bluuebunny/crossref_metadata_2025 huggingface dataset:
The VarS/VarA two-component system modulates the activity of the Vibrio cholerae quorum-sensing transcriptional regulator HapR
Authors: Tsou Amy M. , Liu Zhi , Cai Tao , Zhu Jun
Published: March 2011

The human pathogen Vibrio cholerae uses quorum sensing to regulate the expression of a number of phenotypes, including virulence factor production, in response to changes in cell density. It produces small molecules called autoinducers that increase in concentration as cell density increases, and these autoinducers bind to membrane sensors once they reach a certain threshold. This binding leads to signalling through a downstream phosphorelay pathway to alter the expression of the transcriptional regulator HapR. Previously, it was shown that the VarS/VarA two-component system acts on a component of the phosphorelay pathway upstream of HapR to regulate HapR expression levels. Here, we show that in addition to this mechanism of regulation, VarS and VarA also indirectly modulate HapR protein activity. This modulation is mediated by the small RNA CsrB but is independent of the known quorum-sensing system that links the autoinducers to HapR. Thus, the VarS/VarA two-component system intersects with the quorum-sensing network at two levels. In both cases, the effect of VarS and VarA on quorum sensing is dependent on the Csr small RNAs, which regulate carbon metabolism, suggesting that V. cholerae may integrate nutrient status and cell density sensory inputs to tailor its gene expression profile more precisely to surrounding conditions.
Embedded elements in the IncPβ plasmids R772 and R906 can be mobilized and can serve as a source of diverse and novel elements
Authors: Petrovski Steve , Stanisich Vilma A.
Published: March 2011

IncP plasmids are important contributors to bacterial adaptation. Their phenotypic diversity is due largely to accessory regions located in one or two specific parts of the plasmid. The accessory regions are themselves diverse, as judged from sequenced plasmids mostly isolated from non-clinical sources. To further understand the diversity, evolutionary history and functional attributes of the accessory regions, we compared R906 and R772, focusing on the oriV–trfA accessory region. These IncPβ plasmids were from porcine and clinical sources, respectively. We found that the accessory regions formed potentially mobile elements, Tn510 (from R906) and Tn511 (from R772), that differed internally but had identical borders. Both elements appeared to have evolved from a TnAO22-like mer transposon that had inserted into an ancestral IncPβ plasmid and then accrued additional transposable elements and genes from various proteobacteria. Structural comparisons suggested that Tn510 (and a descendent in pB10), Tn511 and the mer element in pJP4 represent three lineages that evolved from the same widely dispersed IncPβ carrier. Functional studies on Tn511 revealed that its mer module is inactive due to a merT mutation, and that its aphAI region is prone to deletion. More significantly, we showed that by providing a suitable transposase gene in trans, the defective Tn510 and Tn511 could transpose intact or in part, and could also generate new elements (stable cointegrates and novel transposons). The ingredients for assisted transposition events similar to those observed here occur in natural microcosms, providing non-self-mobile elements with avenues for dispersal to new replicons and for structural diversification. This work provides an experimental demonstration of how the complex embedded elements uncovered in IncP plasmids and in other plasmid families may have been generated.
The role of two SARP family transcriptional regulators in regulation of the auricin gene cluster in Streptomyces aureofaciens CCM 3239
Authors: Novakova Renata , Rehakova Alena , Kutas Peter , Feckova Lubomira , Kormanec Jan
Published: March 2011

Two regulators, Aur1P and Aur1R, have been previously found to control expression of the aur1 polyketide gene cluster involved in biosynthesis of the angucycline-like antibiotic auricin in Streptomyces aureofaciens CCM 3239 in a cascade mechanism. Here, we describe the characterization of two additional regulatory genes, aur1PR2 and aur1PR3, encoding homologues of the SARP family of transcriptional activators that were identified in the upstream part of the aur1 cluster. Expression of both genes is directed by a single promoter, aur1PR2p and aur1Pr3p, respectively, induced in late exponential phase. Disruption of aur1PR2 in S. aureofaciens CCM 3239 had no effect on auricin production. However, the disruption of aur1PR3 dramatically reduced auricin compared with its parental wild-type strain. Transcription from the aur1Ap promoter, directing expression of the first biosynthetic gene in the auricin gene cluster, was similarly decreased in the S. aureofaciens CCM 3239 aur1PR3 mutant. Transcription from the aur1PR3p promoter increased in the S. aureofaciens CCM 3239 aur1R mutant strain, and the TetR family negative regulator Aur1R was shown to specifically bind the aur1PR3p promoter. These results indicate a complex regulation of the auricin cluster by the additional SARP family transcriptional activator Aur1PR3.
Silencing of Soybean Seed Storage Proteins Results in a Rebalanced Protein Composition Preserving Seed Protein Content without Major Collateral Changes in the Metabolome and Transcriptome
Authors: Schmidt Monica A. , Barbazuk W. Brad , Sandford Michael , May Greg , Song Zhihong , Zhou Wenxu , Nikolau Basil J. , Herman Eliot M.
Published: March 2011

