bluuebunny/crossref_metadata_2025 huggingface dataset:
Reverse magnetostructural transformation in Co-doped NiMnGa multifunctional alloys
Authors: Fabbrici S. , Albertini F. , Paoluzi A. , Bolzoni F. , Cabassi R. , Solzi M. , Righi L. , Calestani G.
Published: July 2009

We studied the composition dependence of the structural and magnetic properties of Co-doped Ni–Mn–Ga alloys around the Mn-rich composition Ni50Mn30Ga20. By varying the Co and Mn content we have been able to tune the critical temperatures. In particular, in a suitable composition range, the Curie temperature of martensite is lower than Curie temperature of austenite and lower than martensitic transformation temperature, giving rise to a paramagnetic gap between magnetically ordered martensite and austenite and to the occurrence of a reverse magnetostructural transformation.
Kinetics of the initial stage of silicon surface oxidation: Deal–Grove or surface nucleation?
Authors: Levchenko I. , Cvelbar U. , Ostrikov K.
Published: July 2009

The nucleation-initiated oxidation of a Si surface at very low temperatures in plasmas is demonstrated experimentally, in contrast to the Deal–Grove mechanism, which predicts Si oxidation at a Si/SiO interface and cannot adequately describe the formation of SiO nanodots and oxidation rates at very low (several nanometers) oxide thickness. Based on the experimental results, an alternative oxidation scenario is proposed and supported by multiscale numerical simulations suggesting that saturation of micro- and nanohillocks with oxygen is a trigger mechanism for initiation of Si surface oxidation. This approach is generic and can be applied to describe the kinetics of low-temperature oxidation of other materials.
Spin conserving natural orbital functional theory
Authors: Piris M. , Matxain J. M. , Lopez X. , Ugalde J. M.
Published: July 2009

The natural orbital functional theory is considered for spin uncompensated systems, i.e., systems that have one or more unpaired electrons. The well-known cumulant expansion is used to reconstruct the two-particle reduced density matrix. A new condition to ensure the conservation of the total spin is obtained for the two-particle cumulant matrix. An extension of the Piris natural orbital functional 1 (PNOF1), based on an explicit form for the cumulant, to spin uncompensated systems is also considered. The theory is applied to the calculation of energy differences between the ground state and the lowest lying excited state with different spins for first-row atoms (Li, Be, B, C, N, O, and F) and diatomic oxygen molecule (O2). The values we obtained are very accurate results as compared to the CCSD(T) method and the experimental data.
Enhancement of magnetization in Eu doped BiFeO3 nanoparticles
Authors: Liu Jian , Fang Liang , Zheng Fengang , Ju Sheng , Shen Mingrong
Published: July 2009

Bi 1 − x Eu x FeO 3  (BEFOx) nanoparticles have been synthesized by a sol-gel method. The samples maintain the pure rhombohedral structure up to x=0.1, while an impure phase of EuFeO3 is observed at x=0.15. The remenant magnetization of the BEFOx, which is significantly higher than those in nonmagnetically rare-earth doped BiFeO3, is found to increase with the increase of Eu concentration. Ferromagnetic coupling between Eu3+ and Fe3+ ions, evidenced by our first-principles calculations, is found to be the main reason for such a magnetization enhancement. In the mean time, the appearance of EuFeO3 phase is demonstrated to be another factor for the further magnetization enhancement in BEFOx=0.15.
Canola residues do not reduce establishment, growth, and yield of following summer crops
Authors: Robertson M. J. , Holland J. F. , Bambach R.
Published: July 2009

Sowing of summer-growing species (e.g. grain sorghum, cotton, mungbeans, maize) into the stubble of recently harvested winter crops (e.g. wheat, barley, chickpea, canola) is practised widely in the north-eastern cropping zone of Australia. With the recent increase in canola area in the region, there are concerns that canola crop residues may be antagonistic to the germination, establishment, growth, and yield of summer crops, in addition to the well documented non-host effect of Brassica species on vesicular-arbuscular mycorrhizae (VAM). We report five field studies conducted at two locations in the north-eastern grains region of Australia where grain sorghum and mungbean were grown after canola, Indian mustard, and wheat. The experiments included treatments that varied residue removal and retention, irrigation, and time between winter crop harvest and sowing date of the summer crop. Non-host effects of brassicas on VAM and phosphorus nutrition were eliminated by conducting field experiments in soils of relatively high P status.
This study failed to find consistent evidence that Brassica crops reduce the establishment, growth, and yield of following sorghum and mungbean crops. This is despite evidence from the literature on pot studies that extracts from Brassica residues can reduce germination and growth of a variety of crops, and anecdotal field evidence from farmers and the authors in the region. Based on our study, there does not seem to be a strong case for avoiding double-cropping summer crops into canola residues in the northern grains region.
A unified and universal explanation for Lévy laws and 1/f noises
Authors: Eliazar Iddo , Klafter Joseph
Published: July 2009

