bluuebunny/crossref_metadata_2025 huggingface dataset:
The Cranston Library, Reigate: The First Three Hundred Years
Authors: Thomas Andrea , Ely Hilary
Published: December 2011

The Cranston Library, Reigate, is a remarkable example of an early eighteenth-century parish library, which retains almost all of its original collection in its original location. It was founded by Revd Andrew Cranston in 1701 and was established as a charitable trust in 1708. It was the only library specifically exempted from the provisions of the 1708/09 Parochial Libraries Act. From the start it operated as a public lending library and, until the establishment of the Surrey County Library Service in the 1920s, it provided intellectual stimulus for all the people of Reigate, not just the clergy. The collection is not entirely theological, but contains some 2350 volumes on a wide range of subjects. The Library's records of donors, borrowers, and trustees, and the books themselves, provide a fascinating insight into the intellectual climate of the period.

In the twenty-first century we endeavour to maintain the Library in good condition as a jewel of the local heritage, and as an academic resource for scholars. All our trustees and helpers are volunteers and we have no financial endowment behind us. We are therefore reliant on the generosity of our supporters and the good offices of the Reigate Decorative and Fine Arts Society and the Cowlishaw conservation workshop to achieve our aims. The opportunities and pitfalls of the digital age present the current trustees with many new challenges as we try to balance the demands of access with security, and preservation with utilization. We take inspiration from our founder and seek to ensure that the Library should flourish for at least another three hundred years.
Quaker Meeting Libraries
Authors: Hall David J
Published: December 2011

The paper offers a very brief introduction to the history of Quaker meeting libraries. It is based on printed catalogues, meeting histories, rules and advice issued at the national level, and some secondary sources. The possible number of such libraries is considered. Examples are given of the size of some libraries. Finally, something is said about the present situation in the Society of Friends.
Mitochondrial dysfunction in ataxia-telangiectasia
Authors: Valentin-Vega Yasmine A. , MacLean Kirsteen H. , Tait-Mulder Jacqueline , Milasta Sandra , Steeves Meredith , Dorsey Frank C. , Cleveland John L. , Green Douglas R. , Kastan Michael B.
Published: December 2011

Ataxia-telangiectasia mutated (ATM) plays a central role in DNA damage responses, and its loss leads to development of T-cell malignancies. Here, we show that ATM loss also leads to intrinsic mitochondrial abnormalities in thymocytes, including elevated reactive oxygen species, increased aberrant mitochondria, high cellular respiratory capacity, and decreased mitophagy. A fraction of ATM protein is localized in mitochondria, and it is rapidly activated by mitochondrial dysfunction. Unexpectedly, allelic loss of the autophagy regulator Beclin-1 significantly delayed tumor development in ATM-null mice. This effect was not associated with rescue of DNA damage signaling but rather with a significant reversal of the mitochondrial abnormalities. These data support a model in which ATM plays direct roles in modulating mitochondrial homeostasis and suggest that mitochondrial dysfunction and associated increases in mitochondrial reactive oxygen species contribute to the cancer-prone phenotype observed in organisms lacking ATM. Thus, ataxia-telangiectasia should be considered, at least in part, as a mitochondrial disease.
Specificity and selectivity profile of EP217609: a new neutralizable dual-action anticoagulant that targets thrombin and factor Xa
Authors: Olson Steven T. , Swanson Richard , Petitou Maurice
Published: December 2011

EP217609 is a new dual-action parenteral anticoagulant that combines an indirect factor Xa inhibitor (fondaparinux analog) and a direct thrombin inhibitor (α-NAPAP analog) in a single molecule together with a biotin tag to allow avidin neutralization. EP217609 exhibits an unprecedented pharmacologic profile in showing high bioavailability, long plasma half-life, and potent antithrombotic activity in animals without the complications of thrombin rebound. Here we report the exceptional specificity and selectivity profile of EP217609. EP217609 inhibited thrombin with rapid kinetics (kon > 107M−1s−1), a high affinity (KI = 30-40pM), and more than 1000-fold selectivity over other coagulation and fibrinolytic protease targets, comparing favorably with the best direct thrombin inhibitors known. EP217609 bound antithrombin with high affinity (KD = 30nM) and activated the serpin to rapidly (kass ∼ 106M−1s−1) and selectively (> 20-fold) inhibit factor Xa. The dual inhibitor moieties of EP217609 acted largely independently with only modest linkage effects of ligand occupancy of one inhibitor moiety on the potency of the other (∼ 5-fold). In contrast, avidin binding effectively neutralized the potency of both inhibitor moieties (20- to 100-fold). These findings demonstrate the superior anticoagulant efficacy and rapid avidin neutralizability of EP217609 compared with anticoagulants that target thrombin or factor Xa alone.
FGFR2 genotype and risk of radiation-associated breast cancer in Hodgkin lymphoma
Authors: Ma Yussanne P. , van Leeuwen Flora E. , Cooke Rosie , Broeks Annegien , Enciso-Mora Victor , Olver Bianca , Lloyd Amy , Broderick Peter , Russell Nicola S. , Janus Cecile , Ashworth Alan , Houlston Richard S. , Swerdlow Anthony J.
Published: December 2011