The ontogeny of seed structure and the accumulation of seed storage substances is the result of a determinant genetic program. Using RNA interference, the synthesis of soybean (Glycine max) glycinin and conglycinin storage proteins has been suppressed. The storage protein knockdown (SP−) seeds are overtly identical to the wild type, maturing to similar size and weight, and in developmental ontogeny. The SP− seeds rebalance the proteome, maintaining wild-type levels of protein and storage triglycerides. The SP− soybeans were evaluated with systems biology techniques of proteomics, metabolomics, and transcriptomics using both microarray and next-generation sequencing transcript sequencing (RNA-Seq). Proteomic analysis shows that rebalancing of protein content largely results from the selective increase in the accumulation of only a few proteins. The rebalancing of protein composition occurs with small alterations to the seed’s transcriptome and metabolome. The selectivity of the rebalancing was further tested by introgressing into the SP− line a green fluorescent protein (GFP) glycinin allele mimic and quantifying the resulting accumulation of GFP. The GFP accumulation was similar to the parental GFP-expressing line, showing that the GFP glycinin gene mimic does not participate in proteome rebalancing. The results show that soybeans make large adjustments to the proteome during seed filling and compensate for the shortage of major proteins with the increased selective accumulation of other proteins that maintains a normal protein content.
HISTONE DEACETYLASE6 Interacts with FLOWERING LOCUS D and Regulates Flowering in Arabidopsis
Authors: Yu Chun-Wei , Liu Xuncheng , Luo Ming , Chen Chiayang , Lin Xiaodong , Tian Gang , Lu Qing , Cui Yuhai , Wu Keqiang
Published: March 2011

Histone acetylation and deacetylation play an important role in epigenetic controls of gene expression. HISTONE DEACETYLASE6 (HDA6) is a REDUCED POTASSIUM DEPENDENCY3-type histone deacetylase, and the Arabidopsis (Arabidopsis thaliana) hda6 mutant axe1-5 displayed a late-flowering phenotype. axe1-5/flc-3 double mutants flowered earlier than axe1-5 plants, indicating that the late-flowering phenotype of axe1-5 was FLOWERING LOCUS C (FLC) dependent. Bimolecular fluorescence complementation, in vitro pull-down, and coimmunoprecipitation assays revealed the protein-protein interaction between HDA6 and the histone demethylase FLD. It was found that the SWIRM domain in the amino-terminal region of FLD and the carboxyl-terminal region of HDA6 are responsible for the interaction between these two proteins. Increased levels of histone H3 acetylation and H3K4 trimethylation at FLC, MAF4, and MAF5 were found in both axe1-5 and fld-6 plants, suggesting functional interplay between histone deacetylase and demethylase in flowering control. These results support a scenario in which histone deacetylation and demethylation cross talk are mediated by physical association between HDA6 and FLD. Chromatin immunoprecipitation analysis indicated that HDA6 bound to the chromatin of several potential target genes, including FLC and MAF4. Genome-wide gene expression analysis revealed that, in addition to genes related to flowering, genes involved in gene silencing and stress response were also affected in hda6 mutants, revealing multiple functions of HDA6. Furthermore, a subset of transposons was up-regulated and displayed increased histone hyperacetylation, suggesting that HDA6 can also regulate transposons through deacetylating histone.
Biased amplification of human papillomavirus DNA in specimens containing multiple human papillomavirus types by PCR with consensus primers
Authors: Mori Seiichiro , Nakao Sari , Kukimoto Iwao , Kusumoto‐Matsuo Rika , Kondo Kazunari , Kanda Tadahito
Published: March 2011

Genotyping human papillomavirus (HPV) in clinical specimens is important because each HPV type has different oncogenic potential. Amplification of HPV DNA by PCR with the consensus primers that are derived from the consensus sequences of the L1 gene has been used widely for the genotyping. As recent studies have shown that the cervical specimens often contain HPV of multiple types, it is necessary to confirm whether the PCR with the consensus primers amplifies multiple types of HPV DNA without bias. We amplified HPV DNA in the test samples by PCR with three commonly used consensus primer pairs (L1C1/L1C2+C2M, MY09/11, and GP5+/6+), and the resultant amplicons were identified by hybridization with type‐specific probes on a nylon membrane. L1C1/L1C2+C2M showed a higher sensitivity than the other primers, as defined by the ability to detect HPV DNA, on test samples containing serially diluted one of HPV16, 18, 51, 52, and 58 plasmids. L1C1/L1C2+C2M failed to amplify HPV16 in the mixed test samples containing HPV16, and either 18 or 51. The three consensus primers frequently caused incorrect genotyping in the selected clinical specimens containing HPV16 and one or two of HPV18, 31, 51, 52, and 58. The data indicate that PCR with consensus primers is not suitable for genotyping HPV in specimens containing multiple HPV types, and suggest that the genotyping data obtained by such a method should be carefully interpreted. (Cancer Sci 2011; 102: 1223–1227)
The pharmacodynamic and pharmacokinetic profile of intranasal crushed buprenorphine and buprenorphine/naloxone tablets in opioid abusers
Authors: Middleton Lisa S. , Nuzzo Paul A. , Lofwall Michelle R. , Moody David E. , Walsh Sharon L.
Published: March 2011

Aims  Sublingual buprenorphine and buprenorphine/naloxone are efficacious opioid dependence pharmacotherapies, but there are reports of their diversion and misuse by the intranasal route. The study objectives were to characterize and compare their intranasal pharmacodynamic and pharmacokinetic profiles.

Design  A randomized, double‐blind, placebo‐controlled, cross‐over study.

Setting  An in‐patient research unit at the University of Kentucky.

Participants  Healthy adults (n = 10) abusing, but not physically dependent on, intranasal opioids.

