bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new endoconidial black meristematic genus,Atramixtia, associated with declining white spruce and phylogenetically allied to a lineage of dothidealean conifer pathogens
Authors: Tsuneda A. , Davey M.L. , Currah R.S. 
Published: May 2011

An endoconidial, black meristematic taxon Atramixtia arboricola gen. et. sp. nov. (Dothideales) from the black subicula found on twigs of declining white spruce, Picea glauca (Moench) Voss, in Alberta is described. It is morphologically distinguishable from other endoconidial taxa by the conidioma composed of clumps of endoconidial conidiogenous cells, scattered meristematically dividing cells, dematiaceous hyphae, abundant brown, granular matrix materials, and sometimes plant tissue. Endoconidia also occur in conidiogenous cellular clumps that are not organized into a conidioma but develop directly from stromatic cells on the bark. In culture, it forms similar endoconidial conidiomata and also a mycelial, blastic synanamorph that superficially resembles Hormonema . Atramixtia arboricola is a member of the Dothideales and shows phylogenetic affinities to a clade of conifer-stem and -needle pathogens, including Sydowia and Delphinella , although no teleomorph was found either on the natural substrate or in culture. It has not been determined whether A. arboricola is pathogenic to its host, but the occurrence of abundant intracellular hyphae in the host periderm suggests that the fungus is at least parasitic.
Role of selected dark septate endophyte species and other hyphomycetes as saprobes on moss gametophytes
Authors: Day Melissa J. , Currah Randolph S. 
Published: May 2011

Dark septate endophytes (DSEs) live asymptomatically in the roots of vascular plants, are common in arctic and alpine areas, and are thought to play a quasimycorrhizal role. It is not known, however, whether they precede or arrive with their hosts. Previously reported enzymatic abilities of Phialocephala fortinii suggest that DSEs can live on organic debris in the soil, but there is little direct or experimental evidence for this. Phialocephala fortinii , Leptodontidium orchidicola , Cadophora melinii , Cadophora luteo-olivacea , and Lecythophora sp. were inoculated onto autoclaved Hylocomium splendens gametophytes and incubated for 3 months to determine if they degrade this organic material based on observations made using light and scanning electron microscopy. All fungi were able to colonize the bryophyte tissue to some extent. Lecythophora sp. and L. orchidicola penetrated cells by forming bore holes. Cadophora luteo-olivacea and P. fortinii were also observed inside cells, but bore holes through bryophyte cell walls were not observed. Cadophora melinii sporulated and grew abundantly on the surface of gametophytes but did not appear to penetrate cell walls. Phialocephala fortinii and L. orchidicola formed sclerotia in the gametophytes similar to those formed in roots. These results suggest that DSE fungi can persist and produce propagules, i.e., sclerotia and conidia, in the absence of host roots. These observations support the hypothesis that DSE fungi are able to precede their hosts during primary succession events.
Pharmacogenomics of bortezomib test-dosing identifies hyperexpression of proteasome genes, especially PSMD4, as novel high-risk feature in myeloma treated with Total Therapy 3
Authors: Shaughnessy John D. , Qu Pingping , Usmani Saad , Heuck Christoph J. , Zhang Qing , Zhou Yiming , Tian Erming , Hanamura Ichiro , van Rhee Frits , Anaissie Elias , Epstein Joshua , Nair Bijay , Stephens Owen , Williams Ryan , Waheed Sarah , Alsayed Yazan , Crowley John , Barlogie Bart 
Published: May 2011

Abstract
Gene expression profiling (GEP) of purified plasma cells 48 hours after thalidomide and dexamethasone test doses showed these agents' mechanisms of action and provided prognostic information for untreated myeloma patients on Total Therapy 2 (TT2). Bortezomib was added in Total Therapy 3 (TT3), and 48 hours after bortezomib GEP analysis identified 80 highly survival-discriminatory genes in a training set of 142 TT3A patients that were validated in 128 patients receiving TT3B. The 80-gene GEP model (GEP80) also distinguished outcomes when applied at baseline in both TT3 and TT2 protocols. In context of our validated 70-gene model (GEP70), the GEP80 model identified 9% of patients with a grave prognosis among those with GEP70-defined low-risk disease and 41% of patients with favorable prognosis among those with GEP70-defined high-risk disease. PMSD4 was 1 of 3 genes common to both models. Residing on chromosome 1q21, PSMD4 expression is highly sensitive to copy number. Both higher PSMD4 expression levels and higher 1q21 copy numbers affected clinical outcome adversely. GEP80 baseline-defined high risk, high lactate dehydrogenase, and low albumin were the only independent adverse variables surviving multivariate survival model. We are investigating whether second-generation proteasome inhibitors (eg, carfilzomib) can overcome resistance associated with high PSMD4 levels.
MiR-17/20/93/106 promote hematopoietic cell expansion by targeting sequestosome 1–regulated pathways in mice
Authors: Meenhuis Annemarie , van Veelen Peter A. , de Looper Hans , van Boxtel Nicole , van den Berge Iris J. , Sun Su M. , Taskesen Erdogan , Stern Patrick , de Ru Arnoud H. , van Adrichem Arjan J. , Demmers Jeroen , Jongen-Lavrencic Mojca , Löwenberg Bob , Touw Ivo P. , Sharp Phillip A. , Erkeland Stefan J. 
Published: May 2011

