bluuebunny/crossref_metadata_2025 huggingface dataset:
High-throughput immunoglobulin repertoire analysis distinguishes between human IgM memory and switched memory B-cell populations
Authors: Wu Yu-Chang , Kipling David , Leong Hui Sun , Martin Victoria , Ademokun Alexander A. , Dunn-Walters Deborah K.
Published: May 2010

B-cell receptor (BCR) diversity is achieved centrally by rearrangement of Variable, Diversity, and Joining genes, and peripherally by somatic hypermutation and class-switching of the rearranged genes. Peripheral B-cell populations are subject to both negative and positive selection events in the course of their development that have the potential to shape the BCR repertoire. The origin of IgM+IgD+CD27+ (IgM memory) cells is controversial. It has been suggested that they may be a prediversified, antigen-independent, population of cells or that they are a population of cells that develop in response to T-independent antigens. Most recently, it was suggested that the majority of IgM memory cells are directly related to switched memory cells and are early emigrants from the germinal center reaction. Advances in sequencing technology have enabled us to undertake large scale IGH repertoire analysis of transitional, naive, IgM memory and switched memory B-cell populations. We find that the memory B-cell repertoires differ from the transitional and naive repertoires, and that the IgM memory repertoire is distinct from that of class-switched memory. Thus we conclude that a large proportion of IgM memory cells develop in response to different stimuli than for class-switched memory cell development.
Characterization of adipocyte differentiation from human mesenchymal stem cells in bone marrow
Authors: Qian Shu-Wen , Li Xi , Zhang You-You , Huang Hai-Yan , Liu Yuan , Sun Xia , Tang Qi-Qun
Published: May 2010

Background

Adipocyte hyperplasia is associated with obesity and arises due to adipogenic differentiation of resident multipotent stem cells in the vascular stroma of adipose tissue and remote stem cells of other organs. The mechanistic characterization of adipocyte differentiation has been researched in murine pre-adipocyte models (i.e. 3T3-L1 and 3T3-F442A), revealing that growth-arrest pre-adipocytes undergo mitotic clonal expansion and that regulation of the differentiation process relies on the sequential expression of three key transcription factors (C/EBPβ, C/EBPα and PPARγ). However, the mechanisms underlying adipocyte differentiation from multipotent stem cells, particularly human mesenchymal stem cells (hBMSCs), remain poorly understood. This study investigated cell cycle regulation and the roles of C/EBPβ, C/EBPα and PPARγ during adipocyte differentiation from hBMSCs.

Results

Utilising a BrdU incorporation assay and manual cell counting it was demonstrated that induction of adipocyte differentiation in culture resulted in 3T3-L1 pre-adipocytes but not hBMSCs undergoing mitotic clonal expansion. Knock-down and over-expression assays revealed that C/EBPβ, C/EBPα and PPARγ were required for adipocyte differentiation from hBMSCs. C/EBPβ and C/EBPα individually induced adipocyte differentiation in the presence of inducers; PPARγ alone initiated adipocyte differentiation but the cells failed to differentiate fully. Therefore, the roles of these transcription factors during human adipocyte differentiation are different from their respective roles in mouse.

Conclusions

The characteristics of hBMSCs during adipogenic differentiation are different from those of murine cells. These findings could be important in elucidating the mechanisms underlying human obesity further.
Survey of transcripts expressed by the invasive juvenile stage of the liver fluke Fasciola hepatica
Authors: Cancela Martín , Ruétalo Natalia , Dell'Oca Nicolás , da Silva Edileuza , Smircich Pablo , Rinaldi Gabriel , Roche Leda , Carmona Carlos , Alvarez-Valín Fernando , Zaha Arnaldo , Tort José F
Published: May 2010

Background

The common liver flukeFasciola hepaticais the agent of a zoonosis with significant economic consequences in livestock production worldwide, and increasing relevance to human health in developing countries. Although flukicidal drugs are available, re-infection and emerging resistance are demanding new efficient and inexpensive control strategies. Understanding the molecular mechanisms underlying the host-parasite interaction provide relevant clues in this search, while enlightening the physiological adaptations to parasitism. Genomics and transcriptomics are still in their infancy inF. hepatica, with very scarce information available from the invasive newly excysted juveniles (NEJ). Here we provide an initial glimpse to the transcriptomics of the NEJ, the first stage to interact with the mammalian host.

Results

We catalogued more than 500 clusters generated from the analysis ofF. hepaticajuvenile expressed sequence tags (EST), several of them not detected in the adult stage. A set of putativeF. hepaticaspecific transcripts, and a group of sequences conserved exclusively in flatworms were identified. These novel sequences along with a set of parasite transcripts absent in the host genomes are putative new targets for future anti-parasitic drugs or vaccine development.

Comparisons of theF. hepaticasequences with other metazoans genomes or EST databases were consistent with the basal positioning of flatworms in the bilaterian phylogeny. Notably, GC content, codon usage and amino acid frequencies are remarkably different in Schistosomes toF. hepaticaand other trematodes.

Functional annotation of predicted proteins showed a general representation of diverse biological functions. Besides proteases and antioxidant enzymes expected to participate in the early interaction with the host, various proteins involved in gene expression, protein synthesis, cell signaling and mitochondrial enzymes were identified. Differential expression of secreted protease gene family members between juvenile and adult stages may respond to different needs during host colonization.

