bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional Analysis of Long-Term Adaptation ofYersinia enterocoliticato Low-Temperature Growth
Authors: Bresolin Geraldine , Neuhaus Klaus , Scherer Siegfried , Fuchs Thilo M. 
Published: April 2006

ABSTRACTTo analyze the transcriptional response ofYersinia enterocoliticacells to prolonged growth at low temperature, a collection ofluxCDABEtransposon mutants was cultivated in parallel at optimal (30°C) and suboptimal (10°C) temperatures and screened for enhanced promoter activities during growth until entering stationary phase. Among 5,700Y. enterocoliticamutants, 42 transcriptional units were identified with strongly enhanced or reduced promoter activity at 10°C compared to 30°C, and changes in their transcriptional levels over time were measured. Green fluorescent protein fusions to 10 promoter regions confirmed the data. The temporal order of induction of the temperature-responsive genes ofY. enterocoliticawas deduced, starting with the expression of cold shock genescspAandcspBand the elevated transcription of a glutamate-aspartate symporter. Subsequently, cold-adapted cells drastically up-regulated genes encoding environmental sensors and regulators, such as UhpABC, ArcA, and methyl-accepting chemotaxis protein I (MCPI). Among the most prominent cold-responsive elements that were transcriptionally induced during growth in early and middle exponential phase are the insecticidal toxin genestcaAandtcaB, as well as genes involved in flagellar synthesis and chemotaxis. The expression pattern of the late-exponential- to early-stationary-growth phase is dominated by factors involved in biodegradative metabolism, namely, a histidine ammonia lyase, three enzymes responsible for uptake and utilization of glycogen, the urease complex, and a subtilisin-like protease. Double-knockout mutants and complementation studies demonstrate inhibitory effects of MCPI and UhpC on the expression of a putative hemolysin transporter. The data partially delineate the spectrum of gene expression ofY. enterocoliticaat environmental temperatures, providing evidence that an as-yet-unknown insect phase is part of the life cycle of this human pathogen.
TheErwinia chrysanthemi3937 PhoQ Sensor Kinase Regulates Several Virulence Determinants
Authors: Venkatesh Balakrishnan , Babujee Lavanya , Liu Hui , Hedley Pete , Fujikawa Takashi , Birch Paul , Toth Ian , Tsuyumu Shinji 
Published: April 2006

ABSTRACTThe PhoPQ two-component system regulates virulence factors inErwinia chrysanthemi, a pectinolytic enterobacterium that causes soft rot in several plant species. We characterized the effect of a mutation inphoQ, the gene encoding the sensor kinase PhoQ of the PhoPQ two-component regulatory system, on the global transcriptional profile ofE. chrysanthemiusing cDNA microarrays and further confirmed our results by quantitative reverse transcription-PCR analysis. Our results indicate that a mutation inphoQaffects transcription of at least 40 genes, even in the absence of inducing conditions. Enhanced expression of several genes involved in iron metabolism was observed in the mutant, including that of theacsoperon that is involved in achromobactin biosynthesis and transport. This siderophore is required for full virulence ofE. chrysanthemi, and its expression is governed by the global repressor protein Fur. Changes in gene expression were also observed for membrane transporters, stress-related genes, toxins, and transcriptional regulators. Our results indicate that the PhoPQ system governs the expression of several additional virulence factors and may also be involved in interactions with other regulatory systems.
Differential Biofilm Formation and Motility Associated with Lipopolysaccharide/Exopolysaccharide-Coupled Biosynthetic Genes inStenotrophomonas maltophilia
Authors: Huang Tzu-Pi , Somers Eileen B. , Wong Amy C. Lee 
Published: April 2006

ABSTRACTStenotrophomonas maltophiliaWR-C is capable of forming biofilm on polystyrene and glass. The lipopolysaccharide/exopolysaccharide-coupled biosynthetic genesrmlA,rmlC, andxanBare necessary for biofilm formation and twitching motility. Mutants with mutations inrmlACandxanBdisplay contrasting biofilm phenotypes on polystyrene and glass and differ in swimming motility.
An Allele of
gyrA
Prevents
Salmonella enterica
Serovar Typhimurium from Using Succinate as a Carbon Source
Authors: Schmitz George E. , Downs Diana M. 
Published: April 2006

