bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of 5‐Methylcytosine in DNA of Breast and Colon Cancer Tissues
Authors: Barciszewska Anna‐Maria , Murawa Dawid , Gawronska Iwona , Murawa Pawel , Nowak Stanislaw , Barciszewska Miroslawa Z. 
Published: December 2007

Abstract5‐methylcytosine (m5C) can be used as a sensitive marker of progress of the tumor formation induced by the oxidative damage reactions. We have analyzed the amount of m5C in DNA of patients with breast and colon cancers. Two dimensional thin layer chromatography (TLC) has been used to monitor 5‐methylcytosine level in DNA extracted from cancer tissues. The level of methylation of cytosine at C‐5 position in DNA from breast cancer patients correlates well with the malignancy of tumors. Interestingly higher amount of m5C in DNA for the breast cancer patients treated with different chemotherapeutics was observed. It suggests an activation of DNA methyltransferase as well as a genomic suppression of the DNA repair genes expression. These differences clearly reflect the health condition of patients and support the global analysis of m5C in DNA as a good marker for diagnosis of neoplasia in clinical practice.
Concentrations of Dapivirine in the Rhesus Macaque and Rabbit following Once Daily Intravaginal Administration of a Gel Formulation of [
14
C]Dapivirine for 7 Days
Authors: Nuttall Jeremy P. , Thake Daryl C. , Lewis Mark G. , Ferkany John W. , Romano Joseph W. , Mitchnick Mark A. 
Published: December 2007

ABSTRACT

Dapivirine is a nonnucleoside reverse transcriptase inhibitor being developed as a topical microbicide for the prevention of human immunodeficiency virus infection. The distribution of radioactivity and drug in plasma and in vaginal, cervical, and draining lymph node tissues was investigated after daily application of a vaginal gel formulation of [
14
C]dapivirine to rhesus macaques. This was preceded by a preliminary study with rabbits. Following the intravaginal administration of [
14
C]dapivirine (∼0.1 mg/ml [15 μCi/ml]) to rabbits (0.5 ml/day) and macaques (1 ml/day) for 7 days, the dapivirine levels associated with vaginal and cervical tissue samples 1 h after the final dose were high (quantities of μg/g of tissue) and remained detectable at 24 h (mean, ≥2.5 ng/g in rabbits) and 48 h (mean, >80 ng/g in macaques). Radioactivity levels were low in the plasma and very low or unquantifiable in the draining lymph nodes of the macaques. Microautoradiography identified drug-related material (DRM) on the surfaces of the vaginal and cervical tissues of the rabbits and macaques. Although DRM was primarily associated with the outermost layer of shedding cells in rabbits, two animals showed some evidence of small quantities in the mucosal epithelium of the cervix. In macaques, DRM was seen within the keratinized layer of the vaginal epithelium and and was found to extend into the superficial cellular layers, and in at least one animal it appeared to be present in the deepest (germinal) layer of the epithelium and in submucosal tissues. The persistence of biologically significant concentrations of dapivirine in vaginal and cervical tissues for >24 h supports the development of dapivirine as a microbicide for once daily application.
Dectin-1 Fc Targeting of
Aspergillus fumigatus
Beta-Glucans Augments Innate Defense against Invasive Pulmonary Aspergillosis
Authors: Mattila Polly E. , Metz Allison E. , Rapaka Rekha R. , Bauer Lynne D. , Steele Chad 
Published: December 2007

ABSTRACT

Invasive pulmonary aspergillosis (IPA) has significantly increased over the last decade. Here, a fusion protein consisting of the Dectin-1 extracellular domain linked to the Fc portion of murine immunoglobulin G1 augmented alveolar macrophage killing of
Aspergillus fumigatus
and shifted mortality associated with IPA via attenuation of
A. fumigatus
growth in the lung.
Isolation and Purification of Enterocin E-760 with Broad Antimicrobial Activity against Gram-Positive and Gram-Negative Bacteria
Authors: Line J. E. , Svetoch E. A. , Eruslanov B. V. , Perelygin V. V. , Mitsevich E. V. , Mitsevich I. P. , Levchuk V. P. , Svetoch O. E. , Seal B. S. , Siragusa G. R. , Stern N. J. 
Published: December 2007

