bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between gastroesophageal reflux and asthma: an update
Authors: McCallister Jennifer W. , Parsons Jonathan P. , Mastronarde John G.
Published: October 2010

Asthma and gastroesophageal reflux disease (GERD) are both common conditions and, hence, they often coexist. However, asthmatics have been found to have a much greater prevalence of GERD symptoms than the general population. There remains debate regarding the underlying physiologic mechanism(s) of this relationship and whether treatment of GERD actually translates into improved asthma outcomes. Based on smaller trials with somewhat conflicting results regarding improved asthma control with treatment of GERD, current guidelines recommend a trial of GERD treatment for symptomatic asthmatics even without symptoms of GERD. However, recently a large multicenter trial demonstrated that the treatment of asymptomatic GERD with proton-pump inhibitors did not improve asthma control in terms of pulmonary function, rate of asthma exacerbations, asthma-related quality of life, or asthma symptom frequency. These data suggest empiric treatment of asymptomatic GERD in asthmatics is not a useful practice. This review article provides an overview of the epidemiology and pathophysiologic relationships between asthma and GERD as well as a summary of current data regarding links between treatment of GERD with asthma outcomes.
High doses of mother's lymphocyte infusion to treat EBV-positive T-cell lymphoproliferative disorders in childhood
Authors: Wang Qian , Liu Hongxing , Zhang Xian , Liu Qian , Xing Yanping , Zhou Xiaoge , Tong Chunrong , Zhu Ping
Published: October 2010

Donor lymphocyte infusion is an alternative treatment for Epstein-Barr virus (EBV)–associated lymphoproliferative disorders (LPDs) but with risk of graft-versus-host diseases (GVHDs). According to the fetal-maternal microchimerism tolerance, we assumed that maternal lymphocyte infusion may be effective without causing GVHD. In 54 cases when a child required cytotherapy or hematopoietic stem cell transplantation, we studied the mother for child-mother microchimerism with use of insertion-deletion polymorphisms as allogeneic markers and a combination of nested polymerase chain reaction (PCR) and real-time quantitative PCR. Thirteen mothers were child-microchimerism–positive at the ratio of 10−5-10−3. Among them, 5 children had non–transplant-associated, EBV+ T-cell LPD. In these 5 cases, high doses of human leukocyte antigen–haploidentical maternal peripheral blood mononuclear cells (> 108/kg/infusion) were infused 1-4 times. Symptoms of all 5 patients improved between 3 and 10 days after the infusion; thereafter, 3 cases showed complete remission for 6-18 months without further therapy and 2 had partial remission. During the period of observation, none developed obvious GVHD. By quantitative PCR, in some patients maternal cells were found to be eliminated or decreased after infusions, indicating existence of host-versus-graft reaction. We suggest that high doses of mother's lymphocyte infusion may be an effective and safe treatment for non–transplant-associated EBV+ T-cell LPD.
X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease
Authors: Booth Claire , Gilmour Kimberly C. , Veys Paul , Gennery Andrew R. , Slatter Mary A. , Chapel Helen , Heath Paul T. , Steward Colin G. , Smith Owen , O'Meara Anna , Kerrigan Hilary , Mahlaoui Nizar , Cavazzana-Calvo Marina , Fischer Alain , Moshous Despina , Blanche Stephane , Pachlopnik Schmid Jana , Latour Sylvain , de Saint-Basile Genevieve , Albert Michael , Notheis Gundula , Rieber Nikolaus , Strahm Brigitte , Ritterbusch Henrike , Lankester Arjan , Hartwig Nico G. , Meyts Isabelle , Plebani Alessandro , Soresina Annarosa , Finocchi Andrea , Pignata Claudio , Cirillo Emilia , Bonanomi Sonia , Peters Christina , Kalwak Krzysztof , Pasic Srdjan , Sedlacek Petr , Jazbec Janez , Kanegane Hirokazu , Nichols Kim E. , Hanson I. Celine , Kapoor Neena , Haddad Elie , Cowan Morton , Choo Sharon , Smart Joanne , Arkwright Peter D. , Gaspar Hubert B.
Published: October 2010

X-linked lymphoproliferative disease (XLP1) is a rare immunodeficiency characterized by severe immune dysregulation and caused by mutations in the SH2D1A/SAP gene. Clinical manifestations are varied and include hemophagocytic lymphohistiocytosis (HLH), lymphoma and dysgammaglobulinemia, often triggered by Epstein-Barr virus infection. Historical data published before improved treatment regimens shows very poor outcome. We describe a large cohort of 91 genetically defined XLP1 patients collected from centers worldwide and report characteristics and outcome data for 43 patients receiving hematopoietic stem cell transplant (HSCT) and 48 untransplanted patients. The advent of better treatment strategies for HLH and malignancy has greatly reduced mortality for these patients, but HLH still remains the most severe feature of XLP1. Survival after allogeneic HSCT is 81.4% with good immune reconstitution in the large majority of patients and little evidence of posttransplant lymphoproliferative disease. However, survival falls to 50% in patients with HLH as a feature of disease. Untransplanted patients have an overall survival of 62.5% with the majority on immunoglobulin replacement therapy, but the outcome for those untransplanted after HLH is extremely poor (18.8%). HSCT should be undertaken in all patients with HLH, because outcome without transplant is extremely poor. The outcome of HSCT for other manifestations of XLP1 is very good, and if HSCT is not undertaken immediately, patients must be monitored closely for evidence of disease progression.
Differential regulation of p53 function by the N-terminal ΔNp53 and Δ113p53 isoforms in zebrafish embryos
Authors: Davidson William R , Kari Csaba , Ren Qing , Daroczi Borbala , Dicker Adam P , Rodeck Ulrich
Published: October 2010

