bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signaling and cytoskeletal requirements in erythroblast enucleation
Authors: Konstantinidis Diamantis G. , Pushkaran Suvarnamala , Johnson James F. , Cancelas Jose A. , Manganaris Stefanos , Harris Chad E. , Williams David A. , Zheng Yi , Kalfa Theodosia A. 
Published: March 2012

AbstractTo understand the role of cytoskeleton and membrane signaling molecules in erythroblast enucleation, we developed a novel analysis protocol of multiparameter high-speed cell imaging in flow. This protocol enabled us to observe F-actin and phosphorylated myosin regulatory light chain (pMRLC) assembled into a contractile actomyosin ring (CAR) between nascent reticulocyte and nucleus, in a population of enucleating erythroblasts. CAR formation and subsequent enucleation were not affected in murine erythroblasts with genetic deletion of Rac1 and Rac2 GTPases because of compensation by Rac3. Pharmacologic inhibition or genetic deletion of all Rac GTPases altered the distribution of F-actin and pMRLC and inhibited enucleation. Erythroblasts treated with NSC23766, cytochalasin-D, colchicine, ML7, or filipin that inhibited Rac activity, actin or tubulin polymerization, MRLC phosphorylation, or lipid raft assembly, respectively, exhibited decreased enucleation efficiency, as quantified by flow cytometry. As assessed by high-speed flow-imaging analysis, colchicine inhibited erythroblast polarization, implicating microtubules during the preparatory stage of enucleation, whereas NSC23766 led to absence of lipid raft assembly in the reticulocyte-pyrenocyte border. In conclusion, enucleation is a multistep process that resembles cytokinesis, requiring establishment of cell polarity through microtubule function, followed by formation of a contractile actomyosin ring, and coalescence of lipid rafts between reticulocyte and pyrenocyte.
Spiral cleavage and early embryology of a loxosomatid entoproct and the usefulness of spiralian apical cross patterns for phylogenetic inferences
Authors: Merkel Julia , Wollesen Tim , Lieb Bernhard , Wanninger Andreas 
Published: March 2012

Abstract

Background
Among the four major bilaterian clades, Deuterostomia, Acoelomorpha, Ecdysozoa, and Lophotrochozoa, the latter shows an astonishing diversity of bodyplans. While the largest lophotrochozoan assemblage, the Spiralia, which at least comprises Annelida, Mollusca, Entoprocta, Platyhelminthes, and Nemertea, show a spiral cleavage pattern, Ectoprocta, Brachiopoda and Phoronida (the Lophophorata) cleave radially. Despite a vast amount of recent molecular phylogenetic analyses, the interrelationships of lophotrochozoan phyla remain largely unresolved. Thereby, Entoprocta play a key role, because they have frequently been assigned to the Ectoprocta, despite their differently cleaving embryos. However, developmental data on entoprocts employing modern methods are virtually non-existent and the data available rely exclusively on sketch drawings, thus calling for thorough re-investigation.

Results
By applying fluorescence staining in combination with confocal microscopy and 3D-imaging techniques, we analyzed early embryonic development of a basal loxosomatid entoproct. We found that cleavage is asynchronous, equal, and spiral. An apical rosette, typical for most spiralian embryos, is formed. We also identified two cross-like cellular arrangements that bear similarities to both, a "molluscan-like" as well as an "annelid-like" cross, respectively.

Conclusions
A broad comparison of cleavage types and apical cross patterns across Lophotrochozoa shows high plasticity of these character sets and we therefore argue that these developmental traits should be treated and interpreted carefully when used for phylogenetic inferences.
Utilization of insecticide treated nets during pregnancy among postpartum women in Ibadan, Nigeria: a cross-sectional study
Authors: Aluko Joel O , Oluwatosin Abimbola O 
Published: March 2012

Abstract

Background
Pregnant women are susceptible to symptomatic malaria due to invasion of the placenta by plasmodium. Malaria increases the risk of adverse pregnancy outcomes for mothers, the foetuses and newborns. The effective use of Insecticide Treated Nets (ITNs) would be of benefit to these vulnerable women. Previous studies have focused on prenatal-women but this study sought to explore the actual trend of utilization of the proven strategy across all the pregnancy stages among postpartum women in Ibadan.

