bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conserved cryptic recombination signals in Vκ gene segments are cleaved in small pre-B cells
Authors: Lieberman Anne E , Kuraoka Masayuki , Davila Marco , Kelsoe Garnett , Cowell Lindsay G 
Published: June 2009

AbstractBackgroundThe cleavage of recombination signals (RS) at the boundaries of immunoglobulin V, D, and J gene segments initiates the somatic generation of the antigen receptor genes expressed by B lymphocytes. RS contain a conserved heptamer and nonamer motif separated by non-conserved spacers of 12 or 23 nucleotides. Under physiologic conditions, V(D)J recombination follows the "12/23 rule" to assemble functional antigen-receptor genes,i.e., cleavage and recombination occur only between RS with dissimilar spacer types. Functional, cryptic RS (cRS) have been identified in VHgene segments; these VHcRS were hypothesized to facilitate self-tolerance by mediating VH→ VHDJHreplacements. At theIgκlocus, however, secondary,de novorearrangements can delete autoreactive VκJκ joins. Thus, under the hypothesis that V-embedded cRS are conserved to facilitate self-tolerance by mediating V-replacement rearrangements, there would be little selection for Vκ cRS. Recent studies have demonstrated that VHcRS cleavage is only modestly more efficient than V(D)J recombination in violation of the 12/23 rule and first occurs in pro-B cells unable to interact with exogenous antigens. These results are inconsistent with a model of cRS cleavage during autoreactivity-induced VHgene replacement.ResultsTo test the hypothesis that cRS are absent from Vκ gene segments, a corollary of the hypothesis that the need for tolerizing VHreplacements is responsible for the selection pressure to maintain VHcRS, we searched for cRS in mouse Vκ gene segments using a statistical model of RS. Scans of 135 mouse Vκ gene segments revealed highly conserved cRS that were shown to be cleaved in the 103/BCL2 cell line and mouse bone marrow B cells. Analogous to results for VHcRS, we find that Vκ cRS are conserved at multiple locations in Vκ gene segments and are cleaved in pre-B cells.ConclusionOur results, together with those for VHcRS, support a model of cRS cleavage in which cleavage is independent of BCR-specificity. Our results are inconsistent with the hypothesis that cRS are conserved solely to support receptor editing. The extent to which these sequences are conserved, and their pattern of conservation, suggest that they may serve an as yet unidentified purpose.
Characterization of Zur-dependent genes and direct Zur targets in Yersinia pestis
Authors: Li Yingli , Qiu Yefeng , Gao He , Guo Zhaobiao , Han Yanping , Song Yajun , Du Zongmin , Wang Xiaoyi , Zhou Dongsheng , Yang Ruifu 
Published: June 2009

Abstract

Background
The zinc uptake regulator Zur is a Zn2+-sensing metalloregulatory protein involved in the maintenance of bacterial zinc homeostasis. Up to now, regulation of zinc homeostasis by Zur is poorly understood in Y. pestis.

Results
We constructed a zur null mutant of Y. pestis biovar microtus strain 201. Microarray expression analysis disclosed a set of 154 Zur-dependent genes of Y. pestis upon exposure to zinc rich condition. Real-time reverse transcription (RT)-PCR was subsequently used to validate the microarray data. Based on the 154 Zur-dependent genes, predicted regulatory Zur motifs were used to screen for potential direct Zur targets including three putative operons znuA, znuCB and ykgM-RpmJ2. The LacZ reporter fusion analysis verified that Zur greatly repressed the promoter activity of the above three operons. The subsequent electrophoretic mobility shift assay (EMSA) demonstrated that a purified Zur protein was able to bind to the promoter regions of the above three operons. The DNase I footprinting was used to identify the Zur binding sites for the above three operons, verifying the Zur box sequence as predicted previously in γ-Proteobacteria. The primer extension assay was further used to determine the transcription start sites for the above three operons and to localize the -10 and -35 elements. Zur binding sites overlapped the -10 sequence of its target promoters, which was consistent with the previous observation that Zur binding would block the entry of the RNA polymerase to repress the transcription of its target genes.