Background

The p53 protein family coordinates stress responses of cells and organisms. Alternative promoter usage and/or splicing of p53 mRNA gives rise to at least nine mammalian p53 proteins with distinct N- and C-termini which are differentially expressed in normal and malignant cells. The human N-terminal p53 variants contain either the full-length (FL), or a truncated (ΔN/Δ40) or no transactivation domain (Δ133) altogether. The functional consequences of coexpression of the different p53 isoforms are poorly defined. Here we investigated functional aspects of the zebrafish ΔNp53 ortholog in the context of FLp53 and the zebrafish Δ133p53 ortholog (Δ113p53) coexpressed in the developing embryo.

Results

We cloned the zebrafish ΔNp53 isoform and determined that ionizing radiation increased expression of steady-state ΔNp53 and Δ113p53 mRNA levels in zebrafish embryos. Ectopic ΔNp53 expression by mRNA injection caused hypoplasia and malformation of the head, eyes and somites, yet partially counteracted lethal effects caused by concomitant expression of FLp53. FLp53 expression was required for developmental aberrations caused by ΔNp53 and for ΔNp53-dependent expression of the cyclin-dependent kinase inhibitor 1A (CDKN1A, p21, Cip1, WAF1). Knockdown of p21 expression markedly reduced the severity of developmental malformations associated with ΔNp53 overexpression. By contrast, forced Δ113p53 expression had little effect on ΔNp53-dependent embryonal phenotypes. These functional attributes were shared between zebrafish and human ΔNp53 orthologs ectopically expressed in zebrafish embryos. All 3 zebrafish isoforms could be coimmunoprecipitated with each other after transfection into Saos2 cells.

Conclusions

Both alternative N-terminal p53 isoforms were expressed in developing zebrafish in response to cell stress and antagonized lethal effects of FLp53 to different degrees. However, in contrast to Δ113p53, forced ΔNp53 expression itself led to developmental defects which depended, in part, on p21 transactivation. In contrast to FLp53, the developmental abnormalities caused by ΔNp53 were not counteracted by concomitant expression of Δ113p53.
Erratum to: Influence of mutation rate on estimators of genetic differentiation - lessons from Arabidopsis thaliana
Authors: Kronholm Ilkka , Loudet Olivier , de Meaux Juliette
Published: October 2010

It has been brought to our attention that our paper (Kronholm et al. BMC Genetics 2010, 11:33) may have caused some confusion for readers interested in the correct quantification of population differentiation. We feel that this issue is of some importance and wish to clarify any confusion that might have resulted.
Aberrant host immune response induced by highly virulent PRRSV identified by digital gene expression tag profiling
Authors: Xiao Shuqi , Mo Delin , Wang Qiwei , Jia Jianyu , Qin Limei , Yu Xiangchun , Niu Yuna , Zhao Xiao , Liu Xiaohong , Chen Yaosheng
Published: October 2010

Background

There was a large scale outbreak of the highly pathogenic porcine reproductive and respiratory syndrome (PRRS) in China and Vietnam during 2006 and 2007 that resulted in unusually high morbidity and mortality among pigs of all ages. The mechanisms underlying the molecular pathogenesis of the highly virulent PRRS virus (H-PRRSV) remains unknown. Therefore, the relationship between pulmonary gene expression profiles after H-PRRSV infection and infection pathology were analyzed in this study using high-throughput deep sequencing and histopathology.

Results

H-PRRSV infection resulted in severe lung pathology. The results indicate that aberrant host innate immune responses to H-PRRSV and induction of an anti-apoptotic state could be responsible for the aggressive replication and dissemination of H-PRRSV. Prolific rapid replication of H-PRRSV could have triggered aberrant sustained expression of pro-inflammatory cytokines and chemokines leading to a markedly robust inflammatory response compounded by significant cell death and increased oxidative damage. The end result was severe tissue damage and high pathogenicity.

Conclusions

The systems analysis utilized in this study provides a comprehensive basis for better understanding the pathogenesis of H-PRRSV. Furthermore, it allows the genetic components involved in H-PRRSV resistance/susceptibility in swine populations to be identified.
Activated mammalian target of rapamycin is a potential therapeutic target in gastric cancer
Authors: Xu Da-zhi , Geng Qi-rong , Tian Ying , Cai Mu-yan , Fang Xin-juan , Zhan You-qing , Zhou Zhi-wei , Li Wei , Chen Ying-bo , Sun Xiao-wei , Guan Yuan-xiang , Li Yuan-fang , Lin Tong-yu
Published: October 2010

Background

The mammalian target of rapamycin (mTOR) plays a key role in cellular growth and homeostasis. The purpose of our present study is to investigate the expression of activated mTOR (p-mTOR) in gastric cancer patients, their prognostic significance and the inhibition effect of RAD001 on tumor growth and to determine whether targeted inhibition of mTOR could be a potential therapeutic strategy for gastric cancer.

Methods

The expression of p-mTOR was detected in specimens of 181 gastric cancers who underwent radical resection (R0) by immunohistochemistry. The correlation of p-mTOR expression to clinicopathologic features and survival of gastric cancer was studied. We also determined the inhibition effect of RAD001 on tumor growth using BGC823 and AGS human gastric cancer cell lines.