Abstract
MicroRNAs (miRNAs) are pivotal for regulation of hematopoiesis but their critical targets remain largely unknown. Here, we show that ectopic expression of miR-17, -20,-93 and -106, all AAAGUGC seed-containing miRNAs, increases proliferation, colony outgrowth and replating capacity of myeloid progenitors and results in enhanced P-ERK levels. We found that these miRNAs are endogenously and abundantly expressed in myeloid progenitors and down-regulated in mature neutrophils. Quantitative proteomics identified sequestosome 1 (SQSTM1), an ubiquitin-binding protein and regulator of autophagy-mediated protein degradation, as a major target for these miRNAs in myeloid progenitors. In addition, we found increased expression of Sqstm1 transcripts during CSF3-induced neutrophil differentiation of 32D-CSF3R cells and an inverse correlation of SQSTM1 protein levels and miR-106 expression in AML samples. ShRNA-mediated silencing of Sqstm1 phenocopied the effects of ectopic miR-17/20/93/106 expression in hematopoietic progenitors in vitro and in mice. Further, SQSTM1 binds to the ligand-activated colony-stimulating factor 3 receptor (CSF3R) mainly in the late endosomal compartment, but not in LC3 positive autophagosomes. SQSTM1 regulates CSF3R stability and ligand-induced mitogen-activated protein kinase signaling. We demonstrate that AAAGUGC seed-containing miRNAs promote cell expansion, replating capacity and signaling in hematopoietic cells by interference with SQSTM1-regulated pathways.
Engineering Klebsiella sp. 601 multicopper oxidase enhances the catalytic efficiency towards phenolic substrates
Authors: Li Yadong , Gong Zijun , Li Xin , Li Yang , Wang Xing-Guo 
Published: May 2011

Abstract

Background
Structural comparison between bacterial CueO and fungal laccases has suggested that a charged residue Glu (E106) in CueO replaces the corresponding residue Phe in fungal laccases at the gate of the tunnel connecting type II copper to the protein surface and an extra α-helix (L351-G378) near the type I copper site covers the substrate binding pocket and might compromise the electron transfer from substrate to type I copper. To test this hypothesis, several mutants were made in Klebsiella sp. 601 multicopper oxidase, which is highly homologous to E. coli CueO with a similarity of 90% and an identity of 78%.

Results
The E106F mutant gave smaller K

m
(2.4-7fold) and k

cat
(1-4.4 fold) values for all three substrates DMP, ABTS and SGZ as compared with those for the wild-type enzyme. Its slightly larger k

cat

/K

m
values for three substrates mainly come from the decreased K

m
. Deleting α-helix (L351-G378) resulted in the formation of inactive inclusion body when the mutant Δα351-378 was expressed in E. coli. Another mutant α351-380M was then made via substitution of seven amino acid residues in the α-helix (L351-G378) region. The α351-380M mutant was active, and displayed a far-UV CD spectrum markedly different from that for wild-type enzyme. Kinetic studies showed the α351-380M mutant gave very low K

m
values for DMP, ABTS and SGZ, 4.5-, 1.9- and 7-fold less than those for the wild type. In addition, k

cat

/K

m
values were increased, 9.4-fold for DMP, similar for ABTS and 3-fold for SGZ.

Conclusion
The Glu residue at position 106 appears not to be the only factor affecting the copper binding, and it may also play a role in maintaining enzyme conformation. The α-helix (L351-G378) may not only block access to the type I copper site but also play a role in substrate specificities of bacterial MCOs. The α351-380M mutant catalyzing oxidation of the phenolic substrate DMP effectively would be very useful in green chemistry.
RAG: An update to the RNA-As-Graphs resource
Authors: Izzo Joseph A , Kim Namhee , Elmetwaly Shereef , Schlick Tamar 
Published: May 2011

Abstract

Background
In 2004, we presented a web resource for stimulating the search for novel RNAs, RNA-As-Graphs (RAG), which classified, catalogued, and predicted RNA secondary structure motifs using clustering and build-up approaches. With the increased availability of secondary structures in recent years, we update the RAG resource and provide various improvements for analyzing RNA structures.

