bluuebunny/crossref_metadata_2025 huggingface dataset:
The Low Linolenic Acid Soybean Line PI 361088B Contains a NovelGmFAD3AMutation
Authors: Chappell Andrew S. , Bilyeu Kristin D.
Published: August 2007

Characterization of genetic mutations at the molecular level allows for the development of perfect genetic markers and rapid assays to detect those markers, which enables breeders to directly select for desired alleles and accelerate the breeding process. The objectives of this study were to identify genetic lesions found in theGmFAD3Agene in the low linolenic acid soybean[Glycine max(L.) Merr] line PI 361088B, which contains afanallele, and to develop rapid molecular marker assays that distinguish between the wild‐type and PI 361088B alleles. The entire genomic sequence of theGmFAD3Agene was determined for PI 361088B. Two thymine nucleotides are inserted into a run of four thymines from nucleotide position 307 to 310 of theGmFAD3Acoding sequence, resulting in a frameshift and the introduction of a premature stop codon at nucleotide 328. Two molecular marker assays were developed that rely on polymerase chain reaction (PCR) amplification of the region of interest followed by restriction endonuclease digestion and agarose gel electrophoresis or melting curve analysis. A third assay is an allele‐specific PCR‐based assay that does not require any endonuclease step and requires only melting curve analysis. In conclusion, the low linolenic acid soybean line PI 361088B contains a coding mutation inGmFAD3A; this allele can easily be distinguished from the corresponding wild‐type allele using any of three rapid molecular marker assays that were developed.
Mutant-prevention concentrations of enrofloxacin for Escherichia coli isolates from chickens
Authors: Li Qianxue , Bi Xingming , Diao Youjiang , Deng Xuming
Published: August 2007

Objective—To investigate the development of enrofloxacin resistance among Escherichia coli isolates obtained from chickens by determining mutant-prevention concentrations (MPCs) and sequence the quinolone resistance–determining regions (QRDRs) of gyrA and parC genes in selected isolates.

Sample Population—15 chicken-derived E coli isolates.

Procedures—For all isolates, MPC and minimal inhibition concentration (MIC) of enrofloxacin were determined. The MPCs and maximum serum drug concentrations attained with enrofloxacin doses recommended for treatment of E coli infections in chickens were compared. Mutation frequencies and QRDR sequence changes in gyrA and parC were also determined.

Results—In 2 of 15 E coli strains, MPCs were low (0.016 and 0.062 μg/mL), MPC:MIC ratios were 2 and 4, and the GyrA and ParC proteins had no mutations. In 9 susceptible isolates with a GyrA point mutation, MPCs ranged from 2 to 16 μg/mL. For isolates with double mutations in GyrA and a single mutation in ParC, MPCs were > 32 μg/mL (several fold greater than the maximal plasma concentration of enrofloxacin in chickens); mutation frequencies were also much lower, compared with frequencies for single-mutation isolates.

Conclusions and Clinical Relevance—For E coli infections of chickens, MPC appears to be useful for determining enrofloxacin-dosing strategies. The high MPC:MIC ratio may result in enrofloxacin-treatment failure in chickens infected with some wild-type gyrA E coli isolates despite the isolates' enrofloxacin susceptibility (MICs 0.125 to 1 μg/mL). For infections involving isolates with high MPCs, especially those containing mutations in gyrA and parC genes, treatment with combinations of antimicrobials should be adopted.
Validity of goniometric joint measurements in cats
Authors: Jaeger Gayle H. , Marcellin-Little Denis J. , DePuy Venita , Lascelles B. Duncan X.
Published: August 2007

Objective—To compare and validate goniometric joint measurements obtained from nonsedated and sedated cats with measurements from radiographic evaluation.

Animals—20 adult cats with no evidence of joint disease.

Procedures—Measurements of flexion and extension of the carpus, elbow, shoulder, tarsus, stifle, and hip joints and of carpal and tarsal joints during varus and valgus angulation were made by a single investigator before and after sedation of cats. Measurements were made by use of a goniometer with a masked dial. Joint angle measurements were compared between nonsedated and sedated cats and also with measurements from radiographs made while cats were sedated. Each series of measurements was repeated 4 times. To evaluate repeatability, Cronbach α values were calculated for repeated measure results of goniometric joint measurements of nonsedated and sedated cats. An intraclass correlation was calculated to determine reliability among the 3 measurement types (ie, measurements from nonsedated and sedated cats and on radiographic evaluation).

Results—Joint measurements did not differ significantly by measurement type, when comparing radiographic measurements with goniometric measurements in sedated and nonsedated cats. Cronbach α values were > 0.99 for goniometric joint measurements within individual nonsedated and sedated cats and also for comparison of mean meaurements obtained from sedated cats versus nonsedated cats versus radiographs. An intraclass correlation of 0.999 revealed high reliability among measurement types.

Conclusions and Clinical Relevance—Results indicated that goniometric joint measurements in nonsedated and sedated cats are repeatable and valid.
Effects of Rho-kinase and Src protein tyrosine kinase inhibition on agonist-induced vasoconstriction of arteries and veins of the equine laminar dermis
Authors: Robertson Tom P. , Moore James N. , Noschka Erik , Lewis Tristan H. , Lewis Stephen J. , Peroni John F.
Published: August 2007

Objective—To determine the effects of inhibition of Rho-kinase or Src-family protein tyrosine kinases (srcPTK) on agonist-induced contractile responses in equine laminar arteries and veins.

Sample Population—Laminar arteries and veins obtained from 13 adult mixed-breed horses.