ABSTRACT

Strain NRRL B-30745, isolated from chicken ceca and identified as
Enterococcus durans
,
Enterococcus faecium
, or
Enterococcus hirae
, was initially identified as antagonistic to
Campylobacter jejuni
. The isolate produced a 5,362-Da bacteriocin (enterocin) that inhibits the growth of
Salmonella enterica
serovar Enteritidis,
S. enterica
serovar Choleraesuis,
S. enterica
serovar Typhimurium,
S. enterica
serovar Gallinarum,
Escherichia coli
O157:H7,
Yersinia enterocolitica
,
Citrobacter freundii
,
Klebsiella pneumoniae
,
Shigella dysenteriae
,
Pseudomonas aeruginosa
,
Proteus mirabilis
,
Morganella morganii
,
Staphylococcus aureus
,
Staphylococcus epidermidis
,
Listeria monocytogenes
,
Campylobacter jejuni
, and 20 other
Campylobacter
species isolates. The enterocin, E-760, was isolated and purified by cation-exchange and hydrophobic-interaction chromatographies. The proteinaceous nature of purified enterocin E-760 was demonstrated upon treatment with various proteolytic enzymes. Specifically, the antimicrobial peptide was found to be sensitive to beta-chymotrypsin, proteinase K, and papain, while it was resistant to lysozyme and lipase. The enterocin demonstrated thermostability by retaining activity after 5 min at 100°C and was stable at pH values between 5.0 and 8.7. However, activity was lost below pH 3.0 and above pH 9.5. Administration of enterocin E-760-treated feed significantly (
P
< 0.05) reduced the colonization of young broiler chicks experimentally challenged and colonized with two strains of
C. jejuni
by more than 8 log
10
CFU. Enterocin E-760 also significantly (
P
< 0.05) reduced the colonization of naturally acquired
Campylobacter
species in market age broiler chickens when administered in treated feed 4 days prior to analysis.
ViableBorrelia burgdorferiEnhances Interleukin-10 Production and Suppresses Activation of Murine Macrophages
Authors: Lazarus John J. , Kay Maria A. , McCarter Akisha L. , Wooten R. Mark 
Published: December 2007

ABSTRACTAlthough it is capable of eliciting strong innate and adaptive immune responses,Borrelia burgdorferioften evades immune clearance through largely unknown mechanisms. Our previous studies determined that infected interlukin-10−/−(IL-10−/−) mice show significantly lowerB. burgdorferilevels than wild-type (B6) mice and that IL-10 inhibits innate immune responses critical for controllingB. burgdorferiinfection. To determine whether virulentB. burgdorferipreferentially enhances IL-10 production, we developed an in vitro coculture medium (RPMI.B) in which bothB. burgdorferiand primary macrophages (Mφs) remain viable.B. burgdorferigrew at similar rates and was able to regulate expression of immunoreactive proteins with similar kinetics in RPMI.B and in traditional BSK medium; in contrast,B. burgdorfericultured in conventional tissue culture medium (RPMI) rapidly lost viability. Coculture of viableB. burgdorferiin RPMI.B with Mφs resulted in more rapid and significant increases in IL-10 transcripts and secreted proteins than coculture with nonviableB. burgdorferiin RPMI, which corresponded with decreased production of proinflammatory cytokines. Addition of liveB. burgdorferito Mφs in RPMI.B also elicited substantially higher IL-10 levels than heat-killed bacteria elicited, confirming that increased IL-10 production was not inherent to coculture in RPMI.B. Transfer of supernatants fromB. burgdorferi-stimulated Mφs into naïve Mφ cultures resulted in suppressed activation upon subsequent stimulation with different bacterial agonists, and this suppression was obviated by IL-10-specific antibody. In vivo analyses determined that murine skin samples exhibited substantial upregulation of IL-10 within 24 h of injection ofB. burgdorferi. Together, these results suggest that viableB. burgdorferican suppress early Mφ responses during infection by causing increased release of IL-10.
RIN1 Is a Breast Tumor Suppressor Gene
Authors: Milstein Marc , Mooser Chelsea K. , Hu Hailiang , Fejzo Marlena , Slamon Dennis , Goodglick Lee , Dry Sarah , Colicelli John 
Published: December 2007

Abstract
Breast cancer progression is driven by altered gene expression. We show that the RIN1 gene, which encodes a RAS effector regulating epithelial cell properties, is silenced in breast tumor cell lines compared with cultured human mammary epithelial cells. We also report that RIN1 is often reduced in human breast tumor cells compared with morphologically normal breast glandular cells. At least two silencing mechanisms seem to be involved. Overexpression of the transcription repressor SNAI1 (Snail) was observed in ZR75-1 cells, and SNAI1 knockdown restored RIN1 expression. In addition, DNA methylation within the RIN1 promoter and the first exon in KPL-1 cells suggested that epigenetic modifications may contribute to silencing, and demethylation was shown to restore RIN1 expression. Reexpression of RIN1 was shown to inhibit anchorage-independent growth in soft agar. In addition, RIN1 expression inhibited both the initiation and progression of tumorigenesis for two breast tumor cell lines in a mouse model, consistent with a tumor suppressor function. We also show that RIN1 acts as a negative regulator of tumor cell invasive growth and that this requires the ABL kinase–signaling function of RIN1, suggesting a mechanism through which RIN1 silencing may contribute to breast cancer progression. [Cancer Res 2007;67(24):11510–6]
Cytosolic Phospholipase A2α Regulates Cell Growth in RET/PTC-Transformed Thyroid Cells
Authors: Mariggiò Stefania , Filippi Beatrice Maria , Iurisci Cristiano , Dragani Luana Katia , De Falco Valentina , Santoro Massimo , Corda Daniela 
Published: December 2007

