bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of PI 3‐kinase p110β in AKT signally, cell survival, and proliferation in human prostate cancer cells
Authors: Hill Karen M. , Kalifa Sara , Das Jharna R. , Bhatti Tahira , Gay Martha , Williams Danielle , Taliferro‐Smith LaTonia , De Marzo Angelo M. 
Published: January 2010

AbstractBACKGROUNDClass IA PI 3‐kinases produce phosphatidylinositol (3,4,5)‐trisphosphate (PIP3). PIP3 is bound by AKT which facilities its activation by PDK1. Activated AKT promotes cell survival and stimulates cell proliferation. Class IA PI 3‐kinases are heterodimers consisting of a regulatory subunit p85 and a catalytic subunit p110. The p110α isoform has been shown to be mutated in a number of tumor types. A number of recent studies suggest that the p110β isoform may be functionally relevant in prostate cancer. In this study we extend this work to include the examination of the expression and functional properties of p110α and p110β in three different prostate cancer cell lines, DU145, LNCaP, PC3, as well as the non‐tumorigenic but immortalized RWPE1 prostate epithelial cell line.METHODSWestern blot analysis was used to measure protein expression and quantitative real‐time PCR was used to measure mRNA levels. After targeted knockdown using isoform‐specific siRNAs to reduce PI 3‐kinase p110α or p110β isoform expression, we measured downstream signally events such as phosphorylation of AKT, ERK 1/2, PDK, and FOXO, as well as biological consequences such as changes in apoptosis, and alterations in cell cycle progression.RESULTSIn all three prostate cancer cell lines examined, targeted knockdown of p110β, and not p110α, resulted in significantly reduced AKT, PDK, and FOXO phosphorylation. While knockdown of either p110 isoform resulted in an increase in apoptosis and a cell cycle arrest in G1 in the remaining non‐apoptotic cells, these effects were much more pronounced with knockdown of p110β.CONCLUSIONSOur results support the concept that p110β appears to be the predominant functional class I PI 3‐kinase isoform in prostate cancer cells. Prostate 70: 755–764, 2010. © 2010 Wiley‐Liss, Inc.
Prostate‐specific antigen (PSA) is activated by KLK2 in prostate cancer ex vivo models and in prostate‐targeted PSA/KLK2 double transgenic mice
Authors: Williams Simon A. , Xu Yi , De Marzo Angelo M. , Isaacs John T. , Denmeade Samuel R. 
Published: January 2010

AbstractBACKGROUNDProstate‐specific antigen (PSA) is a serine protease secreted as a zymogen. Previously, cell‐free biochemical studies have identified various kallikreins (KLK) as candidate activating proteases. In this study, KLK2‐mediated activation of PSA in cell‐based in vitro, xenograft, and transgenic models was evaluated.METHODSDu145‐derived PSA‐ or KLK2‐expressing clones were coincubated in vitro and in vivo to evaluate KLK2‐induced PSA activity. While mice possess orthologs of KLK4‐15, they do not have functional orthologs of PSA or KLK2. Therefore, transgenic animals expressing PSA or both PSA and KLK2 were generated to assess orthotopic PSA activation.RESULTSPSA is activated by KLK2 when the cells are physically in contact, and through co‐conditioned media. In vivo, the free (inactive PSA) to total (active + inactive PSA) ratio in the blood is decreased when PSA and KLK2‐expressing cells are co‐inoculated subcutaneously, suggesting increased active PSA. Additionally, double‐transgenic mice expressing both genes in the prostate produce more active PSA compared to single transgenic animals. A longitudinal evaluation over a 2‐year period demonstrated no morphologic changes (i.e., no PIN or prostate cancer) due to PSA or PSA/KLK2 double transgene expression relative to non‐transgenic mice.CONCLUSIONSThese data demonstrate, with biologically relevant models, that KLK2 is the protease responsible for activating PSA. While PSA is involved in the processing and release of a number of important growth factors, our results suggest that active PSA is not sufficient to induce the development of prostate cancer or prostate cancer precursors in aging PSA transgenic mice. Prostate 70: 788–796, 2010. © 2010 Wiley‐Liss, Inc.
Should Routine Analysis of the MEN1 Gene be Performed in all Patients with Primary Hyperparathyroidism Under 40 Years of Age?
Authors: Skandarajah Anita , Barlier Anne , Morlet‐Barlat Nathalie , Sebag Frederic , Enjalbert Alain , Conte‐Devolx Bernard , Henry Jean‐François 
Published: January 2010