Methods
This cross-sectional survey utilized a validated structured questionnaire for data collection. A calculated sample of 335 postpartum women was proportionately recruited from three fee-paying facilities within Ibadan, Nigeria using a simple random sampling technique. These hospitals have high client flow for maternity cases and are known for provision of care under traditional ANC model. The data collected were analyzed using descriptive and inferential statistics by means of Statistical Package of Social Sciences (SPSS) version 15. The level of significance was set at = 0.05.

Results
The women's age ranged between 18 and 47 years, mean age was 29.4 ± 0.8 years. Various irregularities marked the traditional model of ANC provided at the settings and no exposure to preconception care. Also, 276 (82.4%) had heard of ITNs. Antenatal clinics formed the major source of information. Low utilization and compliance rates were observed. One hundred and twenty-seven (37.9%) of the women had high knowledge of Malaria in Pregnancy (MIP) but only 70 (20.9%) demonstrated positive attitude towards the use of ITNs. Participants' educational status, family types, employment and residential areas significantly influenced ITNs utilization.

Conclusions
The women knew and learned about ITNs from ANC visits. Majority of the women did not own ITNs because of lack of access to free distribution. The existing traditional model of ANC was marked by irregularities and none of the women was exposed to preconception care. In addition, negative attitude in spite of increased knowledge of MIP was observed among the women. Therefore, evaluation of free distribution of ITNs is recommended. Integration of focused ANC and preconception care are advocated to promote early access to health information.
Report on emerging technologies for translational bioinformatics: a symposium on gene expression profiling for archival tissues
Authors: Waldron Levi , Simpson Peter , Parmigiani Giovanni , Huttenhower Curtis 
Published: March 2012

Abstract

Background
With over 20 million formalin-fixed, paraffin-embedded (FFPE) tissue samples archived each year in the United States alone, archival tissues remain a vast and under-utilized resource in the genomic study of cancer. Technologies have recently been introduced for whole-transcriptome amplification and microarray analysis of degraded mRNA fragments from FFPE samples, and studies of these platforms have only recently begun to enter the published literature.

Results
The Emerging Technologies for Translational Bioinformatics symposium on gene expression profiling for archival tissues featured presentations of two large-scale FFPE expression profiling studies (each involving over 1,000 samples), overviews of several smaller studies, and representatives from three leading companies in the field (Illumina, Affymetrix, and NuGEN). The meeting highlighted challenges in the analysis of expression data from archival tissues and strategies being developed to overcome them. In particular, speakers reported higher rates of clinical sample failure (from 10% to 70%) than are typical for fresh-frozen tissues, as well as more frequent probe failure for individual samples. The symposium program is available at http://www.hsph.harvard.edu/ffpe.

Conclusions
Multiple solutions now exist for whole-genome expression profiling of FFPE tissues, including both microarray- and sequencing-based platforms. Several studies have reported their successful application, but substantial challenges and risks still exist. Symposium speakers presented novel methodology for analysis of FFPE expression data and suggestions for improving data recovery and quality assessment in pre-analytical stages. Research presentations emphasized the need for careful study design, including the use of pilot studies, replication, and randomization of samples among batches, as well as careful attention to data quality control. Regardless of any limitations in quantitave transcriptomics for FFPE tissues, they are often the only biospecimens available for large patient populations with long-term history and clinical follow-up. Current challenges can be expected to remain as RNA sequencing matures, and they will thus motivate ongoing research efforts into noise reduction and identification of robust, translationally relevant biological signals in expression data from FFPE tissues.
The surfactant protein C mutation A116D alters cellular processing, stress tolerance, surfactant lipid composition, and immune cell activation
Authors: Zarbock Ralf , Woischnik Markus , Sparr Christiane , Thurm Tobias , Kern Sunčana , Kaltenborn Eva , Hector Andreas , Hartl Dominik , Liebisch Gerhard , Schmitz Gerd , Griese Matthias 
Published: March 2012

