bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycobacterium iranicum sp. nov., a rapidly growing scotochromogenic species isolated from clinical specimens on three different continents
Authors: Shojaei Hasan , Daley Charles , Gitti Zoe , Hashemi Abodolrazagh , Heidarieh Parvin , Moore Edward R. B. , Naser Abass Daei , Russo Cristina , van Ingen Jakko , Tortoli Enrico
Published: July 2012

The isolation and characterization of a novel, rapidly growing, scotochromogenic mycobacterial species is reported. Eight independent strains were isolated from clinical specimens from six different countries of the world, two in Iran, two in Italy and one in each of following countries: Greece, the Netherlands, Sweden and the USA. Interestingly, two of the strains were isolated from cerebrospinal fluid. The strains were characterized by rapid growth and presented orange-pigmented scotochromogenic colonies. DNA-based analysis revealed unique sequences in the four regions investigated: the 16S rRNA gene, the rRNA gene internal transcribed spacer 1 and the genes encoding the 65 kDa heat-shock protein and the beta-subunit of RNA polymerase. The phylogenetic analysis placed the strains among the rapidly growing mycobacteria, being most closely related to

Mycobacterium gilvum

. The genotypic and phenotypic data both strongly supported the inclusion of the strains investigated here as members of a novel species within the genus Mycobacterium; the name Mycobacterium iranicum sp. nov. is proposed to indicate the isolation in Iran of the first recognized strains. The type strain is M05T ( = DSM 45541T = CCUG 62053T = JCM 17461T).
Weissella oryzae sp. nov., isolated from fermented rice grains
Authors: Tohno Masanori , Kitahara Maki , Inoue Hidehiko , Uegaki Ryuichi , Irisawa Tomohiro , Ohkuma Moriya , Tajima Kiyoshi
Published: July 2012

A taxonomic study was conducted on two Gram-reaction-positive, catalase-negative, irregular short-rod-shaped or coccoid lactic acid bacteria, designated strains SG25T and SG23, that were isolated from grains of fermented Japanese rice (Oryza sativa L. subsp. japonica). A phylogenetic analysis based on 16S rRNA gene sequence data clearly showed that the strains belonged to the genus

Weissella

and were most closely related to

Weissella soli

LMG 20113T (with a sequence similarity of 96.9 % for each novel strain). The peptidoglycan of each strain contained the amino acids glutamic acid, lysine, serine and alanine in a molar ratio of 1.0 : 1.2 : 0.5 : 3.0, respectively. On the basis of the unusual phenotypic characteristics of the novel strains and the low levels of DNA–DNA relatedness recorded between each novel strain and

Weissella soli

JCM 12536T, strains SG25T and SG23 represent a single novel species in the genus

Weissella

, for which the name Weissella oryzae sp. nov. is proposed. The type strain is SG25T ( = JCM 18191T  = DSM 25784T).
Rheinheimera tilapiae sp. nov., isolated from a freshwater culture pond
Authors: Chen Wen-Ming , Yang Shwu-Harn , Young Chiu-Chung , Sheu Shih-Yi
Published: July 2012

A bacterial strain designated Ruye-90T was isolated from a freshwater tilapiine cichlid fish culture pond in Taiwan and characterized using a polyphasic taxonomic approach. Strain Ruye-90T was Gram-negative, aerobic, yellow-coloured, rod-shaped, and motile by means of a single polar flagellum. Growth occurred at 4–30 °C (optimum, 20–30 °C), at pH 7.0–9.0 (optimum, pH 8.0–9.0) and with 0–2 % NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Ruye-90T belonged to the genus

Rheinheimera

and its most closely related neighbour was

Rheinheimera tangshanensis

JA3-B52T with sequence similarity of 97.5 %. The major fatty acids were summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c, 41.3 %), C16 : 0 (19.3 %), C18 : 1ω7c (8.4 %) and C12 : 0 3-OH (7.0 %). The major respiratory quinone was Q-8. The DNA G+C content of the genomic DNA was 49.0 mol%. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine, aminolipid and two uncharacterized phospholipids. The DNA–DNA relatedness of strain Ruye-90T with respect to recognized members of the genus

Rheinheimera

was less than 70 %. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain Ruye-90T represents a novel species in the genus

Rheinheimera

, for which the name Rheinheimera tilapiae sp. nov. is proposed. The type strain is Ruye-90T ( = LMG 26339T = BCRC 80263T = KCTC 23315T).
Cecembia calidifontis sp. nov., isolated from a hot spring runoff, and emended description of the genus

Cecembia
Authors: Albuquerque Luciana , Tiago Igor , Nobre M. Fernanda , Veríssimo António , da Costa Milton S.
Published: July 2012

Two red-pigmented isolates, designated RQ-33T and TU-13, were recovered from hot spring runoffs on the Island of São Miguel in the Azores, Portugal. These organisms have an optimum growth temperature of approximately 45 °C and an optimum pH for growth between 7.5 and 8.5. Based on 16S rRNA gene sequence analysis, the novel isolates were most closely related to the type strain of

Cecembia lonarensis

at 96.4 % pairwise similarity. Cells of the two isolates were non-motile, rod-shaped, Gram-stain-negative, strictly aerobic, and oxidase- and catalase-positive. The major fatty acids were iso-C15 : 0 and C15 : 0, phosphatidylethanolamine was the major polar lipid, and menaquinone 7 was the major respiratory quinone. Based on phylogenetic analyses, and physiological and biochemical characteristics, these isolates from the Azores represent a novel species of the genus

Cecembia

for which the name Cecembia calidifontis is proposed with strain RQ-33T ( = DSM 21411T = LMG 24596T) as the type strain. The description of the genus

Cecembia

is also emended.
Urinary continence after radical prostatectomy: Predictive factors of recovery after 1 year of surgery
Authors: Jeong Seong Jin , Kim Hyeon June , Kim Jeong Hyun , Oh Jong Jin , Lee Sang Cheol , Jeong Chang Wook , Yoon Cheol Yong , Hong Sung Kyu , Byun Seok‐Soo , Lee Sang Eun
Published: July 2012

Objectives:  To evaluate the clinical prognosis of incontinence and to determine the predictors for further recovery of urinary continence in patients not achieving urinary continence within 1 year after radical prostatectomy.

