bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular mechanisms of retinal pigment epithelium damage and development of age‐related macular degeneration
Authors: Kinnunen Kati , Petrovski Goran , Moe Morten C. , Berta András , Kaarniranta Kai 
Published: November 2011

Abstract.Age‐related macular degeneration (AMD) is attributed to a complex interaction of genetic and environmental factors. It is characterized by degeneration involving the retinal photoreceptors, retinal pigment epithelium (RPE) and Bruch’s membrane, as well as alterations in choroidal capillaries. AMD pathogenesis is strongly associated with chronic oxidative stress and inflammation that ultimately lead to protein damage, aggregation and degeneration of RPE. Specific degenerative findings for AMD are accumulation of intracellular lysosomal lipofuscin and extracellular drusens. In this review, we discuss thoroughly RPE‐derived mechanisms in AMD pathology.
Cellular Architecture Mediates DivIVA Ultrastructure and Regulates Min Activity in Bacillus subtilis
Authors: Eswaramoorthy Prahathees , Erb Marcella L. , Gregory James A. , Silverman Jared , Pogliano Kit , Pogliano Joe , Ramamurthi Kumaran S. 
Published: November 2011

ABSTRACT

The assembly of the cell division machinery at midcell is a critical step of cytokinesis. Many rod-shaped bacteria position septa using nucleoid occlusion, which prevents division over the chromosome, and the Min system, which prevents division near the poles. Here we examined the
in vivo
assembly of the
Bacillus subtilis
MinCD targeting proteins DivIVA, a peripheral membrane protein that preferentially localizes to negatively curved membranes and resembles eukaryotic tropomyosins, and MinJ, which recruits MinCD to DivIVA. We used structured illumination microscopy to demonstrate that both DivIVA and MinJ localize as double rings that flank the septum and first appear early in septal biosynthesis. The subsequent recruitment of MinCD to these double rings would separate the Min proteins from their target, FtsZ, spatially regulating Min activity and allowing continued cell division. Curvature-based localization would also provide temporal regulation, since DivIVA and the Min proteins would localize to midcell after the onset of division. We use time-lapse microscopy and fluorescence recovery after photobleaching to demonstrate that DivIVA rings are highly stable and are constructed from newly synthesized DivIVA molecules. After cell division, DivIVA rings appear to collapse into patches at the rounded cell poles of separated cells, with little or no incorporation of newly synthesized subunits. Thus, changes in cell architecture mediate both the initial recruitment of DivIVA to sites of cell division and the subsequent collapse of these rings into patches (or rings of smaller diameter), while curvature-based localization of DivIVA spatially and temporally regulates Min activity.

IMPORTANCE
The Min systems of
Escherichia coli
and
Bacillus subtilis
both inhibit FtsZ assembly, but one key difference between these two species is that whereas the
E. coli
Min proteins localize to the poles, the
B. subtilis
proteins localize to nascent division sites by interaction with DivIVA and MinJ. It is unclear how MinC activity at midcell is regulated to prevent it from interfering with FtsZ engaged in medial cell division. We used superresolution microscopy to demonstrate that DivIVA and MinJ, which localize MinCD, assemble double rings that flank active division sites and septa. This curvature-based localization mechanism holds MinCD away from the FtsZ ring at midcell, and we propose that this spatial organization is the primary mechanism by which MinC activity is regulated to allow division at midcell. Curvature-based localization also conveys temporal regulation, since it ensures that MinC localizes after the onset of division.
Long-term effects of increment coring on Norway spruce mortality
Authors: Wunder Jan , Reineking Björn , Hillgarter Franz-Werner , Bigler Christof , Bugmann Harald 
Published: November 2011