Results

Immunostaining for p-mTOR was positive in 93 of 181 (51.4%) gastric cancers, closely correlated with lymph node status and pTNM stage. Patients with p-mTOR positive showed significantly shorter disease-free survival (DFS) and overall survival (OS) rates than those with p-mTOR-negative tumors in univariable analyses, and there was a trend toward a correlation between p-mTOR expression and survival in multivariable analyses. RAD001 markedly inhibited dose-dependently proliferation of human gastric carcinoma cells by down-regulating expression of p70s6k, p-p70s6k, C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53.

Conclusions

In gastric cancer, p-mTOR is a potential therapeutic target and RAD001 was a promising treatment agent with inducing cell cycle arrest and apoptosis by down-regulating expression of C-myc, CyclinD1 and Bcl-2, up-regulating expression of P53.
Recombinant human follicle-stimulating hormone produces more oocytes with a lower total dose per cycle in assisted reproductive technologies compared with highly purified human menopausal gonadotrophin: a meta-analysis
Authors: Lehert Philippe , Schertz Joan C , Ezcurra Diego
Published: October 2010

Background

Human menopausal gonadotrophins and recombinant human follicle stimulating hormone are the two main gonadotrophin products utilized for controlled ovarian stimulation in assisted reproductive technologies. In this meta-analysis, the number of oocytes was designated as the most relevant endpoint directly resulting from ovarian stimulation, and therefore where the drug effect may be estimated with the best sensitivity.

Methods

All published randomized controlled trials on ovarian stimulation comparing the two gonadotrophin products were evaluated. Internal validity was determined using Chalmers' validated scale. If trials did not meet the established quality criteria, a sensitivity analysis assessed the stability of the results. The comparison of continuous variables was conducted following the weighted mean difference and the standardized mean difference (Cohen's effect size) with the random model. Given the known relationship of baseline conditions on treatment endpoints, results were adjusted for age, body mass index and type of infertility.

Results

Sixteen studies involving 4040 patients were included. Treatment with human menopausal gonadotrophins resulted in fewer oocytes (-1.54; 95% CI: -2.53 to -0.56; P < 0.0001) compared to recombinant human follicle-stimulating hormone. When adjusting for baseline conditions, the mean difference estimate was -2.10 (95% CI: -2.83 to -1.36; P < 0.001). A higher total dose of human menopausal gonadotrophin was necessary (mean difference, 235.46 IU [95% CI: 16.62 to 454.30; P = 0.03]; standardized mean difference, 0.33 [95% CI: 0.08 to 0.58; P = 0.01]). The pregnancy absolute risk difference (RD [hMG-r-hFSH]) for fresh transfers was 3% (P = 0.051), and the relative risk 1.10 (P = 0.06). When adjusted for baseline conditions, the relative risk was 1.04 (P = 0.49) and absolute difference was 0.01 (P = 0.34), respectively.

Conclusions

Because baseline conditions are predictive of outcome, meta-analytic results are more sensitive when these variables are considered. Using an endpoint closely associated with the stimulation period, sufficient sensitivity is achieved to compare gonadotrophin treatments. As the largest meta-analysis published to date on this subject, treatment with human menopausal gonadotrophins is characterized by fewer oocytes and a higher total dose. When considering only fresh transfers, pregnancy rates were similar.
Phagocytosis and LPS alter the maturation state of β-amyloid precursor protein and induce different Aβ peptide release signatures in human mononuclear phagocytes
Authors: Spitzer Philipp , Herrmann Martin , Klafki Hans-Wolfgang , Smirnov Alexander , Lewczuk Piotr , Kornhuber Johannes , Wiltfang Jens , Maler Juan Manuel
Published: October 2010

Background

The classic neuritic β-amyloid plaque of Alzheimer's disease (AD) is typically associated with activated microglia and neuroinflammation. Similarly, cerebrovascular β-amyloid (Aβ) deposits are surrounded by perivascular macrophages. Both observations indicate a contribution of the mononuclear phagocyte system to the development of β-amyloid.

Methods

Human CD14-positive mononuclear phagocytes were isolated from EDTA-anticoagulated blood by magnetic activated cell sorting. After a cultivation period of 72 hours in serum-free medium we assessed the protein levels of amyloid precursor protein (APP) as well as the patterns and the amounts of released Aβ peptides by ELISA or one-dimensional and two-dimensional urea-based SDS-PAGE followed by western immunoblotting.

Results

We observed strong and significant increases in Aβ peptide release upon phagocytosis of acetylated low density lipoprotein (acLDL) or polystyrene beads and also after activation of the CD14/TLR4 pathway by stimulation with LPS. The proportion of released N-terminally truncated Aβ variants was increased after stimulation with polystyrene beads and acLDL but not after stimulation with LPS. Furthermore, strong shifts in the proportions of single Aβ1-40and Aβ2-40variants were detected resulting in a stimulus-specific Aβ signature. The increased release of Aβ peptides was accompanied by elevated levels of full length APP in the cells. The maturation state of APP was correlated with the release of N-terminally truncated Aβ peptides.

Conclusions

These findings indicate that mononuclear phagocytes potentially contribute to the various N-truncated Aβ variants found in AD β-amyloid plaques, especially under neuroinflammatory conditions.
Comparative biochemical analysis of recombinant reverse transcriptase enzymes of HIV-1 subtype B and subtype C
Authors: Xu Hong-Tao , Quan Yudong , Asahchop Eugene , Oliveira Maureen , Moisi Daniella , Wainberg Mark A
Published: October 2010

Background

HIV-1 subtype C infections account for over half of global HIV infections, yet the vast focus of HIV-1 research has been on subtype B viruses which represent less than 12% of the global pandemic. Since HIV-1 reverse transcriptase (RT) is a major target of antiviral therapy, and since differential drug resistance pathways have been observed among different HIV subtypes, it is important to study and compare the enzymatic activities of HIV-1 RT derived from each of subtypes B and C as well as to determine the susceptibilities of these enzymes to various RT inhibitors in biochemical assays.