Methods:  A total of 708 patients were evaluated regarding urinary continence status at 1 year after surgery from a prospectively maintained radical prostatectomy database. Of these, 73 (10.3%) did not recover urinary continence within 1 year after surgery. For these patients, incontinence status and the number of pads for urinary control were assessed serially.

Results:  In 708 patients, factors associated with the recovery of urinary continence within 1 year after radical prostatectomy were membranous urethral length, prostatic apex shape and patient age. Among 73 patients with urinary incontinence, 41 (56.2%) achieved urinary continence with a mean time of 15.4 months subsequent to the first year after radical prostatectomy (baseline). A younger age at surgery (P = 0.027) and one pad being required (vs≥2 pads) at baseline (P = 0.046) were identified as independent factors for achievement of urinary continence within a further 2 years. Only the number of pads was a significant factor for further recovery of urinary continence in the longer follow up (hazard ratio 0.36, P = 0.029).

Conclusion:  Compared with factors related to the prostate or membranous urethra, patient age and severity of incontinence at 1 year after radical prostatectomy are more strongly related to the recovery of urinary continence later than 1 year after surgery. These findings might help to decide whether a definite treatment is required for persistent incontinence beyond 1 year after radical prostatectomy.
Fatty Acids Regulate Stress Resistance and Virulence Factor Production for Listeria monocytogenes
Authors: Sun Yvonne , Wilkinson Brian J. , Standiford Theodore J. , Akinbi Henry T. , O'Riordan Mary X. D.
Published: July 2012

Fatty acids (FAs) are the major structural component of cellular membranes, which provide a physical and chemical barrier that insulates intracellular reactions from environmental fluctuations. The native composition of membrane FAs establishes the topological and chemical parameters for membrane-associated functions and is therefore modulated diligently by microorganisms especially in response to environmental stresses. However, the consequences of altered FA composition during host-pathogen interactions are poorly understood. The food-borne pathogen
Listeria monocytogenes
contains mostly saturated branched-chain FAs (BCFAs), which support growth at low pH and low temperature. In this study, we show that anteiso-BCFAs enhance bacterial resistance against phagosomal killing in macrophages. Specifically, BCFAs protect against antimicrobial peptides and peptidoglycan hydrolases, two classes of phagosome antimicrobial defense mechanisms. In addition, the production of the critical virulence factor, listeriolysin O, was compromised by FA modulation, suggesting that FAs play a key role in virulence regulation. In summary, our results emphasize the significance of FA metabolism, not only in bacterial virulence regulation but also in membrane barrier function by providing resistance against host antimicrobial stress.
Functional Characterization of the Role of the Chromosome I Partitioning System in Genome Segregation in Deinococcus radiodurans
Authors: Charaka Vijay Kumar , Misra Hari S.
Published: July 2012

Deinococcus radiodurans, a radiation-resistant bacterium, harbors a multipartite genome. Chromosome I contains three putative centromeres (segS1,segS2, andsegS3), and ParA (ParA1) and ParB (ParB1) homologues. The ParB1 interaction withsegSwas sequence specific, and ParA1 was shown to be a DNA binding ATPase. The ATPase activity of ParA1 was stimulated whensegSelements were coincubated with ParB1, but the greatest increase was observed withsegS3. ParA1 incubated with thesegS-ParB1 complex showed increased light scattering in the absence of ATP. In the presence of ATP, this increase was continued withsegS1-ParA1B1 andsegS2-ParA1B1 complexes, while it decreased rapidly after an initial increase for 30 min in the case ofsegS3.D. radioduranscells expressing green fluorescent protein (GFP)-ParB1 produced foci on nucleoids, and the ΔparB1mutant showed growth retardation and ∼13%-higher anucleation than the wild type. Unstable mini-F plasmids carryingsegS1andsegS2showed inheritance inEscherichia coliwithout ParA1B1, whilesegS3-mediated plasmid stability required the intransexpression of ParA1B1. Unlike untransformedE. colicells, cells harboring pDAGS3, a plasmid carryingsegS3and also expressing ParB1-GFP, produced discrete GFP foci on nucleoids. These findings suggested that bothsegSelements and the ParA1B1 proteins ofD. radioduransare functionally active and have a role in genome segregation.
Factors Limiting SOS Expression in Log-Phase Cells of Escherichia coli
Authors: Massoni Shawn C. , Leeson Michael C. , Long Jarukit Edward , Gemme Kristin , Mui Alice , Sandler Steven J.
Published: July 2012

