bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prostatic inflammation enhances basal-to-luminal differentiation and accelerates initiation of prostate cancer with a basal cell origin
Authors: Kwon Oh-Joon , Zhang Li , Ittmann Michael M. , Xin Li 
Published: December 2013

SignificanceInflammation promotes the initiation of various malignancies by inducing genetic and epigenetic changes. Here we show that bacterial infection-induced prostatitis results in microenvironmental changes that enhance the differentiation of prostate basal cells into luminal cells, a cellular process that rarely occurs under normal physiological conditions. Previously, we showed in a mouse model that disease initiation for prostate cancer with a basal cell origin requires and is limited by basal-to-luminal differentiation and that prostatic inflammation induced by bacterial infection accelerates disease initiation by enhancing basal-to-luminal differentiation. Collectively, our results show that inflammation-induced microenvironmental changes alter the prostate epithelial lineage differentiation program, and we propose this alteration as a distinct and complementary process through which inflammation promotes tumor initiation.
Optical control of trimeric P2X receptors and acid-sensing ion channels
Authors: Browne Liam E. , Nunes João P. M. , Sim Joan A. , Chudasama Vijay , Bragg Laricia , Caddick Stephen , Alan North R. 
Published: December 2013

Significance
P2X receptors are trimeric proteins in which an extracellular transmitter (ATP) binds to open a transmembrane ion permeation pathway. We have designed a thiol-reactive, light-sensitive azobenzene molecule that can attach between cysteines introduced by mutagenesis into different channel subunits. Such chemically modified channels can be opened within milliseconds by irradiation at 440 nm, and closed by light at 360 nm, in the absence of any extracellular ligand. A similar result was obtained for heterotrimeric P2X2/3 receptors and for structurally unrelated (but trimeric) acid-sensing ion channels. The work extends our understanding of the molecular mechanism of gating and provides a tool to investigate the role of P2X receptors and acid-sensing ion channels in intact cells and tissues.
Evidence of Lévy walk foraging patterns in human hunter–gatherers
Authors: Raichlen David A. , Wood Brian M. , Gordon Adam D. , Mabulla Audax Z. P. , Marlowe Frank W. , Pontzer Herman 
Published: December 2013

SignificanceLévy walks are a random walk search strategy used by a wide variety of organisms when searching for heterogeneously distributed food. This type of search involves mostly short move steps (defined as the distance traveled before pausing or changing direction) combined with rarer longer move steps. Here, we show that the Hadza, hunter–gatherers from northern Tanzania, perform Lévy walks when foraging for a wide variety of food items, suggesting that Lévy walks are an important movement pattern for the most cognitively complex foragers on Earth. Our results suggest that scale-invariant, superdiffusive movement profiles are a fundamental feature of human landscape use, regardless of the physical or cultural environment, and may have played an important role in the evolution of human mobility.
Interplay of mevalonate and Hippo pathways regulates RHAMM transcription via YAP to modulate breast cancer cell motility
Authors: Wang Zhongyuan , Wu Yanping , Wang Haifeng , Zhang Yangqing , Mei Lin , Fang Xuexun , Zhang Xudong , Zhang Fang , Chen Hongbo , Liu Ying , Jiang Yuyang , Sun Shengnan , Zheng Yi , Li Na , Huang Laiqiang 
Published: December 2013

SignificanceHow receptor for hyaluronan-mediated motility (RHAMM) expression is regulated, how statins exert anticancer effects, and what roles mevalonate and Hippo pathways play in tumors are important issues in cancer biology. We find that the two pathways converge onto Yes-associated protein (YAP)/TEAD to control RHAMM transcription leading to ERK activation and cancer metastasis, which is inhibited by simvastatin. YAP/TEAD binds RHAMM promoter at specific sites to activate RHAMM transcription, and mevalonate/simvastatin affects RHAMM transcription by modulating YAP phosphorylation and nuclear-cytoplasmic distribution. These in vitro and in vivo findings identify a mechanism regulating RHAMM expression and cancer metastasis wherein RHAMM is a downstream effector of mevalonate/Hippo pathways, and a YAP/TEAD-transcription and simvastatin-inhibition target, revealing interesting interplay of the pathways and potential targets for cancer therapeutic agents.
Protein kinase LKB1 regulates polarized dendrite formation of adult hippocampal newborn neurons
Authors: Huang Wei , She Liang , Chang Xing-ya , Yang Rong-rong , Wang Liang , Ji Hong-bin , Jiao Jian-wei , Poo Mu-ming 
Published: December 2013