ABSTRACT

A mutant
gyrA
allele resulting in an A271E substitution in the DNA gyrase protein generated a strain unable to grow on the C
4
-dicarboxylates succinate, malate, and fumarate. Bacteria harboring
gyrA751
displayed decreased negative supercoiling in cells. Expression of the
dctA
gene, which encodes the C
4
-dicarboxylate transporter, was reduced in a
gyrA751
mutant, providing the first evidence that
dctA
expression is supercoiling sensitive and uncovering a simple metabolic screen for lesions in gyrase that reduce negative supercoiling.
BacA-Mediated Bleomycin Sensitivity in
Sinorhizobium meliloti
Is Independent of the Unusual Lipid A Modification
Authors: Ferguson Gail P. , Jansen An , Marlow Victoria L. , Walker Graham C. 
Published: April 2006

ABSTRACT

Sinorhizobium meliloti bacA
mutants are symbiotically defective, deoxycholate sensitive, and bleomycin resistant. We show that the bleomycin resistance phenotype is independent of the lipid A alteration and that the changes giving rise to both phenotypes are likely to be involved in the inability of
bacA
mutants to persist within their hosts.
Seasonal pattern of leaf production and its effects on assimilation in giant summer-green herbs in deciduous forests in northern Japan
Authors: Tani Tomokazu , Kudo Gaku 
Published: April 2006

Understory vegetation of northern deciduous forests in far eastern Asia is characterized by giant summer-green herbs. We examined the patterns of height growth, leaf accumulation, photosynthetic characteristics, daily net assimilation, and dry matter allocation within aboveground parts of six giant summer-green herbs with reference to light conditions in deciduous forests. Plant height, leaf number, and total leaf area per plant increased with progressing tree-canopy closure in five species ( Cacalia hastata L. subsp. orientalis Kitam., Cirsium kamtschaticum Ledeb., Filipendula kamtschatica (Pall.) Maxim. f. kamtschatica, Senecio cannabifolius Less., and Urtica platyphylla Wedd.) that had continuous leaf production throughout the growing season, whereas one species ( Veratrum album L. subsp. oxysepalum Hulten) with early leaf production, completed leaf production mostly before the beginning of tree-canopy closure. Maximum photosynthetic and dark respiration rates decreased seasonally in all species. Species with continuous leaf emergence accumulated leaves acclimatized to shade conditions, which offset the decreasing photosynthesis of individual leaves with progressing tree-canopy closure, resulting in stable carbon gain even under decreasing light availability. In contrast, V. album assimilated vigorously during the short period of high irradiance before tree-canopy closure, and decreased its assimilation rate continuously thereafter.
A new invasive hawkweed, Hieracium glomeratum (Lactuceae, Asteraceae), in the Pacific Northwest
Authors: Wilson Linda M. , Fehrer Judith , Bräutigam Siegfried , Grosskopf Gitta 
Published: April 2006

During the summer of 2001, a newly recorded species of exotic hawkweed ( Hieracium glomeratum Froel.) for North America was identified from specimens collected in southeastern British Columbia, Canada, and eastern Washington state, United States. The specimens had previously been identified as the closely related Hieracium caespitosum Dumort. DNA fingerprints of plants from different localities proved to be identical. Their clonality, along with a spot-like distribution, indicates that this apomictic species probably originated from a single introduction from Europe, which subsequently spread. This species adds to the complex of 14 other exotic Hieracium species belonging to the Eurasian subgenus Pilosella that are adventive in the United States and Canada. A distribution map of the native and adventive range of H. glomeratum, and a key to distinguish it from related species in subgenus Pilosella that occur in North America are provided. The evolutionary and invasive potential of H. glomeratum is also discussed.
Effects of pollinators and flower bud herbivores on reproductive success of two ericaceous woody species differing in flowering season
Authors: Osada Noriyuki , Sugiura Shinji 
Published: April 2006