InEscherichia coli, RecA–single-stranded DNA (RecA-ssDNA) filaments catalyze DNA repair, recombination, and induction of the SOS response. It has been shown that, while many (15 to 25%) log-phase cells have RecA filaments, few (about 1%) are induced for SOS. It is hypothesized that RecA's ability to induce SOS expression in log-phase cells is repressed because of the potentially detrimental effects of SOS mutagenesis. To test this, mutations were sought to produce a population where the number of cells with SOS expression more closely equaled the number of RecA filaments. Here, it is shown that deletingradA(important for resolution of recombination structures) and increasingrecAtranscription 2- to 3-fold with arecAo1403operator mutation act independently to minimally satisfy this condition. This allows 24% of mutant cells to have elevated levels of SOS expression, a percentage similar to that of cells with RecA-green fluorescent protein (RecA-GFP) foci. In anxthA(exonuclease III gene) mutant where there are 3-fold more RecA loading events,recX(a destabilizer of RecA filaments) must be additionally deleted to achieve a population of cells where the percentage having elevated SOS expression (91%) nearly equals the percentage with at least one RecA-GFP focus (83%). It is proposed that, in thexthAmutant, there are three independent mechanisms that repress SOS expression in log-phase cells. These are the rapid processing of RecA filaments by RadA, maintaining the concentration of RecA below a critical level, and the destabilizing of RecA filaments by RecX. Only the first two mechanisms operate independently in a wild-type cell.
Membrane Disruption by Antimicrobial Fatty Acids Releases Low-Molecular-Weight Proteins from Staphylococcus aureus
Authors: Parsons Joshua B. , Yao Jiangwei , Frank Matthew W. , Jackson Pamela , Rock Charles O.
Published: July 2012

The skin represents an important barrier for pathogens and is known to produce fatty acids that are toxic toward Gram-positive bacteria. A screen of fatty acids as growth inhibitors of
Staphylococcus aureus
revealed structure-specific antibacterial activity. Fatty acids like oleate (18:1Δ9) were nontoxic, whereas palmitoleate (16:1Δ9) was a potent growth inhibitor. Cells treated with 16:1Δ9 exhibited rapid membrane depolarization, the disruption of all major branches of macromolecular synthesis, and the release of solutes and low-molecular-weight proteins into the medium. Other cytotoxic lipids, such as glycerol ethers, sphingosine, and acyl-amines blocked growth by the same mechanisms. Nontoxic 18:1Δ9 was used for phospholipid synthesis, whereas toxic 16:1Δ9 was not and required elongation to 18:1Δ11 prior to incorporation. However, blocking fatty acid metabolism using inhibitors to prevent acyl-acyl carrier protein formation or glycerol-phosphate acyltransferase activity did not increase the toxicity of 18:1Δ9, indicating that inefficient metabolism did not play a determinant role in fatty acid toxicity. Nontoxic 18:1Δ9 was as toxic as 16:1Δ9 in a strain lacking wall teichoic acids and led to growth arrest and enhanced release of intracellular contents. Thus, wall teichoic acids contribute to the structure-specific antimicrobial effects of unsaturated fatty acids. The ability of poorly metabolized 16:1 isomers to penetrate the cell wall defenses is a weakness that has been exploited by the innate immune system to combat
S. aureus
.
Epoxide-Mediated CifR Repression of
cif
Gene Expression Utilizes Two Binding Sites in Pseudomonas aeruginosa
Authors: Ballok Alicia E. , Bahl Christopher D. , Dolben Emily L. , Lindsay Allia K. , St. Laurent Jessica D. , Hogan Deborah A. , Madden Dean R. , O'Toole George A.
Published: July 2012

Pseudomonas aeruginosa
secretes an epoxide hydrolase virulence factor that reduces the apical membrane expression of ABC transporters such as the cystic fibrosis transmembrane conductance regulator (CFTR). This virulence factor, named CFTR inhibitory factor (Cif), is regulated by a TetR-family, epoxide-responsive repressor known as CifR via direct binding and repression. We identified two sites of CifR binding in the intergenic space between
cifR
and
morB
, the first gene in the operon containing the
cif
gene. We have mapped these binding sites and found they are 27 bp in length, and they overlap the −10 and +1 sites of both the
cifR
and
morB
regulatory region and the start of transcription, respectively. In addition, we found that CifR binds to each repression site with differing affinity. Mutagenesis of these binding sites resulted in a loss of DNA binding
in vitro
, and mutation of one of these sites
in vivo
resulted in an increase in transcription of both the
cif
and
cifR
genes. We characterized
cif
and
cifR
gene expression in sputum and found that, whereas
cif
gene expression varied relative to an
in vitro
coculture control,
cifR
gene expression was consistently higher. Analysis of a longitudinal sample of CF isolates from nine patients revealed that Cif protein was expressed over time, although variably, and these changes could not be linked to mutations in the
cifR
gene or the promoters of these genes. Finally, we tested CifR responsiveness to other epoxides and showed that CifR can respond to multiple epoxides to various degrees.
Interaction of the Extreme N-Terminal Region of FliH with FlhA Is Required for Efficient Bacterial Flagellar Protein Export
Authors: Hara Noritaka , Morimoto Yusuke V. , Kawamoto Akihiro , Namba Keiichi , Minamino Tohru
Published: July 2012

The flagellar type III protein export apparatus plays an essential role in the formation of the bacterial flagellum. FliH forms a complex along with FliI ATPase and is postulated to provide a link between FliI ring formation and flagellar protein export. Two tryptophan residues of FliH, Trp7 and Trp10, are required for the effective docking of the FliH-FliI complex to the export gate made of six membrane proteins. However, it remains unknown which export gate component interacts with these two tryptophan residues. Here, we performed targeted photo-cross-linking of the extreme N-terminal region of FliH (FliH
EN
) with its binding partners. We replaced Trp7 and Trp10 of FliH with
p
-benzoyl-phenylalanine (pBPA), a photo-cross-linkable unnatural amino acid, to produce FliH(W7pBPA) and FliH(W10pBPA). They were both functional and were photo-cross-linked with one of the export gate proteins, FlhA, but not with the other gate proteins, indicating that these two tryptophan residues are in close proximity to FlhA. Mutant FlhA proteins that are functional in the presence of FliH and FliI but not in their absence showed a significantly reduced function also by N-terminal FliH mutations even in the presence of FliI. We suggest that the interaction of FliH
EN
with FlhA is required for anchoring the FliI hexamer ring to the export gate for efficient flagellar protein export.
Activity of the Osmotically Regulated
yqiHIK
Promoter from Bacillus subtilis Is Controlled at a Distance
Authors: Fischer Kathleen E. , Bremer Erhard
Published: July 2012