Significance
Dendrites are highly polarized structures that are important for synaptic input and signal integration. However, the molecular and cellular mechanism underlying the polarized dendrite development in vivo remains largely unknown. This report shows that LKB1, a serine-threonine protein kinase known to be involved in axon formation in embryonic cortical pyramidal neurons, is essential for the polarized initiation and oriented extension of the primary dendrite in adult-born hippocampal granule cells, and provides further evidence that this morphogenic effect of LKB1 is mediated via regulation of polarized distribution of Golgi apparatus. These findings not only add a unique function to the growing list of LKB1 cellular actions, but also provide new clues to the subcellular mechanism of LKB1’s action.
Kondo conductance across the smallest spin 1/2 radical molecule
Authors: Requist Ryan , Modesti Silvio , Baruselli Pier Paolo , Smogunov Alexander , Fabrizio Michele , Tosatti Erio 
Published: December 2013

Significance
Molecular electronics, with molecules functioning as the basic building blocks of circuits, is considered by some to be one of the contenders for next-generation electronics. Radical molecules are interesting because a quantum phenomenon, the Kondo effect, involving the radical’s unpaired electron and its spin, has the potential to enhance and control conductance. Examples of molecular Kondo are known experimentally in geometries including mechanical break junctions and scanning tunneling spectroscopy (STS), but so far it has not been possible to make accurate theoretical predictions. Here we predict the Kondo effect expected for the simplest molecular radical, nitric oxide, on a gold surface. Subsequently we verify that experimentally by STS. Both agreements and discrepancies offer a quantitative lesson of considerable future use.
Comparison of explicit and incidental learning strategies in memory-impaired patients
Authors: Smith Christine N. , Urgolites Zhisen J. , Hopkins Ramona O. , Squire Larry R. 
Published: December 2013

Significance
Declarative memory for rapidly learned, novel associations is thought to depend on structures in the medial temporal lobe (MTL). A recent study suggested that rapidly learned associations can nevertheless be supported by structures outside the MTL when a promising, incidental encoding procedure termed “fast mapping” (FM) is used. In two experiments with memory-impaired patients, we found that the FM procedure yielded the same deficits in learning and memory that have been obtained with the use of other more traditional paradigms. We suggest that the effects of the FM procedure are not robust and, if replicable, depend on yet-unknown aspects of how the test is given.
Automated Alerts Coupled with Antimicrobial Stewardship Intervention Lead to Decreases in Length of Stay in Patients with Gram-Negative Bacteremia
Authors: Pogue Jason M. , Mynatt Ryan P. , Marchaim Dror , Zhao Jing J. , Barr Viktorija O. , Moshos Judy , Sunkara Bharath , Chopra Teena , Chidurala Sowmya , Kaye Keith S. 
Published: December 2013

Objective.To assess the impact of active alerting of positive blood culture data coupled with stewardship intervention on time to appropriate therapy, length of stay, and mortality in patients with gram-negative bacteremia.Design.Quasi-experimental retrospective cohort study in patients with gram-negative bacteremia at the Detroit Medical Center from 2009 to 2011.Setting.Three hospitals (1 community, 2 academic) with active antimicrobial stewardship programs within the Detroit Medical Center.Patients.All patients with monomicrobial gram-negative bacteremia during the study period.Intervention.Active alerting of positive blood culture data coupled with stewardship intervention (2010-2011) compared with patients who received no formalized stewardship intervention (2009).Results.Active alerting and intervention led to a decreased time to appropriate therapy (8 [interquartile range (IQR), 2-24] vs 14 [IQR, 2-35] hours; P = .014) in patients with gram-negative bacteremia. After controlling for differences between groups, being in the intervention arm was associated with an independent reduction in length of stay (odds ratio [OR], 0.73 [95% confidence interval (CI), 0.62-0.86]), correlating to a median attributable decrease in length of stay of 2.2 days. Additionally, multivariate modeling of patients who were not on appropriate antimicrobial therapy at the time of initial culture positivity showed that patients in the intervention group had a significant reduction in both length of stay (OR, 0.76 [95% CI, 0.66-0.86]) and infection-related mortality (OR, 0.24 [95% CI, 0.08-0.76]).Conclusions.Active alerting coupled with stewardship intervention in patients with gram-negative bacteremia positively impacted time to appropriate therapy, length of stay, and mortality and should be a target of antimicrobial stewardship programs.
Chlorhexidine Bathing in a Tertiary Care Neonatal Intensive Care Unit: Impact on Central Line–Associated Bloodstream Infections
Authors: Quach Caroline , Milstone Aaron M. , Perpête Chantal , Bonenfant Mario , Moore Dorothy L. , Perreault Therese 
Published: December 2013

