bluuebunny/crossref_metadata_2025 huggingface dataset:
98 THE EXPRESSION OF TIGHT JUNCTION GENES IN THE PLACENTA BY CALCIUM OR VITAMIN D DEFICIENCY IN WILD TYPE AND CaBP-9k OR CaBP-28k KNOCKOUT MICE
Authors: Hwang I. , Jeung E. B.
Published: December 2012

The placenta is responsible for calcium transport from mother to fetus. Tight junction genes are responsible for the passive paracellular pathway, which is one of the major calcium transport pathways. Therefore, we examined whether the tight junction genes are differently expressed in the placenta by calcium, vitamin D, or both deficiency. We also investigated the correlation between transcellular transport and paracellular transport by using calbindin-D9k (CaBP-9k), calbindin-D28K (CaBP-28k), or both knockout (KO) mice. We administrated C57BL/6 wild type and CaBP-D9K, CaBP-D28K KO, or both mice with calcium, vitamin D, or both deficiency diets for 19 days (during pregnant Day 0 to 18). The expression levels and localization of tight junction genes including zona occludens 1 (Zo-1), junction adhesion molecules A (Jam-A), and claudins (Cldn) were tested. The mRNA and protein expression of these genes were investigated by real-time PCR and Western blotting assay. Five samples from 3 animals for each treated group were used and the data analyzed using a one-way ANOVA. P-values <0.05 were considered statistically significant. The localization of the genes was also examined by immunohistochemistry. The mRNA and protein expressions of Cldn1 were increased in calcium and calcium/vitamin D deficient CaBP-D9K KO mice and in calcium/vitamin D deficient CaBP-D9/28K mice, whereas those of Zo-1 and Jam-A were not affected. Gene Cldn5 mRNA expression showed a decrease in CaBP-9k, CaBP-28k, or both KO mice compared with wild type mice. Interestingly, Cldn5 mRNA expression was augmented in vitamin D or calcium deficient CaBP-D9K KO mice. Other tested Cldns did not show significant changes in any dietary or CaBP KO conditions. All the tight junction genes were localized in the trophoblast layer of the placenta. Taken together, the expression of tight junction genes was dynamically regulated by different dietary conditions and in the condition that transcellular calcium transport was altered by ablation of CaBPs, suggesting that these genes were involved in the placental calcium homeostasis.
99 THE DIFFERENTIAL EXPRESSION OF CALCIUM-RELATED PROTEINS BY HYPOXIC STRESS IN THE DUODENUM, KIDNEY, AND PLACENTA OF PREGNANT RATS
Authors: Yang H. , Jeung E. B.
Published: December 2012

Preeclampsia is a pregnancy-specific disease characterized by the de novo development of concurrent hypertension, proteinuria, and oxidative stress in placenta. Hypoxia occurs during the development of placenta in the first trimester and is implicated in trophoblast differentiation. Oxidative stress, resulting from deficient remodeling of spiral arteries, is an important inducer of preeclampsia. The potassium-dependent sodium/calcium exchangers including NCKX3 and NCX1 play critical roles in the transport of intracellular calcium that is exchanged with extracellular sodium ions. Calcium-related proteins, NCXs, calbindin, calcium pumping proteins (TRPV5-6, PMCA1b), transcripts are abundant in the smooth muscle, uterus, aorta, and intestine. The expressions of calcium-related proteins in the kidney, duodenum, and placenta after hypoxic stress in rats at gestation Day 19.5 (GD 19.5) were examined by real-time PCR and Western blot analysis. Hypoxic condition did not change fetal weight; however, it significantly increased the weight of placenta compared to normoxic condition. In GD 19.5, renal NCKX3 and TRPV6 expressions were increased, whereas the levels of NCX1 were decreased in hypoxic rats compared with normoxic pregnant rats. The expressions of CaBP-9k, TRPV5, and PMCA1b were not altered in normoxic or hypoxic rat tissues. Duodenal expressions of CaBP-9k, TRPV5-6, and PMCA1 were decreased in hypoxic rats, whereas NCXs were not changed. The transcripts of NCKX3, TRPV5-6, and PMCA1b were highly expressed in the placenta of hypoxic rat. Taken together, the expressions of renal, duodenal, and placental calcium-related proteins appear to be modulated by hypoxia-induced oxidative stress, implying that calcium-related proteins may be involved in preeclamptic oxidative stress.
Direct visualization of the alamethicin pore formed in a planar phospholipid matrix
Authors: Pieta Piotr , Mirza Jeff , Lipkowski Jacek
Published: December 2012

We present direct visualization of pores formed by alamethicin (Alm) in a matrix of phospholipids using electrochemical scanning tunneling microscopy (EC-STM). High-resolution EC-STM images show individual peptide molecules forming channels. The channels are not dispersed randomly in the monolayer but agglomerate forming 2D nanocrystals with a hexagonal lattice in which the average channel–channel distance is 1.90 ± 0.1 nm. The STM images suggest that each Alm is shared between the two adjacent channels. Every channel consists of six Alm molecules. Three or four of these molecules have the hydrophilic group oriented toward the center of the channel allowing for water column formation inside the channel. The dimensions of the central pore in the images are consistent with the dimension of the water column in a model of hexameric pore proposed in the literature. The images obtained in this work validate the barrel-stave model of the pore formed in phospholipid membranes by amphiphatic peptides. They also provide direct evidence for cluster formation by such pores.
Evolutionarily conserved protein ERH controls CENP-E mRNA splicing and is required for the survival of KRAS mutant cancer cells
Authors: Weng Meng-Tzu , Lee Jih-Hsiang , Wei Shu-Chen , Li Qiuning , Shahamatdar Sina , Hsu Dennis , Schetter Aaron J. , Swatkoski Stephen , Mannan Poonam , Garfield Susan , Gucek Marjan , Kim Marianne K. H. , Annunziata Christina M. , Creighton Chad J. , Emanuele Michael J. , Harris Curtis C. , Sheu Jin-Chuan , Giaccone Giuseppe , Luo Ji
Published: December 2012

