bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two generation reproduction study of styrene by inhalation in Crl‐CD rats
Authors: Cruzan George , Faber Willem D. , Johnson Keith A. , Roberts Linda S. , Hellwig Juergen , Carney Ed , Yarrington John T. , Stump Donald G. 
Published: May 2005

AbstractThis study was conducted to evaluate the potential adverse effects of styrene on reproductive capability from whole‐body inhalation exposure of F0 and F1 parental animals. Assessments included gonadal function, estrous cyclicity, mating behavior, conception rate, gestation, parturition, lactation, and weaning in the F0 and F1 generations, and F1 generation offspring growth and development. Four groups of male and female Crl:CD(SD)IGS BR rats (25/sex/group) were exposed to 0, 50, 150, and 500 ppm styrene for 6 hr daily for at least 70 consecutive days prior to mating for the F0 and F1 generations. Inhalation exposure for the F0 and F1 females continued throughout mating and gestation through gestation day 20. Inhalation exposure of the F0 and F1 females was suspended from gestation day 21 through lactation day 4. On lactation days 1 through 4, the F0 and F1 females received styrene in virgin olive oil via oral gavage at dose levels of 66, 117, and 300 mg/kg/day (divided into three equal doses, approximately 2 hr apart). These oral dosages were calculated to provide similar maternal blood peak concentrations as provided by the inhalation exposures. Inhalation exposure of the F0 and F1 females was re‐initiated on lactation day 5. Styrene exposure did not affect survival or clinical observations. Rats in the 150‐ and 500‐ppm groups in both parental generations gained weight more slowly than the controls. There were no indications of adverse effects on reproductive performance in either the F0 or F1 generation. Male and female mating and fertility indices, pre‐coital intervals, spermatogenic endpoints, reproductive organ weights, lengths of estrous cycle and gestation, live litter size and postnatal survival were similar in all exposure groups. Additionally, ovarian follicle counts and corpora lutea counts for the F1 females in the high‐exposure group were similar to the control values. No adverse exposure‐related macroscopic pathology was noted at any exposure level in the F0 and F1 generations. A previously characterized pattern of degeneration of the olfactory epithelium that lines the dorsal septum and dorsal and medial aspects of the nasal turbinates occurred in the F0 and F1 generation animals from the 500‐ppm group. In the 500‐ppm group, F2 birthweights were reduced compared to the control and F2 offspring from both the 150‐ and 500‐ppm exposure groups gained weight more slowly than the controls. Based on the results of this study, an exposure level of 50 ppm was considered to be the NOAEL for F0 and F1 parental systemic toxicity; the NOAEL for F0 and F1 reproductive toxicity was 500 ppm or greater. Birth Defects Res B 2005. © 2005 Wiley‐Liss, Inc.
Antimicrobial peptides: New candidates in the fight against bacterial infections
Authors: Toke Orsolya 
Published: May 2005

AbstractAntimicrobial peptides (AMPs) of innate origin are agents of the most ancient form of defense systems. They can be found in a wide variety of species ranging from bacteria through insects to humans. Through the course of evolution, host organisms developed arsenals of AMPs that protect them against a large variety of invading pathogens including both Gram‐negative and Gram‐positive bacteria. At a time of increasing bacterial resistance, AMPs have been the focus of investigation in a number of laboratories worldwide. Although recent studies show that some of the peptides are likely to have intracellular targets, the vast majority of AMPs appear to act by permeabilization of the bacterial cell membrane. Their activity and selectivity are governed by the physicochemical parameters of the peptide chains as well as the properties of the membrane system itself. In this review, we will summarize some of the recent developments that provide us with a better understanding of the mode of action of this unique family of antibacterial agents. Particular attention will be given to the determinants of AMP–lipid bilayer interactions as well as to the different pore formation mechanisms. The emphasis will be on linear AMPs but representatives of cysteine‐bridged AMPs will also be discussed. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 80: 717–735, 2005This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
“Parallel” and “Antiparallel Tail‐Clamps” Increase the Efficiency of Triplex Formation with Structured DNA and RNA Targets
Authors: Nadal Anna , Eritja Ramon , Esteve Teresa , Pla Maria 
Published: May 2005

