bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure of betaglycan zona pellucida (ZP)-C domain provides insights into ZP-mediated protein polymerization and TGF-β binding
Authors: Lin S. Jack , Hu YaoXiong , Zhu Jie , Woodruff Teresa K. , Jardetzky Theodore S.
Published: March 2011

The zona pellucida (ZP) domain is a bipartite protein structural element comprised of ZP-N and ZP-C regions. Most notable for its ability to mediate protein polymerization, many ZP proteins polymerize and assemble into long fibrils that form specialized extracellular matrices. Other ZP proteins (namely, betaglycan and endoglin) do not polymerize but serve as important membrane coreceptors for ligands in the transforming growth factor-β (TGF-β) superfamily. Here, we present the 2.0-Å resolution crystal structure of the betaglycan ZP-C region in combination with a downstream region known as the external hydrophobic patch (EHP). Similar to the ZP-N region, the ZP-C region also adopts an immunoglobulin-like fold, despite sharing no sequence homology and possessing different disulfide linkages. The EHP region, which was previously thought to be external to the ZP region, is integral to the ZP-C domain and corresponds to the ZP-C G strand. Our structure also indicates that the critical maturation cleavage of ZP proteins, a process that activates nascent ZP proteins for polymerization, occurs within the immunoglobulin domain at the FG loop. Nonpolymerizing ZP proteins such as betaglycan and endoglin do not contain this cleavage site. Finally, our structure suggests that the AB loop and the convex surface pocket are regions important for TGF-β ligand binding.
Episodic radiations in the fly tree of life
Authors: Wiegmann Brian M. , Trautwein Michelle D. , Winkler Isaac S. , Barr Norman B. , Kim Jung-Wook , Lambkin Christine , Bertone Matthew A. , Cassel Brian K. , Bayless Keith M. , Heimberg Alysha M. , Wheeler Benjamin M. , Peterson Kevin J. , Pape Thomas , Sinclair Bradley J. , Skevington Jeffrey H. , Blagoderov Vladimir , Caravas Jason , Kutty Sujatha Narayanan , Schmidt-Ott Urs , Kampmeier Gail E. , Thompson F. Christian , Grimaldi David A. , Beckenbach Andrew T. , Courtney Gregory W. , Friedrich Markus , Meier Rudolf , Yeates David K.
Published: March 2011

Flies are one of four superradiations of insects (along with beetles, wasps, and moths) that account for the majority of animal life on Earth. Diptera includes species known for their ubiquity (Musca domesticahouse fly), their role as pests (Anopheles gambiaemalaria mosquito), and their value as model organisms across the biological sciences (Drosophila melanogaster). A resolved phylogeny for flies provides a framework for genomic, developmental, and evolutionary studies by facilitating comparisons across model organisms, yet recent research has suggested that fly relationships have been obscured by multiple episodes of rapid diversification. We provide a phylogenomic estimate of fly relationships based on molecules and morphology from 149 of 157 families, including 30 kb from 14 nuclear loci and complete mitochondrial genomes combined with 371 morphological characters. Multiple analyses show support for traditional groups (Brachycera, Cyclorrhapha, and Schizophora) and corroborate contentious findings, such as the anomalous Deuterophlebiidae as the sister group to all remaining Diptera. Our findings reveal that the closest relatives of the Drosophilidae are highly modified parasites (including the wingless Braulidae) of bees and other insects. Furthermore, we use micro-RNAs to resolve a node with implications for the evolution of embryonic development in Diptera. We demonstrate that flies experienced three episodes of rapid radiation—lower Diptera (220 Ma), lower Brachycera (180 Ma), and Schizophora (65 Ma)—and a number of life history transitions to hematophagy, phytophagy, and parasitism in the history of fly evolution over 260 million y.
Recent thymic emigrants are preferentially incorporated only into the depleted T-cell pool
Authors: Houston Evan G. , Higdon Lauren E. , Fink Pamela J.
Published: March 2011

Recent thymic emigrants (RTEs) are the youngest subset of peripheral T cells, and they differ functionally and phenotypically from the rest of the naïve T-cell pool. RTEs are present in the peripheral T-cell pool throughout life but are the most common subset of T cells in neonates and adults recovering from lymphoablation. Using a murine model to study the homeostasis of RTEs, we show that under lymphoreplete conditions, RTEs are at a competitive disadvantage to already established mature naïve (MN) T cells. This disadvantage may be caused by a defect in survival, because RTEs may transduce homeostatic signals inefficiently, and their ability to survive is enhanced with increased expression of IL-7 receptor or B-cell lymphoma 2 (Bcl-2). Conversely, under lymphopenic conditions, enhanced proliferation by RTEs allows them to out-compete their MN T-cell counterparts. These results suggest that in times of need, such as in neonates or lymphopenic adults, RTEs perform well to fill the gaps in the peripheral T-cell pool, but when the periphery already is full, many RTEs are not incorporated into the pool of recirculating lymphocytes.
Network structure of production
Authors: Atalay Enghin , Hortaçsu Ali , Roberts James , Syverson Chad
Published: March 2011