Description
Our RAG update includes a new supervised clustering algorithm that can suggest RNA motifs that may be "RNA-like". We use this utility to describe RNA motifs as three classes: existing, RNA-like, and non-RNA-like. This produces 126 tree and 16,658 dual graphs as candidate RNA-like topologies using the supervised clustering algorithm with existing RNAs serving as the training data. A comparison of this clustering approach to an earlier method shows considerable improvements. Additional RAG features include greatly expanded search capabilities, an interface to better utilize the benefits of relational database, and improvements to several of the utilities such as directed/labeled graphs and a subgraph search program.

Conclusions
The RAG updates presented here augment the database's intended function - stimulating the search for novel RNA functionality - by classifying available motifs, suggesting new motifs for design, and allowing for more specific searches for specific topologies. The updated RAG web resource offers users a graph-based tool for exploring available RNA motifs and suggesting new RNAs for design.
The 5S rDNA family evolves through concerted and birth-and-death evolution in fish genomes: an example from freshwater stingrays
Authors: Pinhal Danillo , Yoshimura Tatiana S , Araki Carlos S , Martins Cesar 
Published: May 2011

Abstract

Background
Ribosomal 5S genes are well known for the critical role they play in ribosome folding and functionality. These genes are thought to evolve in a concerted fashion, with high rates of homogenization of gene copies. However, the majority of previous analyses regarding the evolutionary process of rDNA repeats were conducted in invertebrates and plants. Studies have also been conducted on vertebrates, but these analyses were usually restricted to the 18S, 5.8S and 28S rRNA genes. The recent identification of divergent 5S rRNA gene paralogs in the genomes of elasmobranches and teleost fishes indicate that the eukaryotic 5S rRNA gene family has a more complex genomic organization than previously thought. The availability of new sequence data from lower vertebrates such as teleosts and elasmobranches enables an enhanced evolutionary characterization of 5S rDNA among vertebrates.

Results
We identified two variant classes of 5S rDNA sequences in the genomes of Potamotrygonidae stingrays, similar to the genomes of other vertebrates. One class of 5S rRNA genes was shared only by elasmobranches. A broad comparative survey among 100 vertebrate species suggests that the 5S rRNA gene variants in fishes originated from rounds of genome duplication. These variants were then maintained or eliminated by birth-and-death mechanisms, under intense purifying selection. Clustered multiple copies of 5S rDNA variants could have arisen due to unequal crossing over mechanisms. Simultaneously, the distinct genome clusters were independently homogenized, resulting in the maintenance of clusters of highly similar repeats through concerted evolution.

Conclusions
We believe that 5S rDNA molecular evolution in fish genomes is driven by a mixed mechanism that integrates birth-and-death and concerted evolution.
Global analysis of gene expression in response to L-Cysteine deprivation in the anaerobic protozoan parasite Entamoeba histolytica
Authors: Husain Afzal , Jeelani Ghulam , Sato Dan , Nozaki Tomoyoshi 
Published: May 2011

Abstract

Background

Entamoeba histolytica, an enteric protozoan parasite, causes amebic colitis and extra intestinal abscesses in millions of inhabitants of endemic areas. E. histolytica completely lacks glutathione metabolism but possesses L-cysteine as the principle low molecular weight thiol. L-Cysteine is essential for the structure, stability, and various protein functions, including catalysis, electron transfer, redox regulation, nitrogen fixation, and sensing for regulatory processes. Recently, we demonstrated that in E. histolytica, L-cysteine regulates various metabolic pathways including energy, amino acid, and phospholipid metabolism.

Results
In this study, employing custom-made Affymetrix microarrays, we performed time course (3, 6, 12, 24, and 48 h) gene expression analysis upon L-cysteine deprivation. We identified that out of 9,327 genes represented on the array, 290 genes encoding proteins with functions in metabolism, signalling, DNA/RNA regulation, electron transport, stress response, membrane transport, vesicular trafficking/secretion, and cytoskeleton were differentially expressed (≥3 fold) at one or more time points upon L-cysteine deprivation. Approximately 60% of these modulated genes encoded proteins of no known function and annotated as hypothetical proteins. We also attempted further functional analysis of some of the most highly modulated genes by L-cysteine depletion.