Methods

Recombinant subtype B and C HIV-1 RTs in heterodimeric form were purified from Escherichia coli and enzyme activities were compared in cell-free assays. The efficiency of (-) ssDNA synthesis was measured using gel-based assays with HIV-1 PBS RNA template and tRNA3
Lys as primer. Processivity was assayed under single-cycle conditions using both homopolymeric and heteropolymeric RNA templates. Intrinsic RNase H activity was compared using 5'-end labeled RNA template annealed to 3'-end recessed DNA primer in a time course study in the presence and absence of a heparin trap. A mis-incorporation assay was used to assess the fidelity of the two RT enzymes. Drug susceptibility assays were performed both in cell-free assays using recombinant enzymes and in cell culture phenotyping assays.

Results

The comparative biochemical analyses of recombinant subtype B and subtype C HIV-1 reverse transcriptase indicate that the two enzymes are very similar biochemically in efficiency of tRNA-primed (-) ssDNA synthesis, processivity, fidelity and RNase H activity, and that both enzymes show similar susceptibilities to commonly used NRTIs and NNRTIs. Cell culture phenotyping assays confirmed these results.

Conclusions

Overall enzyme activity and drug susceptibility of HIV-1 subtype C RT are comparable to those of subtype B RT. The use of RT inhibitors (RTIs) against these two HIV-1 enzymes should have comparable effects.
Use of a highly sensitive strand-specific quantitative PCR to identify abortive replication in the mouse model of respiratory syncytial virus disease
Authors: Bannister Richard , Rodrigues Deborah , Murray Edward J , Laxton Carl , Westby Mike , Bright Helen
Published: October 2010

Background

The BALB/c mouse is commonly used to study RSV infection and disease. However, despite the many advantages of this well-characterised model, the inoculum is large, viral replication is restricted and only a very small amount of virus can be recovered from infected animals. A key question in this model is the fate of the administered virus. Is replication really being measured or is the model measuring the survival of the virus over time? To answer these questions we developed a highly sensitive strand-specific quantitative PCR (QPCR) able to accurately quantify the amount of RSV replication in the BALB/c mouse lung, allowing characterisation of RSV negative and positive strand RNA dynamics.

Results

In the mouse lung, no increase in RSV genome was seen above the background of the original inoculum whilst only a limited transient increase (< 1 log) in positive strand, replicative intermediate (RI) RNA occurred. This RNA did however persist at detectable levels for 59 days post infection. As expected, ribavirin therapy reduced levels of infectious virus and RI RNA in the mouse lung. However, whilst Palivizumab therapy was also able to reduce levels of infectious virus, it failed to prevent production of intracellular RI RNA. A comparison of RSV RNA kinetics in human (A549) and mouse (KLN205) cell lines demonstrated that RSV replication was also severely delayed and impaired in vitro in the mouse cells.

Conclusions

This is the first time that such a sensitive strand-specific QPCR technique has been to the RSV mouse system. We have accurately quantified the restricted and abortive nature of RSV replication in the mouse. Further in vitro studies in human and mouse cells suggest this restricted replication is due at least in part to species-specific host cell-viral interactions.
Simultaneous detection and differentiation by multiplex real time RT-PCR of highly pathogenic avian influenza subtype H5N1 classic (clade 2.2.1 proper) and escape mutant (clade 2.2.1 variant) lineages in Egypt
Authors: Abdelwhab El-Sayed M , Erfan Ahmed M , Grund Christian , Ziller Mario , Arafa Abdel-Satar , Beer Martin , Aly Mona M , Hafez Hafez M , Harder Timm C
Published: October 2010

Background

The endemic status of highly pathogenic avian influenza virus (HPAIV) of subtype H5N1 in Egypt continues to devastate the local poultry industry and poses a permanent threat for human health. Several genetically and antigenically distinct H5N1 lineages co-circulate in Egypt: Strains of clade 2.2.1 proper replicate mainly in backyard birds causing the bulk of human infections, while a variant lineage within 2.2.1 (2.2.1v) appears to be perpetuated mainly in commercial poultry farms in Egypt. Viruses of the 2.2.1v lineage represent drift variants escaping from conventional vaccine-induced immunity and some of these strains also escaped detection by commercial real time reverse transcriptase PCR (RT-qPCR) protocols due to mismatches in the primers/probe binding sites.

Results

We developed therefore a versatile, sensitive and lineage-specific multiplex RT-qPCR for detection and typing of H5N1 viruses in Egypt. Analytical characterization was carried out using 50 Egyptian HPAIV H5N1 strains isolated since 2006 and 45 other avian influenza viruses (AIV). A detection limit of 400 cRNA copies per ml sample matrix was found. Higher diagnostic sensitivity of the multiplex assay in comparison to other generic H5 or M-gene based RT-qPCR assays were found by examination of 63 swab samples from experimentally infected chickens and 50 AIV-positive swab samples from different host species in the field in Egypt.

