bluuebunny/crossref_metadata_2025_split huggingface dataset:
FLIP: a novel regulator of macrophage differentiation and granulocyte homeostasis
Authors: Huang Qi-Quan , Perlman Harris , Huang Zan , Birkett Robert , Kan Lixin , Agrawal Hemant , Misharin Alexander , Gurbuxani Sandeep , Crispino John D. , Pope Richard M. 
Published: August 2010

Abstract
FLIP is a well-established suppressor of death receptor-mediated apoptosis. To define its essential in vivo role in myeloid cells, we generated and characterized mice with Flip conditionally deleted in the myeloid lineage. Myeloid specific Flip-deficient mice exhibited growth retardation, premature death, and splenomegaly with altered architecture and extramedullary hematopoiesis. They also displayed a dramatic increase of circulating neutrophils and multiorgan neutrophil infiltration. In contrast, although circulating inflammatory monocytes were also significantly increased, macrophages in the spleen, lymph nodes, and the peritoneal cavity were reduced. In ex vivo cultures, bone marrow progenitor cells failed to differentiate into macrophages when Flip was deleted. Mixed bone marrow chimera experiments using cells from Flip-deficient and wild-type mice did not demonstrate an inflammatory phenotype. These observations demonstrate that FLIP is necessary for macrophage differentiation and the homeostatic regulation of granulopoiesis.
Rapid generation of maturationally synchronized human dendritic cells: contribution to the clinical efficacy of extracorporeal photochemotherapy
Authors: Berger Carole , Hoffmann Kristin , Vasquez Juan G. , Mane Shrikant , Lewis Julia , Filler Renata , Lin Aiping , Zhao Hongyu , Durazzo Tyler , Baird Abigail , Lin William , Foss Francine , Christensen Inger , Girardi Michael , Tigelaar Robert , Edelson Richard 
Published: August 2010

AbstractExtracorporeal photochemotherapy (ECP) is widely used to treat cutaneous T-cell lymphoma, graft-versus-host disease, and allografted organ rejection. Its clinical and experimental efficacy in cancer immunotherapy and autoreactive disorders suggests a novel mechanism. This study reveals that ECP induces a high percentage of processed monocytes to enter the antigen-presenting dendritic cell (DC) differentiation pathway, within a single day, without added cytokines, as determined by enhanced expression of relevant genes. The resulting DCs are capable of processing and presentation of exogenous and endogenous antigen and are largely maturationally synchronized, as assessed by the level of expression of costimulatory surface molecules. Principal component analysis of the ECP-induced monocyte transcriptome reveals that activation or suppression of more than 1100 genes produces a reproducible distinctive molecular signature, common to ECP-processed monocytes from normal subjects, and those from patients. Because ECP induces normal monocytes to enter the DC differentiation pathway, this phenomenon is independent of disease state. The efficiency with which ECP stimulates new functional DCs supports the possibility that these cells participate prominently in the clinical successes of the treatment. Appropriately modified by future advances, ECP may potentially offer a general source of therapeutic DCs.
Glycosidic Tn-based vaccines targeting dermal dendritic cells favor germinal center B-cell development and potent antibody response in the absence of adjuvant
Authors: Freire Teresa , Zhang Xiaoming , Dériaud Edith , Ganneau Christelle , Vichier-Guerre Sophie , Azria Elie , Launay Odile , Lo-Man Richard , Bay Sylvie , Leclerc Claude 
Published: August 2010

