hung Wei , Chen Chia-Hao , Beattie David Allan
Published: April 2011

Scanning photoemission microscopy (SPEM) has been applied to the investigation of homogeneous and heterogeneous metal sulfide mineral surfaces. Three mineral samples were investigated: homogeneous chalcopyrite, heterogeneous chalcopyrite with bornite, and heterogeneous chalcopyrite with pyrite. Sulfur, copper and iron SPEM images,i.e.surface-selective elemental maps with high spatial resolution acquired using the signal from the S 2pand Cu and Fe 3pphotoemission peaks, were obtained for the surfaces after exposure to different oxidation conditions (either exposed to air or oxidized in pH 9 solution), in addition to high-resolution photoemission spectra from individual pixel areas of the images. Investigation of the homogeneous chalcopyrite sample allowed for the identification of step edges using the topography SPEM image, and high-resolution S 2pspectra acquired from the different parts of the sample image revealed a similar rate of surface oxidation from solution exposure for both step edge and a nearby terrace site. SPEM was able to successfully distinguish between chalcopyrite and bornite on the heterogeneous sample containing both minerals, based upon sulfur imaging. The high-resolution S 2pspectra acquired from the two regions highlighted the faster air oxidation of the bornite relative to the chalcopyrite. Differentiation between chalcopyrite and pyrite based upon contrast in SPEM images was not successful, owing to either the poor photoionization cross section of the Cu and Fe 3pelectrons or issues with rough fracture of the composite surface. In spite of this, high-resolution S 2pspectra from each mineral phase were successfully obtained using a step-scan approach.
Modeling Load Redistribution Attacks in Power Systems
Authors: Yuan Yanling , Li Zuyi , Ren Kui
Published: April 2011

State estimation is a key element in today's power systems for reliable system operation and control. State estimation collects information from a large number of meter measurements and analyzes it in a centralized manner at the control center. Existing state estimation approaches were traditionally assumed to be able to tolerate and detect random bad measurements. They were, however, recently shown to be vulnerable to intentional false data injection attacks. This paper fully develops the concept of load redistribution (LR) attacks, a special type of false data injection attacks, and analyzes their damage to power system operation in different time steps with different attacking resource limitations. Based on damaging effect analysis, we differentiate two attacking goals from the adversary's perspective, i.e., immediate attacking goal and delayed attacking goal. For the immediate attacking goal, this paper identifies the most damaging LR attack through a max-min attacker-defender model. Then, the criterion of determining effective protection strategies is explained. The effectiveness of the proposed model is tested on a 14-bus system. To the author's best knowledge, this is the first work of its kind, which quantitatively analyzes the damage of the false data injection attacks to power system operation and security. Our analysis hence provides an in-depth insight on effective attack prevention with limited protection resource budget.
Interplay of individual interactions and turbidity affects the functional response of three‐spined sticklebacks Gasterosteus aculeatus
Authors: Vollset K. W. , Bailey K. M.
Published: April 2011

The effects of turbidity, size and the presence of conspecifics on the functional response, feeding latency and activity in the three‐spined stickleback Gasterosteus aculeatus were examined. A significant interaction between standard length and presence of conspecifics demonstrated an increase in attack rates of larger individuals in the presence of conspecifics. Attack rate was also higher in turbid water. Feeding latency decreased with prey concentration and presence of conspecifics, but was not affected by turbidity. Activity level did not change with prey levels, but increased with turbidity. These results can help to better understand how individual flexibility in the functional response can affect prey mortality according to environmental perturbation and social interaction at the level of the predator.
Straight‐nosed pipefish Nerophis ophidion and broad‐nosed pipefish Syngnathus typhle avoid eelgrass overgrown with filamentous algae
Authors: Sundin J. , Jacobsson Ö. , Berglund A. , Rosenqvist G.
Published: April 2011

In a habitat choice experiment straight‐nosed pipefish Nerophis ophidion and broad‐nosed pipefish Syngnathus typhle avoided eelgrass Zostera marina covered with filamentous algae. Both juveniles as well as brooding adult males of the two species clearly preferred to position themselves in Z. marina without growth of filamentous algae.
Advances in tagging syngnathids, with the effects of dummy tags on behaviour of Hippocampus guttulatus
Authors: Caldwell I. R. , Correia M. , Palma J. , Vincent A. C. J.
Published: April 2011

