bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased claudin‐3, ‐4 and ‐18 levels in bronchoalveolar lavage fluid reflect severity of acute lung injury
Authors: Jin Wenting , Rong Linyi , Liu Yinkun , Song Yuanlin , Li Yan , Pan Jue 
Published: December 2012

AbstractBackground and objectiveAcute lung injury (ALI) is characterized by disruption of lung epithelial and endothelial cells, leading to increased membrane permeability and loss of barrier function. Claudins are key components of tight junctions (TJ) that regulate paracellular permeability, and play an important role in alveolar epithelial barrier function and fluid clearance. However, whether claudin‐3, ‐4, ‐18 or ‐5 expression changes in Pseudomonas aeruginosa (PA)‐induced ALI and the clinical significance of such change is unknown.MethodsRats underwent intratracheal instillation of PA, and samples were collected prior to and 3, 9 and 24 h after instillation. Lung injury was evaluated by bronchoalveolar lavage fluid (BALF) total protein, arterial blood gas analysis, lung injury score, and expression of surfactant protein and von Willebrand factor. Claudin expression in lung was measured with quantitative real‐time polymerase chain reaction and western blotting, and in BALF by enzyme‐linked immunosorbent assay. The relationship between claudins in BALF and lung injury grade were analysed with Spearman's rank correlation. Alveolar epithelium, endothelium and TJ ultrastructure were observed with electron microscopy.ResultsClaudin‐4, ‐18 and ‐5 mRNA levels increased significantly 24 h after PA instillation in the most severe lung injury cases, whereas there was no significant change in protein levels. Claudin‐3, ‐4 and ‐18 levels in BALF increased most 24 h after PA instillation; this paralleled alveolar epithelial disruption and lung injury severity.ConclusionsClaudin‐3, ‐4 and ‐18 released into the alveolar compartment is highly associated with barrier function loss caused by alveolar epithelial injury.
Whole animal knockout of smooth muscle alpha‐actin does not alter excisional wound healing or the fibroblast‐to‐myofibroblast transition
Authors: Tomasek James J. , Haaksma Carol J. , Schwartz Robert J. , Howard Eric W. 
Published: December 2012

AbstractThe contractile phenotype and function of myofibroblasts have been proposed to play a critical role in wound closure. It has been hypothesized that smooth muscle α‐actin expressed in myofibroblasts is critical for its formation and function. We have used smooth muscle α‐actin‐null mice to test this hypothesis. Full‐thickness excisional wounds closed at a similar rate in smooth muscle α‐actin‐null and wild‐type mice. In addition, fibroblasts in smooth muscle α‐actin‐null granulation tissue when immunostained with a monoclonal antibody that recognizes all muscle actin isoforms exhibited a myofibroblast‐like distribution and a stress fiber‐like pattern, showing that these cells acquired the myofibroblast phenotype. Dermal fibroblasts from smooth muscle α‐actin‐null and wild‐type mice formed stress fibers and supermature focal adhesions, and generated similar amounts of contractile force in response to transforming growth factor‐β1. Smooth muscle γ‐actin and skeletal muscle α‐actin were expressed in smooth muscle α‐actin‐null myofibroblasts, as shown by immunostaining, real‐time polymerase chain reaction, and mass spectrometry. These results show that smooth muscle α‐actin is not necessary for myofibroblast formation and function and for wound closure, and that smooth muscle γ‐actin and skeletal muscle α‐actin may be able to functionally compensate for the lack of smooth muscle α‐actin in myofibroblasts.
Cattle Drive Salmonella Infection in the Wildlife–Livestock Interface
Authors: Mentaberre G. , Porrero M. C. , Navarro‐Gonzalez N. , Serrano E. , Domínguez L. , Lavín S. 
Published: December 2012