Complex social networks have received increasing attention from researchers. Recent work has focused on mechanisms that produce scale-free networks. We theoretically and empirically characterize the buyer–supplier network of the US economy and find that purely scale-free models have trouble matching key attributes of the network. We construct an alternative model that incorporates realistic features of firms’ buyer–supplier relationships and estimate the model’s parameters using microdata on firms’ self-reported customers. This alternative framework is better able to match the attributes of the actual economic network and aids in further understanding several important economic phenomena.
PU.1 and C/EBPα synergistically program distinct response to NF-κB activation through establishing monocyte specific enhancers
Authors: Jin Fulai , Li Yan , Ren Bing , Natarajan Rama
Published: March 2011

Unraveling the complexity of transcriptional programs coded by different cell types has been one of the central goals of cell biology. By using genome-wide location analysis, we examined how two different cell types generate different responses to the NF-κB signaling pathway. We showed that, after TNF-α treatment, the NF-κB p65 subunit binds to distinct genome locations and subsequently induces different subsets of genes in human monocytic THP-1 cells versus HeLa cells. Interestingly, the differential p65 binding in two cell types correlates with preexisting cell type-specific enhancers before TNF-α stimulation, marked by histone modifications. We also found that two transcription factors, PU.1 and C/EBPα, appear to synergistically mediate enhancer creation and affect NF-κB target selection in THP-1 cells. In HeLa cells, coexpression of PU.1 and C/EBPα conferred TNF-α responsiveness to a subset of THP-1–specific NF-κB target genes. These results suggest that the diversity of transcriptional programs in mammalian cells arises, at least in part, from preexisting enhancers that are established by cell-specific transcription factors.
Interdomain communication revealed in the diabetes drug target mitoNEET
Authors: Baxter Elizabeth L. , Jennings Patricia A. , Onuchic José N.
Published: March 2011

MitoNEET is a recently identified drug target for a commonly prescribed diabetes drug, Pioglitazone. It belongs to a previously uncharacterized ancient family of proteins for which the hallmark is the presence of a unique 39 amino acid CDGSH domain. In order to characterize the folding landscape of this novel fold, we performed thermodynamic simulations on MitoNEET using a structure-based model. Additionally, we implement a method of contact map clustering to partition out alternate pathways in folding. This cluster analysis reveals a detour late in folding and enables us to carefully examine the folding mechanism of each pathway rather than the macroscopic average. We observe that tightness in a region distal to the iron–sulfur cluster creates a constraint in folding and additionally appears to mediate communication in folding between the two domains of the protein. We demonstrate that by making changes at this site we are able to tweak the order of folding events in the cluster binding domain as well as decrease the barrier to folding.
Evolutionary approach to predicting the binding site residues of a protein from its primary sequence
Authors: Tseng Yan Yuan , Li Wen-Hsiung
Published: March 2011

Protein binding site residues, especially catalytic residues, play a central role in protein function. Because more than 99% of the ∼12 million protein sequences in the nonredundant protein database have no structural information, it is desirable to develop methods to predict the binding site residues of a protein from its primary sequence. This task is highly challenging, because the binding site residues constitute only a small portion of a protein. However, the binding site residues of a protein are clustered in its functional pocket(s), and their spatial patterns tend to be conserved in evolution. To take advantage of these evolutionary and structural principles, we constructed a database of ∼50,000 templates (called the pocket-containing segment database), each of which includes not only a sequence segment that contains a functional pocket but also the structural attributes of the pocket. To use this database, we designed a template-matching technique, termed residue-matching profiling, and established a criterion for selecting templates for a query sequence. Finally, we developed a probabilistic model for assigning spatial scores to matched residues between the template and query sequence in local alignments using a set of selected scoring matrices and for computing the binding likelihood of each matched residue in the query sequence. From the likelihoods, one can predict the binding site residues in the query sequence. An automated computational pipeline was developed for our method. A performance evaluation shows that our method achieves a 70% precision in predicting binding site residues at 60% sensitivity.
A CHOP-regulated microRNA controls rhodopsin expression
Authors: Behrman Shannon , Acosta-Alvear Diego , Walter Peter
Published: March 2011

Using genome-wide microribonucleic acid (microRNA [miRNA]) expression profiling, bioinformatics, and biochemical analyses, we identified miR-708, an endoplasmic reticulum (ER) stress-inducible miRNA whose expression is regulated by the transcription factor CCAAT enhancer-binding protein homologous protein (CHOP) in vertebrates. miR-708 is encoded within an intron of the CHOP-regulated gene Odz4, a member of the highly conserved teneurin family of developmental regulators. Odz4 and mir-708 expression is coregulated by CHOP, and the two transcripts are coexpressed in the brain and eyes of mice, suggesting common physiological functions in these tissues. We validated rhodopsin as a target of miR-708 through loss- and gain-of-function experiments. Together, our data implicate miR-708 in the homeostatic regulation of ER function in mammalian rod photoreceptors, whereby miR-708 may help prevent an excessive rhodopsin load from entering the ER. Hence, miR-708 may function analogously to other unfolded protein response controls that throttle protein influx into the ER to avoid ER stress through mechanisms, such as general translational attenuation by protein kinase RNA–like ER kinase or membrane-bound messenger RNA decay by inositol-requiring enzyme 1.
Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase
Authors: Ewald Sarah E. , Engel Alex , Lee Jiyoun , Wang Miqi , Bogyo Matthew , Barton Gregory M.
Published: March 2011