Measurements  Six sessions (72 hours apart) tested five intranasal doses [0/0, crushed buprenorphine (2, 8 mg), crushed buprenorphine/naloxone (2/0.5, 8/2 mg)] and one intravenous dose (0.8 mg buprenorphine/0.2 mg naloxone for bioavailability assessment). Plasma samples, physiological, subject‐ and observer‐rated measures were collected before and for up to 72 hours after drug administration.

Findings  Both formulations produced time‐ and dose‐dependent increases on subjective and physiological mu‐opioid agonist effects (e.g. ‘liking’, miosis). Subjects reported higher subjective ratings and street values for 8 mg compared to 8/2 mg, but these differences were not statistically significant. No significant formulation differences in peak plasma buprenorphine concentration or time–course were observed. Buprenorphine bioavailability was 38–44% and Tmax was 35–40 minutes after all intranasal doses. Naloxone bioavailability was 24% and 30% following 2/0.5 and 8/2 mg, respectively.

Conclusions  It is difficult to determine if observed differences in abuse potential between intranasal buprenorphine and buprenorphine/naloxone are clinically relevant at the doses tested. Greater bioavailability and faster onset of pharmacodynamic effects compared to sublingual administration suggests a motivation for intranasal misuse in non‐dependent opioid abusers. However, significant naloxone absorption from intranasal buprenorphine/naloxone administration may deter the likelihood of intranasal misuse of buprenorphine/naloxone, but not buprenorphine, in opioid‐dependent individuals.
Inhibitors of the initiation of coagulation
Authors: Ott Ilka
Published: March 2011

Initiation of blood coagulation occurs mainly through tissue factor (TF) that becomes exposed to blood following vascular injury. Cell‐associated TF binds to the serine protease FVIIa and initiates a cascade of amplified zymogen activation reactions leading to thrombus formation. As TF‐FVIIa directed inhibitors might achieve anticoagulant efficacy without significantly interfering with normal haemostasis, the TF‐FVIIa complex is an interesting target in thrombosis‐related disease. Various approaches have been used to inhibit the TF‐FVIIa complex including active site‐inhibited FVIIa, TF antibodies, tissue factor pathway inhibitor (TFPI), naturally occurring inhibitors, peptide exosite inhibitors and active site inhibitors. Several experimental studies using these inhibitors have displayed promise. However, none of these TF/FVIIa inhibitors has reached clinical testing. Further studies are required to evaluate the clinical efficacy of these novel inhibitors.
Population pharmacokinetic analysis of sorafenib in patients with solid tumours
Authors: Jain Lokesh , Woo Sukyung , Gardner Erin R. , Dahut William L. , Kohn Elise C. , Kummar Shivaani , Mould Diane R. , Giaccone Giuseppe , Yarchoan Robert , Venitz Jürgen , Figg William D.
Published: March 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Sorafenib is a multikinase inhibitor with activity against B‐raf, C‐raf, VEGFR2, PDGFRβ and FGFR1.

• Sorafenib is clinically approved for the treatment of renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC).

• The pharmacokinetics (PK) of sorafenib are highly variable between subjects.

• Sorafenib exposure increases less than dose proportionally (likely due to limited solubility).

• Sorafenib undergoes enterohepatic recycling (EHC).

WHAT THIS STUDY ADDS

• This is the first study to characterize the PK of sorafenib using a model based on sorafenib's known disposition characteristics such as delayed/solubility‐limited GI absorption and EHC. The parameterization of the EHC model used a square wave function to describe the gall bladder emptying.

• This study evaluated the effect of baseline bodyweight, BSA, age, gender, liver function parameters, kidney function parameters and genotype with respect to CYP3A4*1B, CYP3A5*3C, UGT1A9*3 and UGT1A9*5 on sorafenib PK. No clinically important covariates were identified.

• This model can be used to simulate and explore alternative dosing regimens and to develop exposure–response relationships for sorafenib.

AIMS To characterize the pharmacokinetics (PK) of sorafenib in patients with solid tumours and to evaluate the possible effects of demographic, clinical and pharmacogenetic (CYP3A4*1B, CYP3A5*3C, UGT1A9*3 and UGT1A9*5) covariates on the disposition of sorafenib.

METHODS PK were assessed in 111 patients enrolled in five phase I and II clinical trials, where sorafenib 200 or 400 mg was administered twice daily as a single agent or in combination therapy. All patients were genotyped for polymorphisms in metabolic enzymes for sorafenib. Population PK analysis was performed by using nonlinear mixed effects modelling (NONMEM). The final model was validated using visual predictive checks and nonparametric bootstrap analysis.

RESULTS A one compartment model with four transit absorption compartments and enterohepatic circulation (EHC) adequately described sorafenib disposition. Baseline bodyweight was a statistically significant covariate for distributional volume, accounting for 4% of inter‐individual variability (IIV). PK model parameter estimates (range) for an 80 kg patient were clearance 8.13 l h−1 (3.6–22.3 l h−1), volume 213 l (50–1000 l), mean absorption transit time 1.98 h (0.5–13 h), fraction undergoing EHC 50% and average time to gall bladder emptying 6.13 h.

CONCLUSIONS Overall, population PK analysis was consistent with known biopharmaceutical/PK characteristics of oral sorafenib. No clinically important PK covariates were identified.
Oleanolic acid inhibits hypertrophic scarring in the rabbit ear model
Authors: Wei Y.-J. , Yan X.-Q. , Ma L. , Wu J.-G. , Zhang H. , Qin L.-P.
Published: March 2011

Background. Hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, results from an overproduction of collagen and excessive deposition of extracellular matrix. Although treatment with surgical excision or steroid hormones can modify the symptoms, numerous treatment-related complications have been described.

