bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of student activity in a virtual learning environment on their final mark
Authors: Mogus Ana M , Djurdjevic Ivana , Suvak Nenad
Published: September 2012

By studying the use of a virtual learning environment, many have focused on automatically logged web data in order to detect factors that enhance students’ use of the virtual learning environment and that may impact their productive and efficient learning via this means. Following their footsteps, the aim of this research is to examine data (activity logs) obtained by students’ while they are logged into the virtual learning environment in order to detect frequencies and priorities of students’ choice of activities in a virtual learning environment. The activity logs are used to measure students’ effectiveness of learning to determine whether students’ activity logs, within courses supported by a virtual learning environment as part of a blended learning approach, correlate with their final marks and the students’ perceptions of using the virtual learning environment. Observed activities involved course view, assignment view, resource view, forum view, assignment upload and project upload when seen against their final mark. Data log features of a virtual learning environment and an instrument used to gather data on the students’ perceptions of using the virtual learning environment were used. Results show that there are positive correlations between students’ logs of particular activities and their final mark.
Translating Policies Into Practice
Authors: Beets Michael W. , Webster Collin , Saunders Ruth , Huberty Jennifer L. ,   Healthy Afterschool Program Network
Published: September 2012

Afterschool programs (3-6 p.m.) are positioned to play a critical role in combating childhood obesity. To this end, state and national organizations have developed policies related to promoting physical activity and guiding the nutritional quality of snacks served in afterschool programs. No conceptual frameworks, however, are available that describe the process of how afterschool programs will translate such policies into daily practice to reach eventual outcomes. Drawing from complex systems theory, this article describes the development of a framework that identifies critical modifiable levers within afterschool programs that can be altered and/or strengthened to reach policy goals. These include the policy environment at the national, state, and local levels; individual site, afterschool program leader, staff, and child characteristics; and existing outside organizational partnerships. Use of this framework and recognition of its constituent elements have the potential to lead to the successful and sustainable adoption and implementation of physical activity and nutrition policies in afterschool programs nationwide.
Addressing the Information Gap
Authors: Moore-Monroy Martha , Wilkinson-Lee Ada M. , Verdugo Lorena , Lopez Elvia , Paez Lourdes , Rodriguez Debora , Wilhelm Mari , Garcia Francisco
Published: September 2012

Despite significant advances in prevention, Mexican American women continue to experience disparities related to cervical cancer and access to current and relevant health information. To address this disparity a community–campus partnership initiated an outreach program to Latinas in Arizona as one part of an integrated approach. Promotoras (community health workers) provided the leadership in the development of a curriculum to (a) train promotoras on cervical cancer, (b) meet informational needs of community members, (c) address relevant social determinants of heath, and (d) promote access to health care. The purpose of this article is to describe the community-based participatory approach used in the development of the curriculum. Specifically, the article describes the leadership of promotoras, the curriculum development, and the use of continual feedback to inform the quality control. To address cervical cancer disparities for Mexican American women, the Pima County Cervical Cancer Prevention Partnership used principles of community-based participatory action.
Dissemination of Colorectal Cancer Screening by Filipino American Community Health Advisors
Authors: Maxwell Annette E. , Danao Leda L. , Bastani Roshan
Published: September 2012

Background. Filipino Americans underutilize life-saving screening tests for colorectal cancer, resulting in late stage of diagnosis and poor survival relative to other racial/ethnic groups. Education regarding colorectal cancer screening and distribution of free fecal occult blood test (FOBT) kits are evidence-based interventions that can significantly increase screening. However, this community will only benefit if the intervention is broadly disseminated. Methods. We assessed the feasibility of promoting colorectal cancer screening in Filipino American community settings working with community health advisors, and the practicality of conducting one-on-one or small group education, in addition to passing out free FOBT kits. Results. Twenty community health advisors from 4 organizations engaged in recruitment and education activities with 132 participants. Community health advisors consistently completed screening questionnaires to establish eligibility and kept logs of FOBT distribution. However, they did not consistently record eligible participants who did not consent to participate. Process checklists that indicated what information was covered in each educational session and postsession follow-up logs were partially completed. Almost all participants reported receipt of intervention components and receipt of screening at 4-month follow-up and reported high acceptability of the program. Discussion. The pilot study established the feasibility of working with community health advisors to promote colorectal cancer screening in Filipino American community settings. Findings informed the design of a dissemination trial that is currently ongoing with regards to monitoring recruitment, intervention implementation and follow-up and allowing flexibility regarding one-on-one or small group education.
Designing a Community-Based Lay Health Advisor Training Curriculum to Address Cancer Health Disparities
Authors: Gwede Clement K. , Ashley Atalie A. , McGinnis Kara , Montiel-Ishino F. Alejandro , Standifer Maisha , Baldwin Julie , Williams Coni , Sneed Kevin B. , Wathington Deanna , Dash-Pitts Lolita , Green B. Lee
Published: September 2012