Abstract
Modulation of cytosolic phospholipase A2 (PLA2) expression levels and production of its metabolites have been reported in several tumor types, indicating involvement of arachidonic acid and its derivatives in tumorigenesis. Following our demonstration that the PLA2 group IV isoform α (PLA2IVα) controls TSH-independent growth of normal thyroid (PCCl3) cells, we have investigated the mitogenic role of PLA2IVα in rat thyroid cells transformed by the RET/PTC oncogenes (PC-PTC cells). We now report that PLA2IVα acts downstream of the RET/PTC oncogenes in a novel pathway controlling RET-dependent cell proliferation. In addition, we show that PLA2IVα is in its phosphorylated/active form not only in RET/PTC-transformed cells and in cells derived from human papillary carcinomas but also in lysates from tumor tissues, thus relating constitutive activation of PLA2IVα to RET/PTC-dependent tumorigenesis. Moreover, p38 stress-activated protein kinase is the downstream effector of RET/PTC that is responsible for PLA2IVα phosphorylation and activity. In summary, our data elucidate a novel mechanism in the control of thyroid tumor cell growth that is induced by the RET/PTC oncogenes and which is distinguishable from that of other oncogenes, such as BRAF. This mechanism is mediated by PLA2IVα and should be amenable to targeted pharmacologic intervention. [Cancer Res 2007;67(24):11769–78]
Vitamin E Analogues Inhibit Angiogenesis by Selective Induction of Apoptosis in Proliferating Endothelial Cells: The Role of Oxidative Stress
Authors: Dong Lan-Feng , Swettenham Emma , Eliasson Johanna , Wang Xiu-Fang , Gold Mikhal , Medunic Yasmine , Stantic Marina , Low Pauline , Prochazka Lubomir , Witting Paul K. , Turanek Jaroslav , Akporiaye Emmanuel T. , Ralph Stephen J. , Neuzil Jiri 
Published: December 2007

Abstract
“Mitocans” from the vitamin E group of selective anticancer drugs, α-tocopheryl succinate (α-TOS) and its ether analogue α-TEA, triggered apoptosis in proliferating but not arrested endothelial cells. Angiogenic endothelial cells exposed to the vitamin E analogues, unlike their arrested counterparts, readily accumulated reactive oxygen species (ROS) by interfering with the mitochondrial redox chain and activating the intrinsic apoptotic pathway. The vitamin E analogues inhibited angiogenesis in vitro as assessed using the “wound-healing” and “tube-forming” models. Endothelial cells deficient in mitochondrial DNA (mtDNA) were resistant to the vitamin E analogues, both in ROS accumulation and apoptosis induction, maintaining their angiogenic potential. α-TOS inhibited angiogenesis in a mouse cancer model, as documented by ultrasound imaging. We conclude that vitamin E analogues selectively kill angiogenic endothelial cells, suppressing tumor growth, which has intriguing clinical implications. [Cancer Res 2007;67(24):11906–13]
Targeting Cdc37 Inhibits Multiple Signaling Pathways and Induces Growth Arrest in Prostate Cancer Cells
Authors: Gray Phillip J. , Stevenson Mary Ann , Calderwood Stuart K. 
Published: December 2007

