bluuebunny/crossref_metadata_2025 huggingface dataset:
Academic cross-fertilization by public screening yields a remarkable class of protein phosphatase methylesterase-1 inhibitors
Authors: Bachovchin Daniel A. , Mohr Justin T. , Speers Anna E. , Wang Chu , Berlin Jacob M. , Spicer Timothy P. , Fernandez-Vega Virneliz , Chase Peter , Hodder Peter S. , Schürer Stephan C. , Nomura Daniel K. , Rosen Hugh , Fu Gregory C. , Cravatt Benjamin F.
Published: March 2011

National Institutes of Health (NIH)-sponsored screening centers provide academic researchers with a special opportunity to pursue small-molecule probes for protein targets that are outside the current interest of, or beyond the standard technologies employed by, the pharmaceutical industry. Here, we describe the outcome of an inhibitor screen for one such target, the enzyme protein phosphatase methylesterase-1 (PME-1), which regulates the methylesterification state of protein phosphatase 2A (PP2A) and is implicated in cancer and neurodegeneration. Inhibitors of PME-1 have not yet been described, which we attribute, at least in part, to a dearth of substrate assays compatible with high-throughput screening. We show that PME-1 is assayable by fluorescence polarization-activity-based protein profiling (fluopol-ABPP) and use this platform to screen the 300,000+ member NIH small-molecule library. This screen identified an unusual class of compounds, the aza-β-lactams (ABLs), as potent (IC
50
values of approximately 10 nM), covalent PME-1 inhibitors. Interestingly, ABLs did not derive from a commercial vendor but rather an academic contribution to the public library. We show using competitive-ABPP that ABLs are exquisitely selective for PME-1 in living cells and mice, where enzyme inactivation leads to substantial reductions in demethylated PP2A. In summary, we have combined advanced synthetic and chemoproteomic methods to discover a class of ABL inhibitors that can be used to selectively perturb PME-1 activity in diverse biological systems. More generally, these results illustrate how public screening centers can serve as hubs to create spontaneous collaborative opportunities between synthetic chemistry and chemical biology labs interested in creating first-in-class pharmacological probes for challenging protein targets.
On the earliest evidence for habitual use of fire in Europe
Authors: Roebroeks Wil , Villa Paola
Published: March 2011

The timing of the human control of fire is a hotly debated issue, with claims for regular fire use by early hominins in Africa at ∼1.6 million y ago. These claims are not uncontested, but most archaeologists would agree that the colonization of areas outside Africa, especially of regions such as Europe where temperatures at time dropped below freezing, was indeed tied to the use of fire. Our review of the European evidence suggests that early hominins moved into northern latitudes
without
the habitual use of fire. It was only much later, from ∼300,000 to 400,000 y ago onward, that fire became a significant part of the hominin technological repertoire. It is also from the second half of the Middle Pleistocene onward that we can observe spectacular cases of Neandertal pyrotechnological knowledge in the production of hafting materials. The increase in the number of sites with good evidence of fire throughout the Late Pleistocene shows that European Neandertals had fire management not unlike that documented for Upper Paleolithic groups.
Structure of a
Plasmodium falciparum
PfEMP1 rosetting domain reveals a role for the N-terminal segment in heparin-mediated rosette inhibition
Authors: Juillerat Alexandre , Lewit-Bentley Anita , Guillotte Micheline , Gangnard Stéphane , Hessel Audrey , Baron Bruno , Vigan-Womas Inès , England Patrick , Mercereau-Puijalon Odile , Bentley Graham A.
Published: March 2011

The human malaria parasite
Plasmodium falciparum
can cause infected red blood cells (iRBC) to form rosettes with uninfected RBC, a phenotype associated with severe malaria. Rosetting is mediated by a subset of the
Plasmodium falciparum
membrane protein 1 (PfEMP1) variant adhesins expressed on the infected host-cell surface. Heparin and other sulfated oligosaccharides, however, can disrupt rosettes, suggesting that therapeutic approaches to this form of severe malaria are feasible. We present a structural and functional study of the N-terminal domain of PfEMP1 from the VarO variant comprising the N-terminal segment (NTS) and the first DBL domain (DBL1
α
1
), which is directly implicated in rosetting. We demonstrate that NTS-DBL1
α
1
-VarO binds to RBC and that heparin inhibits this interaction in a dose-dependent manner, thus mimicking heparin-mediated rosette disruption. We have determined the crystal structure of NTS-DBL1
α
1
, showing that NTS, previously thought to be a structurally independent component of PfEMP1, forms an integral part of the DBL1α domain. Using mutagenesis and docking studies, we have located the heparin-binding site, which includes NTS. NTS, unique to the DBL α-class domain, is thus an intrinsic structural and functional component of the N-terminal VarO domain. The specific interaction observed with heparin opens the way for developing antirosetting therapeutic strategies.
Creoles are typologically distinct from non-creoles
Authors: Bakker Peter , Daval-Markussen Aymeric , Parkvall Mikael , Plag Ingo
Published: March 2011

In creolist circles, there has been a a long-standing debate whether creoles differ structurally from non-creole languages and thus
would form a special class of languages with specific typological properties. This debate about the typological status of creole
languages has severely suffered from a lack of systematic empirical study. This paper presents for the first time a number of
large-scale empirical investigations of the status of creole languages as a typological class on the basis of different and
well-balanced samples of creole and non-creole languages. Using statistical modeling (multiple regression) and recently developed
computational tools of quantitative typology (phylogenetic trees and networks), this paper provides robust evidence that creoles
indeed form a structurally distinguishable subgroup within the world’s languages. The findings thus seriously challenge approaches
that hold that creole languages are structurally indistinguishable from non-creole languages.
The Gulf of Guinea Creoles
Authors: Hagemeijer Tjerk
Published: March 2011