Introduction. Racial and ethnic minorities have disproportionately higher cancer incidence and mortality than their White counterparts. In response to this inequity in cancer prevention and care, community-based lay health advisors (LHAs) may be suited to deliver effective, culturally relevant, quality cancer education, prevention/screening, and early detection services for underserved populations. Approach and Strategies. Consistent with key tenets of community-based participatory research (CBPR), this project engaged community partners to develop and implement a unique LHA training curriculum to address cancer health disparities among medically underserved communities in a tricounty area. Seven phases of curriculum development went into designing a final seven-module LHA curriculum. In keeping with principles of CBPR and community engagement, academic–community partners and LHAs themselves were involved at all phases to ensure the needs of academic and community partners were mutually addressed in development and implementation of the LHA program. Discussion and Conclusions. Community-based LHA programs for outreach, education, and promotion of cancer screening and early detection, are ideal for addressing cancer health disparities in access and quality care. When community-based LHAs are appropriately recruited, trained, and located in communities, they provide unique opportunities to link, bridge, and facilitate quality cancer education, services, and research.
Planning the Growth of a Metropolis
Authors: Stanilov Kiril
Published: September 2012

The article presents the results of a study investigating the growth of metropolitan London from the second half of the nineteenth century to the present. A high-resolution longitudinal land-use database, assembled from historical Ordnance Survey maps, is used to trace the patterns of land development in a 200 km2 area of West London from 1875 to the present. The land-use database is then employed to develop a cellular automata model, which explores the impact of key forces shaping the patterns of metropolitan growth. The analysis highlights the interplay of three critical factors: (1) the preurban spatial structure determined by the patterns of settlements and infrastructure predating the expansion of the metropolis; (2) the urban code representing a set of consistent rules that describe the spatial interaction of land uses with elements of the built environment; and (3) the mixture of planning and development policies advanced by public and private initiatives related to infrastructure investments, density regulation, and open space preservation. Contrary to the popular view rendering the growth of London as an outcome of uncoordinated private initiatives and market-based forces, the study advances the argument that planning played an important role in shaping the patterns of metropolitan expansion. Our analysis reveals, however, that the impact of planning was strongly conditioned by the elements of the preurban spatial structure and the mechanisms of the urban code.
San Francisco’s Diamond Heights
Authors: Brandi Richard
Published: September 2012

In 1951, architect Vernon DeMars produced an ambitious urban renewal plan for a nearly vacant and hilly site in the middle of San Francisco. The plan called for a mix of houses, apartments, and high rises, all suited to take advance of the views, and a shopping center, churches, playgrounds, and schools. Built from 1961 to 1981 with designs by Joseph Esherick, Claude Oakland, working for builder Joseph Eichler, and others, Diamond Heights was critically acclaimed at the time but now is unknown, a unique example of urban renewal and modernist city planning.
Parallel Lives
Authors: Loizidou Elena
Published: September 2012

The effects of the financial crisis (became visible in September 2008) have been multiple: austerity, redundancies, suicides, uprisings. Here I try to understand the effects of this crisis through the prism of ‘suicide’.
Imaging of Sports-Related Midfoot and Forefoot Injuries
Authors: Burge Alissa J. , Gold Stephanie L. , Potter Hollis G.
Published: September 2012

Sports-related injuries of the foot are common and may result in significant morbidity, particularly if inaccurate or delayed diagnosis leads to improper management. While less common than injuries of the ankle, sports-related foot injuries account for 2% to 18% of athletic injuries. Injury may occur as a result of acute trauma or chronic overuse, and high-impact sports that involve running, jumping, or contact place the athlete at higher risk for injury. Accurate and timely diagnosis of injury is the key to proper management, and diagnostic imaging studies often play a critical role in this regard. While radiographs, computerized tomography scans, and ultrasound are useful in the evaluation of the foot, magnetic resonance imaging provides superior tissue contrast as well as the ability to detect stress reaction in bone that precedes discernible fracture line on radiographs, allowing accurate detection of both osseous and soft tissue pathology. This review focuses on imaging of common sports-related injuries of the midfoot and forefoot, including osseous, ligamentous, and tendinous pathology, with emphasis on magnetic resonance imaging diagnosis.
Atypical prediagnosis Epstein-Barr virus serology restricted to EBV-positive Hodgkin lymphoma
Authors: Levin Lynn I. , Chang Ellen T. , Ambinder Richard F. , Lennette Evelyne T. , Rubertone Mark V. , Mann Risa B. , Borowitz Michael , Weir Edward G. , Abbondanzo Susan L. , Mueller Nancy E.
Published: September 2012

An altered anti–Epstein-Barr virus (EBV) serologic profile preceding diagnosis is associated with an increased risk of Hodgkin lymphoma. It is unknown whether this atypical pattern predicts Hodgkin lymphoma risk further subdivided by determination of EBV in tumor cells. A nested case-control study of 128 incident Hodgkin lymphoma cases and 368 matched controls from active-duty military personnel with archived serum in the US Department of Defense Serum Repository was conducted to determine whether a panel of anti-EBV antibody titers differed in EBV+ and EBV− Hodgkin lymphoma. Among 40 EBV+ Hodgkin lymphoma cases and matched controls, statistically significant increased risks were associated with elevated anti-EBV VCA IgG antibody titers (relative risk = 3.1; 95% confidence interval [CI], 1.1-8.7), and an anti–EBNA-1/anti–EBNA-2 antibody ratio ≤ 1.0 versus > 1.0 (relative risk = 4.7; 95% CI, 1.6-13.8). In contrast, no significant associations were found among 88 EBV− Hodgkin lymphoma cases relative to their matched controls. In case-case analysis, EBV+ disease was significantly associated with a low anti–EBNA-1/anti–EBNA-2 antibody ratio. This distinc-tive serologic response to EBV latent antigens, indicative of immune dysfunction in other clinical settings, is associated with an increased risk of developing EBV+ but not EBV− Hodgkin lymphoma.
Structural basis of CBP/p300 recruitment in leukemia induction by E2A-PBX1
Authors: Denis Christopher M. , Chitayat Seth , Plevin Michael J. , Wang Feng , Thompson Patrick , Liu Shuang , Spencer Holly L. , Ikura Mitsuhiko , LeBrun David P. , Smith Steven P.
Published: September 2012

