bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global Transcriptome Changes Underlying Colony Growth in the Opportunistic Human Pathogen Aspergillus fumigatus
Authors: Gibbons John G. , Beauvais Anne , Beau Remi , McGary Kriston L. , Latgé Jean-Paul , Rokas Antonis 
Published: July 2011

ABSTRACT

Aspergillus fumigatus
is the most common and deadly pulmonary fungal infection worldwide. In the lung, the fungus usually forms a dense colony of filaments embedded in a polymeric extracellular matrix. To identify candidate genes involved in this biofilm (BF) growth, we used RNA-Seq to compare the transcriptomes of BF and liquid plankton (PL) growth. Sequencing and mapping of tens of millions sequence reads against the
A. fumigatus
transcriptome identified 3,728 differentially regulated genes in the two conditions. Although many of these genes, including the ones coding for transcription factors, stress response, the ribosome, and the translation machinery, likely reflect the different growth demands in the two conditions, our experiment also identified hundreds of candidate genes for the observed differences in morphology and pathobiology between BF and PL. We found an overrepresentation of upregulated genes in transport, secondary metabolism, and cell wall and surface functions. Furthermore, upregulated genes showed significant spatial structure across the
A. fumigatus
genome; they were more likely to occur in subtelomeric regions and colocalized in 27 genomic neighborhoods, many of which overlapped with known or candidate secondary metabolism gene clusters. We also identified 1,164 genes that were downregulated. This gene set was not spatially structured across the genome and was overrepresented in genes participating in primary metabolic functions, including carbon and amino acid metabolism. These results add valuable insight into the genetics of biofilm formation in
A. fumigatus
and other filamentous fungi and identify many relevant, in the context of biofilm biology, candidate genes for downstream functional experiments.
Autotrophic Methanotrophy in Verrucomicrobia: Methylacidiphilum fumariolicumSolV Uses the Calvin-Benson-Bassham Cycle for Carbon Dioxide Fixation
Authors: Khadem Ahmad F. , Pol Arjan , Wieczorek Adam , Mohammadi Seyed S. , Francoijs Kees-Jan , Stunnenberg Henk G. , Jetten Mike S. M. , Op den Camp Huub J. M. 
Published: July 2011

ABSTRACT

Genome data of the extreme acidophilic verrucomicrobial methanotroph
Methylacidiphilum fumariolicum
strain SolV indicated the ability of autotrophic growth. This was further validated by transcriptome analysis, which showed that all genes required for a functional Calvin-Benson-Bassham (CBB) cycle were transcribed. Experiments with
13
CH
4
or
13
CO
2
in batch and chemostat cultures demonstrated that CO
2
is the sole carbon source for growth of strain SolV. In the presence of CH
4
, CO
2
concentrations in the headspace below 1% (vol/vol) were growth limiting, and no growth was observed when CO
2
concentrations were below 0.3% (vol/vol). The activity of the key enzyme of the CBB cycle, ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), measured with a
13
C stable-isotope method was about 70 nmol CO
2
fixed · min
−1
· mg of protein
−1
. An immune reaction with antibody against the large subunit of RuBisCO on Western blots was found only in the supernatant fractions of cell extracts. The apparent native mass of the RuBisCO complex in strain SolV was about 482 kDa, probably consisting of 8 large (53-kDa) and 8 small (16-kDa) subunits. Based on phylogenetic analysis of the corresponding RuBisCO gene, we postulate that RuBisCO of the verrucomicrobial methanotrophs represents a new type of form I RuBisCO.
Regulated Shift from Helical to Polar Localization of Listeria monocytogenesCell Wall-Anchored Proteins
Authors: Bruck Serawit , Personnic Nicolas , Prevost Marie-Christine , Cossart Pascale , Bierne Hélène 
Published: July 2011

