bluuebunny/crossref_metadata_2025 huggingface dataset:
Rwanda's Vision 2020 halfway through: what the eye does not see
Authors: Ansoms An , Rostagno Donatella
Published: September 2012

This paper considers the progress made in the implementation of Rwanda's Vision 2020 programme since its launch in 2000. At the halfway point, the overall picture is quite encouraging. Rwanda's economy is thriving and reported growth figures have been impressive. The country is on track to meet the Millennium Development Goals in the fields of education and health care. Its political leaders have been praised for their quality of technocratic governance and their proactive approach to creating an attractive business climate. However, some indicators remain problematic. This paper argues that the current strategy – one of maximum growth at any cost – is counterproductive to the objective of achieving the greatest possible poverty reduction. Strong economic growth, concentrated in the hands of a small elite, results in a highly skewed developmental path with limited trickle-down potential. A possible alternative lies in an exploration of a broad-based inclusive growth model founded on existing strengths and the notion of capacity building among rural small-scale farmers. Striving for a more inclusive concept of growth would appear to be crucial not only for successful poverty reduction, but also with a view to promoting long-term stability and peace in Rwanda.

[Vision 2020 du Rwanda à mi-parcours: ce que l'œil ne voit pas.] Le présent article analyse les progrès accomplis dans la mise en œuvre du programme ‘Vision 2020 du Rwanda’ depuis son lancement en 2000. À mi-terme, le tableau d'ensemble est encourageant. L'économie du Rwanda est en plein essor et les chiffres de croissance rapportés sont impressionnants. Le pays est sur la bonne voie pour atteindre les Objectifs du Millénaire pour le développement dans les domaines de l'éducation et de santé. Ses dirigeants politiques ont été félicités pour la qualité de leur gouvernance technocratique et leur approche proactive de la création d'un climat propice au business. Toutefois, plusieurs indicateurs restent problématiques. Cet article soutient que la stratégie actuelle – celle d'une croissance maximale à tout prix – est contre-productive par rapport à l'objectif qui vise à atteindre la plus grande réduction possible de la pauvreté. La forte croissance économique, concentrée dans les mains d'une petite élite, résulte en une voie de développement très inégal avec un potentiel limité de retombées. Une alternative possible réside dans l'exploration d'un modèle fondé sur une croissance inclusive sur la base d'un renforcement des capacités des petits agriculteurs. Ceci semble crucial, non seulement pour réduire la pauvreté, mais aussi en vue de promouvoir la stabilité à long terme et la paix au Rwanda.

Mots-clés: Rwanda ; pauvreté ; croissance ; politiques de développement
Riesz bases consisting of root functions of 1D Dirac operators
Authors: Djakov Plamen , Mityagin Boris
Published: September 2012

For one-dimensional Dirac operators
\[
<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" alttext="upper L y equals i Start 2 By 2 Matrix 1st Row 1st Column 1 2nd Column a m p semicolon 0 2nd Row 1st Column 0 2nd Column a m p semicolon negative 1 EndMatrix StartFraction d y Over d x EndFraction plus v y comma v equals Start 2 By 2 Matrix 1st Row 1st Column 0 2nd Column a m p semicolon upper P 2nd Row 1st Column upper Q 2nd Column a m p semicolon 0 EndMatrix comma y equals StartBinomialOrMatrix y 1 Choose y 2 EndBinomialOrMatrix comma">

L
y
=
i

(

1

a
m
p
;
0

0

a
m
p
;
−
1

)

d
y

d
x

+
v
y
,

v
=

(

0

a
m
p
;
P

Q

a
m
p
;
0

)

,

y
=

(

y
1

y
2

)

,

Ly= i \begin {pmatrix} 1 & 0 \\ 0 & -1 \end {pmatrix} \frac {dy}{dx} + v y, \quad v= \begin {pmatrix} 0 & P \\ Q & 0 \end {pmatrix}, \;\; y=\begin {pmatrix} y_1 \\ y_2 \end {pmatrix},

\]
subject to periodic or antiperiodic boundary conditions, we give necessary and sufficient conditions which guarantee that the system of root functions contains Riesz bases in

L
2

(
[
0
,
π
]
,

C

2

)
.

L^2 ([0,\pi ], \mathbb {C}^2).

In particular, if the potential matrix

v
v

is skew-symmetric (i.e.,

Q
¯

=
−
P

\overline {Q} =-P

), or more generally if

Q
¯

=
t
P

\overline {Q} =t P

for some real

t
≠
0
,

t \neq 0,

then there exists a Riesz basis that consists of root functions of the operator

L
.

L.
Administration of the cyclic peptide COR‐1 in humans (phase I study): ex vivo measurements of anti‐β1‐adrenergic receptor antibody neutralization and of immune parameters
Authors: Münch Götz , Boivin‐Jahns Valerie , Holthoff Hans‐Peter , Adler Kristin , Lappo Mariola , Truöl Stephan , Degen Heidrun , Steiger Nina , Lohse Martin J. , Jahns Roland , Ungerer Martin
Published: September 2012

Aims

A novel concept for the treatment of heart failure is the neutralization of antibodies against the β1‐adrenergic receptor (anti‐β1AR‐ab). In a rat model of autoimmune cardiomyopathy, the cyclic peptide COR‐1 (given i.v. once monthly) neutralized anti‐β1AR‐abs and prevented anti‐β1AR‐ab‐induced myocardial damage, and completely reverted cardiac dysfunction over 3–6 months.