Artificial marking and tagging techniques have been used to study movement, population dynamics, behaviour, ecology, survival and growth of at least 25 syngnathid species. External necklace‐style tags and injection of visible implant elastomer have been the most used techniques, uniquely identifying hundreds of individual syngnathids to study population dynamics, mortality, behaviour, ecology and growth in at least 13 and 12 species, respectively. Only two studies, both on larger syngnathid species, have tested the use of internal or electronic tags. This new case study reveals that dummy tags, weighing up to 6% of individual body mass, have minimal effect on normal ex situ behaviour of the long‐snouted seahorse Hippocampus guttulatus, a smaller syngnathid. In paired aquarium trials, tags did not affect movement, holdfast use or general behavioural state, and only had a short‐term effect (1 day) on vertical orientation. Tagged H. guttulatus gained more mass during the 5 day trials, a result which warrants further exploration but indicates that tags did not reduce feeding. This study shows promise for using electronic tagging to study H. guttulatus and similarly sized syngnathids in the wild.
Meeting the Needs of Vulnerable Young Men: A Study of Service Provider Views
Authors: Campbell Jim , Rondon Janeet , Galway Karen , Leavey Gerry
Published: April 2011

This article uses a qualitative approach to elicit the views of 31 professionals who provide services to vulnerable young men. The findings reveal six key themes following focus group interviews: (i) the importance of masculinity in explaining problematic behaviour; (ii) the misuse of alcohol and drugs; (iii) alienation and social isolation; (iv) concerns about suicide and self‐harm; (v) the quality of existing services; and (vi) recommendations for changes to services. Service providers generally acknowledged the social context in explaining these behaviours and argued for enhanced services and a more developed skills base in working with vulnerable young men.
Inhibition of mTOR by temsirolimus contributes to prolonged survival of mice with pleural dissemination of non‐small‐cell lung cancer cells
Authors: Ohara Toshiaki , Takaoka Munenori , Toyooka Shinichi , Tomono Yasuko , Nishikawa Toshio , Shirakawa Yasuhiro , Yamatsuji Tomoki , Tanaka Noriaki , Fujiwara Toshiyoshi , Naomoto Yoshio
Published: April 2011

Temsirolimus (CCI‐779), a recently synthesized analogue of rapamycin, specifically inhibits mTOR and has been approved for clinical use in renal cell carcinoma. Recent reports have indicated the growth inhibitory effect of temsirolimus in some cancers including non‐small‐cell lung carcinoma (NSCLC). In this study, we aimed to explore the potential therapeutic use of temsirolimus as a treatment for NSCLC. Using cultured NSCLC cells (A549, H1299, and H358), we determined the effect of temsirolimus on cell proliferation and its antitumor effects on subcutaneous tumors, as well as its contribution to the survival of mice having pleural dissemination of cancer cells, mimicking advanced NSCLC. Temsirolimus suppressed proliferation of NSCLC cells in a dose‐dependent manner, with an IC50 of <1 nM. Western blot analysis revealed that temsirolimus treatment specifically inhibited the phosphorylation of mTOR and its downstream effectors in 1 h, accompanied by an increased cell population in the G0/G1 phase, but according to flow cytometry, the cell population did not increase in the sub‐G0 phase. When NSCLC subcutaneous tumor‐bearing mice were treated with temsirolimus, tumor volume was significantly reduced (tumor volume on day 35: vehicle vs temsirolimus = 1239 vs 698 cm3; P < 0.05). Furthermore, prolonged survival was observed in pleural disseminated tumor‐bearing mice with temsirolimus treatment (median survival: vehicle vs temsirolimus = 53.5 vs 72.5 days; P < 0.05). These results suggest that temsirolimus could be useful for NSCLC treatment, due to its antiproliferative effect, and could be a potential treatment for advanced NSCLC, giving prolonged survival. (Cancer Sci 2011; 102: 1344–1349)
Association of mitochondrial DNA content in peripheral blood leukocyte with hepatitis B virus‐related hepatocellular carcinoma in a Chinese Han population
Authors: Zhao Siyuan , Yang Yefa , Liu Juan , Liu Hanqiang , Ge Naijian , Yang Hushan , Zhang Hongxin , Xing Jinliang
Published: April 2011