Toll-like receptor (TLR) 9 requires proteolytic processing in the endolysosome to initiate signaling in response to DNA. However, recent studies conflict as to which proteases are required for receptor cleavage. We show that TLR9 proteolysis is a multistep process. The first step removes the majority of the ectodomain and can be performed by asparagine endopeptidase (AEP) or cathepsin family members. This initial cleavage event is followed by a trimming event that is solely cathepsin mediated and required for optimal receptor signaling. This dual requirement for AEP and cathepsins is observed in all cell types that we have analyzed, including mouse macrophages and dendritic cells. In addition, we show that TLR7 and TLR3 are processed in an analogous manner. These results define the core proteolytic steps required for TLR9 function and suggest that receptor proteolysis may represent a general regulatory strategy for all TLRs involved in nucleic acid recognition.
Notch signaling in stomach epithelial stem cell homeostasis
Authors: Kim Tae-Hee , Shivdasani Ramesh A.
Published: March 2011

The mammalian adult gastric epithelium self-renews continually through the activity of stem cells located in the isthmus of individual gland units. Mechanisms facilitating stomach stem and progenitor cell homeostasis are unknown. Here, we show that Notch signaling occurs in the mouse stomach epithelium during development and becomes restricted mainly to the isthmus in adult glands, akin to its known localization in the proliferative compartment of intestinal villi. Using genetic and chemical inhibition, we demonstrate that Notch signaling is required to maintain the gastric stem cell compartment. Activation of Notch signaling in lineage-committed stomach epithelial cells is sufficient to induce dedifferentiation into stem and/or multipotential progenitors that populate the mucosa with all major cell types. Prolonged Notch activation within dedifferentiated parietal cells eventually enhances cell proliferation and induces adenomas that show focal Wnt signaling. In contrast, Notch activation within native antral stomach stem cells does not affect cell proliferation. These results establish a role for Notch activity in the foregut and highlight the importance of cellular context in gastric tumorigenesis.
Mechanisms of necroptosis in T cells
Authors: Ch’en Irene L. , Tsau Jennifer S. , Molkentin Jeffery D. , Komatsu Masaaki , Hedrick Stephen M.
Published: March 2011

Cell populations are regulated in size by at least two forms of apoptosis. More recently, necroptosis, a parallel, nonapoptotic pathway of cell death, has been described, and this pathway is invoked in the absence of caspase 8. In caspase 8–deficient T cells, necroptosis occurs as the result of antigen receptor–mediated activation. Here, through a genetic analysis, we show that necroptosis in caspase 8–deficient T cells is related neither to the programmed necrosis as defined by the requirement for mitochondrial cyclophilin D nor to autophagy as defined by the requirement for autophagy-related protein 7. Rather, survival of caspase 8–defective T cells can be completely rescued by loss of receptor-interacting serine-threonine kinase (Ripk) 3. Additionally, complementation of a T cell–specific caspase 8 deficiency with a loss of Ripk3 gives rise to lymphoproliferative disease reminiscent of lpr or gld mice. In conjunction with previous work, we conclude that necroptosis in antigen-stimulated caspase 8–deficient T cells is the result of a novel Ripk1- and Ripk3-mediated pathway of cell death.
Trapping a translocating protein within the anthrax toxin channel: implications for the secondary structure of permeating proteins
Authors: Basilio Daniel , Jennings-Antipov Laura D. , Jakes Karen S. , Finkelstein Alan
Published: March 2011

Anthrax toxin consists of three proteins: lethal factor (LF), edema factor (EF), and protective antigen (PA). This last forms a heptameric channel, (PA63)7, in the host cell’s endosomal membrane, allowing the former two (which are enzymes) to be translocated into the cytosol. (PA63)7 incorporated into planar bilayer membranes forms a channel that translocates LF and EF, with the N terminus leading the way. The channel is mushroom-shaped with a cap containing the binding sites for EF and LF, and an ∼100 Å–long, 15 Å–wide stem. For proteins to pass through the stem they clearly must unfold, but is secondary structure preserved? To answer this question, we developed a method of trapping the polypeptide chain of a translocating protein within the channel and determined the minimum number of residues that could traverse it. We attached a biotin to the N terminus of LFN (the 263-residue N-terminal portion of LF) and a molecular stopper elsewhere. If the distance from the N terminus to the stopper was long enough to traverse the channel, streptavidin added to the trans side bound the N-terminal biotin, trapping the protein within the channel; if this distance was not long enough, streptavidin did not bind the N-terminal biotin and the protein was not trapped. The trapping rate was dependent on the driving force (voltage), the length of time it was applied, and the number of residues between the N terminus and the stopper. By varying the position of the stopper, we determined the minimum number of residues required to span the channel. We conclude that LFN adopts an extended-chain configuration as it translocates; i.e., the channel unfolds the secondary structure of the protein. We also show that the channel not only can translocate LFN in the normal direction but also can, at least partially, translocate LFN in the opposite direction.
Silicon nanowires prepared by thermal evaporation and their photoluminescence properties measured at low temperatures
Authors: Pham Van Tuan , Le Van Ngoc , Chu Anh Tuan , Pham Toan Thang , Tran Ngoc Khiem , Pham Hong Duong , Pham Thanh Huy
Published: March 2011