Methods and results

A clinical phase I trial was designed as a single‐blinded, placebo‐controlled study. Fifty human volunteers received COR‐1 or matching placebo as a single i.v. administration with ascending doses (10–240 mg). Primary endpoints were safety and tolerability, while the pharmacokinetic profile of COR‐1 was assessed as a secondary endpoint. All five investigated dose groups were well tolerated; no drug‐related side effects occurred. Pharmacokinetics revealed a favourable profile with an almost complete plasma clearance within 60 min after administration. Pharmacodynamic investigation showed dose‐dependent efficacy with almost complete scavenging of pathological anti‐β1AR‐abs ex vivo at the two highest doses. No anti‐COR‐1 autoantibodies occurred. No other effects on the immune system (such as an increase of crucial cytokines) were observed up to 43 days after drug administration, nor upon incubation of anti‐β1AR‐ab‐positive patient blood samples with COR‐1 ex vivo.

Conclusions

COR‐1 was shown to be safe after i.v. administration in vivo; no relevant side effects occurred. Efficacy was estimated from ex vivo investigation of the potency to neutralize specific anti‐β1‐AR‐abs.
Trial registration: NCT 01043146, Eudra CT 2008‐07745‐31.
Fusarium spp., Cylindrocarpon spp., and Environmental Stress in the Etiology of a Canker Disease of Cold-Stored Fruit and Nut Tree Seedlings in California
Authors: Marek Stephen M. , Yaghmour Mohammad A. , Bostock Richard M.
Published: September 2012

The principal objective of this study was to determine the etiology of a canker disease in dormant stone fruit and apple tree seedlings maintained in refrigerated storage that has significantly impacted California fruit and nut tree nurseries. Signs and symptoms of the disease develop during storage or soon after planting, with subsequent decline and death of young trees. Isolations from both diseased and healthy almond and apple trees and Koch's postulates using stem segments of desiccation-stressed almond trees as hosts implicated Fusarium avenaceum and F. acuminatum as the primary causal agents. F. solani, Ilyonectria robusta, and Cylindrocarpon obtusiusculum were also capable of causing similar symptoms but were less frequently encountered in isolations of diseased tissue. Loss of bark turgidity in excised almond stem segments, as can occur in cold-stored seedlings, correlated with increased susceptibility to F. acuminatum, with maximum canker development occurring after relative bark turgidity dropped below a threshold of approximately 86%. Healthy almond trees, almond scion budwood, and a wheat cover crop used in fields where tree seedlings were grown and maintained until cold storage all possessed asymptomatic infections of F. acuminatum, F. avenaceum, and C. obtusiusculum as determined by activation following overnight freezing, cold storage, or desiccation.
First Report of Colletotrichum boninense Causing Anthracnose on Pepper in China
Authors: Diao Y. Z. , Fan J. R. , Wang Z. W. , Liu X. L.
Published: September 2012

Anthracnose, caused by Colletotrichum spp., is a severe disease and results in large losses in pepper (Capsicum frutescens) production in China (4). Colletotrichum boninense is one of the Colletotrichum species in pepper in China. In August 2011, anthracnose symptoms (circular, sunken lesions with orange to black spore masses) were observed on pepper fruits in De-Yang, Sichuan Province, China. Three single-spore isolates (SC-6-1, SC-6-2, SC-6-3) were obtained from the infected fruits. A 5-mm diameter plug was transferred to potato dextrose agar (PDA); the isolates formed colonies with white margins and circular, dull orange centers. The conidia were cylindrical, obtuse at both ends, and 10.5 to 12.6 × 4.1 to 5.0 μm. The colonies grew rapidly at 25 to 28°C, and the average colony diameter was 51 to 52 mm after 5 days on PDA at 25°C. Based upon these characters, the causal agent was identified as C. boninense. To confirm the identity of the isolates, the internal transcribed spacer (ITS) regions were amplified with the ITS1/ITS4 universal primers (1). The internal transcribed spacer (ITS) sequences (Accession No. JQ926743) of the causal fungus shared 99 to 100% homology with ITS sequences of C. boninense in GenBank (Accession Nos. FN566865 and EU822801). The identity of the causal agent as C. boninense was also confirmed by species-specific primers (Col1/ITS4) (2). In a pathogenicity test, five detached ripe pepper fruits were inoculated with 1 μl of a conidial suspension (106 conidia/mL) or five fruits with 1 μl of sterile water were kept as control. After 7 days in a moist chamber at 25°C, typical anthracnose symptoms had developed on the five inoculated fruits but not on control fruits. C. boninense was reisolated from the lesions, and which was confirmed by morphology and molecular methods as before. There have reports of C. boninense infecting many species of plants, including pepper (3). To our knowledge, this is the first report of C. boninense causing anthracnose on pepper in China.

References: (1) A. K. Lucia et al. Phytopathology 93:581, 2002. (2) S. A. Pileggi et al. Can. J. Microbiol. 55:1081, 2009. (3) H. J. Tozze et al. Plant Dis. 93:106, 2009. (4) M. L. Zhang. J. Anhui Agri. Sci. 2:21, 2000.
First Report of Brown Rot Caused by Monilinia fructicola in Sweet Cherry in Maryland
Authors: Chen F. , Liu X. , Schnabel G.
Published: September 2012