Aim. To investigate the effects of oleanolic acid (OA), a naturally occurring triterpenoid, on hypertrophic scarring in a rabbit ear model.

Methods. A rabbit ear model of hypertrophic scarring was used, with wounds produced with a biopsy punch. Oleanolic acid (2.5%, 5% and 10%) was applied once daily to the scars for 22 days. On postoperative day 28, the scars were excised, and the tissue used for histological examination and assays of the levels of collagens I and III, matrix metalloproteinase (MMP)-1 and transforming growth factor (TGF)-β1. The scar elevation index (SEI) was also determined.

Results. Treatment with different concentrations of oleanolic acid (OA) for 22 days significantly inhibited hypertrophic scarring in rabbit ear tissue. Levels of TGF-β1, collagen I and collagen III were significantly decreased and levels of MMP-1 significantly increased in the scar tissue. SEI was also significantly reduced. Histological findings showed significant amelioration of the scar tissue.

Conclusions. OA suppresses hypertrophic scarring in the rabbit ear model and may be an effective cure for human hypertrophic scarring.
Generalized granuloma annulare with open comedones in photoexposed areas
Authors: Bhushan P. , Aggarwal A. , Yadav R. , Baliyan V.
Published: March 2011

Granuloma annulare (GA) is a noninfectious necrobiotic granuloma, which can present as localized or generalized patterns. We present a case of generalized GA with multiple large open comedones over the lesions in a woman with hypothyroidism and diabetes mellitus. GA is associated with collagen and elastic-fibre damage, which may lead to loss of follicular support and resultant open comedone formation, analogous to solar elastosis or senile comedones. The rapid recovery of our patient after treatment with of oral hypoglycaemics supports the role of insulin resistance as a predisposing factor for GA.
Study of enrofloxacin and flumequine residues depletion in eggs of laying hens after oral administration
Authors: CORNEJO J. , LAPIERRE L. , IRAGÜEN D. , CORNEJO S. , CASSUS G. , RICHTER P. , SAN MARTÍN B.
Published: March 2011

Cornejo, J., Lapierre, L., Iragüen, D., Cornejo, S., Cassus, G., Richter, P., San Martín, B. Study of enrofloxacin and flumequine residues depletion in eggs of laying hens after oral administration. J. vet. Pharmacol. Therap. 35, 67–72.

Two groups of laying hens (each n = 12) were administered 10 mg/kg enrofloxacin (ENRO) (group A) or 26.6 mg/kg flumequine (FLU) (group B) by gastric catheter daily for five consecutive days. A third group (n = 6) was untreated controls. Eggs were collected from day one of treatment and up to 30 days after withdrawal of the drug. Egg white and yolk from each egg were separated, and ENRO, its metabolite ciprofloxacin (CIP) and FLU residues were analysed by a high‐performance liquid chromatography method with fluorescence detection. The sum of ENRO and CIP was detectable in egg white on the first day of treatment in high‐level concentrations (2007.7 μg/kg) and remained steady during administration. In egg yolk, residues were detectable at day one in lower concentrations (324.4 μg/kg), increasing to the end of treatment. After treatment, these residues decreased and were detectable up to day 8 in egg white, and day 10 in yolk. FLU residues during drug administration in white were detectable in high concentrations from day one to five (6788.4–6525.9 μg/kg), and in yolk, concentrations were lower during administration (629.6–853.9 μg/kg). After drug withdrawal, FLU residues remained longer in egg white (30 days) than in yolk (26 days). For both drugs, differences of concentrations between matrices were significant.
Reprogramming the infection mechanism of a filamentous phage
Authors: Lorenz Stefan H. , Schmid Franz X.
Published: March 2011

When they infect Escherichia coli cells, the filamentous phages IF1 and fd first interact with a pilus and then target TolA as their common receptor. They use the domains N2 and N1 of their gene‐3‐proteins (G3P) for these interactions but differ in the mechanism of infection. In G3P of phage IF1, N1 and N2 are independent modules that are permanently binding‐active. G3P of phage fd is usually in a closed state in which N1 and N2 are tightly associated. The TolA binding site is thus inaccessible and the phage incompetent for infection. Partial unfolding and prolyl isomerization must occur to abolish the domain interactions and expose the TolA binding site. This complex mechanism of phage fd could be changed to the simple infection mechanism of phage IF1 by reprogramming its G3P following physicochemical rules of protein stability. The redesigned phage fd was robust and as infectious as wild‐type phage fd.
Alanyl‐phosphatidylglycerol synthase: mechanism of substrate recognition during tRNA‐dependent lipid modification in Pseudomonas aeruginosa
Authors: Hebecker Stefanie , Arendt Wiebke , Heinemann Ilka U. , Tiefenau Jana H. J. , Nimtz Manfred , Rohde Manfred , Söll Dieter , Moser Jürgen
Published: March 2011