Women treated at young ages with supradiaphragmatic radiotherapy for Hodgkin lymphoma (HL) have a highly increased risk of breast cancer. For personalized advice and follow-up regimens for patients, information is needed on how the radiotherapy-related risk is affected by other breast cancer risk factors. Genome-wide association studies have identified 14 independently replicated common single nucleotide polymorphisms that influence breast cancer risk. To examine whether these variants contribute to risk of radiation-associated breast cancer in HL, we analyzed 2 independent case-control series, from the United Kingdom and The Netherlands, totaling 693 HL patients, 232 with breast cancer and 461 without. rs1219648, which annotates the FGFR2 gene, was associated with risk in both series (combined per-allele odds ratio = 1.59, 95% confidence interval: 1.26-2.02; P = .000111). These data provide evidence that genetic variation in FGFR2 influences radiation-induced breast cancer risk.
Human biomonitoring on heavy metals in Ath: methodological aspects
Authors: Rebolledo Javiera , Fierens Sebastien , Versporten Ann , Brits Ethel , De Plaen Pierre , Van Nieuwenhuyse An
Published: December 2011

The municipality of Ath is characterised by the presence, in its center, of two non-ferrous metal industries whose emissions make local residents concerned for their health. Therefore, authorities of the Walloon Region and the municipality of Ath undertook biomonitoring to assess the impact of those industrial emissions on heavy metal body burden in humans.

This paper describes the study design and methodology used to carry out this human biomonitoring.

A random sampling was done in the general population, in two areas of Ath: an area centered around the industries and a peripheral area. The target population was children (2.5-11 years) and adults (40-60 years) without occupational exposure. The three-stage sampling procedure consisted of a mixture of both mail and telephone recruitment. Firstly, 3259 eligible people, identified from a population register, were mailed an introductory letter. In a second stage, eligible individuals were contacted by phone to propose them to participate in the study. They were randomly contacted until the required sample size was obtained. In the third stage, a second mail was sent to those who agreed to participate with a questionnaire to be filled out. Finally, biological samples (blood and urine) from 278 persons were collected. The final participation rate of this study was 24%.

This sampling procedure, especially designed for the purpose of this biomonitoring study in Ath, allowed us to recruit a sample representative of the population of children and adults of Ath, reaching the expected sample size in a short period of time.
How can the results of a qualitative process evaluation be applied in management, improvement and modification of a preventive community trial? The IHHP Study
Authors: Sarrafzadegan Nizal , Rabiei Katayoun , Alavi Mousa , Abedi Heidarali , Zarfeshani Sonia
Published: December 2011

Background

This study reports the results of the qualitative process evaluation (PE) of the Isfahan Healthy Heart Program (IHHP), an integrated community-based trial for prevention and control of non-communicable diseases in Iran.

Methods

The study explored the overall quality of program implementation. The participants, including designers of IHHP, stakeholders and community members (n = 60) were purposefully recruited from the intervention areas. Data collected from semi-structured interviews and field notes were analyzed using a modified thematic analysis.

Results

Four main themes were identified. Our findings highlighted the key role of the resources as both facilitating and hindering factors. IHHP directors faced incompatibilities arising from negative perceptions/attitudes which resulted in decreased adherence to the program. Hence various strategies were used to motivate, strengthen and organize the human workforce implementing the program.

Conclusion

Recommendations arising from evaluation of the program were used in subsequent stages of implementation. Qualitative research is an important component of community trials which can improve their implementation.
TMPRSS2-ERG -specific transcriptional modulation is associated with prostate cancer biomarkers and TGF-β signaling
Authors: Brase Jan C , Johannes Marc , Mannsperger Heiko , Fälth Maria , Metzger Jennifer , Kacprzyk Lukasz A , Andrasiuk Tatjana , Gade Stephan , Meister Michael , Sirma Hüseyin , Sauter Guido , Simon Ronald , Schlomm Thorsten , Beißbarth Tim , Korf Ulrike , Kuner Ruprecht , Sültmann Holger
Published: December 2011

Background

TMPRSS2-ERG gene fusions occur in about 50% of all prostate cancer cases and represent promising markers for molecular subtyping. Although TMPRSS2-ERG fusion seems to be a critical event in prostate cancer, the precise functional role in cancer development and progression is still unclear.

Methods

We studied large-scale gene expression profiles in 47 prostate tumor tissue samples and in 48 normal prostate tissue samples taken from the non-suspect area of clinical low-risk tumors using Affymetrix GeneChip Exon 1.0 ST microarrays.

Results

Comparison of gene expression levels among TMPRSS2-ERG fusion-positive and negative tumors as well as benign samples demonstrated a distinct transcriptional program induced by the gene fusion event. Well-known biomarkers for prostate cancer detection like CRISP3 were found to be associated with the gene fusion status. WNT and TGF-β/BMP signaling pathways were significantly associated with genes upregulated in TMPRSS2-ERG fusion-positive tumors.

Conclusions

The TMPRSS2-ERG gene fusion results in the modulation of transcriptional patterns and cellular pathways with potential consequences for prostate cancer progression. Well-known biomarkers for prostate cancer detection were found to be associated with the gene fusion. Our results suggest that the fusion status should be considered in retrospective and future studies to assess biomarkers for prostate cancer detection, progression and targeted therapy.
The working alliance in a randomized controlled trial comparing online with face-to-face cognitive-behavioral therapy for depression
Authors: Preschl Barbara , Maercker Andreas , Wagner Birgit
Published: December 2011

Background

Although numerous efficacy studies in recent years have found internet-based interventions for depression to be effective, there has been scant consideration of therapeutic process factors in the online setting. In face-to face therapy, the quality of the working alliance explains variance in treatment outcome. However, little is yet known about the impact of the working alliance in internet-based interventions, particularly as compared with face-to-face therapy.