SummaryThe genus Salmonella is found throughout the world and is a potential pathogen for most vertebrates. It is also the most common cause of food‐borne illness in humans, and wildlife is an emerging source of food‐borne disease in humans due to the consumption of game meat. Wild boar is one of the most abundant European game species and these wild swine are known to be carriers of zoonotic and food‐borne pathogens such as Salmonella. Isolation of the pathogen, serotyping and molecular biology are necessary for elucidating epidemiological connections in multi‐host populations. Although disease management at population level can be addressed using a number of different strategies, such management is difficult in free‐living wildlife populations due to the lack of experience with the wildlife–livestock interface. Herein, we provide the results of a 4‐year Salmonella survey in sympatric populations of wild boar and cattle in the Ports de Tortosa i Beseit National Game Reserve (NE Spain). We also evaluated the effects of two management strategies, cattle removal and increased wild boar harvesting (i.e. by hunting and trapping), on the prevalence of the Salmonella serovar community. The serovars Meleagridis and Anatum were found to be shared by cattle and wild boar, a finding that was confirmed by 100% DNA similarity patterns using pulse field gel electrophoresis. Cattle removal was more efficient than the culling of wild boar as a means of reducing the prevalence of shared serotypes, which underlines the role of cattle as a reservoir of Salmonella for wild boar. To our knowledge, this is the first attempt to manage Salmonella in the wild, and the results have implications for management.
Ageing alters perivascular nerve function of mouse mesenteric arteries in vivo
Authors: Westcott Erika B. , Segal Steven S. 
Published: December 2012

Key points
Neural control of the circulation is integral to the regulation of tissue blood flow and systemic blood pressure. Vascular dysfunction occurs with ageing but little is known of corresponding changes in the role(s) of perivascular nerves.
We developed a preparation to study intact mesenteric arteries (MAs) in anaesthetized mice to investigate age‐related changes in the function of perivascular sympathetic and sensory nerves in vivo.
Ageing decreased the diameter of MAs, reduced their sensitivity to α1‐adrenoreceptor stimulation and impaired the ability of sensory nerves to attenuate sympathetic vasoconstriction.
These changes were manifest in males and females and were unaffected by the expression of the GCaMP2 transgene in endothelial cells, confirming the utility of this model.
Our results imply that ageing imposes structural and functional limitations to the splanchnic circulation that impair the ability to mobilize blood from the gut in times of physical stress.
Abstract  Mesenteric arteries (MAs) are studied widely in vitro but little is known of their reactivity in vivo. Transgenic animals have enabled Ca2+ signalling to be studied in isolated MAs but the reactivity of these vessels in vivo is undefined. We tested the hypothesis that ageing alters MA reactivity to perivascular nerve stimulation (PNS) and adrenoreceptor (AR) activation during blood flow control. First‐ (1A), second‐ (2A) and third‐order (3A) MAs of pentobarbital‐anaesthetized Young (3–6 months) and Old (24–26 months) male and female Cx40BAC‐GCaMP2 transgenic mice (C57BL/6 background; positive or negative for the GCaMP2 transgene) were studied with intravital microscopy. A segment of jejunum was exteriorized and an MA network was superfused with physiological salt solution (pH 7.4, 37°C). Resting tone was ≤ 10% in MAs of Young and Old mice; diameters were ∼5% (1A), 20% (2A) and 40% (3A) smaller (P≤ 0.05) in Old mice. Throughout MA networks, vasoconstriction increased with PNS frequency (1–16 Hz) but was ∼20% less in Young vs. Old mice (P≤ 0.05) and was inhibited by tetrodotoxin (1 μm). Capsaicin (10 μm; to inhibit sensory nerves) enhanced MA constriction to PNS (P≤ 0.05) by ∼20% in Young but not Old mice. Phenylephrine (an α1AR agonist) potency was greater in Young mice (P≤ 0.05) with similar efficacy (∼60% constriction) across ages and MA branches. Constrictions to UK14304 (an α2AR agonist) were less (∼20%; P≤ 0.05) and were unaffected by ageing. Irrespective of sex or transgene expression, ageing consistently reduced the sensitivity of MAs to α1AR vasoconstriction while blunting the attenuation of sympathetic vasoconstriction by sensory nerves. These findings imply substantive alterations in splanchnic blood flow control with ageing.
Pharmacokinetic and Pharmacodynamic Modeling To Determine the Dose of ST-246 To Protect against Smallpox in Humans
Authors: Leeds Janet M. , Fenneteau Frederique , Gosselin Nathalie H. , Mouksassi Mohamad-Samer , Kassir Nastya , Marier J. F. , Chen Yali , Grosenbach Doug , Frimm Annie E. , Honeychurch Kady M. , Chinsangaram Jarasvech , Tyavanagimatt Shanthakumar R. , Hruby Dennis E. , Jordan Robert 
Published: December 2012

