bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Amino Terminus of
Bacillus subtilis
TagB Possesses Separable Localization and Functional Properties
Authors: Bhavsar Amit P. , D'Elia Michael A. , Sahakian Tiffany D. , Brown Eric D. 
Published: July 2007

ABSTRACT

The function(s) of gram-positive wall teichoic acid is emerging with recent findings that it is an important virulence factor in the pathogen
Staphylococcus aureus
and that it is crucial to proper rod-shaped cell morphology of
Bacillus subtilis
. Despite its importance, our understanding of teichoic acid biosynthesis remains incomplete. The TagB protein has been implicated in the priming step of poly(glycerol phosphate) wall teichoic acid synthesis in
B. subtilis.
Work to date indicates that the TagB protein is localized to the membrane, where it adds a single glycerol phosphate residue to the nonreducing end of the undecaprenol-phosphate-linked
N
-acetylmannosamine-β(1,4)-
N
-acetylglucosamine-1-phosphate. Thus, membrane association is critical to TagB function. In this work we elucidate the mechanism of TagB membrane localization. We report the identification of a membrane targeting determinant at the amino terminus of TagB that is necessary and sufficient for membrane localization. The putative amphipathicity of this membrane targeting determinant was characterized and shown to be required for TagB function but not localization. This work shows for the first time that the amino terminus of TagB mediates membrane targeting and protein function.
Cryptococcus neoformans
Typing by PCR Fingerprinting Using (GACA)
4
Primers Based on
C. neoformans
Genome Project Data
Authors: Cogliati Massimo , Esposto Maria Carmela , Liberi Giordano , Tortorano Anna Maria , Viviani Maria Anna 
Published: August 2007

ABSTRACT

Four (GACA)
4
PCR fingerprinting sequences, used as markers to identify serotypes A and D and AD hybrids, were retrieved in four
Cryptococcus neoformans
genome databases. Their locations, both in serotype A and D genomes, were confirmed by chromosomal hybridization with specific probes. Two sequences were recognized to code for hypothetical functional proteins.
Serine/Arginine-Rich Proteins Contribute to Negative Regulator of Splicing Element-Stimulated Polyadenylation in Rous Sarcoma Virus
Authors: Maciolek Nicole L. , McNally Mark T. 
Published: August 2007

ABSTRACT
Rous sarcoma virus (RSV) requires large amounts of unspliced RNA for replication. Splicing and polyadenylation are coupled in the cells they infect, which raises the question of how viral RNA is efficiently polyadenylated in the absence of splicing. Optimal RSV polyadenylation requires a far-upstream splicing control element, the negative regulator of splicing (NRS), that binds SR proteins and U1/U11 snRNPs and functions as a pseudo-5′ splice site that interacts with and sequesters 3′ splice sites. We investigated a link between NRS-mediated splicing inhibition and efficient polyadenylation. In vitro, the NRS alone activated a model RSV polyadenylation substrate, and while the effect did not require the snRNP-binding sites or a downstream 3′ splice site, SR proteins were sufficient to stimulate polyadenylation. Consistent with this, SELEX-binding sites for the SR proteins ASF/SF2, 9G8, and SRp20 were able to stimulate polyadenylation when placed upstream of the RSV poly(A) site. In vivo, however, the SELEX sites improved polyadenylation in proviral clones only when the NRS-3′ splice site complex could form. Deletions that positioned the SR protein-binding sites closer to the poly(A) site eliminated the requirement for the NRS-3′ splice site interaction. This indicates a novel role for SR proteins in promoting RSV polyadenylation in the context of the NRS-3′ splice site complex, which is thought to bridge the long distance between the NRS and poly(A) site. The results further suggest a more general role for SR proteins in polyadenylation of cellular mRNAs.
West Nile Virus-Induced Neuroinflammation: Glial Infection and Capsid Protein-Mediated Neurovirulence
Authors: van Marle Guido , Antony Joseph , Ostermann Heather , Dunham Christopher , Hunt Tracey , Halliday William , Maingat Ferdinand , Urbanowski Matt D. , Hobman Tom , Peeling James , Power Christopher 
Published: August 2007