ABSTRACTMany virulence factors of Gram-positive bacterial pathogens are covalently anchored to the peptidoglycan (PG) by sortase enzymes. However, for rod-shaped bacteria little is known about the spatiotemporal organization of these surface proteins in the cell wall. Here we report the three-dimensional (3D) localization of the PG-bound virulence factors InlA, InlH, InlJ, and SvpA in the envelope ofListeria monocytogenesunder different growth conditions. We found that all PG-anchored proteins are positioned along the lateral cell wall in nonoverlapping helices. However, these surface proteins can also become localized at the pole and asymmetrically distributed when specific regulatory pathways are activated. InlA and InlJ are enriched at poles when expressed at high levels in exponential-phase bacteria. InlA and InlH, which are σBdependent, specifically relocalize to the septal cell wall and subsequently to the new pole in cells entering stationary phase. The accumulation of InlA and InlH in the septal region also occurs when oxidative stress impairs bacterial growth. In contrast, the iron-dependent protein SvpA is present at the old pole and is excluded from the septum and new pole of bacteria grown under low-iron conditions. We conclude thatL. monocytogenesrapidly reorganizes the spatial localization of its PG proteins in response to changes in environmental conditions such as nutrient deprivation or other stresses. This dynamic control would distribute virulence factors at specific sites during the infectious process.
Differential Accumulation of
nif
Structural Gene mRNA in Azotobacter vinelandii
Authors: Hamilton Trinity L. , Jacobson Marty , Ludwig Marcus , Boyd Eric S. , Bryant Donald A. , Dean Dennis R. , Peters John W. 
Published: July 2011

ABSTRACT

Northern analysis was employed to investigate mRNA produced by mutant strains of
Azotobacter vinelandii
with defined deletions in the
nif
structural genes and in the intergenic noncoding regions. The results indicate that intergenic RNA secondary structures effect the differential accumulation of transcripts, supporting the high Fe protein-to-MoFe protein ratio required for optimal diazotrophic growth.
Identification of a Chemoreceptor Zinc-Binding Domain Common to Cytoplasmic Bacterial Chemoreceptors
Authors: Draper Jenny , Karplus Kevin , Ottemann Karen M. 
Published: July 2011

ABSTRACT

We report the identification and characterization of a previously unidentified protein domain found in bacterial chemoreceptors and other bacterial signal transduction proteins. This domain contains a motif of three noncontiguous histidines and one cysteine, arranged as
H
xx[WFYL]x
21-28
C
x[LFMVI]Gx[WFLVI]x
18-27
H
xxx
H
(boldface type indicates residues that are nearly 100% conserved). This domain was first identified in the soluble
Helicobacter pylori
chemoreceptor TlpD. Using inductively coupled plasma mass spectrometry on heterologously and natively expressed TlpD, we determined that this domain binds zinc with a subfemtomolar dissociation constant. We thus named the domain CZB, for chemoreceptor zinc binding. Further analysis showed that many bacterial signaling proteins contain the CZB domain, most commonly proteins that participate in chemotaxis but also those that participate in c-di-GMP signaling and nitrate/nitrite sensing, among others. Proteins bearing the CZB domain are found in several bacterial phyla. The variety of signaling proteins using the CZB domain suggests that it plays a critical role in several signal transduction pathways.
Genome Sequence of the Ethanol-Producing Zymomonas mobilis subsp. mobilis Lectotype Strain ATCC 10988
Authors: Pappas Katherine M. , Kouvelis Vassili N. , Saunders Elizabeth , Brettin Thomas S. , Bruce David , Detter Chris , Balakireva Mariya , Han Cliff S. , Savvakis Giannis , Kyrpides Nikos C. , Typas Milton A. 
Published: July 2011

ABSTRACT

Zymomonas mobilis
ATCC 10988 is the type strain of the
Z. mobilis
subsp.
mobilis
taxon, members of which are some of the most rigorous ethanol-producing bacteria. Isolated from
Agave
cactus fermentations in Mexico, ATCC 10988 is one of the first
Z. mobilis
strains to be described and studied. Its robustness in sucrose-substrate fermentations, physiological characteristics, large number of plasmids, and overall genomic plasticity render this strain important to the study of the species. Here we report the finishing and annotation of the ATCC 10988 chromosomal and plasmid genome.
Performance of the LightCycler SeptiFast Test M
grade
in Detecting Microbial Pathogens in Purulent Fluids
Authors: Sancho-Tello Silvia , Bravo Dayana , Borrás Rafael , Costa Elisa , Muñoz-Cobo Beatriz , Navarro David 
Published: June 2011