To investigate the relative importance of pollinators and flower bud herbivores on final fruit set, the ratios of flower to flower bud (flower/bud), fruit to flower (fruit/flower), and fruit to flower bud (fruit/bud) were examined for the two bumble-bee-pollinated ericaceous species that have different flowering seasons: Pieris japonica (Thunb.) D. Don produces flower buds in autumn and blooms in early spring, whereas Lyonia ovalifolia (Wall.) Drude produces flower buds and blooms in late spring. Floral longevity was longer in P. japonica than in L. ovalifolia, and bagged flowers had an even longer floral longevity. The fruit/flower ratio was similar between the cross-pollinated and control flowers in P. japonica, but was smaller in control flowers than in cross-pollinated flowers in L. ovalifolia. Despite unpredictable pollinator activity in early spring, long flowering duration and no competition for pollinators facilitated reproductive success of P. japonica. In contrast, short flowering duration and severe competition for pollinators limited the reproductive success of L. ovalifolia. Flower bud herbivory was more severe in P. japonica than in L. ovalifolia. In both species, predispersal seed herbivores were negligible. Consequently, the fruit/bud ratio was mainly affected by the flower/bud ratio in P. japonica and by the fruit/flower ratio in L. ovalifolia. Our results suggest that despite intense herbivory of flower buds, early spring flowering of P. japonica facilitates pollination because of less competition for pollinators in comparison to L. ovalifolia. Thus, the relative importance of pollinators and herbivores on fruit set differs between the two studied species that differ in flowering periods.
APPROXIMATE BLOCK SORTING
Authors: MAHAJAN MEENA , RAMA RAGHAVAN , RAMAN VENKATESH , VIJAYKUMAR S. 
Published: April 2006

We consider the problem BLOCK-SORTING: Given a permutation, sort it by using a minimum number of block moves, where a block is a maximal substring of the permutation which is also a substring of the identity permutation, and a block move repositions the chosen block so that it merges with another block. Although this problem has recently been shown to be NP-hard [3], nothing better than a trivial 3-approximation was known. We present here the first non-trivial approximation algorithm to this problem. For this purpose, we introduce the following optimization problem: Given a set of increasing sequences of distinct elements, merge them into one increasing sequence with a minimum number of block moves. We show that the merging problem has a polynomial time algorithm. Using this, we obtain an O(n3) time 2-approximation algorithm for BLOCK-SORTING. We also observe that BLOCK-SORTING, as well as sorting by transpositions, are fixed-parameter-tractable in the framework of [6].
Distinct Tumor Stage–Specific Inhibitory Effects of 2-Methoxyestradiol in a Breast Cancer Mouse Model Associated with Id-1 Expression
Authors: Huh Jung-Im , Calvo Alfonso , Charles Rhonda , Green Jeffrey E. 
Published: April 2006

Abstract
2-Methoxyestradiol (2ME2), a metabolite of 17-β-estradiol, inhibits angiogenesis and has additional antitumor activities. We have analyzed the tumor stage–specific effects of 2ME2 in the C3(1)/Tag transgenic mouse model for breast cancer, which spontaneously develops estrogen receptor–negative mammary tumors following a predictable progression of lesion formation. When given either as a therapeutic agent in established tumors (late intervention study) or in mice with pre-invasive mammary lesions (early intervention study), tumor growth was reduced by 60% compared with untreated controls and was associated with an induction of apoptosis. In a prevention study, a significant reduction in mammary intraepithelial neoplasia (MIN) lesions was observed in animals beginning treatment at 6 weeks of age, before the appearance of histopathologic abnormalities. However, although 2ME2 reduced the number of MIN lesions in the prevention study, a paradoxical increase in tumor multiplicity and growth rate was observed. This was associated with unusual cystic tumor formation, in which significant central necrosis was observed, surrounded by an outer region of proliferative tumor cell growth. The characteristics of the cystic tumor formation in mice treated with 2ME2 at early ages are consistent with an impaired angiogenic response as observed in mice deficient for inhibitor of differentiation (Id-1). We further show that Id-1 expression is negatively regulated by 2ME2, which may be an additional mechanism for the antiangiogenic effect of 2ME2. Although 2ME2 significantly reduced tumor growth at late stages, these results also suggest that altered tumor morphology and accelerated tumor growth may occur if 2ME2 is administered in a prevention setting for prolonged periods. (Cancer Res 2006; 66(7): 3495-503)
Two Transforming C-RAF Germ-Line Mutations Identified in Patients with Therapy-Related Acute Myeloid Leukemia
Authors: Zebisch Armin , Staber Philipp B. , Delavar Ali , Bodner Claudia , Hiden Karin , Fischereder Katja , Janakiraman Manickam , Linkesch Werner , Auner Holger W. , Emberger Werner , Windpassinger Christian , Schimek Michael G. , Hoefler Gerald , Troppmair Jakob , Sill Heinz 
Published: April 2006

