bluuebunny/crossref_metadata_2025 huggingface dataset:
Injuries associated with the cartilages of the foot
Authors: Dyson S. , Nagy A.
Published: July 2011

There is a growing body of evidence that uniaxial or biaxial ossification of the cartilages of the foot should not be discounted as irrelevant in a lame horse, especially if extensive. Potential causes of pain and lameness include primary injury of an ossified cartilage and/or the ipsilateral aspect of the distal phalanx, injury of the chondrocoronal or chondrosesamoidean ligaments and desmopathy of the collateral ligaments of the distal interphalangeal joint.
Implications of urine F2‐isoprostane metabolite concentration in horses with colic and its potential use as a predictor for surgical intervention
Authors: NOSCHKA E. , WERRE S. R. , CRISMAN M. V. , THATCHER C. D. , MILNE G. L. , DAHLGREN L. A.
Published: July 2011

Reasons for performing study:F2‐isoprostanes have been used extensively to quantify lipid peroxidation in association with risk factors in various diseases. Horses with colic may have intestinal ischaemia and/or inflammation characterised by oxidative stress and increased production of isoprostanes.

Objectives:To gather preliminary data regarding the feasibility of using urine F2‐isoprostanes and isoprostane metabolites as early screening tools for the presence of gastrointestinal disease requiring surgical intervention in horses and ultimately develop a stall‐side test capable of identifying these horses as early as possible for timely referral.

Methods:Concentrations of urine isoprostane and isoprostane metabolite were determined by mass spectroscopy and normalised to urine creatinine (Cr) concentrations in urine samples from 42 healthy control horses and 43 horses with gastrointestinal pain or colic.

Results:Horses with colic were treated medically (n = 21) or surgically (n = 22). Mean ± s.d. concentrations of urine isoprostane and isoprostane metabolite were significantly higher in horses with colic (2.94 ± 1.69 and 0.31 ± 0.22 ng/mg Cr, respectively), compared to control horses (1.89 ± 1.39 and 0.22 ± 0.08 ng/mg Cr, respectively). Mean urine isoprostane metabolite concentrations were significantly higher in horses undergoing surgery (0.38 ± 0.28 ng/mg Cr) compared to controls and medical colics (0.26 ± 0.11 ng/mg Cr). Nonsurvivors had significantly higher mean urine isoprostane metabolite concentrations (0.47 ± 0.39 ng/mg Cr) than control or surviving colic horses (0.29 ± 0.24 ng/mg Cr).

Conclusions:Measurement of urine isoprostane metabolite concentration may be a useful prognostic indicator in equine colic.

Potential relevance:Urine isoprostane metabolites may aid in early recognition of surgical colic. Isoprostanes are a potential therapeutic target to prevent further systemic and gastrointestinal tissue injury in horses with colic.
Ultrasonographic evidence of colonic mesenteric vessels as an indicator of right dorsal displacement of the large colon in 13 horses
Authors: GRENAGER N. S. , DURHAM M. G.
Published: July 2011

This report describes the use of ultrasound to diagnose right dorsal displacement of the large colon (RDDLC) in 13 horses prior to surgery. Horses had ultrasonographic examinations performed of the right lateroventral aspect of the abdomen upon admission to the hospital with a 2–5 MHz broadband curvilinear sector scanning transducer after alcohol was used to wet the hair. First, the caecal vessels were identified in the right flank and followed medially and cranially. Next, each intercostal space, from caudal to cranial, was scanned from dorsal to ventral evaluating for abnormally‐located mesenteric vessels associated with the large colon. Abnormally‐located mesenteric vessels associated with the large colon, distinct from the caecal vessels, were identified in 13 of 23 horses with a diagnosis of RDDLC obtained at exploratory laparotomy. In horses, ultrasonographic visualisation of mesenteric vessels along the right lateral abdomen, dorsal to the costochondral junction in at least 2 intercostal spaces, distinct from the caecal vessels, is consistent with a surgical diagnosis of RDDLC.
A note on epistemics and discourse analysis
Authors: van Dijk Teun A.
Published: July 2011

Discursive Psychology has the great merit of having introduced discourse analysis (DA) to social psychology and to have contributed to DA itself by its study of the expression of ‘psychological’ notions in text and talk. Within this perspective, this paper presents some elements of a proposal to study the expression of knowledge in discourse. Beginning with a brief summary of our multidisciplinary approach to knowledge, followed by a summary of discourse structures that express knowledge, the main argument of the paper is that we not only need to take discourse seriously in the study of knowledge, but cannot ignore their cognitive underlying structures if we want to describe and explain many properties of discourse, such as all implicit or presupposed knowledge, as well as the interactional and contextual management of old and new knowledge in text and talk.
Recovery of proprioceptive feedback from nerve crush
Authors: Prather Jonathan F. , Nardelli Paul , Nakanishi Stan T. , Ross Kyla T. , Nichols T. Richard , Pinter Martin J. , Cope Timothy C.
Published: July 2011

Non‐Technical Summary  Regeneration of muscle nerves damaged by crush reconnects the peripheral limb of neural circuits that pass through the spinal cord, but the mechanisms underlying functional recovery remain uncertain. We examined the actions of natural muscle stretch that initiates muscle contraction, i.e. the stretch reflex, through a spinal circuit that aids in adjusting body movement and posture in response to destabilizing forces in the external environment. Stretch applied to muscles reinnervated by crushed nerves produced reflexive contraction that was more forceful than normal, despite yielding less than normal synaptic excitation to spinal motoneurons. Incomplete recovery of synaptic function by stretch‐activated sensory neurons means that the enhanced stretch reflex contraction necessarily involves additional neural adaptations, possibly increased motoneuron excitability. These findings give further support to the importance of the central nervous system in restoring the ability of the regenerated neuromuscular system to respond to external disturbances of movement and posture.
Purinergic modulation of preBötzinger complex inspiratory rhythm in rodents: the interaction between ATP and adenosine
Authors: Zwicker J. D. , Rajani V. , Hahn L. B. , Funk G. D.
Published: July 2011