Background.Despite implementation of recommended best practices, our central line-associated bloodstream infection (CLABSI) rates remained high. Our objective was to describe the impact of chlorhexidine gluconate (CHG) bathing on CLABSI rates in neonates.Methods.Infants with a central venous catheter (CVC) admitted to the neonatal intensive care unit from April 2009 to March 2013 were included. Neonates with a birth weight of 1,000 g or less, aged less than 28 days, and those with a birth weight greater than 1,000 g were bathed with mild soap until March 31, 2012 (baseline), and with a 2% CHG-impregnated cloth starting on April 1, 2012 (intervention). Infants with a birth weight of 1,000 g or less, aged 28 days or more, were bathed with mild soap during the entire period. Neonatal intensive care unit nurses reported adverse events. Adjusted incidence rate ratios (aIRRs), using Poisson regression, were calculated to compare CLABSIs/1,000 CVC-days during the baseline and intervention periods.Results.Overall, 790 neonates with CVCs were included in the study. CLABSI rates decreased during the intervention period for CHG-bathed neonates (6.00 vs 1.92/1,000 CVC-days; aIRR, 0.33 [95% confidence interval (CI), 0.15-0.73]) but remained unchanged for neonates with a birth rate of 1,000 g or less and aged less than 28 days who were not eligible for CHG bathing (8.57 vs 8.62/1,000 CVC-days; aIRR, 0.86 [95% CI, 0.17-4.44]). Overall, 195 infants with a birth weight greater than 1,000 g and 24 infants with a birth weight of 1,000 g or less, aged 28 days or more, were bathed with CHG. There was no reported adverse event.Conclusions.We observed a decrease in CLABSI rates in CHG-bathed neonates in the absence of observed adverse events. CHG bathing should be considered if CLABSI rates remain high, despite the implementation of other recommended measures.
The curious time lags of PG 1244+026: discovery of the iron K reverberation lag
Authors: Kara E. , Cackett E. M. , Fabian A. C. , Reynolds C. , Uttley P. 
Published: December 2013

Abstract
High-frequency iron K reverberation lags, where the red wing of the line responds before the line centroid, are a robust signature of relativistic reflection off the inner accretion disc. In this Letter, we report the discovery of the Fe K lag in PG 1244+026 from ∼120 ks of data (one orbit of the XMM–Newton telescope). The amplitude of the lag with respect to the continuum is 1000 s at a frequency of ∼10−4 Hz. We also find a possible frequency dependence of the line: as we probe higher frequencies (i.e. shorter time-scales from a smaller emitting region) the Fe K lag peaks at the red wing of the line, while at lower frequencies (from a larger emitting region) we see the dominant reflection lag from the rest-frame line centroid. The mean energy spectrum shows a strong soft excess, though interestingly, there is no indication of a soft lag. Given that this source has radio emission and it has little reported correlated variability between the soft excess and the hard band, we explore one possible explanation in which the soft excess in this source is dominated by the steep power-law-like emission from a jet, and that a corona (or base of the jet) irradiates the inner accretion disc, creating the blurred reflection features evident in the spectrum and the lag. General relativistic ray-tracing models fit the Fe K lag well, with the best fit giving a compact X-ray source at a height of 5rg and a black hole mass of 1.3 × 107 M⊙.
Base-displaced intercalation of the 2-amino-3-methylimidazo[4,5-f]quinolone N2-dG adduct in the NarI DNA recognition sequence
Authors: Stavros Kallie M. , Hawkins Edward K. , Rizzo Carmelo J. , Stone Michael P. 
Published: December 2013

Abstract
2-Amino-3-methylimidazo[4,5-f]quinolone (IQ), a heterocyclic amine found in cooked meats, undergoes bioactivation to a nitrenium ion, which alkylates guanines at both the C8-dG and N2-dG positions. The conformation of a site-specific N2-dG-IQ adduct in an oligodeoxynucleotide duplex containing the iterated CG repeat restriction site of the NarI endonuclease has been determined. The IQ moiety intercalates, with the IQ H4a and CH3 protons facing the minor groove, and the IQ H7a, H8a and H9a protons facing the major groove. The adducted dG maintains the anti-conformation about the glycosyl bond. The complementary dC is extruded into the major groove. The duplex maintains its thermal stability, which is attributed to stacking between the IQ moiety and the 5′- and 3′-neighboring base pairs. This conformation is compared to that of the C8-dG-IQ adduct in the same sequence, which also formed a ‘base-displaced intercalated’ conformation. However, the C8-dG-IQ adopted the syn conformation placing the Watson−Crick edge of the modified dG into the major groove. In addition, the C8-dG-IQ adduct was oriented with the IQ CH3 group and H4a and H5a facing the major groove. These differences may lead to differential processing during DNA repair and replication.
Cellular trafficking determines the exon skipping activity of Pip6a-PMO in mdx skeletal and cardiac muscle cells
Authors: Lehto Taavi , Castillo Alvarez Alejandra , Gauck Sarah , Gait Michael J. , Coursindel Thibault , Wood Matthew J. A. , Lebleu Bernard , Boisguerin Prisca 
Published: December 2013