Increment coring of trees is a standard method in dendrochronology, wood anatomy, forest ecology, and forestry. However, increment coring is an invasive method that may result in tree decay and decreased physical stability of the cored tree. The long-term effects of coring on tree mortality are poorly understood for any tree species because long-term data sets are rare. We present results from a 40-year study on the effects of coring on tree mortality in a near-primary Norway spruce ( Picea abies (L.) Karst.) forest in the Swiss Alps (forest reserve Scatlè). In 1965–1966, 551 trees with a diameter at breast height ≥8 cm were cored within a 5.9 ha plot. Following a reassessment of the plot in 2006, we compared the mortality rates of the 551 trees cored in 1965 with those of similar trees from the uncored control group, i.e., trees that were similar in size (diameter at breast height), vitality, and forest layer class. Neither nonparametric tests nor logistic regression models indicate a significant influence of coring on tree mortality. Our results suggest that increment coring does not influence the mortality rate of P. abies within the study region. Additional studies in different environments and on different tree species are needed to evaluate the generality of our findings.
Relationships between salmon abundance and tree-ring δ15N: three objective tests
Authors: Drake D.C. , Sheppard Paul J. , Naiman Robert J. 
Published: November 2011

Quantification of a relationship between salmon escapement in rivers and riparian tree-ring δ15N could allow reconstruction of prehistorical salmon abundance. Unfortunately, attempts to quantify this link have met with little success. We examined the feasibility of the approach using natural abundance of δ15N in riparian tree rings formed before and after extirpation of salmon and 15N tracer studies in a river and riparian soils. We concluded that (i) extractable (sap) N must be removed for interpretation of tree-ring δ15N because it contains up to 78% of the N in wood, is mobile, and differs from structural N in isotopic composition, (ii) no significant change in structural tree-ring δ15N was associated with salmon extirpation in a natural system, (iii) 500‰ 15NH4+ added to a stream was detected in riparian tree rings spanning at least 8 years, demonstrating interring movement of N that confounds detection of an annual signal, and (iv) addition of 28 000‰ 15NH4+ to riparian soils at a rate equaling 7.25 kg salmon·50 m–2 resulted in maximum tree-ring δ15N of ∼100‰–600‰. Thus, the calculated maximum signal possible from salmon was 0.08‰–0.43‰, which is within the range of natural variation. Evidence suggested that neither total nor structural tree-ring δ15N was useful for reconstructing salmon abundance.
Metastatic Progression with Resistance to Aromatase Inhibitors Is Driven by the Steroid Receptor Coactivator SRC-1
Authors: McBryan Jean , Theissen Sarah M. , Byrne Christopher , Hughes Eamon , Cocchiglia Sinead , Sande Stephen , O'Hara Jane , Tibbitts Paul , Hill Arnold D.K. , Young Leonie S. 
Published: November 2011

Abstract
Aromatase inhibitors (AI) are a standard-of-care treatment for postmenopausal, estrogen receptor–positive breast cancers. Although tumor recurrence on AI therapy occurs, the mechanisms underlying acquired resistance to AIs remain unknown. In this study, we examined a cohort of endocrine-treated breast cancer patients and used a cell line model of resistance to the AI letrozole. In patients treated with a first-line AI, hormone receptor switching between primary and resistant tumors was a common feature of disease recurrence. Resistant cells exhibited a switch from steroid-responsive growth to growth factor–responsive and endocrine-independent growth, which was accompanied by the development of a more migratory and disorganized phenotype. Both the resistant cells and tumors from AI-resistant patients showed high expression of the steroid receptor coactivator SRC-1. Direct interactions between SRC-1 and the transcription factor Ets2 regulated Myc and MMP9. SRC-1 was required for the aggressive and motile phenotype of AI-resistant cells. Interestingly, SRC-1 expression in primary and/or recurrent tumors was associated with a reduction in disease-free survival in treated patients. Moreover, there was a significant association between SRC-1 and Ets2 in the recurrent tissue compared with the matched primary tumor. Together, our findings elucidate a mechanism of AI-specific metastatic progression in which interactions between SRC-1 and Ets2 promote dedifferentiation and migration in hormone-dependent breast cancer. Cancer Res; 72(2); 548–59. ©2011 AACR.
Curcumin Analogue CDF Inhibits Pancreatic Tumor Growth by Switching on Suppressor microRNAs and Attenuating EZH2 Expression
Authors: Bao Bin , Ali Shadan , Banerjee Sanjeev , Wang Zhiwei , Logna Farah , Azmi Asfar S. , Kong Dejuan , Ahmad Aamir , Li Yiwei , Padhye Subhash , Sarkar Fazlul H. 
Published: November 2011