AbstractBackgroundFamilial hyperparathyroidism, especially Multiple Endocrine Neoplasia Type 1, is more likely to present with primary hyperparathyroidism (1° HPT) at a young age, mandating bilateral exploration of the parathyroid glands. However, the majority of young patients will not be gene carriers or have a family history. Recent evidence suggests that young adults under 40, in whom there is no suspicion of family history, can be managed with the same pre‐ and perioperative strategy as used for sporadic primary HPT of any age. Our aim was to evaluate the prevalence of mutations in the MEN1 gene in young adults under 40 who present with apparent sporadic 1° HPT.MethodsA retrospective review was undertaken of all patients who underwent surgery for 1° HPT between 1993 and 2004. From a total of 1253 patients, 87 (6.2%) were under the age of 40. Thirty‐three patients provided informed consent to a detailed personal and family history, physical examination, and genetic analysis of the MEN1 gene. Twelve patients were subsequently excluded as they were known gene carriers prior to surgery (10 MEN1 and 2 MEN2A patients). Twenty‐one patients underwent genetic analysis.ResultsOf the 21 patients who consented to genetic analysis, the mean age was 30.8 years (range = 18–39 years with 43% younger than 30). These patients had no suspicious family or personal histories suggestive of a MEN phenotype. Fifteen patients presented with symptomatic hypercalcemia. All 21 patients underwent parathyroid surgery by conventional cervicotomy (12) or endoscopic parathyroidectomy in cases (9) where the parathyroid gland was localized preoperatively. Nineteen patients (91%) had uniglandular disease. Surgical cure was achieved in all patients. Of the 21 patients, only one patient (4.7%) was found to have a MEN1 gene mutation (exon 3, at codon 190, c;680_681delGGinsC). This patient was found to have double adenomas at surgery with subsequent histological confirmation. The overall prevalence of MEN1 mutation in all patients under 40 was 13%.ConclusionAlthough young age is often the only criterion to suspect MEN1, our results do not support routine MEN1 analysis in patients under 40. We propose that these patients be managed with the same preoperative and surgical approach as those presenting with sporadic 1° HPT of any age.
Functional embedding for the classification of gene expression profiles
Authors: Wu Ping-Shi , Müller Hans-Georg 
Published: January 2010

Abstract
Motivation: Low sample size n high-dimensional large p data with n≪p are commonly encountered in genomics and statistical genetics. Ill-conditioning of the variance-covariance matrix for such data renders the traditional multivariate data analytical approaches unattractive. On the other side, functional data analysis (FDA) approaches are designed for infinite-dimensional data and therefore may have potential for the analysis of large p data. We herein propose a functional embedding (FEM) technique, which exploits the interface between multivariate and functional data, aiming at borrowing strength across the sample through FDA techniques in order to resolve the difficulties caused by the high dimension p.
Results: Using pairwise dissimilarities among predictor variables, one obtains a univariate configuration of these covariates. This is interpreted as variable ordination that defines the domain of a suitable function space, thus leading to the FEM of the high-dimensional data. The embedding may then be followed by functional logistic regression for the classification of high-dimensional multivariate data as an example for downstream analysis. The resulting functional classification is evaluated on several published gene expression array datasets and a mass spectrometric data, and is shown to compare favorably with various methods that have been employed previously for the classification of these high-dimensional gene expression profiles.
Availability: The implementation of FEM and Classification via Functional Embedding (CFEM) as described in this article was done with the PACE package written in Matlab. The latest version of PACE is publicly accessible at http://anson.ucdavis.edu/∼mueller/data/programs.html. An example MATLAB script for FEM is available at http://www.lehigh.edu/∼psw205/psw205.html
Contact: psw205@lehigh.edu; mueller@wald.ucdavis.edu
Comparative evaluation of a mixed-fisheries effort-management system based on the Faroe Islands example
Authors: Baudron Alan , Ulrich Clara , Nielsen J. Rasmus , Boje Jesper 
Published: January 2010

