bluuebunny/crossref_metadata_2025_split huggingface dataset:
The nucleotide excision repair (NER) system of Helicobacter pylori: Role in mutation prevention and chromosomal import patterns after natural transformation
Authors: Moccia Claudia , Krebes Juliane , Kulick Stefan , Didelot Xavier , Kraft Christian , Bahlawane Christelle , Suerbaum Sebastian 
Published: May 2012

Abstract

Background
Extensive genetic diversity and rapid allelic diversification are characteristics of the human gastric pathogen Helicobacter pylori, and are believed to contribute to its ability to cause chronic infections. Both a high mutation rate and frequent imports of short fragments of exogenous DNA during mixed infections play important roles in generating this allelic diversity. In this study, we used a genetic approach to investigate the roles of nucleotide excision repair (NER) pathway components in H. pylori mutation and recombination.

Results
Inactivation of any of the four uvr genes strongly increased the susceptibility of H. pylori to DNA damage by ultraviolet light. Inactivation of uvrA and uvrB significantly decreased mutation frequencies whereas only the uvrA deficient mutant exhibited a significant decrease of the recombination frequency after natural transformation. A uvrC mutant did not show significant changes in mutation or recombination rates; however, inactivation of uvrC promoted the incorporation of significantly longer fragments of donor DNA (2.2-fold increase) into the recipient chromosome. A deletion of uvrD induced a hyper-recombinational phenotype.

Conclusions
Our data suggest that the NER system has multiple functions in the genetic diversification of H. pylori, by contributing to its high mutation rate, and by controlling the incorporation of imported DNA fragments after natural transformation.
Standardized collection of MNase-seq experiments enables unbiased dataset comparisons
Authors: Rizzo Jason M , Bard Jonathan E , Buck Michael J 
Published: May 2012

Abstract

Background
The organization of eukaryotic DNA into chromatin has a strong influence on the accessibility and regulation of genetic information. The locations and occupancies of a principle component of chromatin, nucleosomes, are typically assayed through use of enzymatic digestion with micrococcal nuclease (MNase). MNase is an endo-exo nuclease that preferentially digests naked DNA and the DNA in linkers between nucleosomes, thus enriching for nucleosome-associated DNA. To determine nucleosome organization genome-wide, DNA remaining from MNase digestion is sequenced using high-throughput sequencing technologies (MNase-seq). Unfortunately, the results of MNase-seq can vary dramatically due to technical differences and this confounds comparisons between MNase-seq experiments, such as examining condition-dependent chromatin organizations.

Results
In this study we use MNase digestion simulations to demonstrate how MNase-seq signals can vary for different nucleosome configuration when experiments are performed with different extents of MNase digestion. Signal variation in these simulations reveals an important DNA sampling bias that results from a neighborhood effect of MNase digestion techniques. The presence of this neighborhood effect ultimately confounds comparisons between different MNase-seq experiments. To address this issue we present a standardized chromatin preparation which controls for technical variance between MNase-based chromatin preparations and enables the collection of similarly sampled (matched) chromatin populations. Standardized preparation of chromatin includes a normalization step for DNA input into MNase digestions and close matching of the extent of digestion between each chromatin preparation using gel densitometry analysis. The protocol also includes directions for successful pairing with multiplex sequencing reactions.

Conclusions
We validated our method by comparing the experiment-to-experiment variation between biological replicates of chromatin preparations from S. cerevisiae. Results from our matched preparation consistently produced MNase-seq datasets that were more closely correlated than other unstandardized approaches. Additionally, we validated the ability of our approach at enabling accurate downstream comparisons of chromatin structures, by comparing the specificity of detecting Tup1-dependent chromatin remodeling events in comparisons between matched and un-matched wild-type and tup1 Δ MNase-seq datasets. Our matched MNase-seq datasets demonstrated a significant reduction in non-specific (technical) differences between experiments and were able to maximize the detection of biologically-relevant (Tup1-dependent) changes in chromatin structure.
5-hydroxytryptamine (5-HT) reduces total peripheral resistance during chronic infusion: direct arterial mesenteric relaxation is not involved
Authors: Davis Robert Patrick , Pattison Jill , Thompson Janice M , Tiniakov Ruslan , Scrogin Karie E , Watts Stephanie W 
Published: May 2012

