bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of Peroxisomes to Secondary Metabolism and Pathogenicity in the Fungal Plant Pathogen Alternaria alternata
Authors: Imazaki Ai , Tanaka Aiko , Harimoto Yoshiaki , Yamamoto Mikihiro , Akimitsu Kazuya , Park Pyoyun , Tsuge Takashi 
Published: March 2010

ABSTRACT

The filamentous fungus
Alternaria alternata
includes seven pathogenic variants (pathotypes) which produce different host-selective toxins and cause diseases on different plants. The Japanese pear pathotype produces the host-selective AK-toxin, an epoxy-decatrienoic acid ester, and causes black spot of Japanese pear. Previously, we identified four genes,
AKT1
,
AKT2
,
AKT3
, and
AKTR
, involved in AK toxin biosynthesis.
AKT1
,
AKT2
, and
AKT3
encode enzyme proteins with peroxisomal targeting signal type 1 (PTS1)-like tripeptides, SKI, SKL, and PKL, respectively, at the C-terminal ends. In this study, we verified the peroxisome localization of Akt1, Akt2, and Akt3 by using strains expressing N-terminal green fluorescent protein (GFP)-tagged versions of the proteins. To assess the role of peroxisome function in AK-toxin production, we isolated Aa
PEX6
, which encodes a peroxin protein essential for peroxisome biogenesis, from the Japanese pear pathotype and made Aa
PEX6
disruption-containing transformants from a GFP-Akt1-expressing strain. The ΔAa
PEX6
mutant strains did not grow on fatty acid media because of a defect in fatty acid β oxidation. The import of GFP-Akt1 into peroxisomes was impaired in the ΔAa
PEX6
mutant strains. These strains completely lost AK toxin production and pathogenicity on susceptible pear leaves. These data show that peroxisomes are essential for AK-toxin biosynthesis. The ΔAa
PEX6
mutant strains showed a marked reduction in the ability to cause lesions on leaves of a resistant pear cultivar with defense responses compromised by heat shock. This result suggests that peroxisome function is also required for plant invasion and tissue colonization in
A. alternata
. We also observed that mutation of Aa
PEX6
caused a marked reduction of conidiation.
Conserved Regulators of Mating Are Essential for Aspergillus fumigatus Cleistothecium Formation
Authors: Szewczyk Edyta , Krappmann Sven 
Published: March 2010

ABSTRACT

Sexual reproduction of the human pathogen
Aspergillus fumigatus
(teleomorph:
Neosartorya fumigata
) was assumed to be absent or cryptic until recently, when fertile crosses among geographically restricted environmental isolates were described. Here, we provide evidence for mating, fruiting body development, and ascosporogenesis accompanied by genetic recombination between unrelated, clinical isolates of
A. fumigatus
, and this evidence demonstrates the generality and reproducibility of this long-time-undisclosed phase in the life cycle of this heterothallic fungus. Successful mating requires the presence of both mating-type idiomorphs
MAT1
-
1
and
MAT1
-
2
, as does expression of genes encoding factors presumably involved in this process. Moreover, analysis of an
A. fumigatus
mutant deleted for the
nsdD
gene suggests a role of this conserved regulator of cleistothecium development in hyphal fusion and hence heterokaryon formation.
Genome Sequence of
Pantoea ananatis
LMG20103, the Causative Agent of
Eucalyptus
Blight and Dieback
Authors: De Maayer Pieter , Chan Wai Yin , Venter Stephanus N. , Toth Ian K. , Birch Paul R. J. , Joubert Fourie , Coutinho Teresa A. 
Published: March 2010

ABSTRACT

Pantoea ananatis
is a Gram-negative plant pathogen that causes disease on a broad range of host plants, including pineapple, maize, rice, onion, melons, and
Eucalyptus
, and has been implicated in several cases of human disease. Here, we report the genome sequence of
P. ananatis
LMG20103 isolated from diseased
Eucalyptus
in South Africa.
Genome Sequence of Naturally Competent
Aggregatibacter actinomycetemcomitans
Serotype a Strain D7S-1
Authors: Chen Casey , Kittichotirat Weerayuth , Chen Weizhen , Downey Jennifer S. , Si Yan , Bumgarner Roger 
Published: March 2010

ABSTRACT

The major clonal lineages of the Gram-negative periodontal pathogen
Aggregatibacter actinomycetemcomitans
include serotype a, b, and c strains. Here, we report the draft genome sequence of a naturally competent serotype a strain, D7S-1, isolated from a patient with aggressive periodontitis.
Complete Genome Sequence of
Lactococcus lactis
subsp.
lactis
KF147, a Plant-Associated Lactic Acid Bacterium
Authors: Siezen Roland J. , Bayjanov Jumamurat , Renckens Bernadet , Wels Michiel , van Hijum Sacha A. F. T. , Molenaar Douwe , van Hylckama Vlieg Johan E. T. 
Published: March 2010