ABSTRACTWest Nile virus (WNV) infection causes neurological disease at all levels of the neural axis, accompanied by neuroinflammation and neuronal loss, although the underlying mechanisms remain uncertain. Given the substantial activation of neuroinflammatory pathways observed in WNV infection, we hypothesized that WNV-mediated neuroinflammation and cell death occurred through WNV infection of both glia and neurons, which was driven in part by WNV capsid protein expression. Analysis of autopsied neural tissues from humans with WNV encephalomyelitis (WNVE) revealed WNV infection of both neurons and glia. Upregulation of proinflammatory genes, CXCL10, interleukin-1β, and indolamine-2′,3′-deoxygenase with concurrent suppression of the protective astrocyte-specific endoplasmic reticulum stress sensor gene, OASIS (for old astrocyte specifically induced substance), was evident in WNVE patients compared to non-WNVE controls. These findings were supported by increased ex vivo expression of these proinflammatory genes in glia infected by WNV-NY99. WNV infection caused endoplasmic reticulum stress gene induction and apoptosis in neurons but did not affect glial viability. WNV-infected astrocytic cells secreted cytotoxic factors, which caused neuronal apoptosis. The expression of the WNV-NY99 capsid protein in neurons and glia by a Sindbis virus-derived vector (SINrep5-WNVc) caused neuronal death and the release of neurotoxic factors by infected astrocytes, coupled with proinflammatory gene induction and suppression of OASIS. Striatal implantation of SINrep5-WNVCinduced neuroinflammation in rats, together with the induction of CXCL10 and diminished OASIS expression, compared to controls. Moreover, magnetic resonance neuroimaging showed edema and tissue injury in the vicinity of the SINrep5-WNVc implantation site compared to controls, which was complemented by neurobehavioral abnormalities in the SINrep5-WNVc-implanted animals. These studies underscore the important interactions between the WNV capsid protein and neuroinflammation in the pathogenesis of WNV-induced neurological disorders.
D2-40 is a sensitive and specific marker in differentiating primary adrenal cortical tumours from both metastatic clear cell renal cell carcinoma and phaeochromocytoma
Authors: Browning L , Bailey D , Parker A 
Published: July 2007

Background:The morphological similarities between the cells of clear cell renal cell carcinoma (CCRCC) and those of the adrenal cortex impose diagnostic difficulties, for example in the context of a solitary nodule in the adrenal gland in a patient with renal cell carcinoma (RCC). This problem is confounded by the variable and patchy staining seen with the established panel of antibodies utilised in this context, namely EMA, cytokeratins, vimentin, inhibin, melan-A, and RCC marker; particularly on biopsy material. D2-40, an antibody commonly used to highlight lymphatic endothelial cells, is consistently positive in the normal adrenal cortex.Aims:To investigate the utility of D2-40 in distinguishing neoplastic and non-neoplastic adrenal cortical cells from those of CCRCC, and from phaeochromocytoma.Methods:D2-40 antibody was applied to tissue sections from 10 normal adrenal glands, 15 renal carcinomas (13 clear cell, 2 papillary variants), 1 metastatic CCRCC in the adrenal gland, 6 adrenal cortical hyperplasias, 5 adrenal cortical adenomas, 3 adrenal cortical carcinomas, and 4 phaeochromocytomas.Results:D2-40 was strongly and diffusely positive in the cells of the neoplastic and non-neoplastic adrenal cortex, but negative in the cells of the CCRCC, both primary and metastatic, in 100% of the cases. The cells of the adrenal medulla, and those of the phaeochromocytomas, were negative for D2-40.Conclusions:D2-40 may be a useful marker for distinguishing primary adrenal cortical neoplasms from both metastatic CCRCC and phaeochromocytoma.
The soil seed bank of a montane meadow: consequences of conifer encroachment and implications for restoration
Authors: Lang Nicole L. , Halpern Charles B. 
Published: August 2007

We examined changes in the soil seed bank associated with conifer encroachment of montane meadows in the western Cascade Range of Oregon. We asked whether, and over what period of time, meadow species maintain viable seeds in the soil, and by implication, whether the seed bank can contribute to restoration if conifers are removed. Seed bank composition, ground vegetation, and forest age structure were quantified for 209 samples representing a chronosequence of open meadow, young forest (<75 years), and old forest (95 to >200 years). The seed bank was substantial (44 taxa and 2332 germinants/m2), but dominated by native ruderals (16 species comprising 71% of germinants). Greater than 70% of meadow species were absent from the seed bank. Thirteen meadow species accounted for 21% of all germinants, but most of these were the dominant sedge, Carex pensylvanica Lam.. Seed density, richness, and composition showed weak relationships to forest age, and little resemblance to the ground vegetation, which changed markedly with forest development. Our results suggest that there is limited potential for recovery of most meadow species via the seed bank. Natural reestablishment of these species will require seed dispersal or gradual vegetative spread from existing openings, but competitive interactions with ruderal or forest species may limit recruitment or recovery.
Sensitivity of breast cancer cells to erlotinib depends on cyclin-dependent kinase 2 activity
Authors: Yamasaki Fumiyuki , Zhang Dongwei , Bartholomeusz Chandra , Sudo Tamotsu , Hortobagyi Gabriel N. , Kurisu Kaoru , Ueno Naoto T. 
Published: August 2007