Conclusions
To our surprise, L-cysteine depletion caused only limited changes in the expression of genes involved in sulfur-containing amino acid metabolism and oxidative stress defense. In contrast, we observed significant changes in the expression of several genes encoding iron sulfur flavoproteins, a major facilitator super-family transporter, regulator of nonsense transcripts, NADPH-dependent oxido-reductase, short chain dehydrogenase, acetyltransferases, and various other genes involved in diverse cellular functions. This study represents the first genome-wide analysis of transcriptional changes induced by L-cysteine deprivation in protozoan parasites, and in eukaryotic organisms where L-cysteine represents the major intracellular thiol.
Song exposure regulates known and novel microRNAs in the zebra finch auditory forebrain
Authors: Gunaratne Preethi H , Lin Ya-Chi , Benham Ashley L , Drnevich Jenny , Coarfa Cristian , Tennakoon Jayantha B , Creighton Chad J , Kim Jong H , Milosavljevic Aleksandar , Watson Michael , Griffiths-Jones Sam , Clayton David F 
Published: May 2011

AbstractBackgroundIn an important model for neuroscience, songbirds learn to discriminate songs they hear during tape-recorded playbacks, as demonstrated by song-specific habituation of both behavioral and neurogenomic responses in the auditory forebrain. We hypothesized that microRNAs (miRNAs or miRs) may participate in the changing pattern of gene expression induced by song exposure. To test this, we used massively parallel Illumina sequencing to analyse small RNAs from auditory forebrain of adult zebra finches exposed to tape-recorded birdsong or silence.ResultsIn the auditory forebrain, we identified 121 known miRNAs conserved in other vertebrates. We also identified 34 novel miRNAs that do not align to human or chicken genomes. Five conserved miRNAs showed significant and consistent changes in copy number after song exposure across three biological replications of the song-silence comparison, with two increasing (tgu-miR-25, tgu-miR-192) and three decreasing (tgu-miR-92, tgu-miR-124, tgu-miR-129-5p). We also detected a locus on the Z sex chromosome that produces three different novel miRNAs, with supporting evidence from Northern blot and TaqMan qPCR assays for differential expression in males and females and in response to song playbacks. One of these, tgu-miR-2954-3p, is predicted (by TargetScan) to regulate eight song-responsive mRNAs that all have functions in cellular proliferation and neuronal differentiation.ConclusionsThe experience of hearing another bird singing alters the profile of miRNAs in the auditory forebrain of zebra finches. The response involves both known conserved miRNAs and novel miRNAs described so far only in the zebra finch, including a novel sex-linked, song-responsive miRNA. These results indicate that miRNAs are likely to contribute to the unique behavioural biology of learned song communication in songbirds.
Study of polymorphisms in tir, eae and tccP2 genes in enterohaemorrhagic and enteropathogenic Escherichia coli of serogroup O26
Authors: Bardiau Marjorie , Labrozzo Sabrina , Mainil Jacques G 
Published: May 2011

AbstractBackgroundEnteropathogenic (EPEC) and enterohaemorrhagic (EHEC)Escherichia coliare responsible for food poisoning (enteritis and enterotoxaemia) in humans in developed countries. Cattle are considered to be an important reservoir of EHEC and EPEC strains for humans. Moreover, some of the strains, belonging to the O26, O111, O118 serogroups, for example, are also responsible for digestive disorders in calves. The Translocated intimin receptor (Tir), the intimin (Eae) and the Tir-cytoskeleton coupling protein (TccP) represent three virulence factors implicated in the intimate attachment of the bacteria to the eukaryotic cell. Major variants have already been described for these genes among the different serogroups but minor variations have not often been studied. In this study, we examined the polymorphisms of thetir,eaeandtccP2genes of O26 strains (EPEC and EHEC isolated from bovines and from humans) with the aim to determine whether these polymorphisms are host specific or not.ResultsOf the 70 tested strains, 10 strains (14% of the strains) presented one or several polymorphisms in thetirandeaegenes, which have never previously been described. ConcerningtccP2detection, 47 of the 70 strains (67% of the strains) were found to be positive for this gene. Most of the strains were found to possesstccP2variants described in strains of serogroup O26. Nevertheless, three strains hadtccP2genes respectively described in strains of serogroup O111, O103 and O55. Moreover, none of the polymorphisms was statistically specific to the bovine or the human isolates. Nevertheless, the two major variants oftccP2were statistically associated with the pathotype (EPEC or EHEC).ConclusionsIn conclusion,tirandeaegene polymorphisms were found not to be numerous and not to be predominantly synonymous. Moreover, no difference was observed between human and bovine strains regarding the presence of polymorphisms. Finally, sometccP2variants appeared to be pathotype specific. Further investigations need to be performed on a larger number of strains in order to confirm this specificity.
MDM2 antagonist Nutlin-3a potentiates antitumour activity of cytotoxic drugs in sarcoma cell lines
Authors: Ohnstad Hege O , Paulsen Erik B , Noordhuis Paul , Berg Marianne , Lothe Ragnhild A , Vassilev Lyubomir T , Myklebost Ola 
Published: May 2011