ABSTRACT

Lactococcus lactis
is a lactic acid bacterium used in the production of many fermented dairy products. We report the complete genome sequence of
L. lactis
subsp.
lactis
KF147, a nondairy strain isolated from mung bean sprouts. The circular chromosome of 2,598,144 bp, the largest among the sequenced lactococcal strains, encodes many properties related to adaptation to the plant environment.
Identification ofChlamydia trachomatisOuter Membrane Complex Proteins by Differential Proteomics
Authors: Liu Xiaoyun , Afrane Mary , Clemmer David E. , Zhong Guangming , Nelson David E. 
Published: March 2010

ABSTRACTThe extracellular chlamydial infectious particle, or elementary body (EB), is enveloped by an intra- and intermolecular cysteine cross-linked protein shell called the chlamydial outer membrane complex (COMC). A few abundant proteins, including the major outer membrane protein and cysteine-rich proteins (OmcA and OmcB), constitute the overwhelming majority of COMC proteins. The identification of less-abundant COMC proteins has been complicated by limitations of proteomic methodologies and the contamination of COMC fractions with abundant EB proteins. Here, we used parallel liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) analyses ofChlamydia trachomatisserovar L2 434/Bu EB, COMC, and Sarkosyl-soluble EB fractions to identify proteins enriched or depleted from COMC. All well-described COMC proteins were specifically enriched in the COMC fraction. In contrast, multiple COMC-associated proteins found in previous studies were strongly enriched in the Sarkosyl-soluble fraction, suggesting that these proteins are not COMC components or are not stably associated with COMC. Importantly, we also identified novel proteins enriched in COMC. The list of COMC proteins identified in this study has provided reliable information for further understanding chlamydial protein secretion systems and modeling COMC and EB structures.
The Sigma Factor AlgU Plays a Key Role in Formation of Robust Biofilms by NonmucoidPseudomonas aeruginosa
Authors: Bazire Alexis , Shioya Kouki , Soum-Soutéra Emmanuelle , Bouffartigues Emeline , Ryder Cynthia , Guentas-Dombrowsky Linda , Hémery Gaëlle , Linossier Isabelle , Chevalier Sylvie , Wozniak Daniel J. , Lesouhaitier Olivier , Dufour Alain 
Published: March 2010

ABSTRACTThe extracytoplasmic function sigma factor AlgU ofPseudomonas aeruginosais responsible for alginate overproduction, leading to mucoidy and chronic infections of cystic fibrosis patients. We investigated here the role of AlgU in the formation of nonmucoid biofilms. ThealgUmutant ofP. aeruginosaPAO1 (PAOU) showed a dramatic impairment in biofilm formation under dynamic conditions. PAOU was defective both in cell attachment to glass and in development of robust, shear-resistant biofilms. This was explained by an impaired production of extracellular matrix, specifically of the exopolysaccharide Psl, as revealed by microscopy and enzyme-linked immunosorbent assay. Complementing thealgUmutation with a plasmid-bornealgUgene restored wild-type phenotypes. Compared with that in PAO1, expression of thepsloperon was reduced in the PAOU strain, and the biofilm formation ability of this strain was partially restored by inducing the transcription of thepsloperon. Furthermore, expression of the lectin-encodinglecAandlecBgenes was reduced in the PAOU strain. In agreement with the requirement of LecB for type IV pilus biogenesis, PAOU displayed impaired twitching motility. Collectively, these genetic downregulation events explain the biofilm formation defect of the PAOU mutant. Promoter mapping indicated that AlgU is probably not directly responsible for transcription of thepsloperon and thelecgenes, but AlgU is involved in the expression of theppyRgene, whose product was reported to positively controlpslexpression. Expressing theppyRgene in PAOU partially restored the formation of robust biofilms.
Variation in Anastrozole Metabolism and Pharmacodynamics in Women with Early Breast Cancer
Authors: Ingle James N. , Buzdar Aman U. , Schaid Daniel J. , Goetz Matthew P. , Batzler Anthony , Robson Mark E. , Northfelt Donald W. , Olson Janet E. , Perez Edith A. , Desta Zeruesenay , Weintraub Randy A. , Williard Clark V. , Flockhart David A. , Weinshilboum Richard M. 
Published: March 2010