Conclusion

The knowledge of the genes expressed by the invasive stage ofFasciola hepaticais a starting point to unravel key aspects of this parasite's biology. The integration of the emerging transcriptomics, and proteomics data and the advent of functional genomics tools in this organism are positioningF. hepaticaas an interesting model for trematode biology.
The Zymomonas mobilis regulator hfq contributes to tolerance against multiple lignocellulosic pretreatment inhibitors
Authors: Yang Shihui , Pelletier Dale A , Lu Tse-Yuan S , Brown Steven D
Published: May 2010

Background

Zymomonas mobilis produces near theoretical yields of ethanol and recombinant strains are candidate industrial microorganisms. To date, few studies have examined its responses to various stresses at the gene level. Hfq is a conserved bacterial member of the Sm-like family of RNA-binding proteins, coordinating a broad array of responses including multiple stress responses. In a previous study, we observed Z. mobilis ZM4 gene ZMO0347 showed higher expression under anaerobic, stationary phase compared to that of aerobic, stationary conditions.

Results

We generated a Z. mobilis hfq insertion mutant AcRIM0347 in an acetate tolerant strain (AcR) background and investigated its role in model lignocellulosic pretreatment inhibitors including acetate, vanillin, furfural and hydroxymethylfurfural (HMF). Saccharomyces cerevisiae Lsm protein (Hfq homologue) mutants and Lsm protein overexpression strains were also assayed for their inhibitor phenotypes. Our results indicated that all the pretreatment inhibitors tested in this study had a detrimental effect on both Z. mobilis and S. cerevisiae, and vanillin had the most inhibitory effect followed by furfural and then HMF for both Z. mobilis and S. cerevisiae. AcRIM0347 was more sensitive than the parental strain to the inhibitors and had an increased lag phase duration and/or slower growth depending upon the conditions. The hfq mutation in AcRIM0347 was complemented partially by trans-acting hfq gene expression. We also assayed growth phenotypes for S. cerevisiae Lsm protein mutant and overexpression phenotypes. Lsm1, 6, and 7 mutants showed reduced tolerance to acetate and other pretreatment inhibitors. S. cerevisiae Lsm protein overexpression strains showed increased acetate and HMF resistance as compared to the wild-type, while the overexpression strains showed greater inhibition under vanillin stress conditions.

Conclusions

We have shown the utility of the pKNOCK suicide plasmid for mutant construction in Z. mobilis, and constructed a Gateway compatible expression plasmid for use in Z. mobilis for the first time. We have also used genetics to show Z. mobilis Hfq and S. cerevisiae Lsm proteins play important roles in resisting multiple, important industrially relevant inhibitors. The conserved nature of this global regulator offers the potential to apply insights from these fundamental studies for further industrial strain development.
The Leishmania amazonensis TRF (TTAGGG repeat-binding factor) homologue binds and co-localizes with telomeres
Authors: da Silva Marcelo S , Perez Arina M , da Silveira Rita de Cássia V , de Moraes Camila E , Siqueira-Neto Jair L , Freitas-Junior Lucio H , Cano Maria Isabel N
Published: May 2010

Background

Telomeres are specialized structures at the end of chromosomes essential for maintaining genome stability and cell viability. The importance of telomeric proteins for telomere maintenance has increased our interest in the identification of homologues within the genus Leishmania. The mammalian TRF1 and TRF2 proteins, for example, bind double-stranded telomeres via a Myb-like DNA-binding domain and are involved with telomere length regulation and chromosome end protection. In addition, TRF2 can modulate the activity of several enzymes and influence the conformation of telomeric DNA. In this work, we identified and characterized a Leishmania protein (LaTRF) homologous to both mammalian TRF1 and TRF2.

Results

LaTRF was cloned using a PCR-based strategy. ClustalW and bl2seq sequence analysis showed that LaTRF shared sequence identity with the Trypanosoma brucei TRF (TbTRF) protein and had the same degree of sequence similarities with the dimerization (TRFH) and the canonical DNA-binding Myb-like domains of both mammalian TRFs. LaTRF was predicted to be an 82.5 kDa protein, indicating that it is double the size of the trypanosome TRF homologues. Western blot and indirect immunofluorescence combined with fluorescence in situ hybridization showed that LaTRF, similarly to hTRF2, is a nuclear protein that also associates with parasite telomeres. Native and full length LaTRF and a mutant bearing the putative Myb-like domain expressed in bacteria bound double-stranded telomeric DNA in vitro. Chromatin immunoprecipitation showed that LaTRF interacted specifically with telomeres in vivo.

Conclusion

The nuclear localization of LaTRF, its association and co-localization with parasite telomeres and its high identity with TbTRF protein, support the hypothesis that LaTRF is a Leishmania telomeric protein.
Dynamic models of pneumococcal carriage and the impact of the Heptavalent Pneumococcal Conjugate Vaccine on invasive pneumococcal disease
Authors: Melegaro Alessia , Choi Yoon Hong , George Robert , Edmunds W John , Miller Elizabeth , Gay Nigel J
Published: May 2010

Background

The 7-valent pneumococcal conjugate vaccine has been introduced in national immunisation programmes of most industrialised countries and recently in two African GAVI eligible countries (Rwanda and The Gambia). However the long term effects of PCV are still unclear, as beneficial direct and herd immunity effects might be countered by serotype replacement.