Non‐technical summary  Hypoxia causes an increase in breathing followed by a secondary depression that is most pronounced, and potentially life‐threatening, in premature infants. Adenosine triphosphate (ATP) is released in brainstem respiratory networks during hypoxia, where it attenuates the secondary respiratory depression. Mechanisms are unknown but likely to be complex because ATP is degraded by enzymes into ADP, which is excitatory, and adenosine (ADO), which is inhibitory. We demonstrate in mouse, like rat, that ATP in the preBötzinger complex (preBötC), a site critical for inspiratory rhythm generation, increases frequency. Unlike rat, this increase is only observed in mouse if ADO receptors are blocked. Differential ATP sensitivity is likely to reflect that ADO is only inhibitory in mouse, and that mouse preBötC enzymes favour ADO production. Thus, purinergic signalling in preBötC networks appears balanced to favour inhibition in mouse but excitation in rat. Knowledge of purinergic signalling increases our understanding of processes underlying respiratory responses to hypoxia.
Dissimilar Properties of Two Recombinant Lactobacillus acidophilus Strains Displaying Salmonella FliC with Different Anchoring Motifs
Authors: Kajikawa Akinobu , Nordone Shila K. , Zhang Lin , Stoeker Laura L. , LaVoy Alora S. , Klaenhammer Todd R. , Dean Gregg A.
Published: July 2011

Display of heterologous antigens on the cell surface is considered a useful technique for vaccine delivery by recombinant lactobacilli. In this study, two recombinant
Lactobacillus acidophilus
derivatives displaying
Salmonella
flagellin (FliC) were constructed using different anchor motifs. In one instance, the FliC protein was fused to the C-terminal region of a cell envelope proteinase (PrtP) and was bound to the cell wall by electrostatic bonds. In the other case, the same antigen was conjugated to the anchor region of mucus binding protein (Mub) and was covalently associated with the cell wall by an LPXTG motif. These two recombinant
L. acidophilus
cell surface displays resulted in dissimilar maturation and cytokine production by human myeloid dendritic cells. The surface-associated antigen was highly sensitive to simulated gastric and small intestinal juices. By supplementation with bicarbonate buffer and soybean trypsin inhibitor, the cell surface antigen was protected from proteolytic enzymes during gastric challenge
in vitro
. The protective reagents also increased the viability of the
L. acidophilus
cells upon challenge with simulated digestive juices. These results demonstrate the importance of protecting cells and their surface-associated antigens during oral immunization.
Persistent, Toxin-Antitoxin System-Independent, Tetracycline Resistance-Encoding Plasmid from a Dairy Enterococcus faecium Isolate
Authors: Li Xinhui , Alvarez Valente , Harper Willis James , Wang Hua H.
Published: July 2011

A tetracycline-resistant (Tet
r
) dairy
Enterococcus faecium
isolate designated M7M2 was found to carry both
tet
(M) and
tet
(L) genes on a 19.6-kb plasmid. After consecutive transfer in the absence of tetracycline, the resistance-encoding plasmid persisted in 99% of the progenies. DNA sequence analysis revealed that the 19.6-kb plasmid contained 28 open reading frames (ORFs), including a
tet
(M)-
tet
(L)-
mob
gene cluster, as well as a 10.6-kb backbone highly homologous (99.9%) to the reported plasmid pRE25, but without an identified toxin-antitoxin (TA) plasmid stabilization system. The derived backbone plasmid without the Tet
r
determinants exhibited a 100% retention rate in the presence of acridine orange, suggesting the presence of a TA-independent plasmid stabilization mechanism, with its impact on the persistence of a broad spectrum of resistance-encoding traits still to be elucidated. The
tet
(M)-
tet
(L) gene cluster from M7M2 was functional and transmissible and led to acquired resistance in
Enterococcus faecalis
OG1RF by electroporation and in
Streptococcus mutans
UA159 by natural transformation. Southern hybridization showed that both the
tet
(M) and
tet
(L) genes were integrated into the chromosome of
S. mutans
UA159, while the whole plasmid was transferred to and retained in
E. faecalis
OG1RF. Quantitative real-time reverse transcription-PCR (RT-PCR) indicated tetracycline-induced transcription of both the
tet
(M) and
tet
(L) genes of pM7M2. The results indicated that multiple mechanisms might have contributed to the persistence of antibiotic resistance-encoding genes and that the plasmids pM7M2, pIP816, and pRE25 are likely correlated evolutionarily.
Spoilage-Related Activity of Carnobacterium maltaromaticum Strains in Air-Stored and Vacuum-Packed Meat
Authors: Casaburi Annalisa , Nasi Antonella , Ferrocino Ilario , Di Monaco Rossella , Mauriello Gianluigi , Villani Francesco , Ercolini Danilo
Published: July 2011