Conclusion
Zur as a repressor directly controls the transcription of znuA, znuCB and ykgM-RpmJ2 in Y. pestis by employing a conserved mechanism of Zur-promoter DNA association as observed in γ-Proteobacteria. Zur contributes to zinc homeostasis in Y. pestis likely through transcriptional repression of the high-affinity zinc uptake system ZnuACB and two alternative ribosomal proteins YkgM and RpmJ2.
Tissue-specific and neural activity-regulated expression of human BDNF gene in BAC transgenic mice
Authors: Koppel Indrek , Aid-Pavlidis Tamara , Jaanson Kaur , Sepp Mari , Pruunsild Priit , Palm Kaia , Timmusk Tõnis 
Published: June 2009

AbstractBackgroundBrain-derived neurotrophic factor (BDNF) is a small secreted protein that has important roles in the developing and adult nervous system. Altered expression or changes in the regulation of the BDNF gene have been implicated in a variety of human nervous system disorders. Although regulation of the rodent BDNF gene has been extensively investigated,in vivostudies regarding the human BDNF gene are largely limited to postmortem analysis. Bacterial artificial chromosome (BAC) transgenic mice harboring the human BDNF gene and its regulatory flanking sequences constitute a useful tool for studying human BDNF gene regulation and for identification of therapeutic compounds modulating BDNF expression.ResultsIn this study we have generated and analyzed BAC transgenic mice carrying 168 kb of the human BDNF locus modified such that BDNF coding sequence was replaced with the sequence of a fusion protein consisting of N-terminal BDNF and the enhanced green fluorescent protein (EGFP). The human BDNF-BAC construct containing all BDNF 5' exons preceded by different promoters recapitulated the expression of endogenous BDNF mRNA in the brain and several non-neural tissues of transgenic mice. All different 5' exon-specific BDNF-EGFP alternative transcripts were expressed from the transgenic human BDNF-BAC construct, resembling the expression of endogenous BDNF. Furthermore, BDNF-EGFP mRNA was induced upon treatment with kainic acid in a promotor-specific manner, similarly to that of the endogenous mouse BDNF mRNA.ConclusionGenomic region covering 67 kb of human BDNF gene, 84 kb of upstream and 17 kb of downstream sequences is sufficient to drive tissue-specific and kainic acid-induced expression of the reporter gene in transgenic mice. The pattern of expression of the transgene is highly similar to BDNF gene expression in mouse and human. This is the first study to show that human BDNF gene is regulated by neural activity.
Agrobacterium rhizogenes-mediated transformation of Superroot-derived Lotus corniculatus plants: a valuable tool for functional genomics
Authors: Jian Bo , Hou Wensheng , Wu Cunxiang , Liu Bin , Liu Wei , Song Shikui , Bi Yurong , Han Tianfu 
Published: June 2009

Abstract

Background
Transgenic approaches provide a powerful tool for gene function investigations in plants. However, some legumes are still recalcitrant to current transformation technologies, limiting the extent to which functional genomic studies can be performed on. Superroot of Lotus corniculatus is a continuous root cloning system allowing direct somatic embryogenesis and mass regeneration of plants. Recently, a technique to obtain transgenic L. corniculatus plants from Superroot-derived leaves through A. tumefaciens-mediated transformation was described. However, transformation efficiency was low and it took about six months from gene transfer to PCR identification.

Results
In the present study, we developed an A. rhizogenes-mediated transformation of Superroot-derived L. corniculatus for gene function investigation, combining the efficient A. rhizogenes-mediated transformation and the rapid regeneration system of Superroot. The transformation system using A. rhizogenes K599 harbouring pGFPGUSPlus was improved by validating some parameters which may influence the transformation frequency. Using stem sections with one node as explants, a 2-day pre-culture of explants, infection with K599 at OD600 = 0.6, and co-cultivation on medium (pH 5.4) at 22°C for 2 days enhanced the transformation frequency significantly. As proof of concept, Superroot-derived L. corniculatus was transformed with a gene from wheat encoding an Na+/H+ antiporter (TaNHX2) using the described system. Transgenic Superroot plants were obtained and had increased salt tolerance, as expected from the expression of TaNHX2.