Especially since Ferraz (1974, 1975, 1979), it has been generally accepted that the four Gulf of Guinea creoles (GGCs) — Santome (ST), Angolar (ANG), Lung’ie (LU), and Fa d’Ambô (FA)2 — are closely related languages based on historical and linguistic data. Ferraz shares his view on the type of genetic relation between these creoles in the following quote:

To take the GG [Gulf of Guinea] case, it would not be plausible to assume that the contact language which developed in the town of São Tomé and the surrounding areas was the same as that which gave rise to Ang[olar], Pr[incipense], and Pag[alu]4. There are enough differences between each of these languages to rule out such a possibility. It would be closer to the truth to say that the four contact languages show many resemblances because, to a large extent, they grew up together, with slaves and settlers introduced through the central administration in São Tomé. (…). Hence different languages developed in the archipelago rather than dialects of one contact language. (Ferraz 1987: 348)

This paper will reassess the linguistic relation between the GGCs and the typological contribution of the African strata. It will be argued that there is substantial linguistic evidence that the GGCs are to a significant extent the result of a common ancestor, which throughout the paper will be labelled the proto-Gulf of Guinea creole (proto-GGC), and that this common ancestor derived most of its features from its Nigerian substrate rather than from western Bantu.
Typology of creole phonology
Authors: Klein Thomas B.
Published: March 2011

This paper reports on the analysis of a typological database of creole phoneme inventories and surface syllables. The sample encompasses a balanced set of creole languages lexified by Indo-European and non-Indo-European languages. The results of the analysis demonstrate that most creole languages exhibit between twenty and thirty-seven contrastive segments, between five and seven phonemic vowel qualities, and between two and three stop series. No creoles show only CV, and many display CCVC surface syllables. These features are quite unremarkable in comparison with non-creole languages around the world, but they represent significant evidence against claims that the structure of creole languages is especially simple. Instead, creole languages cluster in the typological middle.
Similarities among the shapes of writing and their effects on learning
Authors: Treiman Rebecca , Kessler Brett
Published: March 2011

Writing systems are usually studied in terms of the level of language that they represent, with little attention to the shapes that are used to do so. Those shapes are not random or accidental, however. They tend to be similar to one another within a script. Many of the Latin letters have a roughly vertical stem or hasta with an appendage or coda to the right. This arrangement is more common than one with the coda on the left of the hasta. We present data to show that young children are generally better at copying and writing from memory shapes such as  and , which have the typical arrangement with the coda on the right, than those such as  and , which do not. The results suggest that children start to learn about the statistics of the letter shapes before they know how or that these shapes represent language. Keywords: letter shapes; letters; statistical learning; Latin alphabet; reversal; left-right orientation; directionality; hasta-coda-structure
The significance of the morphographic principle for the classification of writing systems
Authors: Joyce Terry
Published: March 2011

The significance of the morphographic principle – by which the orthographic units of a writing system primarily represent morphemes – has been seriously undervalued within the study and classification of writing systems in general and in comprehending kanji within the Japanese writing system in particular. This paper argues for a re-evaluation of the importance of the morphographic principle and suggests that the shift in focus that comes with fully acknowledging that the term morphographic is more precise than the widely (mis)used term logographic has profound consequences for how we think about writing systems and writing, as well as for the kinds of questions that we ask about the nature and organization of the mental lexicon in literate language users. Keywords: morphographic principle; logographic; writing system classification; Japanese writing system; kanji; psycholinguistics; mental lexicon
A tone orthography typology
Authors: Roberts David
Published: March 2011

Discussions about tone orthography have long been hampered by imprecise terminology. This article aims to bring clarity by means of an explicit typology composed of six parameters. Each parameter is defined by a choice: domain, target, symbol, position, density, and depth. The orthographer assesses each typological aspect individually, while always bearing in mind that the six parameters together generate a complex matrix of responses. The result is a precise and informative character profile for any Roman script tone orthography. Keywords: typology; tone; orthography; orthographic depth
Measuring graphematic transparency
Authors: Neef Martin , Balestra Miriam
Published: March 2011

In this article, a quantitative method to calculate the graphematic transparency of an alphabetic writing system is suggested. Graphematic transparency is a part of the traditional concept of orthographic depth, dealing with the direction from written representation to phonological representation only. Based on a thorough analysis of German graphematics given in Neef (2005a) and a tentative analysis of Italian graphematics, the respective gt-values are calculated in a constant theoretical framework. As expected, the gt-value for Italian is lower than that for German. For assessing the relevance of these calculated gt-values, further analyses of other writing systems are necessary. Keywords: orthographic depth; graphematic transparency; graphematics; typology; correspondence rule; phonological filter; geminate; German; Italian
The bone marrow stem cell niche grows up: mesenchymal stem cells and macrophages move in
Authors: Ehninger Armin , Trumpp Andreas
Published: March 2011

Stem cell niches are defined as the cellular and molecular microenvironments that regulate stem cell function together with stem cell autonomous mechanisms. This includes control of the balance between quiescence, self-renewal, and differentiation, as well as the engagement of specific programs in response to stress. In mammals, the best understood niche is that harboring bone marrow hematopoietic stem cells (HSCs). Recent studies have expanded the number of cell types contributing to the HSC niche. Perivascular mesenchymal stem cells and macrophages now join the previously identified sinusoidal endothelial cells, sympathetic nerve fibers, and cells of the osteoblastic lineage to form similar, but distinct, niches that harbor dormant and self-renewing HSCs during homeostasis and mediate stem cell mobilization in response to granulocyte colony-stimulating factor.
Stability of localized modes in rotating tokamak plasmas
Authors: Haverkort J W , de Blank H J
Published: March 2011