One hundred three isolates of
Carnobacterium
spp. from raw meat were analyzed by random amplification of polymorphic DNA (RAPD) and PCR and were identified by 16S rRNA gene sequencing. Forty-five strains of
Carnobacterium maltaromaticum
were characterized for their growth capabilities at different temperatures, NaCl concentrations, and pH values and for
in vitro
lipolytic and proteolytic activities. Moreover, their spoilage potential in meat was investigated by analyzing the release of volatile organic compounds (VOCs) in meat stored in air or vacuum packs. Almost all the strains were able to grow at 4, 10, and 20°C, at pH values of 6 to 9, and in the presence of 2.5% NaCl. The release of VOCs by each strain in beef stored at 4°C in air and vacuum packs was evaluated by headspace solid-phase microextraction (HS-SPME)-gas chromatography-mass spectrometry (GC-MS) analysis. All the meat samples inoculated and stored in air showed higher numbers of VOCs than the vacuum-packed meat samples. Acetoin, 1-octen-3-ol, and butanoic acid were the compounds most frequently found under both storage conditions. The contaminated meat samples were evaluated by a sensory panel; the results indicated that for all sensory odors, no effect of strain was significant (
P
> 0.05). The storage conditions significantly affected (
P
< 0.05) the perception of dairy, spoiled-meat, and mozzarella cheese odors, which were more intense in meat stored in air than in vacuum packs but were never very intense. In conclusion, different strains of
C. maltaromaticum
can grow efficiently in meat stored at low temperatures both in air and in vacuum packs, producing volatile molecules with low sensory impacts, with a negligible contribution to meat spoilage overall.
Genetic Exchange in an Arbuscular Mycorrhizal Fungus Results in Increased Rice Growth and Altered Mycorrhiza-Specific Gene Transcription
Authors: Colard Alexandre , Angelard Caroline , Sanders Ian R.
Published: July 2011

Arbuscular mycorrhizal fungi (AMF) are obligate symbionts with most terrestrial plants. They improve plant nutrition, particularly phosphate acquisition, and thus are able to improve plant growth. In exchange, the fungi obtain photosynthetically fixed carbon. AMF are coenocytic, meaning that many nuclei coexist in a common cytoplasm. Genetic exchange recently has been demonstrated in the AMF
Glomus intraradices
, allowing nuclei of different
Glomus intraradices
strains to mix. Such genetic exchange was shown previously to have negative effects on plant growth and to alter fungal colonization. However, no attempt was made to detect whether genetic exchange in AMF can alter plant gene expression and if this effect was time dependent. Here, we show that genetic exchange in AMF also can be beneficial for rice growth, and that symbiosis-specific gene transcription is altered by genetic exchange. Moreover, our results show that genetic exchange can change the dynamics of the colonization of the fungus in the plant. Our results demonstrate that the simple manipulation of the genetics of AMF can have important consequences for their symbiotic effects on plants such as rice, which is considered the most important crop in the world. Exploiting natural AMF genetic variation by generating novel AMF genotypes through genetic exchange is a potentially useful tool in the development of AMF inocula that are more beneficial for crop growth.
Spatial Distribution and Diffusive Motion of RNA Polymerase in Live Escherichia coli
Authors: Bratton Benjamin P. , Mooney Rachel A. , Weisshaar James C.
Published: July 2011

By labeling the β′ subunit of RNA polymerase (RNAP), we used fluorescence microscopy to study the spatial distribution and diffusive motion of RNAP in live
Escherichia coli
cells for the first time. With a 40-ms time resolution, the spatial distribution exhibits two or three narrow peaks of 300- to 600-nm full width at half-maximum that maintain their positions within 60 nm over 1 s. The intensity in these features is 20 to 30% of the total. Fluorescence recovery after photobleaching (FRAP) measures the diffusive motion of RNAP on the 1-μm length scale. Averaged over many cells, 53% ± 19% of the RNAP molecules were mobile on the 3-s timescale, with a mean apparent diffusion constant 〈
D
RNAP
〉 of 0.22 ± 0.16 μm
2
-s
−1
. The remaining 47% were immobile even on the 30-s timescale. We interpret the immobile fraction as arising from RNAP specifically bound to DNA, either actively transcribing or not. The diffusive motion of the mobile fraction (
f
mobile
) probably involves both one-dimensional sliding during nonspecific binding to DNA and three-dimensional hopping between DNA strands. There is significant cell-to-cell heterogeneity in both
D
RNAP
and
f
mobile
.
Role of Leucine Zipper Motifs in Association of the Escherichia coli Cell Division Proteins FtsL and FtsB
Authors: Robichon Carine , Karimova Gouzel , Beckwith Jon , Ladant Daniel
Published: July 2011

FtsL and FtsB are two inner-membrane proteins that are essential constituents of the cell division apparatus of
Escherichia coli
. In this study, we demonstrate that the leucine zipper-like (LZ) motifs, located in the periplasmic domain of FtsL and FtsB, are required for an optimal interaction between these two essential proteins.
Characterization of the Fur Regulon in Pseudomonas syringae pv. tomato DC3000
Authors: Butcher Bronwyn G. , Bronstein Philip A. , Myers Christopher R. , Stodghill Paul V. , Bolton James J. , Markel Eric J. , Filiatrault Melanie J. , Swingle Bryan , Gaballa Ahmed , Helmann John D. , Schneider David J. , Cartinhour Samuel W.
Published: July 2011

The plant pathogen
Pseudomonas syringae
pv. tomato DC3000 (DC3000) is found in a wide variety of environments and must monitor and respond to various environmental signals such as the availability of iron, an essential element for bacterial growth. An important regulator of iron homeostasis is Fur (ferric uptake regulator), and here we present the first study of the Fur regulon in DC3000. Using chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq), 312 chromosomal regions were highly enriched by coimmunoprecipitation with a C-terminally tagged Fur protein. Integration of these data with previous microarray and global transcriptome analyses allowed us to expand the putative DC3000 Fur regulon to include genes both repressed and activated in the presence of bioavailable iron. Using nonradioactive DNase I footprinting, we confirmed Fur binding in 41 regions, including upstream of 11 iron-repressed genes and the iron-activated genes encoding two bacterioferritins (PSPTO_0653 and PSPTO_4160), a ParA protein (PSPTO_0855), and a two-component system (TCS) (PSPTO_3382 to PSPTO_3380).
A Molecular Basis for Tungstate Selectivity in Prokaryotic ABC Transport Systems
Authors: Bevers Loes E. , Schwarz Guenter , Hagen Wilfred R.
Published: July 2011