AbstractBackgroundSurfactant protein C (SP-C) is important for the function of pulmonary surfactant. Heterozygous mutations inSFTPC, the gene encoding SP-C, cause sporadic and familial interstitial lung disease (ILD) in children and adults. Mutations mapping to the BRICHOS domain located within the SP-C proprotein result in perinuclear aggregation of the proprotein. In this study, we investigated the effects of the mutation A116D in the BRICHOS domain of SP-C on cellular homeostasis. We also evaluated the ability of drugs currently used in ILD therapy to counteract these effects.MethodsSP-CA116Dwas expressed in MLE-12 alveolar epithelial cells. We assessed in vitro the consequences for cellular homeostasis, immune response and effects of azathioprine, hydroxychloroquine, methylprednisolone and cyclophosphamide.ResultsStable expression of SP-CA116Din MLE-12 alveolar epithelial cells resulted in increased intracellular accumulation of proSP-C processing intermediates. SP-CA116Dexpression further led to reduced cell viability and increased levels of the chaperones Hsp90, Hsp70, calreticulin and calnexin. Lipid analysis revealed decreased intracellular levels of phosphatidylcholine (PC) and increased lyso-PC levels. Treatment with methylprednisolone or hydroxychloroquine partially restored these lipid alterations. Furthermore, SP-CA116Dcells secreted soluble factors into the medium that modulated surface expression of CCR2 or CXCR1 receptors on CD4+lymphocytes and neutrophils, suggesting a direct paracrine effect of SP-CA116Don neighboring cells in the alveolar space.ConclusionsWe show that the A116D mutation leads to impaired processing of proSP-C in alveolar epithelial cells, alters cell viability and lipid composition, and also activates cells of the immune system. In addition, we show that some of the effects of the mutation on cellular homeostasis can be antagonized by application of pharmaceuticals commonly applied in ILD therapy. Our findings shed new light on the pathomechanisms underlying SP-C deficiency associated ILD and provide insight into the mechanisms by which drugs currently used in ILD therapy act.
Engineering Escherichia coli for succinate production from hemicellulose via consolidated bioprocessing
Authors: Zheng Zongbao , Chen Tao , Zhao Meina , Wang Zhiwen , Zhao Xueming 
Published: March 2012

Abstract

Background
The recalcitrant nature of hemicellulosic materials and the high cost in depolymerization are the primary obstacles preventing the use of xylan as feedstock for fuel and chemical production. Consolidated bioprocessing, incorporating enzyme-generating, biomass-degrading and bioproduct-producing capabilities into a single microorganism, could potentially avoid the cost of the dedicated enzyme generation in the process of xylan utilization. In this study, we engineered Escherichia coli strains capable of exporting three hemicellulases to the broth for the succinate production directly from beechwood xylan.

Results
Xylanases were extracellular environment-directed by fusing with OsmY. Subsequently, twelve variant OsmY fused endoxylanase-xylosidase combinations were characterized and tested. The combination of XynC-A from Fibrobacter succinogenes S85 and XyloA from Fusarium graminearum which appeared to have optimal enzymatic properties was identified as the best choice for xylan hydrolysis (0.18 ± 0.01 g/l protein in the broth with endoxylanase activity of 12.14 ± 0.34 U/mg protein and xylosidase activity of 92 ± 3 mU/mg protein at 8 h after induction). Further improvements of hemicellulases secretion were investigated by lpp deletion, dsbA overexpression and expression level optimization. With co-expression of α-arabinofuranosidase, the engineered E. coli could hydrolyze beechwood xylan to pentose monosaccharides. The hemicellulolytic capacity was further integrated with a succinate-producing strain to demonstrate the production of succinate directly from xylan without externally supplied hydrolases and any other organic nutrient. The resulting E. coli Z6373 was able to produce 0.37 g/g succinate from xylan anaerobically equivalent to 76% of that from xylan acid hydrolysates.