The ideal magnetohydrodynamic stability is investigated of localized interchange modes in a large-aspect ratio tokamak plasma. The resulting stability criterion includes the effects of toroidal rotation and rotation shear and contains various well-known limiting cases. The analysis allows for a general adiabatic index, resulting in a stabilizing contribution from the convective effect. A further stabilizing effect from rotation exists when the angular frequency squared decreases radially more rapidly than the density. Flow shear, however, also decreases the stabilizing effect of magnetic shear through the Kelvin–Helmholtz mechanism. Numerical simulations reveal the merits and limitations of the performed local analysis.
A force measurement system based on an electrostatic sensing and actuating technique for calibrating force in a micronewton range with a resolution of nanonewton scale
Authors: Chen Sheng-Jui , Pan Sheau-Shi
Published: March 2011

This paper introduces a force measurement system recently established at the Center for Measurement Standards, Industrial Technology Research Institute for calibrating forces in a micronewton range with a resolution of a few nanonewtons. The force balance consists of a monolithic flexure stage and a specially made capacitor for electrostatic sensing and actuating. The capacitor is formed by three electrodes which can be utilized as a capacitive position sensor and an electrostatic force actuator at the same time. Force balance control is implemented with a digital controller by which the signal of the stage deflection is acquired, filtered and fed back to the electrostatic force driver to bring the flexure stage to the null position. The detailed description of the apparatus including the design of a monolithic flexure stage, principle of capacitive position sensing/electrostatic actuation and the force balance control is given in the paper. Finally, we present the results of electrostatic force calibration and the weighing of a 1 mg wire weight.
Erratum to “Infinite finitely generated fields are biinterpretable with ℕ”
Authors: Scanlon Thomas
Published: March 2011

There is a serious error in the valuation recovery argument in the paper Infinite finitely generated fields are biinterpretable with

N

{\mathbb N}

. Consequently, Pop’s Conjecture that elementarily equivalent finitely generated fields are isomorphic remains open.
First Record of Phytophthora nicotianae Causing Leaf Blight on Rhododendron in Greece
Authors: Tsopelas P. , Paplomatas E. J. , Tjamos S. E. , Elena K.
Published: March 2011

Species of Rhododendron and resulting hybrids are very important hosts of the quarantine pathogen Phytophthora ramorum, since they play a major role in the spread of the pathogen in Europe. However, many other Phytophthora species infect these hosts, causing similar symptoms. Widmer (4) listed 17 Phytophthora species as foliar pathogens of rhododendron in the United States. A survey was conducted in Greece in October 2009, in which potted plants of Rhododendron spp. were inspected for symptoms of necrotic lesions on leaves and buds caused by P. ramorum. Symptomatic plants were observed in one of the nurseries inspected in the Triphylia Region in southwestern Peloponnese. Isolations from symptomatic leaves on PARBhy-V8 selective agar medium (1) yielded Phytophthora isolates. Colonies on V8 juice agar appeared white and cottony, with a radial growth of 4.2 to 4.6 mm per day at 28°C with a maximum growth temperature of 36°C. Sporangia were produced abundantly on the medium surface and in water; the sporangia were broadly ovoid and papillate and 35 to 50 × 25 to 35 μm. Chlamydospores, 25 to 40 μm in diameter, were observed in 2-week-old cultures, while no sexual structures were observed. Three of the isolates examined were identified as P. nicotianae B. de Haan on the basis of morphological and physiological features (3,4). Genomic DNA was extracted from pure cultures of an isolate and the internal transcribed spacer (ITS) region was amplified using the ITS4/5 primer pair. Sequence analyses by BLAST indicated that the isolates were most similar to P. nicotianae (GenBank Accession No. AJ 854295.1) with sequence identity values of 99%. One of the isolates was deposited in the culture collection of the University of Athens (ATHUM 6519). Detached wounded leaves of Rhododendron hybrid cv. Red Jack were inoculated with agar plugs. Necrotic lesions, similar to those observed in the nursery, appeared on the inoculated leaves after 7 days of incubation at 26°C, while no symptoms developed on control leaves inoculated with sterile agar plugs. The pathogen was consistently reisolated from infected leaves, but not from the controls. P. nicotianae, being a thermophilic species, is the most common Phytophthora species in Greece, reported on more than 30 plant species (2). This pathogen has been reported on Rhododendron spp. in the United States (3,4), but to our knowledge, there was no record of this pathogen on these hosts as yet in Europe and this is the first published report of the pathogen on Rhododendron in Greece.