E-proteins are critical transcription factors in B-cell lymphopoiesis. E2A, 1 of 3 E-protein–encoding genes, is implicated in the induction of acute lymphoblastic leukemia through its involvement in the chromosomal translocation 1;19 and consequent expression of the E2A-PBX1 oncoprotein. An interaction involving a region within the N-terminal transcriptional activation domain of E2A-PBX1, termed the PCET motif, which has previously been implicated in E-protein silencing, and the KIX domain of the transcriptional coactivator CBP/p300, critical for leukemogenesis. However, the structural details of this interaction remain unknown. Here we report the structure of a 1:1 complex between PCET motif peptide and the KIX domain. Residues throughout the helical PCET motif that contact the KIX domain are important for both binding KIX and bone marrow immortalization by E2A-PBX1. These results provide molecular insights into E-protein–driven differentiation of B-cells and the mechanism of E-protein silencing, and reveal the PCET/KIX interaction as a therapeutic target for E2A-PBX1–induced leukemia.
Inactivation of ribosomal protein L22 promotes transformation by induction of the stemness factor, Lin28B
Authors: Rao Shuyun , Lee Sang-Yun , Gutierrez Alejandro , Perrigoue Jacqueline , Thapa Roshan J. , Tu Zhigang , Jeffers John R. , Rhodes Michele , Anderson Stephen , Oravecz Tamas , Hunger Stephen P. , Timakhov Roman A. , Zhang Rugang , Balachandran Siddharth , Zambetti Gerard P. , Testa Joseph R. , Look A. Thomas , Wiest David L.
Published: September 2012

Ribosomal protein (RP) mutations in diseases such as 5q− syndrome both disrupt hematopoiesis and increase the risk of developing hematologic malignancy. However, the mechanism by which RP mutations increase cancer risk has remained an important unanswered question. We show here that monoallelic, germline inactivation of the ribosomal protein L22 (Rpl22) predisposes T-lineage progenitors to transformation. Indeed, RPL22 was found to be inactivated in ∼ 10% of human T-acute lymphoblastic leukemias. Moreover, monoallelic loss of Rpl22 accelerates development of thymic lymphoma in both a mouse model of T-cell malignancy and in acute transformation assays in vitro. We show that Rpl22 inactivation enhances transformation potential through induction of the stemness factor, Lin28B. Our finding that Rpl22 inactivation promotes transformation by inducing expression of Lin28B provides the first insight into the mechanistic basis by which mutations in Rpl22, and perhaps some other RP genes, increases cancer risk.
Role of the microenvironment in mantle cell lymphoma: IL-6 is an important survival factor for the tumor cells
Authors: Zhang Liang , Yang Jing , Qian Jianfei , Li Haiyan , Romaguera Jorge E. , Kwak Larry W. , Wang Michael , Yi Qing
Published: September 2012

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin lymphoma frequently involved in the lymph nodes, bone marrow, spleen, and gastrointestinal tract. We examined the role of IL-6 in MCL. Human MCL cells expressed the membrane gp130 and soluble gp80, and some of them also secreted IL-6. Neutralizing autocrine IL-6 and/or blocking IL-6 receptors in IL-6+/gp80+ MCL cells inhibited cell growth, enhanced the rate of spontaneous apoptosis, and increased sensitivity to chemotherapy drugs. For IL-6− or gp80low MCL cells, paracrine or exogenous IL-6 or gp80 protected the cells from stress-induced death. Knockdown of gp80 in gp80high MCL cells rendered the cells more sensitive to chemotherapy drugs, even in the presence of exogenous IL-6. In contrast, overexpression of gp80 in gp80low/IL-6+ MCL cells protected the cells from chemotherapy drug-induced apoptosis in vitro and compromised the therapeutic effect of chemotherapy in vivo. IL-6 activated the Jak2/STAT3 and PI3K/Akt pathways in MCL, and the inhibition of these pathways completely or partially abrogated IL-6–mediated protection of MCL cells. Hence, our study identifies IL-6 as a key cytokine for MCL growth and survival and suggests that targeting the IL-6 pathway may be a novel way to improve the efficacy of chemotherapy in MCL patients.
Regulating type 1 IFN effects in CD8 T cells during viral infections: changing STAT4 and STAT1 expression for function
Authors: Gil M. Pilar , Ploquin Mickaël J. Y. , Watford Wendy T. , Lee Seung-Hwan , Kim Kwangsin , Wang Xin , Kanno Yuka , O'Shea John J. , Biron Christine A.
Published: September 2012