Bacterial lipid homeostasis plays an important role for the adaptation to changing environments and under conditions of antimicrobial treatment. The tRNA‐dependent aminoacylation of the phospholipid phosphatidylglycerol catalysed by aminoacyl‐phosphatidylglycerol synthases was shown to render various organisms less susceptible to antibacterial agents. Therefore, this type of enzyme might provide a new target to potentiate the efficacy of existing antimicrobials. This study makes use of the Pseudomonas aeruginosa alanyl‐phosphatidylglycerol synthase to identify the minimal core domain of this transmembrane protein, which is capable of alanyl‐phosphatidylglycerol biosynthesis. Using this catalytic fragment we established a reliable activity assay that was used to study the enzymatic mechanism by analysing an overall of 33 mutant proteins in vitro. Substrate recognition was analysed by using aminoacylated microhelices as analogues of the natural tRNA substrate. The enzyme even tolerated mutated versions of this minimal substrate, which indicates that neither the intact tRNA, nor the individual sequence of the acceptor stem is a determinant for substrate recognition. Furthermore, the analysis of derivatives of phosphatidylglycerol indicated that the polar head group of the phospholipid is specifically recognized by the enzyme, whereas modification of an individual fatty acid or even the deletion of a single fatty acid did not abolish A‐PG synthesis.
Anti‐activator QslA defines the quorum sensing threshold and response in Pseudomonas aeruginosa
Authors: Seet Qihui , Zhang Lian‐Hui
Published: March 2011

Quorum sensing (QS) in a bacterial population is activated when extracellular concentration of QS signal reaches a threshold, but how this threshold is determined remains largely unknown. In this study, we report the identification and characterization of a novel anti‐activator encoded by qslA in Pseudomonas aeruginosa. The null mutation of qslA elevated AHL‐dependent QS and PQS signalling, increased the expression of QS‐dependent genes, and enhanced the virulence factor production and pathogenicity. We further present evidence that modulation of QS by QslA is due to protein–protein interaction with LasR, which prevents LasR from binding to its target promoter. QslA also influences the threshold concentration of QS signal needed for QS activation; in the absence of qslA, QS is activated by nine times less N‐3‐oxo‐dodecanoyl‐homoserine lactone (3‐oxo‐C12‐HSL) than that in wild type. The findings from this study depict a new mechanism that governs the QS threshold in P. aeruginosa.
The Aspergillus nidulans CENP‐E kinesin motor KipA interacts with the fungal homologue of the centromere‐associated protein CENP‐H at the kinetochore
Authors: Herrero Saturnino , Takeshita Norio , Fischer Reinhard
Published: March 2011

Chromosome segregation is an essential process for nuclear and cell division. The microtubule cytoskeleton, molecular motors and protein complexes at the microtubule plus ends and at kinetochores play crucial roles in the segregation process. Here we identified KatA (KipAtarget protein, homologue of CENP‐H) as a kinesin‐7 (KipA, homologue of human CENP‐E) interacting protein in Aspergillus nidulans. KatA located at the kinetochore during the whole cell cycle and colocalized with KipA and partially with the putative microtubule polymerase AlpA (XMAP215) during mitosis. Deletion of katA was lethal at 37°C and caused severe growth and morphology defects at room temperature. KipA was shown before to play an important role in growth directionality determination and our new results suggest a second function of KipA in the interaction between the microtubule plus ends and the kinetochores during mitosis.
Leaf δ18O of remaining trees is affected by thinning intensity in a semiarid pine forest
Authors: MORENO‐GUTIÉRREZ CRISTINA , BARBERÁ GONZALO G. , NICOLÁS EMILIO , DE LUIS MARTÍN , CASTILLO VÍCTOR M. , MARTÍNEZ‐FERNÁNDEZ FAUSTINO , QUEREJETA JOSÉ I.
Published: March 2011

Silvicultural thinning usually improves the water status of remaining trees in water‐limited forests. We evaluated the usefulness of a dual stable isotope approach (δ13C, δ18O) for comparing the physiological performance of remaining trees between forest stands subjected to two different thinning intensities (moderate versus heavy) in a 60‐year‐old Pinus halepensis Mill. plantation in semiarid southeastern Spain. We measured bulk leaf δ13C and δ18O, foliar elemental concentrations, stem water content, stem water δ18O (δ18Ostem water), tree ring widths and leaf gas exchange rates to assess the influence of forest stand density on tree performance. Remaining trees in low‐density stands (heavily thinned) showed lower leaf δ18O, and higher stomatal conductance (gs), photosynthetic rate and radial growth than those in moderate‐density stands (moderately thinned). By contrast, leaf δ13C, intrinsic water‐use efficiency, foliar elemental concentrations and δ18Ostem water were unaffected by stand density. Lower foliar δ18O in heavily thinned stands reflected higher gs of remaining trees due to decreased inter‐tree competition for water, whereas higher photosynthetic rate was largely attributable to reduced stomatal limitation to CO2 uptake. The dual isotope approach provided insight into the early (12 months) effects of stand density manipulation on the physiological performance of remaining trees.
Anatomy of an Upper Triassic continental to marginal‐marine system: the mixed siliciclastic–carbonate Travenanzes Formation (Dolomites, Northern Italy)
Authors: BREDA ANNA , PRETO NEREO
Published: March 2011

