bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serpin genes AtSRP2 and AtSRP3 are required for normal growth sensitivity to a DNA alkylating agent in Arabidopsis
Authors: Ahn Joon-Woo , Atwell Brian J , Roberts Thomas H 
Published: June 2009

Abstract

Background
The complex responses of plants to DNA damage are incompletely understood and the role of members of the serpin protein family has not been investigated. Serpins are functionally diverse but structurally conserved proteins found in all three domains of life. In animals, most serpins have regulatory functions through potent, irreversible inhibition of specific serine or cysteine proteinases via a unique suicide-substrate mechanism. Plant serpins are also potent proteinase inhibitors, but their physiological roles are largely unknown.

Results
Six Arabidopsis genes encoding full-length serpins were differentially expressed in developing seedlings and mature tissues. Basal levels of AtSRP2 (At2g14540) and AtSRP3 (At1g64030) transcripts were highest in reproductive tissues. AtSRP2 was induced 5-fold and AtSRP3 100-fold after exposure of seedlings to low concentrations of methyl methanesulfonate (MMS), a model alkylating reagent that causes DNA damage. Homozygous T-DNA insertion mutants atsrp2 and atsrp3 exhibited no differential growth when mutant and wild-type plants were left untreated or exposed to γ-radiation or ultraviolet light. In contrast, atsrp2 and atsrp3 plants exhibited greater root length, leaf number and overall size than wild-type plants when exposed to MMS. Neither of the two serpins was required for meiosis. GFP-AtSRP2 was localized to the nucleus, whereas GFP-AtSRP3 was cytosolic, suggesting that they target different proteinases. Induction of cell cycle- and DNA damage-related genes AtBRCA1, AtBARD1, AtRAD51, AtCYCB1;1 and AtCYCD1;1, but not AtATM, was reduced relative to wild-type in atsrp2 and atsrp3 mutants exposed to MMS.

Conclusion
Expression of specific serpin genes (AtSRP2 and AtSRP3 in Arabidopsis) is required for normal responses of plants following exposure to alkylating genotoxins such as MMS.
Bioluminescence imaging reveals inhibition of tumor cell proliferation by Alzheimer's amyloid β protein
Authors: Zhao Hong , Zhu Jinmin , Cui Kemi , Xu Xiaoyin , O'Brien Megan , Wong Kelvin K , Kesari Santosh , Xia Weiming , Wong Stephen TC 
Published: June 2009

Abstract

Background
Cancer and Alzheimer's disease (AD) are two seemingly distinct diseases and rarely occur simultaneously in patients. To explore molecular determinants differentiating pathogenic routes towards AD or cancer, we investigate the role of amyloid β protein (Aβ) on multiple tumor cell lines that are stably expressing luciferase (human glioblastoma U87; human breast adenocarcinoma MDA-MB231; and mouse melanoma B16F).

Results
Quantification of the photons emitted from the MDA-MB231 or B16F cells revealed a significant inhibition of cell proliferation by the conditioning media (CM) derived from amyloid precursor protein (APP) over-expressing cells. The inhibition of U87 cells was observed only after the media was conditioned for longer than 2 days with APP over-expressing cells.

Conclusion
Our results suggest that Aβ plays an inhibitory role in tumor cell proliferation; this effect could depend on the type of tumor cells and amount of Aβ.
Corticotropin Releasing Factor promotes breast cancer cell motility and invasiveness
Authors: Androulidaki Ariadne , Dermitzaki Erini , Venihaki Maria , Karagianni Effie , Rassouli Olga , Andreakou Erini , Stournaras Christos , Margioris Andrew N , Tsatsanis Christos 
Published: June 2009

Abstract

Introduction
Cancer cells secrete bioactive peptides that act in an autocrine or paracrine fashion affecting tumor growth and metastasis. Corticotropin-releasing factor (CRF), a hypothalamic neuropeptide that controls the response to stress, has been detected in breast cancer tissues and cell lines. CRF can affect breast cancer cells in an autocrine or paracrine manner via its production from innervating sympathetic neurons or immune cells.

Methods
In the present study we report our findings regarding the impact of CRF on breast cancer cell motility and invasiveness. For this purpose we used the MCF7 breast cancer cell line and evaluated the effect of CRF on motility and invasiveness using the wound-healing and boyden-chamber assays. In addition, we measured the effect of CRF on molecules that mediate motility by western blot, immunofluorescence, ELISA and RT-PCR.