Abstract
Cell-penetrating peptide-mediated delivery of phosphorodiamidate morpholino oligomers (PMOs) has shown great promise for exon-skipping therapy of Duchenne Muscular Dystrophy (DMD). Pip6a-PMO, a recently developed conjugate, is particularly efficient in a murine DMD model, although mechanisms responsible for its increased biological activity have not been studied. Here, we evaluate the cellular trafficking and the biological activity of Pip6a-PMO in skeletal muscle cells and primary cardiomyocytes. Our results indicate that Pip6a-PMO is taken up in the skeletal muscle cells by an energy- and caveolae-mediated endocytosis. Interestingly, its cellular distribution is different in undifferentiated and differentiated skeletal muscle cells (vesicular versus nuclear). Likewise, Pip6a-PMO mainly accumulates in cytoplasmic vesicles in primary cardiomyocytes, in which clathrin-mediated endocytosis seems to be the pre-dominant uptake pathway. These differences in cellular trafficking correspond well with the exon-skipping data, with higher activity in myotubes than in myoblasts or cardiomyocytes. These differences in cellular trafficking thus provide a possible mechanistic explanation for the variations in exon-skipping activity and restoration of dystrophin protein in heart muscle compared with skeletal muscle tissues in DMD models. Overall, Pip6a-PMO appears as the most efficient conjugate to date (low nanomolar EC50), even if limitations remain from endosomal escape.
Human Rev1 polymerase disrupts G-quadruplex DNA
Authors: Eddy Sarah , Ketkar Amit , Zafar Maroof K. , Maddukuri Leena , Choi Jeong-Yun , Eoff Robert L. 
Published: December 2013

AbstractThe Y-family DNA polymerase Rev1 is required for successful replication of G-quadruplex DNA (G4 DNA) in higher eukaryotes. Here we show that human Rev1 (hRev1) disrupts G4 DNA structures and prevents refolding in vitro. Nucleotidyl transfer by hRev1 is not necessary for mechanical unfolding to occur. hRev1 binds G4 DNA substrates with Kd,DNA values that are 4–15-fold lower than those of non-G4 DNA substrates. The pre-steady-state rate constant of deoxycytidine monophosphate (dCMP) insertion opposite the first tetrad-guanine by hRev1 is ∼56% as fast as that observed for non-G4 DNA substrates. Thus, hRev1 can promote fork progression by either dislodging tetrad guanines to unfold the G4 DNA, which could assist in extension by other DNA polymerases, or hRev1 can prevent refolding of G4 DNA structures. The hRev1 mechanism of action against G-quadruplexes helps explain why replication progress is impeded at G4 DNA sites in Rev1-deficient cells and illustrates another unique feature of this enzyme with important implications for genome maintenance.
Effects of Wheat Bran Extract Containing Arabinoxylan Oligosaccharides on Gastrointestinal Parameters in Healthy Preadolescent Children
Authors: François Isabelle E.J.A. , Lescroart Olivier , Veraverbeke Wim S. , Marzorati Massimo , Possemiers Sam , Hamer Henrike , Windey Karen , Welling Gjalt W. , Delcour Jan A. , Courtin Christophe M. , Verbeke Kristin , Broekaert Willem F. 
Published: December 2013