Procedures—Laminar vessels were mounted on myographs and exposed to phenylephrine (PE), 5-hydroxytryptamine (5-HT), prostaglandin F2α (PGF2α), and endothelin-1 (ET-1) with or without the Rho-kinase inhibitor Y-27632 (10μM), srcPTK inhibitor PP2 (10μM), or a negative control analogue for PP2 (PP3; 10μM).

Results—Responses to PE were reduced by use of Y-27632 in laminar vessels (approx inhibition, 55%). However, Y-27632 reduced responses to 5-HT to a greater degree in veins than in arteries (approx inhibition of 55% and 35%, respectively). The Y-27632 also reduced responses of laminar veins to ET-1 by approximately 40% but had no effect on maximum responses of laminar arteries to ET-1, although a rightward shift in the concentration response curve was evident. Addition of PP2 reduced responses to PE, 5-HT, and PGF2α in laminar veins by approximately 40%, 60%, and 65%, respectively, compared with responses after the addition of PP3; PP2 had no effect on responses to ET-1. In laminar arteries, PP2 reduced 5-HT–induced contractions by approximately 50% but did not affect responses to PE or ET-1.

Conclusions and Clinical Relevance—Results of the study were consistent with activation of Rho-kinase being important during agonist-induced constriction in laminar vessels, activation of srcPTK being an agonist-dependent event, and more prominent roles for Rhokinase and srcPTK in veins than in arteries.
Quantification of mitral valve regurgitation in dogs with degenerative mitral valve disease by use of the proximal isovelocity surface area method
Authors: Gouni Vassiliki , Serres François J. , Pouchelon Jean-Louis , Tissier Renaud , Lefebvre Hervé P. , Nicolle Audrey P. , Sampedrano Carolina Carlos , Chetboul Valérie
Published: August 2007

Objective—To determine the within-day and between-day variability of regurgitant fraction (RF) assessed by use of the proximal isovelocity surface area (PISA) method in awake dogs with degenerative mitral valve disease (MVD), measure RF in dogs with MVD, and assess the correlation between RF and several clinical and Doppler echocardiographic variables.

Design—Prospective study.

Animals—6 MVD-affected dogs with no clinical signs and 67 dogs with MVD of differing severity (International Small Animal Cardiac Health Council [ISACHC] classification).

Procedures—The 6 dogs were used to determine the repeatability and reproducibility of the PISA method, and RF was then assessed in 67 dogs of various ISACHC classes. Mitral valve regurgitation was also assessed from the maximum area of regurgitant jet signal-to-left atrium area (ARJ/LAA) ratio determined via color Doppler echocardiographic mapping.

Results—Within- and between-day coefficients of variation of RF were 8% and 11%, respectively. Regurgitation fraction was significantly correlated with ISACHC classification and heart murmur grade and was higher in ISACHC class III dogs (mean ± SD, 72.8 ± 9.5%) than class II (57.9 ± 20.1%) or I (40.7 ± 19.2%) dogs. Regurgitation fraction and left atriumto-aorta ratio, fractional shortening, systolic pulmonary arterial pressure, and ARJ/LAA ratio were significantly correlated.

Conclusions and Clinical Relevance—Results suggested that RF is a repeatable and reproducible variable for noninvasive quantitative evaluation of mitral valve regurgitation in awake dogs. Regurgitation fraction also correlated well with disease severity. It appears that this Doppler echocardiographic index may be useful in longitudinal studies of MVD in dogs.
Clinical features and heritability of hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers: 25 cases (1994–2006)
Authors: Hughes Angela M. , Nelson Richard W. , Famula Thomas R. , Bannasch Danika L.
Published: August 2007

Objective—To evaluate the clinical features and heritability of naturally occurring hypoadrenocorticism in Nova Scotia Duck Tolling Retrievers (NSDTRs).

Design—Retrospective case series.

Animals—25 NSDTRs with hypoadrenocorticism.

Procedures—Questionnaires completed by owners of NSDTRs with hypoadrenocorticism and medical records from veterinarians were reviewed for information regarding diagnosis, age at diagnosis, concurrent diseases, age at death, and cause of death. Pedigrees were analyzed for heritability and mode of inheritance of hypoadrenocorticism (including complex segregation analysis of pedigrees of 1,515 dogs).

Results—On the basis of results of ACTH stimulation testing, hypoadrenocorticism was diagnosed in 16 female and 9 male NSDTRs (including 6 full siblings). Median age at diagnosis was 2.6 years; the diagnosis was made prior to 2 years of age in 11 dogs. Seventeen dogs had hyponatremia, hyperkalemia, or both, and serum electrolyte concentrations were within reference ranges for 8 dogs at the time of diagnosis. Median survival time after diagnosis for 4 dogs that died or were euthanized as a result of medical causes was 1.6 years. Heritability was calculated at 0.98 with no sex effect, and complex segregation analysis fit a major gene model with an autosomal recessive mode of inheritance.

Conclusions and Clinical Relevance—In NSDTRs, hypoadrenocorticism was diagnosed at an earlier age, compared with published reports of age at diagnosis among the general dog population. Among the study dogs, 32% had no serum electrolyte abnormalities at the time of diagnosis, and the disease appeared to have an autosomal recessive mode of inheritance in the breed.
Accuracy of sow culling classifications reported by lay personnel on commercial swine farms
Authors: Knauer Mark , Karriker Locke A. , Baas Thomas J. , Johnson Colin , Stalder Kenneth J.
Published: August 2007

Objective—To determine the accuracy of sow culling classifications reported by lay personnel on commercial swine farms.

Design—Retrospective cohort study.