Cancers with Ras mutations represent a major therapeutic problem. Recent RNAi screens have uncovered multiple nononcogene addiction pathways that are necessary for the survival of Ras mutant cells. Here, we identify the evolutionarily conserved gene enhancer of rudimentary homolog (
ERH
), in which depletion causes greater toxicity in cancer cells with mutations in the small GTPase KRAS compared with KRAS WT cells. ERH interacts with the spliceosome protein SNRPD3 and is required for the mRNA splicing of the mitotic motor protein CENP-E. Loss of ERH leads to loss of CENP-E and consequently, chromosome congression defects. Gene expression profiling indicates that ERH is required for the expression of multiple cell cycle genes, and the gene expression signature resulting from ERH down-regulation inversely correlates with KRAS signatures. Clinically, tumor ERH expression is inversely associated with survival of colorectal cancer patients whose tumors harbor KRAS mutations. Together, these findings identify a role of ERH in mRNA splicing and mitosis, and they provide evidence that KRAS mutant cancer cells are dependent on ERH for their survival.
Small changes in enzyme function can lead to surprisingly large fitness effects during adaptive evolution of antibiotic resistance
Authors: Walkiewicz Katarzyna , Benitez Cardenas Andres S. , Sun Christine , Bacorn Colin , Saxer Gerda , Shamoo Yousif
Published: December 2012

In principle, evolutionary outcomes could be largely predicted if all of the relevant physicochemical variants of a particular protein function under selection were known and integrated into an appropriate physiological model. We have tested this principle by generating a family of variants of the tetracycline resistance protein TetX2 and identified the physicochemical properties most correlated with organismal fitness. Surprisingly, small changes in the
K

m(
MCN
)

, less than twofold, were sufficient to produce highly successful adaptive mutants over clinically relevant drug concentrations. We then built a quantitative model directly relating the in vitro physicochemical properties of the mutant enzymes to the growth rates of bacteria carrying a single chromosomal copy of the
tet(X2)
variants over a wide range of minocycline (MCN) concentrations. Importantly, this model allows the prediction of enzymatic properties directly from cellular growth rates as well as the physicochemical-fitness landscape of TetX2. Using experimental evolution and deep sequencing to monitor the allelic frequencies of the seven most biochemically efficient TetX2 mutants in 10 independently evolving populations, we showed that the model correctly predicted the success of the two most beneficial variants
tet(X2)
T280A
and
tet(X2)
N371I
. The structure of the most efficient variant, TetX2
T280A
, in complex with MCN at 2.7 Å resolution suggests an indirect effect on enzyme kinetics. Taken together, these findings support an important role for readily accessible small steps in protein evolution that can, in turn, greatly increase the fitness of an organism during natural selection.
Stress-induced epigenetic transcriptional memory of acetylcholinesterase by HDAC4
Authors: Sailaja Badi Sri , Cohen-Carmon Dorit , Zimmerman Gabriel , Soreq Hermona , Meshorer Eran
Published: December 2012

Stress induces long-lasting changes in neuronal gene expression and cholinergic neurotransmission, but the underlying mechanism(s) are incompletely understood. Here, we report that chromatin structure and histone modifications are causally involved in this transcriptional memory. Specifically, the AChE gene encoding the acetylcholine-hydrolyzing enzyme acetylcholinesterase is known to undergo long-lasting transcriptional and alternative splicing changes after stress. In mice subjected to stress, we identified two alternative 5′ exons that were down-regulated after stress in the hippocampus, accompanied by reduced acetylation and elevated trimethylation of H3K9 at the corresponding promoter. These effects were reversed completely by daily administration of the histone deacetylase (HDAC) inhibitor sodium butyrate for 1 wk after stress. H3K9 hypoacetylation was associated with a selective, sodium butyrate-reversible promoter accumulation of HDAC4. Hippocampal suppression of HDAC4 in vivo completely abolished the long-lasting AChE-related and behavioral stress effects. Our findings demonstrate long-lasting stress-inducible changes in AChE's promoter choices, identify the chromatin changes that support this long-term transcriptional memory, and reveal HDAC4 as a mediator of these effects in the hippocampus.
Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation
Authors: Qi Wei , Chan HoMan , Teng Lin , Li Ling , Chuai Shannon , Zhang Ruipeng , Zeng Jue , Li Min , Fan Hong , Lin Ying , Gu Justin , Ardayfio Ophelia , Zhang Ji-Hu , Yan Xiaoxia , Fang Jialuo , Mi Yuan , Zhang Man , Zhou Tao , Feng Grace , Chen Zijun , Li Guobin , Yang Teddy , Zhao Kehao , Liu Xianghui , Yu Zhengtian , Lu Chris X. , Atadja Peter , Li En
Published: December 2012