Lévy laws and 1/
f
noises are shown to emerge uniquely and universally from a general model of systems which superimpose the transmissions of many independent stochastic signals. The signals are considered to follow, statistically, a common—yet arbitrary—generic signal pattern which may be either stationary or dissipative. Each signal is considered to have its own random transmission amplitude and frequency. We characterize the amplitude-frequency randomizations which render the system output's stationary law and power-spectrum universal—i.e., independent of the underlying generic signal pattern. The classes of universal stationary laws and power spectra are shown to coincide, respectively, with the classes of Lévy laws and 1/
f
noises—thus providing a unified and universal explanation for the ubiquity of these classes of “anomalous statistics” in various fields of science and engineering.
Genomewide SNP variation reveals relationships among landraces and modern varieties of rice
Authors: McNally Kenneth L. , Childs Kevin L. , Bohnert Regina , Davidson Rebecca M. , Zhao Keyan , Ulat Victor J. , Zeller Georg , Clark Richard M. , Hoen Douglas R. , Bureau Thomas E. , Stokowski Renee , Ballinger Dennis G. , Frazer Kelly A. , Cox David R. , Padhukasahasram Badri , Bustamante Carlos D. , Weigel Detlef , Mackill David J. , Bruskiewich Richard M. , Rätsch Gunnar , Buell C. Robin , Leung Hei , Leach Jan E.
Published: July 2009

Rice, the primary source of dietary calories for half of humanity, is the first crop plant for which a high-quality reference genome sequence from a single variety was produced. We used resequencing microarrays to interrogate 100 Mb of the unique fraction of the reference genome for 20 diverse varieties and landraces that capture the impressive genotypic and phenotypic diversity of domesticated rice. Here, we report the distribution of 160,000 nonredundant SNPs. Introgression patterns of shared SNPs revealed the breeding history and relationships among the 20 varieties; some introgressed regions are associated with agronomic traits that mark major milestones in rice improvement. These comprehensive SNP data provide a foundation for deep exploration of rice diversity and gene–trait relationships and their use for future rice improvement.
Maximum-entropy network analysis reveals a role for tumor necrosis factor in peripheral nerve development and function
Authors: Dhadialla Prabhjot S. , Ohiorhenuan Ifije E. , Cohen Andrew , Strickland Sidney
Published: July 2009

Gene regulatory interactions that shape developmental processes can often can be inferred from microarray analysis of gene expression, but most computational methods used require extensive datasets that can be difficult to generate. Here, we show that maximum-entropy network analysis allows extraction of genetic interactions from limited microarray datasets. Maximum-entropy networks indicated that the inflammatory cytokine TNF-α plays a pivotal role in Schwann cell–axon interactions, and these data suggested that TNF mediates its effects by orchestrating cytoplasmic movement and axon guidance. In vivo and in vitro experiments confirmed these predictions, showing that Schwann cells in TNF
−/−
peripheral sensory bundles fail to envelop axons efficiently, and that recombinant TNF can partially correct these defects. These data demonstrate the power of maximum-entropy network-based methods for analysis of microarray data, and they indicate that TNF-α plays a direct role in Schwann cell–axon communication.
A basal ganglia-forebrain circuit in the songbird biases motor output to avoid vocal errors
Authors: Andalman Aaron S. , Fee Michale S.
Published: July 2009

In songbirds, as in mammals, basal ganglia-forebrain circuits are necessary for the learning and production of complex motor behaviors; however, the precise role of these circuits remains unknown. It has recently been shown that a basal ganglia-forebrain circuit in the songbird, which projects directly to vocal–motor circuitry, has a premotor function driving exploration necessary for vocal learning. It has also been hypothesized that this circuit, known as the anterior forebrain pathway (AFP), may generate an instructive signal that improves performance in the motor pathway. Here, we show that the output of the AFP directly implements a motor correction that reduces vocal errors. We use disruptive auditory feedback, contingent on song pitch, to induce learned changes in song structure over the course of hours and find that reversible inactivation of the output of the AFP produces an immediate regression of these learned changes. Thus, the AFP is involved in generating an error-reducing bias, which could increase the efficiency of vocal exploration and instruct synaptic changes in the motor pathway. We also find that learned changes in the song generated by the AFP are incorporated into the motor pathway within 1 day. Our observations support a view that basal ganglia-related circuits directly implement behavioral adaptations that minimize errors and subsequently stabilize these adaptations by training premotor cortical areas.
Redefining the p53 response element
Authors: Wang Bei , Xiao Ziwei , Ren Ee Chee
Published: July 2009

The tumor suppressor p53 is a master transcriptional regulator that affects a diverse range of cellular events. Surprisingly, even with >100 validated p53 response element (RE) sequences available, the effect of p53 binding on transcriptional behavior is seldom predictable and no functional rules have been described. Here, we report a systematic study on the role of specific nucleotides within the p53RE by using p21, a well-known target for p53 activation and contrasting it with Lasp1, a gene recently identified to be repressed by p53. Functional assays revealed a specific dinucleotide core combination within the CWWG motif of the p53RE to be the key factor that determines whether p53 transcriptionally activates or represses a target gene. The triplet RRR and YYY sequences flanking the core CWWG motif were also shown to play an important role in modulating the transcriptional behavior of p53. With the establishment of a set of predictive rules, we were able to reassess 162 published p53REs and showed that the attributed function for 20/162 p53REs studied were in fact erroneous. A significant proportion of p53REs (39/162) were found to be repressive, which is substantially higher than what is currently thought. Hence this clearer definition of the transcriptional behavior of p53 interaction with its RE will provide better insight toward the understanding of its fundamental role in cellular networks.
Legumes regulate
Rhizobium
bacteroid development and persistence by the supply of branched-chain amino acids
Authors: Prell J. , White J. P. , Bourdes A. , Bunnewell S. , Bongaerts R. J. , Poole P. S.
Published: July 2009