The Travenanzes Formation is a terrestrial to shallow‐marine, siliciclastic–carbonate succession (200 m thick) that was deposited in the eastern Southern Alps during the Late Triassic. Sedimentary environments and depositional architecture have been reconstructed in the Dolomites, along a 60 km south–north transect. Facies alternations in the field suggest interfingering between alluvial‐plain, flood‐basin and shallow‐lagoon deposits, with a transition from terrestrial to marine facies belts from south to north. The terrestrial portion of the Travenanzes Formation consists of a dryland river system, characterized by multicoloured floodplain mudstones with scattered conglomeratic fluvial channels, merging downslope into small ephemeral streams and sheet‐flood sandstones, and losing their entire discharge subaerially before the shoreline. Calcic and vertic palaeosols indicate an arid/semi‐arid climate with strong seasonality and intermittent discharge. The terrestrial/marine transition shows a coastal mudflat, the flood basin, which is usually exposed, but at times is inundated by both major river floods and sea‐water storm surges. Locally coastal sabkha deposits occur. The marine portion of the Travenanzes Formation comprises carbonate tidal‐flat and shallow‐lagoon deposits, characterized by metre‐scale shallowing‐upward peritidal cycles and subordinate intercalations of dark clays from the continent. The depositional architecture of the Travenanzes Formation suggests an overall transgressive pattern organized in three carbonate–siliciclastic cycles, corresponding to transgressive–regressive sequences with internal higher‐frequency sedimentary cycles. The metre‐scale sedimentary cyclicity of the Travenanzes Formation continues without a break in sedimentation into the overlying Dolomia Principale. The onset of the Dolomia Principale epicontinental platform is marked by the exhaustion of continental sediment supply.
Lifetime cigarette smoking is associated with striatal volume measures
Authors: Das Debjani , Cherbuin Nicolas , Anstey Kaarin J. , Sachdev Perminder S. , Easteal Simon
Published: March 2011

Nicotine, the primary addictive component of tobacco, affects the mammalian brain. Smokers' brains have smaller cortical grey matter volumes and/or lower densities compared with non‐smokers'. Differences in subcortical structures like the striatum are however, less clear. A high concentration of nicotinic receptors makes the striatum a potential target for nicotine. In addition, striatal nuclei are essential components of the reward/reinforcement pathway involved in addiction. The aim of this study was to explore the relationship between striatal nuclei (caudate, putamen and nucleus accumbens area) volumes and lifetime smoking in a large community‐based sample of ‘young–old’ individuals. Brain volumes were measured using a semi‐automated method in 315 participants aged 64–70 years who were selected from a larger randomly sampled cohort and who consented to a magnetic resonance imaging scan. Multiple regression analysis was used to assess the relationship between striatal volumes and cigarette smoking measures while controlling for age, sex, intracranial and total brain volumes and general physical and mental health measures. Greater lifetime use of cigarettes (measured in pack‐years) was associated with smaller left nucleus accumbens area volume (P = 0.018) and larger left putamen volume (P = 0.025). Greater putaminal volume was also associated with a lower age at smoking initiation (P = 0.004). In this generally healthy cohort, lifetime use of cigarettes is significantly associated with striatal volume measures. These changes could indicate predisposing factors for nicotine addiction, or an effect of chronic nicotine exposure or a combination of both.
Sigma‐1 receptor function is critical for both the discriminative stimulus and aversive effects of the kappa‐opioid receptor agonist U‐50488H
Authors: Mori Tomohisa , Yoshizawa Kazumi , Nomura Mutsuko , Isotani Kana , Torigoe Kazuhiro , Tsukiyama Yoshi , Narita Minoru , Suzuki Tsutomu
Published: March 2011

The present study was undertaken to identify possible similarities between the effects of kappa‐opioid receptor agonist, N‐methyl‐D‐aspartate‐receptor antagonist, and sigma receptor agonist on the discriminative stimulus effects of U‐50488H, and the possible involvement of sigma receptors in the discriminative stimulus and aversive effects of U‐50488H. The kappa‐opioid receptor agonist U‐50488H produced significant place aversion as measured by the conditioned place preference procedure, and this effect was completely abolished by treatment with the putative sigma‐1 receptor antagonist NE‐100. In addition, phencyclidine (+)‐SKF‐10047 and (+)‐pentazocine, which are sigma receptor agonists, generalized to the discriminative stimulus effects of U‐50488H in rats that had been trained to discriminate between U‐50488H (3.0 mg/kg) and saline. Furthermore, NE‐100 significantly attenuated the discriminative stimulus effects of U‐50488H and the U‐50488H‐like discriminative stimulus effects of phencyclidine. These results suggest that the sigma‐1 receptor is responsible for both the discriminative stimulus effects and aversive effects of U‐50488H.
Ghrelin system in alcohol‐dependent subjects: role of plasma ghrelin levels in alcohol drinking and craving
Authors: Leggio Lorenzo , Ferrulli Anna , Cardone Silvia , Nesci Antonio , Miceli Antonio , Malandrino Noemi , Capristo Esmeralda , Canestrelli Benedetta , Monteleone Palmiero , Kenna George A. , Swift Robert M. , Addolorato Giovanni
Published: March 2011

Animal studies suggest that the gut‐brain peptide ghrelin plays an important role in the neurobiology of alcohol dependence (AD). Human studies show an effect of alcohol on ghrelin levels and a correlation between ghrelin levels and alcohol craving in alcoholics.

This investigation consisted of two studies. Study 1 was a 12‐week study with alcohol‐dependent subjects, where plasma ghrelin determinations were assessed four times (T0‐T3) and related to alcohol intake and craving [Penn Alcohol Craving Score (PACS) and Obsessive Compulsive Drinking Scale (OCDS)]. Serum growth hormone levels and assessment of the nutritional/metabolic status were also performed. Study 2 was a pilot case‐control study to assess ghrelin gene polymorphisms (Arg51Gln and Leu72Met) in alcohol‐dependent individuals. Study 1 showed no significant differences in ghrelin levels in the whole sample, while there was a statistical difference for ghrelin between non‐abstinent and abstinent subjects. Baseline ghrelin levels were significantly and positively correlated with the PACS score at T1 and with all craving scores both at T2 and T3 (PACS, OCDS, obsessive and compulsive OCDS subscores). In Study 2, although there was a higher frequency of the Leu72Met ghrelin gene polymorphism in alcohol‐dependent individuals, the distribution between healthy controls and alcohol dependent individuals was not statistically significant.