ABSTRACT
The performance of the LightCycler SeptiFast (SF) assay was compared to that of culture methods in the detection of microorganisms in 43 purulent fluids from patients with pyogenic infections. The SF assay was more sensitive than the culture methods (86% versus 61%, respectively), irrespective of whether the infections were mono- or polymicrobial.
CD4-Like Immunological Function by CD4
−
T Cells in Multiple Natural Hosts of Simian Immunodeficiency Virus
Authors: Vinton Carol , Klatt Nichole R. , Harris Levelle D. , Briant Judith A. , Sanders-Beer Brigitte E. , Herbert Richard , Woodward Ruth , Silvestri Guido , Pandrea Ivona , Apetrei Cristian , Hirsch Vanessa M. , Brenchley Jason M. 
Published: June 2011

ABSTRACT

Many species of African nonhuman primates are natural hosts for individual strains of simian immunodeficiency virus (SIV). These infected animals do not, however, develop AIDS. Here we show that multiple species of African nonhuman primate species characteristically have low frequencies of CD4
+
T cells and high frequencies of both T cells that express only the alpha-chain of CD8 and double-negative T cells. These subsets of T cells are capable of eliciting functions generally associated with CD4
+
T cells, yet these cells lack surface expression of the CD4 protein and are, therefore, poor targets for SIV
in vivo
. These data demonstrate that coevolution with SIV has, in several cases, involved downregulation of receptors for the virus by otherwise-susceptible host target cells. Understanding the genetic factors that lead to downregulation of these receptors may lead to therapeutic interventions that mimic this modulation in progressive infections.
Novel Histone H3 Binding Protein ORF158L from the Singapore Grouper Iridovirus
Authors: Tran Bich Ngoc , Chen Liming , Liu Yang , Wu Jinlu , Velázquez-Campoy Adrián , Sivaraman J. , Hew Choy Leong 
Published: June 2011

ABSTRACT

Singapore grouper iridovirus (SGIV), a major pathogen of concern for grouper aquaculture, has a double-stranded DNA (dsDNA) genome with 162 predicted open reading frames, for which a total of 62 SGIV proteins have been identified. One of these, ORF158L, bears no sequence homology to any other known protein. Knockdown of
orf158L
using antisense morpholino oligonucleotides resulted in a significant decrease in virus yield in grouper embryonic cells. ORF158L was observed in nuclei and virus assembly centers of virus-infected cells. This observation led us to study the structure and function of ORF158L. The crystal structure determined at 2.2-Å resolution reveals that ORF158L partially exhibits a structural resemblance to the histone binding region of antisilencing factor 1 (Asf1), a histone H3/H4 chaperon, despite the fact that there is no significant sequence identity between the two proteins. Interactions of ORF158L with the histone H3/H4 complex and H3 were demonstrated by isothermal titration calorimetry (ITC) experiments. Subsequently, the results of ITC studies on structure-based mutants of ORF158L suggested Arg67 and Ala93 were key residues for histone H3 interactions. Moreover, a combination of approaches of ORF158L knockdown and isobaric tags/mass spectrometry for relative and absolute quantifications (iTRAQ) revealed that ORF158L may be involved in both the regulation and the expression of histone H3 and H3 methylation. Our present studies suggest that ORF158L may function as a histone H3 chaperon, enabling it to control host cellular gene expression and to facilitate viral replication.
Comparison of clinical outcome of patients with non-small-cell lung cancer harbouring epidermal growth factor receptor exon 19 or exon 21 mutations
Authors: Won Young-Woong , Han Ji-Youn , Lee Geon Kook , Park Seog-Yun , Lim Kun Young , Yoon Kyong-Ah , Yun Tak , Kim Heung Tae , Lee Jin Soo 
Published: July 2011

AimsDeletion of exon 19 of the epidermal growth factor receptor (EGFR) and mutation of exon 21 are the most commonEGFRmutations and predict higher response to EGFR tyrosine kinase inhibitors (TKI). Accumulating data show clinical differences in both response and survival between these twoEGFRmutations. This study investigated the clinical impact ofEGFRexon 19 deletion and L858R mutation by retrospectively analysing the clinical outcome of patients with advanced non-small-cell lung cancer (NSCLC) treated with EGFR TKI.MethodsPatients harbouringEGFRexon 19 deletion or L858R mutations and who had received gefitinib or erlotinib treatment were identified. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were determined for the two groups.EGFRmutation was determined by PCR-based direct sequencing.ResultsThe study indentified 87 patients harbouringEGFRexon 19 deletion (n=61) or L858R mutation (n=26) who were treated with either gefitinib (n=83) or erlotinib (n=4). Patients with exon 19 deletion had significantly longer PFS, compared with patients with L858R mutation (9.3 vs 6.9 months, p=0.02). In a multivariate Cox regression model,EGFRexon 19 deletion was independently predictive of longer PFS (p=0.02). However, no significant differences in RR (64% vs 62%, p=0.83) and OS (17.7 vs 20.5 months, p=0.65) were observed between these two mutations.ConclusionsWhile no significant difference in OS was observed betweenEGFRexon 19 deletion and L858R mutation,EGFRexon 19 deletion was predictive of longer PFS following EGFR TKI treatment in patients with advanced NSCLC.
Recent advances in opioid prescription for chronic non-cancer pain
Authors: Snidvongs Saowarat , Mehta Vivek 
Published: July 2011