AbstractInhibitors of epidermal growth factor receptor (EGFR) tyrosine kinases, such as erlotinib and gefitinib, have not been very effective in the treatment of breast cancer although many breast cancer cells express EGFR. To address this apparent paradox, we examined possible predictors of the sensitivity of 10 breast cancer cell lines to erlotinib in light of cyclin-dependent kinase 2 (CDK2), considered the farthest downstream kinase that controls cell cycling in the EGFR signaling pathway. Expression of EGFR and HER2 were not associated with sensitivity to erlotinib. Expression of phosphorylated (p-)tyrosine, p-Akt, phosphorylated extracellular signal-regulated kinase (p-ERK) 1/ERK2 (p42/p44), and p27 after treatment of erlotinib was not associated with erlotinib sensitivity. However, suppression of CDK2 activity after erlotinib treatment correlated with erlotinib sensitivity (P &lt; 0.0001). Restoration of CDK2 activity partially restored proliferation and induced erlotinib resistance in erlotinib-sensitive cell lines, indicating that sensitivity to erlotinib in these breast cancer cells depends, at least in part, on CDK2 activity. p27, an inhibitor of CDK2, was not translocated into the nucleus in erlotinib-resistant cell lines. Knocking down p27 protein partially blocked erlotinib-induced cell death and cell cycle arrest. These findings indicate that the ability of erlotinib to suppress CDK2 activity is critical for cellular sensitivity to erlotinib, regardless of EGFR expression level, and that the presence of p27 in the cytoplasm also participates in erlotinib resistance. [Mol Cancer Ther 2007;6(8):2168–77]
Differentially expressed genes in radioresistant nasopharyngeal cancer cells: gp96 and GDF15
Authors: Chang Joseph Tung-Chieh , Chan Shih-Hsuan , Lin Chien-Yu , Lin Ting-Yang , Wang Hung-Ming , Liao Chun-Ta , Wang Tzu-Hao , Lee Li-Yu , Cheng Ann-Joy 
Published: August 2007

Abstract
Radiotherapy is the major treatment modality for nasopharyngeal cancer (NPC), but in some cases, the disease is radioresistant. We designed this study to identify genes that may be involved in this resistance. We first established two radioresistant subclone cell lines derived from NPC parental cell lines (NPC-076 and NPC-BM1) by treating the cells with four rounds of sublethal ionizing radiation. cDNA microarray analysis was then done, comparing the two resistant cell lines with their corresponding parental cell lines. Seven genes were found to be up-regulated in radioresistant subclones, including gp96 and GDF15, which had shown highest overexpressions. We constructed small interfering RNA plasmids (gp96si and GDF15si) and transfected them into NPC cells to knock down these genes and examine whether this changed their response to radiation. Both gp96si and GDF15si transfectants had radiation-induced growth delay and reduction in colonogenic survival compared with control cells. Knockdown of either gp96 or GDF15 increased the proportion of the cells in G2-M phase, the most radiosensitive phase of the cell cycle. We have therefore identified at least two genes, gp96 and GDF15, involved in radioresistance of NPC cell lines and showed that knockdown of the genes enhances radiosensitivity. [Mol Cancer Ther 2007;6(8):2271–9]
A novel, potent, and selective insulin-like growth factor-I receptor kinase inhibitor blocks insulin-like growth factor-I receptor signaling in vitro and inhibits insulin-like growth factor-I receptor–dependent tumor growth in vivo
Authors: Ji Qun-sheng , Mulvihill Mark J. , Rosenfeld-Franklin Maryland , Cooke Andrew , Feng Lixin , Mak Gilda , O'Connor Matthew , Yao Yan , Pirritt Caroline , Buck Elizabeth , Eyzaguirre Alexandra , Arnold Lee D. , Gibson Neil W. , Pachter Jonathan A. 
Published: August 2007