Methods

This study explored the working alliance between client and therapist in the middle and at the end of a cognitive-behavioral intervention for depression. The participants were randomized to an internet-based treatment group (n = 25) or face-to-face group (n = 28). Both groups received the same cognitive behavioral therapy over an 8-week timeframe. Participants completed the Beck Depression Inventory (BDI) post-treatment and the Working Alliance Inventory at mid- and post- treatment. Therapists completed the therapist version of the Working Alliance Inventory at post-treatment.

Results

With the exception of therapists' ratings of the tasks subscale, which were significantly higher in the online group, the two groups' ratings of the working alliance did not differ significantly. Further, significant correlations were found between clients' ratings of the working alliance and therapy outcome at post-treatment in the online group and at both mid- and post-treatment in the face-to-face group. Correlation analysis revealed that the working alliance ratings did not significantly predict the BDI residual gain score in either group.

Conclusions

Contrary to what might have been expected, the working alliance in the online group was comparable to that in the face-to-face group. However, the results showed no significant relations between the BDI residual gain score and the working alliance ratings in either group.

Trial registration

ACTRN12611000563965
Influence of the Chungkookjang on histamine-induced wheal and flare skin response: a randomized, double-blind, placebo controlled trial
Authors: Kwon Dae-Young , Yang Hye-Jeong , Kim Min-Jeong , Kang Hee-Joo , Kim Hyun-Jin , Ha Ki-Chan , Back Hyang-Im , Kim Sun-Young , Park Eun-Ok , Kim Min-Gul , Yun Seok-Kwon , Chae Soo-Wan , Cho Back-Hwan
Published: December 2011

Abstracts

Background

Allergic disease is a consequence of exposure to normally innocuous substances that elicit the activation of mast cells. Mast-cell-mediated allergic response is involved in many diseases such as anaphylaxis, urticaria, allergic rhinitis, asthma and allergic dermatitis. The development of food products for the prevention of allergic disease is an important subject in human health. The chungkookjang (CKJ) has been reported to exhibit antiallergic inflammatory activity. Therefore, the aim of the study is to examine the effects of the CKJ to reduce histamine-induced wheal and flare skin responses.

Methods/Design

A randomized, double-blind, placebo-controlled study in 60 healthy subjects will be carried out. Sixty volunteers (aged 20-80) who gave a written consent before entering the study will be randomized in two groups of thirty subjects each. The skin prick test with histamine solution of 10 mg/ml will be performed on the ventral forearm, 10 cm from the elbow. The subjects will be instructed to take 35 g per day of either the CKJ pills or a placebo pills for a period of 3 months. Diameters of wheal and flare will be assessing 15 minutes after performing the above-mentioned skin prick test. The primary outcome is change in wheal and flare responses. Secondary outcomes will be include change in serum histamine, immunoglobulin E, cytokines (interferon-gamma, interleukin-4, -10, and tumor necrosis factor-alpha), and eosinophil cationic protein.

Discussion

This study will show the potential anti-inflammatory properties of the CKJ in their skin activity when histamine is the challenging agent as occurs in the clinical situation. And the present protocol will confirm the efficacy and safety of the CKJ for allergy symptoms, suggesting more basic knowledge to conduct further randomized controlled trials (RCT). If this study will be successfully performed, the CKJ will be an alternative dietary supplemental remedy for allergy patients.

Trial Registration

NCT01402141
Sexual recombination is a signature of a persisting malaria epidemic in Peru
Authors: Sutton Patrick L , Torres Lindsay P , Branch OraLee H
Published: December 2011

Background

The aim of this study was to consider the impact that multi-clone, complex infections have on a parasite population structure in a low transmission setting. In general, complexity of infection (minimum number of clones within an infection) and the overall population level diversity is expected to be minimal in low transmission settings. Additionally, the parasite population structure is predicted to be clonal, rather than sexual due to infrequent parasite inoculation and lack of recombination between genetically distinct clones. However, in this low transmission of the Peruvian Amazon, complex infections are becoming more frequent, in spite of decreasing infection prevalence. In this study, it was hypothesized that sexual recombination between distinct clonal lineages of Plasmodium falciparum parasites were altering the subpopulation structure and effectively maintaining the population-level diversity.

Methods

Fourteen microsatellite markers were chosen to describe the genetic diversity in 313 naturally occurring P. falciparum infections from Peruvian Amazon. The population and subpopulation structure was characterized by measuring: clusteredness, expected heterozygosity (He), allelic richness, private allelic richness, and linkage disequilibrium. Next, microsatellite haplotypes and alleles were correlated with P. falciparum merozoite surface protein 1 Block 2 (Pf msp1-B2) to examine the presence of recombinant microsatellite haplotypes.

Results

The parasite population structure consists of six genetically diverse subpopulations of clones, called "clusters". Clusters 1, 3, 4, and 6 have unique haplotypes that exceed 70% of the total number of clones within each cluster, while Clusters 2 and 5 have a lower proportion of unique haplotypes, but still exceed 46%. By measuring the He, allelic richness, and private allelic richness within each of the six subpopulations, relatively low levels of genetic diversity within each subpopulation (except Cluster 4) are observed. This indicated that the number of alleles, and not the combination of alleles, are limited. Next, the standard index of association (IA
S) was measured, which revealed a significant decay in linkage disequilibrium (LD) associated with Cluster 6, which is indicative of independent assortment of alleles. This decay in LD is a signature of this subpopulation approaching linkage equilibrium by undergoing sexual recombination. To trace possible recombination events, the two most frequent microsatellite haplotypes observed over time (defined by either a K1 or Mad20) were selected as the progenitors and then potential recombinants were identified in within the natural population.