References: (1) A. Belisario et al. Plant Dis. 87:101, 2003. (2) K. Elena. Technical Bulletin No 13. Benaki Phytopathological Institute. Athens, Greece (in Greek), 1999. (3) D. C. Erwin and O. K. Ribeiro. Phytophthora Diseases Worldwide. The American Phytopathological Society, St. Paul, MN, 1996. (4) T. L. Widmer. Online publication. doi: 10.1094/PHP-2010-0317-01-RS, Plant Health Progress, 2010.
Penetration and Establishment of Phakopsora pachyrhizi in Soybean Leaves as Observed by Transmission Electron Microscopy
Authors: Edwards H. H. , Bonde M. R.
Published: March 2011

For over 30 years, it has been known that Phakopsora pachyrhizi is unusual in that it penetrates from urediniospores directly through the leaf cuticle without entering stomates. This unusual mode of penetration suggests that disease resistance mechanisms might exist for soybean rust that do not exist for most rust diseases. As a result, we decided to conduct a histological study using transmission electron microscopy to further elucidate the mechanisms of penetration and early establishment of P. pachyrhizi in soybean leaves. Based on our study, it was concluded that P. pachyrhizi utilizes primarily mechanical force, perhaps with the aid of digestive enzymes, to penetrate the cuticle on the leaf surface. However, the lack of deformation lines in micrographs indicated that digestive enzymes, without mechanical force, are used by the penetration hypha to penetrate the outer and inner epidermal cell walls. Digestive enzymes, again indicated by the lack of deformation lines, are used by haustorial mother cells to breach the walls of mesophyll cells to form haustoria. The possibility exists for eventual determination of the precise roles of pressure and digestive enzymes in the development of soybean rust and elucidation of some of the determinants of resistance and susceptibility to this important plant disease.
From three-dimensional weavings to swollen corneocytes
Authors: Evans Myfanwy E. , Hyde Stephen T.
Published: March 2011

A novel technique to generate three-dimensional Euclidean weavings, composed of close-packed, periodic arrays of one-dimensional fibres, is described. Some of these weavings are shown to dilate by simple shape changes of the constituent fibres (such as fibre straightening). The free volume within a chiral cubic example of a dilatant weaving, the ideal conformation of the
G
129
weaving related to the
Σ
+
rod packing, expands more than fivefold on filament straightening. This remarkable three-dimensional weaving, therefore, allows an unprecedented variation of packing density without loss of structural rigidity and is an attractive design target for materials. We propose that the
G
129
weaving (ideal
Σ
+
weaving) is formed by keratin fibres in the outermost layer of mammalian skin, probably templated by a folded membrane.
Clinical and experimental advances in congenital and paediatric cataracts
Authors: Churchill Amanda , Graw Jochen
Published: March 2011

Cataracts (opacities of the lens) are frequent in the elderly, but rare in paediatric practice. Congenital cataracts (in industrialized countries) are mainly caused by mutations affecting lens development. Much of our knowledge about the underlying mechanisms of cataractogenesis has come from the genetic analysis of affected families: there are contributions from genes coding for transcription factors (such as FoxE3, Maf, Pitx3) and structural proteins such as crystallins or connexins. In addition, there are contributions from enzymes affecting sugar pathways (particularly the galactose pathway) and from a quite unexpected area: axon guidance molecules like ephrins and their receptors. Cataractous mouse lenses can be identified easily by visual inspection, and a remarkable number of mutant lines have now been characterized. Generally, most of the mouse mutants show a similar phenotype to their human counterparts; however, there are some remarkable differences. It should be noted that many mutations affect genes that are expressed not only in the lens, but also in tissues and organs outside the eye. There is increasing evidence for pleiotropic effects of these genes, and increasing consideration that cataracts may act as early and readily detectable biomarkers for a number of systemic syndromes.
Vitreoretinal influences on lens function and cataract
Authors: Beebe David C. , Holekamp Nancy M. , Siegfried Carla , Shui Ying-Bo
Published: March 2011

The lens is composed of a thin metabolically active outer layer, consisting of epithelial and superficial fibre cells. Lying within this outer shell are terminally differentiated, metabolically inactive fibre cells, which are divided into an outer cortex and central nucleus. Mature fibre cells contain a very high protein concentration, which is important for the transparency and refractive power of the lens. These proteins are protected from oxidation by reducing substances, like glutathione, and by the low-oxygen environment around the lens. Glutathione reaches the mature fibre cells by diffusing from the metabolically active cells at the lens surface. With age, the cytoplasm of the nucleus becomes stiffer, reducing the rate of diffusion and making nuclear proteins more susceptible to oxidation. Low pO2is maintained at the posterior surface of the lens by the physical and physiological properties of the vitreous body, the gel filling the space between the lens and the retina. Destruction or degeneration of the vitreous body increases exposure of the lens to oxygen from the retina. Oxygen reaches the lens nucleus, increasing protein oxidation and aggregation and leading to nuclear cataract. We suggest that maintaining low pO2around the lens should prevent the formation of nuclear cataracts.
The ageing lens and cataract: a model of normal and pathological ageing
Authors: Michael R. , Bron A. J.
Published: March 2011

Cataract is a visible opacity in the lens substance, which, when located on the visual axis, leads to visual loss. Age-related cataract is a cause of blindness on a global scale involving genetic and environmental influences. With ageing, lens proteins undergo non-enzymatic, post-translational modification and the accumulation of fluorescent chromophores, increasing susceptibility to oxidation and cross-linking and increased light-scatter. Because the human lens grows throughout life, the lens core is exposed for a longer period to such influences and the risk of oxidative damage increases in the fourth decade when a barrier to the transport of glutathione forms around the lens nucleus. Consequently, as the lens ages, its transparency falls and the nucleus becomes more rigid, resisting the change in shape necessary for accommodation. This is the basis of presbyopia. In some individuals, the steady accumulation of chromophores and complex, insoluble crystallin aggregates in the lens nucleus leads to the formation of a brown nuclear cataract. The process is homogeneous and the affected lens fibres retain their gross morphology. Cortical opacities are due to changes in membrane permeability and enzyme function and shear-stress damage to lens fibres with continued accommodative effort. Unlike nuclear cataract, progression is intermittent, stepwise and non-uniform.
Lens fibre cell differentiation and organelle loss: many paths lead to clarity
Authors: Wride Michael A.
Published: March 2011