This investigation suggests that ghrelin is potentially able to affect alcohol‐seeking behaviors, such as alcohol drinking and craving, representing a new potential neuropharmacological target for AD.
Caspase recruitment domain 15 gene haplotypes in sarcoidosis
Authors: Pabst S. , Golebiewski M. , Herms S. , Karpushova A. , Díaz‐Lacava A. , Walier M. , Zimmer S. , Cichon S. , Wienker T. F. , Nöthen M. M. , Nickenig G. , Meyer R. , Skowasch D. , Grohé C.
Published: March 2011

Sarcoidosis is a systematic granulomatous disorder. Genetic susceptibility could play a central role in the disease development and progression. In this study, we investigated whether caspase recruitment domain 15 (CARD15) gene haplotypes are associated with the onset or the clinical course of sarcoidosis. Three hundred Caucasian sarcoidosis patients and 381 matched controls were included. Eight haplotype‐tagging single nucleotide polymorphisms (SNPs) in the CARD15 gene were examined by mass spectrometry‐based SNP genotyping. By haplotype analysis, mutations located in between tested SNPs can also be identified. Therefore, we can conclude that there is no association between the CARD15 gene and the development or a special phenotype of sarcoidosis in our cohort.
Identification of a novel HLA‐B*52 allele in a Brazilian individual: B*52:21
Authors: Veiga T. R. , Rampim G. F. , Gerbase‐DeLima M.
Published: March 2011

HLA‐B*52:21 differs from the closest, HLA‐B*52:01:02, by two nucleotides (CTG →TGG), leading to an amino acid substitution from Leu to Trp at codon 156.
An ankyrin repeat protein is involved in anthocyanin biosynthesis in Arabidopsis
Authors: Yoo Jihye , Shin Dong Ho , Cho Man‐Ho , Kim Tae‐Lim , Bhoo Seong Hee , Hahn Tae‐Ryong
Published: March 2011

The ankyrin domain is one of the most common protein motifs in eukaryotic proteins. Repeated ankyrin domains are ubiquitous and their mediation of protein–protein interactions is involved in a number of physiological and developmental responses such as the cell cycle, signal transduction and cell differentiation. A novel putative phytochrome‐interacting ankyrin repeat protein 2 (PIA2) containing three repeated ankyrin domains was identified in Arabidopsis. An in vitro pull‐down and phosphorylation assay revealed that PIA2 is phosphorylated and interacts directly with oat phytochrome A. The N‐terminal domain of PIA2 was specifically phosphorylated, whereas interactions between the domains of PIA2 and phytochrome A had no Pr/Pfr preference. PIA2 was ubiquitously expressed in most tissues and was localized in both the nucleus and the cytoplasm independent of treatment with light of specific wavelengths. Anthocyanin accumulation in seedlings grown under far‐red light, a typical phenotype of wild‐type plants, was reduced in a loss‐of‐function mutant of PIA2 (pia2), whereas anthocyanin accumulation was increased in an overexpressing plant (PIA2‐OX). The gene expression of UDP‐flavonoid‐3′‐glucosyl‐transferase (UF3GT), a major enzyme in the anthocyanin biosynthesis processes, was decreased in pia2 knockout plants suggesting that decreased anthocyanin was because of the decreased expression of UF3GT. Our results suggest that PIA2 plays a role in the anthocyanin biosynthesis during seedling development as a novel phytochrome‐interacting protein.
The nuclear proteins in the liver of rabbits with an inherited motorial failure
Authors: Pałyga J. , Zelník J. , Luboń H. , Kołątaj A.
Published: March 2011

The composition and electrophoretic patterns of nuclear sap and chromatin proteins from the liver of normal and genetically immobilized rabbits were compared. It was found that RNA content and the amount of some nonhistone proteins changed in defective animals. These variations may result from genetic differences between normal rabbits and rabbits with an inborn motorial insufficiency or may appear in consequence of the effect of limb paresis on the liver metabolism.

Die Kernproteine in der Leber von Kaninchen mit genetischem Bewegungsdefekt

Die Zusammensetzung und das elektrophoretische Muster des Kernsaftes und der Kernproteine aus der Leber normaler und genetisch immobilisierter Kaninchen werden verglichen. Es zeigt sich, daß der RNS‐Gehalt und die Menge einiger Nicht‐Histonproteine in defekten Tieren sich geändert hat. Diese Variabilität kann von genetischen Unterschieden zwischen normalen und Kaninchen mit angeborener Bewegungsinsuffizienz herrühren oder kann eine Folge der Wirkung der Lähmung der Extremitäten auf den Lebermetabolismus darstellen.

Les protéines nucléaires dans le foie de lapins avec défaut moteur génétique

Les auteurs ont comparés la composition et le modèle éléctrophorétique du suc nucléaire et des protéines nucléaires du foie de lapins normaux et génétiquement immobilisés. On a observé que la teneur ARN et la quantité de quelques protéines non‐histones changeaient dans les animaux défectifs. Ces variabilités peuvent résulter des différences génétiques entre lapins normaux et lapins avec insuffisance motrice congénitale ou peuvent représenter la suite de l'effet de paralysie des extrémités sur le métabolisme du foie.