Conclusions

The new multiplex RT-qPCR assay could be useful for rapid high-throughput monitoring for the presence of HPAIV H5N1 in commercial poultry in Egypt. It may also aid in prospective epidemiological studies to further delineate and better control spread of HPAIV H5N1 in Egypt.
Genome-wide analysis of host-chromosome binding sites for Epstein-Barr Virus Nuclear Antigen 1 (EBNA1)
Authors: Lu Fang , Wikramasinghe Priyankara , Norseen Julie , Tsai Kevin , Wang Pu , Showe Louise , Davuluri Ramana V , Lieberman Paul M
Published: October 2010

The Epstein-Barr Virus (EBV) Nuclear Antigen 1 (EBNA1) protein is required for the establishment of EBV latent infection in proliferating B-lymphocytes. EBNA1 is a multifunctional DNA-binding protein that stimulates DNA replication at the viral origin of plasmid replication (OriP), regulates transcription of viral and cellular genes, and tethers the viral episome to the cellular chromosome. EBNA1 also provides a survival function to B-lymphocytes, potentially through its ability to alter cellular gene expression. To better understand these various functions of EBNA1, we performed a genome-wide analysis of the viral and cellular DNA sites associated with EBNA1 protein in a latently infected Burkitt lymphoma B-cell line. Chromatin-immunoprecipitation (ChIP) combined with massively parallel deep-sequencing (ChIP-Seq) was used to identify cellular sites bound by EBNA1. Sites identified by ChIP-Seq were validated by conventional real-time PCR, and ChIP-Seq provided quantitative, high-resolution detection of the known EBNA1 binding sites on the EBV genome at OriP and Qp. We identified at least one cluster of unusually high-affinity EBNA1 binding sites on chromosome 11, between the divergent FAM55 D and FAM55B genes. A consensus for all cellular EBNA1 binding sites is distinct from those derived from the known viral binding sites, suggesting that some of these sites are indirectly bound by EBNA1. EBNA1 also bound close to the transcriptional start sites of a large number of cellular genes, including HDAC3, CDC7, and MAP3K1, which we show are positively regulated by EBNA1. EBNA1 binding sites were enriched in some repetitive elements, especially LINE 1 retrotransposons, and had weak correlations with histone modifications and ORC binding. We conclude that EBNA1 can interact with a large number of cellular genes and chromosomal loci in latently infected cells, but that these sites are likely to represent a complex ensemble of direct and indirect EBNA1 binding sites.
Epigenetic modifications as key regulators of Waldenstrom's Macroglobulinemia biology
Authors: Sacco Antonio , Issa Ghayas C , Zhang Yong , Liu Yang , Maiso Patricia , Ghobrial Irene M , Roccaro Aldo M
Published: October 2010

Waldenstrom's Macroglobulinemia is a low-grade B-cell lymphoma characterized by the presence of lymphoplasmacytic cells in the bone marrow and a monoclonal immunoglobulin M in the circulation. Recent evidences support the hypothesis that epigenetic modifications lead to Waldesntrom cell proliferation and therefore play a crucial role in the pathogenesis of this disease. Indeed, while cytogenetic and gene expression analysis have demonstrated minimal changes; microRNA aberrations and modification in the histone acetylation status of primary Waldenstrom Macroglobulinemia tumor cells have been described. These findings provide a better understanding of the underlying molecular changes that lead to the initiation and progression of this disease.
A COLUMN ON THE HISTORY AND CULTURE OF GEOPHYSICS AND SCIENCE IN GENERAL
Authors: Liner Christopher L.
Published: October 2010

De Rerum Fractura. These days it is much in the mind of petroleum seismic researchers to get into the “fracture game.” This is driven by the remarkable rise in natural gas reserves from shale reservoirs, primarily in the US for now but quickly being exported worldwide. Shale formations have long been of interest as source rock and reservoir seal, but in the last 20 years shale has taken center stage as a reservoir in its own right. Gone are the days when we would drill through shale and get a gas kick, ignore it, then drill on down to conventional reservoirs. Gas shale is considered an unconventional reservoir, mainly because of very low porosity and permeability compared to those Swiss cheese sandstones and limestones. For a 25% porosity conventional reservoir, you need only to punch a hole through it, open the choke, and production will scream out for decades. But shale, like tight gas sand, must be modified to open channels for production. Wells must be horizontally drilled to expose more reservoir rock and they must be fractured.
Introduction to this special section: Multicomponent seismic
Authors: Chopra Satinder , Stewart Robert
Published: October 2010

A seismic source excites a rich variety of elastic waves in the Earth, so it seems reasonable to try to use them all to create a more compelling picture of the subsurface. While P-wave imaging has been enormously successful in this regard, there are conditions when it is less so. But, the demands of energy discovery and recovery require an increasingly comprehensive portrayal of reservoir lithologies, stresses, fractures, and fluids. The multicomponent seismic method is a superset of conventional seismic technology and has the potential to answer to some of these demands. Recording horizontal motion, as well as vertical vibrations and pressures, allows further capturing of the full seismic wavefield, and the additional resultant pictures can provide greater comprehension of subsurface properties, fluids, and their changes. We might liken this to a more complete conversation with “loud” waves (P-waves arriving first with high amplitudes) and “shy” waves (S-waves with lower voices and a more complicated message).
Delineating oil-sand reservoirs with high-resolution PP/PS processing and joint inversion in the Junggar Basin, Northwest China
Authors: Dang Yufang , Lou Bing , Miao Xiaogui , Wang Pu , Zhang Sihai , Shen Liang
Published: October 2010