Abstract
Serotonin (5-hydroxytryptamine; 5-HT) delivered over 1 week results in a sustained fall in blood pressure in the sham and deoxycorticosterone acetate (DOCA)-salt rat. We hypothesized 5-HT lowers blood pressure through direct receptor-mediated vascular relaxation. In vivo, 5-HT reduced mean arterial pressure (MAP), increased heart rate, stroke volume, cardiac index, and reduced total peripheral resistance during a 1 week infusion of 5-HT (25 µg/kg/min) in the normotensive Sprague Dawley rat. The mesenteric vasculature was chosen as an ideal candidate for the site of 5-HT receptor mediated vascular relaxation given the high percentage of cardiac output the site receives. Real-time RT-PCR demonstrated that mRNA transcripts for the 5-HT2B, 5-HT1B, and 5-HT7 receptors are present in sham and DOCA-salt superior mesenteric arteries. Immunohistochemistry and Western blot validated the presence of the 5-HT2B, 5- HT1B and 5-HT7 receptor protein in sham and DOCA-salt superior mesenteric artery. Isometric contractile force was measured in endothelium-intact superior mesenteric artery and mesenteric resistance arteries in which the contractile 5- HT2A receptor was antagonized. Maximum concentrations of BW-723C86 (5- HT2B agonist), CP 93129 (5-HT1B agonist) or LP-44 (5-HT7 agonist) did not relax the superior mesenteric artery from DOCA-salt rats vs. vehicle. Additionally, 5-HT (10–9 M to 10–5 M) did not cause relaxation in either contracted mesenteric resistance arteries or superior mesenteric arteries from normotensive Sprague- Dawley rats. Thus, although 5-HT receptors known to mediate vascular relaxation are present in the superior mesenteric artery, they are not functional, and are therefore not likely involved in a 5-HT-induced fall in total peripheral resistance and MAP.
Lipocalin 2 expression is associated with aggressive features of endometrial cancer
Authors: Mannelqvist Monica , Stefansson Ingunn M , Wik Elisabeth , Kusonmano Kanthida , Raeder Maria B , Øyan Anne M , Kalland Karl-Henning , Moses Marsha A , Salvesen Helga B , Akslen Lars A 
Published: May 2012

Abstract

Background
Increased expression of lipocalin 2 (LCN2) has been observed in several cancers. The aim of the present study was to investigate LCN2 in endometrial cancer in relation to clinico-pathologic phenotype, angiogenesis, markers of epithelial-mesenchymal transition (EMT), and patient survival.

Methods
Immunohistochemical staining was performed using a human LCN2 antibody on a population-based series of endometrial cancer patients collected in Hordaland County (Norway) during 1981-1990 (n = 256). Patients were followed from the time of primary surgery until death or last follow-up in 2007. The median follow-up time for survivors was 17 years. Gene expression data from a prospectively collected endometrial cancer series (n = 76) and a publicly available endometrial cancer series (n = 111) was used for gene correlation studies.

Results
Expression of LCN2 protein, found in 49% of the cases, was associated with non-endometrioid histologic type (p = 0.001), nuclear grade 3 (p = 0.001), >50% solid tumor growth (p = 0.001), ER and PR negativity (p = 0.028 and 0.006), and positive EZH2 expression (p < 0.001). LCN2 expression was significantly associated with expression of VEGF-A (p = 0.021), although not with other angiogenesis markers examined (vascular proliferation index, glomeruloid microvascular proliferation, VEGF-C, VEGF-D or bFGF2 expression). Further, LCN2 was not associated with several EMT-related markers (E-cadherin, N-cadherin, P-cadherin, β-catenin), nor with vascular invasion (tumor cells invading lymphatic or blood vessels). Notably, LCN2 was significantly associated with distant tumor recurrences, as well as with the S100A family of metastasis related genes. Patients with tumors showing no LCN2 expression had the best outcome with 81% 5-year survival, compared to 73% for intermediate and 38% for the small subgroup with strong LCN2 staining (p = 0.007). In multivariate analysis, LCN2 expression was an independent prognostic factor in addition to histologic grade and FIGO stage.