The essential trace compounds tungstate and molybdate are taken up by cells via ABC transporters. Despite their similar ionic radii and chemical properties, the WtpA protein selectively binds tungstate in the presence of molybdate. Using site-directed mutagenesis of conserved binding pocket residues, we established a molecular basis for tungstate selectivity.
TroA of Streptococcus suis Is Required for Manganese Acquisition and Full Virulence
Authors: Schreur Paul J. Wichgers , Rebel Johanna M. J. , Smits Mari A. , van Putten Jos P. M. , Smith Hilde E.
Published: July 2011

Streptococcus suis
causes infections in pigs and occasionally in humans, resulting in manifestations as meningitis, sepsis, arthritis, and septic shock. For survival within the host,
S. suis
requires numerous nutrients including trace metals. Little is known about the specific proteins involved in metal scavenging in
S. suis
. In this study we evaluated the role of the putative high-affinity metal binding lipoprotein TroA in metal acquisition and virulence. A mutant strain deficient in the expression of TroA (Δ
troA
mutant) was constructed. Growth of the Δ
troA
mutant in Todd-Hewitt broth was similar to wild-type growth; however, growth of the Δ
troA
mutant in cation-deprived Todd-Hewitt broth and in porcine serum was strongly reduced compared to growth of wild-type bacteria. Supplementing the medium with extra manganese but not with magnesium, zinc, copper, nickel, or iron restored growth to wild-type levels, indicating that TroA is specifically required for growth in environments low in manganese. The Δ
troA
mutant also showed increased susceptibility to H
2
O
2
, suggesting that TroA is involved in counteracting oxidative stress. Furthermore, the expression of the
troA
gene was subject to environmental regulation at the transcript level. In a murine
S. suis
infection model, the Δ
troA
mutant displayed a nonvirulent phenotype. These data indicate that
S. suis
TroA is involved in manganese acquisition and is required for full virulence in mice.
SpoIIE Is Necessary for Asymmetric Division, Sporulation, and Expression of σ
F
, σ
E
, and σ
G
but Does Not Control Solvent Production in Clostridium acetobutylicum ATCC 824
Authors: Bi Changhao , Jones Shawn W. , Hess Daniel R. , Tracy Bryan P. , Papoutsakis Eleftherios T.
Published: July 2011

In order to better characterize the initial stages of sporulation past Spo0A activation and the associated solventogenesis in the important industrial and model organism
Clostridium acetobutylicum
, the
spoIIE
gene was successfully disrupted and its expression was silenced. By silencing
spoIIE
, sporulation was blocked prior to asymmetric division, and no mature spores or any distinguishable morphogenetic changes developed. Upon plasmid-based complementation of
spoIIE
, sporulation was restored, although the number of spores formed was below that of the plasmid control strain. To investigate the impact of silencing
spoIIE
on the regulation of sporulation, transcript levels of
sigF
,
sigE
, and
sigG
were examined by semiquantitative reverse transcription-PCR, and the corresponding σ
F
, σ
E
, and σ
G
protein levels were determined by Western analysis. Expression of
sigF
was significantly reduced in the inactivation strain, and this resulted in very low σ
F
protein levels. Expression of
sigE
was barely detected, and no
sigG
transcript was detected at all; consequently, no σ
E
or σ
G
proteins were detected. These data suggest an autostimulatory role for σ
F
in
C. acetobutylicum
, in contrast to the model organism for endospore formation,
Bacillus subtilis
, and confirm that high-level expression of σ
F
is required for expression of σ
E
and σ
G
. Unlike the σ
F
and σ
E
inactivation strains, the SpoIIE inactivation strain did not exhibit inoculum-dependent solvent formation and produced good levels of solvents from both exponential- and stationary-phase inocula. Thus, we concluded that SpoIIE does not control solvent formation.
Mutations in Flavobacterium johnsoniae
sprE
Result in Defects in Gliding Motility and Protein Secretion
Authors: Rhodes Ryan G. , Samarasam Mudiarasan Napoleon , Van Groll Eric J. , McBride Mark J.
Published: July 2011

Cells of the gliding bacterium
Flavobacterium johnsoniae
move rapidly over surfaces. Transposon mutagenesis was used to identify
sprE
, which is involved in gliding. Mutations in
sprE
resulted in the formation of nonspreading colonies on agar.
sprE
mutant cells in wet mounts were almost completely deficient in attachment to and movement on glass, but a small percentage of cells exhibited slight movements, indicating that the motility machinery was not completely disrupted. SprE is a predicted lipoprotein with a tetratricopeptide repeat domain. SprE is similar in sequence to
Porphyromonas gingivalis
PorW, which is required for secretion of gingipain protease virulence factors. Disruption of
F. johnsoniae
sprE
resulted in decreased extracellular chitinase activity and decreased secretion of the cell surface motility protein SprB. Reduced secretion of cell surface components of the gliding machinery, such as SprB, may account for the defects in gliding. Orthologs of
sprE
are found in many gliding and nongliding members of the phylum
Bacteroidetes
, suggesting that similar protein secretion systems are common among members of this large and diverse group of bacteria.
Installation and lateral loading tests of suction caissons in silt
Authors: Zhu Bin , Kong De-qiong , Chen Ren-peng , Kong Ling-gang , Chen Yun-min
Published: July 2011