One of the largest contributions to biologically available nitrogen comes from the reduction of N
2
to ammonia by rhizobia in symbiosis with legumes. Plants supply dicarboxylic acids as a carbon source to bacteroids, and in return they receive ammonia. However, metabolic exchange must be more complex, because effective N
2
fixation by
Rhizobium leguminosarum
bv
viciae
bacteroids requires either one of two broad-specificity amino acid ABC transporters (Aap and Bra). It was proposed that amino acids cycle between plant and bacteroids, but the model was unconstrained because of the broad solute specificity of Aap and Bra. Here, we constrain the specificity of Bra and ectopically express heterologous transporters to demonstrate that branched-chain amino acid (LIV) transport is essential for effective N
2
fixation. This dependence of bacteroids on the plant for LIV is not due to their known down-regulation of glutamate synthesis, because ectopic expression of glutamate dehydrogenase did not rescue effective N
2
fixation. Instead, the effect is specific to LIV and is accompanied by a major reduction in transcription and activity of LIV biosynthetic enzymes. Bacteroids become symbiotic auxotrophs for LIV and depend on the plant for their supply. Bacteroids with
aap bra
null mutations are reduced in number, smaller, and have a lower DNA content than wild type. Plants control LIV supply to bacteroids, regulating their development and persistence. This makes it a critical control point for regulation of symbiosis.
Dating the emergence of pandemic influenza viruses
Authors: Smith Gavin J. D. , Bahl Justin , Vijaykrishna Dhanasekaran , Zhang Jinxia , Poon Leo L. M. , Chen Honglin , Webster Robert G. , Peiris J. S. Malik , Guan Yi
Published: July 2009

Pandemic influenza viruses cause significant mortality in humans. In the 20th century, 3 influenza viruses caused major pandemics: the 1918 H1N1 virus, the 1957 H2N2 virus, and the 1968 H3N2 virus. These pandemics were initiated by the introduction and successful adaptation of a novel hemagglutinin subtype to humans from an animal source, resulting in antigenic shift. Despite global concern regarding a new pandemic influenza, the emergence pathway of pandemic strains remains unknown. Here we estimated the evolutionary history and inferred date of introduction to humans of each of the genes for all 20th century pandemic influenza strains. Our results indicate that genetic components of the 1918 H1N1 pandemic virus circulated in mammalian hosts, i.e., swine and humans, as early as 1911 and was not likely to be a recently introduced avian virus. Phylogenetic relationships suggest that the A/Brevig Mission/1/1918 virus (BM/1918) was generated by reassortment between mammalian viruses and a previously circulating human strain, either in swine or, possibly, in humans. Furthermore, seasonal and classic swine H1N1 viruses were not derived directly from BM/1918, but their precursors co-circulated during the pandemic. Mean estimates of the time of most recent common ancestor also suggest that the H2N2 and H3N2 pandemic strains may have been generated through reassortment events in unknown mammalian hosts and involved multiple avian viruses preceding pandemic recognition. The possible generation of pandemic strains through a series of reassortment events in mammals over a period of years before pandemic recognition suggests that appropriate surveillance strategies for detection of precursor viruses may abort future pandemics.
MiR-21 is an EGFR-regulated anti-apoptotic factor in lung cancer in never-smokers
Authors: Seike Masahiro , Goto Akiteru , Okano Tetsuya , Bowman Elise D. , Schetter Aaron J. , Horikawa Izumi , Mathe Ewy A. , Jen Jin , Yang Ping , Sugimura Haruhiko , Gemma Akihiko , Kudoh Shoji , Croce Carlo M. , Harris Curtis C.
Published: July 2009

Fifteen percent of lung cancer cases occur in never-smokers and show characteristics that are molecularly and clinically distinct from those in smokers. Epidermal growth factor receptor (
EGFR
) gene mutations, which are correlated with sensitivity to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), are more frequent in never-smoker lung cancers. In this study, microRNA (miRNA) expression profiling of 28 cases of never-smoker lung cancer identified aberrantly expressed miRNAs, which were much fewer than in lung cancers of smokers and included miRNAs previously identified (e.g., up-regulated miR-21) and unidentified (e.g., down-regulated miR-138) in those smoker cases. The changes in expression of some of these miRNAs, including miR-21, were more remarkable in cases with
EGFR
mutations than in those without these mutations. A significant correlation between phosphorylated-EGFR (
p
-EGFR) and miR-21 levels in lung carcinoma cell lines and the suppression of miR-21 by an EGFR-TKI, AG1478, suggest that the EGFR signaling is a pathway positively regulating miR-21 expression. In the never-smoker–derived lung adenocarcinoma cell line H3255 with mutant
EGFR
and high levels of
p
-EGFR and miR-21, antisense inhibition of miR-21 enhanced AG1478-induced apoptosis. In a never-smoker–derived adenocarcinoma cell line H441 with wild-type
EGFR
, the antisense miR-21 not only showed the additive effect with AG1478 but also induced apoptosis by itself. These results suggest that aberrantly increased expression of miR-21, which is enhanced further by the activated EGFR signaling pathway, plays a significant role in lung carcinogenesis in never-smokers, as well as in smokers, and is a potential therapeutic target in both
EGFR
-mutant and wild-type cases.
A plant-specific calreticulin is a key retention factor for a defective brassinosteroid receptor in the endoplasmic reticulum
Authors: Jin Hua , Hong Zhi , Su Wei , Li Jianming
Published: July 2009