Method

A dynamic, age-structured, compartmental model ofStreptococcus pneumoniaetransmission was developed to predict the potential impact of PCV7 on the incidence of invasive disease accounting for both herd immunity and serotype replacement effects. The model was parameterised using epidemiological data from England and Wales and pre and post-vaccination surveillance data from the US.

Results

Model projections showed that serotype replacement plays a crucial role in determining the overall effect of a PCV7 vaccination programme and could reduce, negate or outweigh its beneficial impact. However, using the estimate of the competition parameter derived from the US post-vaccination experience, an infant vaccination programme would prevent 39,000 IPD cases in the 20 years after PCV7 introduction in the UK. Adding a catch-up campaign for under 2 or under 5 year olds would provide a further reduction of 1,200 or 3,300 IPD cases respectively, mostly in the first few years of the programme.

Conclusions

This analysis suggests that a PCV vaccination programme would eradicate vaccine serotypes from circulation. However, the increase in carriage of non-vaccine serotypes, and the consequent increase in invasive disease, could reduce, negate or outweigh the benefit. These results are sensitive to changes in the protective effect of the vaccine, and, most importantly, to the level of competition between vaccine and non-vaccine types. The techniques developed here can be used to assess the introduction of vaccination programmes in developing countries and provide the basis for cost-effectiveness analyses.
Beneficial effect of aurothiomalate on murine malaria
Authors: Alesutan Ioana , Bobbala Diwakar , Qadri Syed M , Estremera Adriana , Föller Michael , Lang Florian
Published: May 2010

Background

Premature death of Plasmodium-infected erythrocytes is considered to favourably influence the clinical course of malaria. Aurothiomalate has previously been shown to trigger erythrocyte death or eryptosis, which is characterized by cell membrane scrambling leading to phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing cells are rapidly cleared from circulating blood. The present study thus tested whether sodium aurothiomalate influences the intraerythrocytic parasite development in vitro and the clinical course of murine malaria in vivo.

Methods

Human erythrocytes were infected with Plasmodium falciparum BinH in vitro and mice were infected (intraperitoneal injection of 1 × 106 parasitized murine erythrocytes) with Plasmodium berghei ANKA in vivo.

Results

Exposure to aurothiomalate significantly decreased the in vitro parasitemia of P. falciparum-infected human erythrocytes without influencing the intraerythrocytic DNA/RNA content. Administration of sodium aurothiomalate in vivo (daily 10 mg/kg b.w. s.c. from the 8th day of infection) enhanced the percentage of phosphatidylserine-exposing infected and noninfected erythrocytes in blood. All nontreated mice died within 30 days of infection. Aurothiomalate-treatment delayed the lethal course of malaria leading to survival of more than 50% of the mice 30 days after infection.

Conclusions

Sodium aurothiomalate influences the survival of Plasmodium berghei-infected mice, an effect only partially explained by stimulation of eryptosis.
Incremental value of contrast myocardial perfusion to detect intermediate versus severe coronary artery stenosis during stress-echocardiography
Authors: Gaibazzi Nicola , Rigo Fausto , Squeri Angelo , Ugo Fabrizio , Reverberi Claudio
Published: May 2010

Background

We aimed to compare the incremental value of contrast myocardial perfusion imaging (MPI) for the detection of intermediate versus severe coronary artery stenosis during dipyridamole-atropine echocardiography (DASE).

Wall motion (WM) assessment during stress-echocardiography demonstrates suboptimal sensitivity to detect coronary artery disease (CAD), particularly in patients with isolated intermediate (50%-70%) coronary stenosis.

Methods

We performed DASE with MPI in 150 patients with a suspected chest pain syndrome who were given clinical indication to coronary angiography.

Results and discussion

When CAD was defined as the presence of a ≥50% stenosis, the addition of MPI increased sensitivity (+30%) and decreased specificity (-14%), with a final increase in total diagnostic accuracy (+16%, p < 0.001). The addition of MPI data substantially increased the sensitivity to detect patients with isolated intermediate stenosis from 37% to 98% (p < 0.001); the incremental sensitivity was much lower in patients with severe stenosis, from 85% to 96% (p < 0.05), at the expense of a higher decrease in specificity and a final decrease in total diagnostic accuracy (-18%, p < 0.001).

Conclusions

The addition of MPI on top of WM analysis during DASE increases the diagnostic sensitivity to detect obstructive CAD, whatever its definition (≥50% or > 70% stenosis), but it is mainly driven by the sensitivity increase in the intermediate group (50%-70% stenosis).

The total diagnostic accuracy increased only when defining CAD as ≥50% stenosis, since in patients with severe stenosis (> 70%) the decrease in specificity is not counterbalanced by the minor sensitivity increase.
Membrane-initiated actions of estradiol (E2) in the regulation of LH secretion in ovariectomized (OVX) ewes
Authors: Arreguin-Arevalo J Alejandro , Ashley Ryan L , Wagenmaker Elizabeth R , Oakley Amy E , Karsch Fred J , Nett Terry M
Published: May 2010

Background

We demonstrated that E2 conjugated to BSA (E2BSA) induces a rapid membrane-initiated inhibition of LH secretion followed hours later by a slight increase in LH secretion. Whether these actions of E2BSA are restricted to the pituitary gland and whether the membrane-initiated pathway of E2BSA contributes to the up-regulation of the number of GnRH receptors during the positive feedback effect of E2 were evaluated here. We have shown that the suppression of LH secretion induced by E2 and E2BSA is the result of a decreased responsiveness of the pituitary gland to GnRH. In this study we further tested the ability of E2BSA to decrease the responsiveness of the pituitary gland to GnRH under the paradigm of the preovulatory surge of LH induced by E2.