Monilinia fructicola (G. Wint.) Honey is the most important causal agent of brown rot of stone fruits in North America. In July 2010, 20 sweet cherry fruit (Prunus avium) of unknown variety with symptoms resembling brown rot were collected from one commercial orchard in Maryland. Each cherry fruit came from a different tree. Symptoms included necrotic areas up to 10 mm in diameter with brown conidia and conidiophores developing from the infection center. Spores from nine symptomatic fruit collected each from different trees of a single orchard were suspended in sterile water, spread onto the surface of 1% agar plates, and incubated at 22°C. After 12 h, single, germinated spores were transferred onto 9-cm petri dishes with potato dextrose agar (PDA). Nine fungal colonies, each from a different fruit, were investigated in three replicates for cultural characteristics on separate petri dishes containing PDA. They were very similar in morphology and grew 12.4 mm per day on average at 22°C, forming branched, monilioid chains of grayish colonies with concentric rings and little sporulation. Rich sporulation was observed on tomato sauce medium (250 ml tomato sauce and 20 g agar in 750 ml water). The lemon-shaped spores had an average size of 15 × 10 μm, which is consistent with M. fructicola. Two colonies were randomly selected to identify the pathogen to the species level using a PCR technique based on cytochrome b sequence amplifications (2). Resulting gel electrophoresis patterns were consistent with M. fructicola. Koch's postulates were fulfilled by inoculating 15 mature sweet cherry fruits of cv. Bing with a conidial suspension (105 spores/ml) of one of the single-spore isolates from cherry. Fruit were stab-inoculated at a point to a depth of 2 mm using a sterile needle. A 10-μl droplet was placed on each wound; control fruit received sterile water without conidia. After 3 days of incubation at room temperature in airtight plastic bags, the inoculated fruit developed typical brown rot symptoms with lesions that were 20.6 mm in diameter. The developing spores on inoculated fruit were confirmed to be M. fructicola. All control fruit remained healthy. The entire detached fruit experiment was repeated 1 week later. M. fructicola is assumed to be the main causal agent of brown rot of sweet cherry in the northeastern United States, but recent studies show that M. laxa is also causing the disease on sweet cherry in many northeastern states (1). For this reason, it is important to delineate species for accurate disease assessments. This study confirms assumptions that M. fructicola is a causal agent of sweet cherry in Maryland.

References: (1) K. D. Cox et al. Plant Dis. 12:1584. 2011. (2) J.-M. Hily et al. Pest Manag. Sci. 67:385, 2011.
TAKAYASU RETINOPATHY PRESENTING AS AMAUROSIS FUGAX IN A YOUNG PATIENT
Authors: Strauss Danielle S. , Barbazetto Irene
Published: September 2012

Purpose:

The purpose of this article was to report a case of Stage 3 Takayasu retinopathy with marked venous staining.

Methods:

Case report with funduscopic, fluorescein angiography, computed tomography angiography, and magnetic resonance imaging angiography correlations.

Results:

A 25-year-old woman presented with Stage 3 Takayasu retinopathy with striking venous staining while maintaining visual acuity of 20/30 because of arterial collateralization to the internal carotid arteries.

Conclusion:

Patients with Takayasu arteritis should be evaluated promptly for Takayasu retinopathy even with good vision because stenosis of major vessels off the aorta is associated with worse visual prognosis.
Retention of ice-associated amphipods: possible consequences for an ice-free Arctic Ocean
Authors: Berge J. , Varpe Ø. , Moline M. A. , Wold A. , Renaud P. E. , Daase M. , Falk-Petersen S.
Published: September 2012

Recent studies predict that the Arctic Ocean will have ice-free summers within the next 30 years. This poses a significant challenge for the marine organisms associated with the Arctic sea ice, such as marine mammals and, not least, the ice-associated crustaceans generally considered to spend their entire life on the underside of the Arctic sea ice. Based upon unique samples collected within the Arctic Ocean during the polar night, we provide a new conceptual understanding of an intimate connection between these under-ice crustaceans and the deep Arctic Ocean currents. We suggest that downwards vertical migrations, followed by polewards transport in deep ocean currents, are an adaptive trait of ice fauna that both increases survival during ice-free periods of the year and enables re-colonization of sea ice when they ascend within the Arctic Ocean. From an evolutionary perspective, this may have been an adaptation allowing success in a seasonally ice-covered Arctic. Our findings may ultimately change the perception of ice fauna as a biota imminently threatened by the predicted disappearance of perennial sea ice.
Causes of hatching failure in endangered birds
Authors: Hemmings N. , West M. , Birkhead T. R.
Published: September 2012

About 10 per cent of birds' eggs fail to hatch, but the incidence of failure can be much higher in endangered species. Most studies fail to distinguish between infertility (due to a lack of sperm) and embryo mortality as the cause of hatching failure, yet doing so is crucial in order to understand the underlying problem. Using newly validated techniques to visualize sperm and embryonic tissue, we assessed the fertility status of unhatched eggs of five endangered species, including both wild and captive birds. All eggs were classified as ‘infertile’ when collected, but most were actually fertile with numerous sperm on the ovum. Eggs of captive birds had fewer sperm and were more likely to be infertile than those of wild birds. Our findings raise important questions regarding the management of captive breeding programmes.
On the evolution of noise-dependent vocal plasticity in birds
Authors: Schuster Sophie , Zollinger Sue Anne , Lesku John A. , Brumm Henrik
Published: September 2012