Abstract
Members of the 90-kDa heat shock protein (HSP90) family are known to bind and stabilize intermediates in a wide variety of cell signaling pathways and contribute to their dysregulation in cancer. An important intracellular cofactor for HSP90 is Cdc37, a protein with a broad role in fostering the activities of protein kinases. By targeting Cdc37 using RNA interference, we have shown that the loss of Cdc37 function induces irreversible growth arrest in androgen receptor-positive and -negative prostate carcinoma cells. In contrast to HSP90-directed agents, Cdc37 targeting seems to affect cancer cells through a distinct mechanism and does not significantly deplete the intracellular levels of most known HSP90 client proteins. Instead, Cdc37 depletion inhibits cellular kinase activity and flux through growth-promoting signal transduction cascades. We show that the loss of Cdc37 leads to reduced activity of the Erk, Akt, mTOR, and androgen-induced pathways. We have also discovered synergistic interactions between Cdc37 inactivation and the HSP90-inhibitory anticancer drug 17-(allylamino)-17-demethoxygeldanamycin (17AAG). These interactions involve enhanced degradation of proteins essential for growth and inhibition of 17AAG-induced expression of the antiapoptotic HSP70. Thus, Cdc37 is essential for maintaining prostate tumor cell growth and may represent a novel target in the search for multitargeted therapies based on the HSP90 chaperone system. [Cancer Res 2007;67(24):11942–50]
Chemosensitization of head and neck cancer cells by PUMA
Authors: Sun Quanhong , Sakaida Tsukasa , Yue Wen , Gollin Susanne M. , Yu Jian 
Published: December 2007

Abstract
Head and neck squamous cell carcinoma (HNSCC) ranks the eighth most common cancer worldwide. The patients often present with advanced disease, which responds poorly to chemoradiation therapy. PUMA is a BH3-only Bcl-2 family protein and a p53 target that is required for apoptosis induced by p53 and various chemotherapeutic agents. In this study, we found that PUMA induction by chemotherapeutic agents is abrogated in most HNSCC cell lines. Adenoviral gene delivery of PUMA induced apoptosis and chemosensitization more potently than did adenoviral delivery of p53 in HNSCC cells. Finally, we showed that PUMA suppressed the growth of HNSCC xenograft tumors and sensitized them to cisplatin through induction of apoptosis. Our data suggest that absence of PUMA activation in HNSCC cells contributes to chemoresistance and that gene therapy with PUMA might be an efficient substitute for p53 to enhance the responses of HNSCC cells to chemotherapy. [Mol Cancer Ther 2007;6(12):3180–8]
Novel E-ring camptothecin keto analogues (S38809 and S39625) are stable, potent, and selective topoisomerase I inhibitors without being substrates of drug efflux transporters
Authors: Takagi Kazutaka , Dexheimer Thomas S. , Redon Christophe , Sordet Olivier , Agama Keli , Lavielle Gilbert , Pierré Alain , Bates Susan E. , Pommier Yves 
Published: December 2007

Abstract
Camptothecin (CPT) analogues are powerful anticancer agents but are chemically unstable due to their α-hydroxylactone six-membered E-ring structure, which is essential for trapping topoisomerase I (Top1)-DNA cleavage complexes. To stabilize the E-ring, CPT keto analogues with a five-membered E-ring lacking the oxygen of the lactone ring (S38809 and S39625) have been synthesized. S39625 has been selected for advanced preclinical development based on its promising activity in tumor models. Here, we show that both keto analogues are active against purified Top1 and selective against Top1 in yeast and human cancer cells. The keto analogues show improved cytotoxicity toward colon, breast, and prostate cancer cells and leukemia cells compared with CPT. The drug-induced Top1-DNA cleavage complexes induced by the keto analogues show remarkable persistence both with purified Top1 and in cells following 1-h drug treatments. Moreover, we find that S39625 is not a substrate for either the ABCB1 (multidrug resistance-1/P-glycoprotein) or ABCG2 (mitoxantrone resistance/breast cancer resistance protein) drug efflux transporters, which sets S39625 apart from the clinically used CPT analogues topotecan or SN-38 (active metabolite of irinotecan). Finally, we show that nanomolar concentrations of S38809 or S39625 induce intense and persistent histone γ-H2AX. The chemical stability of the keto analogues and the ability of S39625 to produce high levels of persistent Top1-DNA cleavage complex and its potent antiproliferative activity against human cancer cell lines make S39625 a promising new anticancer drug candidate. Histone γ-H2AX could be used as a biomarker for the upcoming clinical trials of S39625. [Mol Cancer Ther 2007;6(12):3229–38]
Collecting Families: An Institutional Approach to Human Genetic Biobanking in Indonesia
Authors: Sleeboom-Faulkner Margaret 
Published: December 2007