Ezh2 (Enhancer of zeste homolog 2) protein is the enzymatic component of the Polycomb repressive complex 2 (PRC2), which represses gene expression by methylating lysine 27 of histone H3 (H3K27) and regulates cell proliferation and differentiation during embryonic development. Recently, hot-spot mutations of Ezh2 were identified in diffused large B-cell lymphomas and follicular lymphomas. To investigate if tumor growth is dependent on the enzymatic activity of Ezh2, we developed a potent and selective small molecule inhibitor, EI1, which inhibits the enzymatic activity of Ezh2 through direct binding to the enzyme and competing with the methyl group donor S-Adenosyl methionine. EI1-treated cells exhibit genome-wide loss of H3K27 methylation and activation of PRC2 target genes. Furthermore, inhibition of Ezh2 by EI1 in diffused large B-cell lymphomas cells carrying the Y641 mutations results in decreased proliferation, cell cycle arrest, and apoptosis. These results provide strong validation of Ezh2 as a potential therapeutic target for the treatment of cancer.
Mass extinction of lizards and snakes at the Cretaceous–Paleogene boundary
Authors: Longrich Nicholas R. , Bhullar Bhart-Anjan S. , Gauthier Jacques A.
Published: December 2012

The Cretaceous–Paleogene (K-Pg) boundary is marked by a major mass extinction, yet this event is thought to have had little effect on the diversity of lizards and snakes (Squamata). A revision of fossil squamates from the Maastrichtian and Paleocene of North America shows that lizards and snakes suffered a devastating mass extinction coinciding with the Chicxulub asteroid impact. Species-level extinction was 83%, and the K-Pg event resulted in the elimination of many lizard groups and a dramatic decrease in morphological disparity. Survival was associated with small body size and perhaps large geographic range. The recovery was prolonged; diversity did not approach Cretaceous levels until 10 My after the extinction, and resulted in a dramatic change in faunal composition. The squamate fossil record shows that the end-Cretaceous mass extinction was far more severe than previously believed, and underscores the role played by mass extinctions in driving diversification.
Misregulation of human sortilin splicing leads to the generation of a nonfunctional progranulin receptor
Authors: Prudencio Mercedes , Jansen-West Karen R. , Lee Wing C. , Gendron Tania F. , Zhang Yong-Jie , Xu Ya-Fei , Gass Jennifer , Stuani Cristiana , Stetler Caroline , Rademakers Rosa , Dickson Dennis W. , Buratti Emanuele , Petrucelli Leonard
Published: December 2012

Sortilin 1 regulates the levels of brain progranulin (PGRN), a neurotrophic growth factor that, when deficient, is linked to cases of frontotemporal lobar degeneration with TAR DNA-binding protein-43 (TDP-43)–positive inclusions (FTLD-TDP). We identified a specific splicing enhancer element that regulates the inclusion of a sortilin exon cassette (termed Ex17b) not normally present in the mature sortilin mRNA. This enhancer element is consistently present in sortilin RNA of mice and other species but absent in primates, which carry a premature stop codon within the Ex17b sequence. In the absence of TDP-43, which acts as a regulatory inhibitor, Ex17b is included in the sortilin mRNA. In humans, in contrast to mice, the inclusion of Ex17b in sortilin mRNA generates a truncated, nonfunctional, extracellularly released protein that binds to but does not internalize PGRN, essentially acting as a decoy receptor. Based on these results, we propose a potential mechanism linking misregulation of sortilin splicing with altered PGRN metabolism.
Structural elements in the Girk1 subunit that potentiate G protein–gated potassium channel activity
Authors: Wydeven Nicole , Young Daniele , Mirkovic Kelsey , Wickman Kevin
Published: December 2012

G protein–gated inwardly rectifying K
+
(Girk/K
IR
3) channels mediate the inhibitory effect of many neurotransmitters on excitable cells. Girk channels are tetramers consisting of various combinations of four mammalian Girk subunits (Girk1 to -4). Although Girk1 is unable to form functional homomeric channels, its presence in cardiac and neuronal channel complexes correlates with robust channel activity. This study sought to better understand the potentiating influence of Girk1, using the GABA
B
receptor and Girk1/Girk2 heteromer as a model system. Girk1 did not increase the protein levels or alter the trafficking of Girk2-containing channels to the cell surface in transfected cells or hippocampal neurons, indicating that its potentiating influence involves enhancement of channel activity. Structural elements in both the distal carboxyl-terminal domain and channel core were identified as key determinants of robust channel activity. In the distal carboxyl-terminal domain, residue Q404 was identified as a key determinant of receptor-induced channel activity. In the Girk1 core, three unique residues in the pore (P) loop (F137, A142, Y150) were identified as a collective potentiating influence on both receptor-dependent and receptor-independent channel activity, exerting their influence, at least in part, by enhancing mean open time and single-channel conductance. Interestingly, the potentiating influence of the Girk1 P-loop is tempered by residue F162 in the second membrane-spanning domain. Thus, discontinuous and sometime opposing elements in Girk1 underlie the Girk1-dependent potentiation of receptor-dependent and receptor-independent heteromeric channel activity.
Designing a functional type 2 copper center that has nitrite reductase activity within α-helical coiled coils
Authors: Tegoni Matteo , Yu Fangting , Bersellini Manuela , Penner-Hahn James E. , Pecoraro Vincent L.
Published: December 2012