AbstractBaudron, A., Ulrich, C., Nielsen, J. R., and Boje, J. 2010. Comparative evaluation of a mixed-fisheries effort-management system based on the Faroe Islands example. – ICES Journal of Marine Science, 67: 1036–1050. Total allowable catch (TAC) management has in many fisheries, especially mixed fisheries, failed to meet conservation objectives. For instance, for the Faroe Plateau mixed demersal fisheries, the TAC system failed to achieve the objective of an average annual fishing mortality of 0.45 for the three gadoid stocks cod (Gadus morhua), haddock (Melanogrammus aeglefinus), and saithe (Pollachius virens). Therefore, in 1996, an effort-regulation system with individual transferable effort quotas was introduced to manage the fisheries. Experience has shown that effort management without additional stock-specific measures may not be appropriate for such fisheries. A management strategy evaluation model was developed to compare an effort-management system based on the Faroese example with a TAC system as currently applied in EU fisheries. Results show that when stocks are considered in isolation, a total allowable effort system does not necessarily perform better than a TAC one. It depends on stock status and dynamics, the level of uncertainty, and the reactivity of the system to changes in scientific advice. When the stocks are considered together in mixed fisheries, effort management seems, however, to be appropriate, and interannual flexibility of the system appears to be the best compromise between short- and long-term objectives, as well as between biological sustainability and economic return.
CORNET: A User-Friendly Tool for Data Mining and Integration
Authors: De Bodt Stefanie , Carvajal Diana , Hollunder Jens , Van den Cruyce Joost , Movahedi Sara , Inzé Dirk 
Published: January 2010

AbstractAs an overwhelming amount of functional genomics data have been generated, the retrieval, integration, and interpretation of these data need to be facilitated to enable the advance of (systems) biological research. For example, gathering and processing microarray data that are related to a particular biological process is not straightforward, nor is the compilation of protein-protein interactions from numerous partially overlapping databases identified through diverse approaches. However, these tasks are inevitable to address the following questions. Does a group of differentially expressed genes show similar expression in diverse microarray experiments? Was an identified protein-protein interaction previously detected by other approaches? Are the interacting proteins encoded by genes with similar expression profiles and localization? We developed CORNET (for CORrelation NETworks) as an access point to transcriptome, protein interactome, and localization data and functional information on Arabidopsis (Arabidopsis thaliana). It consists of two flexible and versatile tools, namely the coexpression tool and the protein-protein interaction tool. The ability to browse and search microarray experiments using ontology terms and the incorporation of personal microarray data are distinctive features of the microarray repository. The coexpression tool enables either the alternate or simultaneous use of diverse expression compendia, whereas the protein-protein interaction tool searches experimentally and computationally identified protein-protein interactions. Different search options are implemented to enable the construction of coexpression and/or protein-protein interaction networks centered around multiple input genes or proteins. Moreover, networks and associated evidence are visualized in Cytoscape. Localization is visualized in pie charts, thereby allowing multiple localizations per protein. CORNET is available at http://bioinformatics.psb.ugent.be/cornet.
Channel-Like Characteristics of the Low-Affinity Barley Phosphate Transporter PHT1;6 When Expressed inXenopusOocytes
Authors: Preuss Christian P. , Huang Chun Y. , Gilliham Matthew , Tyerman Stephen D. 
Published: January 2010

AbstractRemobilization of inorganic phosphate (Pi) within a plant is critical for sustaining growth and seed production under external Pi fluctuation. The barley (Hordeum vulgare) transporter HvPHT1;6 has been implicated in Pi remobilization. In this report, we expressed HvPHT1;6 in Xenopus laevis oocytes, allowing detailed characterization of voltage-dependent fluxes and currents induced by HvPHT1;6. HvPHT1;6 increased efflux of Pi near oocyte resting membrane potentials, dependent on external Pi concentration. Time-dependent inward currents were observed when membrane potentials were more negative than −160 mV, which was consistent with nH+:HPO42− (n &gt; 2) cotransport, based on simultaneous radiotracer and oocyte voltage clamping, dependent upon Pi concentration gradient and pH. Time- and voltage-dependent inward currents through HvPHT1;6 were also observed for SO42−and to a lesser degree for NO3−Cl−but not for malate. Inward and outward currents showed linear dependence on the concentration of external HPO42−similar to low-affinity Pi transport in plant studies. The electrophysiological properties of HvPHT1;6, which locates to the plasma membrane when expressed in onion (Allium cepa) epidermal cells, are consistent with its suggested role in the remobilization of Pi in barley plants.
Elucidating the apparent maize tolerance to weed competition in long‐term organically managed systems
Authors: RYAN M R , MORTENSEN D A , BASTIAANS L , TEASDALE J R , MIRSKY S B , CURRAN W S , SEIDEL R , WILSON D O , HEPPERLY P R 
Published: January 2010