Methods

For the first experiment GnRH and LH secretions were determined in samples of pituitary portal and jugular blood, respectively, in ewes treated with 12 mg E2BSA. In the second experiment, the number of GnRH receptors was quantified in ewes 12 h after administration of 25 micrograms E2 (the expected time for the increase in the number of GnRH receptors and the positive feedback effect of E2 in LH secretion) or 12 mg E2BSA. In the third experiment, the preovulatory-like surge of LH was characterized in ewes injected with 25 micrograms E2 alone or followed 8 h later (before the beginning of the LH surge) with 60 mg E2BSA.

Results

a) the decrease in LH secretion induced by E2BSA was not accompanied by changes in the pulsatile pattern of GnRH, b) E2BSA increased the number of GnRH receptors, and c) the presence of E2BSA in E2-treated ewes delayed the onset, reduced the length, and decreased the amount of LH released during the preovulatory surge of LH.

Conclusions

a) the rapid suppression of LH secretion induced by E2BSA is mediated only via a direct action on the pituitary gland, b) E2 acting via a membrane-initiated pathway contributes to increase the number of GnRH receptors and, c) administration of E2BSA near the beginning of the pre-ovulatory surge of LH delays and reduces the magnitude of the surge.
What is my walking neighbourhood? A pilot study of English adults' definitions of their local walking neighbourhoods
Authors: Smith Graham , Gidlow Christopher , Davey Rachel , Foster Charles
Published: May 2010

Background

Existing measures of perceptions of the environment associated with walking commonly rely on providing a definition of 'neighbourhood', e.g. 1 mile area around the home. We have little understanding of how these examples relate with adults' own geographical definitions of their neighbourhood area. Our pilot study examined the congruence between definitions used in environmental questionnaires and adults' own definitions of neighbourhood.

Methods

We conducted 58 face-to-face interviews with participants randomly selected from 10 areas of Stoke-on-Trent, England. Participants were shown printed maps showing their local area with road names and places of interest (e.g. shops, services, green space) and were asked: (i) to recall usual walking destinations (from their home); (ii) to draw their 'neighbourhood walking area' on the map. Annotated maps were scanned back into GIS for analysis.

Results

When asked to draw their 'neighbourhood' boundary, the resulting area drawn by participants on average represented only 16 ± 20% of the commonly used total straight-line buffer of 1 mile (or 1.6 km) with a range of 0.3% to 111%. Even when repeated using a network buffer (rather than straight-line) the same comparison resulted in a mean of 36% (± 47%) and a range of 0.6 to 245%.

Conclusions

We found that adults' interpretation of their neighbourhood area does not appear to relate accurately to the definitions typically used in research into environmental perceptions and walking. This mis-match warrants further investigation as definitions used in existing measures may be consistently misclassifying perceived local walking neighbourhoods.
Stepwise mechanism for transcription fidelity
Authors: Yuzenkova Yulia , Bochkareva Aleksandra , Tadigotla Vasisht R , Roghanian Mohammad , Zorov Savva , Severinov Konstantin , Zenkin Nikolay
Published: May 2010

Background

Transcription is the first step of gene expression and is characterized by a high fidelity of RNA synthesis. During transcription, the RNA polymerase active centre discriminates against not just non-complementary ribo NTP substrates but also against complementary 2'- and 3'-deoxy NTPs. A flexible domain of the RNA polymerase active centre, the Trigger Loop, was shown to play an important role in this process, but the mechanisms of this participation remained elusive.

Results

Here we show that transcription fidelity is achieved through a multi-step process. The initial binding in the active centre is the major discrimination step for some non-complementary substrates, although for the rest of misincorporation events discrimination at this step is very poor. During the second step, non-complementary and 2'-deoxy NTPs are discriminated against based on differences in reaction transition state stabilization and partly in general base catalysis, for correct versus non-correct substrates. This step is determined by two residues of the Trigger Loop that participate in catalysis. In the following step, non-complementary and 2'-deoxy NTPs are actively removed from the active centre through a rearrangement of the Trigger Loop. The only step of discrimination against 3'-deoxy substrates, distinct from the ones above, is based on failure to orient the Trigger Loop catalytic residues in the absence of 3'OH.

Conclusions

We demonstrate that fidelity of transcription by multi-subunit RNA polymerases is achieved through a stepwise process. We show that individual steps contribute differently to discrimination against various erroneous substrates. We define the mechanisms and contributions of each of these steps to the overall fidelity of transcription.
A simple powerful bivariate test for two sample location problems in experimental and observational studies
Authors: Tabesh Hamed , Ayatollahi S MT , Towhidi Mina
Published: May 2010

Background

In many areas of medical research, a bivariate analysis is desirable because it simultaneously tests two response variables that are of equal interest and importance in two populations. Several parametric and nonparametric bivariate procedures are available for the location problem but each of them requires a series of stringent assumptions such as specific distribution, affine-invariance or elliptical symmetry.