In the present work, silicon nanowires were prepared by a thermal evaporation method. The evaporating source was a mixture of silicon and carbon nanopowders. Surface morphology, structural characteristics and emission properties of the silicon nanowires were investigated by several techniques. The results showed that the obtained products have the shape of nanowires with diameters ranging from 30 to 120 nm and lengths from 300 to 400 nm. The x-ray diffraction (XRD) patterns confirmed the presence of crystalline silicon. Transmission electron microscope (TEM) images revealed the core-shell structure of the wires. In the photoluminescence (PL) spectra recorded at room temperature, only a broad emission band peaking at about 650 nm was observed. In addition to the red emission, two other bands centered at around 455 nm and 510 nm appeared when measured at low temperatures. The origin and emission mechanism of these bands are discussed.
Essentially finite vector bundles on varieties with trivial tangent bundle
Authors: Biswas Indranil , Parameswaran A. J. , Subramanian S.
Published: March 2011

Let

X
X

be a smooth projective variety, defined over an algebraically closed field of positive characteristic, such that the tangent bundle

T
X

TX

is trivial. Let

F
X

:

X

⟶

X

F_X\, :\, X\,\longrightarrow \, X

be the absolute Frobenius morphism of

X
X

. We prove that for any

n

≥

1

n\, \geq \,1

, the

n
n

–fold composition

F
X
n

F^n_X

is a torsor over

X
X

for a finite group–scheme that depends on

n
n

. For any vector bundle

E

⟶

X

E\,\longrightarrow \, X

, we show that the direct image

(

F
X
n

)
∗

E

(F^n_X)_*E

is essentially finite (respectively,

F
F

–trivial) if and only if

E
E

is essentially finite (respectively,

F
F

–trivial).
First Report of Leaf Spot Disease on Dictamnus dasycarpus Caused by Phoma dictamnicola in China
Authors: Bai Q. , Xie Y. , Gao J. , Lu B. , Wang W. , Men X. , Lin Y.
Published: March 2011

Fraxinella, Dictamnus dasycarpus Turcz (Rutaceae), is a perennial herbal plant and mainly distributed in Eurasia and North America. It is often used to treat jaundice, cough, rheumatism, and other diseases and is extensively cultivated in the northeast and northwest of China (3). In June 2009, a severe foliar disease was observed on D. dasycarpus in medicinal plantations in Antu, China. The disease occurred on 100% of the plants and at least 25% of the surface was affected. In the early stages of disease development, symptoms were visible on the top and bottom of infected leaves as small brown spots. Subsequently, these spots became elliptical to irregularly shaped, with beige or grayish white centers and dark brown margins. Within the spots, numerous, dark brown or black, subglobose or ostiolate pycnidia measuring 152 to 367 μm in diameter were observed. Fungal isolates were obtained from the infected leaves on potato dextrose agar (PDA) medium, with conidia that were aseptate or one-septate and ellipsoidal or reniform, measuring approximately 4.7 to 12.6 × 2.1 to 4.5 μm. On the basis of these characteristics, the fungus was identified as a Phoma sp. Four well-sporulating isolates, designated as DdPh-1, DdPh-2, DdPh-3, and DdPh-4, were selected for further studies. The morphological and cultural characteristics of these four isolates were studied as described by Boerema et al. and the fungus was identified as Phoma dictamnicola Boerema et al. (1). The internal transcribed spacer (ITS) region of the nuclear rDNA was amplified and sequenced using primers ITS4/ITS5 (2). All four of the ITS sequences were identical (GenBank Accession No. FR681861) and were 99% identical to P. dictamnicola strains CBS507.91 (Accession No. GU237877) and KACC42445 (Accession No. EF600960). Pathogenicity tests were performed by spraying the leaves of healthy D. dasycarpus plants with a conidial suspension (1 × 106 conidia/ml). Five plants were inoculated with each isolate (DdPh-1, DdPh-2, DdPh-3, and DdPh-4) and five plants were mock inoculated with sterile water. The plants were covered with plastic bags and kept in a greenhouse at 20 to 25° for 72 h. After 9 to 13 days, all inoculated plants showed characteristic symptoms as previously described, while the control plants remained healthy. The fungus was reisolated from the leaf spots of inoculated plants. Currently, the economic importance of this disease is limited, but it may become a more significant problem in production of D. dasycarpus with the cultivation area increasing. The fungus was found in the Netherlands and Korea, but to our knowledge, this is the first report of P. dictamnicola on D. dasycarpus in China.

References: (1) G. H. Boerema et al. Phoma Identificatión Manual: Differentiation of Specific and Infra-Specific Taxa in Culture. CABI Publishing. Wallingford, U.K., 2004. (2) D. E. L. Cooke et al. Mycol. Res. 101:667, 1997. (3) S. S. Jiang et al. Biosci. Biotechnol. Biochem. 72:660, 2008.
Polyphasic Characterization of Pigmented Strains of Xanthomonas Pathogenic to Cashew Trees
Authors: Gama Marco A. S. , Mariano Rosa L. R. , Viana Francisco M. P. , Ferreira Marisa A. S. V. , Souza Elineide B.
Published: March 2011