Dramatic lateral lithological variations in the fluvial sediments in Chepaizi, in the Junggar Basin of Northwest China, have posed challenges in distinguishing true and false “bright spots” in oil-bearing sand reservoirs. A high-resolution multicomponent seismic survey and joint prestack PP and PS inversion conducted recently provided an effective technique for solving the problem and successfully delineating the characteristics of the reservoir. This is due to the different reflection response of shear waves to the lithology and fluid content, and their ability to resolve thin layers. Surface-consistent amplitude- and resolution-preserving pro-cessing produced high-quality prestack PP and PS migrated gathers and stacks for extracting seismic attributes. Application of joint prestack PP and PS inversion resulted in higher fluid factors and lower [Formula: see text] in oil-bearing sands compared with dry sands. The correlation between the inversion and the existing well data suggests that high-resolution multicomponent AVO can reduce drilling risks and provide more accurate reservoir characterization.
The case for separate sensor processing: Meeting the imaging challenge in a producing carbonate field in the Middle East
Authors: Reilly Joseph M. , Shatilo Andrew P. , Shevchek Zyg J.
Published: October 2010

Carbonate platforms in the Middle East continue to represent an important source of hydrocarbon reserves. For more than 20 years, interpretation and attribute extraction from time-based 3D seismic imaging products have been base geoscience data in this production setting. With the continuing advances in seismic imaging, geophysicists have an obvious interest in applying the most current algorithms to their projects. However, many of these carbonate reservoirs have accompanying imaging challenges that cannot be addressed solely through the application of new imaging technology. Alternative processing strategies must be considered, either to replace more conventional approaches and/or to prepare the data so that they conform to the limitations of the imaging algorithm.
Specific Involvement of Gonadal Hormones in the Functional Maturation of Growth Hormone Releasing Hormone (GHRH) Neurons
Authors: Gouty-Colomer Laurie-Anne , Méry Pierre-François , Storme Emilie , Gavois Elodie , Robinson Iain C. , Guérineau Nathalie C. , Mollard Patrice , Desarménien Michel G.
Published: October 2010

Growth hormone (GH) is the key hormone involved in the regulation of growth and metabolism, two functions that are highly modulated during infancy. GH secretion, controlled mainly by GH releasing hormone (GHRH), has a characteristic pattern during postnatal development that results in peaks of blood concentration at birth and puberty. A detailed knowledge of the electrophysiology of the GHRH neurons is necessary to understand the mechanisms regulating postnatal GH secretion. Here, we describe the unique postnatal development of the electrophysiological properties of GHRH neurons and their regulation by gonadal hormones. Using GHRH-eGFP mice, we demonstrate that already at birth, GHRH neurons receive numerous synaptic inputs and fire large and fast action potentials (APs), consistent with effective GH secretion. Concomitant with the GH secretion peak occurring at puberty, these neurons display modifications of synaptic input properties, decrease in AP duration, and increase in a transient voltage-dependant potassium current. Furthermore, the modulation of both the AP duration and voltage-dependent potassium current are specifically controlled by gonadal hormones because gonadectomy prevented the maturation of these active properties and hormonal treatment restored it. Thus, GHRH neurons undergo specific developmental modulations of their electrical properties over the first six postnatal weeks, in accordance with hormonal demand. Our results highlight the importance of the interaction between the somatotrope and gonadotrope axes during the establishment of adapted neuroendocrine functions.
Rapid Signaling Actions of Environmental Estrogens in Developing Granule Cell Neurons Are Mediated by Estrogen Receptor β
Authors: Le Hoa H. , Belcher Scott M.
Published: October 2010

Estrogenic endocrine disrupting chemicals (EDCs) constitute a diverse group of man-made chemicals and natural compounds derived from plants and microbial metabolism. Estrogen-like actions are mediated via the nuclear hormone receptor activity of estrogen receptor (ER)α and ERβ and rapid regulation of intracellular signaling cascades. Previous study defined cerebellar granule cell neurons as estrogen responsive and that granule cell precursor viability was developmentally sensitive to estrogens. In this study experiments using Western blot analysis and pharmacological approaches have characterized the receptor and signaling modes of action of selective and nonselective estrogen ligands in developing cerebellar granule cells. Estrogen treatments were found to briefly increase ERK1/2-phosphorylation and then cause prolonged depression of ERK1/2 activity. The sensitivity of granule cell precursors to estrogen-induced cell death was found to require the integrated activation of membrane and intracellular ER signaling pathways. The sensitivity of granule cells to selective and nonselective ER agonists and a variety of estrogenic and nonestrogenic EDCs was also examined. The ERβ selective agonist DPN, but not the ERα selective agonist 4,4′,4′-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol or other ERα-specific ligands, stimulated cell death. Only EDCs with selective or nonselective ERβ activities like daidzein, equol, diethylstilbestrol, and bisphenol A were observed to induce E2-like neurotoxicity supporting the conclusion that estrogen sensitivity in granule cells is mediated via ERβ. The presented results also demonstrate the utility of estrogen sensitive developing granule cells as an in vitro assay for elucidating rapid estrogen-signaling mechanisms and to detect EDCs that act at ERβ to rapidly regulate intracellular signaling.
BAX-Dependent and BAX-Independent Regulation of Kiss1 Neuron Development in Mice
Authors: Semaan Sheila J. , Murray Elaine K. , Poling Matthew C. , Dhamija Sangeeta , Forger Nancy G. , Kauffman Alexander S.
Published: October 2010