AbstractSequence‐specific triple‐helix structures can be formed by parallel and antiparallel DNA clamps interacting with single‐stranded DNA or RNA targets. Single‐stranded nucleic acid molecules are known to adopt secondary structures that might interfere with intermolecular interactions. We demonstrate the correlation between a secondary structure involving the target—a stable stem predicted by in silico folding and experimentally confirmed by thermal stability and competition analyses—and an inhibitory effect on triplex formation. We overcame structural impediments by designing a new type of clamp: “tail‐clamps”. A combination of gel‐shift, kinetic analysis, UV thermal melting and thermodynamic techniques was used to demonstrate that tail‐clamps efficiently form triple helices with a structured target sequence. The performance of parallel and antiparallel tail‐clamps was compared: antiparallel tail‐clamps had higher binding efficiencies than parallel tail‐clamps both with structured DNA and RNA targets. In addition, the reported triplex‐stabilizing property of 8‐aminopurine residues was confirmed for tail‐clamps. Finally, we discuss the possible use of this improved triplex technology as a new tool for applications in molecular biology.
Chemical Synthesis of Triple‐Labelled Three‐Helix Bundle Binding Proteins for Specific Fluorescent Detection of Unlabelled Protein
Authors: Engfeldt Torun , Renberg Björn , Brumer Harry , Nygren Per Åke , Eriksson Karlström Amelie 
Published: May 2005

AbstractSite‐specifically triple‐labelled three‐helix bundle affinity proteins (affibody molecules) have been produced by total chemical synthesis. The 58 aa affinity proteins were assembled on an automated peptide synthesizer, followed by manual on‐resin incorporation of three different reporter groups. An orthogonal protection strategy was developed for the site‐specific introduction of 5‐(2‐aminethylamino)‐1‐naphthalenesulfonic acid (EDANS) and 6‐(7‐nitrobenzofurazan‐4‐ylamino)‐hexanoic acid (NBDX), constituting a donor/acceptor pair for fluorescence resonance energy transfer (FRET), and a biotin moiety, used for surface immobilization. Circular dichroism and biosensor studies of the synthetic proteins and their recombinant counterparts revealed that the synthetic proteins were folded and retained their binding specificities. The biotin‐conjugated protein could be immobilized onto a streptavidin surface without loss of activity. The synthetic, doubly fluorescent‐labelled affinity proteins were shown to function as fluorescent biosensors in an assay for the specific detection of unlabelled human IgG and IgA.
Design and Synthesis of Hierarchical Materials from Ordered Zeolitic Building Units
Authors: Kirschhock Christine E. A. , Kremer Sebastien P. B. , Vermant Jan , Van Tendeloo Gustaaf , Jacobs Pierre A. , Martens Johan A. 
Published: May 2005

AbstractThe crystallization of colloidal silicalite‐1 from clear solution is one of the best understood zeolite formation processes. Colloidal silicalite‐1 formation involves a self‐assembly process in which nanoslabs and nanotablets with a silicalite‐1 type connectivity are formed at intermediate stages. During the assembly process, with strongly anisometric particles present, regions appear with orientational correlations, as evidenced with measurements of dynamic light scattering, viscosity, and rotation of polarized light. The presence of such regions rationalizes the unexpected differences between the crystallization kinetics under microgravity and on earth. The discovery of the locally oriented regions sheds new light on currently poorly understood hydrodynamic effects on the zeolite formation processes, such as the influence of stirring on the phases obtained and the subsequent kinetics. Addition of surfactants or polymers modifies the ordering of the zeolitic building units in the correlated regions, and new types of hierarchical materials named zeogrids and zeotiles can be obtained.
Evidence that one subset of anaplastic thyroid carcinomas are derived from papillary carcinomas due to BRAF and p53 mutations
Authors: Quiros Roderick M. , Ding Helen G. , Gattuso Paolo , Prinz Richard A. , Xu Xiulong 
Published: May 2005