Increasing epidemiological evidence has indicated that inherited variations of mtDNA content could affect the genetic susceptibility of many malignancies in a tumor‐specific manner. However, the association between mtDNA content and hepatocellular carcinoma (HCC) remains undetermined. In this study, mtDNA content of peripheral blood leukocytes was determined using quantitative real‐time PCR in a case–control study consisting of 274 HCC cases, 126 non‐cancer patient controls with chronic liver diseases (CLD), and 258 healthy controls. We found that HCC cases had a significant lower mtDNA content than CLD controls (median [range]: 0.77 [0.17–2.30] vs 0.84 [0.32–3.37]; P = 0.012) and healthy controls (0.77 [0.17–2.30] vs 0.84 [0.35–3.44]; P = 0.035). There was no difference in mtDNA content between CLD and healthy controls (0.84 [0.32–3.37] vs 0.84 [0.35–3.44]; P = 0.261). We further assessed the association between mtDNA content and HCC and found that, compared to individuals with high mtDNA content, those with low mtDNA content had a significantly increased risk of HCC when health controls (adjusted odds ratio [aOR] = 1.64, 95% confidence interval [CI] = 1.06–2.55), CLD controls (aOR = 1.57, 95% CI = 1.10–2.25) or combined controls (aOR = 1.55, 95% CI = 1.12–2.14) were used as reference. In addition, stratified analyses showed that the significant association was only evident in younger individuals, male individuals, ever‐smokers, and never‐drinkers. Collectively, our findings provided the first epidemiological evidence that mtDNA content in peripheral blood leukocytes is significantly associated with HCC, which warrants further validation in prospective studies. (Cancer Sci 2011; 102: 1553–1558)
Drug selection in French university hospitals: analysis of formularies for nine competitive pharmacological classes
Authors: Gallini Adeline , Juillard‐Condat Blandine , Saux Marie‐Claude , Taboulet Florence
Published: April 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Variations in hospital drug formularies have been reported in Germany and the Netherlands for competitive classes.

• Since a spill‐over effect on the community may be expected, assessment of hospital formularies is needed.

• No study has yet explored French hospitals' drug formularies.

WHAT THIS STUDY ADDS

• Large variations in the number and the nature of selected drugs were found among French university hospitals for competitive classes.

• The wide range in the number of selected drugs suggests an unaccomplished rationalization process by some hospitals.

AIM To give a panorama of the selectivity and agreement of French university hospitals' drug formularies (HDF) for nine competitive classes.

METHODS All university hospitals were asked to send their HDF and selection criteria as of January 2009 for nine competitive pharmacological classes (proton pump inhibitors, serotonin antagonists, low molecular weight heparins, erythropoietins, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, statins, α‐adrenoreceptor antagonists and selective serotonin re‐uptake inhibitors). Selectivity of HDF was estimated by the percentage of drug entities selected by the hospital within the pharmacological class. Agreement between hospitals was assessed with modified kappa coefficients for multi‐raters.

RESULTS Twenty‐one out of the 29 hospitals agreed to participate. These hospitals selected between 34% and 63% of the drug entities available for the nine classes, which represented 18 to 35 agents. Regarding the nature of chosen drug entities, the overall level of agreement was ‘fair’ and varied with pharmacological classes. Selection criteria were sent by only 12 hospitals. The technical component was the most important element in all hospitals. The weight of the economic component varied between 20% and 40% in the tender's grade.

DISCUSSION Large variations were seen in the number and nature of drugs selected by university hospitals which can be attributable to two successive decision‐making processes (evaluation by the Drug and Therapeutics Committee followed by the purchasing process).
Pharmacotherapy of heart failure with normal ejection fraction (HFNEF) – a systematic review
Authors: Rajagopalan Sujit , Arora Anjuman , Shafiq Nusrat , Reddy S Srinivas , Pandhi Promila , Mittal Niti , Malhotra Samir
Published: April 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The treatment options for heart failure with normal ejection fraction (HFNEF), which constitutes about 50% of the cases of heart failure, is varied and consists of β‐adrenoceptor blockers, angiotensin converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs), calcium channel blockers and digoxin. However none of the treatment options have shown consistent results in improving the condition.