AbstractIn vivo targeting of C-type lectin receptors is an effective strategy for increasing antigen uptake and presentation by dendritic cells (DCs). To induce efficient immune response, glycosylated tumor-associated Tn antigens were used to target DCs through binding to macrophage galactose-type lectin (MGL). The capacity of Tn-glycosylated antigens—and the multiple antigenic glycopeptide Tn3 therapeutic candidate vaccine—to target mouse and human MGL+ DCs are demonstrated, especially regarding dermal DCs. In mice, MGL+ CD103− dermal DCs efficiently captured and processed glycosylated Tn antigen in vivo, inducing a potent major histocompatibility complex (MHC) class II–restricted T-cell response. Intradermal immunization with Tn-glycopeptides induced high levels of Th2 cytokines—even in the presence of unmethylated cytosine-phosphate-guanosine—and was associated with increased expansion of the germinal center B-cell population. Therefore, MGL acts as an efficient endocytic antigen receptor on dermal DCs in vivo, able to prime Tn-specific T- and B-cell responses. Moreover, even in the absence of adjuvant, immunization with this glycosidic Tn-based vaccine induced high levels of anti-Tn antibody responses, recognizing human tumor cells. In vivo DC-targeting strategies, based on Tn-MGL interactions, constitute a promising strategy for enhancing antigen presentation and inducing potent antibody response.
MicroRNA expression in maturing murine megakaryocytes
Authors: Opalinska Joanna B. , Bersenev Alexey , Zhang Zhe , Schmaier Alec A. , Choi John , Yao Yu , D'Souza Janine , Tong Wei , Weiss Mitchell J. 
Published: August 2010

AbstractMicroRNAs are small noncoding RNAs that regulate cellular development by interfering with mRNA stability and translation. We examined global microRNA expression during the differentiation of murine hematopoietic progenitors into megakaryocytes. Of 435 miRNAs analyzed, 13 were up-regulated and 81 were down-regulated. Many of these changes are consistent with miRNA profiling studies of human megakaryocytes and platelets, although new patterns also emerged. Among 7 conserved miRNAs that were up-regulated most strongly in murine megakaryocytes, 6 were also induced in the related erythroid lineage. MiR-146a was strongly up-regulated during mouse and human megakaryopoiesis but not erythropoiesis. However, overexpression of miR-146a in mouse bone marrow hematopoietic progenitor populations produced no detectable alterations in megakaryocyte development or platelet production in vivo or in colony assays. Our findings extend the repertoire of differentially regulated miRNAs during murine megakaryopoiesis and provide a useful new dataset for hematopoiesis research. In addition, we show that enforced hematopoietic expression of miR-146a has minimal effects on megakaryopoiesis. These results are compatible with prior studies indicating that miR-146a inhibits megakaryocyte production indirectly by suppressing inflammatory cytokine production from innate immune cells, but cast doubt on a different study, which suggests that this miRNA inhibits megakaryopoiesis cell-autonomously.
rSW-seq: Algorithm for detection of copy number alterations in deep sequencing data
Authors: Kim Tae-Min , Luquette Lovelace J , Xi Ruibin , Park Peter J 
Published: August 2010

Abstract

Background
Recent advances in sequencing technologies have enabled generation of large-scale genome sequencing data. These data can be used to characterize a variety of genomic features, including the DNA copy number profile of a cancer genome. A robust and reliable method for screening chromosomal alterations would allow a detailed characterization of the cancer genome with unprecedented accuracy.

Results
We develop a method for identification of copy number alterations in a tumor genome compared to its matched control, based on application of Smith-Waterman algorithm to single-end sequencing data. In a performance test with simulated data, our algorithm shows >90% sensitivity and >90% precision in detecting a single copy number change that contains approximately 500 reads for the normal sample. With 100-bp reads, this corresponds to a ~50 kb region for 1X genome coverage of the human genome. We further refine the algorithm to develop rSW-seq, (recursive Smith-Waterman-seq) to identify alterations in a complex configuration, which are commonly observed in the human cancer genome. To validate our approach, we compare our algorithm with an existing algorithm using simulated and publicly available datasets. We also compare the sequencing-based profiles to microarray-based results.

Conclusion
We propose rSW-seq as an efficient method for detecting copy number changes in the tumor genome.
The effect of Aloe ferox Mill. in the treatment of loperamide-induced constipation in Wistar rats
Authors: Wintola Olubunmi A , Sunmonu Taofik O , Afolayan Anthony J 
Published: August 2010

Abstract

Background
Constipation is the most common gastrointestinal complaint all over the world and it is a risk factor of colorectal cancer. In this study, the efficacy of aqueous leaf extract of Aloe
ferox Mill. was studied against loperamide-induced constipation in Wistar rats.