Animals—A convenience sample of 923 sows from 8 conventional, farrow-to-wean farms that followed standard operating procedures.

Procedures—Sows were examined at slaughter, and lesions were recorded. Individual production records were reviewed to determine the farm-reported reason for culling the sows, and criteria were developed to assess the accuracy of recorded culling classifications.

Results—For 209 of the 923 (23%) sows, the farm-reported culling classification was judged to be inaccurate. The culling code was considered to be inaccurate for 62 of 322 (19%) sows reportedly culled because of old age, 48 of 172 (28%) sows reportedly culled because of failure to conceive, 31 of 90 (34%) sows reportedly culled because of poor body condition, and 23 of 73 (32%) sows reportedly culled because of poor farrowing productivity.

Conclusions and Clinical Relevance—Results suggested that for commercial swine farms, farm-reported culling code classifications were frequently inaccurate. This degree of inaccuracy may cause severe limitations for studies that rely on farm-reported assessments of clinical conditions.
Proteins separation and purification by salt gradient ion‐exchange SMB
Authors: Li Ping , Xiu Guohua , Rodrigues Alirio E.
Published: August 2007

The process performance of the separation and purification of proteins by ion‐exchange simulated moving bed (IE‐SMB) can be improved when a step‐wise salt concentration is formed in the SMB unit, called salt gradient IE‐SMB. In this paper, a gradient SMB model is used to analyze the performance of the salt gradient IE‐SMB process, based on literature data for linear adsorption of proteins. Some strategies are discussed for the selection of salt gradient in IE‐SMB chromatography for proteins effective separation. Three configurations of the gradient SMB process, open loop, closed loop, and closed loop with a holding vessel are compared. When running a gradient SMB with closed loop configuration, a holding vessel with a given volume is added to the system to mix online the desorbent with the recycled stream from section IV during the switching interval, in order to reduce the fluctuation of salt or solvent strength in the columns. Moreover, we also present a comparison of two strategies of modeling, the gradient SMB model and the equivalent gradient TMB model, for the prediction of internal concentration profiles in gradient SMB chromatography with open loop and closed loop, respectively. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Flowsheet optimization with complex cost and size functions using process simulators
Authors: Caballero José A. , Odjo Andrew , Grossmann Ignacio E.
Published: August 2007

In this article we address the design and optimization of chemical processes using Chemical Modular Process Simulators—that include state of the art models—including discontinuous cost and sizing equations. Equations are divided into “implicit” ones which include all the equations in the process simulators with an input–output black box structure, and other third party equations (i.e. sizing and costing correlations for any database) and “explicit” constraints in the form of equalities or inequalities like in any regular equation based optimization environment. Using this modular framework, the problem is formulated as a generalized disjunctive programming problem and reformulated and solved as a mixed‐integer nonlinear programming problem. Different algorithms (branch and bound, outer approximation, and LP/NLP based branch and bound) have been adapted to deal with implicit equations and their capabilities have been studied. Several examples are presented in order to illustrate the performance of the algorithms. © 2007 American Institute of Chemical Engineers AIChE J, 2007
Autosomal linkage analysis of a Japanese single multiplex schizophrenia pedigree reveals two candidate loci on chromosomes 4q and 3q
Authors: Kaneko Naoshi , Muratake Tatsuyuki , Kuwabara Hideki , Kurosaki Takanori , Takei Mitsuru , Ohtsuki Tsuyuka , Arinami Tadao , Tsuji Shoji , Someya Toshiyuki
Published: August 2007

We analyzed a large multiplex schizophrenia pedigree collected in mid‐eastern Japan using 322 microsatellite markers distributed throughout the whole autosome. Under an autosomal‐dominant inheritance model, the highest pairwise LOD score (LOD = 1.69) was found at 4q (D4S2431: theta = 0.0), and LOD scores at two other loci 3q (ATA34G06) and 8q (D8S1128) were 1.62 and 1.46, respectively. In multipoint analysis, LOD scores of the regions on 4q and 3q remained at a similar level; however, the LOD score of the region on 8q apparently decreased. Additional dense map analysis revealed haplotypes on 4q and 3q regions shared by affected individuals. On chromosome 4q, the haplotype spanning about 8 centiMorgans (cM) was shared by four of six genotyped individuals with schizophrenia and one affected individual whose haplotype was estimated. On 3q, the haplotype spanning about 20 cM was shared by five genotyped individuals with schizophrenia. We obtained two candidate regions of major susceptibility loci for schizophrenia on chromosomes 3q and 4q. © 2007 Wiley‐Liss, Inc.
Atorvastatin in patients with primary biliary cirrhosis and incomplete biochemical response to ursodeoxycholic acid
Authors: Stojakovic Tatjana , Putz-Bankuti Csilla , Fauler Günter , Scharnagl Hubert , Wagner Martin , Stadlbauer Vanessa , Gurakuqi Gerald , Stauber Rudolf E. , März Winfried , Trauner Michael
Published: August 2007

Statin therapy may target both hypercholesterolemia and cholestasis in primary biliary cirrhosis (PBC). However, little is known about the efficacy and safety of statins in PBC. The aim of this single-center study was therefore to prospectively examine the effects of atorvastatin on serum markers of cholestasis, aminotransferases, and lipid and bile acid metabolism as well as inflammatory and immunological markers in patients with PBC. Fifteen patients with early-stage PBC and an incomplete biochemical response to ursodeoxycholic acid (UDCA) therapy (defined as alkaline phosphatase 1.5-fold above the upper limit of normal after 1 year) were treated with atorvastatin 10 mg/day, 20 mg/day, and 40 mg/day for 4 weeks, respectively. Serum levels of alkaline phosphatase increased during atorvastatin 20 mg and 40 mg (

P

< 0.05), whereas leucine aminopeptidase and γ-glutamyltransferase remained unchanged. No statistical differences in overall serum ALT, AST, bilirubin, and IgM levels were observed. However, atorvastatin was discontinued in 1 out of 15 patients because of ALT 2-fold above baseline, and 2 patients showed ALT elevations 3-fold above the upper limit of normal at the end of the atorvastatin treatment period. Serum total cholesterol and low-density lipoprotein cholesterol levels decreased by 35% and 49%, respectively (

P

< 0.001). Precursors of cholesterol biosynthesis (lanosterol, desmosterol, lathosterol) showed a similar pattern. No changes in serum bile acid levels and composition were observed during treatment.