The programmed removal of organelles from differentiating lens fibre cells contributes towards lens transparency through formation of an organelle-free zone (OFZ). Disruptions in OFZ formation are accompanied by the persistence of organelles in lens fibre cells and can contribute towards cataract. A great deal of work has gone into elucidating the nature of the mechanisms and signalling pathways involved. It is apparent that multiple, parallel and redundant pathways are involved in this process and that these pathways form interacting networks. Furthermore, it is possible that the pathways can functionally compensate for each other, for example in mouse knockout studies. This makes sense given the importance of lens clarity in an evolutionary context. Apoptosis signalling and proteolytic pathways have been implicated in both lens fibre cell differentiation and organelle loss, including the Bcl-2 and inhibitor of apoptosis families, tumour necrosis factors, p53 and its regulators (such as Mdm2) and proteolytic enzymes, including caspases, cathepsins, calpains and the ubiquitin–proteasome pathway. Ongoing approaches being used to dissect the molecular pathways involved, such as transgenics, lens-specific gene deletion and zebrafish mutants, are discussed here. Finally, some of the remaining unresolved issues and potential areas for future studies are highlighted.
Understanding the role of growth factors in embryonic development: insights from the lens
Authors: Lovicu F. J. , McAvoy J. W. , de Iongh R. U.
Published: March 2011

Growth factors play key roles in influencing cell fate and behaviour during development. The epithelial cells and fibre cells that arise from the lens vesicle during lens morphogenesis are bathed by aqueous and vitreous, respectively. Vitreous has been shown to generate a high level of fibroblast growth factor (FGF) signalling that is required for secondary lens fibre differentiation. However, studies also show that FGF signalling is not sufficient and roles have been identified for transforming growth factor-β and Wnt/Frizzled families in regulating aspects of fibre differentiation. In the case of the epithelium, key roles for Wnt/β-catenin and Notch signalling have been demonstrated in embryonic development, but it is not known if other factors are required for its formation and maintenance. This review provides an overview of current knowledge about growth factor regulation of differentiation and maintenance of lens cells. It also highlights areas that warrant future study.
The lens as a model for fibrotic disease
Authors: Eldred J. A. , Dawes L. J. , Wormstone I. M.
Published: March 2011

Fibrosis affects multiple organs and is associated with hyperproliferation, cell transdifferentiation, matrix modification and contraction. It is therefore essential to discover the key drivers of fibrotic events, which in turn will facilitate the development of appropriate therapeutic strategies. The lens is an elegant experimental model to study the processes that give rise to fibrosis. The molecular and cellular organization of the lens is well defined and consequently modifications associated with fibrosis can be clearly assessed. Moreover, the avascular and non-innervated properties of the lens allow effectivein vitrostudies to be employed that complementin vivosystems and relate to clinical data. Using the lens as a model for fibrosis has direct relevance to millions affected by lens disorders, but also serves as a valuable experimental tool to understand fibrosisper se.
Sphaerochaeta globosa gen. nov., sp. nov. and Sphaerochaeta pleomorpha sp. nov., free-living, spherical spirochaetes
Authors: Ritalahti Kirsti M. , Justicia-Leon Shandra D. , Cusick Kathleen D. , Ramos-Hernandez Natalia , Rubin Michael , Dornbush Jessica , Löffler Frank E.
Published: March 2011

Free-living bacteria with spherical cells 0.5–2.5 µm in diameter were isolated from freshwater sediment. 16S rRNA gene sequence analysis placed the new isolates within the phylumSpirochaetes(‘spirochaetes’). The isolates never displayed a helical morphology or motility. Growth occurred in the presence of 100 mg ampicillin l−1in complex and defined mineral salts medium amended with vitamins, yeast extract and monosaccharides, disaccharides or soluble starch as fermentable substrates. Two distinct isolates, designated BuddyTand GrapesT, exhibited doubling times of 21±2 and 15±1 h in glucose-amended medium and grew at 15–37 and 15–30 °C. Optimum growth was observed between 25 and 30 °C and pH 6.5–7.5, with no growth below pH 5 or above pH 10. Hexose and pentose fermentation yielded ethanol, acetate and formate as major end products. Growth was strictly fermentative and anaerobic, but the isolates tolerated brief oxygen exposure. Nitrate, sulfate, thiosulfate and carbon dioxide were not used as electron acceptors, but soluble Fe(III) was reduced to Fe(II) in glucose-amended medium. The DNA G+C base contents of isolates BuddyTand GrapesTwere 45.5–46.4 and 47.0–49.2 mol%, respectively. Phospholipid fatty acid (PLFA) profiles contained large proportions of C14 : 0and C16 : 0straight-chain saturated fatty acids; C16 : 1ω7cand C16 : 1ω9cdominated the mono-unsaturated PLFAs in isolate GrapesT, whereas isolate BuddyTalso possessed C18 : 1ω5c, C18 : 1ω7cand C18 : 1ω9cfatty acids. Branched monoenoic acids accounted for up to 12.4 and 30 % of the total PLFA in isolates GrapesTand BuddyT, respectively. Based on their unique morphological features and the phylogenetic distance from their closest relatives, we propose the new genus,Sphaerochaetagen. nov., to accommodate the new isolates within the novel speciesSphaerochaeta globosasp. nov. (type strain BuddyT = DSM 22777T = ATCC BAA-1886T) andSphaerochaeta pleomorphasp. nov. (type strain GrapesT = DSM 22778T = ATCC BAA-1885T).Sphaerochaeta globosais the type species of the genus.
Huaishuia halophila gen. nov., sp. nov., isolated from coastal seawater
Authors: Wang Hong , Zhang Xiuming , Yan Shulin , Qi Zizhong , Yu Yong , Zhang Xiao-Hua
Published: March 2011