Signal plasticity is considered an important step in the evolution of animal communication. In acoustic communication, signal transmission is often constrained by background noise. One adaptation to evade acoustic signal masking is the Lombard effect, in which an animal increases its vocal amplitude in response to an increase in background noise. This form of signal plasticity has been found in mammals, including humans, and some birds, but not frogs. However, the evolution of the Lombard effect is still unclear. Here we demonstrate for the first time the Lombard effect in a phylogentically basal bird species, the tinamou
Eudromia elegans
. By doing so, we take a step towards reconstructing the evolutionary history of noise-dependent vocal plasticity in birds. Similar to humans, the tinamous also raised their vocal pitch in noise, irrespective of any release from signal masking. The occurrence of the Lombard effect in a basal bird group suggests that this form of vocal plasticity was present in the common ancestor of all living birds and thus evolved at least as early as 119 Ma.
Margaret Mary Gowing CBE FBA. 26 April 1921 — 7 November 1998
Authors: MacLeod Roy
Published: September 2012

If some historians are born great, few achieve greatness. But some have greatness thrust upon them. This was certainly true of Margaret Mary Gowing, civil servant, archivist, and Britain’s first official historian of the nuclear age. From modest origins, but armed with a good education, and favoured by the circumstances of Britain at war, Gowing met and seized opportunities that led her eventually to occupy a position of national prominence that few historians—and, at the time, few women historians—could have anticipated, and which even fewer achieved. Her greatest, lasting scholarly contribution takes the form of two books, which in their mastery of official records laid the foundations of archival research upon which later generations of scholars have built. But her progress was never easy, nor were her successes complete. Ever entwined, her personal and her professional lives were deeply touched by moments of acute stress, tinged with tragedy, that came to affect not only her academic performance but also the lives of family, friends, colleagues and students.
Analytical investigation of self-organized criticality in neural networks
Authors: Droste Felix , Do Anne-Ly , Gross Thilo
Published: September 2012

Dynamical criticality has been shown to enhance information processing in dynamical systems, and there is evidence for self-organized criticality in neural networks. A plausible mechanism for such self-organization is activity-dependent synaptic plasticity. Here, we model neurons as discrete-state nodes on an adaptive network following stochastic dynamics. At a threshold connectivity, this system undergoes a dynamical phase transition at which persistent activity sets in. In a low-dimensional representation of the macroscopic dynamics, this corresponds to a transcritical bifurcation. We show analytically that adding activity-dependent rewiring rules, inspired by homeostatic plasticity, leads to the emergence of an attractive steady state at criticality and present numerical evidence for the system's evolution to such a state.
Jet noise: sound generation by disc and cylinder sources
Authors: Carley M. J. , Martin P. A.
Published: September 2012

An exact analysis of the field radiated by tonal and random non-axisymmetric sources distributed over a disc or cylinder is presented. The analysis is exact, without recourse to near- or far-field approximations, and leads to a direct relationship between source frequency and the nature of the radiated field. The implications of the analysis for a number of applications are discussed, finding in particular that source identification is inherently ill-conditioned as a result of a ‘filtering’ effect that removes information from the radiation field; low-frequency sources generate fields that are indistinguishable from each other; jet noise fields are inherently simpler than the flow that gives rise to them, a finding that has previously been noted for experimental data.
An inclusive fitness analysis of synergistic interactions in structured populations
Authors: Taylor Peter , Maciejewski Wes
Published: September 2012

We study the evolution of a pair of competing behavioural alleles in a structured population when there are non-additive or ‘synergistic’ fitness effects. Under a form of weak selection and with a simple symmetry condition between a pair of competing alleles, Tarnita
et al.
provide a surprisingly simple condition for one allele to dominate the other. Their condition can be obtained from an analysis of a corresponding simpler model in which fitness effects are additive. Their result uses an average measure of selective advantage where the average is taken over the long-term—that is, over all possible allele frequencies—and this precludes consideration of any frequency dependence the allelic fitness might exhibit. However, in a considerable body of work with non-additive fitness effects—for example, hawk–dove and prisoner's dilemma games—frequency dependence plays an essential role in the establishment of conditions for a stable allele-frequency equilibrium. Here, we present a frequency-dependent generalization of their result that provides an expression for allelic fitness at any given allele frequency
p
. We use an inclusive fitness approach and provide two examples for an infinite structured population. We illustrate our results with an analysis of the hawk–dove game.
The impact of past climate change on genetic variation and population connectivity in the Icelandic arctic fox
Authors: Mellows Andrew , Barnett Ross , Dalén Love , Sandoval-Castellanos Edson , Linderholm Anna , McGovern Thomas H. , Church Mike J. , Larson Greger
Published: September 2012

Previous studies have suggested that the presence of sea ice is an important factor in facilitating migration and determining the degree of genetic isolation among contemporary arctic fox populations. Because the extent of sea ice is dependent upon global temperatures, periods of significant cooling would have had a major impact on fox population connectivity and genetic variation. We tested this hypothesis by extracting and sequencing mitochondrial control region sequences from 17 arctic foxes excavated from two late-ninth-century to twelfth-century AD archaeological sites in northeast Iceland, both of which predate the Little Ice Age (approx. sixteenth to nineteenth century). Despite the fact that five haplotypes have been observed in modern Icelandic foxes, a single haplotype was shared among all of the ancient individuals. Results from simulations within an approximate Bayesian computation framework suggest that the rapid increase in Icelandic arctic fox haplotype diversity can only be explained by sea-ice-mediated fox immigration facilitated by the Little Ice Age.
Mating system affects population performance and extinction risk under environmental challenge
Authors: Plesnar-Bielak Agata , Skrzynecka Anna M. , Prokop Zofia M. , Radwan Jacek
Published: September 2012