Conclusion:

Atorvastatin does not improve cholestasis in PBC patients with an incomplete biochemical response to UDCA but effectively reduces serum cholesterol levels. (Hepatology 2007.)
Suppressor of cytokine signaling 3 (SOCS3) expression and hepatitis C virus–related chronic hepatitis
Authors: Persico Marcello , Capasso Mario , Persico Eliana , Svelto Monica , Russo Roberta , Spano Daniela , Crocè Lori , La Mura Vincenzo , Moschella Francesco , Masutti Flora , Torella Roberto , Tiribelli Claudio , Iolascon Achille
Published: August 2007

The response to antiviral therapy is lower in hepatitis C virus (HCV) patients with genotype 1 than in those with genotype 2. Overexpression of the suppressor of cytokine signaling 3 (SOCS3) gene in liver tissue is associated with a poorer treatment outcome in patients with chronic hepatitis C viral genotype 1. Also, insulin resistance has been implicated in nonresponse to an anti-HCV treatment. To understand why HCV genotype 1 patients respond differently, we investigated SOCS3 gene expression, metabolic syndrome (MS), and the response to therapy in a cohort of patients with HCV-related hepatitis. A total of 198 patients (108 with genotype 1 and 90 with genotype 2) treated with pegylated interferon plus ribavirin were consecutively enrolled in the study. We measured SOCS3 expression in Epstein-Barr virus–transformed lymphoblastoid cell lines derived from peripheral lymphocytes of a subset of 130 patients. MS was more frequent in genotype 1 patients than in genotype 2 patients (

P

< 0.01). Nonresponders (

P

< 0.01), MS (

P

< 0.001), and genotype 1 (

P

< 0.001) were significantly related to SOCS3 overexpression. However, SOCS3 levels were higher in nonresponders also, regardless of the genotype (

P

< 0.01). In a univariate analysis, the genotype (

P

< 0.001), age (

P

< 0.001), SOCS3 (

P

< 0.001), and MS (

P

< 0.001) were significantly related to the response to therapy. However, in a multivariate analysis, SOCS3 was the only independent predictor of the response (odds ratio = 6.7;

P

< 0.005).

Conclusion:

We speculate that SOCS3 expression per se may influence the response to antiviral therapy and that the genotype 1b virus might induce its up-regulation. This may account for the different responses to therapy between genotype 1–infected and genotype 2–infected patients. (HEPATOLOGY 2007.)
Alpha-1 antitrypsin Z protein (PiZ) increases hepatic fibrosis in a murine model of cholestasis
Authors: Mencin Ali , Seki Ekihiro , Osawa Yosuke , Kodama Yuzo , De Minicis Samuele , Knowles Michael , Brenner David A.
Published: August 2007

Alpha-1 antitrypsin (α1-AT) deficiency is the most common genetic cause of liver disease in children. The homozygous α1-ATZ mutation (PiZZ) results in significant liver disease in 10% of all affected patients. The α1-ATZ mutation also may lead to worse liver injury in the setting of other liver diseases such as cystic fibrosis, nonalcoholic fatty liver disease, and hepatitis C. Although cholestatic injury is common to many forms of liver disease, its effect on the PiZZ phenotype is unknown. To elucidate the interplay of cholestasis and the PiZZ phenotype, we performed bile duct ligation (BDL) on C57BL/6 mice possessing a transgenic α1-ATZ mutation and littermate controls. PiZ transgenic mice undergoing BDL developed more liver fibrosis by quantification of Sirius red staining (

P

= 0.0003) and hydroxyproline (

P

= 0.007) than wild-type mice after BDL. More activated hepatic stellate cells (HSCs) and apoptotic cells also were observed in the PiZ BDL model. Quantitative real time polymerase chain reaction (PCR) of the endoplasmic reticulum (ER) stress markers CHOP and GRP78 were 4-fold and 2-fold more up-regulated, respectively, in PiZ BDL mice when compared with wild-type BDL mice (

P

= 0.02,

P

= 0.02). Increased apoptosis was also noted in PiZ BDL mice by terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) and cleaved caspase-3 histological staining.