Abstract
Aromatase inhibitors play a prominent role in the management of postmenopausal women with endocrine-sensitive breast cancer, but there is large variability in both efficacy and tolerability. The purpose of our study was to define interindividual variation in anastrozole metabolism and pharmacodynamics among patients treated with the approved daily dose of 1 mg in a standard practice setting as adjuvant therapy for resected early breast cancer. This study was performed in 191 women in whom pretreatment and during anastrozole plasma concentrations of estrone (E1), estradiol (E2), estrone conjugates, androstenedione, and testosterone were determined and correlated with plasma concentrations of anastrozole and anastrozole metabolites. There were large interindividual variations in plasma anastrozole and anastrozole metabolite concentrations, as well as pretreatment and postdrug plasma E1, E2, and E1 conjugate and estrogen precursor (androstenedione and testosterone) concentrations. E1 and E2 concentrations were below the lower limit of quantitation (LLQ) in most patients after anastrozole therapy (83% for both), but those with detectable concentrations had a broad range (1.58–45.2 and 0.635–97.0 pg/mL, respectively). E1 conjugates after anastrozole therapy were above the LLQ in most patients (93%), with wide interpatient variability (3.50–2,990 pg/mL). Two patients seemed to extensively metabolize anastrozole and failed to display substantial decreases in estrogens. Acknowledging the potential factor of variable compliance, our results showed large interindividual variation in anastrozole metabolism and its effect on circulating estrogens in postmenopausal patients. These findings may have implications with regard to efficacy and adverse events and may indicate the need to “individualize” therapy with this drug. Cancer Res; 70(8); 3278–86. ©2010 AACR.
The Antidepressant Sertraline Inhibits Translation Initiation by Curtailing Mammalian Target of Rapamycin Signaling
Authors: Lin Chen-Ju , Robert Francis , Sukarieh Rami , Michnick Stephen , Pelletier Jerry 
Published: March 2010

Abstract
Sertraline, a selective serotonin reuptake inhibitor, is a widely used antidepressant agent. Here, we show that sertraline also exhibits antiproliferative activity. Exposure to sertraline leads to a concentration-dependent decrease in protein synthesis. Moreover, polysome profile analysis of sertraline-treated cells shows a reduction in polysome content and a concomitant increase in 80S ribosomes. The inhibition in translation caused by sertraline is associated with decreased levels of the eukaryotic initiation factor (eIF) 4F complex, altered localization of eIF4E, and increased eIF2α phosphorylation. The latter event leads to increased REDD1 expression, which in turn impinges on the mammalian target of rapamycin (mTOR) pathway by affecting TSC1/2 signaling. Sertraline also independently targets the mTOR signaling pathway downstream of Rheb. In the Eμ-myc murine lymphoma model where carcinogenesis is driven by phosphatase and tensin homologue (PTEN) inactivation, sertraline is able to enhance chemosensitivity to doxorubicin. Our results indicate that sertraline exerts antiproliferative activity by targeting the mTOR signaling pathway in a REDD1-dependent manner. Cancer Res; 70(8); 3199–208. ©2010 AACR.
MicroRNA-155 Functions as an OncomiR in Breast Cancer by Targeting theSuppressor of Cytokine Signaling 1Gene
Authors: Jiang Shuai , Zhang Hong-Wei , Lu Ming-Hua , He Xiao-Hong , Li Yong , Gu Hua , Liu Mo-Fang , Wang En-Duo 
Published: March 2010

AbstractMicroRNA-155 (miR-155) is overexpressed in many human cancers; however, the mechanisms by which miR-155 functions as a putative oncomiR are largely unknown. Here, we report that the tumor suppressor gene suppressor of cytokine signaling 1 (socs1) is an evolutionarily conserved target of miR-155 in breast cancer cells. We found that mir-155 expression is inversely correlated with socs1 expression in breast cancer cell lines as well as in a subset of primary breast tumors. We also identified a 24A→G mutation in the miR-155 binding site of the SOCS1 3′ untranslated region in a breast tumor that reduced miR-155 repression, implicating a mechanism for miRNA targets to avoid repression. Ectopic expression of miR-155 significantly promoted the proliferation of breast cancer cells, the formation of soft agar foci in vitro, and the development of tumors in nude mice. In breast cancer cells, RNA interference silencing of socs1 recapitulates the oncogenic effects of miR-155, whereas restoration of socs1 expression attenuates the protumorigenesis function of miR-155, suggesting that miR-155 exerts its oncogenic role by negatively regulating socs1. Overexpression of miR-155 in breast cancer cells leads to constitutive activation of signal transducer and activator of transcription 3 (STAT3) through the Janus-activated kinase (JAK) pathway, and stimulation of breast cancer cells by the inflammatory cytokines IFN-γ and interleukin-6 (IL-6), lipopolysaccharide (LPS), and polyriboinosinic:polyribocytidylic acid [poly(I:C)] significantly upregulates mir-155 expression, suggesting that miR-155 may serve as a bridge between inflammation and cancer. Taken together, our study reveals that miR-155 is an oncomiR in breast cancer and that miR-155 may be a potential target in breast cancer therapy. Cancer Res; 70(8); 3119–27. ©2010 AACR.
Signaling From the Golgi: Mechanisms and Models for Golgi Phosphoprotein 3–Mediated Oncogenesis
Authors: Scott Kenneth L. , Chin Lynda 
Published: March 2010