The export of cashew (Anacardium occidentale) nuts generates millions of dollars for the Brazilian economy annually. However, production may be limited by the occurrence of diseases that affect cashew trees, such as Xanthomonas spot and angular leaf spot, which are caused by pigmented strains of Xanthomonas and Xanthomonas citri pv. anacardii, respectively. Thirty-one pigmented strains of Xanthomonas were characterized for phenotypic, pathogenic, and molecular attributes. These strains were similar to X. citri pv. anacardii in phenotypical characteristics, sensitivity to antibiotics and copper compounds used in agriculture, epidemiology, and repetitive sequence-based polymerase chain reaction (rep-PCR) profiles. When inoculated into Brazilian pepper, cashew, mango, and hog plum seedlings, the pigmented strains of Xanthomonas and X. citri pv. anacardii produced similar symptoms. However, the pigmented strains of Xanthomonas were more aggressive toward cashew plants than toward the other hosts tested, which confirms their specificity. We conclude that pigmented strains of Xanthomonas are very aggressive on cashew trees and should not be considered casual pathogens of these hosts. Moreover, based on our results from rep-PCR and IS1595-PCR amplification, we suggest that these strains constitute a variant of X. citri pv. anacardii.
Evaluation of Nonpathogenic Fusarium oxysporum and Pseudomonas fluorescens for Panama Disease Control
Authors: Belgrove A. , Steinberg C. , Viljoen A.
Published: March 2011

Nonpathogenic Fusarium oxysporum endophytes from healthy banana roots were evaluated for their ability to reduce Fusarium wilt of banana (Panama disease). Isolates were identified morphologically and by using species-specific primers. Pathogenicity was confirmed by inoculating banana plantlets in the greenhouse. Nonpathogenic F. oxysporum isolates were grouped into 14 haplotype groups by polymerase chain reaction restriction fragment length polymorphism analysis of the intergenic spacer region, and representative isolates evaluated for biocontrol of F. oxysporum f. sp. cubense. In the greenhouse, 10 nonpathogenic F. oxysporum isolates were able to significantly reduce Fusarium wilt of banana. The isolate that protected banana plantlets best in the greenhouse, a nonpathogenic F. oxysporum from the root rhizosphere, and Pseudomonas fluorescens WCS 417 were then field tested. When the putative biological control organisms were tested in the field, neither the nonpathogenic F. oxysporum, P. fluorescens, nor combinations thereof reduced Fusarium wilt development significantly. A number of factors could contribute to the lack of field protection, including soil microbial and chemical composition and reduced survival of biocontrol organisms in banana roots. A lack of knowledge regarding the etiology of Fusarium wilt of ‘Cavendish’ banana in the subtropics and the effect of F. oxysporum f. sp. cubense race and banana cultivar in protection of banana by biocontrol organisms should be further investigated.
Cinnamic-Derived Acids Significantly Affect Fusarium graminearum Growth and In Vitro Synthesis of Type B Trichothecenes
Authors: Ponts Nadia , Pinson-Gadais Laetitia , Boutigny Anne-Laure , Barreau Christian , Richard-Forget Florence
Published: March 2011

The impact of five phenolic acids (ferulic, coumaric, caffeic, syringic, and p-hydroxybenzoic acids) on fungal growth and type B trichothecene production by four strains of Fusarium graminearum was investigated. All five phenolic acids inhibited growth but the degree of inhibition varied between strains. Our results suggested that the more lipophilic phenolic acids are, the higher is the effect they have on growth. Toxin accumulation in phenolic acid-supplemented liquid glucose, yeast extract, and peptone cultures was enhanced in the presence of ferulic and coumaric acids but was reduced in the presence of p-hydroxybenzoic acid. This modulation was shown to correlate with a regulation of TRI5 transcription. In this study, addition of phenolic acids with greater antioxidant properties resulted in a higher toxin accumulation, indicating that the modulation of toxin accumulation may be linked to the antioxidant properties of the phenolic acids. These data suggest that, in planta, different compositions in phenolic acids of kernels from various cultivars may reflect different degrees of sensitivity to “mycotoxinogenesis.”
Activation of miR-31 function in already-established metastases elicits metastatic regression
Authors: Valastyan Scott , Chang Amelia , Benaich Nathan , Reinhardt Ferenc , Weinberg Robert A.
Published: March 2011

Distant metastases, rather than the primary tumors from which these lesions arise, are responsible for >90% of carcinoma-associated mortality. Many patients already harbor disseminated tumor cells in their bloodstream, bone marrow, and distant organs when they initially present with cancer. Hence, truly effective anti-metastatic therapeutics must impair the proliferation and survival of already-established metastases. Here, we assess the therapeutic potential of acutely expressing the microRNA miR-31 in already-formed breast cancer metastases. Activation of miR-31 in established metastases elicits metastatic regression and prolongs survival. Remarkably, even brief induction of miR-31 in macroscopic pulmonary metastases diminishes metastatic burden. In contrast, acute miR-31 expression fails to affect primary mammary tumor growth. miR-31 triggers metastatic regression in the lungs by eliciting cell cycle arrest and apoptosis; these responses occur specifically in metastases and can be explained by miR-31-mediated suppression of integrin-α5, radixin, and RhoA. Indeed, concomitant re-expression of these three proteins renders already-seeded pulmonary metastases refractory to miR-31-conferred regression. Upon miR-31 activation, Akt-dependent signaling is attenuated and the proapoptotic molecule Bim is induced; these effects occur in a metastasis-specific manner in pulmonary lesions and are abrogated by concurrent re-expression of integrin-α5, radixin, and RhoA. Collectively, these findings raise the possibility that intervention strategies centered on restoring miR-31 function may prove clinically useful for combating metastatic disease.
RNAi genes pave their own way
Authors: Kamminga Leonie M. , Ketting René F.
Published: March 2011