Conclusion :

PiZ transgenic mice are more susceptible to liver fibrosis induced by cholestasis from BDL. Cholestasis therefore may lead to increased fibrosis in α1-AT deficiency, and the α1-ATZ mutation may act as a modifier gene in patients with concurrent cholestatic liver diseases such as cystic fibrosis.
Electrical stimulation enhances viability of human cutaneous fibroblasts on conductive biodegradable substrates
Authors: Shi Guixin , Rouabhia Mahmoud , Meng Shiyun , Zhang Ze
Published: August 2007

Electrically conductive biodegradable polymer membranes were prepared by mixing conductive polypyrrole particles with poly(L‐lactic acid) solution followed by solution casting and solvent evaporation. Multi‐well electrical cell culture plates were fabricated to host electrically stimulated cell culture and monitor parameters. Human cutaneous fibroblasts were cultured on conductive membranes with or without electrical stimulation (ES). Cell count, MTT, Hoechst staining, and SEM were performed to characterize the cells. The membranes supported the adhesion and proliferation of the fibroblasts in both the presence and absence of ES. In the presence of direct electrical field strength of 100 mV/mm, cell viability on the PPy/PLLA membranes at 2 and 24 h was 2.2‐ and 4.0‐fold (p < 0.05) respectively of that on the same membranes without ES. Direct electrical current ranging from 2.5 to 250 μA/mm had no effect on the viability of cells cultured on the gold‐coated Petri dish. Electrical field applied to conductive biodegradable polymer surfaces is therefore an effective approach to upregulate the mitochondrial activity of human skin fibroblasts. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2008
Hardness and elastic modulus of TiO2 anodic films measured by instrumented indentation
Authors: Soares Paulo , Mikowski Alexandre , Lepienski Carlos M. , Santos Emanuel , Soares Glória A. , Filho Vitoldo Swinka , Kuromoto Neide K.
Published: August 2007

The aim of this work was to investigate the mechanical properties of the titanium anodic films (TiO2) produced by anodic oxidation under galvanostatic conditions, using a 1.4M phosphoric acid electrolyte, with different current densities (J) on commercially pure titanium (cp‐Ti). The morphology of the oxide films were observed by scanning electron microscopy (SEM), whereas the composition of the film was determined by Raman spectroscopy. Porosity, average roughness (Ra) and thickness of the TiO2 films increased with the applied J. Hardness and elastic modulus were measured by instrumented indentation technique, and the influence of the substrate was corrected using analytical models. The anodic films presented higher hardness and lower elastic modulus values compared with the cp‐Ti. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
The p53 mutation “gradient effect” and its clinical implications
Authors: Zambetti Gerard P.
Published: August 2007

The p53 tumor suppressor‐signaling pathway is inactivated in most human cancers. Depending on how p53 is targeted during tumorigenesis impacts whether partial or full tumor suppressor activity is lost. The degree of remaining p53 activity, if any, intuitively impacts the tumor phenotype. This review focuses on recent findings from human cancer studies and genetically engineered mouse models to highlight a p53 functional “gradient effect” and its clinical implications. J. Cell. Physiol. 213: 370–373, 2007. © 2007 Wiley‐Liss, Inc.
Akt kinase targets association of CBP with SMAD 3 to regulate TGFβ‐induced expression of plasminogen activator inhibitor‐1
Authors: Das Falguni , Ghosh‐Choudhury Nandini , Venkatesan Balachandar , Li Xiaonan , Mahimainathan Lenin , Choudhury Goutam Ghosh
Published: August 2007

Transforming growth factor‐β (TGFβ) controls expression of plasminogen activator inhibitor type 1 (PAI‐1), which regulates degradation of extracellular matrix proteins in fibrotic diseases. The TGFβ receptor‐specific Smad 3 has been implicated in the PAI‐1 expression. The mechanism by which non‐Smad signaling contributes to this process is not known. We studied the cross‐talk between Smad 3 and PI 3 kinase/Akt signaling in TGFβ‐induced PAI‐1 expression in renal mesangial cells. Inhibition of PI 3 kinase and Akt kinase blocked TGFβ‐ and Smad 3‐mediated expression of PAI‐1. In contrast, constitutively active PI 3 kinase and Akt kinase increased PAI‐1 expression, similar to TGFβ. Inhibition of PI 3 kinase and Akt kinase had no effect on TGFβ‐induced Smad 3 phosphorylation and its translocation to the nucleus. Notably, inhibition of PI 3 kinase‐dependent Akt kinase abrogated TGFβ‐induced PAI‐1 transcription, without affecting binding of Smad 3 to the PAI‐1 Smad binding DNA element. However, PI 3 kinase inhibition and dominant negative Akt kinase antagonized the association of the transcriptional coactivator CBP with Smad 3 in response to TGFβ, resulting in inhibition of Smad 3 acetylation. Together our findings identify TGFβ‐induced PI 3 kinase/Akt signaling as a critical regulator of Smad 3‐CBP interaction and Smad 3 acetylation, which cause increased PAI‐1 expression. J. Cell. Physiol. 214: 513–527, 2008. © 2007 Wiley‐Liss, Inc.
Comparative spermatology of selected polyclad flatworms (Platyhelminthes)
Authors: Liana Marcin K. , Litvaitis Marian K.
Published: August 2007

Sperm ultrastructure of four acotylean (Idioplana atlantica, Armatoplana leptalea, Styloplanocera fasciata, Melloplana ferruginea) and three cotylean polyclads (Pseudoceros bicolor, Phrikoceros mopsus, Enchiridium evelinae) was investigated. All spermatozoa are biflagellate, exhibiting a 9+“1” axoneme pattern. All acotylean axonemes originate and extend within the sperm shaft, and once exiting the shaft, remain attached to it. The flagella of all cotylean spermatozoa exit the shaft immediately and remain free. Structures shared by all species include: an elongated nucleus, in acotyleans located only in the posterior part of the shaft, whereas in cotyleans it extends along the entire sperm body; mitochondria along with small and large dense bodies arranged in a specific pattern; and a ring of microtubules that extends along the entire sperm shaft just beneath the cell membrane. A unique spermatozoon has been found in E. evelinae, where round vesicle‐like structures fill the anterior part of the nucleus, and a different type of large dense bodies is present. The spermatozoa of all studied species exhibit numerous characters (axoneme/flagella position, distribution and position of large and small dense bodies, of mitochondria, presence of nuclear vesicles) that may be of phylogenetic value at the family and higher taxonomic levels. J. Morphol., 2007. © 2007 Wiley‐Liss, Inc.
Immunohistochemical localization of adrenergic receptors in the rat organ of corti and spiral ganglion
Authors: Khan Khalid M. , Drescher Marian J. , Hatfield James S. , Ramakrishnan Neeliyath A. , Drescher Dennis G.
Published: August 2007