Results
Our findings show that: 1. CRF transiently inhibited the apoptosis of MCF7 cells. 2. CRF enhanced MCF7 cell motility in a wound healing assay and their invasiveness through extracellular matrix. 3. CRF increased actin polymerization, phosphorylation of Focal Adhesion Kinase (FAK), providing a potential mechanism for the observed induction of MCF7 motility. 4. CRF induced the expression of Cox-1 but not Cox-2 in MCF7 cells as well as the production of prostaglandins, factors known to promote invasiveness and metastasis.

Conclusion
Overall, our data suggest that CRF stimulates cell motility and invasiveness of MCF7 cells most probably via induction of FAK phosphorylation and actin filament reorganization and production of prostaglandins via Cox1. Based on these findings we postulate that the stress neuropeptide CRF present in the vicinity of tumors (either produced locally by the tumor cells themselves or by nearby normal cells or secreted from the innervations of surrounding tissues) may play an important role on breast tumor growth and metastatic capacity, providing a potential link between stress and tumor progression.
Cip/Kip cyclin-dependent protein kinase inhibitors and the road to polyploidy
Authors: Ullah Zakir , Lee Chrissie Y , DePamphilis Melvin L 
Published: June 2009

AbstractCyclin-dependent kinases (CDKs) play a central role in the orderly transition from one phase of the eukaryotic mitotic cell division cycle to the next. In this context, p27Kip1(one of the CIP/KIP family of CDK specific inhibitors in mammals) or its functional analogue in other eukarya prevents a premature transition from G1 to S-phase. Recent studies have revealed that expression of a second member of this family, p57Kip2, is induced as trophoblast stem (TS) cells differentiate into trophoblast giant (TG) cells. p57 then inhibits CDK1 activity, an enzyme essential for initiating mitosis, thereby triggering genome endoreduplication (multiple S-phases without an intervening mitosis). Expression of p21Cip1, the third member of this family, is also induced in during differentiation of TS cells into TG cells where it appears to play a role in suppressing the DNA damage response pathway. Given the fact that p21 and p57 are unique to mammals, the question arises as to whether one or both of these proteins are responsible for the induction and maintenance of polyploidy during mammalian development.
Engineering fusogenic molecules to achieve targeted transduction of enveloped lentiviral vectors
Authors: Lei Yuning , Joo Kye-Il , Wang Pin 
Published: June 2009

AbstractBackgroundLentiviral vectors with broad tropism are one of the most promising gene delivery systems capable of efficiently delivering genes of interest into both dividing and non-dividing cells while maintaining long-term transgene expression. However, there are needs for developing lentiviral vectors with the capability to deliver genes to specific cell types, thus reducing the "off-target" effect of gene therapy. In the present study, we investigated the possibility of engineering the fusion-active domain of a fusogenic molecule (FM) with the aim to improve targeted transduction of lentiviral vectors co-displaying an anti-CD20 antibody (αCD20) and a FM.ResultsSpecific mutations were introduced into the fusion domain of a binding-deficient Sindbis virus glycoprotein to generate several mutant FMs. Lentiviral vectors incorporated with αCD20 and one of the engineered FMs were successfully produced and demonstrated to be able to preferentially deliver genes to CD-20-expressing cells. Lentiviral vectors bearing engineered FMs exhibited 8 to 17-fold enhanced transduction towards target cells as compared to the parental FM. Different levels of enhancement were observed for the different engineered FMs. A pH-dependent study of vector transduction showed that the broader pH range of the engineered FM is a possible mechanism for the resulted increase in transduction efficiency.ConclusionThe fusion domain of Sindbis virus glycoprotein is amenable for engineering and the engineered proteins provide elevated capacity to mediate lentiviral vectors for targeted transduction. Our data suggests that application of such an engineering strategy can optimize the two-molecular targeting method of lentiviral vectors for gene delivery to predetermined cells.
Does metformin affect ovarian morphology in patients with polycystic ovary syndrome? A retrospective cross-sectional preliminary analysis
Authors: Falbo Angela , Orio Francesco , Venturella Roberta , Rania Erika , Materazzo Caterina , Tolino Achille , Zullo Fulvio , Palomba Stefano 
Published: June 2009

Abstract

Background
The significance of polycystic ovarian morphology and its relation to polycystic ovary syndrome (PCOS) is unclear, but probably it is associated with higher androgen and insulin levels and lower sex hormone binding globulin (SHBG) in absence of identifiable differences in gonadotropin dynamics. The aim of this study was to evaluate ovarian morphology in patients affected by PCOS with different ovulatory responses to metformin.