Conclusions
This report represents a promising step towards the goal of hemicellulosic chemical production. This engineered E. coli expressing and secreting three hemicellulases demonstrated a considerable succinate production on the released monosaccharides from xylan. The ability to use lower-cost crude feedstock will make biological succinate production more economically attractive.
Involvement of Src family of kinases and cAMP phosphodiesterase in the luteinizing hormone/chorionic gonadotropin receptor-mediated signaling in the corpus luteum of monkey
Authors: Kunal Shah B , Killivalavan Asaithambi , Medhamurthy Rudraiah 
Published: March 2012

Abstract

Background
In higher primates, during non-pregnant cycles, it is indisputable that circulating LH is essential for maintenance of corpus luteum (CL) function. On the other hand, during pregnancy, CL function gets rescued by the LH analogue, chorionic gonadotropin (CG). The molecular mechanisms involved in the control of luteal function during spontaneous luteolysis and rescue processes are not completely understood. Emerging evidence suggests that LH/CGR activation triggers proliferation and transformation of target cells by various signaling molecules as evident from studies demonstrating participation of Src family of tyrosine kinases (SFKs) and MAP kinases in hCG-mediated actions in Leydig cells. Since circulating LH concentration does not vary during luteal regression, it was hypothesized that decreased responsiveness of luteal cells to LH might occur due to changes in LH/CGR expression dynamics, modulation of SFKs or interference with steroid biosynthesis.

Methods
Since, maintenance of structure and function of CL is dependent on the presence of functional LH/CGR its expression dynamics as well as mRNA and protein expressions of SFKs were determined throughout the luteal phase. Employing well characterized luteolysis and CL rescue animal models, activities of SFKs, cAMP phosphodiesterase (cAMP-PDE) and expression of SR-B1 (a membrane receptor associated with trafficking of cholesterol ester) were examined. Also, studies were carried out to investigate the mechanisms responsible for decline in progesterone biosynthesis in CL during the latter part of the non-pregnant cycle.

Results and discussion
The decreased responsiveness of CL to LH during late luteal phase could not be accounted for by changes in LH/CGR mRNA levels, its transcript variants or protein. Results obtained employing model systems depicting different functional states of CL revealed increased activity of SFKs [pSrc (Y-416)] and PDE as well as decreased expression of SR-B1correlating with initiation of spontaneous luteolysis. However, CG, by virtue of its heroic efforts, perhaps by inhibition of SFKs and PDE activation, prevents CL from undergoing regression during pregnancy.

Conclusions
The results indicated participation of activated Src and increased activity of cAMP-PDE in the control of luteal function in vivo. That the exogenous hCG treatment caused decreased activation of Src and cAMP-PDE activity with increased circulating progesterone might explain the transient CL rescue that occurs during early pregnancy.
Some convergence results for iterative sequences of Prešić type and applications
Authors: Khan Mohammad Saeed , Berzig Maher , Samet Bessem 
Published: March 2012

Abstract
In this article, we study the convergence of iterative sequences of Prešić type involving new general classes of operators in the setting of metric spaces. As application, we derive some convergence results for a class of nonlinear matrix difference equations. Numerical experiments are also presented to illustrate the convergence algorithms.

Mathematics Subject Classification 2000: 54H25; 47H10; 15A24; 65H05.
The immunoregulatory effects of CMV-infection in human fibroblasts and the impact on cellular senescence
Authors: Wolf Juliane , Weinberger Birgit , Grubeck-Loebenstein Beatrix 
Published: March 2012

Abstract

Background
As a chronic antigenic stressor human Cytomegalovirus (CMV) contributes substantially to age-related alterations of the immune system. Even though monocytes have the greatest propensity for CMV-infection and seem to be an important host for the virus during latency, fibroblasts are also discussed to be target cells of CMV in vivo. However, little is known so far about general immunoregulatory properties of CMV in fibroblasts. We therefore investigated the immunoregulatory effects of CMV-infection in human lung fibroblasts and the impact on replicative senescence.

Findings
We observed that CMV-infection led to the induction of several immunoregulatory host cell genes associated with the innate and adaptive immune system. These were genes of different function such as genes regulating apoptosis, cytokines/chemokines and genes that are responsible for the detection of pathogens. Some of the genes upregulated following CMV-infection are also upregulated during cellular senescence, indicating that CMV causes an immunological phenotype in fibroblasts, which is partially reminiscent of replicative senescent cells.