A novel Gram-negative, non-motile bacterium, designated ZXM137T, was isolated from seawater collected from a coastal region of Qingdao, China, during a massive green algae (Enteromorpha prolifera) bloom. Strain ZXM137T was strictly aerobic and did not accumulate poly-β-hydroxybutyrate. Growth occurred with 0.5–11.0 % (w/v) NaCl, at pH 6–9 (optimum of pH 7) and at 4–45 °C (optimum at 28 °C). It contained Q-10 as the predominant ubiquinone and the major polar lipids were phosphatidylglycerol, phospholipids, and an unidentified aminolipid and lipid. The major cellular fatty acids of strain ZXM137T were C18 : 1ω7c, C18 : 1ω6c and 11-methyl C18 : 1ω7c. The DNA G+C content was 60.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain ZXM137T formed a distinct evolutionary lineage within the Roseobacter group in the class Alphaproteobacteria. On the basis of phenotypic, chemotaxonomic and phylogenetic evidence, strain ZXM137T represents a novel species in a new genus, for which the name Huaishuia halophila gen. nov., sp. nov. is proposed; the type strain is ZXM137T ( = CGMCC 1.8891T = LMG 24854T).
Emended descriptions of Bacillus sporothermodurans and Bacillus oleronius with the inclusion of dairy farm isolates of both species
Authors: Heyndrickx Marc , Coorevits An , Scheldeman Patsy , Lebbe Liesbeth , Schumann P. , Rodríguez-Diaz Marína , Forsyth Gillian , Dinsdale Anna , Heyrman Jeroen , Logan Niall A. , De Vos Paul
Published: March 2011

Bacillus sporothermodurans is an industrially important micro-organism because of its ability to produce endospores which resist ultra-high temperature (UHT) and industrial sterilization processes. It was described by Pettersson et al. (1996) [Pettersson, B., Lembke, F., Hammer, P., Stackebrandt, E. & Priest, F. G. (1996). Int J Syst Bacteriol
46, 759–764] based on seven genetically homogeneous isolates all from UHT milk. Bacillus oleronius, the closest phylogenetic neighbour of B. sporothermodurans, was described by Kuhnigk et al. (1995) [Kuhnigk, T., Borst, E.-M., Breunig, A., König, H., Collins, M. D., Hutson, R. A. & Kämpfer, P. (1995). Can J Microbiol
41, 699–706] based on a single strain, isolated from the hindgut of the termite Reticulitermes santonensis. A polyphasic study of a heterogeneous collection of B. sporothermodurans and B. oleronius strains isolated from various sources and geographical origins led to an emended description of both species. Additional data presented are the results of fatty acid, quinone and/or cell wall (polar lipid) analyses. DNA–DNA hybridization confirmed 3 subgroups of strains obtained after SDS-PAGE analysis of cellular proteins as B. sporothermodurans. One named B. sporothermodurans strain (R-7489) was reclassified as a Bacillus fordii strain. The phenotypic profiles of both species were rather heterogeneous, sometimes different from the original descriptions and did not differ in a large number of characteristics, although B. oleronius generally gave stronger reactions in its positive tests than did B. sporothermodurans; the variable and weak reactions for both organisms with some substrates blurred the distinction between the two. However, differences in polar lipid, SDS-PAGE and menaquinone profiles clearly allow distinction between the two species.
Micromonospora yangpuensis sp. nov., isolated from a sponge
Authors: Zhang Limin , Xi Lijun , Ruan Jisheng , Huang Ying
Published: March 2011

An actinomycete, strain FXJ6.011T, was isolated from a cup-shaped sponge collected at Dachan reef, Yangpu in the South China Sea. The strain had morphological characteristics of members of the family Micromonosporaceae. Phylogenetic analysis of the 16S rRNA gene sequence of strain FXJ6.011T indicated the highest similarity (98.7 %) to Micromonospora auratinigra JCM 12357T, Micromonospora chaiyaphumensis JCM 12873T and Micromonospora echinofusca JCM 3327T. Analysis of the gyrB gene sequence also showed that strain FXJ6.011T should be assigned to the genus Micromonospora. It contained dd-diaminopimelic acid as the major cell-wall diamino acid and MK-10(H2) as predominant menaquinone. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidyl mannosides and phosphatidylinositol dimannoside. The major cellular fatty acids were iso-C16 : 0, C17 : 1ω8c and C16 : 0. Physiological and biochemical data and low DNA–DNA relatedness values enabled the strain to be differentiated from members of closely related species. Based on phenotypic and genotypic data, strain FXJ6.011T represents a novel Micromonospora species, for which the name Micromonospora yangpuensis sp. nov. is proposed; the type strain is FXJ6.011T ( = CGMCC 4.5736T = NBRC 107727T).
Streptomyces cocklensis sp. nov., a dioxamycin-producing actinomycete
Authors: Kim Byung-Yong , Zucchi Tiago Domingues , Fiedler Hans-Peter , Goodfellow Michael
Published: March 2011