Conclusion
A rapid and efficient tool for gene function investigation in L. corniculatus was developed, combining the simplicity and high efficiency of the Superroot regeneration system and the availability of A. rhizogenes-mediated transformation. This system was improved by validating some parameters influencing the transformation frequency, which could reach 92% based on GUS detection. The combination of the highly efficient transformation and the regeneration system of Superroot provides a valuable tool for functional genomics studies in L. corniculatus.
Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis
Authors: Selzer-Plon Joanna , Bornholdt Jette , Friis Stine , Bisgaard Hanne C , Lothe Inger MB , Tveit Kjell M , Kure Elin H , Vogel Ulla , Vogel Lotte K 
Published: June 2009

Abstract

Background
Clinical trials where cancer patients were treated with protease inhibitors have suggested that the serine protease, prostasin, may act as a tumour suppressor. Prostasin is proteolytically activated by the serine protease, matriptase, which has a very high oncogenic potential. Prostasin is inhibited by protease nexin-1 (PN-1) and the two isoforms encoded by the mRNA splice variants of hepatocyte growth factor activator inhibitor-1 (HAI-1), HAI-1A, and HAI-1B.

Methods
Using quantitative RT-PCR, we have determined the mRNA levels for prostasin and PN-1 in colorectal cancer tissue (n = 116), severe dysplasia (n = 13), mild/moderate dysplasia (n = 93), and in normal tissue from the same individuals. In addition, corresponding tissues were examined from healthy volunteers (n = 23). A part of the cohort was further analysed for the mRNA levels of the two variants of HAI-1, here denoted HAI-1A and HAI-1B. mRNA levels were normalised to β-actin. Immunohistochemical analysis of prostasin and HAI-1 was performed on normal and cancer tissue.

Results
The mRNA level of prostasin was slightly but significantly decreased in both mild/moderate dysplasia (p < 0.001) and severe dysplasia (p < 0.01) and in carcinomas (p < 0.05) compared to normal tissue from the same individual. The mRNA level of PN-1 was more that two-fold elevated in colorectal cancer tissue as compared to healthy individuals (p < 0.001) and elevated in both mild/moderate dysplasia (p < 0.01), severe dysplasia (p < 0.05) and in colorectal cancer tissue (p < 0.001) as compared to normal tissue from the same individual. The mRNA levels of HAI-1A and HAI-1B mRNAs showed the same patterns of expression. Immunohistochemistry showed that prostasin is located mainly on the apical plasma membrane in normal colorectal tissue. A large variation was found in the degree of polarization of prostasin in colorectal cancer tissue.

Conclusion
These results show that the mRNA level of PN-1 is significantly elevated in colorectal cancer tissue. Future studies are required to clarify whether down-regulation of prostasin activity via up regulation of PN-1 is causing the malignant progression or if it is a consequence of it.
The 2005 census and mapping of slums in Bangladesh: design, select results and application
Authors: Angeles Gustavo , Lance Peter , Barden-O'Fallon Janine , Islam Nazrul , Mahbub AQM , Nazem Nurul Islam 
Published: June 2009

Abstract

Background
The concentration of poverty and adverse environmental circumstances within slums, particularly those in the cities of developing countries, are an increasingly important concern for both public health policy initiatives and related programs in other sectors. However, there is a dearth of information on the population-level implications of slum life for human health. This manuscript describes the 2005 Census and Mapping of Slums (CMS), which used geographic information systems (GIS) tools and digital satellite imagery combined with more traditional fieldwork methodologies, to obtain detailed, up-to-date and new information about slum life in all slums of six major cities in Bangladesh (including Dhaka).

Results
The CMS found that Bangladeshi slums are very diverse: there are wide intra- and inter-city variations in population size, density, the percent of urban populations living in slums, and sanitation conditions. Findings also show that common beliefs about slums may be outdated; of note, tenure insecurity was found to be an issue in only a small minority of slums.