ABSTRACTObjectives:We assessed whether wheat bran extract (WBE) containing arabinoxylan‐oligosaccharides (AXOS) elicited a prebiotic effect and modulated gastrointestinal (GI) parameters in healthy preadolescent children upon consumption in a beverage.Methods:This double‐blind randomized placebo‐controlled crossover trial evaluated the effects of consuming WBE at 0 (control) or 5.0 g/day for 3 weeks in 29 healthy children (8–12 years). Fecal levels of microbiota, short‐chain fatty acids, branched‐chain fatty acids, ammonia, moisture, and fecal pH were assessed at the end of each treatment and at the end of a 1‐week run‐in (RI) period. In addition, the subjects completed questionnaires scoring distress severity of 3 surveyed GI symptoms. Finally, subjects recorded defecation frequency and stool consistency.Results:Nominal fecal bifidobacteria levels tended to increase after 5 g/day WBE consumption (P = 0.069), whereas bifidobacteria expressed as percentage of total fecal microbiota was significantly higher upon 5 g/day WBE intake (P = 0.002). Additionally, 5 g/day WBE intake induced a significant decrease in fecal content of isobutyric acid and isovaleric acid (P < 0.01), markers of protein fermentation. WBE intake did not cause a change in distress severity of the 3 surveyed GI symptoms (flatulence, abdominal pain/cramps, and urge to vomit) (P > 0.1).Conclusions:WBE is well tolerated at doses up to 5 g/day in healthy preadolescent children. In addition, the intake of 5 g/day exerts beneficial effects on gut parameters, in particular an increase in fecal bifidobacteria levels relative to total fecal microbiota, and reduction of colonic protein fermentation.
S-Carvone Suppresses Cellulase-Induced Capsidiol Production in Nicotiana tabacum by Interfering with Protein Isoprenylation
Authors: Huchelmann Alexandre , Gastaldo Clément , Veinante Mickaël , Zeng Ying , Heintz Dimitri , Tritsch Denis , Schaller Hubert , Rohmer Michel , Bach Thomas J. , Hemmerlin Andréa 
Published: December 2013

Abstract
S-Carvone has been described as a negative regulator of mevalonic acid (MVA) production by interfering with 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGR) activity, a key player in isoprenoid biosynthesis. The impact of this monoterpene on the production of capsidiol in Nicotiana tabacum, an assumed MVA-derived sesquiterpenoid phytoalexin produced in response to elicitation by cellulase, was investigated. As expected, capsidiol production, as well as early stages of elicitation such as hydrogen peroxide production or stimulation of 5-epi-aristolochene synthase activity, were repressed. Despite the lack of capsidiol synthesis, apparent HMGR activity was boosted. Feeding experiments using (1-13C)Glc followed by analysis of labeling patterns by 13C-NMR, confirmed an MVA-dependent biosynthesis; however, treatments with fosmidomycin, an inhibitor of the MVA-independent 2-C-methyl-d-erythritol 4-phosphate (MEP) isoprenoid pathway, unexpectedly down-regulated the biosynthesis of this sesquiterpene as well. We postulated that S-carvone does not directly inhibit the production of MVA by inactivating HMGR, but possibly targets an MEP-derived isoprenoid involved in the early steps of the elicitation process. A new model is proposed in which the monoterpene blocks an MEP pathway–dependent protein geranylgeranylation necessary for the signaling cascade. The production of capsidiol was inhibited when plants were treated with some inhibitors of protein prenylation or by further monoterpenes. Moreover, S-carvone hindered isoprenylation of a prenylable GFP indicator protein expressed in N. tabacum cell lines, which can be chemically complemented with geranylgeraniol. The model was further validated using N. tabacum cell extracts or recombinant N. tabacum protein prenyltransferases expressed in Escherichia coli. Our study endorsed a reevaluation of the effect of S-carvone on plant isoprenoid metabolism.
Amplicon pyrosequencing reveals spatial and temporal consistency in diazotroph assemblages of the Acropora millepora microbiome
Authors: Lema Kimberley A. , Willis Bette L. , Bourne David G. 
Published: December 2013

SummaryDiazotrophic bacteria potentially play an important functional role in supplying fixed nitrogen to the coral holobiont, but the value of such a partnership depends on the stability of the association. Here we evaluate the composition of diazotroph assemblages associated with the coral Acropora millepora throughout four seasons and at two reefs, an inshore and an offshore (mid‐shelf) reef on the Great Barrier Reef, Australia. Amplicon pyrosequencing of the nifH gene revealed that diazotrophs are ubiquitous members of the bacterial community associated with A. millepora. Rhizobia (65% of the overall nifH sequences retrieved) and particularly Bradyrhizobia sp.‐affiliated sequences (> 50% of rhizobia sequences) dominated diazotrophic assemblages across all coral samples from the two sites throughout the year. In contrast to this consistency in the spatial and temporal patterns of occurrence of diazotroph assemblages, the overall coral‐associated bacterial community, assessed through amplicon sequencing of the general bacterial 16S ribosomal RNA gene, differed between inshore and mid‐shelf reef locations. Sequences associated with the Oceanospirillales family, particularly with Endozoicomonas sp., dominated bacterial communities associated with inshore corals. Although rhizobia represented a variable and generally small fraction of the overall bacterial community associated with A. millepora, consistency in the structure of these diazotrophic assemblages suggests that they have a functional role in the coral holobiont.