ABSTRACT
Although smallpox has been eradicated, the United States government considers it a “material threat” and has funded the discovery and development of potential therapeutic compounds. As reported here, the human efficacious dose for one of these compounds, ST-246, was determined using efficacy studies in nonhuman primates (NHPs), together with pharmacokinetic and pharmacodynamic analysis that predicted the appropriate dose and exposure levels to provide therapeutic benefit in humans. The efficacy analysis combined the data from studies conducted at three separate facilities that evaluated treatment following infection with a closely related virus, monkeypox virus (MPXV), in a total of 96 NHPs. The effect of infection on ST-246 pharmacokinetics in NHPs was applied to humans using population pharmacokinetic models. Exposure at the selected human dose of 600 mg is more than 4-fold higher than the lowest efficacious dose in NHPs and is predicted to provide protection to more than 95% of the population.
A Trial of Discontinuation of Empiric Vancomycin Therapy in Patients with Suspected Methicillin-Resistant Staphylococcus aureus Health Care-Associated Pneumonia
Authors: Boyce John M. , Pop Olivia-Fabiola , Abreu-Lanfranco Odaliz , Hung Whitney Y. , Fisher Ann , Karjoo Afshin , Thompson Benjamin , Protopapas Zenon 
Published: December 2012

ABSTRACT

Healthcare-associated pneumonia (HCAP) guidelines recommend de-escalating initial antibiotic therapy based on results from lower-respiratory-tract cultures. In the absence of adequate lower respiratory cultures, physicians are sometimes reluctant to discontinue empirical vancomycin, which is given for suspected methicillin-resistant
Staphylococcus aureus
(MRSA) HCAP. We evaluated a strategy of discontinuing vancomycin if both nasal and throat cultures were negative for MRSA when lower-respiratory-tract cultures were not available. An antimicrobial stewardship team identified patients receiving empirical vancomycin for suspected or proven HCAP but for whom adequate lower-respiratory-tract cultures were not available. Nasal and throat swab specimens were obtained and plated on MRSA selective media. If both nasal and throat MRSA cultures were negative, the stewardship team recommended discontinuation of empirical vancomycin. Demographic and clinical aspects, a clinical pulmonary infection score (CPIS) on the day of the stewardship recommendation, and mortality of patients for whom vancomycin was discontinued were obtained by retrospective chart review. A convenience sample of 91 patients with nasal and throat cultures negative for MRSA in the absence of adequate respiratory cultures had empirical vancomycin therapy discontinued. A retrospective review revealed that 88 (97%) patients had a CPIS of ≤6 on the day of the stewardship recommendation. In-hospital mortality (7.7%) was similar to that of a previous study of de-escalation of antibiotics in pneumonia patients without adequate cultures. In the absence of adequate lower-respiratory-tract cultures, it is reasonable to discontinue empirical vancomycin HCAP therapy in patients with negative MRSA nasal and throat cultures and a CPIS of <6.
Lucidone Suppresses Hepatitis C Virus Replication by Nrf2-Mediated Heme Oxygenase-1 Induction
Authors: Chen Wei-Chun , Wang Sheng-Yang , Chiu Chien-Chih , Tseng Chin-Kai , Lin Chun-Kuang , Wang Hui-Chun , Lee Jin-Ching 
Published: December 2012

ABSTRACT

Upon screening of plant-derived natural products against hepatitis C virus (HCV) in the replicon system, we demonstrate that lucidone, a phytocompound, isolated from the fruits of
Lindera erythrocarpa
Makino, significantly suppressed HCV RNA levels with 50% effective concentrations of 15 ± 0.5 μM and 20 ± 1.1 μM in HCV replicon and JFH-1 infectious assays, respectively. There was no significant cytotoxicity observed at high concentrations, with a 50% cytotoxic concentration of 620 ± 5 μM. In addition, lucidone significantly induced heme oxygenase-1 (HO-1) production and led to the increase of its product biliverdin for inducing antiviral interferon response and inhibiting HCV NS3/4A protease activity. Conversely, the anti-HCV activity of lucidone was abrogated by blocking HO-1 activity or silencing gene expression of HO-1 or NF-E2-related factor 2 (Nrf2) in the presence of lucidone, indicating that the anti-HCV action of lucidone was due to the stimulation of Nrf-2-mediated HO-1 expression. Moreover, the combination of lucidone and alpha interferon, the protease inhibitor telaprevir, the NS5A inhibitor BMS-790052, or the NS5B polymerase inhibitor PSI-7977, synergistically suppressed HCV RNA replication. These findings suggest that lucidone could be a potential lead or supplement for the development of new anti-HCV agent in the future.
The Polysaccharide Capsule of Campylobacter jejuni Modulates the Host Immune Response
Authors: Maue Alexander C. , Mohawk Krystle L. , Giles David K. , Poly Frédéric , Ewing Cheryl P. , Jiao Yuening , Lee Ginyoung , Ma Zuchao , Monteiro Mario A. , Hill Christina L. , Ferderber Jason S. , Porter Chad K. , Trent M. Stephen , Guerry Patricia 
Published: December 2012