The Kiss1 gene and its product kisspeptin are important regulators of reproduction. In rodents, Kiss1 is expressed in the hypothalamic arcuate (ARC) and anteroventral periventricular (AVPV)/rostral periventricular (PeN) nuclei. In the AVPV/PeN, females have more Kiss1 and tyrosine hydroxylase (TH) neurons than males. We explored the ontogeny of the Kiss1 sex difference, and the role of cell death in establishing Kiss1 and TH cell number. We also determined whether Kiss1 cells in AVPV/PeN coexpress TH. AVPV/PeN Kiss1 neurons were first detected in both sexes on postnatal d 10, but the Kiss1 sex difference did not emerge until postnatal d 12. The role of BAX-mediated apoptosis in generating this sex difference was tested in adult Bax knockout (KO) and wild-type mice. Deletion of Bax did not diminish the sex difference in Kiss1 expression in the AVPV/PeN. TH expression was sexually dimorphic in the AVPV of both wild-type and Bax KO mice but, unlike Kiss1, was not sexually dimorphic in the PeN of either genotype. Double-label analysis determined that most Kiss1 neurons coexpress TH mRNA, but many TH neurons do not coexpress Kiss1, especially in the PeN. These findings suggest that several subpopulations of TH cells reside within the AVPV/PeN, only one of which coexpresses Kiss1. In the ARC, Kiss1 cell number was markedly increased in Bax KO mice of both sexes, indicating that although BAX-dependent apoptosis does not generate the sex difference in either Kiss1 or TH expression in AVPV/PeN, BAX does importantly regulate Kiss1 cell number in the ARC.
The Unknown Origins of the March on Washington: Civil Rights Politics and the Black Working Class
Authors: Jones William P.
Published: October 2010

“The very decade which has witnessed the decline of legal Jim Crow has also seen the rise of de facto segregation in our most fundamental socioeconomic institutions,” veteran civil rights activist Bayard Rustin wrote in 1965, pointing out that black workers were more likely to be unemployed, earn low wages, work in “jobs vulnerable to automation,” and live in impoverished ghettos than when the U.S. Supreme Court banned legal segregation in 1954. Historians have attributed that divergence to a narrowing of African American political objectives during the 1950s and early 1960s, away from demands for employment and economic reform that had dominated the agendas of civil rights organizations in the 1940s and later regained urgency in the late 1960s. Jacquelyn Dowd Hall and other scholars emphasize the negative effects of the Cold War, arguing that the National Association for the Advancement of Colored People (NAACP) and other civil rights organizations responded to domestic anticommunism by distancing themselves from organized labor and the Left and by focusing on racial rather than economic forms of inequality. Manfred Berg and Adam Fairclough offer the more positive assessment that focusing on racial equality allowed civil rights activists to appropriate the democratic rhetoric of anticommunism and solidify alliances with white liberals during the Cold War, although they agree that “anticommunist hysteria retarded the struggle for racial justice and narrowed the political options of the civil rights movement.” Meanwhile, Thomas Sugrue, Nancy MacLean, and Timothy Minchin focus on renewed attention to economic inequality in the late 1960s, attributing it to a resurgence of black working-class activism inspired by the Civil Rights Act of 1964 and a resurfacing of radical voices previously “driven underground by McCarthyism.” These and other studies remind us that Rustin, A. Philip Randolph, and Martin Luther King Jr. remained committed to economic radicalism between 1954 and 1965 but portray them as isolated individuals who, as Sugrue writes of Randolph, “did not have much of a movement under his aegis.”
ATF3, an adaptive-response gene, enhances TGFβ signaling and cancer-initiating cell features in breast cancer cells
Authors: Yin Xin , Wolford Christopher C. , Chang Yi-Seok , McConoughey Stephen J. , Ramsey Stephen A. , Aderem Alan , Hai Tsonwin
Published: October 2010

The activating transcription factor 3 (ATF3) gene is induced by a variety of signals, including many of those encountered by cancer cells. We present evidence that ATF3 is induced by TGFβ in the MCF10CA1a breast cancer cells and plays an integral role for TGFβ to upregulate its target genes snail, slug and twist, and to enhance cell motility. Furthermore, ATF3 upregulates the expression of the TGFb gene itself, forming a positive-feedback loop for TGFβ signaling. Functionally, ectopic expression of ATF3 leads to morphological changes and alterations of markers consistent with epithelial-to-mesenchymal transition (EMT). It also leads to features associated with breast-cancer-initiating cells: increased CD24low–CD44high population of cells, mammosphere formation and tumorigenesis. Conversely, knockdown of ATF3 reduces EMT, CD24low–CD44high cells and mammosphere formation. Importantly, knocking down twist, a downstream target, reduces the ability of ATF3 to enhance mammosphere formation, indicating the functional significance of twist in ATF3 action. To our knowledge, this is the first report demonstrating the ability of ATF3 to enhance breast cancer-initiating cell features and to feedback on TGFβ. Because ATF3 is an adaptive-response gene and is induced by various stromal signals, these findings have significant implications for how the tumor microenvironment might affect cancer development.
Neuronal connexin-36 can functionally replace connexin-45 in mouse retina but not in the developing heart
Authors: Frank Marina , Eiberger Britta , Janssen-Bienhold Ulrike , de Sevilla Müller Luis Pérez , Tjarks Antje , Kim Jung-Sun , Maschke Stefan , Dobrowolski Radoslaw , Sasse Philipp , Weiler Reto , Fleischmann Bernd K. , Willecke Klaus
Published: October 2010