Heterochromatin formation in fission yeast and the role of RNAi in this process have been intensively studied. So far, however, nothing is known about the regulation of expression of RNAi components during these events. Gullerova and colleagues (pp. 556–568) reveal an autoregulatory loop that regulates the expression of RNAi genes and centromeric heterochromatin formation during the cell cycle. Gene orientation plays a surprising role in this process.
The Transcriptional Regulator LEUNIG_HOMOLOG Regulates Mucilage Release from the Arabidopsis Testa
Authors: Walker Murray , Tehseen Muhammad , Doblin Monika S. , Pettolino Filomena A. , Wilson Sarah M. , Bacic Antony , Golz John F.
Published: March 2011

Exposure of the mature Arabidopsis (Arabidopsis thaliana) seed to water results in the rapid release of pectinaceous mucilage from the outer cells of the testa. Once released, mucilage completely envelops the seed in a gel-like capsule. The physical force required to rupture the outer cell wall of the testa comes from the swelling of the mucilage as it expands rapidly following hydration. In this study, we show that mutations in the transcriptional regulator LEUNIG_HOMOLOG (LUH) cause a mucilage extrusion defect due to altered mucilage swelling. Based on sugar linkage and immunomicroscopic analyses, we show that the structure of luh mucilage is altered, having both an increase in substituted rhamnogalacturonan I and in methyl-esterified homogalacturonan. Also correlated with the structural modification of luh mucilage is a significant decrease in MUCILAGE MODIFIED2 (MUM2; a β-galactosidase) expression in the luh seed coat, raising the possibility that reduced activity of this glycosidase is directly responsible for the luh mucilage defects. Consistent with this is the structural similarity between mum2 and luh mucilage as well as the observation that elevating MUM2 expression in luh mutants completely suppresses the mucilage extrusion defect. Suppression of the luh mutant phenotype was also observed when LEUNIG, a transcriptional corepressor closely related to LUH, was introduced in luh mutants under the control of the LUH promoter. Based on these data, we propose a new model for the regulation of pectin biosynthesis during plant growth and development.
Hymenoscyphus species associated with European ash1
Authors: Hietala A. M. , Solheim H.
Published: March 2011

The causative agent of dieback on European ash (Fraxinus excelsior) was first described as Chalara fraxinea based on cultural morphology because no sexual stage of the fungus was known. Later, based on culturing of ascospores of a candidate teleomorph, morphological comparison and nuclear ribosomal internal transcribed spacer sequencing, the sexual stage of C. fraxinea was assigned as Hymenoscyphus albidus, a native and widespread species in Europe. Recently, the morphological species concept of H. albidus was shown to cover two species that cannot be separated from each other based on teleomorph characters, but which can be distinguished by several DNA markers. As a result, the strains causing ash dieback were reassigned as H. pseudoalbidus. The closely related H. albidus is presumably a non‐pathogenic endophyte, but pathogenicity tests to confirm this hypothesis have not yet been performed. Genotyping of herbarium specimens has shown that H. pseudoalbidus was present in Switzerland for at least a decade prior to the epidemic outbreak in Europe. The origin of the ash dieback pathogen, and the general importance of correct pathogen identification to development of effective disease control, are discussed.
Seeking alternatives to probit 9 when developing treatments for wood packaging materials under ISPM No. 15
Authors: Haack R. A. , Uzunovic A. , Hoover K. , Cook J. A.
Published: March 2011

ISPM No. 15 presents guidelines for treating wood packaging material used in international trade. There are currently two approved phytosanitary treatments: heat treatment and methyl bromide fumigation. New treatments are under development, and are needed given that methyl bromide is being phased out. Probit 9 efficacy (100% mortality of at least 93 613 test organisms) has been suggested as an evaluation criterion for new wood treatments, and is based on fruit fly research. We question requiring probit 9 efficacy for wood pests (insects, nematodes and fungi) and discuss challenges to meeting this requirement. Instead, we suggest a 3‐step, laboratory‐based alternative approach. Step 1 involves laboratory experiments (screening) to estimate the lethal dose for the most tolerant stage of each target pest. We consider each infested piece of wood as an experimental unit, not the individual pests, to avoid pseudoreplication. Step 2 requires replicated experiments (with no survivors) at the estimated lethal dose. We suggest a minimum sample size of 60 experimental units, which achieves 0.95 statistical reliability at the 95% confidence level. Step 3 entails studies under simulated operational conditions using wood samples similar in size to wood packaging material and infested to levels that reflect field conditions.
Diverse marsh plant communities are more consistently productive across a range of different environmental conditions through functional complementarity
Authors: Steudel Bastian , Hautier Yann , Hector Andy , Kessler Michael
Published: March 2011

1. Understanding the influence of biodiversity on ecosystem functionality is crucial in modern ecosystem management, especially with regard to the resistance and resilience of ecosystems to future environmental changes. In this study, we assessed the effects of three different environmental regimes on the relationship between diversity and biomass production among marsh plants in comparison with a control treatment to elucidate the underlying classes of proximate mechanisms.

2. We subjected assemblages of up to 23 marsh plant species to four different treatments (control, drought, salt, shade) for 4 months. We examined the treatment effect on the relationship between species diversity and biomass production and explored the underlying mechanism.