Ryan MR, Mortensen DA, Bastiaans L, Teasdale JR, Mirsky SB, Curran WS, Seidel R, Wilson DO & Hepperly PR (2010). Elucidating the apparent maize tolerance to weed competition in long‐term organically managed systems. Weed Research50, 25–36.SummaryIn a long‐term cropping systems trial comparing organically and conventionally managed systems, organic maize production sustained crop yields equal to conventional methods despite higher weed levels. In 2005 and 2006, an experiment nested within the trial was conducted to gain insight into this apparent crop tolerance to weed competition. Density of mixed weed species was experimentally manipulated to achieve a broad range of weed infestation levels. Under standard management conditions, all cropping systems produced equivalent maize yields, even though weedy plant biomass in the organic treatments was between fourfold and sevenfold greater than in the conventionally managed maize. Increased yield capacity, evidenced when plots were maintained weed‐free, and enhanced crop competitiveness, were the main pillars of this apparent crop tolerance to weed competition in the organic systems. Increased soil resource availability and a faster relative crop growth rate in the organic systems probably contributed to these factors, which play an important role in buffering crop fitness during years of less than ideal weed control. Simultaneously, the experiment illustrated the poor efficacy of mechanical weed management in the organic systems, which is the main reason organic maize did not out‐yield conventional maize under standard management conditions.
Examination of the change in Assessment of Motor and Process Skills performance in patients with acquired brain injury between the hospital and home environment
Authors: Toneman Michelle , Brayshaw Julie , Lange Bridget , Trimboli Connie 
Published: January 2010

Aim:  The Assessment of Motor and Process Skills (AMPS) is a standardised, valid, reliable, observational assessment that is sensitive to change over time. This research aimed to examine the change in AMPS performance in patients discharged from a neurosurgical rehabilitation ward to a home‐based therapy programme over a four‐week time frame. Methods:  A total of 15 individuals with acquired brain injury who were participating in rehabilitation were recruited to the study. The AMPS was conducted with each individual during the participant’s inpatient rehabilitation and again approximately four weeks later, while participating in home‐based rehabilitation. Assessment results were collated using the AMPS computer programme and entered into a statistics package from which data were analysed. Results:  As a group, no statistically significant change in function was identified between the home and hospital environments; however, individual results did indicate a change in occupational performance for many of the participants. Conclusions:  The AMPS was shown to reflect a change in occupational performance for many of the research participants. This research supports previous studies which indicate that some individuals’ motor and process skill abilities appear to be affected by the environment in which they perform. This suggests that occupational therapists wishing to know how an individual will perform activities of daily living should evaluate the individual’s performance in the environment in which they will be functioning.
Gene expression profiling of Dunaliella sp. acclimated to different salinities
Authors: Kim Minjung , Park Seunghye , Polle Jürgen E.W. , Jin EonSeon 
Published: January 2010

SUMMARYTo investigate which genes may be important for growth under extreme conditions such as very low or high salinities, a survey of the Dunaliella sp. transcriptome was performed with a cDNA microarray which had been generated previously representing 778 expressed sequence tags. The comparative microarray analysis indicated that 142 genes differed in expression levels by more than twofold in cells grown at extreme salinities (0.08 M and 4.5 M NaCl) when compared with cells grown at intermediate salinity (1.5 M NaCl). Of these genes, 28 had increased expression and 57 were suppressed in cells grown at low salinity. In cells grown at high salinity, 43 genes showed increased expression and 69 genes showed suppressed expression. However, we did observe a large overlap in the expression of extreme salinity‐responsive genes based on Venn diagram analysis, which found 55 genes that responded to both of the two extreme salinity conditions. Further, we found that several genes had similar expression levels under low and high salinities, including some general stress response genes that were upregulated in both extreme salinity conditions. For confirmation of the validity of the cDNA microarray analysis, expression of several genes was independently confirmed by the use of gene‐specific primers and real‐time polymerase chain reaction. The present study is the first large‐scale comparative survey of the transcriptome from the microalga Dunaliella sp. acclimated to extreme salinities, thus providing a platform for further functional investigation of differentially expressed genes in Dunaliella.
Spatial variations in nutrient supply to the red algae Eucheuma serra (J. Agardh) J. Agardh
Authors: Nishihara Gregory N. , Terada Ryuta 
Published: January 2010