Proteínas nucleares en el hígado del conejo con defectos genéticos motores

Fueron comparadas la composición y los patrones electroforeticos de proteínas nucleares del fluido y cromatina desde el hígado de conejos normales y conejos geneticamente paralíticos. Fue encontrado que el contenido de RNA y la cantidad de algunas proteínas no‐histonas, cambían en los animales con el defecto. Esta variabilidad puede resultar de las diferencias genéticas en los conejos normales y conejos con insuficiencia motora al nacimiento o puede aparecer como consecuencia del efecto paralítico en las extremidades debido al metabolismo hepático.
BUCHBESPRECHUNGEN
Authors: Sambraus H.
Published: March 2011

Smyth, D. H.: Alternativen zu Tierversuchen. Deutsche Ausgabe, übersetzt und herausgegeben von A. Spiegel.

Dawkins, Marian Stamp: Leiden und Wohlbefinden bei Tieren – Ein Beitrag zu Fragen der Tierhaltung und des Tierschutzes.
Effect of the size of the class of comparison on the accuracy of a sire's evaluation
Authors: Ojala M. , Syväjärvi J. , Hellman T.
Published: March 2011

The effect of the size of the fixed class of comparison on the accuracy of a dairy sire's evaluation was investigated at different levels of progeny group sizes. Using simulated data for fat corrected milk production records, the great impact of the size of a progeny group on the accuracy of a sire's evaluation was verified. The accuracy of a sire's predicted transmitting ability improved with increasing size of the class of comparison. A substantial improvement in the accuracy of a sire's evaluation was observed when the size of the class of comparison increased from 2 to 3 records.

Effet du magnitude des classes sur l'exactitude de l'évaluation des pères

L'effet du magnitude d'une classe comparative fixe sur l'exactitude de l'évaluation d'un taureau reproducteur a été examiné pour des groupes de descendance de numéraux différents. La grande influence des groupes de descendance sur l'exactitude de l'évaluation du taureau a été vérifiée en utilisant des dates simulées corrigées pour la graisse de la production laitière. L'exactitude de la performance héréditaire prédite d'un père s'améliorait avec l'augmentation de numéraux de la classe comparative. Une amélioration essentielle de l'exactitude a été observée lorsque le magnitude de la classe comparative augmentait de deux à trois.

Efecto del tamaño de las clases de comparación sobre la exactitud de la evaluación paterna

Fue investigada para grupos de progenies de diferentes tamanõs, el efecto del tamaño de las clases fijas de comparación sobre la exactitud de la evaluación paterna en ganado lechero. Fue verificado, usando datos simulados para grasa en la leche corregida, el gran impacto del tamaño de los grupos de progenies sobre la exactitud en la evaluación de un padre. La exactitud de la habilidad transmitiva predicha de un padre aumenta al aumentar el tamoño de las clases de comparación. Fue observado un sustancial progreso en la exactitud de la evaluación de padres cuando el tamaño de las clases de comparación aumenta de 2 a 3 registros.

Wirkung der Klassengróße auf die Genauigkeit der Vatertierbewertung

Die Wirkung der Größe einer gegebenen Vergleichsklasse auf die Genauigkeit der Bewertung eines Zuchtstieres wurde für verschiedene Größen von Nachkommengruppen untersucht. Unter Verwendung simulierter Daten für fettkorrigierte Milch wurde der erhebliche Einfluß größerer Nachkommengruppen auf die Genauigkeit der Stierbewertung verifiziert. Die Genauigkeit der vorausgeschätzten Vererbungsleistung eines Vatertieres steigt mit steigender Größe der Vergleichsgruppenklasse. Eine wesentliche Verbesserung der Genauigkeit wurde beobachtet bei Steigerung der Vergleichsgruppe von zwei auf drei.
Index selection efficiency with continuous and discontinuous traits
Authors: Cue R. I. , Hayes J. F.
Published: March 2011

A simplified method for examining the efficiency of selection indices for a mixture of all‐or‐none traits and continuous traits was proposed. It was shown that by a suitable transformation, analytical solutions are possible, and that the proportion of the response due to particular traits may be easily calculated.

Efficience des indices de selection des caractères continues et binaires

Une methode simplifiée a éte proposé pour examiner d'efficience des indices de sélection quand il y a une mélange des caractères continues et binaires. Il est demontré qu'il est possible d'obtenir des solutions analytiques par une transformation appropriée, et que la proportion de la reponse causée par un caractère peut ètre calculé très facilement.

Eficiencia del Indice de Selección en características con distribución continua y discontinua

Es propuesto un método simplificado para exáminar la eficiencia del Indice de Selección para una mezcla de características de distribución continua y discontinua. Se demuestra que a traves de adecuada transformación, son posibles soluciones análiticas y que la proporción de la respuesta debido a las características particulares puede ser facilmente calculada.

Index‐Selektion bei kontinuierlich und diskontinuierlich verteilten Merkmalen

Eine vereinfachte Methode der Prüfung der Effizienz der Selektionsindizes für eine Mischung von kontinuierlichen und Alles‐oder‐Nichts Merkmalen wird vorgeschlagen. Es wird gezeigt, daß durch entsprechende Transformation analytische Lösungen möglich sind. Der Anteil des Selektionserfolges, der auf bestimmte Merkmale zurückgeht, kann leicht berechnet werden.