Mammalian calreticulin (CRT) is a multifunctional Ca
2+
-binding protein involved in more than 40 cellular processes in various subcellular compartments, such as Ca
2+
storage and protein folding in the endoplasmic reticulum (ER). CRT homologues were discovered in plants almost 15 years ago, and recent studies revealed that many plant species contain 2 or more CRTs that are members of 2 distinct families, the CRT1/2 family and the plant-specific CRT3 family. However, little is known about their physiological functions. Here we report
ebs2
(
EMS-mutagenized bri1 suppressor 2
) as an allele-specific suppressor of
bri1–9
, a dwarf Arabidopsis mutant caused by retention of a defective brassinosteroid receptor in the ER.
EBS2
encodes the Arabidopsis CRT3 that interacts with ER-localized bri1–9 in a glycan-dependent manner. Loss-of-function
ebs2
mutations compromise ER retention of bri1–9 and suppress its dwarfism, whereas
EBS2
over-expression enhances its dwarf phenotype. In contrast, mutations of 2 other CRTs or their membrane-localized homologues calnexins had little effect on
bri1–9
. A domain-swapping experiment revealed that the positively charged C-terminal tail of CRT3 is crucial for its “bri1–9-retainer” function. Our study revealed not only a functional role for a plant-specific CRT, but also functional diversity among the 3 Arabidopsis CRT paralogues.
The therapeutic encounter in same‐sex couple counselling – the client's perspective
Authors: Grove Jan , Blasby Simon
Published: July 2009

Aim: To gain insight into the client's experiences of the counsellor and the therapeutic encounter in same‐sex couple counselling. Method: Opportunity sampling using e‐mail and agency contacts and advertising in a journal and magazines resulted in nine respondents being interviewed. The transcripts were analysed using thematic analysis. Results: Respondents were sensitive to the way in which the counsellor related to them and their couple relationship. Four themes were identified: the counsellor's comfort and discomfort; overcompensating for sexual orientation; needing to protect the counsellor; and the uncertainty and not knowing about the counsellor. Discussion: The client's perception of the counsellor's underlying sense of discomfort will impact on the counselling relationship and therefore the efficacy of the process. This applies when the counsellor is perceived as tentative through being over cautious, or through lack of knowledge of same‐sex relationships. In addition, being overly gay affirmative was seen as a block to exploring negative aspects of the relationship. Implications for practice: Counsellors need an understanding of same‐sex relationships, and to be able to discuss the intimate details of these with a level of knowledge and comfort. In addition, being overly affirmative can prevent negative aspects of the relationships being addressed.
S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination
Authors: Wang Lili , Wuerffel Robert , Feldman Scott , Khamlichi Ahmed Amine , Kenter Amy L.
Published: July 2009

Immunoglobulin class switch recombination is governed by long-range interactions between enhancers and germline transcript promoters to activate transcription and modulate chromatin accessibility to activation-induced cytidine deaminase (AID). However, mechanisms leading to the differential targeting of AID to switch (S) regions but not to constant (CH) regions remain unclear. We show that S and CH regions are dynamically modified with histone marks that are associated with active and repressed chromatin states, respectively. Chromatin accessibility is superimposable with the activating histone modifications, which extend throughout S regions irrespective of length. High density elongating RNA polymerase II (RNAP II) is detected in S regions, suggesting that the transcription machinery has paused and stalling is abolished by deletion of the S region. We propose that RNAP II enrichment facilitates recruitment of histone modifiers to generate accessibility. Thus, the histone methylation pattern produced by transcription localizes accessible chromatin to S regions, thereby focusing AID attack.
IL-9 as a mediator of Th17-driven inflammatory disease
Authors: Nowak Elizabeth C. , Weaver Casey T. , Turner Henrietta , Begum-Haque Sakhina , Becher Burkhard , Schreiner Bettina , Coyle Anthony J. , Kasper Lloyd H. , Noelle Randolph J.
Published: July 2009

We report that like other T cells cultured in the presence of transforming growth factor (TGF) β, Th17 cells also produce interleukin (IL) 9. Th17 cells generated in vitro with IL-6 and TGF-β as well as purified ex vivo Th17 cells both produced IL-9. To determine if IL-9 has functional consequences in Th17-mediated inflammatory disease, we evaluated the role of IL-9 in the development and progression of experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. The data show that IL-9 neutralization and IL-9 receptor deficiency attenuates disease, and this correlates with decreases in Th17 cells and IL-6–producing macrophages in the central nervous system, as well as mast cell numbers in the regional lymph nodes. Collectively, these data implicate IL-9 as a Th17-derived cytokine that can contribute to inflammatory disease.
Group B Streptococcus suppression of phagocyte functions by protein-mediated engagement of human Siglec-5
Authors: Carlin Aaron F. , Chang Yung-Chi , Areschoug Thomas , Lindahl Gunnar , Hurtado-Ziola Nancy , King Charles C. , Varki Ajit , Nizet Victor
Published: July 2009

Group B Streptococcus (GBS) is a leading cause of invasive bacterial infections in human newborns. A key GBS virulence factor is its capsular polysaccharide (CPS), displaying terminal sialic acid (Sia) residues which block deposition and activation of complement on the bacterial surface. We recently demonstrated that GBS Sia can bind human CD33-related Sia-recognizing immunoglobulin (Ig) superfamily lectins (hCD33rSiglecs), a family of inhibitory receptors expressed on the surface of leukocytes. We report the unexpected discovery that certain GBS strains may bind one such receptor, hSiglec-5, in a Sia-independent manner, via the cell wall–anchored β protein, resulting in recruitment of SHP protein tyrosine phosphatases. Using a panel of WT and mutant GBS strains together with Siglec-expressing cells and soluble Siglec-Fc chimeras, we show that GBS β protein binding to Siglec-5 functions to impair human leukocyte phagocytosis, oxidative burst, and extracellular trap production, promoting bacterial survival. We conclude that protein-mediated functional engagement of an inhibitory host lectin receptor promotes bacterial innate immune evasion.
Cooperative regulation of Cav1.2 channels by intracellular Mg2+, the proximal C-terminal EF-hand, and the distal C-terminal domain
Authors: Brunet Sylvain , Scheuer Todd , Catterall William A.
Published: July 2009