Conclusion
The methodology used in the 2005 Bangladesh CMS provides a useful approach to mapping slums that could be applied to urban areas in other low income societies. This methodology may become an increasingly important analytic tool to inform policy, as cities in developing countries are forecasted to continue increasing their share of total global population in the coming years, with slum populations more than doubling in size during the same period.
The change in attitude and knowledge of health care personnel and general population following trainings provided during integration of mental health in Primary Health Care in Iran: a systematic review
Authors: Mansouri Naghmeh , Gharaee Banafsheh , Shariat Seyed Vahid , Bolhari Jafar , Yousefi Nooraie Reza , Rahimi-Movaghar Afarin , Alirezaie Narges 
Published: June 2009

Abstract

Background
Mental health has been integrated in the primary health care program in small cities and villages of Iran in a national level since the late 1980s. We performed a systematic review of literature to investigate the effect of education on change in attitude and knowledge of mental health care providers and the population covered in the program during the recent two decades in Iran.

Methods
Electronic bibliographic databases including Pubmed, PsycINFO and EMBase as well as the main Iranian databases (Scientific Information Database, IranMedex, IranPsych, and IranDoc) were searched. Additionally, hand searching, personal contacts and tracking of reference lists were performed. All of the studies which compared the attitude and knowledge of the related population before and after an educational intervention were recruited.

Results
Six articles met the inclusion criteria and entered the review. All of these studies showed an improvement in the attitude and knowledge of the studied population. Although the studies were different in many respects, a meta-analysis on the two more similar studies showed a significant effect of training on long term improvement of the knowledge and attitude of the population.

Conclusion
A short term training improved knowledge and attitude of the population and health personnel immediately after the intervention. There is also evidence for a long term change in the attitude and knowledge of general population after short term training.
Myeloperoxidase: A Useful Biomarker for Cardiovascular Disease Risk Stratification?
Authors: Schindhelm Roger K , van der Zwan Leonard P , Teerlink Tom , Scheffer Peter G 
Published: June 2009

Abstract
Background: Inflammation and oxidative stress are associated with atherosclerosis. Myeloperoxidase (MPO) is linked to both inflammation and oxidative stress by its location in leukocytes and its role in catalyzing the formation of oxidizing agents. Recent evidence suggests that MPO activity precipitates atherogenesis. Measurement of MPO in plasma may therefore contribute to cardiovascular disease (CVD) risk stratification.
Content: Cross-sectional studies, case-control studies, and prospective-cohort studies investigating the relation between MPO and CVD have been evaluated. Differences in study populations, sample materials, sample handling, and assays were ascertained. Potential causal mechanisms linking MPO to accelerated atherosclerosis are discussed here. A majority of studies indicate that measurement of MPO in plasma was associated with improved CVD risk stratification above and beyond risk stratification results obtained with markers used in routine clinical practice. However, comparison of these epidemiological studies with regard to MPO and outcome is hampered because the reported MPO concentration depends on the assay method, sampling material, and preanalytical and analytical procedures. The link between MPO and CVD can, at least partly, be explained by MPO-dependent oxidation of LDL and HDL, subsequently leading to cholesterol accumulation in the arterial wall. Furthermore, MPO may reduce the bioavailability of nitric oxide, resulting in endothelial dysfunction. Finally, MPO destabilizes atherosclerotic plaques.
Summary: Increasing evidence suggests that MPO is causally linked to atherosclerosis and its measurement may improve CVD risk estimation. Before MPO can be used in routine clinical practice, however, standardization of sampling and laboratory procedures is needed.
THE SILTING OF IMPOUNDING RESERVOIRS.
Authors: WINTER T S R 
Published: June 2009

Synopsis The Paper describes a method of assessing the quantity of silt and debris discharged by streams and by the run-off from catchment-areas, with the consequent loss in storage-capacity of the reservoirs. This method is intended to be used when the original contoured plans of the valley are not available and when the reservoirs cannot be placed out of commission for surveying.
Model Uncertainty in Claims Reserving within Tweedie's Compound Poisson Models
Authors: Peters Gareth W. , Shevchenko Pavel V. , Wüthrich Mario V. 
Published: June 2009

AbstractIn this paper we examine the claims reserving problem using Tweedie's compound Poisson model. We develop the maximum likelihood and Bayesian Markov chain Monte Carlo simulation approaches to fit the model and then compare the estimated models under different scenarios. The key point we demonstrate relates to the comparison of reserving quantities with and without model uncertainty incorporated into the prediction. We consider both the model selection problem and the model averaging solutions for the predicted reserves. As a part of this process we also consider the sub problem of variable selection to obtain a parsimonious representation of the model being fitted.
Predictive Distributions for Reserves which Separate True IBNR and IBNER Claims
Authors: Liu Huijuan , Verrall Richard 
Published: June 2009