ABSTRACT

Campylobacter jejuni
is a major cause of bacterial diarrheal disease worldwide. The organism is characterized by a diversity of polysaccharide structures, including a polysaccharide capsule. Most
C. jejuni
capsules are known to be decorated nonstoichiometrically with methyl phosphoramidate (MeOPN). The capsule of
C. jejuni
81-176 has been shown to be required for serum resistance, but here we show that an encapsulated mutant lacking the MeOPN modification, an
mpnC
mutant, was equally as sensitive to serum killing as the nonencapsulated mutant. A nonencapsulated mutant, a
kpsM
mutant, exhibited significantly reduced colonization compared to that of wild-type 81-176 in a mouse intestinal colonization model, and the
mpnC
mutant showed an intermediate level of colonization. Both mutants were associated with higher levels of interleukin 17 (IL-17) expression from lamina propria CD4
+
cells than from cells from animals infected with 81-176. In addition, reduced levels of Toll-like receptor 4 (TLR4) and TLR2 activation were observed following
in vitro
stimulation of human reporter cell lines with the
kpsM
and
mpnC
mutants compared to those with wild-type 81-176. The data suggest that the capsule polysaccharide of
C. jejuni
and the MeOPN modification modulate the host immune response.
PRSS3/Mesotrypsin Is a Therapeutic Target for Metastatic Prostate Cancer
Authors: Hockla Alexandra , Miller Erin , Salameh Moh'd A. , Copland John A. , Radisky Derek C. , Radisky Evette S. 
Published: December 2012

Abstract
PRSS3/mesotrypsin is an atypical isoform of trypsin that has been associated with breast, lung, and pancreatic cancer cell malignancy. In analyses of open source transcriptional microarray data, we find that PRSS3 expression is upregulated in metastatic prostate cancer tissue, and that expression of PRSS3 in primary prostate tumors is prognostic of systemic progression following prostatectomy. Using a mouse orthotopic model with bioluminescent imaging, we show that PRSS3/mesotrypsin is critical for prostate cancer metastasis. Silencing of PRSS3 inhibits anchorage-independent growth of prostate cancer cells in soft agar assays, and suppresses invasiveness in Matrigel transwell assays and three-dimensional (3D) cell culture models. We further show that treatment with recombinant mesotrypsin directly promotes an invasive cellular phenotype in prostate cancer cells and find that these effects are specific and require the proteolytic activity of mesotrypsin, because neither cationic trypsin nor a mesotrypsin mutant lacking activity can drive the invasive phenotype. Finally, we show that a newly developed, potent inhibitor of mesotrypsin activity can suppress prostate cancer cell invasion to a similar extent as PRSS3 gene silencing. This study defines mesotrypsin as an important mediator of prostate cancer progression and metastasis, and suggests that inhibition of mesotrypsin activity may provide a novel modality for prostate cancer treatment. Mol Cancer Res; 10(12); 1555–66. ©2012 AACR.
Context-dependent Semantic Processing in the Human Brain: Evidence from Idiom Comprehension
Authors: Rommers Joost , Dijkstra Ton , Bastiaansen Marcel 
Published: December 2012

Abstract
Language comprehension involves activating word meanings and integrating them with the sentence context. This study examined whether these routines are carried out even when they are theoretically unnecessary, namely, in the case of opaque idiomatic expressions, for which the literal word meanings are unrelated to the overall meaning of the expression. Predictable words in sentences were replaced by a semantically related or unrelated word. In literal sentences, this yielded previously established behavioral and electrophysiological signatures of semantic processing: semantic facilitation in lexical decision, a reduced N400 for semantically related relative to unrelated words, and a power increase in the gamma frequency band that was disrupted by semantic violations. However, the same manipulations in idioms yielded none of these effects. Instead, semantic violations elicited a late positivity in idioms. Moreover, gamma band power was lower in correct idioms than in correct literal sentences. It is argued that the brain's semantic expectancy and literal word meaning integration operations can, to some extent, be “switched off” when the context renders them unnecessary. Furthermore, the results lend support to models of idiom comprehension that involve unitary idiom representations.
Segregating the Neural Correlates of Physical and Perceived Change in Auditory Input using the Change Deafness Effect
Authors: Puschmann Sebastian , Weerda Riklef , Klump Georg , Thiel Christiane M. 
Published: December 2012

