bluuebunny/crossref_metadata_2025_split huggingface dataset:
"Glucose and ethanol-dependent transcriptional regulation of the astaxanthin biosynthesis pathway in Xanthophyllomyces dendrorhous"
Authors: Marcoleta Andrés , Niklitschek Mauricio , Wozniak Aniela , Lozano Carla , Alcaíno Jennifer , Baeza Marcelo , Cifuentes Víctor 
Published: August 2011

Abstract

Background
The yeast Xanthophyllomyces dendrorhous is one of the most promising and economically attractive natural sources of astaxanthin. The biosynthesis of this valuable carotenoid is a complex process for which the regulatory mechanisms remain mostly unknown. Several studies have shown a strong correlation between the carbon source present in the medium and the amount of pigments synthesized. Carotenoid production is especially low when high glucose concentrations are used in the medium, while a significant increase is observed with non-fermentable carbon sources. However, the molecular basis of this phenomenon has not been established.

Results
In this work, we showed that glucose caused transcriptional repression of the three genes involved in the synthesis of astaxanthin from geranylgeranyl pyrophosphate in X. dendrorhous, which correlates with a complete inhibition of pigment synthesis. Strikingly, this regulatory response was completely altered in mutant strains that are incapable of synthesizing astaxanthin. However, we found that addition of ethanol caused the induction of crtYB and crtS gene expression and promoted de novo synthesis of carotenoids. The induction of carotenogenesis was noticeable as early as 24 h after ethanol addition.

Conclusion
For the first time, we demonstrated that carbon source-dependent regulation of astaxanthin biosynthesis in X. dendrorhous involves changes at the transcriptional level. Such regulatory mechanism provides an explanation for the strong and early inhibitory effect of glucose on the biosynthesis of this carotenoid.
Purinergic receptor antagonists inhibit odorant-mediated CREB phosphorylation in sustentacular cells of mouse olfactory epithelium
Authors: Dooley Ruth , Mashukova Anastasia , Toetter Bastian , Hatt Hanns , Neuhaus Eva M 
Published: August 2011

AbstractBackgroundExtracellular nucleotides have long been known to play neuromodulatory roles and to be involved in intercellular signalling. In the olfactory system, ATP is released by olfactory neurons, and exogenous ATP can evoke an increase in intracellular calcium concentration in sustentacular cells, the nonneuronal supporting cells of the olfactory epithelium. Here we investigate the hypothesis that olfactory neurons communicate with sustentacular cells via extracellular ATP and purinergic receptor activation.ResultsHere we show that exposure of mice to a mixture of odorants induced a significant increase in the levels of the transcription factor CREB phosphorylated at Ser-133 in the nuclei of both olfactory sensory neurons and sustentacular cells. This activation was dependent on adenylyl cyclase III-mediated olfactory signaling and on activation of P2Y purinergic receptors on sustentacular cells. Purinergic receptor antagonists inhibited odorant-dependent CREB phosphorylation specifically in the nuclei of the sustentacular cells.ConclusionOur results point to a possible role for extracellular nucleotides in mediating intercellular communication between the neurons and sustentacular cells of the olfactory epithelium in response to odorant exposure. Maintenance of extracellular ionic gradients and metabolism of noxious chemicals by sustentacular cells may therefore be regulated in an odorant-dependent manner by olfactory sensory neurons.
[Cost]effectiveness of withdrawal of fall-risk increasing drugs versus conservative treatment in older fallers: design of a multicenter randomized controlled trial (IMPROveFALL-study)
Authors: Hartholt Klaas A , Boyé Nicole DA , Van der Velde Nathalie , Van Lieshout Esther MM , Polinder Suzanne , De Vries Oscar J , Kerver Albert JH , Ziere Gijsbertus , Bruijninckx Milko MM , De Vries Mark R , Mattace-Raso Francesco US , Uitterlinden André G , Van Beeck Ed F , Lips Paul , Patka Peter , Van der Cammen Tischa JM 
Published: August 2011

Abstract

Background
Fall incidents represent an increasing public health problem in aging societies worldwide. A major risk factor for falls is the use of fall-risk increasing drugs. The primary aim of the study is to compare the effect of a structured medication assessment including the withdrawal of fall-risk increasing drugs on the number of new falls versus 'care as usual' in older adults presenting at the Emergency Department after a fall.