Conclusion
In summary our results demonstrate that CMV not only affects the T cell pool but also induces inflammatory processes in human fibroblasts.
In vivo efficacy of the histone deacetylase inhibitor suberoylanilide hydroxamic acid in combination with radiotherapy in a malignant rhabdoid tumor mouse model
Authors: Thiemann Markus , Oertel Susanne , Ehemann Volker , Weichert Wilko , Stenzinger Albrecht , Bischof Marc , Weber Klaus-J , Perez Ramon Lopez , Haberkorn Uwe , Kulozik Andreas E , Debus Jürgen , Huber Peter E , Battmann Claudia 
Published: March 2012

Abstract

Purpose
Histone deacetylase inhibitors are promising new substances in cancer therapy and have also been shown to sensitize different tumor cells to irradiation (XRT). We explored the effect as well as the radiosensitizing properties of suberoylanilide hydroxamic acid (SAHA) in vivo in a malignant rhabdoid tumor (MRT) mouse model.

Methods and material
Potential radiosensitization by SAHA was assessed in MRT xenografts by analysis of tumor growth delay, necrosis (HE), apoptosis (TUNEL), proliferation (ki-67) and γH2AX expression as well as dynamic 18F-Fluorodeoxyglucose Positron Emission Tomography (18F-FDG -PET) after treatment with either SAHA alone, single-dose (10 Gy) or fractionated XRT (3 × 3Gy) solely as well as in combination with SAHA compared to controls.

Results
SAHA only had no significant effect on tumor growth. Combination of SAHA for 8 days with single-dose XRT resulted in a higher number of complete remissions, but failed to prove a significant growth delay compared to XRT only. In contrast fractionated XRT plus SAHA for 3 weeks did induce significant tumor growth delay in MRT-xenografts.
The histological examination showed a significant effect of XRT in tumor necrosis, expression of Ki-67, γH2AX and apoptosis. SAHA only had no significant effect in the histological examination. Comparison of xenografts treated with XRT and XRT plus SAHA revealed a significantly increased γH2AX expression and apoptosis induction in the mice tumors after combination treatment with single-dose as well as fractionated XRT. The combination of SAHA with XRT showed a tendency to increased necrosis and decrease of proliferation compared to XRT only, which, however, was not significant. The 18F-FDG-PET results showed no significant differences in the standard uptake value or glucose transport kinetics after either treatment.

Conclusion
SAHA did not have a significant effect alone, but proved to enhance the effect of XRT in our MRT in vivo model.
Comparison of accelerated partial breast irradiation via multicatheter interstitial brachytherapy versus whole breast radiation
Authors: Ferraro Daniel J , Garsa Adam A , DeWees Todd A , Margenthaler Julie A , Naughton Michael , Aft Rebecca , Gillanders William E , Eberlein Timothy , Matesa Melissa A , Zoberi Imran 
Published: March 2012

Abstract

Background
Brachytherapy as adjuvant treatment for early-stage breast cancer has become widely available and offers patients an expedited treatment schedule. Given this, many women are electing to undergo brachytherapy in lieu of standard fractionation radiotherapy. We compare outcomes between patients treated with accelerated partial breast irradiation (APBI) via multicatheter interstitial brachytherapy versus patients who were also eligible for and offered APBI but who chose whole breast radiation (WBI).

Methods
Patients treated from December 2002 through May 2007 were reviewed. Selection criteria included patients with pTis-T2N0 disease, ≤ 3 cm unifocal tumors, and negative margins who underwent breast conservation surgery. Local control (LC), cause-specific (CSS) and overall survival (OS) were analyzed.

Results
202 patients were identified in the APBI cohort and 94 patients in the WBI cohort. Median follow-up for both groups exceeded 60 months. LC was 97.0% for the APBI cohort and 96.2% for the WBI cohort at 5 years (ns). Classification by 2010 ASTRO APBI consensus statement categories did not predict worse outcomes.

Conclusion
APBI via multicatheter interstitial brachytherapy provides similar local failure rates compared to WBI at 5 years for properly selected patients. Excellent results were seen despite the high fraction of younger patients (< 60 years old) and patients with DCIS.