WHAT THIS STUDY ADDS

• The meta‐analysis conducted by us on the pooled data from the clinical trials on the various treatment options has revealed no definite benefit with pharmacotherapy in HFNEF. A systematic review of these data reveals a possible benefit with β‐adrenoceptor blockers in this condition. But to evaluate this larger studies with preplanned subgroup analysis, longer follow up periods and with echocardiographic parameters as outcomes to measure the LV diastolic dysfunction are required.

AIM The pharmacotherapy for heart failure with normal ejection fraction (HFNEF) is not as well defined as that for the treatment for heart failure with reduced ejection fraction (HFREF). Studies of the various drugs given for HFNEF have revealed conflicting results. The aim of this systematic review was to determine whether there is any benefit with pharmacotherapy in HFNEF in terms of cardiac outcomes.

METHODS Electronic and printed sources were searched until August 2010 for randomized controlled clinical trials (RCTs) comparing drug therapy with placebo in HFNEF. Weighted mean difference and pooled odds ratio (OR) with 95% confidence intervals were calculated.

RESULTS A total of six RCTs including 8410 patients with a mean follow‐up period of 21 months were included in the analysis. Although there were no significant differences in all cause mortality between the two groups (pooled OR 0.95, 95% CI 0.79, 1.13, P= 0.55), the subgroup analysis revealed a slight but non significant advantage with the β‐adrenoceptor blocker group. There was no significant difference between the two groups in terms of cardiovascular mortality, hospitalization, worsening heart failure, ejection fraction, E : A ratio, deceleration time and E : E′ ratio.

CONCLUSION There was no significant benefit of pharmacotherapy in HFNEF. This might have been because of a lack of stringent inclusion criteria for patients in the trials and lower power of the studies. Hence trials with well defined inclusion criteria, better power, longer follow‐up periods and with echocardiographic parameters as endpoints are required to shed further light on this topic.
Anti‐platelet therapy: ADP receptor antagonists
Authors: Wijeyeratne Yanushi Dullewe , Heptinstall Stan
Published: April 2011

The P2Y12receptor on platelets with which ADP interacts has an important role in promoting platelet function and thereby platelet involvement in both haemostasis and thrombosis. Agents that act as antagonists at this receptor are thus likely to provide effective antithrombotic therapy, provided that there are no adverse effects on haemostasis. Here we describe the ADP receptor antagonists that are available and in development. We also consider their mode of action and ask whether there are additional mechanisms through which they exert their inhibitory effects on platelet function.
Long‐term adherence to a local guideline on postoperative body temperature measurement: mixed methods analysis
Authors: Storm‐Versloot Marja N. , Knops Anouk M. , Ubbink Dirk T. , Goossens Astrid , Legemate Dink A. , Vermeulen Hester
Published: April 2011

Aim  To find out whether a successful multifaceted implementation approach of a local evidence‐based guideline on postoperative body temperature measurements (BTM) was persistent over time, and which factors influenced long‐term adherence.

Methods  Mixed methods analysis. Patient records were retrospectively examined to measure guideline adherence. Data on influencing factors were collected in focus group meetings for nurses and a plenary meeting with an interactive questionnaire for doctors.

Results  Records from 102 surgical patients were studied, totalling 1226 BTM. According to the guideline, an indication for BTM was present in 55% (679/1226). Actually, BTM were taken in 60% (736/1226), of which 55% (403/736) was in accordance with the guideline. The overall adherence rate to the guideline was 50% (617/1226). Belief in the advantages of the guideline and strong staff support appeared to facilitate long‐term adherence. Barriers were, the controversial nature of the guideline, the lack of self‐efficacy among nurses and doctors as to clinical judgement to identify an infection when refraining from BTM, and a lack of management and staff doctor support. Furthermore, newly appointed nurses and doctors were trained to measure BTM during their initial medical or nursing education, which was in contradiction with the guideline.

Conclusions  A multifaceted implementation strategy is not sufficient to maintain long‐term adherence. To ensure long‐term adherence, especially of controversial guidelines, adherence should be monitored and reported regularly over time. Strong staff support and leadership on all wards is crucial to maintain awareness. Medical and nursing curricula should include the pros and cons of taking BTM, combined with enhancing self‐efficacy.