The
yqiHIK
gene cluster from
Bacillus subtilis
is predicted to encode an extracellular lipoprotein (YqiH), a secreted
N
-acetylmuramoyl-
l
-alanine amidase (YqiI), and a cytoplasmic glycerophosphodiester phosphodiesterase (YqiK). Reverse transcriptase PCR (RT-PCR) analysis showed that the
yqiHIK
genes are transcribed as an operon. Consistent with the
in silico
prediction, we found that the purified YqiI protein exhibited hydrolytic activity toward peptidoglycan sacculi. Transcription studies with
yqiH-treA
reporter fusion strains revealed that the expression of
yqiHIK
is subjected to finely tuned osmotic control, but enhanced expression occurs only in severely osmotically stressed cells. Primer extension analysis pinpointed the osmotically responsive
yqiHIK
promoter, and site-directed mutagenesis was employed to assess functionally important sequences required for promoter activity and osmotic control. Promoter variants with constitutive activity were isolated. A deletion analysis of the
yqiHIK
regulatory region showed that a 53-bp AT-rich DNA segment positioned 180 bp upstream of the −35 sequence is critical for the activity and osmotic regulation of the
yqiHIK
promoter. Hence, the expression of
yqiHIK
is subjected to genetic control at a distance. Upon the onset of growth of cells of the
B. subtilis
wild-type strain in high-salinity medium (1.2 M NaCl), we observed gross morphological deformations of cells that were then reversed to a rod-shaped morphology again when the cells had adjusted to the high-salinity environment. The products of the
yqiHIK
gene cluster were not critical for reestablishing rod-shaped morphology, but the deletion of this operon yielded a
B. subtilis
mutant impaired in growth in a defined minimal medium and at high salinity.
Novel Rapidly Diversifiable Antimicrobial RNA Polymerase Switch Region Inhibitors with Confirmed Mode of Action in Haemophilus influenzae
Authors: Buurman Ed T. , Foulk Melinda A. , Gao Ning , Laganas Valerie A. , McKinney David C. , Moustakas Demetri T. , Rose Jonathan A. , Shapiro Adam B. , Fleming Paul R.
Published: July 2012

A series of inhibitors with a squaramide core was synthesized following its discovery in a high-throughput screen for novel inhibitors of a transcription-coupled translation assay using
Escherichia coli
S30 extracts. The inhibitors were inactive when the plasmid substrate was replaced with mRNA, suggesting they interfered with transcription. This was confirmed by their inhibition of purified
E. coli
RNA polymerase. The series had antimicrobial activity against efflux-negative strains of
E. coli
and
Haemophilus influenzae
. Like rifampin, the squaramides preferentially inhibited synthesis of RNA and protein over fatty acids, peptidoglycan, and DNA. However, squaramide-resistant mutants were not cross-resistant to rifampin. Nine different mutations were found in parts of
rpoB
or
rpoC
that together encode the so-called switch region of RNA polymerase. This is the binding site of the natural antibiotics myxopyronin, corallopyronin, and ripostatin and the drug fidaxomicin. Computational modeling using the X-ray crystal structure of the myxopyronin-bound RNA polymerase of
Thermus thermophilus
suggests a binding mode of these inhibitors that is consistent with the resistance mutations. The squaramides are the first reported non-natural-product-related, rapidly diversifiable antibacterial inhibitors acting via the switch region of RNA polymerase.
Residues in the N-Terminal Domain of MutL Required for Mismatch Repair in Bacillus subtilis
Authors: Bolz Nicholas J. , Lenhart Justin S. , Weindorf Steven C. , Simmons Lyle A.
Published: July 2012

Mismatch repair is a highly conserved pathway responsible for correcting DNA polymerase errors incorporated during genome replication. MutL is a mismatch repair protein known to coordinate several steps in repair that ultimately results in strand removal following mismatch identification by MutS. MutL homologs from bacteria to humans contain well-conserved N-terminal and C-terminal domains. To understand the contribution of the MutL N-terminal domain to mismatch repair, we analyzed 14 different missense mutations in
Bacillus subtilis
MutL that were conserved with missense mutations identified in the human MutL homolog MLH1 from patients with hereditary nonpolyposis colorectal cancer (HNPCC). We characterized missense mutations in or near motifs important for ATP binding, ATPase activity, and DNA binding. We found that 13 of the 14 missense mutations conferred a substantial defect to mismatch repair
in vivo
, while three mutant alleles showed a dominant negative increase in mutation frequency to wild-type
mutL
. We performed immunoblot analysis to determine the relative stability of each mutant protein
in vivo
and found that, although most accumulated, several mutant proteins failed to maintain wild-type levels, suggesting defects in protein stability. The remaining missense mutations located in areas of the protein important for DNA binding, ATP binding, and ATPase activities of MutL compromised repair
in vivo
. Our results define functional residues in the N-terminal domain of
B. subtilis
MutL that are critical for mismatch repair
in vivo
.
Torsional injuries of the lower limb: an analysis of the frictional torque between different types of football turf and the shoe outsole
Authors: Smeets Kristof , Jacobs Pieter , Hertogs Robbin , Luyckx Jean-Philippe , Innocenti Bernardo , Corten Kristoff , Ekstrand Jan , Bellemans Johan
Published: July 2012

Background

Football turf is increasingly used in European soccer competition. Little is known on the rotational torque that players experience on these fields. High rotational torques between the shoe outsole and the sports surface has been correlated with torsional injuries of the lower limb and knee.