Conclusion
Increased LCN2 expression is associated with aggressive features and poor prognosis in endometrial cancer.
Untranslated regions of diverse plant viral RNAs vary greatly in translation enhancement efficiency
Authors: Fan Qiuling , Treder Krzysztof , Miller W Allen 
Published: May 2012

Abstract

Background
Whole plants or plant cell cultures can serve as low cost bioreactors to produce massive amounts of a specific protein for pharmacological or industrial use. To maximize protein expression, translation of mRNA must be optimized. Many plant viral RNAs harbor extremely efficient translation enhancers. However, few of these different translation elements have been compared side-by-side. Thus, it is unclear which are the most efficient translation enhancers. Here, we compare the effects of untranslated regions (UTRs) containing translation elements from six plant viruses on translation in wheat germ extract and in monocotyledenous and dicotyledenous plant cells.

Results
The highest expressing uncapped mRNAs contained viral UTRs harboring Barley yellow dwarf virus (BYDV)-like cap-independent translation elements (BTEs). The BYDV BTE conferred the most efficient translation of a luciferase reporter in wheat germ extract and oat protoplasts, while uncapped mRNA containing the BTE from Tobacco necrosis virus-D translated most efficiently in tobacco cells. Capped mRNA containing the Tobacco mosaic virus omega sequence was the most efficient mRNA in tobacco cells. UTRs from Satellite tobacco necrosis virus, Tomato bushy stunt virus, and Crucifer-infecting tobamovirus (crTMV) did not stimulate translation efficiently. mRNA with the crTMV 5′ UTR was unstable in tobacco protoplasts.

Conclusions
BTEs confer the highest levels of translation of uncapped mRNAs in vitro and in vivo, while the capped omega sequence is most efficient in tobacco cells. These results provide a basis for understanding mechanisms of translation enhancement, and for maximizing protein synthesis in cell-free systems, transgenic plants, or in viral expression vectors.
Crystal structure of a new benzoic acid inhibitor of influenza neuraminidase bound with a new tilt induced by overpacking subsite C6
Authors: Venkatramani Lalitha , Johnson Eric S , Kolavi Gundurao , Air Gillian M , Brouillette Wayne J , Mooers Blaine HM 
Published: May 2012

Abstract

Background
Influenza neuraminidase (NA) is an important target for antiviral inhibitors since its active site is highly conserved such that inhibitors can be cross-reactive against multiple types and subtypes of influenza. Here, we discuss the crystal structure of neuraminidase subtype N9 complexed with a new benzoic acid based inhibitor (2) that was designed to add contacts by overpacking one side of the active site pocket. Inhibitor 2 uses benzoic acid to mimic the pyranose ring, a bis-(hydroxymethyl)-substituted 2-pyrrolidinone ring in place of the N-acetyl group of the sialic acid, and a branched aliphatic structure to fill the sialic acid C6 subsite.

Results
Inhibitor 2 {4-[2,2-bis(hydroxymethyl)-5-oxo-pyrrolidin-1-yl]-3-[(dipropylamino)methyl)]benzoic acid} was soaked into crystals of neuraminidase of A/tern/Australia/G70c/75 (N9), and the structure refined with 1.55 Å X-ray data. The benzene ring of the inhibitor tilted 8.9° compared to the previous compound (1), and the number of contacts, including hydrogen bonds, increased. However, the IC50 for compound 2 remained in the low micromolar range, likely because one propyl group was disordered. In this high-resolution structure of NA isolated from virus grown in chicken eggs, we found electron density for additional sugar units on the N-linked glycans compared to previous neuraminidase structures. In particular, seven mannoses and two N-acetylglucosamines are visible in the glycan attached to Asn200. This long, branched high-mannose glycan makes significant contacts with the neighboring subunit.