Abstract
The histone methyltransferase EZH2 is a central epigenetic regulator of cell survival, proliferation, and cancer stem cell (CSC) function. EZH2 expression is increased in various human cancers, including highly aggressive pancreatic cancers, but the mechanisms underlying for its biologic effects are not yet well understood. In this study, we probed EZH2 function in pancreatic cancer using diflourinated-curcumin (CDF), a novel analogue of the turmeric spice component curcumin that has antioxidant properties. CDF decreased pancreatic cancer cell survival, clonogenicity, formation of pancreatospheres, invasive cell migration, and CSC function in human pancreatic cancer cells. These effects were associated with decreased expression of EZH2 and increased expression of a panel of tumor-suppressive microRNAs (miRNA), including let-7a, b, c, d, miR-26a, miR-101, miR-146a, andmiR-200b, c that are typically lost in pancreatic cancer. Mechanistic investigations revealed that reexpression of miR-101 was sufficient to limit the expression of EZH2 and the proinvasive cell surface adhesion molecule EpCAM. In an orthotopic xenograft model of human pancreatic cancer, administration of CDF inhibited tumor growth in a manner associated with reduced expression of EZH2, Notch-1, CD44, EpCAM, and Nanog and increased expression of let-7, miR-26a, and miR-101. Taken together, our results indicated that CDF inhibited pancreatic cancer tumor growth and aggressiveness by targeting an EZH2-miRNA regulatory circuit for epigenetically controlled gene expression. Cancer Res; 72(1); 335–45. ©2011 AACR.
Dual Inhibition of the PI3K/mTOR Pathway Increases Tumor Radiosensitivity by Normalizing Tumor Vasculature
Authors: Fokas Emmanouil , Im Jae Hong , Hill Sally , Yameen Sabira , Stratford Michael , Beech John , Hackl Wolfgang , Maira Sauveur-Michel , Bernhard Eric J. , McKenna W. Gillies , Muschel Ruth J. 
Published: November 2011

Abstract
The aberrant vascular architecture of solid tumors results in hypoxia that limits the efficacy of radiotherapy. Vascular normalization using antiangiogenic agents has been proposed as a means to improve radiation therapy by enhancing tumor oxygenation, but only short-lived effects for this strategy have been reported so far. Here, we show that NVP-BEZ235, a dual inhibitor of phosphoinositide-3-kinase (PI3K) and mTOR, can improve tumor oxygenation and vascular structure over a prolonged period that achieves the aim of effective vascular normalization. Because PI3K inhibition can radiosensitize tumor cells themselves, our experimental design explicitly distinguished effects on the blood vasculature versus tumor cells. Drug administration coincident with radiation enhanced the delay in tumor growth without changing tumor oxygenation, establishing that radiosensitization is a component of the response. However, the enhanced growth delay was substantially greater after induction of vascular normalization, meaning that this treatment enhanced the tumoral radioresponse. Importantly, changes in vascular morphology persisted throughout the entire course of the experiment. Our findings indicated that targeting the PI3K/mTOR pathway can modulate the tumor microenvironment to induce a prolonged normalization of blood vessels. The substantial therapeutic gain observed after combination of NVP-BEZ235 with irradiation has conceptual implications for cancer therapy and could be of broad translational importance. Cancer Res; 72(1); 239–48. ©2011 AACR.
The use of multiple sclerosis condition-specific measures to inform health policy decision-making: mapping from the MSWS-12 to the EQ-5D
Authors: Hawton A , Green C , Telford CJ , Wright DE , Zajicek JP 
Published: November 2011

Background: Walking impairment has a major influence on the quality of life of people with multiple sclerosis (MS). The Multiple Sclerosis Walking Scale (MSWS-12) assesses the impact of MS on walking ability from the patient’s perspective, but in its current form, is not amenable for use in many policy decision-making settings. Objectives: Statistical ‘mapping’ methods were used to convert MSWS-12 scores to EQ-5D health state values. Methods: The relationship between the measures was estimated using cohort data from people with MS in South West England. Regression analyses were conducted, estimation errors assessed, and predictive performance of the best models tested using longitudinal data. Results: Model performance was in line with that of other mapping studies, with the best-performing models being an ordinary least squares (OLS) model using MSWS-12 item scores, and an OLS model using the total MSWS-12 score and its squared term. Conclusions: A process has been described whereby data from a patient-reported outcome measure (MSWS-12) can be converted to (EQ-5D) health state values. These values may be used to consider the health-related quality of life of people with MS, to estimate quality adjusted life-years for use in effectiveness and cost-effectiveness analyses, and to inform health policy decisions.
Maternal topoisomerase II alpha, not topoisomerase II beta, enables embryonic development of zebrafish top2a
-/-
mutants
Authors: Sapetto-Rebow Beata , McLoughlin Sarah C , O'Shea Lynne C , O'Leary Olivia , Willer Jason R , Alvarez Yolanda , Collery Ross , O'Sullivan Jacintha , Van Eeden Freek , Hensey Carmel , Kennedy Breandán N 
Published: November 2011