A number of potential offshore wind turbines in China will be constructed in sandy silt seabeds, and the mono-caisson foundation is an important choice for these offshore wind turbines. A program of large-scale model tests on suction installation and lateral loading of caisson foundations in saturated silt were carried out in a large soil tank at Zhejiang University. Test results of installation resistance during suction installation show that the seepage effect is limited in silt, and the suction required to penetrate the caisson can be well predicted based on the sleeve friction and cone resistance of cone penetration tests. The deformation mechanism and soil-structure interaction of a caisson subjected to lateral loads were investigated. The instantaneous rotation center of the model caisson at failure was at the depth of about four-fifths of the skirt length, almost directly below the lid center. Based on the assumption of a common position of the instantaneous rotation center and dominating resistance forces on the caisson, an analytical expression for the ultimate moment capacity was presented.
Riparian canopy type, management history, and successional stage control fluxes of plant litter to streams
Authors: Hoover Trent M. , Pinto Xavier , Richardson John S.
Published: July 2011

The food webs of forest stream ecosystems are based primarily on cross-boundary flows of terrestrial plant litter (PL). As such, changes in the composition of riparian forest canopies can alter flows of PL, affecting the ecosystem functioning of adjacent streams. We measured seasonal changes in PL fluxes to 20 small streams flowing through temperate rain forests in southwestern British Columbia to determine how riparian forest type and riparian management history influence resource availability in these systems. Differences in PL fluxes among the four riparian forest types studied were most pronounced in the summer, when PL fluxes from clearcuts < riparian reserve strips and coniferous forests, and PL fluxes from deciduous-dominated forests < riparian reserve strips. PL fluxes also varied among seasons (spring < summer < autumn). Fluxes were similar in riparian reserve strips and coniferous forests of similar age, indicating that reserve strips maintain this crucial ecosystem process. Clearcutting of riparian forests dramatically increased light availability while reducing leaf litter inputs; these effects, however, lasted only a few years. As riparian forest stand age increased, inputs shifted from broadleaf to coniferous inputs, indicating a possible long-term decrease in the lability of the leaf litter resources available to stream consumers.
CONSTRAINTS ON THE CHARGED HIGGS BOSON OF THE TWO-HIGGS DOUBLET MODEL TYPE III
Authors: CARDENAS H. , DUARTE J. , ALEXIS RODRIGUEZ J.
Published: July 2011

The D0 experiment has reported a direct search for a charged Higgs boson produced by [Formula: see text] annihilation and decaying to [Formula: see text] final state, in the 180≤MH+≤300 GeV mass range. The analysis has led to upper limits on the production cross-section in the framework of the two-Higgs doublet model types I, II and III. We compare the predictions of two different scenarios in the framework of the two-Higgs doublet type III to the cross-section limits reported by D0 collaboration, and we obtain constraints on the charged Higgs mass, for the case when the charged Higgs mass is bigger than the top quark mass. Also, searches for the charged Higgs boson with a mass smaller than top quark mass are considered, we discuss the possible limits on the charged Higgs boson mass obtained from measurements of the ratio [Formula: see text] within the two-Higgs doublet model type III.
PLASMA-LIKE VACUUM IN PODOLSKY REGULARIZED CLASSICAL ELECTRODYNAMICS
Authors: SANTOS ROBERTO BAGINSKI B.
Published: July 2011

We analyze wave propagation in the vacuum of Podolsky regularized electrodynamics. Two kinds of waves were found in the theory: the traditional non-dispersive waves of Maxwell electrodynamics, and a dispersive wave reminiscent of wave propagation in a collisionless plasma. Charged particle concentration was determined, and found to be huge in this vacuum. We interpret the results in terms of vacuum polarization effects induced in an otherwise classical theory.
Reversal of diabetic vasculopathy in a rat model of type 1 diabetes by opiorphin-related peptides
Authors: Calenda Giulia , Tong Yuehong , Kanika Nirmala D. , Tar Moses T. , Suadicani Sylvia O. , Zhang Xinhua , Melman Arnold , Rougeot Catherine , Davies Kelvin P.
Published: July 2011

Diabetes results in a myriad of vascular complications, often referred to as diabetic vasculopathy, which encompasses both microvascular [erectile dysfunction (ED), retinopathy, neuropathy, and nephropathy] and macrovascular complications (hypertension, coronary heart disease, and myocardial infarction). In diabetic animals and patients with ED, there is decreased opiorphin or opiorphin-related gene expression in corporal tissue. Both opiorphin and the rat homologous peptide sialorphin are found circulating in the plasma. In the present study, we investigated if diabetes induced changes in plasma sialorphin levels and if changes in these levels could modulate the biochemistry and physiology of vascular smooth muscle. We show that circulating sialorphin levels are reduced in a rat model of type I diabetes. Intracorporal injection of plasmids expressing sialorphin into diabetic rats restores sialorphin levels to those seen in the blood of nondiabetic animals and results in both improved erectile function and blood pressure. Sialorphin modulated the ability of C-type natriuretic peptide to relax both corporal and aortic smooth muscle strips and of bradykinin to regulate intracellular calcium levels in both corporal and aortic smooth muscle cells. We have previously shown that expression of genes encoding opiorphins is increased when erectile function is improved. Our findings thus suggest that by affecting circulating levels of opiorphin-related peptides, proper erectile function is not only an indicator but also a modulator of overall vascular health of a man.
Reactivity of the aorta and mesenteric resistance arteries from the obese spontaneously hypertensive rat: effects of glitazones
Authors: Mendizábal Yolanda , Llorens Silvia , Nava Eduardo
Published: July 2011