Abstract
Chronic pain is pain that persists past the normal time of healing, and is seen as a common problem with a significant socioeconomic impact. Pharmacological management for chronic non-cancer pain also involves the prescription of opioids, with the aim of an improved quality of life for the patient. New guidelines have been published to aid prescribing clinicians improve opioid safety and patient care, and include recommendations on when to refer patients to a pain specialist. In recent years there has been a rapid increase in opioid prescription in the UK and USA, prompting further concern regarding opioid abuse and side effects. Opioid use may also result in physical dependence and tolerance. Earlier recognition and diagnosis of unwanted effects of long term opioid use is needed, such as opioid induced suppression of the hypothalamic–pituitary–gonadal axis, and opioid induced immunosuppression. Patients may themselves discontinue opioids, however, due to minor side effects. Recent advances in opioid prescription include the increasing use of transdermal preparations and extended release, oral, once daily preparations. New formulations of existing drugs have been developed, as well as a new chemical entity. Abuse deterrent formulations and delivery systems may prevent the artificial acceleration of drug delivery and reduce the potential for opioid addiction. Overdose concerns and the potential for fatal overdose may necessitate mandatory training for all clinicians who prescribe opioids. Despite the widespread use of opioids in the management of chronic non-cancer pain, significant research gaps remain. An improvement in the evidence base for its prescription is required.
Effect of losartan on proteinuria and urinary angiotensinogen excretion in non-diabetic patients with chronic kidney disease
Authors: Lee Yu-Ji , Cho Seong , Kim Sung Rok , Jang Hye Ryoun , Lee Jung Eun , Huh Wooseong , Kim Dae Joong , Oh Ha Young , Kim Yoon-Goo 
Published: June 2011

ABSTRACT

Purpose
Activation of the rennin–angiotensin system (RAS) is thought to contribute to hypertension and proteinuria, and eventually to the progression of chronic kidney disease (CKD). Recent evidence suggests that urinary angiotensinogen (UAGT) excretion reflects activation of the intrarenal RAS. This study was performed to determine the effect of losartan on proteinuria and UAGT excretion in non-diabetic patients with CKD with non-nephrotic-range proteinuria.

Study design
Thirty-two patients with non-nephrotic-range proteinuria (0.045–0.23 g/mmol creatinine) and normal renal function between April 2005 and April 2006 were randomised to a losartan (n=17) or a control (n=15) group. Patients in the losartan group received losartan 50 mg/day, and the doses were titrated up to 100 mg/day after 6 weeks. Serum and urinary angiotensinogen concentrations were measured by sandwich ELISA. The primary end point was the percentage change in proteinuria. The secondary end points were changes in estimated glomerular filtration rate and UAGT excretion. The follow-up period was 24 months.

Results
Baseline characteristics in the two groups were similar. After 24 months, losartan had reduced urinary protein excretion by 43% (from mean±SD 0.13±0.04 to 0.073±0.03 g/mmol, p&lt;0.0001), but proteinuria had not changed in the control group. The percentage change in mean arterial pressure did not differ between the groups. Losartan decreased logarithmically converted UAGT excretion (from 1.58±0.47 to 1.00±0.52, p=0.001). Estimated glomerular filtration rate decreased significantly only in the control group.