Abstract
Mutations leading to activation of the RAF-mitogen-activated protein kinase/extracellular signal-regulated (ERK) kinase (MEK)-ERK pathway are key events in the pathogenesis of human malignancies. In a screen of 82 acute myeloid leukemia (AML) samples, 45 (55%) showed activated ERK and thus were further analyzed for mutations in B-RAF and C-RAF. Two C-RAF germ-line mutations, S427G and I448V, were identified in patients with therapy-related AML in the absence of alterations in RAS and FLT3. Both exchanges were located within the kinase domain of C-RAF. In vitro and in vivo kinase assays revealed significantly increased activity for S427GC-RAF but not for I448VC-RAF. The involvement of the S427G C-RAF mutation in constitutive activation of ERK was further confirmed through demonstration of activating phosphorylations on C-RAF, MEK, and ERK in neoplastic cells, but not in nonneoplastic cells. Transformation and survival assays showed oncogenic and antiapoptotic properties for both mutations. Screening healthy individuals revealed a &lt;1/400 frequency of these mutations and, in the case of I448V, inheritance was observed over three generations with another mutation carrier suffering from cancer. Taken together, these data are the first to relate C-RAF mutations to human malignancies. As both mutations are of germ-line origin, they might constitute a novel tumor-predisposing factor. (Cancer Res 2006; 66(7): 3401-8)
Mouse Double Minute 2 Associates with Chromatin in the Presence of p53 and Is Released to Facilitate Activation of Transcription
Authors: White David E. , Talbott Kathryn E. , Arva Nicoleta C. , Bargonetti Jill 
Published: April 2006

Abstract
The tumor suppressor p53 is a potent transcription factor of which the ability to mediate transcription is inhibited through an interaction with the oncoprotein mouse double minute 2 (Mdm2). The present study has tested the hypothesis that Mdm2 inhibits the p53 response in normally growing cells by binding to chromatin-associated p53. Using chromatin immunoprecipitation, we show that Mdm2 localizes with p53 at its responsive elements on the waf1 and mdm2 genes in human cell lines expressing p53, but not in cell lines lacking p53 expression, indicating that Mdm2 is recruited to regions of DNA in a p53-dependent manner. Interestingly, our results show a decrease of Mdm2 protein associated with p53-responsive elements on the waf1 and mdm2 genes when p53-induced transcription is activated either by DNA damage or through controlled overexpression of p53. Rapid activation of p53 transcriptional activity before increasing p53 protein levels was observed with addition of either small-molecule inhibitors to disrupt the p53-Mdm2 interaction or small interfering RNA to mdm2. These findings indicate Mdm2 transiently localizes with p53 at responsive elements and suggest that latent p53 results from the recruitment of Mdm2 to chromatin. (Cancer Res 2006; 66(7): 3463-70)
Growth and Motility Inhibition of Breast Cancer Cells by Epidermal Growth Factor Receptor Degradation Is Correlated with Inactivation of Cdc42
Authors: Hirsch Dianne S. , Shen Yi , Wu Wen Jin 
Published: April 2006

Abstract
Overexpression of epidermal growth factor receptor (EGFR) contributes to increased cell proliferation and migration in breast cancer. However, mechanisms of EGFR overexpression remain elusive and often cannot be attributed to gene amplification. In NIH3T3 fibroblasts, active Cdc42 inhibits c-Cbl-regulated EGFR degradation to induce cellular transformation. Here, we use two EGFR-overexpressing breast cancer cell lines, MDA-MB-231 and BT20, as models to test the hypothesis that up-regulated Cdc42 activity impairs c-Cbl-mediated EGFR degradation and contributes to EGFR overexpression. We show that silencing Cdc42 significantly reduces protein levels of EGFR, leading to a marked reduction in cell proliferation and migration, and c-Cbl knockdown increases the levels of EGFR. Expression of c-Cbl-N480, a c-Cbl mutant that is not regulated by Cdc42 and blocks Cdc42-induced transformation but still binds and ubiquitinates EGFR, enhances the rate of EGFR degradation and subsequently inhibits cell proliferation. Moreover, down-regulated EGFR signaling induced by c-Cbl-N480 decreased activity of Cdc42 and Rac1, resulting in inhibition of cell migration. These findings indicate that Cdc42 and c-Cbl are critical components involved in the regulation of EGFR protein levels and that restoration of proper EGFR degradation by disrupting Cdc42 regulation of c-Cbl can reduce cell proliferation and migration in MDA-MB-231 and BT20 cells. (Cancer Res 2006; 66(7): 3523-30)
N-Methyl-d-Aspartate Receptor Type 2B Is Epigenetically Inactivated and Exhibits Tumor-Suppressive Activity in Human Esophageal Cancer
Authors: Kim Myoung Sook , Yamashita Keishi , Baek Jin Hyen , Park Hannah Lui , Carvalho Andre Lopes , Osada Motonobu , Hoque Mohammad Obaidul , Upadhyay Sunil , Mori Masaki , Moon Chulso , Sidransky David 
Published: April 2006