Abstract
Golgi phosphoprotein 3 (GOLPH3; also known as GPP34/GMx33/MIDAS) represents an exciting new class of oncoproteins involved in vesicular trafficking. Encoded by a gene residing on human chromosome 5p13, which is frequently amplified in multiple solid tumor types, GOLPH3 was initially discovered as a phosphorylated protein localized to the Golgi apparatus. Recent functional, cell biological, and biochemical analyses show that GOLPH3 can function as an oncoprotein to promote cell transformation and tumor growth by enhancing activity of the mammalian target of rapamycin, a serine/threonine protein kinase known to regulate cell growth, proliferation, and survival. Although its precise mode of action in cancer remains to be elucidated, the fact that GOLPH3 has been implicated in protein trafficking, receptor recycling, and glycosylation points to potential links of these cellular processes to tumorigenesis. Understanding how these processes may be deregulated and contribute to cancer pathogenesis and drug response will uncover new avenues for therapeutic intervention. Clin Cancer Res; 16(8); 2229–34. ©2010 AACR.
Upregulation of DNA Methyltransferase–Mediated Gene Silencing, Anchorage-Independent Growth, and Migration of Colon Cancer Cells by Interleukin-6
Authors: Foran Eilis , Garrity-Park Megan M. , Mureau Coralie , Newell John , Smyrk Thomas C. , Limburg Paul J. , Egan Laurence J. 
Published: March 2010

Abstract
Inflammatory bowel disease is characterized by chronic inflammation which predisposes to colorectal cancer. The mechanisms by which inflammation promotes tumorigenesis are not fully known. We aimed to investigate the links between colonic inflammation and tumorigenesis via epigenetic gene silencing. Colon cancer specimens were assessed for the expression of DNA methyltransferase-1 (DNMT-1) using immunohistochemistry. Colorectal carcinoma cell lines were assessed for DNMT1 expression, methylcytosine content, promoter methylation, gene expression, and tumorigenesis in response to interleukin (IL)-6. DNMT1 was expressed at higher levels in both the peritumoral stroma and tumor in inflammatory bowel disease–associated cancers compared with sporadic colon cancers. IL-6 treatment of colon cancer cells resulted in an increase in DNMT1 expression, independent of de novo gene expression. IL-6 increased the methylation of promoter regions of genes associated with tumor suppression, adhesion, and apoptosis resistance. Expression of a subset of these genes was downregulated by IL-6, an effect that was prevented by preincubation with 5-azadeoxycytidine, a DNMT1 inhibitor. Anchorage-independent growth and migration of colon cancer cells was also increased by IL-6 in a 5-azadeoxycytidine–sensitive manner. Our results indicate that DNMT-mediated gene silencing may play a role in inflammation-associated colon tumorigenesis. Mol Cancer Res; 8(4); 471–81. ©2010 AACR.
Microvascular Obstruction Remains a Portent of Adverse Remodeling in Optimally Treated Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction
Authors: Weir Robin A.P. , Murphy Charles Aengus , Petrie Colin J. , Martin Thomas N. , Balmain Sean , Clements Suzanne , Steedman Tracey , Wagner Galen S. , Dargie Henry J. , McMurray John J.V. 
Published: March 2010

Background—
Microvascular obstruction (MO) is associated with large acute myocardial infarction and lower left ventricular (LV) ejection fraction and predicts greater remodeling, but whether this effect is abolished by contemporary antiremodeling therapies is subject to debate. We examined the influence of several infarct characteristics, including MO, on LV remodeling in an optimally treated post–acute myocardial infarction cohort, using contrast-enhanced cardiac magnetic resonance.