Failure of organisms to adapt to sudden environmental changes may lead to extinction. The type of mating system, by affecting fertility and the strength of sexual selection, may have a major impact on a population's chances to adapt and survive. Here, we use experimental evolution in bulb mites (
Rhizoglyphus robini
) to examine the effects of the mating system on population performance under environmental change. We demonstrate that populations in which monogamy was enforced suffered a dramatic fitness decline when evolving at an increased temperature, whereas the negative effects of change in a thermal environment were alleviated in polygamous populations. Strikingly, within 17 generations, all monogamous populations experiencing higher temperature went extinct, whereas all polygamous populations survived. Our results show that the mating system may have dramatic effects on the risk of extinction under environmental change.
Extensive somatic L1 retrotransposition in colorectal tumors
Authors: Solyom Szilvia , Ewing Adam D. , Rahrmann Eric P. , Doucet Tara , Nelson Heather H. , Burns Michael B. , Harris Reuben S. , Sigmon David F. , Casella Alex , Erlanger Bracha , Wheelan Sarah , Upton Kyle R. , Shukla Ruchi , Faulkner Geoffrey J. , Largaespada David A. , Kazazian Haig H.
Published: September 2012

L1 retrotransposons comprise 17% of the human genome and are its only autonomous mobile elements. Although L1-induced insertional mutagenesis causes Mendelian disease, their mutagenic load in cancer has been elusive. Using L1-targeted resequencing of 16 colorectal tumor and matched normal DNAs, we found that certain cancers were excessively mutagenized by human-specific L1s, while no verifiable insertions were present in normal tissues. We confirmed de novo L1 insertions in malignancy by both validating and sequencing 69/107 tumor-specific insertions and retrieving both 5′ and 3′ junctions for 35. In contrast to germline polymorphic L1s, all insertions were severely 5′ truncated. Validated insertion numbers varied from up to 17 in some tumors to none in three others, and correlated with the age of the patients. Numerous genes with a role in tumorigenesis were targeted, including ODZ3, ROBO2, PTPRM, PCM1, and CDH11. Thus, somatic retrotransposition may play an etiologic role in colorectal cancer.
Genomics and Localization of the Arabidopsis DHHC-Cysteine-Rich Domain S-Acyltransferase Protein Family
Authors: Batistič Oliver
Published: September 2012

Protein lipid modification of cysteine residues, referred to as S-palmitoylation or S-acylation, is an important secondary and reversible modification that regulates membrane association, trafficking, and function of target proteins. This enzymatic reaction is mediated by protein S-acyl transferases (PATs). Here, the phylogeny, genomic organization, protein topology, expression, and localization pattern of the 24 PAT family members from Arabidopsis (Arabidopsis thaliana) is described. Most PATs are expressed at ubiquitous levels and tissues throughout the development, while few genes are expressed especially during flower development preferentially in pollen and stamen. The proteins display large sequence and structural variations but exhibit a common protein topology that is preserved in PATs from various organisms. Arabidopsis PAT proteins display a complex targeting pattern and were detected at the endoplasmic reticulum, Golgi, endosomal compartments, and the vacuolar membrane. However, most proteins were targeted to the plasma membrane. This large concentration of plant PAT activity to the plasma membrane suggests that the plant cellular S-acylation machinery is functionally different compared with that of yeast (Saccharomyces cerevisiae) and mammalians.
HDT701, a Histone H4 Deacetylase, Negatively Regulates Plant Innate Immunity by Modulating Histone H4 Acetylation of Defense-Related Genes in Rice
Authors: Ding Bo , Bellizzi Maria del Rosario , Ning Yuese , Meyers Blake C. , Wang Guo-Liang
Published: September 2012

Histone acetylation and deacetylation play an important role in the modification of chromatin structure and regulation of gene expression in eukaryotes. Chromatin acetylation status is modulated antagonistically by histone acetyltransferases and histone deacetylases (HDACs). In this study, we characterized the function of histone deacetylase701 (HDT701), a member of the plant-specific HD2 subfamily of HDACs, in rice (Oryza sativa) innate immunity. Transcription of HDT701 is increased in the compatible reaction and decreased in the incompatible reaction after infection by the fungal pathogen Magnaporthe oryzae. Overexpression of HDT701 in transgenic rice leads to decreased levels of histone H4 acetylation and enhanced susceptibility to the rice pathogens M. oryzae and Xanthomonas oryzae pv oryzae (Xoo). By contrast, silencing of HDT701 in transgenic rice causes elevated levels of histone H4 acetylation and elevated transcription of pattern recognition receptor (PRR) and defense-related genes, increased generation of reactive oxygen species after pathogen-associated molecular pattern elicitor treatment, as well as enhanced resistance to both M. oryzae and Xoo. We also found that HDT701 can bind to defense-related genes to regulate their expression. Taken together, these results demonstrate that HDT701 negatively regulates innate immunity by modulating the levels of histone H4 acetylation of PRR and defense-related genes in rice.
High-throughput counter-diffusion capillary crystallization andin situdiffraction using high-pressure freezing in protein crystallography
Authors: Kurz Mareike , Blattmann Beat , Kaech Andres , Briand Christophe , Reardon Paul , Ziegler Urs , Gruetter Markus G.
Published: September 2012