Methods
Constipation was induced by oral administration of loperamide (3 mg/kg body weight) while the control rats received normal saline. The constipated rats were treated with 50, 100 and 200 mg/kg body weight/day of the extract for 7 days during which the feeding characteristics, body weight, fecal properties and gastrointestinal transit ratio were monitored.

Results
The extract improved intestinal motility, increased fecal volume and normalized body weight in the constipated rats, which are indications of laxative property of the herb with the 200 mg/kg body weight of the extract showing the best efficacy.

Conclusion
The effect of the extract compares favourably well with senokot, a standard laxative drug. These findings have therefore, lent scientific credence to the folkloric use of the herb as a laxative agent by the people of the Eastern Cape of South Africa.
Enhancing chemosensitivity to gemcitabine via RNA interference targeting the catalytic subunits of protein kinase CK2 in human pancreatic cancer cells
Authors: Kreutzer Jan N , Ruzzene Maria , Guerra Barbara 
Published: August 2010

Abstract

Background
Pancreatic cancer is a complex genetic disorder that is characterized by rapid progression, invasiveness, resistance to treatment and high molecular heterogeneity. Various agents have been used in clinical trials showing only modest improvements with respect to gemcitabine-based chemotherapy, which continues to be the standard first-line treatment for this disease. However, owing to the overwhelming molecular alterations that have been reported in pancreatic cancer, there is increasing focus on targeting molecular pathways and networks, rather than individual genes or gene-products with a combination of novel chemotherapeutic agents.

Methods
Cells were transfected with small interfering RNAs (siRNAs) targeting the individual CK2 subunits. The CK2 protein expression levels were determined and the effect of its down-regulation on chemosensitization of pancreatic cancer cells was investigated.

Results
The present study examined the impact on cell death following depletion of the individual protein kinase CK2 catalytic subunits alone or in combination with gemcitabine and the molecular mechanisms by which this effect is achieved. Depletion of the CK2α or -α' subunits in combination with gemcitabine resulted in marked apoptotic and necrotic cell death in PANC-1 cells. We show that the mechanism of cell death is associated with deregulation of distinct survival signaling pathways. Cellular depletion of CK2α leads to phosphorylation and activation of MKK4/JNK while down-regulation of CK2α' exerts major effects on the PI3K/AKT pathway.

Conclusions
Results reported here show that the two catalytic subunits of CK2 contribute differently to enhance gemcitabine-induced cell death, the reduced level of CK2α' being the most effective and that simultaneous reduction in the expression of CK2 and other survival factors might be an effective therapeutic strategy for enhancing the sensitivity of human pancreatic cancer towards chemotherapeutic agents.
Detection and quantitation of HPV in genital and oral tissues and fluids by real time PCR
Authors: Seaman William T , Andrews Elizabeth , Couch Marion , Kojic Erna M , Cu-Uvin Susan , Palefsky Joel , Deal Allison M , Webster-Cyriaque Jennifer 
Published: August 2010

Abstract

Background
Human papillomaviruses (HPVs) remain a serious world health problem due to their association with anogenital/oral cancers and warts. While over 100 HPV types have been identified, a subset is associated with malignancy. HPV16 and 18 are the most prevalent oncogenic types, while HPV6 and 11 are most commonly responsible for anogenital warts. While other quantitative PCR (qPCR) assays detect oncogenic HPV, there is no single tube assay distinguishing the most frequent oncogenic types and the most common types found in warts.

Results
A Sybr Green-based qPCR assay was developed utilizing degenerate primers to the highly conserved HPV E1 theoretically detecting any HPV type. A single tube multiplex qPCR assay was also developed using type-specific primer pairs and TaqMan probes that allowed for detection and quantitation of HPV6,11,16,18. Each HPV type was detected over a range from 2 × 101 to 2 × 106copies/reaction providing a reliable method of quantitating type-specific HPV in 140 anogenital/cutaneous/oral benign and malignant specimens. 35 oncogenic and low risk alpha genus HPV types were detected. Concordance was detected in previously typed specimens. Comparisons to the gold standard detected an overall sensitivity of 89% (95% CI: 77% - 96%) and specificity of 90% (95%CI: 52% - 98%).