Purpose

To evaluate the effect of six parameters that could influence the rotational torque between the shoe outsole and the latest generation football turf.

Study design

Controlled laboratory study.

Methods

A testing apparatus was constructed to measure the peak torque generated during a controlled rotation of the foot. Six parameters that could potentially influence the frictional forces, were considered: (1) the sports surface, (2) the shoe outsole cleat design, (3) the weather conditions, (4) the weight, (5) the presence of an impact and (6) the direction of rotation.

Results

The football turf without infill showed significantly lower frictional torques than natural grass whereas a football turf with sand/rubber infill had significantly higher torques. Blades were associated with significantly higher torques than studs on natural grass and on one football turf with sand/rubber infill. Dry weather was associated with higher torques only for the football turf without infill. The torque increased linearly and significantly with an increasing vertical load. The rotational torque increased significantly following an impact. Torques on external rotational movements were significantly higher with blades.

Conclusions

Important differences in rotational torques are found and could be seen as potential risk factors for torsional injuries of the lower limb.
The effectiveness of a preconditioning programme on preventing running-related injuries in novice runners: a randomised controlled trial
Authors: Bredeweg Steef W , Zijlstra Sjouke , Bessem Bram , Buist Ida
Published: July 2012

Objectives

There is no consensus on the aetiology and prevention of running-related injuries in runners. Preconditioning studies among different athlete populations show positive effects on the incidence of sports injuries.

Hypothesis

A 4-week preconditioning programme in novice runners will reduce the incidence of running-related injuries.

Study design

Randomised controlled clinical trial; level of evidence, 1.

Methods

Novice runners (N=432) prepared for a four-mile recreational running event. Participants were allocated to the 4-week preconditioning (PRECON) group (N=211) or the control group (N=221). The PRECON group started a 4-week training programme, prior to the running programme, with walking and hopping exercises. After the 4-week period both groups started a 9-week running programme. In both groups information was registered on running exposure and running-related injuries (RRIs) using an internet-based running log. Primary outcome measure was RRIs per 100 runners. An RRI was defined as any musculoskeletal complaint of the lower extremity or lower back causing restriction of running for at least a week.

Results

The incidence of RRIs was 15.2% in the PRECON group and 16.8% in the control group. The difference in RRIs between the groups was not significant (χ2=0.161, df=1, p=0.69).

Conclusion

This prospective study demonstrated that a 4-week PRECON programme with walking and hopping exercises had no influence on the incidence of RRIs in novice runners.
Pipeline embolization device and subsequent vessel sacrifice for treatment of a bleeding carotid pseudoaneurysm at the skull base: a case report
Authors: Kadkhodayan Yasha , Shetty Vilaas S , Blackburn Spiros L , Reynolds Matthew R , Cross DeWitte T , Moran Christopher J
Published: July 2012

An attempt at parent vessel reconstruction with Pipeline embolization devices to treat a mycotic pseudoaneurysm of the internal carotid artery at the skull base is presented. A 50-year-old woman with malignant otitis externa and bilateral temporal bone osteomyelitis presented with brisk bleeding from her left ear. She had bony dehiscence of the left carotid canal at CT and extravasation from a pseudoaneurysm of the carotid petrous segment at angiography. Carotid tortuosity proximally precluded placing a covered stent. After the lesion stopped bleeding spontaneously and given the presence of bilateral osteomyelitis putting the contralateral carotid at risk, the decision was made to attempt preservation of the parent vessel with flow diversion. However, bleeding recurred after 12 days, necessitating carotid sacrifice. This first reported experience in treating a carotid pseudoaneurysm at the skull base with the Pipeline device shows that transient cessation of bleeding is insufficient for flow diversion to be effective.
Pharmacodynamics of oxytetracycline administered alone and in combination with carprofen in calves
Authors: Brentnall C. , Cheng Z. , McKellar Q. A. , Lees P.
Published: July 2012

The pharmacodynamics (PD) of oxytetracycline was investigated against a strain of Mannheimia haemolytica. In vitro measurements, comprising minimum inhibitory concentration (MIC), minimum bactericidal concentration and time‐kill curves, were conducted in five matrices; Mueller Hinton Broth (MHB), cation‐adjusted MHB (CAMHB) and calf serum, exudate and transudate. MICs were much higher in the biological fluids than in MHB and CAMHB. Ratios of MIC were, serum: CAMHB 19 : 1; exudate:CAMHB 16.1; transudate:CAMHB 14 : 1. Ex vivo data, generated in the tissue cage model of inflammation, demonstrated that oxytetracycline, administered to calves intramuscularly at a dose rate of 20 mg/kg, did not inhibit the growth of M haemolytica in serum, exudate and transudate, even at peak concentration. However, using in vitro susceptibility in CAMHB and in vivo‐determined pharmacokinetic (PK) variables, average and minimum oxytetracycline concentrations relative to MIC (Cav /MIC and Cmin /MIC) predicted achievement of efficacy for approximately 48 hours after dosing. Similar Cav /MIC and Cmin /MIC data were obtained when oxytetracycline was administered in the presence of carprofen. PK‐PD integration of data for oxytetracycline, based on MICs determined in the three biological fluids, suggests that it possesses, at most, limited direct killing activity against M haemolytica. These data raise questions concerning the mechanism(s) of action of oxytetracycline, when administered at clinically recommended dose rates.
Chronic administration of hexarelin attenuates cardiac fibrosis in the spontaneously hypertensive rat
Authors: Xu Xiangbin , Ding Fan , Pang Jinjiang , Gao Xue , Xu Rong-Kun , Hao Wei , Cao Ji-Min , Chen Chen
Published: July 2012