L-type Ca2+ currents conducted by Cav1.2 channels initiate excitation–contraction coupling in cardiac myocytes. Intracellular Mg2+ (Mgi) inhibits the ionic current of Cav1.2 channels. Because Mgi is altered in ischemia and heart failure, its regulation of Cav1.2 channels is important in understanding cardiac pathophysiology. Here, we studied the effects of Mgi on voltage-dependent inactivation (VDI) of Cav1.2 channels using Na+ as permeant ion to eliminate the effects of permeant divalent cations that engage the Ca2+-dependent inactivation process. We confirmed that increased Mgi reduces peak ionic currents and increases VDI of Cav1.2 channels in ventricular myocytes and in transfected cells when measured with Na+ as permeant ion. The increased rate and extent of VDI caused by increased Mgi were substantially reduced by mutations of a cation-binding residue in the proximal C-terminal EF-hand, consistent with the conclusion that both reduction of peak currents and enhancement of VDI result from the binding of Mgi to the EF-hand (KD ≈ 0.9 mM) near the resting level of Mgi in ventricular myocytes. VDI was more rapid for L-type Ca2+ currents in ventricular myocytes than for Cav1.2 channels in transfected cells. Coexpression of Cavβ2b subunits and formation of an autoinhibitory complex of truncated Cav1.2 channels with noncovalently bound distal C-terminal domain (DCT) both increased VDI in transfected cells, indicating that the subunit structure of the Cav1.2 channel greatly influences its VDI. The effects of noncovalently bound DCT on peak current amplitude and VDI required Mgi binding to the proximal C-terminal EF-hand and were prevented by mutations of a key divalent cation-binding amino acid residue. Our results demonstrate cooperative regulation of peak current amplitude and VDI of Cav1.2 channels by Mgi, the proximal C-terminal EF-hand, and the DCT, and suggest that conformational changes that regulate VDI are propagated from the DCT through the proximal C-terminal EF-hand to the channel-gating mechanism.
The Budding Yeast “Saccharomyces cerevisiae” as a Drug Discovery Tool to Identify Plant‐Derived Natural Products with Anti‐Proliferative Properties
Authors: Qaddouri Bouchra , Guaadaoui Abdelkarim , Bellirou Ahmed , Hamal Abdellah , Melhaoui Ahmed , Brown Grant W. , Bellaoui Mohammed
Published: July 2009

The budding yeast Saccharomyces cerevisiae is a valuable system to study cell‐cycle regulation, which is defective in cancer cells. Due to the highly conserved nature of the cell‐cycle machinery between yeast and humans, yeast studies are directly relevant to anticancer‐drug discovery. The budding yeast is also an excellent model system for identifying and studying antifungal compounds because of the functional conservation of fungal genes. Moreover, yeast studies have also contributed greatly to our understanding of the biological targets and modes of action of bioactive compounds. Understanding the mechanism of action of clinically relevant compounds is essential for the design of improved second‐generation molecules. Here we describe our methodology for screening a library of plant‐derived natural products in yeast in order to identify and characterize new compounds with anti‐proliferative properties.
Isolation and characterization of bacteriophages specific for Campylobacter jejuni
Authors: Hwang Sunyoung , Yun Jiae , Kim Kwang‐Pyo , Heu Sunggi , Lee Seungdon , Ryu Sangryeol
Published: July 2009

Human infection by Campylobacter jejuni is mainly through the consumption of contaminated poultry products, which results in gastroenteritis and, rarely, bacteremia and polyneuropathies. In this study, six C. jejuni‐specific bacteriophages (CPS1–6) were isolated by the spot‐on‐the‐lawn technique from chicken samples in Korea and characterized for potential use as biocontrol agents. All isolated bacteriophages exhibited a high specificity, being able to lyse only C. jejuni, but not other Gram–negative bacteria, including C. coli, Escherichia coli, Salmonella spp., and Gram–positive bacteria. Bacteriophages contain an icosahedral head and a contractile tail sheath in transmission electron microscopy, and possess ds‐DNA with an average genome size of approximately 145 kb; therefore, all bacteriophages are categorized into the Myoviridae family. Bacterial lysis studies in liquid media revealed that CPS2 could be used to control the growth of C. jejuni.
Identification of new target moleculesPTK2,TGFBR2andCD9overexpressed during advanced bone marrow remodelling in primary myelofibrosis
Authors: Bock Oliver , Muth Michaela , Theophile Katharina , Winter Melissa , Hussein Kais , Büsche Guntram , Kröger Nicolaus , Kreipe Hans
Published: July 2009