Methods/Design
A prospective, multi-center, randomized controlled trial will be conducted in hospitals in the Netherlands. Persons aged ≥65 years who visit the Emergency Department due to a fall are invited to participate in this trial. All patients receive a full geriatric assessment at the research outpatient clinic. Patients are randomized between a structured medication assessment including withdrawal of fall-risk increasing drugs and 'care as usual'. A 3-monthly falls calendar is used for assessing the number of falls, fallers and associated injuries over a one-year follow-up period. Measurements will be at three, six, nine, and twelve months and include functional outcome, healthcare consumption, socio-demographic characteristics, and clinical information. After twelve months a second visit to the research outpatient clinic will be performed, and adherence to the new medication regimen in the intervention group will be measured. The primary outcome will be the incidence of new falls. Secondary outcome measurements are possible health effects of medication withdrawal, health-related quality of life (Short Form-12 and EuroQol-5D), costs, and cost-effectiveness of the intervention. Data will be analyzed using an intention-to-treat analysis.

Discussion
The successful completion of this trial will provide evidence on the effectiveness of withdrawal of fall-risk increasing drugs in older patients as a method for falls reduction.

Trial Registration
The trial is registered in the Netherlands Trial Register (NTR1593)
Collagen induced arthritis increases secondary metastasis in MMTV-PyV MT mouse model of mammary cancer
Authors: Roy Lopamudra Das , Ghosh Sriparna , Pathangey Latha B , Tinder Teresa L , Gruber Helen E , Mukherjee Pinku 
Published: August 2011

AbstractBackgroundSeveral studies have demonstrated that sites of chronic inflammation are often associated with the establishment and growth of various malignancies. A common inflammatory condition in humans is autoimmune arthritis (AA). Although AA and cancer are different diseases, many of the underlying processes that contribute to the disorders of the joints and connective tissue that characterize AA also affect cancer progression and metastasis. Systemically, AA can lead to cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge being available, there has been minimal research linking breast cancer, arthritis, and metastasis associated with breast cancer. Notably both diseases are extremely prevalent in older post-menopausal women.MethodsTo establish the novel link between arthritis induced inflammation and secondary metastasis associated with breast cancer, PyV MT mice that spontaneously develop mammary gland carcinoma were injected with Type II collagen (CII) to induce arthritis at 9 and 18 weeks of age for pre-metastatic and metastatic condition. The sites of secondary metastasis and the associated inflammatory microenvironment were evaluated.ResultsA significant increase in breast cancer-associated secondary metastasis to the lungs and bones was observed in the arthritic versus the non-arthritic PyV MT mice along with an increase in primary tumor burden. We report significant increases in the levels of interstitial cellular infiltrates and pro-inflammatory cytokines such as interleukin-17 (IL-17), interleukin-6 (IL-6), Pro- Matrix metallopeptidase 9 (Pro-MMP9), insulin like growth factor-II (GF-II) and macrophage colony stimulating factor (M-CSF) in the arthritic lung and bone milieu as well as in the circulation. These pro-inflammatory cytokines along with the inflammatory microenvironment may be the underlying factors facilitating tumor progression and metastasis in arthritic PyV MT mice. This was further substantiated by treatment with celecoxib, an anti-inflammatory drug + αIL-17 antibody that significantly reduced the secondary metastasis to lung and bone.ConclusionsThe data generated not only reveal the underlying mechanism of high susceptibility to bone and lung metastasis in an arthritic condition but our combination therapies may lead to treatment modalities that will be capable of reducing tumor burden, and preventing relapse and metastasis in arthritic patients with breast cancer.
A randomized, phase III trial of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in first-line treatment of metastatic colorectal cancer: The AIO KRK 0110 Trial/ML22011 Trial
Authors: Giessen Clemens , von Weikersthal Ludwig Fischer , Hinke Axel , Stintzing Sebastian , Kullmann Frank , Vehling-Kaiser Ursula , Mayerle Julia , Bangerter Markus , Denzlinger Claudio , Sieber Markus , Teschendorf Christian , Freiberg-Richter Jens , Schulz Christoph , Modest Dominik Paul , Moosmann Nicolas , Aubele Philipp , Heinemann Volker 
Published: August 2011

Abstract

Background
Several randomized trials have indicated that combination chemotherapy applied in metastatic colorectal cancer (mCRC) does not significantly improve overall survival when compared to the sequential use of cytotoxic agents (CAIRO, MRC Focus, FFCD 2000-05). The present study investigates the question whether this statement holds true also for bevacizumab-based first-line treatment including escalation- and de-escalation strategies.