The taxonomic position of a streptomycete isolated from soil collected from Cockle Park Experimental Farm, Northumberland, UK, was determined by using a polyphasic approach. The organism had chemical and morphological features consistent with its classification in the genus Streptomyces. 16S rRNA gene sequence analysis supported classification of the strain in the genus Streptomyces and showed that it formed a distinct phyletic line loosely associated with members of the Streptomyces yeochonensis clade. It was related most closely to Streptomyces paucisporeus 1413T (98.6 %16S rRNA gene sequence similarity), but could be distinguished from the latter based on the low level of DNA–DNA relatedness (40 %). It was readily distinguished from the type strains of all species assigned to the S. yeochonensis clade based on a combination of phenotypic properties. Strain BK168T ( = KACC 20908T = NCIMB 14704T) should therefore be classified as the type strain of a novel species of the genus Streptomyces, for which the name Streptomyces cocklensis sp. nov. is proposed. The organism produces the antibiotic dioxamycin.
Characterization of specific antibodies against cytomegalovirus (CMV)-encoded interleukin 10 produced by 28 % of CMV-seropositive blood donors
Authors: de Lemos Rieper Carina , Galle Pia , Pedersen Bente Klarlund , Hansen Morten Bagge
Published: March 2011

Cytomegalovirus (CMV) has evolved multiple immunological evasion strategies, including the encoding of viral interleukin (IL)-10 homologues (cmvIL-10). In this study, cmvIL-10 bound avidly to the same receptors on blood mononuclear cells and was as bio-potent as native human IL-10. Seventeen percent of plasma samples from 3200 Danish blood donors (corresponding to 28 % of the anti-CMV IgG-positive donors) contained substantial levels of anti-cmvIL-10 IgG antibodies, as measured by a radioimmunoassay for human anti-cmvIL-10 antibodies. The antibodies neither cross-reacted with native human IL-10 nor with Epstein–Barr virus-encoded IL-10. Anti-cmvIL-10 antibodies potently inhibited the binding of cmvIL-10 to cellular receptors, and they specifically inhibited cmvIL-10-induced JAK–STAT signalling. Ultimately, anti-cmvIL-10 antibodies blocked the inhibitory effect of cmvIL-10 on lipopolysaccharide-induced tumour necrosis factor alpha and IL-1β from blood mononuclear cells. Taken together, our data signify that cmvIL-10 has been produced during CMV infection, and that anti-cmvIL-10 IgG antibodies represent an effective immunological counter reaction against cmvIL-10.
Metagenomic identification of a novel anellovirus in Pacific harbor seal (Phoca vitulina richardsii) lung samples and its detection in samples from multiple years
Authors: Ng Terry Fei Fan , Wheeler Elizabeth , Greig Denise , Waltzek Thomas B. , Gulland Frances , Breitbart Mya
Published: March 2011

To investigate viral pathogens potentially involved in a mortality event of 21 Pacific harbor seals (Phoca vitulina richardsii) in California in 2000, viral metagenomics was performed directly on lung samples from five individuals. Metagenomics revealed a novel seal anellovirus (SealAV), which clusters phylogenetically with anelloviruses from California sea lions and domestic cats. Using specific PCR, SealAV was identified in lung tissue from two of five animals involved in the 2000 mortality event, as well as one of 20 harbor seal samples examined post-mortem in 2008. The identification of SealAV in multiple years demonstrates that this virus is persistent in the harbor seal population. SealAV is the second anellovirus reported in the lungs of pinnipeds, suggesting that anellovirus infections may be common amongst marine mammals and that more research is needed to understand the roles of these viruses in marine mammal health and disease.
The multifunctional Ccr4–Not complex directly promotes transcription elongation
Authors: Kruk Jennifer A. , Dutta Arnob , Fu Jianhua , Gilmour David S. , Reese Joseph C.
Published: March 2011

The Ccr4–Not complex has been implicated in the control of multiple steps of mRNA metabolism; however, its functions in transcription remain ambiguous. The discovery that Ccr4/Pop2 is the major cytoplasmic mRNA deadenylase and the detection of Not proteins within mRNA processing bodies have raised questions about the roles of the Ccr4–Not complex in transcription. Here we firmly establish Ccr4–Not as a positive elongation factor for RNA polymerase II (RNAPII). The Ccr4–Not complex is targeted to the coding region of genes in a transcription-dependent manner similar to RNAPII and promotes elongation in vivo. Furthermore, Ccr4–Not interacts directly with elongating RNAPII complexes and stimulates transcription elongation of arrested polymerase in vitro. Ccr4–Not can reactivate backtracked RNAPII using a mechanism different from that of the well-characterized elongation factor TFIIS. While not essential for its interaction with elongation complexes, Ccr4–Not interacts with the emerging transcript and promotes elongation in a manner dependent on transcript length, although this interaction is not required for it to bind RNAPII. Our comprehensive analysis shows that Ccr4–Not directly regulates transcription, and suggests it does so by promoting the resumption of elongation of arrested RNAPII when it encounters transcriptional blocks in vivo.
Arabidopsis NDR1 Is an Integrin-Like Protein with a Role in Fluid Loss and Plasma Membrane-Cell Wall Adhesion
Authors: Knepper Caleb , Savory Elizabeth A. , Day Brad
Published: March 2011