Conclusions

Contrary to conventional low transmission models, this study provides evidence of a parasite population structure that is superficially defined by a clonal backbone. Sexual recombination does occur and even arguably is responsible for maintaining the substructure of this population.
Weak and strong convergence theorems for relatively nonexpansive multi-valued mappings in Banach spaces
Authors: Homaeipour Simin , Razani Abdolrahman
Published: December 2011

In this paper, an iterative sequence for relatively nonexpansive multi-valued mappings by using the notion of generalized projection is introduced, and then weak and strong convergence theorems are proved.

2000 Mathematics Subject Classification: 47H09; 47H10; 47J25.
Weak and strong convergence theorems of implicit iteration process on Banach spaces
Authors: Lin Lai-Jiu , Chuang Chih-Sheng , Yu Zenn-Tsun
Published: December 2011

In this article, we first consider weak convergence theorems of implicit iterative processes for two nonexpansive mappings and a mapping which satisfies condition (C). Next, we consider strong convergence theorem of an implicit-shrinking iterative process for two nonexpansive mappings and a relative nonexpansive mapping on Banach spaces. Note that the conditions of strong convergence theorem are different from the strong convergence theorems for the implicit iterative processes in the literatures. Finally, we discuss a strong convergence theorem concerning two nonexpansive mappings and the resolvent of a maximal monotone operator in a Banach space.
Effects of Lactobacillus rhamnosus GG supplementation on cow's milk allergy in a mouse model
Authors: Thang Cin L , Baurhoo Bushansingh , Boye Joyce I , Simpson Benjamin K , Zhao Xin
Published: December 2011

Background

Cow's milk allergy (CMA) is one of the most prevalent human food-borne allergies, particularly in infants and young children from developed countries. Our study aims to evaluate the effects ofLactobacillus rhamnosusGG (LGG) administration on CMA development using whole cow's milk proteins (CMP) sensitized Balb/C mice by two different sensitization methods.

Methods

LGG supplemented mice were either sensitized orally with CMP and cholera toxin B-subunit (CTB) as adjuvant, or intraperitoneally (IP) with CMP but without the adjuvant. Mice were then orally challenged with CMP and allergic responses were accessed by monitoring hypersensitivity scores, measuring the levels of CMP-specific immunoglobulins (IgG1, IgG2a and IgG) and total IgE from sera, and cytokines (IL-4 and IFN-γ) from spleen lysates.

Results

Sensitization to CMP was successful only in IP sensitized mice, but not in orally sensitized mice with CMP and CTB. Interestingly, LGG supplementation appeared to have reduced cow's milk allergy (CMA) in the IP group of mice, as indicated by lowered allergic responses.

Conclusions

Adjuvant-free IP sensitization with CMP was successful in inducing CMA in the Balb/C mice model. LGG supplementation favourably modulated immune reactions by shifting Th2-dominated trends toward Th1-dominated responses in CMP sensitized mice. Our results also suggest that oral sensitization by the co-administration of CMP and CTB, as adjuvant, might not be appropriate to induce CMA in mice.
Prolonged control of replication-competent dual- tropic human immunodeficiency virus-1 following cessation of highly active antiretroviral therapy
Authors: Salgado Maria , Rabi S Alireza , O'Connell Karen A , Buckheit III Robert W , Bailey Justin R , Chaudhry Amina A , Breaud Autumn R , Marzinke Mark A , Clarke William , Margolick Joseph B , Siliciano Robert F , Blankson Joel N
Published: December 2011

Background

While initiation of highly active antiretroviral therapy (HAART) during primary HIV-1 infection occasionally results in transient control of viral replication after treatment interruption, the vast majority of patients eventually experience a rebound in plasma viremia.

Results

Here we report a case of a patient who was started on HAART during symptomatic primary infection and who has subsequently maintained viral loads of < 50 copies/mL for more than nine years after the cessation of treatment. This patient had a high baseline viral load and has maintained a relatively high frequency of latently infected CD4+T cells. In addition, he does not have any known protective HLA alleles. Thus it is unlikely that he was destined to become a natural elite controller or suppressor. The mechanism of control of viral replication is unclear; he is infected with a CCR5/CXCR4 dual-tropic virus that is fully replication-competentin vitro. In addition, his spouse, who transmitted the virus to him, developed AIDS. The patient's CD4+T cells are fully susceptible to HIV-1 infection, and he has low titers of neutralizing antibodies to heterologous and autologous HIV-1 isolates. Furthermore, his CD8+T cells do not have potent HIV suppressive activity.

Conclusion

This report suggests that some patients may be capable of controlling pathogenic HIV-1 isolates for extended periods of time after the cessation of HAART through a mechanism that is distinct from the potent cytotoxic T lymphocyte (CTL) mediated suppression that has been reported in many elite suppressors.
Analysis of chicken anemia virus genome: evidence of intersubtype recombination
Authors: Eltahir Yassir M , Qian Kun , Jin Wenjie , Qin Aijian
Published: December 2011

Background

Chicken anemia virus (CAV) is the causative agent of chicken infectious anemia. CAV putative intergenotypic recombinants have been reported previously. This fact is based on the previous classification of CAV sequences into three genotypes. However, it is unknown whether intersubtype recombination occurs between the recently reported four CAV genotypes and five subtypes of genome sequences.