One of the ultimate objectives of de novo protein design is to realize systems capable of catalyzing redox reactions on substrates. This goal is challenging as redox-active proteins require design considerations for both the reduced and oxidized states of the protein. In this paper, we describe the spectroscopic characterization and catalytic activity of a de novo designed metallopeptide Cu(I/II)(TRIL23H)3+/2+, where Cu(I/II) is embeded in α-helical coiled coils, as a model for the CuT2center of copper nitrite reductase. In Cu(I/II)(TRIL23H)3+/2+, Cu(I) is coordinated to three histidines, as indicated by X-ray absorption data, and Cu(II) to three histidines and one or two water molecules. Both ions are bound in the interior of the three-stranded coiled coils with affinities that range from nano- to micromolar [Cu(II)], and picomolar [Cu(I)]. The Cu(His)3active site is characterized in both oxidation states, revealing similarities to the CuT2site in the natural enzyme. The species Cu(II)(TRIL23H)32+in aqueous solution can be reduced to Cu(I)(TRIL23H)3+using ascorbate, and reoxidized by nitrite with production of nitric oxide. At pH 5.8, with an excess of both the reductant (ascorbate) and the substrate (nitrite), the copper peptide Cu(II)(TRIL23H)32+acts as a catalyst for the reduction of nitrite with at least five turnovers and no loss of catalytic efficiency after 3.7 h. The catalytic activity, which is first order in the concentration of the peptide, also shows a pH dependence that is described and discussed.
Versatile design and synthesis platform for visualizing genomes with Oligopaint FISH probes
Authors: Beliveau Brian J. , Joyce Eric F. , Apostolopoulos Nicholas , Yilmaz Feyza , Fonseka Chamith Y. , McCole Ruth B. , Chang Yiming , Li Jin Billy , Senaratne Tharanga Niroshini , Williams Benjamin R. , Rouillard Jean-Marie , Wu Chao-ting
Published: December 2012

A host of observations demonstrating the relationship between nuclear architecture and processes such as gene expression have led to a number of new technologies for interrogating chromosome positioning. Whereas some of these technologies reconstruct intermolecular interactions, others have enhanced our ability to visualize chromosomes in situ. Here, we describe an oligonucleotide- and PCR-based strategy for fluorescence in situ hybridization (FISH) and a bioinformatic platform that enables this technology to be extended to any organism whose genome has been sequenced. The oligonucleotide probes are renewable, highly efficient, and able to robustly label chromosomes in cell culture, fixed tissues, and metaphase spreads. Our method gives researchers precise control over the sequences they target and allows for single and multicolor imaging of regions ranging from tens of kilobases to megabases with the same basic protocol. We anticipate this technology will lead to an enhanced ability to visualize interphase and metaphase chromosomes.
Structural and biochemical analysis of the assembly and function of the yeast pre-mRNA 3′ end processing complex CF I
Authors: Barnwal Ravi Pratap , Lee Susan D. , Moore Claire , Varani Gabriele
Published: December 2012

The accuracy of the 3′-end processing by cleavage and polyadenylation is essential for mRNA biogenesis and transcription termination. In yeast, two poorly conserved neighboring elements upstream of cleavage sites are important for accuracy and efficiency of this process. These two RNA sequences are recognized by the RNA binding proteins Hrp1 and Rna15, but efficient processing in vivo requires a bridging protein (Rna14), which forms a stable dimer of hetero-dimers with Rna15 to stabilize the RNA–protein complex. We earlier reported the structure of the ternary complex of Rna15 and Hrp1 bound to the RNA processing element. We now report the use of solution NMR to study the interaction of Hrp1 with the Rna14–Rna15 heterodimer in the presence and absence of 3′-end processing signals. By using methyl selective labeling on Hrp1, in vivo activity and pull-down assays, we were able to study this complex of several hundred kDa, identify the interface within Hrp1 responsible for recruitment of Rna14 and validate the functional significance of this interaction through structure-driven mutational analysis.
Unifying model of shoot gravitropism reveals proprioception as a central feature of posture control in plants
Authors: Bastien Renaud , Bohr Tomas , Moulia Bruno , Douady Stéphane
Published: December 2012

Gravitropism, the slow reorientation of plant growth in response to gravity, is a key determinant of the form and posture of land plants. Shoot gravitropism is triggered when statocysts sense the local angle of the growing organ relative to the gravitational field. Lateral transport of the hormone auxin to the lower side is then enhanced, resulting in differential gene expression and cell elongation causing the organ to bend. However, little is known about the dynamics, regulation, and diversity of the entire bending and straightening process. Here, we modeled the bending and straightening of a rod-like organ and compared it with the gravitropism kinematics of different organs from 11 angiosperms. We show that gravitropic straightening shares common traits across species, organs, and orders of magnitude. The minimal dynamic model accounting for these traits is not the widely cited gravisensing law but one that also takes into account the sensing of local curvature, what we describe here as a graviproprioceptive law. In our model, the entire dynamics of the bending/straightening response is described by a single dimensionless “bending number”
B
that reflects the ratio between graviceptive and proprioceptive sensitivities. The parameter
B
defines both the final shape of the organ at equilibrium and the timing of curving and straightening.
B
can be estimated from simple experiments, and the model can then explain most of the diversity observed in experiments. Proprioceptive sensing is thus as important as gravisensing in gravitropic control, and the
B
ratio can be measured as phenotype in genetic studies.
Production of unique immunotoxin cancer therapeutics in algal chloroplasts
Authors: Tran Miller , Van Christina , Barrera Daniel J. , Pettersson Pär L. , Peinado Carlos D. , Bui Jack , Mayfield Stephen P.
Published: December 2012