The obese spontaneously hypertensive rat (SHROB) is a model of metabolic syndrome in which, to our knowledge, vascular function has never been studied. The actions of insulin sensitizers (glitazones) on vascular function have not been analyzed either. Our purpose was to characterize microvascular and macrovascular responses of the SHROB and to study the effects of glitazones on these responses. The reactivity of mesenteric resistance arteries (MRAs) and the aorta from SHROBs and control rats to cumulative concentrations of phenylephrine, ACh, and sodium nitroprusside (SNP) was myographically analyzed. Some animals were orally treated with rosiglitazone (3 mg·kg−1·day−1, 3 wk), and myography was performed. Phenylephrine, ACh, and SNP dose-response curves were impaired to different extents in arteries of SHROBs. Incubation with N-nitro-l-arginine methyl ester caused little effects on phenylephrine and ACh curves in MRAs but enhanced phenylephrine contractions and abolished ACh-induced relaxations of aortae. Incubation with indomethacin reduced phenylephrine reactivity and improved ACh-induced relaxations of all vessels studied. NS-398 and tempol increased relaxations to ACh of MRAs. Incubation with pioglitazone or rosiglitazone (both 10−5 M) or oral treatment with rosiglitazone improved, to different extents, ACh and SNP curves in all vessels. Glitazone incubation diminished aortic ACh sensitivity. The release of thromboxane A2 and PGI2 metabolites (thromboxane B2 and 6-keto-PGF1α) was analyzed. ACh increased the MRA release of thromboxane B2 from SHROBs but not control rats, and the former was prevented by rosiglitazone coincubation. In contrast, in aortae, ACh failed to alter the release of metabolites, and rosiglitazone treatment increased that of 6-keto-PGF1α. Thus, SHROBs displayed microvascular and macrovascular dysfunction. MRAs, but not aortae, of SHROBs revealed an impaired endothelial nitric oxide pathway, whereas both, but especially MRAs, displayed an impaired cyclooxygenase pathway. Glitazones elicited beneficial effects on macrovascular and, especially, microvascular function of SHROBs.
S-nitrosoglutathione supplementation to ovalbumin-sensitized and -challenged mice ameliorates methacholine-induced bronchoconstriction
Authors: Foster Matthew W. , Yang Zhonghui , Potts Erin N. , Michael Foster W. , Que Loretta G.
Published: July 2011

S-nitrosoglutathione (GSNO) is an endogenous bronchodilator present in micromolar concentrations in airway lining fluid. Airway GSNO levels decrease in severe respiratory failure and asthma, which is attributable to increased metabolism by GSNO reductase (GSNOR). Indeed, we have found that GSNOR expression and activity correlate inversely with lung S-nitrosothiol (SNO) content and airway hyperresponsiveness (AHR) to methacholine (MCh) challenge in humans with asthmatic phenotypes (Que LG, Yang Z, Stamler JS, Lugogo NL, Kraft M. Am J Respir Crit Care Med 180: 226–231, 2009). Accordingly, we hypothesized that local aerosol delivery of GSNO could ameliorate AHR and inflammation in the ovalbumin-sensitized and -challenged (OVA) mouse model of allergic asthma. Anesthetized, paralyzed, and tracheotomized 6-wk-old male control and OVA C57BL/6 mice were administered a single 15-s treatment of 0–100 mM GSNO. Five minutes later, airway resistance to MCh was measured and SNOs were quantified in bronchoalveolar lavage (BAL). Duration of protection was evaluated following nose-only exposure to 10 mM GSNO for 10 min followed by measurements of airway resistance, inflammatory cells, and cytokines and chemokines at up to 4 h later. Acute delivery of GSNO aerosol protected OVA mice from MCh-induced AHR, with no benefit seen above 20 mM GSNO. The antibronchoconstrictive effects of GSNO aerosol delivered via nose cone were sustained for at least 4 h. However, administration of GSNO did not alter total BAL cell counts or cell differentials and had modest effects on cytokine and chemokine levels. In conclusion, in the OVA mouse model of allergic asthma, aerosolized GSNO has rapid and sustained antibronchoconstrictive effects but does not substantially alter airway inflammation.
Evidence for early fibrosis and increased airway resistance in bone marrow transplant recipient mice deficient in MMP12
Authors: England Kristen A. , Price Andrew P. , Tram Kevin V. , Shapiro Steven D. , Blazar Bruce R. , Panoskaltsis-Mortari Angela
Published: July 2011

Idiopathic pneumonia syndrome (IPS) is a significant cause of morbidity and mortality post-bone marrow transplantation (BMT) in humans. In our established murine IPS model in which lethally conditioned recipients are given allogeneic bone marrow and splenocytes, recruitment of host monocytes occurs early post-BMT, followed by donor T cells concomitant with development of severe lung dysfunction. Because matrix metalloproteinase 12 (MMP12) is important for macrophage infiltration and injury in other mouse models of lung disease such as emphysema, lethally conditioned MMP12−/−mice were used as allogeneic recipients to determine whether MMP12 plays a similar role in potentiating lung injury in IPS. Surprisingly, MMP12−/−mice developed IPS and exhibited an accelerated allogeneic T cell-dependent decrease in compliance compared with wild-type (WT) recipients. MMP12−/−, but not WT, mice also had allogeneic T cell-dependent elevated lung resistance post-BMT. Recruitment of monocytes and T cells into the lungs was not altered on day 7 post-BMT, but the lungs of MMP12−/−recipients had increased collagen deposition, a feature normally not seen in our IPS model. MMP12−/−mice had a compensatory increase in MMP2 in the lungs post-BMT, as well as increased β6-integrin compared with WT recipients, and only in the presence of allogeneic T cells. Levels of total transforming growth factor (TGF)-β1 protein in the lungs were elevated compared with WT recipients, consistent with the profibrotic function of β6-integrin as an activator of TGF-β. These data indicate that host-derived MMP12 may be important in limiting development of IPS by allowing proper remodeling of extracellular matrix and effective repair of BMT-related injury.
NCS 613, a potent and specific PDE4 inhibitor, displays anti-inflammatory effects on human lung tissues
Authors: Yougbare Issaka , Morin Caroline , Senouvo Farid Yannick , Sirois Chantal , Albadine Roula , Lugnier Claire , Rousseau Eric
Published: July 2011