Type 1 IFNs can conditionally activate all of the signal transducers and activators of transcription molecules (STATs), including STAT4. The best-characterized signaling pathways use STAT1, however, and type 1 IFN inhibition of cell proliferation is STAT1 dependent. We report that type 1 IFNs can basally stimulate STAT1- and STAT4-dependent effects in CD8 T cells, but that CD8 T cells responding to infections of mice with lymphocytic choriomenigitis virus have elevated STAT4 and lower STAT1 expression with significant consequences for modifying the effects of type 1 IFN exposure. The phenotype was associated with preferential type 1 IFN activation of STAT4 compared with STAT1. Stimulation through the TCR induced elevated STAT4 expression, and STAT4 was required for peak expansion of antigen-specific CD8 T cells, low STAT1 levels, and resistance to type 1 IFN-mediated inhibition of proliferation. Thus, a mechanism is discovered for regulating the consequences of type 1 IFN exposure in CD8 T cells, with STAT4 acting as a key molecule in driving optimal antigen-specific responses and overcoming STAT1-dependent inhibition of proliferation.
ADAMTS13 deficiency exacerbates VWF-dependent acute myocardial ischemia/reperfusion injury in mice
Authors: Gandhi Chintan , Motto David G. , Jensen Melissa , Lentz Steven R. , Chauhan Anil K.
Published: September 2012

Epidemiologic studies suggest that elevated VWF levels and reduced ADAMTS13 activity in the plasma are risk factors for myocardial infarction. However, it remains unknown whether the ADAMTS13-VWF axis plays a causal role in the pathophysiology of myocardial infarction. In the present study, we tested the hypothesis that ADAMTS13 reduces VWF-mediated acute myocardial ischemia/reperfusion (I/R) injury in mice. Infarct size, neutrophil infiltration, and myocyte apoptosis in the left ventricular area were quantified after 30 minutes of ischemia and 23.5 hours of reperfusion injury. Adamts13−/− mice exhibited significantly larger infarcts concordant with increased neutrophil infiltration and myocyte apoptosis compared with wild-type (WT) mice. In contrast, Vwf−/− mice exhibited significantly reduced infarct size, neutrophil infiltration, and myocyte apoptosis compared with WT mice, suggesting a detrimental role for VWF in myocardial I/R injury. Treating WT or Adamts13−/− mice with neutralizing Abs to VWF significantly reduced infarct size compared with control Ig–treated mice. Finally, myocardial I/R injury in Adamts13−/−/Vwf−/− mice was similar to that in Vwf−/− mice, suggesting that the exacerbated myocardial I/R injury observed in the setting of ADAMTS13 deficiency is VWF dependent. These findings reveal that ADAMTS13 and VWF are causally involved in myocardial I/R injury.
High-throughput polymorphism detection and genotyping in Brassica napus using next-generation RAD sequencing
Authors: Bus Anja , Hecht Jochen , Huettel Bruno , Reinhardt Richard , Stich Benjamin
Published: September 2012

Background

The complex genome of rapeseed (Brassica napus) is not well understood despite the economic importance of the species. Good knowledge of sequence variation is needed for genetics approaches and breeding purposes. We used a diversity set of B. napus representing eight different germplasm types to sequence genome-wide distributed restriction-site associated DNA (RAD) fragments for polymorphism detection and genotyping.

Results

More than 113,000 RAD clusters with more than 20,000 single nucleotide polymorphisms (SNPs) and 125 insertions/deletions were detected and characterized. About one third of the RAD clusters and polymorphisms mapped to the Brassica rapa reference sequence. An even distribution of RAD clusters and polymorphisms was observed across the B. rapa chromosomes, which suggests that there might be an equal distribution over the Brassica oleracea chromosomes, too. The representation of Gene Ontology (GO) terms for unigenes with RAD clusters and polymorphisms revealed no signature of selection with respect to the distribution of polymorphisms within genes belonging to a specific GO category.

Conclusions

Considering the decreasing costs for next-generation sequencing, the results of our study suggest that RAD sequencing is not only a simple and cost-effective method for high-density polymorphism detection but also an alternative to SNP genotyping from transcriptome sequencing or SNP arrays, even for species with complex genomes such as B. napus.
In depth comparison of an individual’s DNA and its lymphoblastoid cell line using whole genome sequencing
Authors: Nickles Dorothee , Madireddy Lohith , Yang Shan , Khankhanian Pouya , Lincoln Steve , Hauser Stephen L , Oksenberg Jorge R , Baranzini Sergio E
Published: September 2012

Background

A detailed analysis of whole genomes can be now achieved with next generation sequencing. Epstein Barr Virus (EBV) transformation is a widely used strategy in clinical research to obtain an unlimited source of a subject’s DNA. Although the mechanism of transformation and immortalization by EBV is relatively well known at the transcriptional and proteomic level, the genetic consequences of EBV transformation are less well understood. A detailed analysis of the genetic alterations introduced by EBV transformation is highly relevant, as it will inform on the usefulness and limitations of this approach.