The aim of this study is to propose a powerful test statistic that requires none of the aforementioned assumptions. We have reduced the bivariate problem to the univariate problem of sum or subtraction of measurements. A simple bivariate test for the difference in location between two populations is proposed.

Method

In this study the proposed test is compared with Hotelling'sT2test, two sample Rank test, Cramer test for multivariate two sample problem and Mathur's test using Monte Carlo simulation techniques. The power study shows that the proposed test performs better than any of its competitors for most of the populations considered and is equivalent to the Rank test in specific distributions.

Conclusions

Using simulation studies, we show that the proposed test will perform much better under different conditions of underlying population distribution such as normality or non-normality, skewed or symmetric, medium tailed or heavy tailed. The test is therefore recommended for practical applications because it is more powerful than any of the alternatives compared in this paper for almost all the shifts in location and in any direction.
Radiotherapy of large target volumes in Hodgkin's lymphoma: normal tissue sparing capability of forward IMRT versus conventional techniques
Authors: Cella Laura , Liuzzi Raffaele , Magliulo Mario , Conson Manuel , Camera Luigi , Salvatore Marco , Pacelli Roberto
Published: May 2010

Background

This paper analyses normal tissue sparing capability of radiation treatment techniques in Hodgkin's lymphoma with large treatment volume.

Methods

10 patients with supradiaphragmatic Hodgkin's lymphoma and planning target volume (PTV) larger than 900 cm3 were evaluated. Two plans were simulated for each patient using 6 MV X-rays: a conventional multi-leaf (MLC) parallel-opposed (AP-PA) plan, and the same plan with additional MLC shaped segments (forward planned intensity modulated radiation therapy, FPIMRT). In order to compare plans, dose-volume histograms (DVHs) of PTV, lungs, heart, spinal cord, breast, and thyroid were analyzed. The Inhomogeneity Coefficient (IC), the PTV receiving 95% of the prescription dose (V95), the normal tissue complication probability (NTCP) and dose-volume parameters for the OARs were determined.

Results

the PTV coverage was improved (mean V95AP-PA = 95.9 and ICAP-PA = 0.4 vs. V95FPIMRT = 96.8 and ICFPIMRT = 0.31, p ≤ 0.05) by the FPIMRT technique compared to the conventional one. At the same time, NTCPs of lung, spinal cord and thyroid, and the volume of lung and thyroid receiving ≥ 30 Gy resulted significantly reduced when using the FPIMRT technique.

Conclusions

The FPIMRT technique can represent a very useful and, at the same time, simple method for improving PTV conformity while saving critical organs when large fields are needed as in Hodgkin's lymphoma.
Efficiency of Xist-mediated silencing on autosomes is linked to chromosomal domain organisation
Authors: Tang Y Amy , Huntley Derek , Montana Giovanni , Cerase Andrea , Nesterova Tatyana B , Brockdorff Neil
Published: May 2010

Background

X chromosome inactivation, the mechanism used by mammals to equalise dosage of X-linked genes in XX females relative to XY males, is triggered by chromosome-wide localisation of a cis-acting non-coding RNA, Xist. The mechanism of Xist RNA spreading and Xist-dependent silencing is poorly understood. A large body of evidence indicates that silencing is more efficient on the X chromosome than on autosomes, leading to the idea that the X chromosome has acquired sequences that facilitate propagation of silencing. LINE-1 (L1) repeats are relatively enriched on the X chromosome and have been proposed as candidates for these sequences. To determine the requirements for efficient silencing we have analysed the relationship of chromosome features, including L1 repeats, and the extent of silencing in cell lines carrying inducible Xist transgenes located on one of three different autosomes.

Results

Our results show that the organisation of the chromosome into large gene-rich and L1-rich domains is a key determinant of silencing efficiency. Specifically genes located in large gene-rich domains with low L1 density are relatively resistant to Xist-mediated silencing whereas genes located in gene-poor domains with high L1 density are silenced more efficiently. These effects are observed shortly after induction of Xist RNA expression, suggesting that chromosomal domain organisation influences establishment rather than long-term maintenance of silencing. The X chromosome and some autosomes have only small gene-rich L1-depleted domains and we suggest that this could confer the capacity for relatively efficient chromosome-wide silencing.

Conclusions

This study provides insight into the requirements for efficient Xist mediated silencing and specifically identifies organisation of the chromosome into gene-rich L1-depleted and gene-poor L1-dense domains as a major influence on the ability of Xist-mediated silencing to be propagated in a continuous manner in cis.
Transcriptome analyses of mouse and human mammary cell subpopulations reveal multiple conserved genes and pathways
Authors: Lim Elgene , Wu Di , Pal Bhupinder , Bouras Toula , Asselin-Labat Marie-Liesse , Vaillant François , Yagita Hideo , Lindeman Geoffrey J , Smyth Gordon K , Visvader Jane E
Published: May 2010

Introduction

Molecular characterization of the normal epithelial cell types that reside in the mammary gland is an important step toward understanding pathways that regulate self-renewal, lineage commitment, and differentiation along the hierarchy. Here we determined the gene expression signatures of four distinct subpopulations isolated from the mouse mammary gland. The epithelial cell signatures were used to interrogate mouse models of mammary tumorigenesis and to compare with their normal human counterpart subsets to identify conserved genes and networks.