The idea of targeted therapy, whereby drug or protein molecules are delivered to specific cells, is a compelling approach to treating disease. Immunotoxins are one such targeted therapeutic, consisting of an antibody domain for binding target cells and molecules of a toxin that inhibits the proliferation of the targeted cell. One major hurdle preventing these therapies from reaching the market has been the lack of a suitable production platform that allows the cost-effective production of these highly complex molecules. The chloroplast of the green algaChlamydomonas reinhardtiihas been shown to contain the machinery necessary to fold and assemble complex eukaryotic proteins. However, the translational apparatus of chloroplasts resembles that of a prokaryote, allowing them to accumulate eukaryotic toxins that otherwise would kill a eukaryotic host. Here we show expression and accumulation of monomeric and dimeric immunotoxin proteins in algal chloroplasts. These fusion proteins contain an antibody domain targeting CD22, a B-cell surface epitope, and the enzymatic domain of exotoxin A fromPseudomonas aeruginosa. We demonstrated that algal-produced immunotoxins accumulate as soluble and enzymatically active proteins that bind target B cells and efficiently kill them in vitro. We also show that treatment with either the mono- or dimeric immunotoxins significantly prolongs the survival of mice with implanted human B-cell tumors.
Depopulation of rural landscapes exacerbates fire activity in the western Amazon
Authors: Uriarte María , Pinedo-Vasquez Miquel , DeFries Ruth S. , Fernandes Katia , Gutierrez-Velez Victor , Baethgen Walter E. , Padoch Christine
Published: December 2012

Destructive fires in Amazonia have occurred in the past decade, leading to forest degradation, carbon emissions, impaired air quality, and property damage. Here, we couple climate, geospatial, and province-level census data, with farmer surveys to examine the climatic, demographic, and land use factors associated with fire frequency in the Peruvian Amazon from 2000 to 2010. Although our results corroborate previous findings elsewhere that drought and proximity to roads increase fire frequency, the province-scale analysis further identifies decreases in rural populations as an additional factor. Farmer survey data suggest that increased burn scar frequency and size reflect increased flammability of emptying rural landscapes and reduced capacity to control fire. With rural populations projected to decline, more frequent drought, and expansion of road infrastructure, fire risk is likely to increase in western Amazonia. Damage from fire can be reduced through warning systems that target high-risk locations, coordinated fire fighting efforts, and initiatives that provide options for people to remain in rural landscapes.
Loss of CDKL5 disrupts kinome profile and event-related potentials leading to autistic-like phenotypes in mice
Authors: Wang I-Ting Judy , Allen Megan , Goffin Darren , Zhu Xinjian , Fairless Andrew H. , Brodkin Edward S. , Siegel Steve J. , Marsh Eric D. , Blendy Julie A. , Zhou Zhaolan
Published: December 2012

Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been identified in neurodevelopmental disorders including atypical Rett syndrome (RTT), autism spectrum disorders (ASDs), and early infantile epileptic encephalopathy. The biological function of CDKL5 and its role in the etiology of these disorders, however, remain unclear. Here we report the development of a unique knockout mouse model of CDKL5-related disorders and demonstrate that mice lacking CDKL5 show autistic-like deficits in social interaction, as well as impairments in motor control and fear memory. Neurophysiological recordings reveal alterations in event-related potentials (ERPs) similar to those observed in RTT and ASDs. Moreover, kinome profiling uncovers disruption of multiple signal transduction pathways, including the AKT-mammalian target of rapamycin (mTOR) cascade, uponCdkl5loss-of-function. These data demonstrate that CDKL5 regulates signal transduction pathways and mediates autistic-like phenotypes and together establish a causal role forCdkl5loss-of-function in neurodevelopmental disorders.
English in action: school based teacher development in Bangladesh
Authors: Power Tom , Shaheen Robina , Solly Mike , Woodward Clare , Burton Sonia
Published: December 2012

In the Least Economically Developed Countries (LEDCs), School Based Teacher Development (SBTD) is sometimes advocated as a potential mechanism for improving the classroom practices experienced by millions of children in a complete school system, as quickly as possible. Robust evidence is required for approaches to be implemented with some confidence by Government development agencies, such as the UK Department for International Development (DFID). SBTD has a long history stemming from ideas of school‐based curriculum development, which underlay the ideas on teacher‐as‐researcher, and is typically advocated in the developed world based on a view of the teacher as a professional. How might such notions play out, and to what effect, in LEDC contexts? This article examines the issues at stake in introducing SBTD in LEDCs, by examining: the nature of the evidence for various forms of teacher development, the nature of SBTD in particular and the evidence for its effectiveness. The latter issues will be illustrated through examination of English in Action (EIA, www.eiabd.com), a large‐scale SBTD programme for primary and secondary English language (EL) teachers serving government schools across Bangladesh.
Palatability of Diets for Channel Catfish that Contain Amprolium or Salinomycin Using Feed Conversion Ratio as the Criterion
Authors: Manning Bruce B , Griffin Matthew J , Khoo Lester H , Wise David J , Greenway Terry
Published: December 2012