Conclusion
There was good agreement between the ability of the qPCR assays described here to identify HPV types in malignancies previously typed using standard methods. These novel qPCR assays will allow rapid detection and quantitation of HPVs to assess their role in viral pathogenesis.
Diagnosis of systemic toxoplasmosis with HIV infection using DNA extracted from paraffin-embedded tissue for polymerase chain reaction: a case report
Authors: Okubo Yoichiro , Shinozaki Minoru , Yoshizawa Sadako , Nakayama Haruo , Wakayama Megumi , Hatori Tsutomu , Mituda Aki , Hirano Takayuki , Shimodaira Kayoko , Yuzhu Zhi , Shibuya Kazutoshi 
Published: August 2010

Abstract

Introduction
Toxoplasmosis can be a life-threatening disease when it occurs in patients with HIV infection. In particular, meningioencephalitis has been regarded as the most common toxoplasmic complication in such patients. However, toxoplasmic meningitis in a patient with HIV infection is extremely rare and purulent or tuberculous meningitis should be considered initially as a disease for differential diagnosis in Japan.

Case presentation
Toxoplasmic meningitis in a patient with HIV infection is reported. A 36-year-old Japanese man presented with fever, pulsating headache, lumbago, nausea, and vomiting. No examinations suggested toxoplasmosis including cerebrospinal fluid examinations, images, and serological tests. The result of a polymerase chain reaction assay using paraffin-embedded section was regarded as the conclusive evidence for the diagnosis.

Conclusions
We wish to emphasize the usefulness of polymerase chain reaction assays with nucleic acid extracted from paraffin-embedded tissue sections processed for routine histopathological examination, if the section shows the infectious agents or findings suggesting some infectious diseases.
Comparable Sensitivity of Postmenopausal and Young Women to the Effects of Intranasal Insulin on Food Intake and Working Memory
Authors: Krug Rosemarie , Benedict Christian , Born Jan , Hallschmid Manfred 
Published: August 2010

Context: We have previously shown that enhancing brain insulin signaling by intranasal administration of a single dose of the hormone acutely reduces food intake in young men but not women, whereas its improving effects on spatial and working memory are restricted to young women.
Objective: Against the background of animal studies suggesting that low estrogen concentrations are a prerequisite for the anorexigenic impact of central nervous insulin, we extended our foregoing study by assessing intranasal insulin effects in postmenopausal women with comparatively low estrogen concentrations, expecting them to be more sensitive than young women to the anorexigenic effects of the hormone.
Design, Setting, Participants, and Intervention: In a within-subject, double-blind comparison performed at the University of Lübeck, 14 healthy postmenopausal women (body mass index, 23.71 ± 0.6 kg/m2; age, 57.61 ± 1.14 yr) were intranasally administered 160 IU regular human insulin or vehicle.
Main Outcome Measures: Subjects performed a working memory task (digit span) and a hippocampus-dependent visuospatial memory task. Subsequently, free-choice food intake from an ad libitum breakfast buffet was measured.
Results: Contrary to expectations, results in postmenopausal women mirrored those found in young women (22.44 ± 0.63 yr), i.e. insulin administration did not affect food intake (P &gt; 0.46), but did enhance performance in the prefrontal cortex-dependent working memory task (P &lt; 0.05).
Conclusions: Low estrogen levels as present in postmenopausal women do not modulate the effects of intranasal insulin in females, suggesting that in humans as opposed to rats, estrogen signaling does not critically alter central nervous system sensitivity to the effects of insulin on energy homeostasis and cognition.
The Diagnosis and Management of Central Hypoadrenalism
Authors: Grossman Ashley B. 
Published: August 2010