Methods/Design
The AIO KRK 0110/ML22011 trial is a two-arm, multicenter, open-label randomized phase III trial comparing the efficacy and safety of capecitabine plus bevacizumab (Cape-Bev) versus capecitabine plus irinotecan plus bevacizumab (CAPIRI-Bev) in the first-line treatment of metastatic colorectal cancer. Patients with unresectable metastatic colorectal cancer, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, will be assigned in a 1:1 ratio to receive either capecitabine 1250 mg/m2 bid for 14d (d1-14) plus bevacizumab 7.5 mg/kg (d1) q3w (Arm A) or capecitabine 800 mg/m2 BID for 14d (d1-14), irinotecan 200 mg/m2 (d1) and bevacizumab 7.5 mg/kg (d1) q3w (Arm B). Patients included into this trial are required to consent to the analysis of tumour tissue and blood for translational investigations. In Arm A, treatment escalation from Cape-Bev to CAPIRI-Bev is recommended in case of progressive disease (PD). In Arm B, de-escalation from CAPIRI-Bev to Cape-Bev is possible after 6 months of treatment or in case of irinotecan-associated toxicity. Re-escalation to CAPIRI-Bev after PD is possible. The primary endpoint is time to failure of strategy (TFS). Secondary endpoints are overall response rate (ORR), overall survival, progression-free survival, safety and quality of life.

Conclusion
The AIO KRK 0110 trial is designed for patients with disseminated, but asymptomatic mCRC who are not potential candidates for surgical resection of metastasis. Two bevacizumab-based strategies are compared: one starting as single-agent chemotherapy (Cape-Bev) allowing escalation to CAPIRI-Bev and another starting with combination chemotherapy (CAPIRI-Bev) and allowing de-escalation to Cape-Bev and subsequent re-escalation if necessary.

Trial Registration
ClinicalTrials.gov Identifier NCT01249638

EudraCT-No.: 2009-013099-38
Enzyme production by filamentous fungi: analysis of the secretome of Trichoderma reesei grown on unconventional carbon source
Authors: Jun He , Kieselbach Thomas , Jönsson Leif J 
Published: August 2011

Abstract

Background
Spent hydrolysates from bioethanolic fermentation processes based on agricultural residues have potential as an abundant and inexpensive source of pentose sugars and acids that could serve as nutrients for industrial enzyme-producing microorganisms, especially filamentous fungi. However, the enzyme mixtures produced in such media are poorly defined. In this study, the secretome of Trichoderma reesei Rut C-30 grown either on a spent hydrolysate model medium (SHMM) or on a lactose-based standard medium (LBSM) was explored using proteomics.

Results
Our results show that both the SHMM and LBSM serve as excellent growth media for T. reesei Rut C-30. In total, 52 protein spots on 2-D gels were identified by using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and electrospray ionization liquid chromatography tandem mass spectrometry (ESI-LC MS/MS). As expected, a considerable number of the identified proteins were related to the degradation of lignocellulosic biomass. The enzyme production profiles in the two media were similar, but β-glucosidase and β-galactosidase were only produced in LBSM. The main cellobiohydrolases (Cel7A/Cel6A) and endoglucanases (Cel7B/Cel5A) were identified in both media and the cellobiohydrolases, i.e. Cel7A and Cel6A, were the most abundant cellulolytic enzymes. Moreover, both media can also serve as a potent inducer of xylanolytic enzymes. Several key enzymes involved in sugar assimilation and regulation of cellulase formation were identified, and were found to be differentially expressed in the two growth media.