AbstractBACKGROUNDAnaplastic thyroid carcinoma (ATC) is the most lethal form of thyroid neoplasia and represents the end stage of thyroid tumor progression. In the current study, genetic alterations in a panel of ATC were profiled to determine the origins of ATC.METHODSEight ATC were analyzed for BRAF mutation at codon 599 by using mutant‐allele‐specific polymerase chain reaction (PCR) and DNA sequencing of the PCR‐amplified exon 15. RAS mutation (HRAS, KRAS, and NRAS) at codons 12, 13, and 61 was analyzed by direct sequencing of PCR‐amplified exons 1 and 2 of the RAS gene. RET/PTC rearrangements and p53 mutation were monitored by immunohistochemical (IHC) staining by anti‐RET antibodies and an anti‐p53 mAb, respectively.RESULTSBRAF was mutated in 5 of the 8 ATCs tested. Histologic examination revealed that 4 of these 5 BRAF‐mutated ATCs contained a PTC component, suggesting that they may be derived from BRAF‐mutated PTC. Of the 3 ATCs with wild‐type BRAF, 2 had spindle cell features; one had follicular neoplastic characteristics mixed with papillary structures. Analysis of RAS mutation revealed only an HRAS mutation at codon 11, due to the transversion of GCC to TCC in one ATC with wild‐type BRAF. This leads to the substitution of valine to serine. IHC analysis of RET/PTC rearrangements revealed no positive staining of RET in any of 8 ATCs, suggesting that these ATCs are not derived from RET/PTC‐ rearranged PTC. In contrast, IHC analysis of p53 mutation revealed that p53 was detected in the nuclei of 5 of 5 BRAF‐mutated ATCs and 2 of 3 ATCs with wild‐type BRAF. p53 staining was present only in anaplastic thyroid tumor cells but not in neighboring papillary thyroid tumor cells.CONCLUSIONSThese results suggest that many ATCs with papillary components are derived from BRAF‐mutated PTC, because of the addition of p53 mutation. Cancer 2005. © 2005 American Cancer Society.
Epidermal growth factor receptor‐targeted treatment for advanced colorectal carcinoma
Authors: Venook Alan P. 
Published: May 2005

AbstractSubstantial effort has focused on the development of novel targeted agents for treating patients with late‐stage colorectal carcinoma. These agents are designed specifically to inhibit biochemical processes associated with pathogenesis. Numerous molecules targeting the epidermal growth factor receptor have been investigated as therapeutic agents and appear to herald a shift in the treatment paradigm for colorectal carcinoma. Cancer 2005. © 2005 American Cancer Society.
Colorectal carcinoma screening among Hispanics and non‐Hispanic whites in a rural setting
Authors: Thompson Beti , Coronado Gloria , Neuhouser Marian , Chen Lu 
Published: May 2005

AbstractBACKGROUNDColorectal carcinoma ranks as the second most common cancer and the second leading cause of cancer death in the United States. Hispanics are less likely than their non‐Hispanic white counterparts to have ever received a fecal occult blood test (FOBT) or sigmoidoscopy/colonoscopy. Little is known about the barriers to screening in the Hispanic population.METHODSThe authors used baseline data from a community randomized trial of cancer prevention to compare screening prevalence and the associations between reported barriers and screening participation between Hispanics (n = 137) and non‐Hispanic whites (n = 491) age ≥ 50 years.RESULTSHispanics were less likely than non‐Hispanic whites to have ever received an FOBT (P = 0.003) or sigmoidoscopy/colonoscopy (P = 0.001). No significant difference across ethnic groups was observed in the prevalence of recent screening using FOBT (29.8% for Hispanics vs. 34.5% for non‐Hispanic whites; P = 0.41), but recent use of sigmoidoscopy/colonoscopy was lower for Hispanics (24.1% for Hispanics vs. 33.7% for non‐Hispanic whites; P 0.06). Lacking health care coverage or having few years of education were directly associated with failure to ever receive an FOBT or sigmoidoscopy/colonoscopy.CONCLUSIONSInterventions to improve adherence to colorectal carcinoma screening recommendations among Hispanics should target initial screening examinations, particularly among those lacking health care coverage or having low levels of education. Cancer 2005. © 2005 American Cancer Society.
Experimental analysis of the transdifferentiation of visceral to parietal endoderm in the mouse
Authors: Ninomiya Youichirou , Davies Timothy J. , Gardner Richard L. 
Published: May 2005