α1‐, β1‐, and β2‐adrenergic receptors (ARs), which mediate responses to adrenergic input, have been immunohistochemically identified within the organ of Corti and spiral ganglion with polyclonal antibodies of established specificity. α1‐AR was immunolocalized to sites overlapping supranuclear regions of inner hair cells as well as to nerve fibers approaching the base of inner hair cells, most evident in the basal cochlear turn. A similar preponderance across cochlear turns for α1‐AR in afferent cell bodies in the spiral ganglion pointed to type I afferent dendrites as a possible neural source of α1‐AR beneath the inner hair cell. Foci of immunoreactivity for α1‐AR, putatively neural, were found overlapping supranuclear and basal sites of outer hair cells for all turns. β1‐ and β2‐ARs were immunolocalized to sites overlapping apical and basal poles of the inner and outer hair cells, putatively neural in part, with immunoreactive nerve fibers observed passing through the habenula perforata. β1‐ and β2‐ARs were also detected in the cell bodies of Deiters' and Hensen's cells. Within the spiral ganglion, β1‐ and β2‐ARs were immunolocalized to afferent cell bodies, with highest expression in the basal cochlear turn, constituting one possible neural source of receptors within the organ of Corti, specifically on type I afferent dendrites. β1‐ and β2‐ARs in Hensen's and Deiters' cells would couple to Gαs, known to be present specifically in the supporting cells. Overall, adrenergic modulation of neural/supporting cell function within the organ of Corti represents a newly considered mechanism for modifying afferent signaling. © 2007 Wiley‐Liss, Inc.
N‐methyl‐D‐aspartate autoreceptors respond to low and high agonist concentrations by facilitating, respectively, exocytosis and carrier‐mediated release of glutamate in rat hippocampus
Authors: Luccini Elisa , Musante Veronica , Neri Elisa , Raiteri Maurizio , Pittaluga Anna
Published: August 2007

Presynaptic NMDA autoreceptors regulating glutamate release have rarely been investigated. High‐micromolar N‐methyl‐D‐aspartate (NMDA) was reported to elicit glutamate release from hippocampal synaptosomes in a Ca2+‐independent manner by reversal of excitatory amino acid transporters. The aim of this work was to characterize excitatory amino acid release evoked by low‐micromolar NMDA from glutamatergic axon terminals. Purified rat hippocampal synaptosomes were prelabelled with [3H]D‐aspartate ([3H]D‐ASP) and exposed in superfusion to varying concentrations of NMDA in the presence of 1 μM glycine. The release of [3H]D‐ASP and also that of endogenous glutamate provoked by 10 μM NMDA were external Ca2+ dependent and sensitive to the NMDA channel blocker MK‐801 but insensitive to the glutamate transporter inhibitor DL‐TBOA, which, on the contrary, prevented the Ca2+‐independent release evoked by 100 μM NMDA. The NMDA (10 μM) response was blocked by 1 nM Zn2+ and 1 μM ifenprodil, compatible with the involvement of a NR1/NR2A/NR2B assembly, although the presence of two separate receptor populations, i.e., NR1/NR2A and NR1/NR2B, cannot be excluded. This response was strongly antagonized by submicromolar (0.01–1 μM) concentrations of kynurenic acid and was mimicked by quinolinic acid (1–100 μM) plus 1 μM glycine. Finally, the HIV‐1 protein gp120 potently mimicked the NMDA coagonists glycine and D‐serine, being significantly effective at 30 pM. In conclusion, glutamatergic nerve terminals possess NMDA autoreceptors mediating different types of release when activated by different agonist concentrations: low‐micromolar glutamate would potentiate glutamate exocytosis, whereas higher glutamate concentrations would also provoke carrier‐mediated release. © 2007 Wiley‐Liss, Inc.
Humidity parameters from temperature: test of a simple methodology for European conditions
Authors: Andersson‐Sköld Yvonne , Simpson David , Ødegaard Viel
Published: August 2007

Atmospheric water content is important for local and regional climate, and for chemical processes of soluble and solute species in the atmosphere. Further, vapour pressure deficit (D) is one of the key controls on the opening of stomata in plants and is thus an important force for evapotransporation, plant respiration and biomass production and for the uptake of harmful pollutants such as ozone through the stomata.

Most meteorological stations typically measure both temperature and relative humidity (RH). However, even if recorded at finer time resolution, it is usually the daily or often monthly means of RH which are published in climate reports. Unfortunately, such data cannot be used to obtain the changes in RH or vapour pressure deficit over the day, as this depends strongly on the diurnal temperature variation during the day and not upon the mean temperature.