AbstractThis paper considers the model suggested by Schnieper (1991), which separates the true IBNR claims from the IBNER. Stochastic models are defined, using both recursive and non-recursive procedures, within the framework of the models described in England and Verrall (2002). Approximations to the prediction error of the reserves are derived analytically.Some extensions to the original Schnieper model are also disussed, together with other possible applications of this type of model.
Full Credibility with Generalized Linear and Mixed Models
Authors: Garrido José , Zhou Jun 
Published: June 2009

AbstractGeneralized linear models (GLMs) are gaining popularity as a statistical analysis method for insurance data. For segmented portfolios, as in car insurance, the question of credibility arises naturally; how many observations are needed in a risk class before the GLM estimators can be considered credible? In this paper we study the limited fluctuations credibility of the GLM estimators as well as in the extended case of generalized linear mixed model (GLMMs). We show how credibility depends on the sample size, the distribution of covariates and the link function. This provides a mechanism to obtain confidence intervals for the GLM and GLMM estimators.
Credible Loss Ratio Claims Reserves: the Benktander, Neuhaus and Mack Methods Revisited
Authors: Hürlimann Werner 
Published: June 2009

AbstractThe Benktander (1976) and Neuhaus (1992) credibility claims reserving methods are reconsidered in the framework of a credible loss ratio reserving method. As a main contribution we provide a simple and practical optimal credibility weight for combining the chain-ladder or individual loss ratio reserve (grossed up latest claims experience of an origin period) with the Bornhuetter-Ferguson or collective loss ratio reserve (experience based burning cost estimate of the total ultimate claims of an origin period). The obtained simple optimal credibility weights minimize simultaneously the mean squared error and the variance of the claims reserve. We note also that the standard Chain-Ladder, Cape Cod and Bornhuetter-Ferguson methods can be reinterpreted in the credible context and extended to optimal credible standard methods. The new approach is inspired from Mack (2000). Two advantages over the Mack method are worthwhile to be mentioned. First, a pragmatic estimation of the required parameters leads to a straightforward calculation of the optimal credibility weights and mean squared errors of the credible reserves. An advantage of the collective loss ratio claims reserve over the Bornhuetter-Ferguson reserve in Mack (2000) is that different actuaries come always to the same results provided they use the same actuarial premiums.
Risk Measures and Efficient use of Capital
Authors: Artzner Philippe , Delbaen Freddy , Koch-Medina Pablo 
Published: June 2009

AbstractThis paper is concerned with clarifying the link between risk measurement and capital efficiency. For this purpose we introduce risk measurement as the minimum cost of making a position acceptable by adding an optimal combination of multiple eligible assets. Under certain assumptions, it is shown that these risk measures have properties similar to those of coherent risk measures. The motivation for this paper was the study of a multi-currency setting where it is natural to use simultaneously a domestic and a foreign asset as investment vehicles to inject the capital necessary to make an unacceptable position acceptable. We also study what happens when one changes the unit of account from domestic to foreign currency and are led to the notion of compatibility of risk measures. In addition, we aim to clarify terminology in the field.
Uncertainty in Mortality Forecasting: An Extension to the Classical Lee-Carter Approach
Authors: Li Johnny Siu-Hang , Hardy Mary R. , Tan Ken Seng 
Published: June 2009

AbstractTraditionally, actuaries have modeled mortality improvement using deterministic reduction factors, with little consideration of the associated uncertainty. As mortality improvement has become an increasingly significant source of financial risk, it has become important to measure the uncertainty in the forecasts. Probabilistic confidence intervals provided by the widely accepted Lee-Carter model are known to be excessively narrow, due primarily to the rigid structure of the model. In this paper, we relax the model structure by considering individual differences (heterogeneity) in each age-period cell. The proposed extension not only provides a better goodness-of-fit based on standard model selection criteria, but also ensures more conservative interval forecasts of central death rates and hence can better reflect the uncertainty entailed. We illustrate the results using US and Canadian mortality data.