Methods

RNA was prepared from freshly sorted mouse mammary cell subpopulations (mammary stem cell (MaSC)-enriched, committed luminal progenitor, mature luminal and stromal cell) and used for gene expression profiling analysis on the Illumina platform. Gene signatures were derived and compared with those previously reported for the analogous normal human mammary cell subpopulations. The mouse and human epithelial subset signatures were then subjected to Ingenuity Pathway Analysis (IPA) to identify conserved pathways.

Results

The four mouse mammary cell subpopulations exhibited distinct gene signatures. Comparison of these signatures with the molecular profiles of different mouse models of mammary tumorigenesis revealed that tumors arising in MMTV-Wnt-1 and p53-/- mice were enriched for MaSC-subset genes, whereas the gene profiles of MMTV-Neu and MMTV-PyMT tumors were most concordant with the luminal progenitor cell signature. Comparison of the mouse mammary epithelial cell signatures with their human counterparts revealed substantial conservation of genes, whereas IPA highlighted a number of conserved pathways in the three epithelial subsets.

Conclusions

The conservation of genes and pathways across species further validates the use of the mouse as a model to study mammary gland development and highlights pathways that are likely to govern cell-fate decisions and differentiation. It is noteworthy that many of the conserved genes in the MaSC population have been considered as epithelial-mesenchymal transition (EMT) signature genes. Therefore, the expression of these genes in tumor cells may reflect basal epithelial cell characteristics and not necessarily cells that have undergone an EMT. Comparative analyses of normal mouse epithelial subsets with murine tumor models have implicated distinct cell types in contributing to tumorigenesis in the different models.
The dissection of transcriptional modules regulated by various drugs of abuse in the mouse striatum
Authors: Piechota Marcin , Korostynski Michal , Solecki Wojciech , Gieryk Agnieszka , Slezak Michal , Bilecki Wiktor , Ziolkowska Barbara , Kostrzewa Elzbieta , Cymerman Iwona , Swiech Lukasz , Jaworski Jacek , Przewlocki Ryszard
Published: May 2010

Background

Various drugs of abuse activate intracellular pathways in the brain reward system. These pathways regulate the expression of genes that are essential to the development of addiction. To reveal genes common and distinct for different classes of drugs of abuse, we compared the effects of nicotine, ethanol, cocaine, morphine, heroin and methamphetamine on gene expression profiles in the mouse striatum.

Results

We applied whole-genome microarray profiling to evaluate detailed time-courses (1, 2, 4 and 8 hours) of transcriptome alterations following acute drug administration in mice. We identified 42 drug-responsive genes that were segregated into two main transcriptional modules. The first module consisted of activity-dependent transcripts (includingFosandNpas4), which are induced by psychostimulants and opioids. The second group of genes (includingFkbp5andS3-12), which are controlled, in part, by the release of steroid hormones, was strongly activated by ethanol and opioids. Using pharmacological tools, we were able to inhibit the induction of particular modules of drug-related genomic profiles. We selected a subset of genes for validation byin situhybridization and quantitative PCR. We also showed that knockdown of the drug-responsive genesSgk1andTsc22d3resulted in alterations to dendritic spines in mice, possibly reflecting an altered potential for plastic changes.

Conclusions

Our study identified modules of drug-induced genes that share functional relationships. These genes may play a critical role in the early stages of addiction.
The 8 June 2008 Mw6.5 Achaia–Elia, Greece Earthquake: Source Characteristics, Ground Motions, and Ground Failure
Authors: Margaris Basil , Athanasopoulos George , Mylonakis George , Papaioannou Christos , Klimis Nikolaos , Theodulidis Nikolaos , Savvaidis Alexandros , Efthymiadou Vicky , Stewart Jonathan P.
Published: May 2010

The Mw6.4 Achaia–Elia (Greece) earthquake on 8 June 2008 was a right-lateral strike-slip event on a nearly vertical faul. Moment tensor solutions coupled with geologic structure and aftershock distributions suggest a fault strike of approximately 210° on a previously unmapped fault. Rupture appears to have been concentrated over a 10–25 km depth range and did not break the surface. The northern rupture limit appears to correspond to a NW-striking normal fault near the Kato Achaia coastline. The mainshock was recorded by 27 accelerometers at distances from the surface projection of the fault ranging from approximately 15 to 350 km. The data demonstrate faster distance attenuation than predicted by contemporary Greek ground motion prediction equations (GMPEs). On the other hand, an NGA GMPE generally captures the distance attenuation but shows underprediction bias at short and long periods. Despite the presence of a range of site conditions at recording stations in the city of Patras, we find no obvious effect of sediment depth on response spectra. We show the possible presence of rupture directivity at the north end of this bilateral rupture, but no apparent effect at the southern end. We described several relatively well-documented incidents of nonground failure and ground failure associated with liquefaction/lateral spreading and landslides.
Fragility of Mechanical, Electrical, and Plumbing Equipment
Authors: Porter Keith , Johnson Gayle , Sheppard Robert , Bachman Robert
Published: May 2010