Although RH typically changes significantly over the day, the ambient vapour pressure is often remarkably constant. Here a simple method to estimate diurnal vapour pressure is evaluated, based upon an assumed constant vapour pressure, and that recorded minimum temperatures approximate dew‐point temperatures. With a knowledge of only temperature, we will show that day to day estimates of vapour pressure, humidity and especially D, can be made with reasonable accuracy. This methodology is tested using meteorological data from 32 sites covering a range of locations in Europe. Such a simple methodology may be used to extract approximate diurnal curves of vapour pressures from published meteorological data which contains only minimum temperatures for each day, or where humidity data are not available. Copyright © 2007 Royal Meteorological Society
A Phase II safety and effect on time to tumor progression study of intratumoral light infusion technology using talaporfin sodium in patients with metastatic colorectal cancer
Authors: Kujundžić M. , Vogl T.J. , Stimac D. , Rustemović N. , Hsi R. Alex , Roh M. , Katičić M. , Cuenca R. , Lustig R.A. , Wang S.
Published: August 2007

Background and Objectives

Twenty‐seven patients with refractory liver metastases from colorectal cancer took part in a Phase II study of the light infusion technology™ (Litx™) light‐activated drug/device system to assess safety and evaluate time to tumor progression (TTP).

Methods

Litx™ consists of the light‐activated drug, talaporfin sodium (LS11), activated intratumorally by a catheter‐like array of light‐emitting diodes (LEDs). After placement of the array via ultrasound or computed tomography (CT) guidance, LS11 was administered intravenously, followed 15–60 min later by light infusion for 2.8 hr. Patients were assessed for adverse events and tumor response using physical examination, laboratory values, and CT scan evaluation over a period of 60 days.

Results

The observed occurrence of Litx™ treatment‐related adverse events was minimal and cumulative toxicity did not occur when combined with chemotherapy. Assessment of TTP and tumor response rate, although statistically non‐robust, suggest potential improvement.

Conclusions

The Litx™ system was shown to be safe for treating liver metastases from colorectal cancer and there was no cumulative toxicity when combined with standard systemic therapy. Preliminary assessments of TTP and tumor response rate justify further evaluation in a Phase III follow‐up study. J. Surg. Oncol. 2007;96:518–524. © 2007 Wiley‐Liss, Inc.
Intrathecal rituximab treatment for pediatric post‐transplant lymphoproliferative disorder of the central nervous system
Authors: van de Glind Gretha , de Graaf Siebold , Klein Christoph , Cornelissen Marlies , Maecker Britta , Loeffen Jan
Published: August 2007

Post‐transplant lymphoproliferative disorder (PTLD) in the central nervous system (CNS) has a poor prognosis. New therapeutic approaches should be explored. We report our experience with intrathecal administration of rituximab in a 10‐year‐old kidney allograft recipient with PTLD in the CNS. After standard treatment had failed, we tried to treat the patient by administering rituximab directly into the cerebral ventricle through an Omaya reservoir, in addition to conventional intrathecal and systemic chemotherapy. This strategy resulted in a disappearance of clinical symptoms and a negative positron emission tomogram. Intrathecal administration of rituximab may be a feasible approach in children with PTLD in the CNS. However, its specific role in our patient remains uncertain. Pediatr Blood Cancer 2008;50:886–888. © 2007 Wiley‐Liss, Inc.
The conformation of the extracellular binding domain of Death Receptor 5 in the presence and absence of the activating ligand TRAIL: A molecular dynamics study
Authors: Wassenaar Tsjerk A. , Quax Wim J. , Mark Alan E.
Published: August 2007

The Death Receptor 5 (DR5), a member of tumor necrosis factor receptor (TNFR) superfamily of receptors, triggers apoptosis (programmed cell death) when stimulated by its tridentate ligand TRAIL. Until recently it was generally assumed that the activation of DR5 resulted from the recruitment of three independent receptor units, leading to the trimerization of intracellular domains. However, there is mounting evidence to suggest that, in the absence of ligand, such cytokine receptors primarily reside as preformed complexes. In this work, molecular dynamics simulations of the TRAIL‐DR5 complex, the unbound receptor trimer and individual receptor monomers are compared to gain insight in the mechanism of activation. The results suggest that, in the absence of TRAIL, DR5 has a strong propensity to self‐associate and that this is primarily mediated through interactions of the membrane proximal domains. The association of the free receptors leads to a loss of the threefold symmetry found within the receptor‐ligand complex. The simulations suggest that the primary role of TRAIL is to induce threefold‐symmetry within the DR5 complex and to constrain the receptor to a specific conformation. The implications of this in terms of the mechanism by which the receptor switches from an inactive to an active state are discussed. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Operons and the effect of genome redundancy in deciphering functional relationships using phylogenetic profiles
Authors: Moreno‐Hagelsieb Gabriel , Janga Sarath Chandra
Published: August 2007

Phylogenetic profiles (PPs) are one of the most promising methods for predicting functional relationships by genomic context. The idea behind PPs is that if the products of two genes have a functional interdependence, the genes should both be either present or absent across genomes. One of the main problems with PPs is that evolutionarily close organisms tend to share a higher number of genes resulting in the overscoring of PP‐relatedness. The proper measure of the overscoring effect of evolutionary redundancy requires examples of both functionally related genes (positive gold standards) and functionally unrelated genes (negative gold standards). Since experimentally verified functional interactions are only available for a few model organisms, there is a need for an alternative to gold standards. The presence of operons (polycistronic transcription units formed of functionally related genes) in prokaryotic genomes offers such an alternative. Genes in operons are located next to each other in the same DNA strand, and thus their presence should result in a higher proportion of predicted functional interactions among adjacent genes in the same strand than among adjacent genes in opposite strands. Under the preceding principle, we present a confidence value (CV) designed for evaluating predictions of functional interactions obtained using PPs. We first show that the CV corresponds to a positive predictive value calculated using experimentally known operons and further validate operon predictions based on this CV in other organisms using available microarray data. Then, we use a fixed CV of 0.90 as a reference to compare PP predictions obtained using different nonredundant genome datasets filtered at varying thresholds of genomic similarity. Our results demonstrate that nonredundant genome datasets increase the number of high‐quality predictions by an average of 20%. Confidence values as those presented here should help compare other strategies and scoring systems to use phylogenetic profiles and other genomic context methods for predicting functional interactions. Proteins 2008. © 2007 Wiley‐Liss, Inc.
Exploring the role of large conformational changes in the fidelity of DNA polymerase β
Authors: Xiang Yun , Goodman Myron F. , Beard William A. , Wilson Samuel H. , Warshel Arieh
Published: August 2007