Methods
In this cross-sectional analysis, we studied 20 young normal-weight PCOS patients who had received a six-month course of metformin treatment. Ten of these patients remained anovulatory (anovulatory group), whereas other ten became ovulatory, but failed to conceive (ovulatory group). Other ten age- and body mass index (BMI)-matched PCOS subjects were also enrolled as controls and observed without any treatment (control group).

Results
After six months of metformin, in both PCOS treated groups, a similar improvement in testosterone (T) and insulin resistance indexes was observed. Moreover, in one (10.0%) and nine (90.0%) subjects from anovulatory and ovulatory PCOS groups, respectively, ovarian morphology changed, whereas a significant reduction in ovarian dimension was observed in the PCOS ovulatory group only.

Conclusion
PCOS patients under metformin administration demonstrate a change in ovarian morphology closely related to ovulatory response.
Closing gaps in the human genome using sequencing by synthesis
Authors: Garber Manuel , Zody Michael C , Arachchi Harindra M , Berlin Aaron , Gnerre Sante , Green Lisa M , Lennon Niall , Nusbaum Chad 
Published: June 2009

AbstractThe most recent release of the finished human genome contains 260 euchromatic gaps (excluding chromosome Y). Recent work has helped explain a large number of these unresolved regions as 'structural' in nature. Another class of gaps is likely to be refractory to clone-based approaches, and cannot be approached in ways previously described. We present an approach for closing these gaps using 454 sequencing. As a proof of principle, we closed all three remaining non-structural gaps in chromosome 15.
Dasatinib in the Treatment of Chronic Myeloid Leukemia in Accelerated Phase After Imatinib Failure: The START A Trial
Authors: Apperley Jane F. , Cortes Jorge E. , Kim Dong-Wook , Roy Lydia , Roboz Gail J. , Rosti Gianantonio , Bullorsky Eduardo O. , Abruzzese Elisabetta , Hochhaus Andreas , Heim Dominik , de Souza Carmino A. , Larson Richard A. , Lipton Jeffrey H. , Khoury H. Jean , Kim Hyeoung-Joon , Sillaber Christian , Hughes Timothy P. , Erben Philipp , Van Tornout Jan , Stone Richard M. 
Published: June 2009

Purpose Patients with chronic myelogenous leukemia in accelerated phase (CML-AP) that is resistant or intolerant to imatinib have limited therapeutic options. Dasatinib, a potent inhibitor of BCR-ABL and SRC-family kinases, has efficacy in patients with CML-AP who have experienced treatment failure with imatinib. We now report follow-up data from the full patient cohort of 174 patients enrolled onto a phase II trial to provide a more complete assessment of the efficacy and safety of dasatinib in this population. Patients and Methods Patients with imatinib-resistant (n = 161) or -intolerant (n = 13) CML-AP received dasatinib 70 mg orally twice daily. Results At a median follow-up of 14.1 months (treatment duration, 0.1 to 21.7 months), major and complete hematologic responses were attained by 64% and 45% of patients, respectively, and major and complete cytogenetic responses were achieved in 39% and 32% of patients, respectively. Responses were achieved irrespective of imatinib status (resistant or intolerant), prior stem-cell transplantation, or the presence of prior BCR-ABL mutation. The 12-month progression-free survival and overall survival rates were 66% and 82%, respectively. Dasatinib was generally well tolerated; the most frequent nonhematologic severe treatment-related adverse event was diarrhea (52%; grade 3 to 4, 8%). Cytopenias were common, including grade 3 to 4 neutropenia (76%) and thrombocytopenia (82%). Pleural effusion occurred in 27% of patients (grade 3 to 4, 5%). Conclusion Dasatinib is effective in patients with CML-AP after imatinib treatment failure.
Metformin and Pathologic Complete Responses to Neoadjuvant Chemotherapy in Diabetic Patients With Breast Cancer
Authors: Jiralerspong Sao , Palla Shana L. , Giordano Sharon H. , Meric-Bernstam Funda , Liedtke Cornelia , Barnett Chad M. , Hsu Limin , Hung Mien-Chie , Hortobagyi Gabriel N. , Gonzalez-Angulo Ana M. 
Published: June 2009