Post-crystallization treatments such as manual fishing of crystals and soaking in cryoprotectant solutions, especially of large macromolecular complexes and membrane proteins, are cumbersome and often lead to crystal damage and reduced diffraction data quality. Here, a capillary crystallization plate is presented that simultaneously allows counter-diffusion crystallization at the nanolitre scale in a high-throughput screening mode, low-temperaturein situdiffraction data collection from crystals after cryoprotection and low-temperaturein situdata collection of crystals without the addition of any cryoprotectant after high-pressure (HP) freezing. The development of this plate and plunge cooling of crystals in the capillaries is a major step towards implementing automatedin situhigh-throughput crystal diffraction data collection at a synchrotron beamline. In combination with HP freezing this offers a new opportunity to obtain structural information from fragile crystals of supramolecular complexes that might otherwise not be feasible.
LiTaO3crystals with near-zero birefringence
Authors: Glazer A. M. , Zhang N. , Bartasyte A. , Keeble D. S. , Huband S. , Thomas P. A. , Gregora I. , Borodavka F. , Margueron S. , Hlinka J.
Published: September 2012

A study of vapour transport equilibrated crystals of LiTaO3shows periodic fringes that change with temperature. The origin of these fringes and their behaviour is explained in terms of domains with slanted walls. Micro-Raman measurements have been used to determine the Li2O concentration through the crystals, and by comparison with the observed fringe pattern the variation of birefringence with Li2O content has been determined.
CRYSTALSenhancements: asymmetric restraints
Authors: Cooper Richard Ian , Thorn Andrea , Watkin David John
Published: September 2012

The traditional Waser distance restraint, the rigid-bond restraint and atomic displacement parameter (ADP) similarity restraints have an equal influence on both atoms involved in the restraint. This may be inappropriate in cases where it can reasonably be expected that the precision of the determination of the positional parameters and ADPs is not equal,e.g.towards the extremities of a librating structure or where one atom is a significantly stronger scatterer than the other. In these cases, the traditional restraint feeds information from the poorly defined atom to the better defined atom, with the possibility that its characteristics become degraded. The modified restraint described here feeds information from the better defined atom to the more poorly defined atom with minimal feedback.
Strain-induced phase transitions in epitaxial NaNbO3thin films grown by metal–organic chemical vapour deposition
Authors: Schwarzkopf Jutta , Schmidbauer Martin , Remmele Thilo , Duk Andreas , Kwasniewski Albert , Bin Anooz Saud , Devi Anjana , Fornari Roberto
Published: September 2012

Epitaxially strained NaNbO3films were grown by liquid-delivery spin metal–organic chemical vapour deposition on several oxide substrates, inducing tensile and compressive lattice strain. High-resolution X-ray diffraction measurements reveal that coherently grown compressively strained NaNbO3films on NdGaO3exhibit the orthorhombiccphase. With increasing in-plane strain a first structural phase transition to the monoclinicrphase and, further on, for films grown under tensile strain on rare earth scandates, a second phase transition to theaaphase, are observed. Our results are in good agreement with the pathway of phase transitions predicted by Diéguez, Rabe & Vanderbilt [Phys. Rev. B, (2005),72, 144101] for NaNbO3films.
Non-robotic high-throughput setup for manual assembly of nanolitre vapour-diffusion protein crystallization screens
Authors: Skrabana Rostislav , Cehlar Ondrej , Novak Michal
Published: September 2012

Nanolitre-sized drops are characteristic of high-throughput protein crystallization screening. Traditionally, reliable nanolitre drop dispensing has required the use of robotics. This work describes the design and development of a protocol for the reproducible manual assembly of nanolitre-sized protein vapour-diffusion crystallization trials in a 96/192-drop format. The protocol exploits the repetitive-pipetting mode of handheld motorized pipettes together with simple tools available in standard laboratories. The method saves precious protein material without sacrificing the effectiveness of the screening process. To verify the approach, two monoclonal antibody Fab fragments were crystallized alone and in a complex with tau peptide antigens in 0.2–0.5 µl drops. Crystals grown directly from the screen conditions in sitting drops on 96-well plates diffracted up to 1.6 Å resolution on a synchrotron source. The results proved that successful crystallization in nanolitre high-throughput format is affordable even in the absence of expensive robotic instrumentation.
Anisotropic microstrain broadening in cementite, Fe3C, caused by thermal microstress: comparison between prediction and results from diffraction-line profile analysis
Authors: Leineweber A.
Published: September 2012

X-ray powder diffraction data of an Fe3C powder consisting of polycrystalline particles shows pronouncedly anisotropic microstrain broadening of the Bragg reflections. The extent and anisotropy of the broadening can quantitatively be attributed to thermal microstresses induced by anisotropic thermal shrinkage from the preparation temperature of 873 K to the ambient analysis temperature, in conjunction with the elastic anisotropy of Fe3C.
Three new [XC(O)NH]P(O)[N(CH2C6H5)2]2phosphoric triamides (X= CClF2, 3-F-C6H4and 3,5-F2-C6H3): a database analysis of tertiary N-atom geometry in compounds with a C(O)NHP(O)[N]2core
Authors: Pourayoubi Mehrdad , Jasinski Jerry P. , Shoghpour Bayraq Samad , Eshghi Hossein , Keeley Amanda C. , Bruno Giuseppe , Amiri Rudbari Hadi
Published: September 2012