This paper analyses the e-discourse surrounding the dream of a Dutch scientist, Dr X, to create a human genetic databank in Bandung, Indonesia. Not only did Dr X hope to fulfil his dream of placing Indonesia on the genetic world map, he also aspired to set up the largest biomedical research centre in Indonesia, using blood samples gathered from various laboratories, medical centres and the jungle. His most important project was to study genes for familial syndromes, such as cancers and forms of mental retardation, some of which are considered to be specific for certain ethnic groups in Indonesia.
Much has been written on the targets of the Human Genome Diversity Project (HGDP), but the incentives for and motives of geneticists to set up biobanks are little understood. Many works have 'framed' scientists as imperialists, Orientalists, racists and positivists or hailed them as explorers of humanity, pioneers of science and saviours of mankind.
By analyzing Dr X's e-letters to fellow scientists, academics and politicians, I claim that the validity of such theories depends on whether they sufficiently take into account the institutional embedding. An institutional approach to biobanking should incorporate an assessment of socioeconomic inequalities, both on an international and national level, public healthcare needs, research regulation, and differences in academic cultures from a comparative perspective.
Determining the Sources of Regional Haze in the Southeastern United States Using the CMAQ Model
Authors: Odman M. Talat , Hu Yongtao , Unal Alper , Russell Armistead G. , Boylan James W. 
Published: December 2007

Abstract
A detailed sensitivity analysis was conducted to help to quantify the impacts of various emission control options in terms of potential visibility improvements at class I national parks and wilderness areas in the southeastern United States. Particulate matter (PM) levels were estimated using the Community Multiscale Air Quality (CMAQ) model, and light extinctions were calculated using the modeled PM concentrations. First, likely changes in visibility at class I areas were estimated for 2018. Then, using emission projections for 2018 as a starting point, the sensitivity of light extinction was evaluated by reducing emissions from various source categories by 30%. Source categories to be analyzed were determined using a tiered approach: any category that showed significant impact in one tier was broken into subcategories for further analysis in the next tier. In the first tier, sulfur dioxide (SO2), nitrogen oxides, ammonia, volatile organic compound, and primary carbon emissions were reduced uniformly over the entire domain. During summer, when most class I areas experience their worst visibility, reduction of SO2 emissions was the most effective control strategy. In the second tier, SO2 sources were separated as ground level and elevated. The elevated sources in 10 southeastern states were differentiated from those in the rest of the domain and broken into three subcategories: coal-fired power plant (CPP), other power plant, and other than power plant [i.e., non–electric generating unit (non EGU)]. The SO2 emissions from the CPP subcategory had the largest impact on visibility at class I areas, followed by the non-EGU subcategory. In the third tier, emissions from these two subcategories were further broken down by state. Most class I areas were affected by the emissions from several states, indicating the regional nature of the haze problem. Here, the visibility responses to all of the aforementioned emission reductions are quantified and deviations from general trends are identified.
Characterization of probiotic Escherichia coliisolates with a novel pan-genome microarray
Authors: Willenbrock Hanni , Hallin Peter F , Wassenaar Trudy M , Ussery David W 
Published: December 2007

Abstract
Background
Microarrays have recently emerged as a novel procedure to evaluate the genetic content of bacterial species. So far, microarrays have mostly covered single or few strains from the same species. However, with cheaper high-throughput sequencing techniques emerging, multiple strains of the same species are rapidly becoming available, allowing for the definition and characterization of a whole species as a population of genomes - the 'pan-genome'.

Results
Using 32 Escherichia coli and Shigella genome sequences we estimate the pan- and core genome of the species. We designed a high-density microarray in order to provide a tool for characterization of the E. coli pan-genome. Technical performance of this pan-genome microarray based on control strain samples (E. coli K-12 and O157:H7) demonstrated a high sensitivity and relatively low false positive rate. A single-channel analysis approach is robust while allowing the possibility for deriving presence/absence predictions for any gene included on our pan-genome microarray. Moreover, the array was highly sufficient to investigate the gene content of non-pathogenic isolates, despite the strong bias towards pathogenic E. coli strains that have been sequenced so far.

Conclusion
This high-density microarray provides an excellent tool for characterizing the genetic makeup of unknown E. coli strains and can also deliver insights into phylogenetic relationships. Its design poses a considerably larger challenge and involves different considerations than the design of single strain microarrays. Here, lessons learned and future directions will be discussed in order to optimize design of microarrays targeting entire pan-genomes.
Fabrication of Octahedral Gold Nanostructures Using an Alcoholic Ionic Liquid
Authors: Ren Lanzheng , Meng Lingjie , Lu Qinghua 
Published: December 2007

Abstract
Octahedral gold nanocrystals have been fabricated in an alcohol ionic liquid by a one-step method in the absence of any extra capping agent. The method is based on a reaction of HAuCl4·4H2O in 1-(3-hydroxylpropyl)-3-methylimidazolium tetrafluoroborate (C3OHmimBF4) by microwave heating. Upon adjusting HAuCl4·4H2O concentration and reaction temperature, nanoplates and micrometer-sized particles have also been obtained.