SUMMARYThe nutrient supply rates within the canopy of the economically important red algal species, Eucheuma serra J. Agardh were determined experimentally in a recirculating flow‐chamber. A single individual was placed in the working section of the 2000 × 200 × 250 mm3 acrylic flow‐chamber and subjected to unidirectional water velocities from 1.0 to 9.3 cm s−1. Rates of nutrient supply were determined using 9.7 mm diameter CaSO4 (gypsum) spheres that were attached to the thallus inside and outside of the canopy. The supply rates within the canopy were 56% less than outside of the canopy. Increases in internal and external water velocity asymptotically increased the nutrient supply rates regardless of location. A model was developed to examine how changes in ammonium and nitrate supply compared with the physiologically maximum uptake rates of these nutrients. The results suggest that when the ammonium concentration in the water was 20 µmol L−1 uptake rates were limited by the supply rate especially at velocities below 5 cm s−1, whereas in the case of 20 µmol L−1 of nitrate, the supply of nitrate was more than adequate to maximize nutrient uptake.
Dutogliptin, a selective DPP4 inhibitor, improves glycaemic control in patients with type 2 diabetes: a 12‐week, double‐blind, randomized, placebo‐controlled, multicentre trial
Authors: Pattzi H. M. R. , Pitale S. , Alpizar M. , Bennett C. , O’Farrell A. M. , Li J. , Cherrington J. M. , Guler H.‐P. ,   PHX1149‐PROT202 Study Group
Published: January 2010

Aim: To determine efficacy and tolerability of dutogliptin, a dipeptidyl peptidase 4 (DPP4) inhibitor, in patients with type 2 diabetes mellitus. Methods: This was a 12‐week, multicentre, randomized, double‐blind, placebo‐controlled trial in 423 patients with type 2 diabetes with suboptimal metabolic control. Following a 2‐week single‐blind placebo run‐in, patients aged 18–75 years with a body mass index of 25–48 kg/m2 and baseline HbA1c of 7.3–11.0% were randomized 2:2:1 to receive once‐daily oral therapy with either dutogliptin (400 or 200 mg) or placebo on a background medication of either metformin alone, a thiazolidinedione (TZD) alone or a combination of metformin plus a TZD. Results: Average HbA1c at baseline was 8.4%. Administration of dutogliptin 400 and 200 mg for 12 weeks decreased HbA1c by −0.52% (p < 0.001) and −0.35% (p = 0.006), respectively (placebo‐corrected values), with absolute changes in HbA1c for the 400 mg, 200 mg and placebo groups of −0.82, −0.64 and −0.3%, respectively. The proportion of patients achieving an HbA1c < 7% was 27, 21 and 12% at dutogliptin doses of 400 and 200 mg or placebo, respectively (p = 0.008 for comparison of 400 mg vs. placebo). Fasting plasma glucose (FPG) levels were significantly reduced in both active treatment groups compared to placebo: the placebo‐corrected difference was −1.00 mmol/l (p < 0.001) for the 400 mg group and −0.88 mmol/l (p = 0.003) for the 200 mg group. Dutogliptin caused significantly greater reductions in postprandial glucose AUC 0–2h in both the 400 and 200 mg groups (placebo corrected values −2.58 mmol/l/h, p < 0.001 and −1.63 mmol/l/h, p = 0.032, respectively). In general, patients tolerated the study drug well. There were minor, not clinically meaningful differences in adverse events (AEs) between dutogliptin‐treated patients and placebo controls, and 60% of all reported AEs were mild. Vital signs and body weight were stable, and routine safety laboratory parameters did not change compared with placebo. Trough ex vivo DPP4 inhibition at the end of the 12‐week treatment period was 80 and 70%, at the 400 and 200 mg doses of dutogliptin, respectively. Conclusions: Dutogliptin treatment for 12 weeks improved glycaemic control in patients with type 2 diabetes who were on a background medication of metformin, a TZD or metformin plus a TZD. Tolerability was favourable for both doses tested. The 400 mg dose of dutogliptin resulted in larger changes of HbA1c and FPG and more subjects reached an HbA1c target of < 7% than the 200 mg dose.