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm characterized by remodelling of the bone marrow, including progressive myelofibrosis and exaggerated angiogenesis. Advanced PMF frequently shows a full‐blown fibre meshwork, which avoids aspiration of cells, and the expression profile of genes related to stroma pathology at this stage remains largely undetermined. We investigated bone marrow core biopsies in PMF showing various degrees of myelofibrosis by custom‐made low density arrays (LDA) representing target genes with designated roles in synthesis of extracellular matrix, matrix remodelling, cellular adhesion and motility. Among a set of 11 genes up‐regulated in advanced stages of PMF (P ≤ 0·01) three candidates, PTK2 protein tyrosine kinase 2 (PTK2), transforming growth factor β type II receptor (TGFBR2) and motility‐related protein‐1 (CD9 molecule,CD9), were investigated in more detail.PTK2,TGFBR2andCD9were significantly overexpressed in larger series of advanced PMF stages (P ≤ 0·01 respectively). Endothelial cells of the increased microvessel network in PMF could be identified as a predominant source forPTK2,TGFBR2andCD9.CD9also strongly identified activated fibroblasts in advanced myelofibrosis. We conclude thatPTK2,TGFBR2andCD9represent new target molecules involved in bone marrow remodelling of PMF and warrant further investigation for potential targeted therapy.
Allogeneic stem cell transplantation for patients with refractory anaemia with matched related and unrelated donors: delay of the transplant is associated with inferior survival
Authors: De Witte Theo , Brand Ronald , Van Biezen Anja , Mufti Ghulam , Ruutu Tapani , Finke Jürgen , Von Dem Borne Peter , Vitek Antonin , Delforge Michel , Alessandrino Paolo , Harlahakis Nicolas , Russell Nigel , Martino Roberto , Verdonck Leo , Kröger Nicholas , Niederwieser Dietger ,   for the European Blood and Marrow Transplantation Group (EBMT), Chronic Leukemia Working Party (CLWP)‐MDS subcommittee
Published: July 2009

Allogeneic stem cell transplantation (alloSCT) for patients with refractory anaemia may result in a 50% event‐free survival, but the high non‐relapse mortality (NRM) precludes a general application of this therapeutic modality. This study evaluated the impact of various pre‐transplant variables, including disease duration, intensity of the conditioning regimen, type of donor and year of transplantation on outcome. The study population consisted of 374 patients; 244 were transplanted from human leucocyte antigen (HLA)‐identical siblings and 130 patients from matched unrelated donors. The median age was 39 years. One hundred and two patients were transplanted after reduced intensity conditioning (RIC). The overall 4‐year survival was 52%. The 4‐year survival of patients transplanted with HLA‐identical sibling donors and matched unrelated donors was 52% and 50%, respectively. Multivariate analysis showed an improved survival (P = 0·05) and a lower NRM (P = 0·02) when the transplantation was performed in recent years. Increasing age, and disease duration of >12 months were associated with inferior survival. RIC resulted in a similar survival despite an increased relapse risk (P = 0·02). This improved outcome permits alloSCT in patients older than 50 years of age, even with the use of matched unrelated donors. AlloSCT should be preferentially performed early after diagnosis after careful analysis of prognostic variables.
Levels of non‐transferrin‐bound iron as an index of iron overload in patients with thalassaemia intermedia
Authors: Taher Ali , Musallam Khaled M. , El Rassi Fouad , Duca Lorena , Inati Adlette , Koussa Suzane , Cappellini Maria D.
Published: July 2009

Non‐transferrin‐bound iron (NTBI) was evaluated as an index of iron overload in a cross‐sectional randomised study in 74 non‐transfused patients with thalassaemia intermedia (TI). Mean NTBI (2·92 ± 3·43 μmol/l), serum ferritin (1023 ± 780 ng/ml) and liver iron concentration (LIC; 9·0 ± 7·4 mg Fe/g dry weight) were increased above reference‐range levels. Significant positive correlations occurred between mean NTBI and LIC (Pearson correlation 0·36; P = 0·002) and serum ferritin (Pearson correlation 0·421; P < 0·0001); with higher levels observed in splenectomised patients. NTBI assessment has potential as a simple reliable approach to determining iron status in TI.
Amyloid beta‐derived neuroplasticity in bone marrow‐derived mesenchymal stem cells is mediated by NPY and 5‐HT2B receptors via ERK1/2 signalling pathways
Authors: Jin H. K. , Bae J. S. , Furuya S. , Carter J. E.
Published: July 2009

Objective:  In Alzheimer's disease, toxic soluble and insoluble forms of amyloid beta (Aβ) cause synaptic dysfunction and neuronal loss. Given its potential role in producing a toxic host microenvironment for transplanted donor stem cells, we investigated the interaction between Aβ and proliferation, survival, and differentiation of bone marrow‐derived mesenchymal stem cells (BM‐MSC) in culture.

Materials and methods:  We used BM‐MSC that had been isolated from mouse bone marrow and cultured, and we also assessed relevant reaction mechanisms using gene microarray, immunocytochemistry, and inhibitors of potential signalling molecules, such as mitogen‐activated protein kinase (MAPK)/extracellular signal‐regulated kinase (ERK)1/2 and tyrosine protein kinase.

Results and conclusions:  Interestingly, we found that treatment with aggregated (1–40 or 1–42) and oligomeric (1–42) Aβ promoted neuronal‐like differentiation of BM‐MSC without toxic effects. This was not dependent on soluble factors released from BM‐MSC progeny nor solely on formation of Aβ fibrils. The effect of Aβ is mediated by G‐protein coupled receptors, neuropeptide Y1 (NPY1R) and serotonin (5‐hydroxytryptamine) receptor 2B, via phosphatidylinositol‐3‐OH kinase‐dependent activation of the MAPK/ERK1/2. Our results lend support to the idea that reciprocal donor stem cell–host interactions may promote a regenerative response that can be exploited by epigenetic modulation of NPY/serotonergic gene expression, for stem cell therapy, in Alzheimer's disease.
A review of research to address carrot fly (Psila rosae) control in the UK1
Authors: Collier R. , Finch S.
Published: July 2009