Two feeding studies were conducted to evaluate the palatability of diets for juvenile Channel Catfish Ictalurus punctatus that contained the poultry anticoccidial drugs Amprolium or Salinomycin, which are candidates to control the Channel Catfish myxozoan parasite, Henneguya ictaluri. These chemotherapeutic drugs can effectively control outbreaks of other myxozoan parasites in various species of aquaculture fish. To evaluate palatability of diets containing these drugs, Channel Catfish maintained in glass aquaria were fed sinking diets composed of commercial catfish feed that had been pulverized and reformed into pellets that contained three levels of each of the two anticoccidial drugs for short periods of time, e.g. 10 d for Amprolium and 8 d for Salinomycin. Results showed that fish readily consumed the basal control diet containing no drug and diets containing all three levels of Amprolium based on comparisons of feed conversion ratios (FCR) for the four dietary treatments. On the other hand, FCR values of the Salinomycin treatments were significantly (P < 0.05) poorer for the two highest inclusion levels (30 and 60 mg/kg diet) of this drug compared with the control diet, which indicated poor palatability of diets containing these levels of Salinomycin by Channel Catfish.
The Sarkisov program
Authors: Hacon Christopher , McKernan James
Published: December 2012

Any two birational Mori fibre spaces are connected by a sequence of Sarkisov links.
First Report on the Occurrence of A2 Mating Type of the Cucurbit Downy Mildew Agent Pseudoperonospora cubensis in China
Authors: Cohen Y. , Rubin A. E. , Liu X. L. , Wang W. Q. , Zhang Y. J. , Hermann D.
Published: December 2012

Pseudoperonospora cubensis is a foliar pathogen of cucurbits. In cucumber, it produces chlorotic, angular lesions with dark sporangia on their under-surface. The distribution of pathotypes and mating types of P. cubensis were investigated in seven provinces in China. Twenty-nine isolates were obtained from Guangdong, Anhui, Hubei, Sichuan, Shandong, Beijing, and Harbin, one to six isolates from each province. They were collected from cucumber during summer 2011, except those from Harbin, which were collected from cucumber in summer 2012. Isolates were tested for pathogenicity and mating type. Pathogenicity was tested by inoculation of detached leaves of: cucumber (Cucumis sativum cvs. Bet-Alpha, SMR18), melon (Cucumis melo reticulatus cv. Ananas-Yokneam), pumpkin (Cucurbita maxima cv. Tripoli), squash (Cucurbita pepo, cv. Beruti), butternut gourd (Cucurbita moschata cv. Waltham), watermelon (Citrullus lanatus, cv. Malali), and sponge gourd (Luffa cylindrica, cultivar unknown). Mating type was determined by oospore production in melon leaf discs inoculated with mixed sporangia of a test isolate and A1 or A2 tester isolates, as recently described (2). The results showed that 22 isolates belonged to pathotype 3, sporulating on cucumber and melon; five isolates belonged to pathotype 6, sporulating on cucumber, melon, pumpkin, squash, and butternut gourd; one isolate belonged to pathotype 5, sporulating on the above five species and watermelon (1), and one isolate was capable of sporulating on the mentioned five species and sponge gourd, herein called pathotype 7. Of the 29 isolates tested, 22 belonged to the A1 mating type, six to the A2 mating type, and one did not produce oospores with either testers. Of the six A2 isolates, two originated from Sichuan, one from Beijing, and three from Harbin. All 22 isolates belonging to pathotype 3 were A1, whereas the other six isolates (four pathotype 6, one pathotype 5, and one pathotype 7) were A2. Crosses made between Chinese isolates belonging to opposite mating types resulted in the formation of abundant oospores in detached melon or cucumber leaves. The results prove that the A2 mating type of P. cubensis occurs in China. This explains the abundant occurrence of oospores of P. cubensis in nature in China (4). The data corroborate with Runge et al. (3), who suggested that the recent changes in the population structure of P. cubensis around the world resulted from the migration of a new genotype of P. cubensis from the Far East to Europe and the U.S.A. In Israel, a new pathotype attacking both Cucumis and Cucurbita appeared in 2002 (1), and A2 mating type first appeared in 2010 (2).

References: (1) Y. Cohen et al. Phytoparasitica 31:458, 2003. (2) Y. Cohen and A. E. Rubin. Eur. J. Plant Pathol. 132:577, 2012. (3) F. Runge et al. Eur. J. Plant Pathol. 129:135, 2011. (4) Y. J. Zhang et al. J. Phytopathol. 160:469, 2012.
First Report of Bacterial Leaf Spot Disease Caused by Pseudomonas syringae pv. syringae on Panax notoginseng
Authors: Zhou L.-H. , Han Y. , Ji G.-H. , Wang Z.-S. , Liu F.
Published: December 2012