Abstract

Background
Frequent failure and severe side effects of current sarcoma therapy warrants new therapeutic approaches. The small-molecule MDM2 antagonist Nutlin-3a activates the p53 pathway and efficiently induces apoptosis in tumours with amplified MDM2 gene and overexpression of MDM2 protein. However, the majority of human sarcomas have normal level of MDM2 and the therapeutic potential of MDM2 antagonists in this group is still unclear. We have investigated if Nutlin-3a could be employed to augment the response to traditional therapy and/or reduce the genotoxic burden of chemotherapy.

Methods
A panel of sarcoma cell lines with different TP53 and MDM2 status were treated with Nutlin-3a combined with Doxorubicin, Methotrexate or Cisplatin, and their combination index determined.

Results
Clear synergism was observed when Doxorubicin and Nutlin-3a were combined in cell lines with wild-type TP53 and amplified MDM2, or with Methotrexate in both MDM2 normal and amplified sarcoma cell lines, allowing for up to tenfold reduction of cytotoxic drug dose. Interestingly, Nutlin-3a seemed to potentiate the effect of classical drugs as Doxorubicin and Cisplatin in cell lines with mutated TP53, but inhibited the effect of Methotrexate.

Conclusion
The use of Nutlin in combination with classical sarcoma chemotherapy shows promising preclinical potential, but since clear biomarkers are still lacking, clinical trials should be followed up with detailed tumour profiling.
The synthetic peptide P111-136 derived from the C-terminal domain of heparin affin regulatory peptide inhibits tumour growth of prostate cancer PC-3 cells
Authors: Hamma-Kourbali Yamina , Bermek Oya , Bernard-Pierrot Isabelle , Karaky Racha , Martel-Renoir Dominique , Frechault Sophie , Courty José , Delbé Jean 
Published: May 2011

Abstract

Background
Heparin affin regulatory peptide (HARP), also called pleiotrophin, is a heparin-binding, secreted factor that is overexpressed in several tumours and associated to tumour growth, angiogenesis and metastasis. The C-terminus part of HARP composed of amino acids 111 to 136 is particularly involved in its biological activities and we previously established that a synthetic peptide composed of the same amino acids (P111-136) was capable of inhibiting the biological activities of HARP. Here we evaluate the ability of P111-136 to inhibit in vitro and in vivo the growth of a human tumour cell line PC-3 which possess an HARP autocrine loop.

Methods
A total lysate of PC-3 cells was incubated with biotinylated P111-136 and pulled down for the presence of the HARP receptors in Western blot. In vitro, the P111-136 effect on HARP autocrine loop in PC-3 cells was determined by colony formation in soft agar. In vivo, PC-3 cells were inoculated in the flank of athymic nude mice. Animals were treated with P111-136 (5 mg/kg/day) for 25 days. Tumour volume was evaluated during the treatment. After the animal sacrifice, the tumour apoptosis and associated angiogenesis were evaluated by immunohistochemistry. In vivo anti-angiogenic effect was confirmed using a mouse Matrigel™ plug assay.

Results
Using pull down experiments, we identified the HARP receptors RPTPβ/ζ, ALK and nucleolin as P111-136 binding proteins. In vitro, P111-136 inhibits dose-dependently PC-3 cell colony formation. Treatment with P111-136 inhibits significantly the PC-3 tumour growth in the xenograft model as well as tumour angiogenesis. The angiostatic effect of P111-136 on HARP was also confirmed using an in vivo Matrigel™ plug assay in mice

Conclusions
Our results demonstrate that P111-136 strongly inhibits the mitogenic effect of HARP on in vitro and in vivo growth of PC-3 cells. This inhibition could be linked to a direct or indirect binding of this peptide to the HARP receptors (ALK, RPTPβ/ζ, nucleolin). In vivo, the P111-136 treatment significantly inhibits both the PC-3 tumour growth and the associated angiogenesis. Thus, P111-136 may be considered as an interesting pharmacological tool to interfere with tumour growth that has now to be evaluated in other cancer types.