In the phosphoric triamidesN,N,N′,N′-tetrabenzyl-N′′-(2-chloro-2,2-difluoroacetyl)phosphoric triamide, C30H29ClF2N3O2P, (I),N,N,N′,N′-tetrabenzyl-N′′-(3-fluorobenzoyl)phosphoric triamide, C35H33FN3O2P, (II), andN,N,N′,N′-tetrabenzyl-N′′-(3,5-difluorobenzoyl)phosphoric triamide, C35H32F2N3O2P, (III), the tertiary N atoms of the dibenzylamido groups havesp2character with minimal deviation from planarity. The sums of the three bond angles about the N atoms in (I)–(III) deviate by less than 8° from the planar value of 360°. The geometries of the tertiary N atoms in all phosphoric triamides with C(O)NHP(O)[N]2skeletons deposited in the Cambridge Structural Database [CSD; Allen (2002).Acta Cryst.B58, 380–388] have been examined and the bond-angle sums at the two tertiary N atoms (SUM1 and SUM2) and the parameter ΔSUM (= SUM1 − SUM2) considered. It was found that in compounds with a considerable ΔSUM value, the more pyramidal N atoms are usually oriented so that the corresponding lone electron pair isantiwith respect to the P=O group. In (I), (II) and (III), the phosphoryl and carbonyl groups, separated by an N atom, areantiwith respect to each other. In the C(O)NHP(O) fragment of (I)–(III), the P—N bond is longer and the O—P—N angle is contracted compared with the other two P—N bonds and the O—P—N angles in the molecules. These effects are also seen in analogous compounds deposited in the CSD. Compounds with [C(O)NH]P(O)[N]X(X≠ N), such as compounds with a [C(O)NH]P(O)[N][O] skeleton, have not been considered here. Also, compounds with a [C(O)NH]2P(O)[N] fragment have not been reported to date. In the crystal structures of all three title compounds, adjacent molecules are linkedviapairs of P=O...H—N hydrogen bonds, forming dimers withCisymmetry.
5-Ethynyl-2′-deoxycytidine: a DNA building block with a `clickable' side chain
Authors: Seela Frank , Mei Hui , Xiong Hai , Budow Simone , Eickmeier Henning , Reuter Hans
Published: September 2012

The title compound [systematic name: 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-5-ethynylpyrimidin-2(1H)-one], C11H13N3O4, shows two conformations in the crystalline state. The N-glycosylic bonds of both conformers adopt similar conformations, with χ = −149.2 (1)° for conformer (I-1) and −151.4 (1)° for conformer (I-2), both in theantirange. The sugar residue of (I-1) shows a C2′-endoenvelope conformation (2E,S-type), withP= 164.7 (1)° and τm= 36.9 (1)°, while (I-2) shows a major C3′-exosugar pucker (C3′-exo-C2′-endo,3T2,S-type), withP= 189.2 (1)° and τm= 33.3 (1)°. Both conformers participate in the formation of a layered three-dimensional crystal structure with a chain-like arrangement of the conformers. The ethynyl groups do not participate in hydrogen bonding, but are arranged in proximal positions.
Comparative modular analysis of two complex sulfosalt structures: sterryite, Cu(Ag,Cu)3Pb19(Sb,As)22(As–As)S56, and parasterryite, Ag4Pb20(Sb,As)24S58
Authors: Moëlo Yves , Guillot-Deudon Catherine , Evain Michel , Orlandi Paolo , Biagioni Cristian
Published: September 2012

The crystal structures of two very close, but distinct complex minerals of the lead sulfosalt group have been solved: sterryite, Cu(Ag,Cu)3Pb19(Sb,As)22(As–As)S56, and parasterryite, Ag4Pb20(Sb,As)24S58. They are analyzed and compared according to modular analysis. The fundamental building block is a complex column centred on a Pb6S12 triangular prismatic core, with two additional long and short arms. The main chemical and topological differences relate to the short arm, which induces a relative a/4 shift (∼ 2 Å along the elongation parameter) of the constitutive rod layers, as illustrated by distinct cell settings within the same space group (P21/n and P21/c, respectively). Selection of the shortest (i.e. strongest) (Sb,As)—S bonds permitted to enhance the polymeric organization of (Sb,As) atoms with triangular pyramidal coordination. These two quasi-homeotypic structures are expanded derivatives of owyheeite, Ag3Pb10Sb11S28. The hierarchy of organization levels from zero- to three-dimensional entities is subordinated to building operators, which appear as the driving force for the construction of such complex structures. Minor cations (Ag, Cu) or the As–As pair in sterryite secure the final locking, which favours the formation of one or the other compound.
Four polymorphs (polytypes) of 5,6-dimethylbenzofurazan 1-oxide
Authors: Britton Doyle , Young Victor G. , Noland Wayland E. , Pinnow Matthew J. , Clark Christopher M.
Published: September 2012

5,6-Dimethylbenzofurazan 1-oxide (Me2BF), C8H8N2O2, occurs in four polymorphic forms that are polytypes of each other. Each polymorph of Me2BF contains molecules disordered about pseudo-twofold axes and arranged head-to-tail in ribbons, with the ribbons forming approximately planar layers held together by weak C—H...N and C—H...O interactions. Adjacent layers interact in different ways in the different polymorphs. In addition to twinning in the individual polymorphs, four examples of allotwining, that is, oriented overgrowths between different polymorphs, were found.
Social cognition and metacognition in schizophrenia: evidence of their independence and linkage with outcomes
Authors: Lysaker P. H. , Gumley A. , Luedtke B. , Buck K. D. , Ringer J. M. , Olesek K. , Kukla M. , Leonhardt B. L. , Popolo R. , Dimaggio G.
Published: September 2012

Lysaker PH, Gumley A, Luedtke B, Buck KD, Ringer JM, Olesek K, Kukla M, Leonhardt BL, Popolo R, Dimaggio G. Social cognition and metacognition in schizophrenia: evidence of their independence and linkage with outcomes.

Objective:  Research suggests that many with schizophrenia experience deficits in the ability to make discrete judgments about the thoughts and feelings of others as well as to form larger integrated representations of themselves and others. Little is known about whether these difficulties may be distinguished from one another and whether they are linked with different outcomes.