Panax notoginseng is a species that produces a rare type of Chinese herbal medicine and is cultivated primarily in Yunnan Province. P. notoginseng has a 3-year-long crop cycle before harvest. A new bacterial disease was observed on P. notoginseng plants in the Wenshan Mountain area of Yunnan in 2012. The disease affected primarily leaves. Symptoms were circular or irregular brown leaf spots, surrounded by a yellow halo, located on the edges of the leaves. Eight creamy white pigmented, rounded strains were isolated consistently from leaf spots on Luria-Bertani agar (LB) medium, incubated at 28°C. Three strains (SQYB-1, SQYB-2, SQYB-3) of eight isolates were prepared for further study. Three isolates were purified and characterized: all were gram-negative, rod-shaped, motile, aerobic, non-spore forming, and negative for oxidase, potato soft rot, arginine dehydrolase, presence of tyrosinase and urease, nitrate, and fluorescent pigment production. Moreover, they were positive for levan production, presence of catalase, and for tobacco hypersensitivity. All three strains isolated were identified as Pseudomonas syringae pv. syringae (Pss) based on morphology, metabolic profile (Biolog Microbial ID System), and 16S rDNA sequence analysis (1). The metabolic similarity index between experiment strain SQYB-1 and a type of strain Pss was 0.619. The primers of 16S rDNA sequence amplification were 27F/1492R. Before sequencing, we cloned the PCR products. There was 99% homology in 16S rDNA sequences between one isolate, SQYB-1 (NCBI Accession No. JX876901) and Pss (HQ840766), supporting the identification of the P. notoginseng strains as Pss (3). For Koch's postulates, 10 surface-disinfected young leaves on three plants were inoculated with SQYB-1 isolates by spraying a phosphate-buffered saline cell suspension (3.0 × 108 CFU/ml) onto the leaves (4). Controls were inoculated similarly with sterile phosphate-buffered saline. Plants were covered with polyethylene bags for 24 h at 25°C and then transferred to a greenhouse. Circular or irregular brown spots were observed on all bacteria-inoculated leaves within 9 to 14 days after inoculation. No symptoms were observed on controls. Bacteria reisolated from inoculated leaves were identical to the original isolates as determined by the methods described above. The present study indicated that isolate SQYB-1 could independently infect P. notoginseng leaves, which was different from the finding of Luo et al. concerning involvement of Pss in root rot (2). To our knowledge, this is the first report of Pseudomonas syringae pv. syringae causing bacterial leaf spot on P. notoginseng in China.

References: (1) M. R. Gillings et al. PNAS 12:102, 2005. (2) W. F. Luo et al. J. Yunnan Agric. Univ. 14:123, 1999 (in Chinese). (3) C. L. Oliver et al. Plant Dis. 4:96, 2012. (4) H. Ornek et al. New Dis. Rep. 13:40, 2006.
Dominance is not always an honest signal of male quality, but females may be able to detect the dishonesty
Authors: Pölkki Mari , Kortet Raine , Hedrick Ann , Rantala Markus J.
Published: December 2012

Females prefer dominant males as mating partners in numerous species. Male dominance rank is considered as an honest signal of male quality, because only healthy males in good condition are thought to be able to win fights with other males. Here, we tested whether activation of the immune system influences the success of males in male–male competition and mating in the field cricket,
Gryllus integer
. We activated the immune system of males with a nylon monofilament (to mimic a parasitoid larva), and arranged fights between male pairs to assess male dominance and associated mating success. Activation of the immune system with nylon monofilament substantially enhanced the fighting success of males during male–male competition but had no effect on mating success. However, sham-manipulation (a wound only) did not have any effect on fighting success although females mated more often with dominant males. Our study suggests that when male crickets meet an apparent survival threat they may behave more dominantly, probably owing to terminal investment. Male success during male–male competition is not always an honest signal of males’ quality, but females may be able to detect this dishonesty.
Behavioural plasticity of social trematodes depends upon social context
Authors: Kamiya T. , Poulin R.
Published: December 2012

Members of some social insects adjust their behaviours depending upon social context. Such plasticity allows colonies to sustain efficiency of the whole without the cost of additional production of individuals or delayed responses to perturbations. Using the recently discovered social clonal stage of trematode parasites, we investigated whether members of the reproductive caste adjust their defensive behaviour according to the local availability of non-reproductive defensive specialists, and if so whether the plasticity affects the short-term reproductive success of reproductive morphs.
In vitro
experiments demonstrated plasticity in competitive interactions of the reproductive morphs depending on the number of non-reproductive defensive specialists present nearby, which lead to differences in reproductive output at the individual level. This study provides support for the benefit of maintaining non-reproductive morphs in competitive situations, arising through socially mediated behavioural plasticity.
Similarity between class A and class B G-protein-coupled receptors exemplified through calcitonin gene-related peptide receptor modelling and mutagenesis studies
Authors: Vohra Shabana , Taddese Bruck , Conner Alex C. , Poyner David R. , Hay Debbie L. , Barwell James , Reeves Philip J. , Upton Graham J. G. , Reynolds Christopher A.
Published: December 2012

Modelling class B G-protein-coupled receptors (GPCRs) using class A GPCR structural templates is difficult due to lack of homology. The plant GPCR, GCR1, has homology to both class A and class B GPCRs. We have used this to generate a class A–class B alignment, and by incorporating maximum lagged correlation of entropy and hydrophobicity into a consensus score, we have been able to align receptor transmembrane regions. We have applied this analysis to generate active and inactive homology models of the class B calcitonin gene-related peptide (CGRP) receptor, and have supported it with site-directed mutagenesis data using 122 CGRP receptor residues and 144 published mutagenesis results on other class B GPCRs. The variation of sequence variability with structure, the analysis of polarity violations, the alignment of group-conserved residues and the mutagenesis results at 27 key positions were particularly informative in distinguishing between the proposed and plausible alternative alignments. Furthermore, we have been able to associate the key molecular features of the class B GPCR signalling machinery with their class A counterparts for the first time. These include the [K/R]KLH motif in intracellular loop 1, [I/L]xxxL and KxxK at the intracellular end of TM5 and TM6, the NPXXY/VAVLY motif on TM7 and small group-conserved residues in TM1, TM2, TM3 and TM7. The equivalent of the class A DRY motif is proposed to involve Arg
2.39
, His
2.43
and Glu
3.46
, which makes a polar lock with T
6.37
. These alignments and models provide useful tools for understanding class B GPCR function.
Quantification of the effects of antibodies on the extra- and intracellular dynamics of
Salmonella enterica
Authors: Restif Olivier , Goh Yun S. , Palayret Matthieu , Grant Andrew J. , McKinley Trevelyan J. , Clark Michael R. , Mastroeni Pietro
Published: December 2012