Results

Phylogenetic analysis, together with a variety of computational recombination detection algorithms, was used to investigate CAV approximately full genomes. Statistically significant evidence of intersubtype recombination was detected in the parent-like and two putative CAV recombinant sequences. This event was shown to occur between CAV subgroup A1 and A2 sequences in the phylogenetic trees.

Conclusions

We revealed that intersubtype recombination in CAV genome sequences played a role in generating genetic diversity within the natural population of CAV.
Albendazole sensitizes cancer cells to ionizing radiation
Authors: Patel Kirtesh , Doudican Nicole A , Schiff Peter B , Orlow Seth J
Published: December 2011

Background

Brain metastases afflict approximately half of patients with metastatic melanoma (MM) and small cell lung cancer (SCLC) and represent the direct cause of death in 60 to 70% of those affected. Standard of care remains ineffective in both types of cancer with the challenge of overcoming the blood brain barrier (BBB) exacerbating the clinical problem. Our purpose is to determine and characterize the potential of albendazole (ABZ) as a cytotoxic and radiosensitizing agent against MM and SCLC cells.

Methods

Here, ABZ's mechanism of action as a DNA damaging and microtubule disrupting agent is assessed through analysis of histone H2AX phosphorylation and cell cyle progression. The cytotoxicity of ABZ alone and in combination with radiation therapy is determined though clonogenic cell survival assays in a panel of MM and SCLC cell lines. We further establish ABZ's ability to act synergistically as a radio-sensitizer through combination index calculations and apoptotic measurements of poly (ADP-ribose) polymerase (PARP) cleavage.

Results

ABZ induces DNA damage as measured by increased H2AX phosphorylation. ABZ inhibits the growth of MM and SCLC at clinically achievable plasma concentrations. At these concentrations, ABZ arrests MM and SCLC cells in the G2/M phase of the cell cycle after 12 hours of treatment. Exploiting the notion that cells in the G2/M phase are the most sensitive to radiation therapy, we show that treatment of MM and SCLC cells treated with ABZ renders them more sensitive to radiation in a synergistic fashion. Additionally, MM and SCLC cells co-treated with ABZ and radiation exhibit increased apoptosis at 72 hours.

Conclusions

Our study suggests that the orally available antihelminthic ABZ acts as a potent radiosensitizer in MM and SCLC cell lines. Further evaluation of ABZ in combination with radiation as a potential treatment for MM and SCLC brain metastases is warranted.
Effects of Erxian decoction, a Chinese medicinal formulation, on serum lipid profile in a rat model of menopause
Authors: Sze Stephen CW , Cheung Ho-Pan , Ng Tzi-Bun , Zhang Zhang-Jing , Wong Kam-Lok , Wong Hei-Kiu , Hu Yong-Mei , Yow Christine MN , Tong Yao
Published: December 2011

Background

The prevalence and risk of cardiovascular disease increase after menopause in correlation with the progression of abnormality in the serum lipid profile and the deprivation of estrogen. Erxian decoction (EXD), a Chinese medicinal formulation for treating menopausal syndrome, stimulates ovarian estrogen biosynthesis. This study investigates whether EXD improves the serum lipid profile in a menopausal rat model.

Methods

Twenty-month-old female Sprague Dawley rats were treated with EXD and its constituent fractions. Premarin was administered for comparison. After eight weeks of treatment, rats were sacrificed and the serum levels of total cholesterol, triglyceride, high-density-lipoprotein cholesterol and low-density-lipoprotein cholesterol were determined. The hepatic protein levels of 3-hydroxy-3-methyl-glutaryl-CoA reductase and low-density-lipoprotein receptor were assessed with Western blot.

Results

The serum levels of total cholesterol and low-density-lipoprotein cholesterol were significantly lower in the EXD-treated group than in the constituent fractions of EXD or premarin groups. However, the serum levels of triglyceride and high-density-lipoprotein cholesterol were not significantly different from the control groups. Results from Western blot suggest that EXD significantly down-regulated the protein level of 3-hydroxy-3-methyl-glutaryl-CoA reductase and up-regulated low-density-lipoprotein receptor. Conclusion EXD improves serum lipid profile in a menopausal rat model through the suppression of the serum levels of total cholesterol and low-density-lipoprotein cholesterol, possibly through the down-regulation of the 3-hydroxy-3-methyl-glutaryl-CoA and up-regulation of the low-density-lipoprotein receptor.
Detection and quantification of poliovirus infection using FTIR spectroscopy and cell culture
Authors: Lee-Montiel Felipe T , Reynolds Kelly A , Riley Mark R
Published: December 2011

Background

In a globalized word, prevention of infectious diseases is a major challenge. Rapid detection of viable virus particles in water and other environmental samples is essential to public health risk assessment, homeland security and environmental protection. Current virus detection methods, especially assessing viral infectivity, are complex and time-consuming, making point-of-care detection a challenge. Faster, more sensitive, highly specific methods are needed to quantify potentially hazardous viral pathogens and to determine if suspected materials contain viable viral particles. Fourier transform infrared (FTIR) spectroscopy combined with cellular-based sensing, may offer a precise way to detect specific viruses. This approach utilizes infrared light to monitor changes in molecular components of cells by tracking changes in absorbance patterns produced following virus infection. In this work poliovirus (PV1) was used to evaluate the utility of FTIR spectroscopy with cell culture for rapid detection of infective virus particles.