3. Biomass production in the manipulated treatments showed a stronger positive effect of biodiversity than the control because of greater declines of biomass production in low diversity mixtures. This effect was owing to an increasingly positive complementarity effect, i.e. a benefit of most species, with increasing diversity, particularly in shade treatment. The selection effect, i.e. a benefit for few species at the expense of the others, was increasingly negative with increasing diversity and dominance by species with lower than average monoculture biomass. The variability of biomass production decreased with increasing species richness in all treatments.

4. Synthesis and applications. We show that the productivity of diverse marsh plant communities is more consistent across a range of environmental conditions than that of depauperate communities and that this unexpectedly resulted from complementarity rather than selection effects. Our results demonstrate that loss of vegetation diversity reduces the average biomass production across a range of environmental conditions and emphasizes the importance of maintaining species‐rich biotic assemblages, especially in the face of global change.
Multiple orphan histidine kinases interact directly with Spo0A to control the initiation of endospore formation in Clostridium acetobutylicum
Authors: Steiner Elisabeth , Dago Angel E. , Young Danielle I. , Heap John T. , Minton Nigel P. , Hoch James A. , Young Michael
Published: March 2011

The phosphorylated Spo0A transcription factor controls the initiation of endospore formation in Clostridium acetobutylicum, but genes encoding key phosphorelay components, Spo0F and Spo0B, are missing in the genome. We hypothesized that the five orphan histidine kinases of C. acetobutylicum interact directly with Spo0A to control its phosphorylation state. Sequential targeted gene disruption and gene expression profiling provided evidence for two pathways for Spo0A activation, one dependent on a histidine kinase encoded by cac0323, the other on both histidine kinases encoded by cac0903 and cac3319. Purified Cac0903 and Cac3319 kinases autophosphorylated and transferred phosphoryl groups to Spo0A in vitro, confirming their role in Spo0A activation in vivo. A cac0437 mutant hyper‐sporulated, suggesting that Cac0437 is a modulator that prevents sporulation and maintains cellular Spo0A∼P homeostasis during growth. Accordingly, Cac0437 has apparently lost the ability to autophosphorylate in vitro; instead it catalyses the ATP‐dependent dephosphorylation of Spo0A∼P releasing inorganic phosphate. Direct phosphorylation of Spo0A by histidine kinases and dephosphorylation by kinase‐like proteins may be a common feature of the clostridia that may represent the ancestral state before the great oxygen event some 2.4 billion years ago, after which additional phosphorelay proteins were recruited in the evolutionary lineage that led to the bacilli.
Diversity analysis of the response to Zn within the Arabidopsis thaliana species revealed a low contribution of Zn translocation to Zn tolerance and a new role for Zn in lateral root development
Authors: RICHARD O. , PINEAU C. , LOUBET S. , CHALIES C. , VILE D. , MARQUÈS L. , BERTHOMIEU P.
Published: March 2011

This work reports the first characterization of the natural variation of Zn tolerance and accumulation in Arabidopsis thaliana. Root and shoot growth as well as Zn content were determined for 27 A. thaliana accessions grown in vitro in presence of Zn concentrations ranging from 1 to 250 µm. All traits varied by at least twofold and their broad sense heritability varied from 0.36 to 0.91. Primary and lateral root developments were differently affected by Zn in the different accessions. Remarkably, Zn was for the first time shown to be essential for the development of lateral roots. As a general rule, the different traits showed uncorrelated variations. In particular, variation in Zn tolerance was not linked to either root or shoot Zn contents. The only detectable relationship between different traits linked Zn sensitivity of roots to root‐to‐shoot Zn translocation but the correlation between variation of these traits was pretty low. This suggests that Zn translocation from root to shoots explains only a part of Zn tolerance. Our analysis opens the way to the characterization of genetic determinants controlling different Zn‐related traits through the identification of particular accessions displaying contrasted phenotypes and representing excellent starting material to develop quantitative trait locus (QTL) studies.
Functional Expression of NOD2 in Freshly Isolated Human Peripheral Blood γδ T Cells
Authors: Marischen L. , Wesch D. , Oberg H.‐H. , Rosenstiel P. , Trad A. , Shomali M. , Grötzinger J. , Janssen O. , Tchikov V. , Schütze S. , Kabelitz D.
Published: March 2011

γδ T cells play an important role in anti‐infective immunity. The major subset of human γδ T cells selectively recognizes phosphorylated bacterial metabolites of the isoprenoid biosynthesis pathway, so‐called phosphoantigens. The activation of γδ T cells is modulated by functionally expressed innate immune receptors, notably Toll‐like receptor 2 and 3. It was also reported that in vitro expanded γδ T cells respond to muramyl dipeptide (MDP), the minimal peptidoglycan motif activating the nucleotide‐binding oligomerization domain containing 2 (NOD2) receptor, although it is unknown whether ex vivo isolated human γδ T cells express functional NOD2. Here, we report that freshly isolated, highly purified peripheral blood γδ T cells express NOD2 mRNA and detectable amounts of NOD2 protein. The biologically active MDP L‐D isomer but not the inactive D‐D isomer augmented the interferon‐γ (IFN‐γ) secretion in phosphoantigen‐stimulated peripheral blood mononuclear cells. Moreover, a moderate but reproducible and statistically significant increase in IFN‐γ secretion was also observed when highly purified peripheral blood γδ T cells were activated by T cell receptor cross‐linking in the presence of MDP. Taken together, our results indicate that in addition to the T cell receptor and Toll‐like receptors, circulating human γδ T cells express NOD2 as a third class of pattern recognition receptor for sensing bacterial products.
Epidemiology, clinical signs, histopathology and molecular characterization of canine leproid granuloma: a retrospective study of cases from Brazil
Authors: Conceição Lissandro Gonçalves , Acha Livia Maria Rosa , Borges Alexandre Secorun , Assis Fernanda G. , Loures Fabricia Hallack , e Silva Fabyano Fonseca
Published: March 2011