Results

We used whole genome sequencing to assess the genomic signature of a low-passage lymphoblastoid cell line (LCL). Specifically, we sequenced the full genome (40X) of an individual using DNA purified from fresh whole blood as well as DNA from his LCL. A total of 217.33 Gb of sequence were generated from the cell line and 238.95 Gb from the normal genomic DNA. We determined with high confidence that 99.2% of the genomes were identical, with no reproducible changes in structural variation (chromosomal rearrangements and copy number variations) or insertion/deletion polymorphisms (indels).

Conclusions

Our results suggest that, at this level of resolution, the LCL is genetically indistinguishable from its genomic counterpart and therefore their use in clinical research is not likely to introduce a significant bias.
Anxiety symptoms among Chinese nurses and the associated factors: a cross sectional study
Authors: Gao Yu-Qin , Pan Bo-Chen , Sun Wei , Wu Hui , Wang Jia-Na , Wang Lie
Published: September 2012

Background

Nurses are an indispensable component of the work force in the health care system. However, many of them are known to work in a stressful environment which may affect their mental well-being; the situation could be worse in rapidly transforming societies such as China. The purpose of this study was to investigate anxiety symptoms and the associated factors in Chinese nurses working in public city hospitals.

Methods

A cross-sectional survey was performed for Chinese nurses in public city hospitals of Liaoning Province, northeast China. Seven hospitals in different areas of the province were randomly selected for the study. The Zung Self-Rating Anxiety Scale was used to measure anxiety symptoms. Effort-reward imbalance questionnaire and Job Content Questionnaire were used to assess the work stressors. Univariate analysis and stepwise multivariate logistic regression analysis were used to identify the factors associated with anxiety symptoms.

Results

All registered nurses in the seven city hospitals, totaling 1807 registered nurses were surveyed. Of the returned questionnaires, 1437 were valid (79.5%) for analysis. Utilizing the total raw score ≥ 40 as the cut-off point, the prevalence of anxiety symptoms in these nurses was 43.4%. Demographic factors (education, chronic disease and life event), lifestyle factors (regular meals and physical exercise), work conditions (hospital grade, job rank, monthly salary, nurse-patient relationships, job satisfaction and intention of leaving), job content (social support and decision latitude), effort-reward imbalance and overcommitment were all significantly related to the anxiety symptoms. Multivariate logistic regression analysis showed main factors associated with anxiety symptoms were lower job rank (OR 2.501), overcommitment (OR 2.018), chronic diseases (OR 1.541), worse nurse-patient relationship (OR 1.434), higher social support (OR 0.573), lower hospital grade (OR 0.629), taking regular meals (OR 0.719) and higher level of job satisfaction (OR 0.722).

Conclusions

A large proportion of Chinese nurses working in public city hospitals had anxiety symptoms, which warrants immediate investigation and intervention from the hospital administrators. Meanwhile, results of the study suggest that proper counseling, promotion of healthy lifestyle behavior and improvements to the social environment in the work place may be helpful toward reducing or preventing the anxiety symptoms.
Antioxidant, genotoxic and antigenotoxic activities of daphne gnidium leaf extracts
Authors: Chaabane Fadwa , Boubaker Jihed , Loussaif Amira , Neffati Aicha , Kilani-Jaziri Somaya , Ghedira Kamel , Chekir-Ghedira Leila
Published: September 2012

Background

Plants play a significant role in maintaining human health and improving the quality of human life. They serve humans well as valuable components of food, as well as in cosmetics, dyes, and medicines. In fact, many plant extracts prepared from plants have been shown to exert biological activity in vitro and in vivo. The present study explored antioxidant and antigenotoxic effects of Daphne gnidium leaf extracts.

Methods

The genotoxic potential of petroleum ether, chloroform, ethyl acetate, methanol and total oligomer flavonoid (TOF) enriched extracts from leaves of Daphne gnidium, was assessed using Escherichia coli PQ37. Likewise, the antigenotoxicity of the same extracts was tested using the “SOS chromotest test”. Antioxidant activities were studied using non enzymatic and enzymatic method: NBT/Riboflavine and xantine oxidase.

Results

None of the different extracts produced a genotoxic effect, except TOF extract at the lowest tested dose. Our results showed that D. gnidium leaf extracts possess an antigenotoxic effect against the nitrofurantoin a mutagen of reference. Ethyl acetate and TOF extracts were the most effective in inhibiting xanthine oxidase activity. While, methanol extract was the most potent superoxide scavenger when tested with the NBT/Riboflavine assay.

Conclusions

The present study has demonstrated that D. gnidium leaf extract possess antioxidant and antigenotoxic effects. These activities could be ascribed to compounds like polyphenols and flavonoid. Further studies are required to isolate the active molecules.
The roots of Atractylodes japonica Koidzumi promote adipogenic differentiation via activation of the insulin signaling pathway in 3T3-L1 cells
Authors: Han Yunkyung , Jung Hyo Won , Park Yong-Ki
Published: September 2012

Background

Type 2 diabetes (T2D) is a complex metabolic disorder characterized by insulin resistance and hyperglycemia. Peroxisome proliferator-activated receptor gamma (PPARγ) is a key transcription factor and plays an important role in the regulation of genes involved in adipogenic differentiation, glucose metabolism and insulin signal transduction.