Results

Buffalo green monkey kidney (BGMK) cells infected with different virus titers were studied at 1 - 12 hours post-infection (h.p.i.). A partial least squares (PLS) regression method was used to analyze and model cellular responses to different infection titers and times post-infection. The model performs best at 8 h.p.i., resulting in an estimated root mean square error of cross validation (RMSECV) of 17 plaque forming units (PFU)/ml when using low titers of infection of 10 and 100 PFU/ml. Higher titers, from 103 to 106 PFU/ml, could also be reliably detected.

Conclusions

This approach to poliovirus detection and quantification using FTIR spectroscopy and cell culture could potentially be extended to compare biochemical cell responses to infection with different viruses. This virus detection method could feasibly be adapted to an automated scheme for use in areas such as water safety monitoring and medical diagnostics.
A2A and A3 adenosine receptor expression in rheumatoid arthritis: upregulation, inverse correlation with disease activity score and suppression of inflammatory cytokine and metalloproteinase release
Authors: Varani Katia , Padovan Melissa , Vincenzi Fabrizio , Targa Martina , Trotta Francesco , Govoni Marcello , Borea Pier Andrea
Published: December 2011

Introduction

The reduction of the inflammatory status represents one of the most important targets in rheumatoid arthritis (RA). A central role of A2A and A3 adenosine receptors (ARs) in mechanisms of inflammation has been reported in different pathologies. The primary aim of this study was to investigate the A2A and A3ARs and their involvement in RA progression measured by Disease Activity Score in 28 or 44 joints (DAS28 or DAS).

Methods

ARs were analyzed by saturation binding assays, mRNA and Western blotting analysis in lymphocytes from early and established RA patients. The effect of A2A and A3AR agonists in nuclear factor kB (NF-kB) pathway was evaluated. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) release was carried out by A2A and A3AR activation. AR pharmacological regulation in matrix metalloproteinase-1 (MMP-1) and metalloproteinase-3 (MMP-3) release was also studied.

Results

In lymphocytes obtained from RA patients, A2A and A3ARs were up-regulated if compared with healthy controls. A2A and A3AR activation inhibited the NF-kB pathway and diminished inflammatory cytokines such as TNF-α, IL-1β and IL-6. A2A and A3AR agonists mediated a reduction of MMP-1 and MMP-3 release. A2A and A3AR density inversely correlated with DAS28 and DAS suggesting a direct role of the endogenous activation of these receptors in the control of RA joint inflammation.

Conclusions

Taken together these data demonstrate that the inflammatory and clinical responses in RA are regulated by A2A and A3ARs and support the use of A2A and/or A3AR agonists as novel and effective pharmacological treatment in RA patients.
Influence of Race, Insurance, Socioeconomic Status, and Hospital Type on Receipt of Guideline-Concordant Adjuvant Systemic Therapy for Locoregional Breast Cancers
Authors: Wu Xiao-Cheng , Lund Mary Jo , Kimmick Gretchen G. , Richardson Lisa C. , Sabatino Susan A. , Chen Vivien W. , Fleming Steven T. , Morris Cyllene R. , Huang Bin , Trentham-Dietz Amy , Lipscomb Joseph
Published: December 2011

For breast cancer, guidelines direct the delivery of adjuvant systemic therapy on the basis of lymph node status, histology, tumor size, grade, and hormonal receptor status. We explored how race/ethnicity, insurance, census tract-level poverty and education, and hospital Commission on Cancer (CoC) status were associated with the receipt of guideline-concordant adjuvant systemic therapy.

Methods

Locoregional breast cancers diagnosed in 2004 (n = 6,734) were from the National Program of Cancer Registries–funded seven-state Patterns of Care study of the Centers for Disease Control and Prevention. Predictors of guideline-concordant (receiving/not receiving) adjuvant systemic therapy, according to National Comprehensive Cancer Network Guidelines, were explored by logistic regression.

Results

Overall, 35% of women received nonguideline chemotherapy, 12% received nonguideline regimens, and 20% received nonguideline hormonal therapy. Significant predictors of nonguideline chemotherapy included Medicaid insurance (odds ratio [OR], 0.66; 95% CI, 0.50 to 0.86), high-poverty areas (OR, 0.77; 95% CI, 0.62 to 0.96), and treatment at non-CoC hospitals (OR, 0.69; 95% CI, 0.56 to 0.85), with adjustment for age, registry, and clinical variables. Predictors of nonguideline regimens among chemotherapy recipients included lack of insurance (OR, 0.47; 95% CI, 0.25 to 0.92), high-poverty areas (OR, 0.71; 95% CI, 0.51 to 0.97), and low-education areas (OR, 0.65; 95% CI, 0.48 to 0.89) after adjustment. Living in high-poverty areas (OR, 0.78; 95% CI, 0.64 to 0.96) and treatment at non-CoC hospitals (OR, 0.68; 95% CI, 0.55 to 0.83) predicted nonguideline hormonal therapy after adjustment. ORs for poverty, education, and insurance were attenuated in the full models.