Conclusions
We designed inhibitor 2 with an extended substituent at C4-corresponding to C6 of sialic acid-to increase the contact surface in the C6-subsite and to force the benzene ring to tilt to maximize these interactions while retaining the interactions of the carboxylate and the pyrolidinone substituents. The crystal structure at 1.55 Å showed that we partially succeeded in that the ring in 2 is tilted relative to 1 and the number of contacts increased, but one hydrophobic branch makes no contacts, perhaps explaining why the IC50 did not decrease. Future design efforts will include branches of unequal length so that both branches may be accommodated in the C6-subsite without conformational disorder. The high-mannose glycan attached to Asn200 makes several inter-subunit contacts and appears to stabilize the tetramer.
Antibacterial activities of gold and silver nanoparticles against Escherichia coli and bacillus Calmette-Guérin
Authors: Zhou Yan , Kong Ying , Kundu Subrata , Cirillo Jeffrey D , Liang Hong 
Published: May 2012

Abstract

Background
Diseases such as tuberculosis (TB) have always had a large impact on human health. Bacillus Calmette-Guérin (BCG) is used as a surrogate for TB during the development of anti-TB drugs. Nanoparticles (NPs) have attracted great interest in drug development. The purpose of this study was to examine the potential of NPs as anti-TB compounds by studying the interacting mechanisms between NPs and bacteria.

Results
We investigated effects of gold and silver NPs on BCG and Escherichia coli. Experimentally, particle size and shape were characterized using transmission electron microscopy (TEM). Different concentrations of NPs were applied in bacterial culture. The growth of E. coli was monitored through colony forming units (CFU). The mechanism of interaction between NPs and bacteria was analyzed through bacterial thin sections followed by TEM and scanning electron microscopy. Antibacterial effects on BCG were observed by recording fluorescent protein expression levels.

Conclusions
The results suggest NPs have potential applications as anti-TB compounds. The antibacterial effects and mechanism of action for NPs were dependent upon composition and surface modifications.
Early stages of growth of gold layers sputter deposited on glass and silicon substrates
Authors: Malinský Petr , Slepička Petr , Hnatowicz Vladimír , Švorčík Václav 
Published: May 2012

Abstract
Extremely thin gold layers were sputter deposited on glass and silicon substrates, and their thickness and morphology were studied by Rutherford backscattering (RBS) and atomic force microscopy (AFM) methods. The deposited layers change from discontinuous to continuous ones for longer deposition times. While the deposition rate on the silicon substrate is constant, nearly independent on the layer thickness, the rate on the glass substrate increases with increasing layer thickness. The observed dependence can be explained by a simple kinetic model, taking into account different sticking probabilities of gold atoms on a bare glass substrate and regions with gold coverage. Detailed analysis of the shape of the RBS gold signal shows that in the initial stages of the deposition, the gold layers on the glass substrate consist of gold islands with significantly different thicknesses. These findings were confirmed by AFM measurements, too. Gold coverage of the silicon substrate is rather homogeneous, consisting of tiny gold grains, but a pronounced worm-like structure is formed for the layer thickness at electrical continuity threshold. On the glass substrate, the gold clusters of different sizes are clearly observed. For later deposition stages, a clear tendency of the gold atoms to aggregate into larger clusters of approximately the same size is observed. At later deposition stages, gold clusters of up to 100 nm in diameter are formed.
Nucleate boiling performance on nano/microstructures with different wetting surfaces
Authors: Jo HangJin , Kim SeolHa , Kim Hyungmo , Kim Joonwon , Kim Moo Hwan 
Published: May 2012