Context: Adrenal failure secondary to hypothalamo-pituitary disease is a common clinical problem which has serious repercussions. It is essential to perform validated diagnostic procedures and manage such patients with clear objectives and based on well-established replacement programs.Evidence Acquisition: PubMed was searched for all data reflecting pituitary hypoadrenalism dating back to 1960 in order to establish a published database.Evidence Synthesis: The results from published studies were assessed in the light of the author’s extensive personal experience dating back some 30 yr in clinical endocrinology, in an attempt to provide clear diagnostic and management advice.Conclusions: While much of the physiology of the hypothalamo-pituitary-adrenal axis is well understood, its clinical assessment and diagnostic procedures to establish the need for replacement are still far from perfect, and to a certain extent clinical judgement is still vital. In terms of replacement therapies, these are still far from optimal in terms of quality of life and mortality, although they are increasingly being based on objective evidence rather than established practice. However, it is anticipated that newer replacement protocols will improve a situation that has previously changed little for many years.
High school students' perceptions of EFL teacher control orientations and their English academic achievement
Authors: Kiany Gholam Reza , Shayestefar Parvaneh 
Published: August 2010

Background. Theories distinguish between student‐initiated and teacher‐initiated regulation of students' learning activities, or between strong, shared, or loose teacher control during the completion of learning tasks. Empirical validations for such distinctions are scarce, however. Aim. The present study aimed at (a) investigating students' perceptions of control behaviours exhibited by their English teachers; and (b) exploring the contribution of different types of teacher control behaviours to students' cognitive outcomes (English Achievement). Sample. The sample comprised 732 English as a Foreign Language (EFL) students studying in three major fields of high school (Mathematics, Natural Science, and Humanities). The participants (16–17 years of age) were selected from third‐grade classes of 27 EFL teachers working in 25 high schools of 6 main different geographical regions in the Isfahan province, Iran. Method. To obtain a comprehensive picture of different control types exhibited by Iranian EFL teachers, the control subscales of the two existing questionnaires, i.e., the Questionnaire on Instructional Behaviours (QIB), adapted by Den Brok et al. (2004) and the Questionnaire on Lesson Activities (QLA) used by Den Brok (2001) were merged to form the Questionnaire of Teacher Control (QTC). The development of this Persian instrument involved several steps: translation and back translation by the researchers, one expert translator, and two EFL teachers; piloting; and a final administration of the questionnaire to the student sample. With respect to the second aim of the study, data regarding students' performances on the Standardized National English Achievement Tests were gathered from local educational offices and schools. Results and conclusion. Statistical analyses supported acceptable reliability and validity of the instrument. A main factor structure with three types of teacher control (strong/high, shared/mid, and loose/low) was found to underlie students' perceptions. The results of multi‐level analyses indicated that a relatively large amount of variance was explained by the control variables and student variables, and teacher control had a statistically significant effect on student outcomes. Students' English achievement was lowest when they felt control was their teachers' prerogative, higher when they themselves exerted their own control (low teacher control), and highest under shared (mid) control behaviours.
The development of early literacy in Steiner‐ and standard‐educated children
Authors: Cunningham Anna J. , Carroll Julia M. 
Published: August 2010

Background. There is evidence that children who are taught to read later in childhood (age 6–7) make faster progress in early literacy than those who are taught at a younger age (4–5 years), as is current practice in the UK. Aims. Steiner‐educated children begin learning how to read at age 7, and have better reading‐related skills at the onset of instruction. Therefore, it is hypothesized that older Steiner‐educated children will make faster progress in early literacy than younger standard‐educated controls. Samples. A total of 30 Steiner‐educated children (age 7–9) were compared to a matched group of 31 standard‐educated controls (age 4–6). Method. Children were tested for reading, spelling, phonological awareness, and letter knowledge at three time points during their first year of formal reading instruction and again at the end of the second year. Results. There were no significant differences between groups in word reading at the end of the first and second year or reading comprehension at the end of the second year; however, the standard group outperformed the Steiner group on spelling at the end of both years. The Steiner group maintained an overall lead in phonological skills while letter knowledge was similar in both groups. Conclusions. The younger children showed similar, and in some cases, better progress in literacy than the older children; this was attributed to more consistent and high‐quality synthetic phonics instruction as is administered in standard schools. Consequently, concerns that 4‐ to 5‐year‐olds are ‘too young’ to begin formal reading instruction may be unfounded.