Conclusions
This study not only provides a catalogue of the prevalent proteins secreted by T. reesei in the two media, but the results also suggest that production of hydrolytic enzymes using unconventional carbon sources, such as components in spent hydrolysates, deserves further attention in the future.
Effect of iron oxide and gold nanoparticles on bacterial growth leading towards biological application
Authors: Chatterjee Saptarshi , Bandyopadhyay Arghya , Sarkar Keka 
Published: August 2011

Abstract

Background
Nanoparticle-metal oxide and gold represents a new class of important materials that are increasingly being developed for use in research and health related activities. The biological system being extremely critical requires the fundamental understanding on the influence of inorganic nanoparticles on cellular growth and functions. Our study was aimed to find out the effect of iron oxide (Fe3O4), gold (Au) nanoparticles on cellular growth of Escherichia coli (E. coli) and also try to channelize the obtained result by functionalizing the Au nanoparticle for further biological applications.

Result
Fe3O4 and Au nanoparticles were prepared and characterized using Transmission electron microscopy (TEM) and Dynamic Light Scattering (DLS). Preliminary growth analysis data suggest that the nanoparticles of iron oxide have an inhibitory effect on E. coli in a concentration dependant manner, whereas the gold nanoparticle directly showed no such activity. However the phase contrast microscopic study clearly demonstrated that the effect of both Fe3O4 and Au nanoparticle extended up to the level of cell division which was evident as the abrupt increase in bacterial cell length. The incorporation of gold nanoparticle by bacterial cell was also observed during microscopic analysis based on which glutathione functionalized gold nanoparticle was prepared and used as a vector for plasmid DNA transport within bacterial cell.

Conclusion
Altogether the study suggests that there is metal nanoparticle-bacteria interaction at the cellular level that can be utilized for beneficial biological application but significantly it also posses potential to produce ecotoxicity, challenging the ecofriendly nature of nanoparticles.
Subtype distribution of lymphomas in Southwest China: Analysis of 6,382 cases using WHO classification in a single institution
Authors: Yang Qun-Pei , Zhang Wen-Yan , Yu Jian-Bo , Zhao Sha , Xu Huan , Wang Wei-Ya , Bi Cheng-Feng , Zuo Zhuo , Wang Xiao-Qing , Huang Juan , Dai Lin , Liu Wei-Ping 
Published: August 2011

Abstract

Background
The subtype distribution of lymphoid neoplasms in Southwest China was analyzed according to WHO classifications. This study aims to analyze subtype distribution of lymphomas in southwest China.

Methods
Lymphoid neoplasms diagnosed within 9 years in a single institution in Southwest China were analyzed according to the WHO classification.

Results
From January 2000 to December 2008, a total number of 6,382 patients with lymphoma were established, of which mature B-cell neoplasms accounted for 56%, mature T- and NK-cell neoplasms occupied 26%, and precursor lymphoid neoplasms and Hodgkin lymphomas were 5% and 13%, respectively. Mixed cellularity (76%) was the major subtype of classical Hodgkin lymphoma; and the bimodal age distribution was not observed. The top six subtypes of non-Hodgkin lymphoma were as follows: diffuse large B-cell lymphoma, extranodal NK/T-cell lymphoma, nasal type, extranodal marginal zone lymphoma of mucosa associated lymphoid tissue, follicular lymphoma, precursor lymphoid neoplasms, and chronic lymphocytic leukemia/small lymphocytic lymphoma. Extranodal lymphomas comprised about half of all cases, and most frequently involved Waldeyer's ring, gastrointestinal tract, sinonasal region and skin.

Conclusions
The lymphoid neoplasms of Southwest China displayed some epidemiologic features similar to those reported in literature from western and Asian countries, as well as other regions of China, whereas some subtypes showed distinct features. The high frequency of mature T/NK cell neoplasms and extranodal lymphomas, especially for extranodal NK/T-cell lymphoma, nasal type, is the most outstanding characteristic of this series.
A glycine zipper motif mediates the formation of toxic β-amyloid oligomers in vitro and in vivo
Authors: Fonte Virginia , Dostal Vishantie , Roberts Christine M , Gonzales Patrick , Lacor Pascale , Magrane Jordi , Dingwell Natalie , Fan Emily Y , Silverman Michael A , Stein Gretchen H , Link Christopher D 
Published: August 2011

Abstract

Background
The β-amyloid peptide (Aβ) contains a Gly-XXX-Gly-XXX-Gly motif in its C-terminal region that has been proposed to form a "glycine zipper" that drives the formation of toxic Aβ oligomers. We have tested this hypothesis by examining the toxicity of Aβ variants containing substitutions in this motif using a neuronal cell line, primary neurons, and a transgenic C. elegans model.