Chronic inflammation is a hallmark of pulmonary diseases, which leads to lung parenchyma destruction (emphysema) and obstructive bronchiolitis occurring in both chronic obstructive pulmonary disease and asthma. Inflammation is strongly correlated with low intracellular cAMP levels and increase in specific cAMP hydrolyzing activity. The aim of the present study was to investigate the role of the cyclic phosphodiesterase type 4 (PDE4) in human lung and to determine the effects of NCS 613, a new PDE4 inhibitor, on lung inflammation and bronchial hyperresponsiveness. High cAMP-PDE activities were found in the cytosoluble fractions from human lung parenchyma and distal bronchi. PDE4 (rolipram sensitive) represented 40% and 56% of total cAMP-PDE activities in the above-corresponding tissues. Moreover, PDE4A, PDE4B, PDE4C, and PDE4D isoforms were detected in all three subcellular fractions (cytosolic, microsomal, and nuclear) with differential distributions according to specific variants. Pharmacological treatments with NCS 613 significantly decreased PDE4 activity and reduced IκBα degradation in cultured parenchyma, both of which are usually correlated with a lower inflammation status. Moreover, NCS 613 pretreatment potentiated isoproterenol-induced relaxations in human distal bronchi, while reducing TNF-α-induced hyperresponsiveness in cultured bronchi, as assessed in the presence of methacholine, U-46619, or histamine. This reducing effect of NCS 613 on human bronchi hyperresponsiveness triggered by TNF-α was related to a lower expression level of PDE4B and PDE4C, as well as a downregulation of the phosphorylated forms of p38-MAPK, CPI-17, and MYPT-1, which are known to control tone. In conclusion, specific PDE4 inhibitors, such as NCS 613, may represent an alternative and isoform-specific approach toward reducing human lung inflammation and airway overreactivity.
Chitosan-Based Macromolecular Biomaterials for the Regeneration of Chondroskeletal and Nerve Tissue
Authors: Guerra Giulio D. , Barbani Niccoletta , Gagliardi Mariacristina , Rosellini Elisabetta , Cristallini Caterina
Published: July 2011

The use of materials, containing the biocompatible and bioresorbable biopolymer poly(1→4)-2-amino-2-deoxy-β-D-glucan, containing some N-acetyl-glucosamine units (chitosan, CHI) and/or its derivatives, to fabricate devices for the regeneration of bone, cartilage and nerve tissue, was reviewed. The CHI-containing devices, to be used for bone and cartilage regeneration and healing, were tested mainly for in vitro cell adhesion and proliferation and for insertion into animals; only the use of CHI in dental surgery has reached the clinical application. Regarding the nerve tissue, only a surgical repair of a 35 mm-long nerve defect in the median nerve of the right arm at elbow level with an artificial nerve graft, comprising an outer microporous conduit of CHI and internal oriented filaments of poly(glycolic acid), was reported. As a consequence, although many positive results have been obtained, much work must still be made, especially for the passage from the experimentation of the CHI-based devices, in vitro and in animals, to their clinical application.
Downregulation of the Proinflammatory State of Circulating Mononuclear Cells by Short-Term Treatment with Pioglitazone in Patients with Type 2 Diabetes Mellitus and Coronary Artery Disease
Authors: Pfützner Andreas , Weise Alexander , Pfützner-Riehn Elisabeth , Lübben Georg , Morcos Michael , Karagiannis Efstrathios , Weber Matthias , Forst Thomas
Published: July 2011

Background. This study was performed to investigate the influence of a short-term treatment with pioglitazone versus placebo on inflammatory activation of mononuclear cells (mRNA expression/protein secretion of inflammatory markers).Methods and Results. Sixty-three patients with well-controlled type 2 diabetes (52 males, 11 females, age (Mean ± SD):66±7 yrs, disease duration:6.6±9.6 yrs, HbA1c:6.7±0.6%) were randomized to additional 45 mg of pioglitazone or placebo to their existing metformin and sulfonylurea therpay for four weeks in a double-blind study design. Protein risk marker levels (hsCRP, MMP-9, MCP-1, etc.) and the expression of NFκB subunits and NFκB-modulated cytokines from isolated peripheral monocyte/macrophages were determined at baseline and endpoint. There were no changes in HbA1c, but significant biomarker improvements were seen with pioglitazone only. The mRNA marker expression was downregulated by pioglitazone and further up-regulated with placebo (e.g., P105 pioglitazone: −19%/placebo: +6%, RelA: −20%/+2%, MMP−9: −36%/+9%, TNFα: −10%/+14%,P<0.05between groups in all cases).Conclusions. Pioglitazone very rapidly down-regulated the activated state of peripheral monocytes/macrophages as assessed by mRNA expression of NFκB and NFκB-modulated cytokines and decreased plasma levels of cardiovascular risk marker proteins independent of glycemic control.
Activation of Tumor-Promoting Type 2 Macrophages by EGFR-Targeting Antibody Cetuximab
Authors: Pander Jan , Heusinkveld Moniek , van der Straaten Tahar , Jordanova Ekaterina S. , Baak-Pablo Renée , Gelderblom Hans , Morreau Hans , van der Burg Sjoerd H. , Guchelaar Henk-Jan , van Hall Thorbald
Published: July 2011

Purpose: In a recent randomized phase III clinical trial in metastatic colorectal cancer patients, the addition of the anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) cetuximab to bevacizumab and chemotherapy resulted in decreased progression-free survival, in particular for patients with the high-affinity FcγRIIIA.