Methods and Results—

One hundred patients (mean age, 58.9±12 years, 77%men) underwent contrast-enhanced cardiac magnetic resonance at baseline (≈4 days) and at 12 and 24 weeks. The effects on LV remodeling (ie, change in LV end-systolic volume index [ΔLVESVi]) of infarct site, transmurality, endocardial extent, and the presence of early and late MO were analyzed. Mean baseline infarct volume index decreased from 34.0 (21.2) mL/m
2
to 20.9 (12.9) mL/m
2
at 24 weeks (
P
<0.001). Infarct site had no influence on remodeling, but greater baseline infarct transmurality (
r
=0.47,
P
<0.001) and endocardial extent (
r
=0.26,
P
<0.01) were associated with higher ΔLVESVi. Early MO was seen in 69 patients (69%) and persisted as late MO in 56 patients (56%). Patients with late MO underwent significantly greater remodeling than those without MO (ΔLVESVi, +4.1 [13.4] versus −7.0 [12.7] mL/m
2
, respectively,
P
=0.001); those with early MO only displayed an intermediate ΔLVESVi (−4.9 [13.0] mL/m
2
). Importantly, late MO was seen frequently despite optimal coronary blood flow having been restored at angiography.

Conclusions—
Late MO on predischarge contrast-enhanced cardiac magnetic resonance remains an ominous predictor of adverse LV remodeling despite powerful antiremodeling therapy and may be useful in the risk stratification of survivors of acute myocardial infarction.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00132093.
Depressive Symptoms and Their Social Contexts: a Qualitative Systematic Literature Review of Contextual Interventions
Authors: Gottlieb Laura , Waitzkin Howard , Miranda Jeanne 
Published: March 2010

Background: Numerous observational studies demonstrate associations between social context and depressive symptoms, yet few intervention trials exist in this arena.Aims: This review examines intervention trials that explore the impact of contextual change on depressive symptoms.Methods: Electronic literature databases of PubMed and PsycINFO, bibliographies of retrieved articles and the publicly available internet were searched for English-language articles published between 1997 and 2008. Peer-reviewed studies were eligible for inclusion if they reported contextual interventions and depressive symptoms measures in adult populations without other significant underlying medical or psychological illness. In total, 2,128 studies met search term criteria. Of these, 13 studies meeting inclusion criteria were classified by type of intervention. Qualitative synthesis was used to interpret the mental health impact of contextual interventions.Results: The interventions focused on employment, housing, poverty, parenting and violence. Eight of these studies reported a decrease in depressive symptoms and/or psychological distress in intervention groups. Interventions varied in focus, length of follow-up and measures of depressive symptoms.Conclusions: Contextual interventions for the prevention and treatment of depressive symptoms and psychological distress can be effective, though very limited data exist in this field. Policy implications include a greater emphasis on improving context to decrease depression and other mental disorders.
Multidisciplinary rehabilitation after primary total knee arthroplasty: a randomized controlled study of its effects on functional capacity and quality of life
Authors: Kauppila Anna-Maija , Kyllönen Eero , Ohtonen Pasi , Hämäläinen Martti , Mikkonen Paula , Laine Vesa , Siira Pertti , Mäki-Heikkilä Paula , Sintonen Harri , Leppilahti Juhana , Arokoski Jari PA 
Published: March 2010

Objective: To examine whether a multidisciplinary rehabilitation programme can improve functional recovery and quality of life and reduce the use of rehabilitation services compared with conventional care one year after total knee arthroplasty. Design: Prospective, randomized, non-blinded, controlled trial. Setting: An outpatient centre-based setting. Subjects: Eighty-six patients who were scheduled for primary total knee arthroplasty due to osteoarthritis of the knee. Interventions: A ten-day multidisciplinary rehabilitation programme, which was focused on enhancing functional capacity, was organized 2—4 months after surgery. In both groups, a standard amount of physiotherapy was included in conventional care. Main measures: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the 15D, 15-m walk test, stair test, isometric strength measurement of the knee. Use of rehabilitation services was asked about with a questionnaire. Outcomes were assessed preoperatively and at 2-, 6- and 12-month follow-ups. Results: In both groups, functional capacity and quality of life improved significantly. The mean absolute change in the WOMAC function score was —32.4 mm (SD 26.4) in the rehabilitation group and —32.8 mm (SD 20.1) in the control group (P-time*group = 0.40). No difference was found between groups in any outcome measure or in the use of rehabilitation services during the study period. Conclusions: This study indicates that for knee osteoarthritis patients treated with primary total knee arthroplasty, a 10-day multidisciplinary outpatient rehabilitation programme 2—4 months after surgery does not yield faster attainment of functional recovery or improvement in quality of life than can be achieved with conventional care.