The relationships between the conformational landscape, nucleotide insertion catalysis and fidelity of DNA polymerase β are explored by means of computational simulations. The simulations indicate that the transition states for incorporation of right (R) and wrong (W) nucleotides reside in substantially different protein conformations. The protein conformational changes that reproduce the experimentally observed fidelity are significantly larger than the small rearrangements that usually accompany motions from the reactant state to the transition state in common enzymatic reactions. Once substrate binding has occurred, different constraints imposed on the transition states for insertion of R and W nucleotides render it highly unlikely that both transition states can occur in the same closed structure, because the predicted fidelity would then be many orders of magnitude too large. Since the conformational changes reduce the transition state energy of W incorporation drastically they decrease fidelity rather than increase it. Overall, a better agreement with experimental data is attained when the R is incorporated through a transition state in a closed conformation and W is incorporated through a transition state in one or perhaps several partially open conformations. The generation of free energy surfaces for R and W also allow us to analyze proposals about the relationship between induced fit and fidelity. Proteins 2008. © 2007 Wiley‐Liss, Inc.
The targets of CAPRI rounds 6–12
Authors: Janin Joël
Published: August 2007

Six protein–protein complexes and two homodimeric proteins involved in a variety of biological processes were offered as targets to CAPRI by crystallographers in Rounds 6–12. CAPRI predictor groups had to predict their structure by docking the free proteins, which they did with a degree of success that depended largely on the amplitude of the conformation changes. In one case at least, the prediction pointed to alternative possibilities of interactions in the crystal of a complex, showing that docking methods have value even when there is an experimental structure. Proteins 2007. © 2007 Wiley‐Liss, Inc.
Identification of wave‐like spatial structure in the SSVEP: Comparison of simultaneous EEG and MEG
Authors: Thorpe Samuel Garrett , Nunez Paul L. , Srinivasan Ramesh
Published: August 2007

Steady‐state visual‐evoked potentials/fields (SSVEPs/SSVEFs) are used in cognitive and clinical electroencephalogram (EEG) and magnetoencephalogram (MEG) studies because of their excellent signal‐to‐noise ratios and relative immunity to artifact. Steady‐state paradigms are also used to characterize preferred frequencies of dynamic neocortical processes. In this study, SSVEPs and SSVEFs were simultaneously recorded while subjects viewed checkerboard patterns alternating (black to white, white to black) with fixed driving frequency between 2 and 20 Hz. Distinct peaks in SSVEP/SSVEF power were observed in the theta (4–8 Hz) and upper alpha (10–14 Hz) bands. A distinct peak in SSVEP power was also observed in the beta band (between 15 and 20 Hz) which had no counterpart in the MEG. One‐dimensional spatial spectra indicate that distinct large‐scale source distributions contribute to SSVEP power in the upper alpha band in the form of long wavelength (λ>20 cm) traveling waves propagating from occipital to prefrontal electrodes. In the beta band, spatial spectra and SSVEF indicate that long‐wavelength source distributions over posterior and anterior regions form standing wave patterns. These results suggest that simple models of SSVEP based on a single dipole source in the occipital lobe are inadequate to explain the dynamic spatial patterns of SSVEP magnitude and phase. Theoretical models of SSVEP should include multiple local and distributed sources and exhibit both traveling and standing wave dynamics. Copyright © 2007 John Wiley & Sons, Ltd.
Effect of Perioperative Allogeneic Red Blood Cell Transfusion on the Immune‐Inflammatory Response After Colorectal Cancer Resection
Authors: Ydy Lenuce Ribeiro Aziz , Slhessarenko Natasha , de Aguilar‐Nascimento José Eduardo
Published: August 2007

Cytokines play an important role in the acute‐phase response to trauma. Few studies have analyzed the effects of allogeneic blood transfusion containing packed red blood cells (RBCs) on the early postoperative immune/inflammatory response after colorectal resection for cancer This study investigated whether allogeneic RBC transfusion influences the postoperative immune/inflammatory response of patients submitted to large bowel resection due to cancer. A total of 26 patients—15 men and 11 women, with a median age of 56.5 years (range 24–87 years)—were prospectively studied. Blood samples were obtained preoperatively and on the first and fourth postoperative days for C‐reactive protein (CRP), interleukin‐6 (IL‐6), and IL‐10 assays and for CD4 and CD8 lymphocyte counts. Transfused (≥3 and <3 units), and nontransfused patients were compared. Both IL‐6 and IL‐10 increased postoperatively in transfused patients (p < 0.01). The serum IL‐6 level was higher in patients receiving ≥3 units of RBCs (p < 0.01). CRP increased postoperatively unrelated to blood transfusion. The CD8 count decreased (p < 0.04) in transfused subjects, whereas CD4 decreased (p < 0.01) only in major‐transfusion patients. Perioperative allogeneic RBC transfusion enhances the inflammatory systemic response and decreased immunity in patients submitted to colorectal resection for cancer.