AbstractPromoter hypermethylation accompanied by gene silencing is a common feature of human cancers. We identified previously several new tumor suppressor genes based on pharmacologic unmasking of the promoter region and detection of reexpression on microarray analysis. In this study, we modified the selection of candidates from our previous microarray data by excluding genes that showed basal expression in cancer cell lines. With the new method, we found novel methylated genes with 90% accuracy. Among these 33 novel methylated genes that we identified in esophageal squamous cell carcinoma (ESCC) cell lines, N-methyl-d-aspartate receptor type 2B (NMDAR2B) was of particular interest. NMDAR2B was methylated in 95% of primary human ESCC tissue specimens and 12 ESCC cell lines by sequence analysis. NMDAR2B expression was silenced in all 12 ESCC cell lines and was reactivated by the demethylating agent 5-aza-2′-deoxycytidine. Moreover, reintroduction of the gene was accompanied by marked Ca2+-independent apoptosis in ESCC cell lines, suggesting that NMDAR2B can suppress tumor growth. Thus, NMDAR2B promoter methylation is common in ESCC, abrogating gene transcription and leading to cellular resistance to apoptosis. (Cancer Res 2006; 66(7): 3409-18)
Constitutive Activation of Extracellular Signal-Regulated Kinase Predisposes Diffuse Large B-Cell Lymphoma Cell Lines to CD40-Mediated Cell Death
Authors: Hollmann C. Annette , Owens Trevor , Nalbantoglu Josephine , Hudson Thomas J. , Sladek Robert 
Published: April 2006

AbstractCD40 promotes survival, proliferation, and differentiation of normal B cells but can cause activation-induced cell death in malignant B lymphocytes. CD40 ligand and anti-CD40 antibodies have been used successfully to induce apoptosis in lymphoma lines both in vitro and in xenograft tumor models. Although this makes CD40 an attractive target for antitumor therapies, the response of malignant B cells to CD40 signaling is variable, and CD40 stimulation can enhance proliferation and can increase chemoresistance in some cell lines. It would therefore be useful to identify markers that predict whether a specific cell line or tumor will undergo apoptosis when stimulated with CD40 and to identify targets downstream of CD40 that affect only the apoptotic arm of CD40 signaling. We have analyzed gene expression patterns in CD40-sensitive and CD40-resistant diffuse large B-cell lymphoma (DLBCL) cell lines to identify signaling pathways that are involved in CD40-mediated apoptosis. CD40-resistant lines expressed pre-B-cell markers, including RAG and VPREB, whereas CD40-sensitive cells resembled mature B cells and expressed higher levels of transcripts encoding several members of the CD40 signaling pathway, including LCK and VAV. In addition, CD40-sensitive DLBCL cell lines also displayed constitutive activation of extracellular signal-regulated kinase (ERK) and failed to undergo apoptosis when ERK phosphorylation was inhibited. In contrast, CD40-resistant lines showed no constitutive activation of ERK and no increase in ERK activity in response to CD40 stimulation. Our results suggest that constitutive activation of ERK may be required for death signaling by CD40. (Cancer Res 2006; 66(77):3550-7)
Onset of Abnormal Blood and Lymphatic Vessel Function and Interstitial Hypertension in Early Stages of Carcinogenesis
Authors: Hagendoorn Jeroen , Tong Ricky , Fukumura Dai , Lin Qingcong , Lobo Jennifer , Padera Timothy P. , Xu Lei , Kucherlapati Raju , Jain Rakesh K. 
Published: April 2006

Abstract
Recent improvements in diagnostic methods have opened avenues for detection and treatment of (pre)malignant lesions at early stages. However, due to the lack of spontaneous tumor models that both mimic human carcinogenesis and allow direct optical imaging of the vasculature, little is known about the function of blood and lymphatic vessels during the early stages of cancer development. Here, we used a spontaneous carcinogenesis model in the skin of DNA polymerase η–deficient mice and found that interstitial fluid pressure was already elevated in the hyperplastic/dysplastic stage. This was accompanied by angiogenic blood vasculature that exhibited altered permeability, vessel compression, and decreased α-smooth muscle actin–positive perivascular cell coverage. In addition, the lymphatic vessels in hyperplastic/dysplastic lesions were partly compressed and nonfunctional. These novel insights may aid early detection and treatment strategies for cancer. (Cancer Res 2006; 66(7): 3360-4)