Methods

In this study, the effects of the root extract of Atractylodes japonica Koidzumi ( Atractylodis Rhizoma Alba, ARA) on the differentiation of 3T3-L1 preadipocytes and the possible mechanism of glucose transport were investigated. 3T3-L1 cells were cultured with insulin and ARA extract.

Results

In 3T3-L1 cells, ARA extract significantly enhanced adipogenic differentiation and upregulated the expression of PPARγ genes and protein in a dose-dependent manner. ARA also promoted glucose transport by increasing the glucose transporter 4 (GLUT-4), phosphatidylinositol 3-kinase (PI3K) and insulin receptor substrates-1 (IRS-1) levels.

Conclusion

Our results suggest that ARA extract may be an attractive therapeutic agent for managing T2D via promoting the differentiation of adipocytes with the upregulation of PPARγ levels and the activation of the insulin signaling pathway.
SRC Homology 2 Domain Binding Sites in Insulin, IGF-1 and FGF receptor mediated signaling networks reveal an extensive potential interactome
Authors: Liu Bernard A , Engelmann Brett W , Jablonowski Karl , Higginbotham Katherine , Stergachis Andrew B , Nash Piers D
Published: September 2012

Specific peptide ligand recognition by modular interaction domains is essential for the fidelity of information flow through the signal transduction networks that control cell behavior in response to extrinsic and intrinsic stimuli. Src homology 2 (SH2) domains recognize distinct phosphotyrosine peptide motifs, but the specific sites that are phosphorylated and the complement of available SH2 domains varies considerably in individual cell types. Such differences are the basis for a wide range of available protein interaction microstates from which signaling can evolve in highly divergent ways. This underlying complexity suggests the need to broadly map the signaling potential of systems as a prerequisite for understanding signaling in specific cell types as well as various pathologies that involve signal transduction such as cancer, developmental defects and metabolic disorders. This report describes interactions between SH2 domains and potential binding partners that comprise initial signaling downstream of activated fibroblast growth factor (FGF), insulin (Ins), and insulin-like growth factor-1 (IGF-1) receptors. A panel of 50 SH2 domains screened against a set of 192 phosphotyrosine peptides defines an extensive potential interactome while demonstrating the selectivity of individual SH2 domains. The interactions described confirm virtually all previously reported associations while describing a large set of potential novel interactions that imply additional complexity in the signaling networks initiated from activated receptors. This study of pTyr ligand binding by SH2 domains provides valuable insight into the selectivity that underpins complex signaling networks that are assembled using modular protein interaction domains.
Phenotypes and clinical significance of circulating CD4+CD25+ regulatory T cells (Tregs) in patients with acute-on-chronic liver failure (ACLF)
Authors: Yang Jiezuan , Yi Ping , Wei Li , Xu Zherong , Chen Yunbo , Tang Lingling , Li Lanjuan
Published: September 2012

Background

CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immunological tolerance to self and foreign antigens. T cell receptors (TCR) reflect the composition and function of T cells. It is not universally agreed that there is a relationship between CD4+CD25+ Treg frequency and the severity of acute-on-chronic liver failure (ACLF). The repertoire of TCR beta chain variable (TCRBV) regions of peripheral Tregs in ACLF patients is not well understood.

Methods

Human PBMCs were separated and sorted into CD4+CD25+ Treg subsets using density gradient centrifugation and magnetic activated cell sorting (MACS). The CD4+CD25high Treg frequency in peripheral blood of ACLF and chronic hepatitis B (CHB) patients was measured by flow cytometry. The molecular profiles of TCRBV CDR3 were determined using gene melting spectral pattern (GMSP) analysis. TCRBV gene families were cloned and sequenced when the GMSP profiles showed a single-peak.

Results

CD4+CD25high Treg prevalence in peripheral blood of ACLF patients is increased significantly compared to healthy donors (HDs) (P < 0.01) and CHB patients (P < 0.01). The prevalence of CD4+CD25high Tregs in ACLF or CHB patients is positively correlated with HBV DNA load. The TCRBV11, BV13.1, BV18, BV20 are the most prevalent TCRBV in CD4+CD25+ Tregs in ACLF and CHB patients. In addition, the CDR3 motifs were relatively conserved in these four TCRBV gene families.

Conclusions

The CD4+CD25high Tregs prevalence in peripheral blood is indicative of disease severity in ACLF or CHB patients. The relatively conserved TCRBV20 CDR3 motif “TGTGHSPLH” and TCRBV11 CDR3 motif “VYNEQ” may be used in helping diagnosis and treat patients with ACLF.
Stop codons in bacteria are not selectively equivalent
Authors: Povolotskaya Inna S , Kondrashov Fyodor A , Ledda Alice , Vlasov Peter K
Published: September 2012

Background

The evolution and genomic stop codon frequencies have not been rigorously studied with the exception of coding of non-canonical amino acids. Here we study the rate of evolution and frequency distribution of stop codons in bacterial genomes.