AbstractThe visceral endoderm (VE) of isolated extraembryonic regions (ExEmbs) of 7 days postcoitum (dpc) prestreak mouse conceptuses have been shown to convert readily to parietal endoderm (PE). The present study addresses the following three unanswered questions. On what does conversion depend, how rapidly does it occur, and is it an enduring general property of a residual small population of relatively immature cells? In situ hybridization reveals that change in cell state occurs within 2 days of culture. Deprivation of the mesoderm also promotes it in later ExEmbs. Conversely, the conversion to PE in isolated 7 dpc ExEmbs is suppressed by grafting 8 dpc or 9 dpc mesoderm. Hence, the conversion provides an example of transdifferentiation that is promoted by the absence of extraembryonic mesoderm. The presence of mesoderm seems to be necessary to enable the VE to grow rather than convert to PE, as occurs if it retains contact with the extraembryonic ectoderm. Developmental Dynamics 233:837–846, 2005. © 2005 Wiley‐Liss, Inc.
Reduced expression of the PTH/PTHrP receptor during development of the mammary gland influences the function of the nipple during lactation
Authors: Kobayashi Tatsuya , Kronenberg Henry M. , Foley John 
Published: May 2005

AbstractSignaling by the parathyroid hormone/parathyroid hormone‐related protein receptor (Ppr) is necessary for mammary gland development beyond the early induction stage in mice. We used a series of murine models of reduced Ppr expression to determine how diminished receptor signaling influences mammary development. Reduction of Ppr expression to very low levels prevented mammary gland development. A less‐severe reduction in Ppr expression permitted progression of mammary gland development beyond the induction stage, but the nipples of these mice were dramatically smaller than those of controls, with altered epidermis and connective tissue. Mothers with reduced expression of Ppr could not successfully nurse pups; however, the lactating glands did produce milk but could not efficiently deliver it. This finding was associated with reduced levels of matrix metalloproteinase‐2 and an absence of pregnancy‐associated remodeling of connective tissue matrix in the nipple. Reduced smooth muscle appears to underlie the majority of nipple deficiencies in mice with lower levels of the Ppr expression. Developmental Dynamics 233:794–803, 2005. © 2005 Wiley‐Liss, Inc.
Expression of all Wnt genes and their secreted antagonists during mouse blastocyst and postimplantation development
Authors: Kemp Caroline , Willems Erik , Abdo Shaaban , Lambiv Louis , Leyns Luc 
Published: May 2005

AbstractIn this extensive study, real‐time reverse transcriptase‐polymerase chain reaction was used to analyze the expression levels of all 19 Wnt genes and their 11 potential antagonists in mouse blastocysts, pregastrula, gastrula, and neurula stages. By complementing these results with in situ hybridization, we revealed new expression domains for Wnt2b and Sfrp1, respectively, in the future primitive streak at the posterior side and in the anterior visceral endoderm before the initiation of gastrulation. Moreover, the anterior visceral endoderm expresses three secreted Wnt antagonists (Sfrp1, Sfrp5, and Dkk1) in partially overlapping domains. We also identified expression patterns for the Wnt1, Wnt3a, Wnt6, Wnt7b, Wnt9a, Wnt10b, and Sfrp1 genes at the blastocyst stage. In particular, the expression of Wnt1 and Sfrp1 predominantly in the inner cell mass and of Wnt9a in the mural trophoblast and inner cell mass cells surrounding the blastocoele suggests new roles for the Wnt pathway in preimplantation development. This article is the first report on the regional expression of Wnt genes in the mouse blastocyst. Developmental Dynamics 233:1064–1075, 2005. © 2005 Wiley‐Liss, Inc.
Genotoxicity and physicochemical characteristics of traffic‐related ambient particulate matter
Authors: de Kok Theo M. , Hogervorst Janneke G. , Briedé Jacco J. , van Herwijnen Marcel H. , Maas Lou M. , Moonen Edwin J. , Driece Hermen A. , Kleinjans Jos C. 
Published: May 2005