Carrot fly (Psila rosae) is a serious pest of umbelliferous crops such as carrot, parsnip, celery and parsley. Carrot fly has been studied in the UK for more than 60 years. Whilst some of these studies have been focused on insecticides, others have demonstrated the potential for non‐insecticidal methods of control that might contribute to an integrated pest management strategy. These include rotation and spatial separation of susceptible crops; carrot varieties with partial resistance to carrot fly; and crop management strategies to avoid oviposition or the development of severe damage. This paper outlines some of the approaches that have been taken and indicates how these are, or might be, used in practice.
Internet sales of plants for planting – an increasing trend and threat?1
Authors: Giltrap N. , Eyre D. , Reed P.
Published: July 2009

The sale of plants for planting on the Internet and by other direct marketing methods (e.g. newspaper offers) has increased dramatically in recent years. Some companies are specialist suppliers in this area and typically with this trade small quantities of plants are sent by mail to a very large number of amateur growers scattered throughout the UK. It is often difficult for the NPPO to keep track of this activity especially when the supplier is located outside its jurisdiction. Also if problems arise with plants sold in this way, taking effective official eradicatory action can be problematic. To demonstrate the issues and problems involved, two examples that occurred in the UK in 2008 are described.
First report of Heterorhabditis bacteriophora (Poinar, 1975) (Nematoda: Heterorhabditidae) isolated from the red palm weevil, Rhynchophorus ferrugineus (Oliver, 1790) (Coleoptera: Curculionidae) in Turkey
Authors: Atakan E. , Elekçioğlu I. H. , Gözel U. , Güneş Ç. , Yüksel O.
Published: July 2009

Infestation levels of the red palm weevil, Rhynchophorus ferrugineus (Oliver, 1790) and its natural enemies on palm trees in recreation areas were investigated in the Adana province of Turkey in 2008. The trunks of dead palms were sampled for R. ferrugineus and for the presence of entomopathogenic nematodes. While 20% of Phoenix canariensis Hort. were found to be killed by R. ferrugineus, only 2 trees from other species, 1 Washingtonia filifera (L. Linden) and 1 Phoenix dactlylifera L., were killed. Only one species of entomopathogenic nematode, Heterorhabditis bacteriophora (Poinar, 1975) (Nematoda: Heterorhabditidae), was isolated from the R. ferrugineus specimens. Seasonal mortality rate in the total larval population (total 565 larval specimens) of R. ferrugineus was 69%. H. bacteriophora resulted in a significant mortality rate (80%) in the pupae population (total 314 pupal specimens). Overall, 70% of the total of 879 pre‐adult specimens were found to be fatally infested by the attacks of this nematode. Heterorhabditis bacteriophora killed few adults, corresponding to 2% of the overall mortality rate. It is concluded that H. bacteriophora could be evaluated as a potential candidate for biological control of R. ferrugineus in the Mediterranean region.
Pathway analysis: aquatic plants imported in 10 EPPO countries
Authors: Brunel S.
Published: July 2009

Pathway analyses are regarded by National Plant Protection Organizations as a very efficient way to address the risks posed by invasive alien species. Data on import of aquatic plants was obtained from 10 EPPO countries (Austria, Czech Republic, Estonia, France, Germany, Hungary, the Netherlands, Latvia, Switzerland and Turkey) and aggregated in order to consider whether invasive or potentially invasive alien plants could be introduced in the EPPO region through this pathway. This study highlights that this pathway mainly consists of the import of tropical plants for use in aquaria, and which do not represent a risk due to their climatic requirements. However, a few species require thorough attention owing to the threats they cause. Of the 247 species recorded as imported, only 10 are currently considered to be a threat, representing 4% of the total number of plants imported. These 10 invasive or potentially invasive species continue to be traded in huge quantities in spite of the fact that Crassula helmsii and Eichhornia crassipes are recommended for regulation by EPPO, Azolla filiculoides, Egeria densa, Elodea nuttalli, Lagarosiphon major, Ludwigia grandiflora and Myriophyllum aquaticum should have their entry and spread prevented by countries and Hydrilla verticillata and Pistia stratiotes are recorded on the EPPO Alert List. Six additional species have been identified as representing a moderate to high potential risk: Alternanthera sessilis, Adiantum raddianum, Gymnocoronis spilanthoides, Hygrophila polysperma, Limnophila sessiliflora and Syngonium podophyllum. These species could be subject to further investigation, possibly a pest risk analysis, to evaluate the risk they may represent.
The erythropoietin and regenerative medicine: a lesson from fish
Authors: Buemi M. , Lacquaniti A. , Bolignano D. , Maricchiolo G. , Favaloro A. , Buemi A. , Grasso G. , Donato V. , Giorgianni G. , Genovese L. , Coppolino G. , Sfacteria A.
Published: July 2009

Background  Erythropoietin (EPO), the main haematopoietic growth factor for the proliferation and differentiation of erythroid progenitor cells, is also known for its angiogenic and regenerative properties.

Materials and methods  In this study, we aimed to test the regenerative effects of EPO administration in an experimental model of Sea bass (Dicentrarchus labrax) subjected to amputation of the caudal fin.