Results

We show that in bacteria stop codons evolve slower than synonymous sites, suggesting the action of weak negative selection. However, the frequency of stop codons relative to genomic nucleotide content indicated that this selection regime is not straightforward. The frequency of TAA and TGA stop codons is GC-content dependent, with TAA decreasing and TGA increasing with GC-content, while TAG frequency is independent of GC-content. Applying a formal, analytical model to these data we found that the relationship between stop codon frequencies and nucleotide content cannot be explained by mutational biases or selection on nucleotide content. However, with weak nucleotide content-dependent selection on TAG, -0.5 < Nes < 1.5, the model fits all of the data and recapitulates the relationship between TAG and nucleotide content. For biologically plausible rates of mutations we show that, in bacteria, TAG stop codon is universally associated with lower fitness, with TAA being the optimal for G-content < 16% while for G-content > 16% TGA has a higher fitness than TAG.

Conclusions

Our data indicate that TAG codon is universally suboptimal in the bacterial lineage, such that TAA is likely to be the preferred stop codon for low GC content while the TGA is the preferred stop codon for high GC content. The optimization of stop codon usage may therefore be useful in genome engineering or gene expression optimization applications.

Reviewers

This article was reviewed by Michail Gelfand, Arcady Mushegian and Shamil Sunyaev. For the full reviews, please go to the Reviewers’ Comments section.
Nursing home administrators’ perspectives on a study feedback report: a cross sectional survey
Authors: Boström Anne-Marie , Cranley Lisa A , Hutchinson Alison M , Cummings Greta G , Norton Peter G , Estabrooks Carole A
Published: September 2012

Background

This project is part of the Translating Research in Elder Care (TREC) program of research, a multi-level and longitudinal research program being conducted in 36 nursing homes in three Canadian Prairie Provinces. The overall goal of TREC is to improve the quality of care for older persons living in nursing homes and the quality of work life for care providers. The purpose of this paper is to report on development and evaluation of facility annual reports (FARs) from facility administrators’ perspectives on the usefulness, meaningfulness, and understandability of selected data from the TREC survey.

Methods

A cross sectional survey design was used in this study. The feedback reports were developed in collaboration with participating facility administrators. FARs presented results in four contextual areas: workplace culture, feedback processes, job satisfaction, and staff burnout. Six weeks after FARs were mailed to each administrator, we conducted structured telephone interviews with administrators to elicit their evaluation of the FARs. Administrators were also asked if they had taken any actions as a result of the FAR. Descriptive and inferential statistics, as well as content analysis for open-ended questions, were used to summarize findings.

Results

Thirty-one facility administrators (representing thirty-two facilities) participated in the interviews. Six administrators had taken action and 18 were planning on taking action as a result of FARs. The majority found the four contextual areas addressed in FAR to be useful, meaningful, and understandable. They liked the comparisons made between data from years one and two and between their facility and other TREC study sites in their province. Twenty-two indicated that they would like to receive information on additional areas such as aggressive behaviours of residents and information sharing. Twenty-four administrators indicated that FARs contained enough information, while eight found FARs ‘too short’. Administrators who reported that the FAR contained enough information were more likely to take action within their facilities than administrators who reported that they needed more information.

Conclusions

Although the FAR was brief, the presentation of the four contextual areas was relevant to the majority of administrators and prompted them to plan or to take action within their facility.
Ceramide sphingolipid signaling mediates Tumor Necrosis Factor (TNF)-dependent toxicity via caspase signaling in dopaminergic neurons
Authors: Martinez Terina N , Chen Xi , Bandyopadhyay Sibali , Merrill Alfred H , Tansey Malú G
Published: September 2012

Background

Dopaminergic (DA) neurons in the ventral midbrain selectively degenerate in Parkinson’s disease (PD) in part because their oxidative environment in the substantia nigra (SN) may render them vulnerable to neuroinflammatory stimuli. Chronic inhibition of soluble Tumor Necrosis Factor (TNF) with dominant-negative TNF inhibitors protects DA neurons in rat models of parkinsonism, yet the molecular mechanisms and pathway(s) that mediate TNF toxicity remain(s) to be clearly identified. Here we investigated the contribution of ceramide sphingolipid signaling in TNF-dependent toxicity.

Results

Ceramide dose-dependently reduced the viability of DA neuroblastoma cells and primary DA neurons and pharmacological inhibition of sphingomyelinases (SMases) with three different inhibitors during TNF treatment afforded significant neuroprotection by attenuating increased endoplasmic reticulum (ER) stress, loss of mitochondrial membrane potential, caspase-3 activation and decreases in Akt phosphorylation. Using lipidomics mass spectrometry we confirmed that TNF treatment not only promotes generation of ceramide, but also leads to accumulation of several atypical deoxy-sphingoid bases (DSBs). Exposure of DA neuroblastoma cells to atypical DSBs in the micromolar range reduced cell viability and inhibited neurite outgrowth and branching in primary DA neurons, suggesting that TNF-inducedde novosynthesis of atypical DSBs may be a secondary mechanism involved in mediating its neurotoxicity in DA neurons.

Conclusions

We conclude that TNF/TNFR1-dependent activation of SMases generates ceramide and sphingolipid species that promote degeneration and caspase-dependent cell death of DA neurons. Ceramide and atypical DSBs may represent novel drug targets for development of neuroprotective strategies that can delay or attenuate the progressive loss of nigral DA neurons in patients with PD.
A simple knowledge-based mining method for exploring hidden key molecules in a human biomolecular network
Authors: Tsuji Shingo , Ihara Sigeo , Aburatani Hiroyuki
Published: September 2012

Background

In the functional genomics analysis domain, various methodologies are available for interpreting the results produced by high-throughput biological experiments. These methods commonly use a list of genes as an analysis input, and most of them produce a more complicated list of genes or pathways as the results of the analysis. Although there are several network-based methods, which detect key nodes in the network, the results tend to include well-studied, major hub genes.