AbstractExposure to ambient particulate matter (PM) has been linked to several adverse health effects. Since vehicular traffic is a PM source of growing importance, we sampled total suspended particulate (TSP), PM10, and PM2.5 at six urban locations with pronounced differences in traffic intensity. The mutagenicity, DNA‐adduct formation, and induction of oxidative DNA damage by the samples were studied as genotoxicological parameters, in relation to polycyclic aromatic hydrocarbon (PAH) levels, elemental composition, and radical‐generating capacity (RGC) as chemical characteristics. We found pronounced differences in the genotoxicity and chemical characteristics of PM from the various locations, although we could not establish a correlation between traffic intensity and any of these characteristics for any of the PM size fractions. Therefore, the differences between locations may be due to local sources of PM, other than traffic. The concentration of total (carcinogenic) PAHs correlated positively with RGC, direct and S9‐mediated mutagenicity, as well as the induction of DNA adducts and oxidative DNA damage. The interaction between total PAHs and transition metals correlated positively with DNA‐adduct formation, particularly from the PM2.5 fraction. RGC was not associated with one specific PM size fraction, but mutagenicity and DNA reactivity after metabolic activation were relatively high in PM10 and PM2.5, when compared with TSP. We conclude that the toxicological characteristics of urban PM samples show pronounced differences, even when PM concentrations at the sample sites are comparable. This implies that emission reduction strategies that take chemical and toxicological characteristics of PM into account may be useful for reducing the health risks associated with PM exposure. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.
Antimutagenicity of green tea polyphenols in the liver of transgenic medaka
Authors: Winn Richard N. , Kling Heather , Norris Michelle B. 
Published: May 2005

AbstractWe examined the ability of a mixture of the predominant green tea polyphenolic compounds (GTP) to reduce benzo[a]pyrene (B[a]P)‐induced mutations in the cII gene of the λ transgenic medaka. Fish were treated with 50 ppb B[a]P for 24 hr, followed by exposure to 2 ppm or 10 ppm GTP for 28 days. cII mutations in livers of fish exposed to B[a]P were increased significantly, 2.6‐fold above controls. In contrast, the addition of GTP significantly reduced the frequency of cII mutants by 84%, comparable to that of controls. The frequencies of mutations at G:C basepairs, mutations that are highly characteristic of B[a]P exposure, were elevated significantly in treated fish. By comparison, B[a]P‐exposed fish also treated with GTP showed reductions in these mutations, demonstrating a protective effect of GTP against B[a]P‐induced mutagenesis. The antioxidant mechanism of GTP possibly played an important role in the reduction of B[a]P mutagenicity. These results corroborate findings from rodent models, showing that the protective effects of green tea extend to different species, and suggesting that similar mechanisms of B[a]P mutagenesis and GTP antimutagenesis are shared among the models. These studies illustrate the utility of λ transgenic medaka for in vivo mutation analyses and suggest that this fish may be a valuable model in chemoprevention studies. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.
Further development of the β‐lactamase MutaGen assay and evaluation by comparison with Ames fluctuation tests and the umu test
Authors: Reifferscheid Georg , Arndt Christian , Schmid Claudia 
Published: May 2005

AbstractA rapid, high‐throughput bacterial mutagenicity test system has been developed (MutaGen test) that detects reversions of inactivating base‐pair substitutions and frameshifts in a TEM‐1 class A β‐lactamase (ampicillinase) gene. To quickly and sensitively detect mutagens, the system utilises a series of plasmids that contain the mutated ampicillinase gene and the mucAB operon. Inactivating mutations in the ampicillinase gene include frameshifts integrated into repetitive GC‐sequences and G‐runs known to be mutagenic hot‐spots, and base‐pair substitutions inserted in or around the β‐lactamase active site. Frameshift mutations completely inactivated the enzyme only when located downstream of the active‐site serine (Ser68). Previous (reporter gene based) assays with this system have detected reversion to ampicillin resistance by luminescence driven by induction of the tet‐promotor controlled lacZ gene. In the present study, we describe the construction and evaluation of 19 additional potential tester strains. We also developed conditions for detecting reversions by pH shift using bromocresol purple and by directly detecting the enzymatic activity of β‐lactamase using nitrocefin. A 384‐well format version of the pH shift MutaGen test was used to assay more than 20 chemicals. The responses in the assay were compared with responses for the same chemicals in the umu test and Ames fluctuation assays. The results indicate that the MutaGen test has high specificity for detecting specific mutations and, in some instances, better sensitivity than the other tests. Since the test is easy to conduct, sterile working conditions are not necessary, and the mutagenicity results are available either within one working day or overnight, the assay shows promise for the rapid screening of potentially genotoxic substances. Environ. Mol. Mutagen., 2005. © 2005 Wiley‐Liss, Inc.