Thirty‐eight cases of canine leproid granuloma were diagnosed between 2000 and 2008. Diagnosis was based upon clinical and histopathological findings and the presence of acid‐fast bacilli in skin sections. The clinical lesions were localized predominantly on the pinnae and included papules, plaques and nodules, with or without ulceration. Boxer dogs were the breed most affected. Histopathological findings included nodular to diffuse pyogranulomatous, lymphoplasmocytic inflammatory infiltrates, with or without necrosis, localized in the dermis or subcutaneous tissue. The bacillary loading and morphology were variable among the lesions analysed. There was no significant correlation between bacterial load and histopathological pattern, dominant type of inflammatory infiltration or the amount of necrosis or giant cells. No correlation was observed between giant cells and histopathological pattern. In the majority of cases where a PCR‐based assay was done, a novel mycobacterium species as the main aetiological agent was identified, as reported in previous studies.
Modelling evolution and management of glyphosate resistance in Amaranthus palmeri
Authors: NEVE P , NORSWORTHY J K , SMITH K L , ZELAYA I A
Published: March 2011

Neve P, Norsworthy JK, Smith KL & Zelaya IA (2011). Modelling evolution and management of glyphosate resistance in Amaranthus palmeri. Weed Research51, 99–112.

A population‐based model was developed to simulate the evolution of glyphosate resistance in populations of Amaranthus palmeri. Model parameters were derived from published and unpublished sources, and the model was implemented using previously established principles and methods. Sensitivity analyses indicated that the model was sensitive to variations in population size, mutation rate and seed bank dynamics. A distribution was assigned to these parameters and Monte Carlo type simulations were performed. Simulation results are therefore derived from a range of possible input parameters, enabling the risk of resistance evolution to be assessed when parameter values were unknown, uncertain or variable. In the ‘worst‐case’ of five annual glyphosate applications in continuous glyphosate resistant cotton, evolution of glyphosate resistance was predicted in 39% of populations after 5 years and in c. 60% of populations after 10 years. These results are consistent with observations of the timescale for evolution of glyphosate resistance in A. palmeri in the field. The main drivers for glyphosate resistance evolution were selection pressure and population size, the greatest risks being associated with the largest A. palmeri populations. Risks of resistance were reduced when one of the five glyphosate applications was replaced by another mode of action with identical efficacy. However, not all glyphosate applications exerted the same selection pressure. Application of a soil residual herbicide at the time of crop sowing can provide control of A. palmeri well into the growing season and significantly reduced the rate and risk of glyphosate resistance evolution.
Differential impact on post‐transplant outcomes between pulsatile‐ and continuous‐flow left ventricular assist devices
Authors: Ventura Pere A. , Alharethi Rami , Budge Deborah , Reid Bruce B. , Horne Benjamin D. , Mason Nathan O. , Stoker Sandi , Caine William T. , Rasmusson Brad , Doty John , Clayson Stephen E. , Kfoury Abdallah G.
Published: March 2011

Ventura PA, Alharethi R, Budge D, Reid BB, Horne BD, Mason NO, Stoker S, Caine WT, Rasmusson B, Doty J, Clayson SE, Kfoury AG. Differential impact on post‐transplant outcomes between pulsatile‐ and continuous‐flow left ventricular assist devices. Clin Transplant 2011: 25: E390–E395. © 2011 John Wiley & Sons A/S.

Abstract:  Background:  The HeartMate II (HMII) left ventricular assist device (LVAD) has proven reliable and durable and has become the preferred choice for bridge to transplant therapy (BTT) when compared with the pulsatile HeartMate XVE (XVE). In this study, we compared the post‐transplant (PTx) outcomes between XVE and HMII using a large national data registry.

Methods:  The Organ Procurement and Transplantation Network (OPTN)/United Network for Organ Sharing (UNOS) Thoracic Registry database was queried for all patients implanted with either an XVE or an HMII as BTT during 2004–2009. Statistical analysis between XVE and HMII were performed using Kaplan–Meier survival analysis and Cox regression analyses.

Results:  A total of 673 patients were implanted with the XVE and 484 with HMII. When adjusted for age, gender, ethnicity, intra‐aortic balloon pump, ventilator, inotropes, dialysis, body mass index, creatinine, bilirubin, transfusion, pulmonary capillary wedge, and pulmonary arterial pressures, the HMII had similar one‐ and three‐yr survival (hazard ratio = 0.95, CI = 0.64, 1.42) and rejection‐free survival PTx compared to XVE. The XVE group had more early incidences of allograft rejection (AR) and hospitalization for infection (HI).

Conclusions:  Compared to XVE, patients with HMII have similar one‐ and three‐yr survival after heart transplantation with less risk of early graft rejection and significant infection. With a strong shift toward use of continuous‐flow LVADs, PTx outcomes are expected to continue to improve.