Abstract
Psychophysical experiments show that auditory change detection can be disturbed in situations in which listeners have to monitor complex auditory input. We made use of this change deafness effect to segregate the neural correlates of physical change in auditory input from brain responses related to conscious change perception in an fMRI experiment. Participants listened to two successively presented complex auditory scenes, which consisted of six auditory streams, and had to decide whether scenes were identical or whether the frequency of one stream was changed between presentations. Our results show that physical changes in auditory input, independent of successful change detection, are represented at the level of auditory cortex. Activations related to conscious change perception, independent of physical change, were found in the insula and the ACC. Moreover, our data provide evidence for significant effective connectivity between auditory cortex and the insula in the case of correctly detected auditory changes, but not for missed changes. This underlines the importance of the insula/anterior cingulate network for conscious change detection.
Using Remote Sensing Data to Improve Groundwater Supply Estimations in Gujarat, India
Authors: Chinnasamy Pennan , Hubbart Jason A. , Agoramoorthy Govindasamy 
Published: December 2012

Abstract
India is the greatest groundwater consumer in the world, with estimated annual withdrawals exceeding 230 km3. More than 60% of irrigated agriculture, 85% of drinking water supplies, and 50% of urban and industrial water needs are dependent on sustainable groundwater management. Regardless, groundwater overextraction is a growing problem in many regions. Predictions of groundwater resource availability in India are problematic in part because of a limited number of monitoring sites and insufficient data quality and quantity. Regional groundwater assessments are further complicated because of sporadic and low-frequency data. To help overcome these issues and more accurately quantify groundwater resource availability, scientists have begun using satellite-derived remote sensing data. In this study, the authors used seasonal and annual hydrologic signals obtained by NASA Gravity Recovery and Climate Experiment (GRACE) satellites and simulated soil moisture variations from land data assimilation systems to show groundwater depletion trends in the northwest state of Gujarat (surface area of 196 030 km2), India. Results were evaluated using direct measurement data from 935 wells. Remote sensing generated results compared favorably with well data (e.g., r2 = 0.89 for Gandhinagar, a representative highly urbanized district in Gujarat: confidence interval (CI) = 0.05 and P = 0.002). Results show that remote sensing is an effective tool to compliment and interpolate observed regional groundwater well data and improve groundwater storage estimations in Gujarat, India. Properly implemented, the method will supply reliable science-based information to enhance management of groundwater resources in India and other geographic locations.
Lagrangian Solution for an Irrotational Progressive Water Wave Propagating on a Uniform Current
Authors: Chen Yang-Yih , Chen Hsuan-Shan , Lin Chu-Yu , Li Meng-Syue 
Published: December 2012

Abstract
Experiments are conducted to measure the motion properties of water particle for the progressive water wave propagation in the presence of following and adverse uniform currents. The experimental data are used to validate the fifth-order Lagrangian solution from Chen and Chen. The experimental results show that the measured data of the particle motion properties such as the b line (denoted as the line connecting the positions of consecutive particles of the same b label), the particle velocity, the particle transport velocity (drift velocity), the particle trajectory, the particle motion period, and the Lagrangian mean level are in close agreement with those of the fifth-order Lagrangian solution. The study also shows that the particle label could adopt the position coordinates of the particle as if it were in still water. The motion of the b line oscillates like wave motion: its wavelength is equal to the progressive wavelength and its wave velocity obeys the Doppler effect so the sum of the velocities of the progressive wave and current, the particle motion period, the Lagrangian mean level, and the particle transport velocity less current velocity are the same as for the case of pure progressive waves.
For following currents, the shape of particle trajectory depends on the horizontal particle velocity at the trajectory trough. For adverse currents, the shape of particle trajectory depends on the horizontal particle velocity at the trajectory crest.
For a description of the flow motion, the Lagrangian solution could be more effective and precise than the Eulerian solution.