Abstract

Background
Genetic alterations in human topoisomerase II alpha (TOP2A) are linked to cancer susceptibility. TOP2A decatenates chromosomes and thus is necessary for multiple aspects of cell division including DNA replication, chromosome condensation and segregation. Topoisomerase II alpha is also required for embryonic development in mammals, as mouse Top2a knockouts result in embryonic lethality as early as the 4-8 cell stage. The purpose of this study was to determine whether the extended developmental capability of zebrafish top2a mutants arises from maternal expression of top2a or compensation from its top2b paralogue.

Results
Here, we describe bloody minded (blm), a novel mutant of zebrafish top2a. In contrast to mouse Top2a nulls, zebrafish top2a mutants survive to larval stages (4-5 day post fertilization). Developmental analyses demonstrate abundant expression of maternal top2a but not top2b. Inhibition or poisoning of maternal topoisomerase II delays embryonic development by extending the cell cycle M-phase. Zygotic top2a and top2b are co-expressed in the zebrafish CNS, but endogenous or ectopic top2b RNA appear unable to prevent the blm phenotype.

Conclusions
We conclude that maternal top2a enables zebrafish development before the mid-zygotic transition (MZT) and that zebrafish top2a and top2b are not functionally redundant during development after activation of the zygotic genome.
Transcriptome analysis of ectopic chloroplast development in green curd cauliflower (Brassica oleracea L. var. botrytis)
Authors: Zhou Xiangjun , Fei Zhangjun , Thannhauser Theodore W , Li Li 
Published: November 2011

Abstract

Background
Chloroplasts are the green plastids where photosynthesis takes place. The biogenesis of chloroplasts requires the coordinate expression of both nuclear and chloroplast genes and is regulated by developmental and environmental signals. Despite extensive studies of this process, the genetic basis and the regulatory control of chloroplast biogenesis and development remain to be elucidated.

Results
Green cauliflower mutant causes ectopic development of chloroplasts in the curd tissue of the plant, turning the otherwise white curd green. To investigate the transcriptional control of chloroplast development, we compared gene expression between green and white curds using the RNA-seq approach. Deep sequencing produced over 15 million reads with lengths of 86 base pairs from each cDNA library. A total of 7,155 genes were found to exhibit at least 3-fold changes in expression between green and white curds. These included light-regulated genes, genes encoding chloroplast constituents, and genes involved in chlorophyll biosynthesis. Moreover, we discovered that the cauliflower ELONGATED HYPOCOTYL5 (BoHY5) was expressed higher in green curds than white curds and that 2616 HY5-targeted genes, including 1600 up-regulated genes and 1016 down-regulated genes, were differently expressed in green in comparison to white curd tissue. All these 1600 up-regulated genes were HY5-targeted genes in the light.

Conclusions
The genome-wide profiling of gene expression by RNA-seq in green curds led to the identification of large numbers of genes associated with chloroplast development, and suggested the role of regulatory genes in the high hierarchy of light signaling pathways in mediating the ectopic chloroplast development in the green curd cauliflower mutant.
Seroprevalence and risk factors of herpes simplex virus type-2 infection among pregnant women in Northeast India
Authors: Biswas Dipankar , Borkakoty Biswajyoti , Mahanta Jagadish , Walia Kamini , Saikia Lahari , Akoijam Brogen S , Jampa Lobsang , Kharkongar Alia , Zomawia Eric 
Published: November 2011

Abstract

Background
Herpes simplex virus type-2 (HSV-2) is one of the most common sexually transmitted infections that facilitate human immunodeficiency virus (HIV) acquisition by over two fold or more. The development of HSV-2 control methods as a measure to control HIV epidemic in high HSV-2/HIV areas has become a priority. Two out of the six high HIV prevalent states of India are located in the Northeastern region of India. Due to lack of documented HSV-2 studies from this part of the country; there was a need for estimating the seroprevalence and risk factors of HSV-2 infection in this defined population.