Conclusion

Sociodemographic and hospital factors are associated with guideline-concordant use of systemic therapy for breast cancer. The identification of modifiable factors that lead to nonguideline treatment may reduce disparities in breast cancer survival.
Adrenal Disease Update 2011
Authors: Carey Robert M.
Published: December 2011

This article is based on an invited lecture entitled “Year-in-the-Adrenal: A Clinical Perspective,” presented at the 92nd Annual Meeting of The Endocrine Society in Boston, Massachusetts, on June 7, 2011. The objective was to provide clinicians with a summary of key, clinically important advances in the field of adrenal disorders over the past 18 months. Paper selection was based on a comprehensive survey of all adrenal articles published in major endocrinology and high-impact general medical journals between December 2009 and May 2011. Participants in the selection process included 15 endocrinologists with expertise in adrenal disorders. The articles highlighted were those that: 1) constitute novel discoveries that may improve the understanding of pathophysiology; 2) address important clinical questions; and 3) most influence the way we diagnose and treat patients with adrenal disorders. An effort was made to include both adrenal cortical and medullary disorders.
Three Notes on China: Past and Present
Authors: Žižek Slavoj
Published: December 2011

The struggle between Confucianism and legalism lasted through thousands of years in Chinese history and even served as the background of the recent developments in China (Mao's preference for legalism versus Deng's promoting of Confucianism). Although legalists are as a rule dismissed as “totalitarian,” as advocates of a ruthless and cynical state authority, perhaps the time has come to bring out their positive side, especially their egalitarianism of law (the same law for all).
Epigenetic reprogramming in mouse pre-implantation development and primordial germ cells
Authors: Saitou Mitinori , Kagiwada Saya , Kurimoto Kazuki
Published: December 2011

Epigenetic modifications are crucial for the identity and stability of cells, and, when aberrant, can lead to disease. During mouse development, the genome-wide epigenetic states of pre-implantation embryos and primordial germ cells (PGCs) undergo extensive reprogramming. An improved understanding of the epigenetic reprogramming mechanisms that occur in these cells should provide important new information about the regulation of the epigenetic state of a cell and the mechanisms of induced pluripotency. Here, we discuss recent findings about the potential mechanisms of epigenetic reprogramming, particularly genome-wide DNA demethylation, in pre-implantation mouse embryos and PGCs.
Cell fate decisions and axis determination in the early mouse embryo
Authors: Takaoka Katsuyoshi , Hamada Hiroshi
Published: December 2011

The mouse embryo generates multiple cell lineages, as well as its future body axes in the early phase of its development. The early cell fate decisions lead to the generation of three lineages in the pre-implantation embryo: the epiblast, the primitive endoderm and the trophectoderm. Shortly after implantation, the anterior-posterior axis is firmly established. Recent studies have provided a better understanding of how the earliest cell fate decisions are regulated in the pre-implantation embryo, and how and when the body axes are established in the pregastrulation embryo. In this review, we address the timing of the first cell fate decisions and of the establishment of embryonic polarity, and we ask how far back one can trace their origins.
Engrailed homeoprotein recruits the adenosine A1 receptor to potentiate ephrin A5 function in retinal growth cones
Authors: Stettler Olivier , Joshi Rajiv L. , Wizenmann Andrea , Reingruber Jürgen , Holcman David , Bouillot Colette , Castagner François , Prochiantz Alain , Moya Kenneth L.
Published: December 2011

Engrailed 1 and engrailed 2 homeoprotein transcription factors (collectively Engrailed) display graded expression in the chick optic tectum where they participate in retino-tectal patterning. In vitro, extracellular Engrailed guides retinal ganglion cell (RGC) axons and synergises with ephrin A5 to provoke the collapse of temporal growth cones. In vivo disruption of endogenous extracellular Engrailed leads to misrouting of RGC axons. Here we characterise the signalling pathway of extracellular Engrailed. Our results show that Engrailed/ephrin A5 synergy in growth cone collapse involves adenosine A1 receptor activation after Engrailed-dependent ATP synthesis, followed by ATP secretion and hydrolysis to adenosine. This is, to our knowledge, the first evidence for a role of the adenosine A1 receptor in axon guidance. Based on these results, together with higher expression of the adenosine A1 receptor in temporal than nasal growth cones, we propose a computational model that illustrates how the interaction between Engrailed, ephrin A5 and adenosine could increase the precision of the retinal projection map.
A model of stem cell population dynamics: in silico analysis and in vivo validation
Authors: Setty Yaki , Dalfó Diana , Korta Dorota Z. , Hubbard E. Jane Albert , Kugler Hillel
Published: December 2011

The proper renewal and maintenance of tissues by stem cell populations is simultaneously influenced by anatomical constraints, cell proliferation dynamics and cell fate specification. However, their relative influence is difficult to examine in vivo. To address this difficulty we built, as a test case, a cell-centered state-based computational model of key behaviors that govern germline development in C. elegans, and used it to drive simulations of cell population dynamics under a variety of perturbations. Our analysis provided unexpected possible explanations for laboratory observations, including certain ‘all-or-none’ phenotypes and complex differentiation patterns. The simulations also offered insights into niche-association dynamics and the interplay between cell cycle and cell fate. Subsequent experiments validated several predictions generated by the simulations. Notably, we found that early cell cycle defects influence later maintenance of the progenitor cell population. This general modeling approach is potentially applicable to other stem cell systems.
Cost-effectiveness of an intensive telephone-based intervention for smoking cessation
Authors: Smith Mark W , An Lawrence C , Fu Steven S , Nelson David B , Joseph Anne M
Published: December 2011