Purpose Population studies have suggested that metformin use in diabetic patients decreases cancer incidence and mortality. Metformin inhibits the growth of cancer cells in vitro and tumors in vivo. However, there is little clinical data to support this. Our purpose was to determine whether metformin use was associated with a change in pathologic complete response (pCR) rates in diabetic patients with breast cancer receiving neoadjuvant chemotherapy. Patients and Methods We identified 2,529 patients who received neoadjuvant chemotherapy for early-stage breast cancer between 1990 and 2007. Patients were compared by groups: 68 diabetic patients taking metformin, 87 diabetic patients not taking metformin, and 2,374 nondiabetic patients. pCR rates were compared between the three groups using χ2 tests of independence and compared pair- wise using a binomial test of proportions. Factors predictive of pCR were assessed using a multivariate logistic regression model. Results The rate of pCR was 24% in the metformin group, 8.0% in the nonmetformin group, and 16% in the nondiabetic group (P = .02). Pairwise comparisons between the metformin and nonmetformin groups (P = .007) and the nonmetformin and nondiabetic groups (P = .04) were significant. Comparison of the pCR rates between the metformin and nondiabetic groups trended toward but did not meet significance (P = .10). Metformin use was independently predictive of pCR (odds ratio, 2.95; P = .04) after adjustment for diabetes, body mass index, age, stage, grade, receptor status, and neoadjuvant taxane use. Conclusion Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pCR rate than do diabetics not receiving metformin. Additional studies to evaluate the potential of metformin as an antitumor agent are warranted.
Haemoglobin A1c: evaluation of a new HbA1c point-of-care analyser Bio-Rad in2it in comparison with the DCA 2000 and central laboratory analysers
Authors: Yeo Chin-Pin , Tan Carol Hui-Chen , Jacob Edward 
Published: June 2009

Background Point-of-care-testing (POCT) of haemoglobin Alc (HbA1c) is popular due to its fast turnaround of results in the outpatient setting. The aim of this project was to evaluate the performance of a new HbA1c POCT analyser, the Bio-Rad in2it, and compare it with the Siemens DCA 2000, Bio-Rad Variant II and Roche Tina-quant HbA1c Gen 2 assay on the cobas c501. Methods Imprecision of the four methods were compared by computing total imprecision from within-run and between-run data. A total of 80 samples were also compared and analysed by Deming regression and Altman–Bland difference test. Results Study of total imprecision of the in2it at HBA1c levels of 6.0% and 10.4% produced a coefficient of variation (%CV) of 3.8% and 3.7%, respectively. These results were more favourable as compared with the DCA 2000 but did not match the low imprecision of the central laboratory methods, the Bio-Rad Variant II and the Roche cobas c501. Comparison between the in2it and the central laboratory analysers, Bio-Rad variant II and cobas c501, revealed positive bias of 12% and 10%, respectively, supported by corresponding Deming regression equation slopes of +1.18 and +1.14. Comparison between the DCA 2000 and the central laboratory analysers revealed a bias that became increasingly positive with rising HbA1c concentrations with Deming regression analysis also revealing proportional and constant differences. Conclusions The in2it is a suitable POCT analyser for HbA1c but its less than ideal precision performance and differences with the central laboratory analysers must be communicated to and noted by the users.
Sweat testing for cystic fibrosis: standards of performance in Australasia
Authors: Coakley John , Scott Sue , Mackay Richard , Greaves Ronda , Jolly Lisa , Massie John , Mishra Avantika , Bransden Anna , Doery James C G , Chiriano Angela , Robins Heather 
Published: June 2009

Background Accurate measurement of sweat chloride concentration is essential for the diagnosis of cystic fibrosis (CF). We surveyed all laboratories enrolled in the Royal College of Pathologists of Australasia Quality Assurance Program (QAP) for Sweat Electrolytes to determine how closely they comply with the Australian Guidelines for the performance of the sweat test for the diagnosis of CF. Methods A detailed questionnaire covering most aspects of sweat collection and analysis was sent to all participating laboratories in 2007. Results Twenty out of 38 laboratories completed the questionnaire. While adherence to accepted guidelines was noted in many areas, the following main variations were recorded: some laboratories were not doing enough sweat tests to maintain expertise; some were not collecting sweat for the recommended collection time; sweat conductivity was the only test available in some laboratories; there was a lack of agreement between the sweat chloride concentration used to indicate CF or define an equivocal result. Conclusions There is room for improvement in the performance of the sweat test in some laboratories in Australasia. The Sweat Testing Working Party of the Australasian Association of Clinical Biochemists is the appropriate body to address the problems involved in sweat testing and to bring about change.
Arms Race or Détente? How Interfirm Alliance Announcements Change the Stock Market Valuation of Rivals
Authors: Oxley Joanne E. , Sampson Rachelle C. , Silverman Brian S. 
Published: June 2009