Results
We found that a Gly37Leu substitution dramatically reduced Aβ toxicity in all models tested, as measured by cell dysfunction, cell death, synaptic alteration, or tau phosphorylation. We also demonstrated in multiple models that Aβ Gly37Leu is actually anti-toxic, thereby supporting the hypothesis that interference with glycine zipper formation blocks assembly of toxic Aβ oligomers. To test this model rigorously, we engineered second site substitutions in Aβ predicted by the glycine zipper model to compensate for the Gly37Leu substitution and expressed these in C. elegans. We show that these second site substitutions restore in vivo Aβtoxicity, further supporting the glycine zipper model.

Conclusions
Our structure/function studies support the view that the glycine zipper motif present in the C-terminal portion of Aβ plays an important role in the formation of toxic Aβ oligomers. Compounds designed to interfere specifically with formation of the glycine zipper could have therapeutic potential.
Rare variants in the ATMgene and risk of breast cancer
Authors: Goldgar David E , Healey Sue , Dowty James G , Da Silva Leonard , Chen Xiaoqing , Spurdle Amanda B , Terry Mary Beth , Daly Mary J , Buys Saundra M , Southey Melissa C , Andrulis Irene , John Esther M ,   BCFR,   kConFab, Khanna Kum Kum , Hopper John L , Oefner Peter J , Lakhani Sunil , Chenevix-Trench Georgia 
Published: August 2011

Abstract
Introduction
The ataxia-telangiectasia mutated (ATM) gene (MIM ID 208900) encodes a protein kinase that plays a significant role in the activation of cellular responses to DNA double-strand breaks through subsequent phosphorylation of central players in the DNA damage-response pathway. Recent studies have confirmed that some specific variants in the ATM gene are associated with increased breast cancer (BC) risk. However, the magnitude of risk and the subset of variants that are pathogenic for breast cancer remain unresolved.

Methods
To investigate the role of ATM in BC susceptibility, we studied 76 rare sequence variants in the ATM gene in a case-control family study of 2,570 cases of breast cancer and 1,448 controls. The variants were grouped into three categories based on their likely pathogenicity, as determined by in silico analysis and analyzed by conditional logistic regression. Likely pathogenic sequence variants were genotyped in 129 family members of 27 carrier probands (15 of which carried c.7271T > G), and modified segregation analysis was used to estimate the BC penetrance associated with these rare ATM variants.

Results
In the case-control analysis, we observed an odds ratio of 2.55 and 95% confidence interval (CI, 0.54 to 12.0) for the most likely deleterious variants. In the family-based analyses, the maximum-likelihood estimate of the increased risk associated with these variants was hazard ratio (HR) = 6.88 (95% CI, 2.33 to 20.3; P = 0.00008), corresponding to a 60% cumulative risk of BC by age 80 years. Analysis of loss of heterozygosity (LOH) in 18 breast tumors from women carrying likely pathogenic rare sequence variants revealed no consistent pattern of loss of the ATM variant.

Conclusions
The risk estimates from this study suggest that women carrying the pathogenic variant, ATM c.7271T > G, or truncating mutations demonstrate a significantly increased risk of breast cancer with a penetrance that appears similar to that conferred by germline mutations in BRCA2.
Cistrome: an integrative platform for transcriptional regulation studies
Authors: Liu Tao , Ortiz Jorge A , Taing Len , Meyer Clifford A , Lee Bernett , Zhang Yong , Shin Hyunjin , Wong Swee S , Ma Jian , Lei Ying , Pape Utz J , Poidinger Michael , Chen Yiwen , Yeung Kevin , Brown Myles , Turpaz Yaron , Liu X Shirley 
Published: August 2011

AbstractThe increasing volume of ChIP-chip and ChIP-seq data being generated creates a challenge for standard, integrative and reproducible bioinformatics data analysis platforms. We developed a web-based application called Cistrome, based on the Galaxy open source framework. In addition to the standard Galaxy functions, Cistrome has 29 ChIP-chip- and ChIP-seq-specific tools in three major categories, from preliminary peak calling and correlation analyses to downstream genome feature association, gene expression analyses, and motif discovery. Cistrome is available at http://cistrome.org/ap/.