Abstract
A study of nucleate boiling phenomena on nano/microstructures is a very basic and useful study with a view to the potential application of modified surfaces as heating surfaces in a number of fields. We present a detailed study of boiling experiments on fabricated nano/microstructured surfaces used as heating surfaces under atmospheric conditions, employing identical nanostructures with two different wettabilities (silicon-oxidized and Teflon-coated). Consequently, enhancements of both boiling heat transfer (BHT) and critical heat flux (CHF) are demonstrated in the nano/microstructures, independent of their wettability. However, the increment of BHT and CHF on each of the different wetting surfaces depended on the wetting characteristics of heating surfaces. The effect of water penetration in the surface structures by capillary phenomena is suggested as a plausible mechanism for the enhanced CHF on the nano/microstructures regardless of the wettability of the surfaces in atmospheric condition. This is supported by comparing bubble shapes generated in actual boiling experiments and dynamic contact angles under atmospheric conditions on Teflon-coated nano/microstructured surfaces.
Controllable growth of ZnO nanorod arrays with different densities and their photoelectric properties
Authors: Wang Shujie , Song Chongshun , Cheng Ke , Dai Shuxi , Zhang Yayan , Du Zuliang 
Published: May 2012

Abstract
Since the photoelectric response and charge carriers transport can be influenced greatly by the density and spacing of the ZnO nanorod arrays, controlling of these geometric parameters precisely is highly desirable but rather challenging in practice. Here, we fabricated patterned ZnO nanorod arrays with different densities and spacing distances on silicon (Si) substrate by electron beam lithography (EBL) method combined with the subsequent hydrothermal reaction process. By using the EBL method, patterned ZnO seed layers with different areas and spacing distances were obtained firstly. ZnO nanorod arrays with different densities and various morphologies were obtained by the subsequent hydrothermal growth process. The combination of EBL and hydrothermal growth process was very attractive and could make us control the geometric parameters of ZnO nanorod arrays expediently. Finally, the vertical transport properties of the patterned ZnO nanorod arrays were investigated through the microprobe station equipment, and the I-V measurement results indicated that the back-to-back Schottky contacts with different barrier heights were formed in dark conditions. Under UV light illumination, the patterned ZnO nanorod arrays showed a high UV light sensitivity, and the response ratio was about 104. The controllable fabrication of patterned ZnO nanorod arrays and understanding their photoelectric transport properties were helpful to improve the performance of nanodevices based on them.
Corrigendum to "Oscillation behavior of third-order neutral Emden-Fowler delay xdynamic equations on time scales" [Adv. Difference Equ., 2010, 1-23 (2010)]
Authors: Ji Tao , Tang Shuhong , Li Tongxing 
Published: May 2012

Abstract
In this article, we revise results obtained by Han et al.

Mathematics Subject Classification 2000: 34K11; 39A10.
Limited SHIV env diversification in macaques failing oral antiretroviral pre-exposure prophylaxis
Authors: Zheng Qi , Ruone Susan , Switzer William M , Heneine Walid , García-Lerma J Gerardo 
Published: May 2012

Abstract

Background
Pre-exposure prophylaxis (PrEP) with daily Truvada [a combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)] is a novel HIV prevention strategy recently found to prevent HIV transmission among men who have sex with men and heterosexual couples. Acute infection in adherent persons who fail PrEP will inevitably occur under concurrent antiretroviral therapy, thus raising questions regarding the potential impact of PrEP on early viral dynamics. We investigated viral evolution dynamics in a macaque model of PrEP consisting of repeated rectal exposures to SHIV162P3 in the presence of PrEP.

Results
Four macaques were infected during daily or intermittent PrEP with FTC or FTC/TDF, and five were untreated controls. SHIV env sequence evolution was monitored by single genome amplification with phylogenetic and sequence analysis. Mean nucleotide divergence from transmitted founder viruses calculated 17 weeks (range = 12–20) post peak viremia was significantly lower in PrEP failures than in control animals (7.2 × 10-3 compared to 1.6 × 10-2 nucleotide substitutions per site per year, respectively, p < 0.0001). Mean virus diversity was also lower in PrEP failures after 17 weeks (0.13% vs. 0.53% in controls, p < 0.0001).

Conclusions
Our results in a macaque model of acute HIV infection suggest that infection during PrEP limits early virus evolution likely because of a direct antiviral effect of PrEP and/or reduced target cell availability. Reduced virus diversification during early infection might enhance immune control by slowing the selection of escape mutants.