Antibodies are known to be essential in controlling
Salmonella
infection, but their exact role remains elusive. We recently developed an
in vitro
model to investigate the relative efficiency of four different human immunoglobulin G (IgG) subclasses in modulating the interaction of the bacteria with human phagocytes. Our results indicated that different IgG subclasses affect the efficacy of
Salmonella
uptake by human phagocytes. In this study, we aim to quantify the effects of IgG on intracellular dynamics of infection by combining distributions of bacterial numbers per phagocyte observed by fluorescence microscopy with a mathematical model that simulates the
in vitro
dynamics. We then use maximum likelihood to estimate the model parameters and compare them across IgG subclasses. The analysis reveals heterogeneity in the division rates of the bacteria, strongly suggesting that a subpopulation of intracellular
Salmonella
, while visible under the microscope, is not dividing. Clear differences in the observed distributions among the four IgG subclasses are best explained by variations in phagocytosis and intracellular dynamics. We propose and compare potential factors affecting the replication and death of bacteria within phagocytes, and we discuss these results in the light of recent findings on dormancy of
Salmonella
.
The algorithmic origins of life
Authors: Walker Sara Imari , Davies Paul C. W.
Published: December 2012

Although it has been notoriously difficult to pin down precisely what is it that makes life so distinctive and remarkable, there is general agreement that its informational aspect is one key property, perhaps the key property. The unique informational narrative of living systems suggests that life may be characterized by context-dependent causal influences, and, in particular, that top-down (or downward) causation—where higher levels influence and constrain the dynamics of lower levels in organizational hierarchies—may be a major contributor to the hierarchal structure of living systems. Here, we propose that the emergence of life may correspond to a physical transition associated with a shift in the causal structure, where information gains direct and context-dependent causal efficacy over the matter in which it is instantiated. Such a transition may be akin to more traditional physical transitions (e.g. thermodynamic phase transitions), with the crucial distinction that determining which phase (non-life or life) a given system is in requires dynamical information and therefore can only be inferred by identifying causal architecture. We discuss some novel research directions based on this hypothesis, including potential measures of such a transition that may be amenable to laboratory study, and how the proposed mechanism corresponds to the onset of the unique mode of (algorithmic) information processing characteristic of living systems.
Stationary states of identical point vortices and vortex foam on the sphere
Authors: O'Neil Kevin A.
Published: December 2012

Stationary configurations of identical point vortices on the sphere are investigated using a simple numerical scheme. Configurations in which the vortices are arrayed along curves on the sphere are exhibited, which approximate equilibrium configurations of vortex sheets on the sphere. Other configurations (found after starting from random initial conditions) exhibit net-like distributions of vorticity, dividing the sphere into many cells that contain no vorticity or diffuse vorticity and forming a stationary ‘vortex foam’ on the sphere. They may be viewed as intermediate-energy elements in the set of all identical point vortex equilibria on the sphere. In the continuum limit, these foam states may correspond to stationary states of multiple intersecting vortex sheets. Stationary configurations of point vortices are not found to have this character when vortices of opposite circulations are included.
Introgression of wing pattern alleles and speciation via homoploid hybridization inHeliconiusbutterflies: a review of evidence from the genome
Authors: Brower Andrew V. Z.
Published: December 2012

The diverse Müllerian mimetic wing patterns of neotropicalHeliconius(Nymphalidae) have been proposed to be not only aposematic signals to potential predators, but also intra- and interspecific recognition signals that allow the butterflies to maintain their specific identities, and which perhaps drive the process of speciation, as well. Adaptive features under differential selection that also serve as cues for assortative mating have been referred to as ‘magic traits’, which can drive ecological speciation. Such traits are expected to exhibit allelic differentiation between closely related species with ongoing gene flow, whereas unlinked neutral traits are expected to be homogenized to a greater degree by introgression. However, recent evidence suggests that interspecific hybridization amongHeliconiusbutterflies may have resulted in adaptive introgression of these very same traits across species boundaries, and in the evolution of new species by homoploid hybrid speciation. The theory and data supporting various aspects of the apparent paradox of ‘magic trait’ introgression are reviewed, with emphasis on population genomic comparisons ofHeliconius melpomeneand its close relatives.
A Silurian myodocope with preserved soft-parts: cautioning the interpretation of the shell-based ostracod record
Authors: Siveter David J. , Briggs Derek E. G. , Siveter Derek J. , Sutton Mark D. , Joomun Sarah C.
Published: December 2012

Ostracod crustaceans are the most abundant fossil arthropods. The SilurianPauline avibellagen. et sp. nov., from the Herefordshire Lagerstätte, UK, is an extremely rare Palaeozoic example with soft-part preservation. Based on its soft-part morphology, especially the exceptionally preserved limbs and presence of lateral eyes, it is assigned to the myodocopid myodocopes. The ostracod is very large, with an epipod on the fifth limb pair, as well as gills implying the presence of a heart and an integrated respiratory–circulatory system as in living cylindroleberidid myodocopids. Features of its shell morphology, however, recall halocyprid myodocopes and palaeocopes, encouraging caution in classifying ostracods based on the carapace alone and querying the interpretation of their shell-based fossil record, especially for the Palaeozoic, where some 500 genera are presently assigned to the Palaeocopida.