Methods
Pregnant women (n = 1640) aged18 years and above attending antenatal clinics of tertiary referral hospitals in five Northeastern states of India were screened for type specific HSV-2 IgG antibodies. Blood samples were collected from all the participants after conducting interviews. Univariate and multivariate analyses were performed to identify the risk factors associated with HSV-2 seropositivity.

Results
Overall seroprevalence of HSV-2 infection was 8.7% (142/1640; 95% CI 7.3-10.0) with a highest prevalence of 15.0% (46/307; 95% CI 11.0-19.0) in the state of Arunachal Pradesh. Higher seroprevalence was observed with increasing age (Adj. Odds Ratio [AOR] 1.9 for 22-25 years old, AOR 2.29 for > 29 years old). The risk factors associated with HSV-2 seropositives were multiple sex partners (AOR 2.5, p = 0.04), condom non-user's (AOR 4.7, p < 0.001), early coitarchal age (age of first intercourse) 'less than 18 years' (AOR 9.6, p = 0.04), middle income group (AOR 2.1, p = 0.001) compared to low income group and low level of education (AOR 3.7, p = 0.02) compared to higher education. HSV-2 seropositivity was higher among Christians (12.6%) compared to Muslims (3.8%). The most frequent clinical symptoms among HSV-2 seropositives were excess vaginal discharge in last one year (53.5%, 76/142) and pelvic pain (26.1%, 37/142). While among subjects with genital ulcers, HSV-2 seroprevalence was 36.8% (7/19).

Conclusions
Overall seroprevalence of HSV-2 infection among pregnant women of Northeast India is relatively low. The generation of awareness among high risk groups may have played key role to limit the infection. The role of vaccination against HSV-2 in near future and elimination of HSV-2 viral shedding along with genital tract inflammation in high HIV/HSV-2 areas may be an option for initiating successful intervention strategies to reduce the transmission and acquisition of HIV infection in Northeast India.
Measuring health-related quality of life in children with cancer living in mainland China: feasibility, reliability and validity of the Chinese mandarin version of PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module
Authors: Ji Yi , Chen Siyuan , Li Kai , Xiao Nong , Yang Xue , Zheng Shan , Xiao Xianmin 
Published: November 2011

AbstractBackgroundThe Pediatric Quality of Life Inventory (PedsQL) is widely used instrument to measure pediatric health-related quality of life (HRQOL) for children aged 2 to 18 years. The purpose of the current study was to investigate the feasibility, reliability and validity of the Chinese mandarin version of the PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module in a group of Chinese children with cancer.MethodsThe PedsQL 4.0 Genetic Core Scales and the PedsQL 3.0 Cancer Module were administered to children with cancer (aged 5-18 years) and parents of such children (aged 2-18 years). For comparison, a survey on a demographically group-matched sample of the general population with children (aged 5-18) and parents of children (aged 2-18 years) was conducted with the PedsQL 4.0 Genetic Core Scales.ResultThe minimal mean percentage of missing item responses (except the School Functioning scale) supported the feasibility of the PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module for Chinese children with cancer. Most of the scales showed satisfactory reliability with Cronbach's α of exceeding 0.70, and all scales demonstrated sufficient test-retest reliability. Assessing the clinical validity of the questionnaires, statistically significant difference was found between healthy children and children with cancer, and between children on-treatment versus off-treatment ≥12 months. Positive significant correlations were observed between the scores of the PedsQL 4.0 Generic Core Scale and the PedsQL 3.0 Cancer Module. Exploratory factor analysis demonstrated sufficient factorial validity. Moderate to good agreement was found between child self- and parent proxy-reports.ConclusionThe findings support the feasibility, reliability and validity of the Chinese Mandarin version of PedsQL 4.0 Generic Core Scales and 3.0 Cancer Module in children with cancer living in mainland China.