We calculated the incremental cost per quit of a telephone care intervention versus usual care using the provider's perspective. The study population was 819 smokers at five US Veterans Affairs (VA) primary care clinics. They enrolled in the clinical trial between June 2001 and December 2002. After 12 months the participants were assessed for short- and long-term abstinence over the previous six months. VA records were used to extract the cost of VA services over 12 months, and the cost of care purchased by the VA from others. Intervention costs were derived through micro-costing. On average, the intervention cost $142 per person, excluding medications. The average cost of all VA-funded medical care during the study period was $8959 in the telephone-care arm and $7939 in the usual care arm ( P = 0.37). Under a standard intent-to-treat analysis the average cost per quit was $11,408 and thus the intervention was cost-effective by conventional standards.
Mobile-phone text messaging (SMS) for providing oral health education to mothers of preschool children in Belgaum City
Authors: Sharma Ratika , Hebbal Mamata , Ankola Anil V , Murugabupathy Vikneshan
Published: December 2011

We compared the effectiveness of two media (text messages and pamphlets) in imparting health education to mothers of preschool children. Mothers and their children were randomized into two groups. There were 72 mothers and their children in the pamphlet group and 71 in the text message group. The mothers were given health education by one of the two modes for four weeks. Knowledge, attitude and practices of the mothers were assessed by a questionnaire pre- and post-intervention. Visible plaque scores of their children were also recorded pre- and post-intervention. There were significant improvements in knowledge ( P < 0.001), attitude ( P < 0.001) and practices ( P < 0.001) in both groups. There was also a significant reduction in visible plaque scores ( P < 0.001) in both groups. Text messaging was more effective than pamphlets in improving knowledge, attitude and practices of mothers, but the comparative reduction in plaque score between groups was not significant. Text messaging appears to be an effective means of imparting oral health education.
Immunization with ovarian autoantigens leads to reduced fertility in mice following follicular dysfunction
Authors: Mande Purvi V , Thomas Susan , Khan Shagufta , Jadhav Sudhir , Khole Vrinda V
Published: December 2011

Immunoproteomics using sera of women with ovarian autoimmune diseases such as primary ovarian insufficiency and IVF embryo transfer recruits led to identification of three proteins namely alpha actinin 4 (α-ACTN4), heat-shock 70 protein 5 (HSPA5), and actin beta (ACTB). This study deals with the establishment of a peptide ELISA for screening sera of antiovarian antibody (AOA)-positive patients and further delves into understanding the role of these three proteins in ovarian autoimmunity in a mouse model. Usingin silicoapproach, antigenic peptides of these proteins were identified and used for peptide ELISA. ELISA results indicated that AOA-positive sera showed reactivity with only specific peptides. The functional significance of the dominant peptides was studied by active immunization of female mice with these peptides. All immunized mice generated high antibody titers and profound effect on ovaries with few primordial (2.4±0.1, 2.4±0.2, and 2±0.1), primary (2.4±0.5, 1.7±0.3, and 2.4±0.3), preantral (2.3±0.5, 3.4±0.3, and 2.9±0.3), antral (0.9±0.2, 1.6±0.8, and 2.3±0.6) follicles, and corpora lutea (2.8±0.8, 2.9±1.7, and 4.6±2.3), and increased number of atretic follicles (5.5±0.4, 4.9±1.8, and 7.5±1.0) in ACTN4-, HSPA5-, and ACTB-immunized mice compared with control animals (3.0±0.2, 3.5±0.6, 3±0.1, 3.6±0.2, 4.7±0.3, and 1.5±0.3) respectively. These mice when mated with fertile male mice showed an overall 25–43% reduction in fertility compared with controls. The data clearly suggest that the dominant antigenic epitopes of the three proteins play critical role in fertility and could possibly be the key autoimmune targets. These epitopes could be used to develop a more specific and sensitive diagnostic test for women with ovarian autoimmune diseases and to design therapy for disease management for reinstatement of ovarian function.
Quantitative Trait Loci Association Mapping by Imputation of Strain Origins in Multifounder Crosses
Authors: Zhou Jin J , Ghazalpour Anatole , Sobel Eric M , Sinsheimer Janet S , Lange Kenneth
Published: December 2011

Although mapping quantitative traits in inbred strains is simpler than mapping the analogous traits in humans, classical inbred crosses suffer from reduced genetic diversity compared to experimental designs involving outbred animal populations. Multiple crosses, for example the Complex Trait Consortium's eight-way cross, circumvent these difficulties. However, complex mating schemes and systematic inbreeding raise substantial computational difficulties. Here we present a method for locally imputing the strain origins of each genotyped animal along its genome. Imputed origins then serve as mean effects in a multivariate Gaussian model for testing association between trait levels and local genomic variation. Imputation is a combinatorial process that assigns the maternal and paternal strain origin of each animal on the basis of observed genotypes and prior pedigree information. Without smoothing, imputation is likely to be ill-defined or jump erratically from one strain to another as an animal's genome is traversed. In practice, one expects to see long stretches where strain origins are invariant. Smoothing can be achieved by penalizing strain changes from one marker to the next. A dynamic programming algorithm then solves the strain imputation process in one quick pass through the genome of an animal. Imputation accuracy exceeds 99% in practical examples and leads to high-resolution mapping in simulated and real data. The previous fastest quantitative trait loci (QTL) mapping software for dense genome scans reduced compute times to hours. Our implementation further reduces compute times from hours to minutes with no loss in statistical power. Indeed, power is enhanced for full pedigree data.