A study for the Multidisciplinary Center for Earthquake Engineering Research (MCEER) provides fragility functions for 52 varieties of mechanical, electrical, and plumbing (MEP) equipment commonly found in commercial and industrial buildings. For the majority of equipment categories, the MCEER study provides multiple fragility functions, reflecting important effects of bracing, anchorage, interaction, etc. The fragility functions express the probability that the component would be rendered inoperative as a function of floor acceleration. That work did not include the evidence underlying the fragility functions. As part of the ATC-58 effort to bring second-generation performance-based earthquake engineering to professional practice, we have compiled the original MCEER specimen-level performance data into a publicly accessible database and validate many of the original fragility functions. In some cases, new fragility functions derived by ATC-58 methods show somewhat closer agreement with the raw data. Average-condition fragility functions are developed here; we will address in subsequent work the effect of potentially important—arguably crucial—performance-modifying factors such as poor anchorage and interaction.
Vibration Studies of Nonstructural Components and Systems within a Full-Scale Building
Authors: Hutchinson Tara C. , Nastase Derek , Kuester Falko , Doerr Kai
Published: May 2010

In contrast to building structural components, very little is known about the dynamic behavior of nonstructural components and systems (NCSs) within buildings. These systems come in such a variety of types that it can be overwhelming from an analysis perspective. Furthermore, an overarching issue is the limited test data available for characterizing their dynamic behavior. In this paper, an interior monitoring system is presented and used to monitor the response of a variety of NCSs within a full-scale building subjected to forced-vibration loading. The remotely operated monitoring system consists of an integrated array of off-the-shelf components, including; analog and digital (camera) sensors, acquisition PCs, and GPS synchronization equipment. Within the test building, the NCSs monitored include: (1) bench and shelf furnishing systems, (2) furnishing mounted equipment, and (3) piping systems. Results from the building vibration tests indicate that the interior furnishing systems considered here are very stiff with first mode frequencies in the range of 7–11 Hz and damping ratios between 4%–13%. Motion amplification at the top of the furnishing systems ranged between 1.5 and 4 times the floor level motion. These measurements highlight the importance of considering the transmissibility characteristics of building furnishings when estimating building NCS dynamic response.
Directivity Correction for the Next Generation Attenuation (NGA) Relations
Authors: Rowshandel Badie
Published: May 2010

Using ground motion residuals of four NGA models, directivity effect and the dependence of directivity on various seismological and geometrical parameters were studied and correction terms for the four models were obtained. Directivity was clearly seen in the ground motion residuals of most earthquakes in the NGA database. Specifically, this phenomenon was found to be significant for large earthquakes, but it was not consistently observed for small events. It was seen to strongly depend on period of ground motion and on source distance, having its largest values in the very near-source region and for long periods. This study further demonstrated that the intensity of directivity depends on the geometry of the fault, orientation of fault surface with respect to the site, and the location of hypocenter. Applying the correction terms to the NGA models resulted in considerable reductions in the uncertainty term sigma, especially at long periods and at short distances.
Enhanced Displacement Coefficient Method for Degrading Multi-Degree-of-Freedom Systems
Authors: Erduran Emrah , Kunnath Sashi K.
Published: May 2010

The displacement coefficient method proposed in FEMA 440 was evaluated using response statistics from a comprehensive set of nonlinear simulations of multi degree of freedom systems under both far-fault and near-fault ground motions. The study finds that it is practically difficult to achieve high relative strength factors ( R values equal to or greater than 6.0) for very stiff systems thereby dictating the need to define R-dependent demand coefficients. The approximate expressions proposed in FEMA 440 for the C2 coefficient is shown to underestimate the displacement demand of stiffness-degrading short period systems. Additional nonlinear simulations were performed to investigate the combined effect of strength degradation and P-Delta effects on the displacement demands of MDOF systems. A new expression for the modification factor that reflect combined P-Delta and degrading effects for the estimation of displacement demands is proposed.
Engineering Analysis of Ground Motion Records from the 2001 Mw 8.4 Southern Peru Earthquake
Authors: Rodriguez-Marek Adrian , Bay James A. , Park Kwangsoo , Montalva Gonzalo A. , Cortez-Flores Adel , Wartman Joseph , Boroschek Rubén
Published: May 2010

The Mw 8.4 23 June 2001 Southern Peru earthquake generated intense ground motions in a large region encompassing southern Peru and northern Chile. The earthquake was recorded by seven strong motion stations with peak ground accelerations ranging from 0.04 g to 0.34 g for site-to-fault distances ranging from about 70 km to 220 km. At this time, there are no other strong motion records for an earthquake of this magnitude. Hence, the strong motion data set from this earthquake is unique and of particular interest to engineers dealing with seismic design in subduction regions. This paper presents an engineering analysis of the strong motion records. Shear-wave velocity profiles were measured using Spectral Analysis of Surface Waves methods at four stations. Measured shear-wave velocities are high, indicating that all sites classify as stiff soil sites (Site C) according to the International Building Code classification scheme. The strong motion set is characterized by strong high frequency content at large distances from the fault. Site response contributed at least in part to the observed high frequency content in the ground motions. In general, current attenuation relationships for spectral acceleration underpredicted the observed ground motions.
NEHRP Site Amplification Factors and the NGA Relationships
Authors: Huang Yin-Nan , Whittaker Andrew S. , Luco Nicolas
Published: May 2010