Abstract
Insulin-like growth factor-I receptor (IGF-IR) and its ligands, IGF-I and IGF-II, are up-regulated in a variety of human cancers. In tumors, such as colorectal, non–small cell lung, ovarian, and pediatric cancers, which may drive their own growth and survival through autocrine IGF-II expression, the role of IGF-IR is especially critical. Here, we present a novel small-molecule IGF-IR kinase inhibitor, cis-3-[3-(4-methyl-piperazin-l-yl)-cyclobutyl]-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-8-ylamine (PQIP), which displayed a cellular IC50 of 19 nmol/L for inhibition of ligand-dependent autophosphorylation of human IGF-IR with 14-fold cellular selectivity relative to the human insulin receptor. PQIP showed minimal activity against a panel of 32 other protein kinases. It also abolished the ligand-induced activation of downstream phosphorylated AKT and phosphorylated extracellular signal-regulated kinase 1/2 in both IGF-IR transfectant cells and a GEO human colorectal cancer cell line. Analysis of GEO cells revealed a significant level of both phosphorylated IGF-IR and IGF-II expression. Furthermore, inactivation of IGF-II in conditioned GEO culture medium by a neutralizing antibody diminished IGF-IR activation, indicating the presence of a functional IGF-II/IGF-IR autocrine loop in GEO cells. Once daily oral dosing of PQIP induced robust antitumor efficacy in GEO xenografts. The antitumor efficacy correlated with the degree and duration of inhibition of tumor IGF-IR phosphorylation in vivo by this compound. Moreover, when mice were treated for 3 days with a dose of PQIP that maximally inhibited tumor growth, only minor changes in blood glucose were observed. Thus, PQIP represents a potent and selective IGF-IR kinase inhibitor that is especially efficacious in an IGF-II–driven human tumor model. [Mol Cancer Ther 2007;6(8):2158–67]
Global Patterns of Low-Mode Internal-Wave Propagation. Part I: Energy and Energy Flux
Authors: Alford Matthew H. , Zhao Zhongxiang 
Published: August 2007

Abstract
Extending an earlier attempt to understand long-range propagation of the global internal-wave field, the energy E and horizontal energy flux F are computed for the two gravest baroclinic modes at 80 historical moorings around the globe. With bandpass filtering, the calculation is performed for the semidiurnal band (emphasizing M2 internal tides, generated by flow over sloping topography) and for the near-inertial band (emphasizing wind-generated waves near the Coriolis frequency). The time dependence of semidiurnal E and F is first examined at six locations north of the Hawaiian Ridge; E and F typically rise and fall together and can vary by over an order of magnitude at each site. This variability typically has a strong spring–neap component, in addition to longer time scales. The observed spring tides at sites northwest of the Hawaiian Ridge are coherent with barotropic forcing at the ridge, but lagged by times consistent with travel at the theoretical mode-1 group speed from the ridge. Phase computed from 14-day windows varies by approximately ±45° on monthly time scales, implying refraction by mesoscale currents and stratification. This refraction also causes the bulk of internal-tide energy flux to be undetectable by altimetry and other long-term harmonic-analysis techniques. As found previously, the mean flux in both frequency bands is O(1 kW m−1), sufficient to radiate a substantial fraction of energy far from each source. Tidal flux is generally away from regions of strong topography. Near-inertial flux is overwhelmingly equatorward, as required for waves generated at the inertial frequency on a β plane, and is winter-enhanced, consistent with storm generation. In a companion paper, the group velocity, ĉg ≡ FE−1, is examined for both frequency bands.
The Effect of a New Drag-Law Parameterization on Ice Shelf Water Plume Dynamics
Authors: Wilchinsky Alexander V. , Feltham Daniel L. , Holland Paul R. 
Published: August 2007

Abstract
A drag law accounting for Ekman rotation adjacent to a flat, horizontal boundary is proposed for use in a plume model that is written in terms of the depth-mean velocity. The drag law contains a variable turning angle between the mean velocity and the drag imposed by the turbulent boundary layer. The effect of the variable turning angle in the drag law is studied for a plume of ice shelf water (ISW) ascending and turning beneath an Antarctic ice shelf with draft decreasing away from the grounding line. As the ISW plume ascends the sloping ice shelf–ocean boundary, it can melt the ice shelf, which alters the buoyancy forcing driving the plume motion. Under these conditions, the typical turning angle is of order −10° over most of the plume area for a range of drag coefficients (the minus sign arises for the Southern Hemisphere). The rotation of the drag with respect to the mean velocity is found to be significant if the drag coefficient exceeds 0.003; in this case the plume body propagates farther along and across the base of the ice shelf than a plume with the standard quadratic drag law with no turning angle.
Distinct gene expression profiles of acute myeloid/T-lymphoid leukemia with silenced CEBPA and mutations in NOTCH1
Authors: Wouters Bas J. , Jordà Meritxell Alberich , Keeshan Karen , Louwers Irene , Erpelinck-Verschueren Claudia A. J. , Tielemans Dennis , Langerak Anton W. , He Yiping , Yashiro-Ohtani Yumi , Zhang Pu , Hetherington Christopher J. , Verhaak Roel G. W. , Valk Peter J. M. , Löwenberg Bob , Tenen Daniel G. , Pear Warren S. , Delwel Ruud 
Published: August 2007