Cardiac fibrosis is a hallmark of heart disease and plays a vital role in cardiac remodeling during heart diseases, including hypertensive heart disease. Hexarelin is one of a series of synthetic growth hormone secretagogues (GHSs) possessing a variety of cardiovascular effects via action on GHS receptors (GHS-Rs). However, the role of hexarelin in cardiac fibrosis in vivo has not yet been investigated. In the present study, spontaneously hypertensive rats (SHRs) were treated with hexarelin alone or in combination with a GHS-R antagonist for 5 wk from an age of 16 wk. Hexarelin treatment significantly reduced cardiac fibrosis in SHRs by decreasing interstitial and perivascular myocardial collagen deposition and myocardial hydroxyproline content and reducing mRNA and protein expression of collagen I and III in SHR hearts. Hexarelin treatment also increased matrix metalloproteinase (MMP)-2 and MMP-9 activities and decreased myocardial mRNA expression of tissue inhibitor of metalloproteinase (TIMP)-1 in SHRs. In addition, hexarelin treatment significantly attenuated left ventricular (LV) hypertrophy, LV diastolic dysfunction, and high blood pressure in SHRs. The effect of hexarelin on cardiac fibrosis, blood pressure, and cardiac function was mediated by its receptor, GHS-R, since a selective GHS-R antagonist abolished these effects and expression of GHS-Rs was upregulated by hexarelin treatment. In summary, our data demonstrate that hexarelin reduces cardiac fibrosis in SHRs, perhaps by decreasing collagen synthesis and accelerating collagen degradation via regulation of MMPs/TIMP. Hexarelin-reduced systolic blood pressure may also contribute to this reduced cardiac fibrosis in SHRs. The present findings provided novel insights and underscore the therapeutic potential of hexarelin as an antifibrotic agent for the treatment of cardiac fibrosis.
Nanomolar ouabain increases NCX1 expression and enhances Ca2+signaling in human arterial myocytes: a mechanism that links salt to increased vascular resistance?
Authors: Linde Cristina I. , Antos Laura K. , Golovina Vera A. , Blaustein Mordecai P.
Published: July 2012

The mechanisms by which NaCl raises blood pressure (BP) in hypertension are unresolved, but much evidence indicates that endogenous ouabain is involved. In rodents, arterial smooth muscle cell (ASMC) Na+pumps with an α2-catalytic subunit (ouabain EC50≤1.0 nM) are crucial for some hypertension models, even though ≈80% of ASMC Na+pumps have an α1-subunit (ouabain EC50≈ 5 μM). Human α1-Na+pumps, however, have high ouabain affinity (EC50≈ 10–20 nM). We used immunoblotting, immunocytochemistry, and Ca2+imaging (fura-2) to examine the expression, distribution, and function of Na+pump α-subunit isoforms in human arteries and primary cultured human ASMCs (hASMCs). hASMCs express α1- and α2-Na+pumps. Further, α2-, but not α1-, pumps are confined to plasma membrane microdomains adjacent to sarcoplasmic reticulum (SR), where they colocalize with Na/Ca exchanger-1 (NCX1) and C-type transient receptor potential-6 (receptor-operated channels, ROCs). Prolonged inhibition (72 h) with 100 nM ouabain (blocks nearly all α1- and α2-pumps) was toxic to most cultured hASMCs. Treatment with 10 nM ouabain (72 h), however, increased NCX1 and sarco(endo)plasmic reticulum Ca2+-ATPase expression and augmented ATP (10 μM)-induced SR Ca2+release in 0 Ca2+, ouabain-free media, and Ca2+influx after external Ca2+restoration. The latter was likely mediated primarily by ROCs and store-operated Ca2+channels. These hASMC protein expression and Ca2+signaling changes are comparable with previous observations on myocytes isolated from arteries of many rat hypertension models. We conclude that the same structurally and functionally coupled mechanisms (α2-Na+pumps, NCX1, ROCs, and the SR) regulate Ca2+homeostasis and signaling in hASMCs and rodent ASMCs. These ouabain/endogenous ouabain-modulated mechanisms underlie the whole body autoregulation associated with increased vascular resistance and elevation of BP in human, salt-sensitive hypertension.
TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes
Authors: Dong Baojun , Qi Dake , Yang Long , Huang Yan , Xiao Xiaoyan , Tai Ningwen , Wen Li , Wong F. Susan
Published: July 2012