Method:  We administered three assessments of social cognition which tapped the ability to identify emotions and intentions and two metacognitive tasks which called for the formation of more integrated and flexible representations of the self and others. We additionally assessed symptoms, social functioning and neurocognition. Participants were 95 individuals with a schizophrenia spectrum disorder.

Results:  A principle components analysis followed by a varimax rotation revealed two factors which accounted for 62% of the variance. The first factor was comprised of the three social cognition tests and the second of two tasks that tapped the ability to create representations of oneself and others which integrate more discreet information. The first factor was uniquely correlated with negative symptoms, and the second was uniquely correlated with social function.

Conclusion:  Results suggest that deficits in social cognition and metacognition represent different forms of dysfunction in schizophrenia.
Probing Secondary Glutaminyl Cyclase (QC) Inhibitor Interactions Applying an in silico‐Modeling/Site‐Directed Mutagenesis Approach: Implications for Drug Development
Authors: Koch Birgit , Buchholz Mirko , Wermann Michael , Heiser Ulrich , Schilling Stephan , Demuth Hans‐Ulrich
Published: September 2012

Glutaminyl cyclases (QCs) catalyze the formation of pyroglutamate‐modified amyloid peptides deposited in neurodegenerative disorders such as Alzheimer’s disease. Inhibitors of QC are currently in development as potential therapeutics. The crystal structures of the potent inhibitor PBD150 bound to human and murine QC (hQC, mQC) have been described recently. The binding modes of a dimethoxyphenyl moiety of the inhibitor are significantly different between the structures, which contrasts with a similar Ki value. We show the conformation of PBD150 prone to disturbance by protein–protein interactions within the crystals. Semi‐empirical calculations of the enzyme–inhibitor interaction within the crystal suggest significant differences in the dissociation constants between the binding modes. To probe for interactions in solution, a site‐directed mutagenesis on hQC was performed. The replacement of F325 and I303 by alanine or asparagine resulted in a 800‐fold lower activity of the inhibitor, whereas the exchange of S323 by alanine or valine led to a 20‐fold higher activity of PBD150. The results provide an example of deciphering the interaction mode between a target enzyme and lead substance in solution, if co‐crystallization does not mirror such interactions properly. Thus, the study might provide implications for rapid screening of binding modes also for other drug targets.
Subspecialist emergency management of diverticulitis is associated with reduced mortality and fewer stomas
Authors: Boyce S. A. , Bartolo D. C. C. , Paterson H. M. ,   on behalf of the Edinburgh Coloproctology Unit
Published: September 2012

Aim  The aim of the study was to compare outcomes for emergency management of diverticulitis before and after the creation of a regional subspecialist colorectal unit.

Method  We retrieved data on all emergency admissions for diverticulitis from the regional surgical audit database and compared results before (January 1998 to August 2002) and after (August 2002 to December 2008) establishment of the subspecialist colorectal surgery unit in August 2002. Additional data were retrieved from electronic patient records. The primary outcome measures were mortality and rate of primary anastomosis following resection.

Results  There were 879 patients before and 1280 patients after subspecialization. Nonoperative management was undertaken in approximately 80% of cases. Total mortality fell from 3.3 to 1.5% (P = 0.008), attributable to reduced operative mortality (9.6 to 4.2%; P = 0.019). The primary anastomosis rate for all left colon resections increased from 50.3 to 77.9%; P < 0.0001. Stoma formation of any type fell from 46.6 to 27.7%; P < 0001).

Conclusion  Emergency management of diverticulitis by subspecialist colorectal surgeons is associated with low overall and operative mortality whilst safely achieving high rates of primary anastomosis.
Influence of peptide dipoles and hydrogen bonds on reactive cysteine pKa values in fission yeast DJ‐1
Authors: Madzelan Peter , Labunska Tetyana , Wilson Mark A.
Published: September 2012

Cysteine residues with depressed pKa values are critical for the functions of many proteins. Several types of interactions can stabilize cysteine thiolate anions, including hydrogen bonds between thiol(ate)s and nearby residues as well as electrostatic interactions involving charged residues or dipoles. Dipolar stabilization of thiolates by peptide groups has been suggested to play a particularly important role near the N‐termini of α‐helices. Using a combination of X‐ray crystallography, site‐directed mutagenesis and spectroscopic methods, we show that the reactive cysteine residue (Cys111) in Schizosaccharomyces pombe DJ‐1 experiences a 0.6 unit depression of its thiol pKa as a consequence of a hydrogen bond donated by a threonine side chain (Thr114) to a nearby peptide carbonyl oxygen at the N‐terminus of an α‐helix. This extended hydrogen bonded interaction is consistent with a sum of dipoles model whereby the distal hydrogen bond polarizes and strengthens the direct hydrogen bond between the proximal amide hydrogen and the cysteine thiol(ate). Therefore, our results suggest that the local dipolar enhancement of hydrogen bonds can appreciably stabilize cysteine thiolate formation. However, the substitution of a valine residue with a proline at the i + 3 position has only a minor effect (0.3 units) on the pKa of Cys111. As proline has a reduced peptide dipole moment, this small effect suggests that a more extended helix macrodipolar effect does not play a major role in this system.

Database

Structural models and diffraction data are available in the Protein Data Bank under the accession number(s) 4GDH (wild‐type SpDJ‐1), 4GE0 (T114P SpDJ‐1) and 4GE3 (T114V SpDJ‐1)

Structured digital abstract

SpDJ‐1 and SpDJ‐1 bind by x‐ray crystallography (View interaction)