Conclusion
Losartan significantly decreased proteinuria and UAGT excretion, and preserved renal function in non-diabetic patients with CKD.
Effective Targeting of Triple-Negative Breast Cancer Cells by PF-4942847, a Novel Oral Inhibitor of Hsp 90
Authors: Mehta Pramod P. , Whalen Pamela , Baxi Sangita M. , Kung Pei-Pei , Yamazaki Shinji , Yin Min-Jean 
Published: June 2011

Abstract
Purpose: Triple-negative breast cancer (TNBC) patients have poor prognoses and survival outcomes such that the development of new targeted therapies is in strong demand. Mechanisms associated with high proliferation and aggressive tumor progression, such as PI3K/PTEN aberration, epidermal growth factor receptor (EGFR) overexpression, and cell-cycle upregulation, play important roles in TNBC. The molecular chaperone Hsp90 is required for the conformational maturation and stability of a variety of proteins in multiple pathways, such as EGFR, AKT, Raf, cdk4, etc. Therefore, an Hsp90 inhibitor may show therapeutic benefit in TNBC by targeting multiple pathways.
Experimental Design: The novel oral Hsp90 inhibitor PF-4942847 was characterized in multiple in vitro and in vivo assays to determine its antitumor activity in TNBC cell lines. In addition, the correlation of AKT degradation and Hsp70 induction in host peripheral blood lymphocytes (PBL) and xenograft tumors was determined.
Results: PF-4942847 induces degradation of multiple client proteins, cell-cycle block, apoptosis, and inhibits cell proliferation in TNBC lines, subsequently leading to tumor growth inhibition in mouse xenograft models. The correlation of AKT degradation and Hsp70 induction between PBLs and xenograft tumors reveals a differential modulation of Hsp90 activity between host and tumor tissues, and suggests that AKT degradation in PBLs may serve as a pharmacodynamic biomarker in future clinical development.
Conclusions: The novel oral Hsp90 inhibitor, PF-4942847, is a candidate for clinical development in TNBC by collaboratively targeting multiple signaling pathways. In addition, AKT degradation in PBLs may serve as a biomarker in clinical development. Clin Cancer Res; 17(16); 5432–42. ©2011 AACR.
Temporal Dissection of Tumorigenesis in Primary Cancers
Authors: Durinck Steffen , Ho Christine , Wang Nicholas J. , Liao Wilson , Jakkula Lakshmi R. , Collisson Eric A. , Pons Jennifer , Chan Sai-Wing , Lam Ernest T. , Chu Catherine , Park Kyunghee , Hong Sung-woo , Hur Joe S. , Huh Nam , Neuhaus Isaac M. , Yu Siegrid S. , Grekin Roy C. , Mauro Theodora M. , Cleaver James E. , Kwok Pui-Yan , LeBoit Philip E. , Getz Gad , Cibulskis Kristian , Aster Jon C. , Huang Haiyan , Purdom Elizabeth , Li Jian , Bolund Lars , Arron Sarah T. , Gray Joe W. , Spellman Paul T. , Cho Raymond J. 
Published: June 2011

Abstract
Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes.
Significance: Our approach reveals sequential ordering of oncogenic events in individual cancers, based on chromosomal rearrangements. Identifying the earliest abnormalities in cancer represents a critical step in timely diagnosis and deployment of targeted therapeutics. Cancer Discovery; 1(2); 137–43. © 2011 AACR.
This article is highlighted in the In This Issue feature, p. 91
Les relations des cités du Pont-Euxin ouest et nord avec les centres cultuels du monde grec
Authors: Dana Madalina 
Published: July 2011

AbstractThe aim of this paper is to examine the interactions between the cities of the western and northern shores of the Black Sea (from Apollonia to the Bosporan Kingdom) and the sanctuaries and oracles of the Aegean world. Through the networks between these peripheral cities and the religious centers like Delphi, Delos, Samothrace or Claros, over the centuries, the purpose is to question the way that the gifts, the theoriai and the consultation of oracles involved assuming and asserting a common Greek identity.
Trust, Tolerance and the Challenge of Difference
Authors: Seligman Adam B. 
Published: July 2011

AbstractThis essay explores the distinction between trust and confidence both analytically and in terms of the historical development of trust in modern societies. It compares a moral community of trust to communities of confidence and questions the ability of such communities to accept, abide by and live with difference. Finally, it presents the age-old idea of tolerance as a plausible if under-theoretized concept for how to live with ethnic and religious differences in our new multicultural societies. Arguments for tolerance are drawn from the work of John Dewey and the American pragmatist tradition.