Toll-like receptor (TLR)4 regulates inflammation and metabolism and has been linked to the pathogenesis of heart disease. TLR4 is upregulated in diabetic cardiomyocytes, and we examined the role of TLR4 in modulating cardiac fatty acid (FA) metabolism and the pathogenesis of diabetic heart disease in nonobese diabetic (NOD) mice. Both wild-type (WT) NOD and TLR4-deficient NOD animals had increased plasma triglyceride levels after the onset of diabetes. However, by comparison, TLR4-deficient NOD mouse hearts had lower triglyceride accumulation in the early stages of diabetes, which was associated with a reduction in myeloid differentiation primary response gene (88) (MyD88), phosphorylation of p38 MAPK (phospho-p38), lipoprotein lipase (LPL), and JNK levels but increased phospho-AMP-activated protein kinase (AMPK). Oleic acid treatment in H9C2 cardiomyocytes also led to cellular lipid accumulation, which was attenuated by TLR4 small interfering RNA. TLR4 deficiency in the cells decreased FA-induced augmentation of MyD88, phospho-p38, and LPL, suggesting that TLR4 may modulate FA-induced lipid metabolism in cardiomyocytes. In addition, although cardiac function was impaired in both diabetic WT NOD and TLR4-deficient NOD animals compared with control nondiabetic mice, this deficit was less in the diabetic TLR4-deficient NOD mice, which had greater ejection fraction, greater fractional shortening, and increased left ventricular developed pressure in the early stages after the development of diabetes compared with their diabetic WT NOD counterparts. Thus, we conclude that TLR4 plays a role in regulating lipid accumulation in cardiac muscle after the onset of type 1 diabetes, which may contribute to cardiac dysfunction.
Particulate Emissions: Health Effects and Labour Market Consequences
Authors: Kruse Marie , Sætterstrøm Bjørn , Bønløkke Jakob , Brønnum-Hansen Henrik , Flachs Esben Meulengracht , Sørensen Jan
Published: July 2012

The objective of this study was to analyse the productivity cost savings associated with mitigation of particulate emissions, as an input to a cost-benefit analysis. Reduced emissions of particulate matter (PM2.5) may reduce the incidence of diseases related to air pollution and potentially increase productivity as a result of better health. Based on data from epidemiological studies, we modelled the impact of air pollution on four different diseases: coronary heart disease, stroke, lung cancer, and chronic obstructive pulmonary disease. We identified individuals with these diseases and modelled changes in disease incidence as an expression of exposure. The labour market affiliation and development in wages over time for exposed individuals was compared to that of a reference group of individuals matched on a number of sociodemographic variables, comorbidity, and predicted smoking status. We identified a productivity cost of about 1.8 million EURO per 100,000 population aged 50–70 in the first year, following an increase inPM2.5emissions. We have illustrated how the potential impact of air pollution may influence social production by application of a matched study design that renders a study population similar to that of a trial. The result suggests that there may be a productivity gain associated with mitigation efforts.
On the Regularized Solutions of Optimal Control Problem in a Hyperbolic System
Authors: Saraç Yeşim , Subaşı Murat
Published: July 2012

We use the initial condition on the state variable of a hyperbolic problem as control function and formulate a control problem whose solution implies the minimization at the final time of the distance measured in a suitable norm between the solution of the problem and given targets. We prove the existence and the uniqueness of the optimal solution and establish the optimality condition. An iterative algorithm is constructed to compute the required optimal control as limit of a suitable subsequence of controls. An iterative procedure is implemented and used to numerically solve some test problems.
Lung Cancer: A Classic Example of Tumor Escape and Progression While Providing Opportunities for Immunological Intervention
Authors: Jadus Martin R. , Natividad Josephine , Mai Anthony , Ouyang Yi , Lambrecht Nils , Szabo Sandor , Ge Lisheng , Hoa Neil , Dacosta-Iyer Maria G.
Published: July 2012

Lung cancers remain one of the most common and deadly cancers in the world today (12.5% of newly diagnosed cancers) despite current advances in chemo- and radiation therapies. Often, by the time these tumors are diagnosed, they have already metastasized. These tumors demonstrate the classic hallmarks of cancer in that they have advanced defensive strategies allowing them to escape various standard oncological treatments. Immunotherapy is making inroads towards effectively treating other fatal cancers, such as melanoma, glioblastoma multiforme, and castrate-resistant prostate cancers. This paper will cover the escape mechanisms of bronchogenic lung cancer that must be overcome before they can be successfully treated. We also review the history of immunotherapy directed towards lung cancers.
Thin Film Limits in Magnetoelastic Interactions
Authors: Hadda Mohammed , Tilioua Mouhcine
Published: July 2012

This paper deals with classical dimensional reductions 3D‐2D and 3D‐1D in magnetoelastic
interactions. We adopt a model described by the Landau‐Lifshitz‐Gilbert
equation for the magnetization field coupled to an evolution equation for the displacement.
We identify the limit problem both for flat and slender media by using the so‐called energy method.
Vertically Stratified Ash-Limb Beetle Fauna in Northern Ohio
Authors: Ulyshen Michael D. , Barrington William T. , Hoebeke E. Richard , Herms Daniel A.
Published: July 2012

To better understand the diversity and ecology of indigenous arthropods at risk from the invasive emerald ash borer (Agrilus planipennisFairmaire) in North American forests, saproxylic beetles (Insecta: Coleoptera) were reared from ash (Fraxinussp.) limbs suspended in the canopy,~10–17 m above the ground, and from those placed on the ground in a mature mixed hardwood forest. In total, 209 specimens from 9 families and 18 species were collected from 30.0 m2of limbs. The generalist cerambycidNeoclytus acuminatus(Fabricius) was the most commonly captured taxon, followed by an assemblage of four exotic ambrosia beetles dominated byXylosandrus crassiusculus(Motschulsky). Two species largely or entirely restricted to ash, the buprestidAgrilus subcinctusGory and the curculionidHylesinus aculeatus(Say), were collected as well. Although there were no differences in beetle richness, abundance, or density between limb positions, community composition differed significantly. This can be largely attributed to phloem and wood-feeding species (i.e., Cerambycidae and Buprestidae) being more common in the suspended limbs and ambrosia beetles being more numerous on the forest floor. Possible explanations for these patterns are discussed.
The Impact of Pulmonary Arterial Pressure on Exercise Capacity in Mild-to-Moderate Cystic Fibrosis: A Case Control Study
Authors: Manika Katerina , Pitsiou Georgia G. , Boutou Afroditi K. , Tsaoussis Vassilis , Chavouzis Nikolaos , Antoniou Marina , Fotoulaki Maria , Stanopoulos Ioannis , Kioumis Ioannis
Published: July 2012