The gap junction protein connexin-45 (Cx45) is expressed in the conduction system of the heart and in certain neurons of the retina and brain. General and cardiomyocyte-directed deficiencies of Cx45 in mice lead to lethality on embryonic day 10.5 as a result of cardiovascular defects. Neuron-directed deletion of Cx45 leads to defects in transmission of visual signals. Connexin-36 (Cx36) is co-expressed with Cx45 in certain types of retinal interneurons. To determine whether these two connexins have similar functions and whether Cx36 can compensate for Cx45, we generated knock-in mice in which DNA encoding Cx45 was replaced with that encoding Cx36. Neuron-directed replacement of Cx45 with Cx36 resulted in viable animals. Electroretinographic and neurotransmitter coupling analyses demonstrated functional compensation in the retina. By contrast, general and cardiomyocyte-directed gene replacement led to lethality on embryonic day 11.5. Mutant embryos displayed defects in cardiac morphogenesis and conduction. Thus, functional compensation of Cx45 by Cx36 did not occur during embryonic heart development. These data suggest that Cx45 and Cx36 have similar functions in the retina, whereas Cx45 fulfills special functions in the developing heart that cannot be compensated by Cx36.
Snail1 suppresses TGF-β-induced apoptosis and is sufficient to trigger EMT in hepatocytes
Authors: Franco D. Lorena , Mainez Jèssica , Vega Sonia , Sancho Patricia , Murillo Miguel M. , de Frutos Cristina A. , del Castillo Gaelle , López-Blau Cristina , Fabregat Isabel , Nieto M. Angela
Published: October 2010

Although TGF-β suppresses early stages of tumour development, it later contributes to tumour progression when cells become resistant to its suppressive effects. In addition to circumventing TGF-β-induced growth arrest and apoptosis, malignant tumour cells become capable of undergoing epithelial-to-mesenchymal transition (EMT), favouring invasion and metastasis. Therefore, defining the mechanisms that allow cancer cells to escape from the suppressive effects of TGF-β is fundamental to understand tumour progression and to design specific therapies. Here, we have examined the role of Snail1 as a suppressor of TGF-β-induced apoptosis in murine non-transformed hepatocytes, rat and human hepatocarcinoma cell lines and transgenic mice. We show that Snail1 confers resistance to TGF-β-induced cell death and that it is sufficient to induce EMT in adult hepatocytes, cells otherwise refractory to this transition upon exposure to TGF-β. Furthermore, we show that Snail1 silencing prevents EMT and restores the cell death response induced by TGF-β. As Snail1 is a known target of TGF-β signalling, our data indicate that Snail1 might transduce the tumour-promoting effects of TGF-β, namely the EMT concomitant with the resistance to cell death.
PtdIns(3,4,5)P3 is a regulator of myosin-X localization and filopodia formation
Authors: Plantard Laure , Arjonen Antti , Lock John G. , Nurani Ghasem , Ivaska Johanna , Strömblad Staffan
Published: October 2010

Phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P3] is a key regulator of cell signaling that acts by recruiting proteins to the cell membrane, such as at the leading edge during cell migration. Here, we show that PtdIns (3,4,5)P3 plays a central role in filopodia formation via the binding of myosin-X (Myo10), a potent promoter of filopodia. We found that the second pleckstrin homology domain (Myo10-PH2) of Myo10 specifically binds to PtdIns(3,4,5)P3, and that disruption of this binding led to impairment of filopodia and partial re-localization of Myo10 to microtubule-associated Rab7-positive endosomal vesicles. Given that the localization of Myo10 was dynamically restored to filopodia upon reinstatement of PtdIns(3,4,5)P3-binding, our results indicate that PtdIns(3,4,5)P3 binding to the Myo10-PH2 domain is involved in Myo10 trafficking and regulation of filopodia dynamics.
Coactivation of the CLOCK–BMAL1 complex by CBP mediates resetting of the circadian clock
Authors: Lee Yool , Lee Jiwon , Kwon Ilmin , Nakajima Yoshihiro , Ohmiya Yoshihiro , Son Gi Hoon , Lee Kun Ho , Kim Kyungjin
Published: October 2010

The transcription factor CLOCK–BMAL1 is a core component of the molecular clock machinery that drives circadian gene expression and physiology in mammals. Recently, we reported that this heterodimeric transcription factor functions as a signaling molecule in response to the resetting stimuli via the Ca2+-dependent protein kinase C pathway. Here, we demonstrate that the CREB-binding protein (CBP) plays a key role in rapid activation of the CLOCK–BMAL1 heterodimer that leads to phase resetting of the circadian clock. Under physiological conditions, a bimolecular fluorescence complementation (BiFC) assay revealed that CLOCK and BMAL1 dimerize in the cytoplasm and subsequently translocate into the nucleus in response to serum stimuli (mean time duration was 29.2 minutes and mean velocity 0.7 μm/minute). Concomitantly, BMAL1 rapidly recruited CBP on Per1 promoter E-box, but not p300 (a functional analog of CBP), in the discrete nuclear foci. However, recruitment of CBP by cAMP/Ca2+ response element-binding (CREB) protein on CRE was not markedly increased upon delivery of the resetting stimuli. Furthermore, overexpression of CBP greatly potentiated the CLOCK–BMAL1-mediated Per1 transcription, and this effect was completely abolished by site-directed mutation of E-box elements, but not by the mutation of CRE in the Per1 promoter. Furthermore, molecular knockdown of CBP severely dampened circadian oscillation of clock gene expression triggered by the resetting stimuli. These findings suggest that CBP recruitment by BMAL1 mediates acute transactivation of CLOCK–BMAL1, thereby inducing immediate-early Per1 transcription and phase resetting of the circadian clock.