Experimental Design: The presence of natural killer (NK) cells and type 2 (M2) macrophages in colorectal cancer was determined by immunohistochemistry, using antibodies to lineage-specific markers NKp46 and CD68 with CD163, respectively. Influence of tumor-bound cetuximab on M2 macrophages was carried out in vitro with EGFR-expressing tumor cells and short-term differentiated monocytes from blood donors, who were typed for the FcγRIIIA polymorphism (CD16).

Results: Antibody-dependent cellular cytotoxicity by NK cells is generally proposed as one of the antitumor mechanisms of mAbs. We found that CD163-positive M2 macrophages are much more abundant in colorectal carcinomas. In vitro analysis of M2 macrophages revealed high levels of Fc-gamma receptors (FcγR) and PD-L1 and production of IL-10 and VEGF but not IL-12. These anti-inflammatory and tumor-promoting mediators were released upon coculture with EGFR-positive tumor cells loaded with low concentrations of cetuximab. Macrophage activation depended on EGFR expression on the tumor cells, FcγRs, target specificity of the mAb and mobility of antibody complexes. Cetuximab-induced macrophage responses were more pronounced for FCGR3A 158-Val (high-affinity) carriers.

Conclusion: These results suggest that tumor-promoting M2 macrophages are activated by the therapeutic mAb cetuximab in the local tumor microenvironment and argue that this immune mechanism should be taken into account for the application of therapeutic antibodies. Clin Cancer Res; 17(17); 5668–73. ©2011 AACR.
Coronary Artery Wall Shear Stress Is Associated With Progression and Transformation of Atherosclerotic Plaque and Arterial Remodeling in Patients With Coronary Artery Disease
Authors: Samady Habib , Eshtehardi Parham , McDaniel Michael C. , Suo Jin , Dhawan Saurabh S. , Maynard Charles , Timmins Lucas H. , Quyyumi Arshed A. , Giddens Don P.
Published: July 2011

Background

Experimental studies suggest that low wall shear stress (WSS) promotes plaque development and high WSS is associated with plaque destabilization. We hypothesized that low-WSS segments in patients with coronary artery disease develop plaque progression and high-WSS segments develop necrotic core progression with fibrous tissue regression.

Methods and Results

Twenty patients with coronary artery disease underwent baseline and 6-month radiofrequency intravascular ultrasound (virtual histology intravascular ultrasound) and computational fluid dynamics modeling for WSS calculation. For each virtual histology intravascular ultrasound segment (n=2249), changes in plaque area, virtual histology intravascular ultrasound–derived plaque composition, and remodeling were compared in low-, intermediate-, and high-WSS categories. Compared with intermediate-WSS segments, low-WSS segments developed progression of plaque area (
P
=0.027) and necrotic core (
P
<0.001), whereas high-WSS segments had progression of necrotic core (
P
<0.001) and dense calcium (
P
<0.001) and regression of fibrous (
P
<0.001) and fibrofatty (
P
<0.001) tissue. Compared with intermediate-WSS segments, low-WSS segments demonstrated greater reduction in vessel (
P
<0.001) and lumen area (
P
<0.001), and high-WSS segments demonstrated an increase in vessel (
P
<0.001) and lumen (
P
<0.001) area. These changes resulted in a trend toward more constrictive remodeling in low- compared with high-WSS segments (73% versus 30%;
P
=0.06) and more excessive expansive remodeling in high- compared with low-WSS segments (42% versus 15%;
P
=0.16).

Conclusions

Compared with intermediate-WSS coronary segments, low-WSS segments develop greater plaque and necrotic core progression and constrictive remodeling, and high-WSS segments develop greater necrotic core and calcium progression, regression of fibrous and fibrofatty tissue, and excessive expansive remodeling, suggestive of transformation to a more vulnerable phenotype.

Clinical Trial Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00576576.
MicroRNA-24 Regulates Vascularity After Myocardial Infarction
Authors: Fiedler Jan , Jazbutyte Virginija , Kirchmaier Bettina C. , Gupta Shashi K. , Lorenzen Johan , Hartmann Dorothee , Galuppo Paolo , Kneitz Susanne , Pena John T.G. , Sohn-Lee Cherin , Loyer Xavier , Soutschek Juergen , Brand Thomas , Tuschl Thomas , Heineke Joerg , Martin Ulrich , Schulte-Merker Stefan , Ertl Georg , Engelhardt Stefan , Bauersachs Johann , Thum Thomas
Published: July 2011

Background—

Myocardial infarction leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after myocardial infarction has been identified as a critical event in this process, although the underlying mechanisms of cardiac angiogenesis are mechanistically not well understood.

Methods and Results—

Here, we show that the small noncoding RNA microRNA-24 (miR-24) is enriched in cardiac endothelial cells and considerably upregulated after cardiac ischemia. MiR-24 induces endothelial cell apoptosis, abolishes endothelial capillary network formation on Matrigel, and inhibits cell sprouting from endothelial spheroids. These effects are mediated through targeting of the endothelium-enriched transcription factor GATA2 and the p21-activated kinase PAK4, which were identified by bioinformatic predictions and validated by luciferase gene reporter assays. Respective downstream signaling cascades involving phosphorylated BAD (Bcl-XL/Bcl-2–associated death promoter) and Sirtuin1 were identified by transcriptome, protein arrays, and chromatin immunoprecipitation analyses. Overexpression of miR-24 or silencing of its targets significantly impaired angiogenesis in zebrafish embryos. Blocking of endothelial miR-24 limited myocardial infarct size of mice via prevention of endothelial apoptosis and enhancement of vascularity, which led to preserved cardiac function and survival.

Conclusions—

Our findings indicate that miR-24 acts as a critical regulator of endothelial cell apoptosis and angiogenesis and is suitable for therapeutic intervention in the setting of ischemic heart disease.