Background. Pulmonary hypertension (PH) is an often complication of severe cystic fibrosis (CF); however, data on the presence and impact of pulmonary vasculopathy in adult CF patients with milder disease, is very limited.Aim. To investigate, for the first time, the impact of systolic pulmonary arterial pressure (PASP) on maximal exercise capacity in adults with mild-to-moderate cystic fibrosis, without PH at rest.Methods. This is a Case Control study. Seventeen adults with mild-to-moderate CF, without PH at rest (cases) and 10 healthy, nonsmoking, age, and height matched controls were studied. All subjects underwent maximal cardiopulmonary exercise testing and echocardiography before and within 1 minute after stopping exercise.Results. Exercise ventilation parameters were similar in the two groups; however, cases, compared to controls, had higher postexercise PASP and decreased exercise capacity, established with lower peak work rate, peak O2uptake, anaerobic threshold, and peak O2pulse. Furthermore, the change in PASP values before and after exercise was strongly correlated to the parameters of exercise capacity among cases but not among controls.Conclusions. CF adults with mild-to-moderate disease should be screened for the presence of pulmonary vasculopathy, since the elevation of PASP during exercise might contribute to impaired exercise capacity.
Oncolytic Viruses in the Treatment of Bladder Cancer
Authors: Potts Kyle G. , Hitt Mary M. , Moore Ronald B.
Published: July 2012

Bladder carcinoma is the second most common malignancy of the urinary tract. Up to 85% of patients with bladder cancer are diagnosed with a tumor that is limited to the bladder mucosa (Ta, T1, and CIS). These stages are commonly termed as non-muscle-invasive bladder cancer (NMIBC). Although the treatment of NMIBC has greatly improved in recent years, there is a need for additional therapies when patients fail bacillus Calmette-Guérin (BCG) and chemotherapeutic agents. We propose that bladder cancer may be an ideal target for oncolytic viruses engineered to selectively replicate in and lyse tumor cells leaving normal cells unharmed. In support of this hypothesis, here we review current treatment strategies for bladder cancer and their shortcomings, as well as recent advancements in oncolytic viral therapy demonstrating encouraging safety profiles and antitumor activity.
Relation of Bicuspid Aortic Valve Morphology to the Dilatation Pattern of the Proximal Aorta: Focus on the Transvalvular Flow
Authors: Girdauskas Evaldas , Disha Kushtrim , Borger Michael-Andrew , Kuntze Thomas
Published: July 2012

Whether the dilatation of proximal aorta in patients with bicuspid aortic valve is secondary to hemodynamic effects related to the abnormal aortic valve or a primary manifestation of the genetic disorder remains controversial. We discuss in this paper the recent data on the BAV function and transvalvular flow patterns in relation with the dilatation type of the proximal aorta. Different morphological forms of bicuspid aortic valve in relation with the specific transvalvular blood flow patterns are focus of the first paragraph of this paper. In the second part of this paper we present the pathogenetic insight into the different clinically observed phenotypes of bicuspid aortic valve disease (i.e., association of proximal aortic shapes with the specific cusp fusion patterns), based on the data from recent rheological studies.
Screening and Health Behaviors among Persons Diagnosed with Familial Adenomatous Polyposis and Their Relatives
Authors: James Aimee S. , Chisholm Phillip , Wolin Kathleen Y. , Baxter Melanie , Kaphingst Kimberly , Davidson Nicholas O.
Published: July 2012

Familial Adenomatous Polyposis (FAP) is a rare autosomal dominantly inherited colorectal cancer syndrome. Individuals with FAP often undergo colectomy and are recommended to follow several surveillance protocols. Biological relatives of persons with FAP may also be at risk and thus should undergo genetic counseling. Screening adherence, genetic testing, and other health behaviors among individuals with FAP and their relatives are not well characterized. We conducted a cross-sectional self-report survey with individuals who have FAP (n=35) and their biological relatives (n=15). Respondents were recruited through a cancer center registry for inherited colon cancers. Most relatives had undergone colon cancer screening; 40% had undergone genetic testing. One fifth of respondents with FAP had not undergone an upper endoscopy, contrary to usual recommendations. Cigarette smoking rates were above average and were higher among FAP respondents. Use of vitamin supplements was fairly common, more so among those with FAP. Although most people had been screened, there are areas for improvement, notably for upper endoscopy among individuals with FAP and genetic testing among family members. Several other health-risk behaviors and health concerns other than FAP were identified. Further research into factors contributing to screening rates and other health behaviors in this high-risk population is warranted.
An Epidemiological Model for Examining Marijuana Use over the Life Course
Authors: Paddock Susan M. , Kilmer Beau , Caulkins Jonathan P. , Booth Marika J. , Pacula Rosalie L.
Published: July 2012

Trajectories of drug use are usually studied empirically by following over time persons sampled from either the general population (most often youth and young adults) or from heavy or problematic users (e.g., arrestees or those in treatment). The former, population-based samples, describe early career development, but miss the years of use that generate the greatest social costs. The latter, selected populations, help to summarize the most problematic use, but cannot easily explain how people become problem users nor are they representative of the population as a whole. This paper shows how microsimulation can synthesize both sorts of data within a single analytical framework, while retaining heterogeneous influences that can impact drug use decisions over the life course. The RAND Marijuana Microsimulation Model is constructed for marijuana use, validated, and then used to demonstrate how such models can be used to evaluate alternative policy options aimed at reducing use over the life course.