The Next Generation Attenuation (NGA) relationships were developed using a large database of strong motion recordings of shallow crustal earthquakes. The functional form of the relationships provides an opportunity to assess and update if necessary the site class coefficients provided in the NEHRP Provisions and ASCE-7. Site amplification factors estimated using the Boore and Atkinson, Campbell and Bozorgnia, and Chiou and Youngs NGA relationships are computed and averaged for a combination of magnitude, distance, faulting type and period and for NEHRP/ASCE-7 Site Classes B, C, D and E and boundaries A/B, B/C, C/D and D/E. The average NGA site amplification factors show a clear dependency on period for V S30 smaller than 270 m/s and are substantially greater than the current NEHRP site class coefficients in some cases. The use of the NEHRP/ASCE-7 site class coefficients and spectral demands for the reference site condition computed using the NGA relationships may produce erroneous results. A family of site class coefficients is proposed to address these issues in a format suitable for inclusion in the NEHRP Provisions and ASCE-7.
Observed Seismic Behavior of Buildings in Northern Pakistan during the 2005 Kashmir Earthquake
Authors: Naseer Amjad , Khan Akhtar Naeem , Hussain Zakir , Ali Qaisar
Published: May 2010

Recent earthquakes in Pakistan demonstrated that the region is highly seismic. Masonry buildings constructed with stones, concrete blocks, and fired-clay bricks and concrete buildings were damaged during the 8 October 2005 Kashmir earthquake. This paper presents the seismic behavior of reinforced concrete and masonry buildings in northern part of the North-West Frontier Province (NWFP) and Kashmir during the earthquake. Most of the buildings were observed to be nonengineered or semi-engineered. The paper presents an overview of the 1937 Quetta building code and the 1986 and 2007 building codes of Pakistan. Lessons learned during the earthquake are also presented.
Modeling Input Motion Boundary Conditions for Simulations of Geotechnical Shaking Table Tests
Authors: Ilankatharan Mahadevan , Kutter Bruce
Published: May 2010

This paper discusses the effects of using different input-motion-boundary-conditions on the sensitivity of numerical simulations results to errors in material properties of a specimen tested on a shaking table. In the flexible-actuator-prescribed-force-boundary-condition, input is specified by a force across an actuator element that connects the shaking table to a reaction mass. In the prescribed-displacement-boundary-condition, the measured shaking table motion in the experiment is prescribed in the simulation. The flexible-actuator-prescribed-force approach yielded smaller, almost constant sensitivity of simulation results to input properties. The prescribed-displacement approach yielded larger and more variable sensitivities. The sensitivity of results depends on the how the boundary conditions are handled has further implications: the assessment of a comparison between a simulation and an experimental result should be performed with due consideration to the effect of the boundary conditions on the comparison, and numerically determined sensitivities may not be physically meaningful if the boundary condition is not accurately modeled.
Observed Natural Frequencies, Damping Ratios, and Mode Shapes of Vibration of a 30-Story Building Excited by a Major Earthquake and Typhoon
Authors: Liu Kun-Sung , Tsai Yi-Ben
Published: May 2010

The safety of building structures and contents, as well as the comfort of occupants, under such strong forces as earthquakes and typhoons remain major engineering concerns. In order to improve our understanding of building structural responses, records of a structural array in the 30-story PS Building in Taipei from the M7.6 Chi-Chi earthquake and Typhoon Aere are analyzed. In addition, wind data measured at the Taipei Meteorological Station are also used. First, the field measurement data clearly demonstrate that serviceability of the PS Building met the criteria for occupant comfort during Typhoon Aere. Secondly, several structural vibration parameters of this highrise building, including the transfer functions, natural frequencies, damping ratios and mode shapes, excited by the Chi-Chi earthquake, Typhoon Aere, and ambient vibrations are also determined and compared. The results show the frequency of the first mode for the longitudinal components is approximately 8.6% lower for the earthquake than the ambient vibrations. The transverse mode frequencies behave similarly. In contrast, frequency changes from the typhoon to ambient vibrations are in the third decimal (1.3% and 0.9% lower in the longitudinal and transverse directions, respectively), indicating little nonlinearity. The damping ratios of the PS Building apparently increase with vibration amplitudes. Finally, results of a spectral ratio analysis of the Chi-Chi earthquake data do not indicate significant SSI effects in the longitudinal and transverse directions.
Cyclic Behavior of Zipper-Braced Frames
Authors: Yang Chuang-Sheng , Leon Roberto T. , DesRoches Reginald
Published: May 2010

Two one-third-scale three-story models of special inverted-V-braced frames with zipper struts were tested under quasistatic cyclic loads. Zipper frames utilize a vertical element at the intersection of chevron braces and floor beams to distribute the unbalanced vertical forces due to brace buckling. Two ground motions representative of a far-field (Chile 1985) and a near-field earthquake (Kobe 1995) were selected for the tests. Two tests with two different amplitudes of the 1985 Chile earthquake were conducted on one frame; three tests with three different amplitudes of the 1995 Kobe record on the other. For each specimen, a pre-experiment numerical model was used to generate the three floor displacement histories that were applied to the test frame. Comparison of the results for the hysteretic behavior of the braces, zipper struts, and overall frame validated the partial-height zipper mechanism envisioned in proportioning the specimens. The frames showed good dissipating-energy capacity and large deformation ductilities without significant strength losses. Moreover, they remained stable even after fracture of some braces occurred and showed significant residual strength.