Results  Erythropoietin‐treated fishes (3000 UI of human recombinant EPO‐alpha immediately after cutting and after 15 days) showed an increased growth rate of their fins compared with those untreated (anova variance: P: 0·01 vs. P: 0·04). By analysing fin length at established times (15 and 30 days after cut), EPO‐treated fishes always showed an increased length compared with untreated ones (T‐15: 1·1 ± 0·2 vs. 0·7 ± 0·2 cm, P: 0·03; T‐30: 1·9 ± 0·3 vs. 1·2 ± 0·2 cm, P: 0·01). Moreover, exogenous EPO administration induced an enormous increase in EPO‐blood levels at each observation time (T‐15: 2240 ± 210 vs. 16·7 ± 1·8 mU mL−1, P < 0·001; T‐30: 2340 ± 190 vs. 17·1 ± 1·9 mU mL−1, P < 0·001), whereas these levels remained quite unmodified in untreated fishes. Immunochemical analyses performed by confocal laser scanning microscopic observations showed an increased expression of EPO‐receptors and PECAM‐1 (an endothelial surface marker of vessels sprout) in the regenerating tissue, whereas no signs of inflammation or fibrosis were recognisable.

Conclusions  All these findings confirm EPO as a new factor involved in regenerative processes, also suggesting a potential, future utility for new therapeutical applications in the field of human regenerative medicine.
BTB protein, dKLHL18/CG3571, serves as an adaptor subunit for a dCul3 ubiquitin ligase complex
Authors: Fujiyama‐Nakamura Sally , Ito Saya , Sawatsubashi Shun , Yamauchi Yoshio , Suzuki Eriko , Tanabe Masahiko , Kimura Shuhei , Murata Takuya , Isobe Toshiaki , Ichi Takeyama Ken– , Kato Shigeaki
Published: July 2009

The BTB domain is a highly conserved protein–protein interaction motif and functions in diverse cellular processes, including transcriptional regulation, ion channel assembly, cytoskeleton dynamics and apoptosis. Recently, it was reported that some BTB domain‐containing proteins associate with Cullin‐3 (Cul3), an E3 ubiquitin ligase, and act as an adaptor for Cul3 recognition of its substrate. However, the target substrates for the Cul3/BTB protein E3 ubiquitin ligase complex are largely unknown. Here, we report the characterization of a novel Drosophila BTB protein, dKLHL18/CG3571. By purification of a dKLHL18‐associated complex, we identified CG10324, CG5808, l(2)37Cb and dCul3/guftagu. Indeed, the physical association of dKLHL18 with these proteins was observed in insect S2 cells, and genetic interactions among the identified factors were also observed in thorax development. Moreover, transient overexpression of dKLHL18 increased the ubiquitinated protein levels of CG10324 and CG5808. These findings suggest that dKLHL18 is an adaptor for a dCul3 E3 ubiquitin ligase to accommodate CG10324, CG5808 and l(2)37Cb proteins for ubiquitination.
DNA conformation‐dependent activities of human mitochondrial RNA polymerase
Authors: Fukuoh Atsushi , Ohgaki Kippei , Hatae Hinako , Kuraoka Isao , Aoki Yoshimasa , Uchiumi Takeshi , Jacobs Howard T. , Kang Dongchon
Published: July 2009

Mitochondrial RNA polymerase (POLRMT) is a core protein for mitochondrial DNA (mtDNA) transcription. In addition, POLRMT is assumed to be involved in replication, although its exact role is not yet clearly elucidated. We have found novel properties of human POLRMT using a reconstituted transcription system. Various lengths of RNA molecules were synthesized from templates even without a defined promoter sequence, when we used supercoiled circular double‐stranded DNA as a template. This promoter‐independent activity was as strong as the promoter‐dependent one. Promoter‐independent DNA conformation‐dependent transcription required TFB2M. On supercoiled templates, the promoter‐independent activity was strongly suppressed by a putatively physiological amount of TFAM, while promoter‐dependent transcription was inhibited to a lesser extent. These different inhibition patterns by TFAM may be important for prevention of random RNA synthesis in vivo. Promoter‐independent activity was also observed on relaxed circular single‐stranded DNA, where its activity no longer required TFB2M. RNA synthesis on single‐stranded DNA was weakly suppressed by a putatively physiological amount of TFAM but restored by the addition of mitochondrial single‐stranded DNA binding protein. We suggest that these properties of POLRMT could explain the characteristic features of mammalian mtDNA transcription and replication.
Herbage mass and nutritive value of herbage of extensively managed temperate grasslands along a gradient of shrub encroachment
Authors: Kesting S. , Wrage N. , Isselstein J.
Published: July 2009

Semi‐natural grasslands often serve as important reserves of biodiversity. In Europe extensive grazing by livestock is considered an appropriate management to conserve biodiversity value and to limit shrub encroachment. However, little is known about the influence of shrubs on agronomic values. A gradient analysis of shrub‐invaded temperate grasslands (from shrub‐free to pioneer forest) in Germany was carried out to test the hypothesis that herbage mass and variables describing nutritive value of herbage decrease with increasing shrub encroachment. The herbage mass of dry matter (DM), variables describing the nutritive value of herbage, composition of the vegetation and mean of Ellenberg’s indicator values were analysed with respect to the extent of shrubs. There was a reduction of herbage mass of DM from 3570 to 210 kg ha−1 with increasing shrub encroachment. Metabolizable energy concentration of herbage ranged from 8·9 to 10·2 MJ kg−1 DM and crude protein concentration from 72 to 171 g kg−1 DM, both measures being positively correlated with shrub occurrence. Increasing shrub occurrence was associated with a decrease in water‐soluble carbohydrates concentration (from 151 to 31 g kg−1) and a reduction in the indicator ‘forage value’. The results indicate a potentially large agronomic value for shrub‐encroached temperate grasslands.