AbstractGene expression profiling of acute myeloid leukemia (AML) allows the discovery of previously unrecognized molecular entities. Here, we identified a specific subgroup of AML, defined by an expression profile resembling that of AMLs with mutations in the myeloid transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα), while lacking such mutations. We found that in these leukemias, the CEBPA gene was silenced, which was associated with frequent promoter hypermethylation. The leukemias phenotypically showed aberrant expression of T-cell genes, of which CD7 was most consistent. We identified 2 mechanisms that may contribute to this phenotype. First, absence of Cebpa led to up-regulation of specific T-cell transcripts (ie, Cd7 and Lck) in hematopoietic stem cells isolated from conditional Cebpa knockout mice. Second, the enhanced expression of TRIB2, which we identify here as a direct target of the T-cell commitment factor NOTCH1, suggested aberrantly activated Notch signaling. Putatively activating NOTCH1 mutations were found in several specimens of the newly identified subgroup, while a large set of control AMLs was mutation negative. A gene expression prediction signature allowed the detection of similar cases of leukemia in independent series of AML.
Late mortality after allogeneic hematopoietic cell transplantation and functional status of long-term survivors: report from the Bone Marrow Transplant Survivor Study
Authors: Bhatia Smita , Francisco Liton , Carter Andrea , Sun Can-Lan , Baker K. Scott , Gurney James G. , McGlave Philip B. , Nademanee Auayporn , O'Donnell Margaret , Ramsay Norma K. C. , Robison Leslie L. , Snyder David , Stein Anthony , Forman Stephen J. , Weisdorf Daniel J. 
Published: August 2007

AbstractWe assessed late mortality in 1479 individuals who had survived 2 or more years after allogeneic hematopoietic cell transplantation (HCT). Median age at HCT was 25.9 years and median length of follow-up was 9.5 years. The conditional survival probability at 15 years from HCT was 80.2% (SE = 1.9%) for those who were disease-free at entry into the cohort, and the relative mortality was 9.9 (95% confidence interval, 8.7-11.2). Relative mortality decreased with time from HCT, but remained significantly elevated at 15 years after HCT (standardized mortality ratio = 2.2). Relapse of primary disease (29%) and chronic graft-versus-host disease (cGVHD: 22%) were the leading causes of premature death. Nonrelapse-related mortality was increased among patients older than 18 years at HCT (18-45 years: relative risk [RR] = 1.7; 46+ years: RR = 3.7) and among those with cGVHD (RR = 2.7), and was lower among patients who received methotrexate for GVHD prophylaxis (RR = 0.5). HCT survivors were more likely to report difficulty in holding jobs (odds ratio [OR] = 13.9), and in obtaining health (OR = 7.1) or life (OR = 9.9) insurance compared with siblings. This study demonstrates that mortality rates remain twice as high as that of the general population among 15-year survivors of HCT, and that the survivors face challenges affecting their health and well-being.
Microbiologically documented infections and infection-related mortality in children with acute myeloid leukemia
Authors: Sung Lillian , Lange Beverly J. , Gerbing Robert B. , Alonzo Todd A. , Feusner James 
Published: July 2007

AbstractThe primary objective was to describe the prevalence and characteristics of microbiologically defined infections and infection-related mortality (IRM) in 492 children with acute myeloid leukemia enrolled on CCG 2961. Secondary objectives were to determine the relationship between demographic, disease-related, and therapeutic variables, and infections and IRM. Institutions documented infections prospectively. Age, ethnicity, body mass index, leukemia karyotype, treatment, and institutional size were examined for association with infection outcomes. More than 60% of children experienced such infections in each of 3 phases of chemotherapy. There were 58 infectious deaths; cumulative incidence of IRM was 11% plus or minus 2%. Thirty-one percent of infectious deaths were associated with Aspergillus, 25.9% with Candida, and 15.5% with alpha hemolytic streptococci. Age older than 16 years (hazard ratio [HR], 3.32; 95% confidence interval [CI], 1.87-5.89; P < .001), nonwhite ethnicity (HR, 1.85; 95% CI, 1.10-3.09; P = .02), and underweight status (HR, 3.06; 95% CI, 1.51-6.22; P = .002) were associated with IRM, while size of the treating institution was not. Thus, age, ethnicity, and BMI were important contributors to IRM. Fungi and Gram-positive cocci were the most common organisms associated with IRM and, in particular, Aspergillus species was the largest contributor to infectious deaths.