Most prior event studies find that the announcement of a new alliance is accompanied by a positive stock market response for the partners. This result has usually been interpreted as evidence for the prevailing view that alliances are effective vehicles for partners to acquire or access new skills and thus become stronger competitors. However, partners should also earn positive abnormal returns if alliances are used to shape competitive interactions, attenuating competitive intensity industry-wide. In this study, we disentangle these different mechanisms by examining how alliance announcements affect the stock market's evaluation of allying firms' rivals: if an alliance is expected to make partner firms more competitive, this should lead to negative abnormal returns for partners' rivals; if an alliance is expected to facilitate a reduction in competitive intensity, this should lead to positive abnormal returns for rivals. Results from an event study analysis of research and development alliances in the telecommunications and electronics industries during 1996–2004 provide evidence consistent with competition attenuation in some alliances. Our research thus challenges the increasingly narrow focus on learning and resource accumulation through alliances, and calls for broader consideration of the roles and effects of collaboration, both for individual firms and for industry structure.
Nutrition and Adults With Intellectual or Developmental Disabilities: Systematic Literature Review Results*
Authors: Humphries Kathleen , Traci Meg Ann , Seekins Tom 
Published: June 2009

AbstractApproximately 4.5 million Americans have an intellectual or developmental disability. Concern is increasing about these individuals' nutrition-related behavior and its implications for their health. This article reports on a systematic search of the current literature listed in the PsycINFO and PubMed databases related to nutritional status of adults with intellectual or developmental disabilities. The authors used key terms for nutrition, secondary conditions, and intellectual and developmental disability and categorized literature pertaining to nutrition-related studies of adults with intellectual or developmental disabilities as follows: dietary intake studies, anthropometric assessments of nutritional risks, biochemical indexes, and clinical evaluations.
Parents' Perceptions of Postschool Years for Young Adults With Developmental Disabilities
Authors: Bianco Margarita , Garrison-Wade Dorothy F. , Tobin Romie , Lehmann Jean P. 
Published: June 2009

Abstract
This qualitative study investigated parents' perceptions of the various roles they played in their adult children's lives during the post–high school years. Individual face-to-face interviews were conducted with 9 families of young adults with developmental disabilities. Findings indicated that families perceived the complexity of their roles as balancing between advocating for their adult children's needs while promoting independence and self-determination. The roles parents assumed as their children entered into adult life were those of collaborators, decision makers, and program evaluators, role models, trainers, mentors and instructors, and systems change agents. Parents often felt they were the safety net for their children and the back-up plan for service agencies. Parents' quotes illustrated the complexity of the roles they played as their young adult children with developmental disabilities entered adulthood.
Dreschgerät und Totenbett. Hölzerne Dreschschlittenfragmente des 1. Jahrhunderts aus einer Nekropole auf der Krim
Authors: Hellström Kirsten , Hochmuth Michael , Zajcev Jurij P. 
Published: June 2009

Die Identifizierung und dendrochronologische Datierung sekundär verbauter Dreschschlitten in zwei Grablegen aus der Nekropole Ust'-Al'ma führten zum ersten sicheren archäologischen Nachweis für den Gebrauch dieses Ackerbaugerätes seit der Mitte des 1. Jahrhunderts v. Chr. auf der Krim. Insgesamt gliedert sich die Krim in ein Gebiet mit ähnlichen klimatischen Bedingungen und vergleichbarer Wirtschaftsweise zwischen Vorderem Orient und Westeuropa ein, in dem zahlreiche archäologische und ethnographische Beispiele den Gebrauch des Dreschschlittens sicher von der Bronze- bis in die heutige Zeit belegen.Darüber hinaus bietet der Fundzusammenhang in Kombination mit ethnographischen Parallelen die Möglichkeit, einen neuen Aspekt des Grabrituals und damit auch der Vorstellungswelt der Krimbewohner in späthellenistischer Zeit zu untersuchen. Einige Beispiele belegen, dass die sekundäre Verwendung von Dreschschlitten als Totenbett offenbar kein Einzelfall oder eine lokale Besonderheit war, aber aufgrund der im Allgemeinen schlechten Erhaltungsbedingungen für Holz oftmals unerkannt bleibt. Eine gezielte Durchsicht von weiteren Grabbefunden würde sicherlich die Datenbasis erheblich erweitern können und möglicherweise eine Verbindung zu sehr ähnlichen Funden im Kaukasusgebiet erschließen helfen.