Arabidopsis (Arabidopsis thaliana) NON-RACE-SPECIFIC DISEASE RESISTANCE1 (NDR1), a plasma membrane-localized protein, plays an essential role in resistance mediated by the coiled-coil-nucleotide-binding site-leucine-rich repeat class of resistance (R) proteins, which includes RESISTANCE TO PSEUDOMONAS  SYRINGAE2 (RPS2), RESISTANCE TO PSEUDOMONAS  SYRINGAE PV MACULICOLA1, and RPS5. Infection with Pseudomonas syringae pv tomato DC3000 expressing the bacterial effector proteins AvrRpt2, AvrB, and AvrPphB activates resistance by the aforementioned R proteins. Whereas the genetic requirement for NDR1 in plant disease resistance signaling has been detailed, our study focuses on determining a global, physiological role for NDR1. Through the use of homology modeling and structure threading, NDR1 was predicted to have a high degree of structural similarity to Arabidopsis LATE EMBRYOGENESIS ABUNDANT14, a protein implicated in abiotic stress responses. Specific protein motifs also point to a degree of homology with mammalian integrins, well-characterized proteins involved in adhesion and signaling. This structural homology led us to examine a physiological role for NDR1 in preventing fluid loss and maintaining cell integrity through plasma membrane-cell wall adhesions. Our results show a substantial alteration in induced (i.e. pathogen-inoculated) electrolyte leakage and a compromised pathogen-associated molecular pattern-triggered immune response in ndr1-1 mutant plants. As an extension of these analyses, using a combination of genetic and cell biology-based approaches, we have identified a role for NDR1 in mediating plasma membrane-cell wall adhesions. Taken together, our data point to a broad role for NDR1 both in mediating primary cellular functions in Arabidopsis through maintaining the integrity of the cell wall-plasma membrane connection and as a key signaling component of these responses during pathogen infection.
Tomato RAV Transcription Factor Is a Pivotal Modulator Involved in the AP2/EREBP-Mediated Defense Pathway
Authors: Li Chia-Wen , Su Ruey-Chih , Cheng Chiu-Ping , Sanjaya  , You Su-Juan , Hsieh Tsai-Hung , Chao To-Chun , Chan Ming-Tsair
Published: March 2011

Ralstonia solanacearum is the causal agent of bacterial wilt (BW), one of the most important bacterial diseases worldwide. We used cDNA microarray to survey the gene expression profile in transgenic tomato (Solanum lycopersicum) overexpressing Arabidopsis (Arabidopsis thaliana) CBF1 (AtCBF1), which confers tolerance to BW. The disease-resistant phenotype is correlated with constitutive expression of the Related-to-ABI3/VP1 (RAV) transcription factor, ethylene-responsive factor (ERF) family genes, and several pathogenesis-related (PR) genes. Using a transient assay system, we show that tomato RAV2 (SlRAV2) can transactivate the reporter gene driven by the SlERF5 promoter. Virus-induced gene silencing of SlERF5 and SlRAV2 in AtCBF1 transgenic and BW-resistant cultivar Hawaii 7996 plants gave rise to plants with enhanced susceptibility to BW. Constitutive overexpression of SlRAV2 in transgenic tomato plants induced the expression of SlERF5 and PR5 genes and increased BW tolerance, while knockdown of expression of SlRAV2 inhibited SlERF5 and PR5 gene expression under pathogen infection and significantly decreased BW tolerance. In addition, transgenic tomato overexpressing SlERF5 also accumulated higher levels of PR5 transcripts and displayed better tolerance to pathogen than wild-type plants. From these results, we conclude that SlERFs may act as intermediate transcription factors between AtCBF1 and PR genes via SlRAV in tomato, which results in enhanced tolerance to BW.
Wheat Grain Development Is Characterized by Remarkable Trehalose 6-Phosphate Accumulation Pregrain Filling: Tissue Distribution and Relationship to SNF1-Related Protein Kinase1 Activity
Authors: Martínez-Barajas Eleazar , Delatte Thierry , Schluepmann Henriette , de Jong Gerhardus J. , Somsen Govert W. , Nunes Cátia , Primavesi Lucia F. , Coello Patricia , Mitchell Rowan A.C. , Paul Matthew J.
Published: March 2011

Trehalose 6-phosphate (T6P) is a sugar signal that regulates metabolism, growth, and development and inhibits the central regulatory SNF1-related protein kinase1 (SnRK1; AKIN10/AKIN11). To better understand the mechanism in wheat (Triticum aestivum) grain, we analyze T6P content and SnRK1 activities. T6P levels changed 178-fold 1 to 45 d after anthesis (DAA), correlating with sucrose content. T6P ranged from 78 nmol g−1 fresh weight (FW) pregrain filling, around 100-fold higher than previously reported in plants, to 0.4 nmol g−1 FW during the desiccation stage. In contrast, maximum SnRK1 activity changed only 3-fold but was inhibited strongly by T6P in vitro. To assess SnRK1 activity in vivo, homologs of SnRK1 marker genes in the wheat transcriptome were identified using Wheat Estimated Transcript Server. SnRK1-induced and -repressed marker genes were expressed differently pregrain filling compared to grain filling consistent with changes in T6P. To investigate this further maternal and filial tissues were compared pre- (7 DAA) and during grain filling (17 DAA). Strikingly, in vitro SnRK1 activity was similar in all tissues in contrast to large changes in tissue distribution of T6P. At 7 DAA T6P was 49 to 119 nmol g−1 FW in filial and maternal tissues sufficient to inhibit SnRK1; at 17 DAA T6P accumulation was almost exclusively endospermal (43 nmol g−1 FW) with 0.6 to 0.8 nmol T6P g−1 FW in embryo and pericarp. The data show a correlation between T6P and sucrose overall that belies a marked effect of tissue type and developmental stage on T6P content, consistent with tissue-specific regulation of SnRK1 by T6P in wheat grain.