Results

To mine the molecules that have biological meaning but to fewer degrees than major hubs, we propose, in this study, a new network-based method for selecting these hidden key molecules based on virtual information flows circulating among the input list of genes. The human biomolecular network was constructed from the Pathway Commons database, and a calculation method based on betweenness centrality was newly developed. We validated the method with the ErbB pathway and applied it to practical cancer research data. We were able to confirm that the output genes, despite having fewer edges than major hubs, have biological meanings that were able to be invoked by the input list of genes.

Conclusions

The developed method, named NetHiKe (Network-based Hidden Key molecule miner), was able to detect potential key molecules by utilizing the human biomolecular network as a knowledge base. Thus, it is hoped that this method will enhance the progress of biological data analysis in the whole-genome research era.
Preoperative diagnosis of a breast hydatid cyst using fine-needle aspiration cytology: a case report and review of the literature
Authors: Cancelo Maria Jesus , Martín Maria , Mendoza Nicolas
Published: September 2012

Introduction

A hydatid cyst of the breast is rare and often goes unnoticed by mammography and ultrasound. Preoperative diagnosis may be performed using fine-needle aspiration cytology, which also minimizes the risk of intraoperative rupture.

Case presentation

We report the case of a 70-year-old Spanish woman who was diagnosed with a hydatid cyst using fine-needle aspiration cytology before surgery.

Conclusion

Fine-needle aspiration cytology is an accurate and safe technique that can allow surgery to be avoided, especially in older patients or patients with high surgical risk.
Docosahexaenoic acid complexed to human albumin in experimental stroke: neuroprotective efficacy with a wide therapeutic window
Authors: Eady Tiffany N , Khoutorova Larissa , Atkins Kristal D , Bazan Nicolas G , Belayev Ludmila
Published: September 2012

Background

Docosahexaenoic acid (DHA) complexed to human serum albumin (Alb) is neuroprotective after experimental stroke. Here we tested using lower concentrations of albumin as part of the complex to achieve neuroprotection. We found that lower Alb concentrations extend the therapeutic window of protection beyond 5 h after stroke onset.

Methods

Sprague–Dawley rats were received 2 h middle cerebral artery occlusion (MCAo). The behavior was evaluated on day 1, 2, 3 and 7 after MCAo. In the dose–response study, animals were given either DHA (5mg/kg), Alb (0.63g/kg), DHA-Alb (5mg/kg + 0.32, 0.63 or 1.25 g/kg) or saline, i.v. 3 h after onset of stroke (n=6-8 per group). In the therapeutic window study, DHA-Alb (5mg/kg + 1.25g/kg) was administered i.v. at either 3, 4, 5, 6 or 7 h after onset of stroke (n=7-9 per group). Alb (1.25g/kg) was given at 3 h or 5 h and saline at 3h after onset of reperfusion. Seven days after MCAo, infarct volumes and number of GFAP, ED-1, NeuN, SMI-71 positive cells and vessels were counted.

Results

Moderate DHA-Alb doses (0.63 and 1.25 g/kg) improved neurological scores compared to albumin-treated rats on days 1, 2, 3 and 7. All DHA-Alb doses (0.32, 0.63 and 1.25 g/kg) markedly reduced cortical (by 65-70%), striatal (by 52-63%) and total infarct volumes (by 60-64%) compared to native Alb group. In the therapeutic window study DHA-Alb led to improved neurological score and significant reductions of infarct volumes (especially in the cortical or penumbral region), even when treatment was initiated as late as 7 hours after onset of MCAo.

Conclusions

The DHA-Alb complex affords high-grade neurobehavioral neuroprotection in focal cerebral ischemia, equaling or exceeding that afforded by native Alb or DHA, at considerably moderate doses. It has a broad therapeutic window extending to 7 h after stroke onset. Taken together, these finding support the potential clinical feasibility of administering DHA-Alb therapy to patients with acute ischemic stroke.
The production of β-glucosidases by Fusarium proliferatum NBRC109045 isolated from Vietnamese forest
Authors: Gao Ziqing , Van Hop Duong , Yen Le Thi Hoang , Ando Katsuhiko , Hiyamuta Shuichi , Kondo Ryuichiro
Published: September 2012

Fusarium proliferatum NBRC109045 is a filamentous fungus isolated from Vietnamese forest due to high production of β-glucosidases. Production of the enzyme was studied on varied carbon source based mediums. The highest activity was obtained in medium containing 1% corn stover + 1% wheat bran (3.31 ± 0.14 U/ml). It is interesting to note that glucose (0.69 ± 0.02 U/ml) gave higher activity and just followed by cellobiose among the di- and mono-saccharides, which is generally regarded as a universal repressor of hydrolases. We improved the zymogram method to prove that in response to various carbon sources, F. proliferatum could express various β-glucosidases. One of the β-glucosidases produced by F. proliferatum growing in corn stover + wheat bran based medium was partially purified and proved to have high catalytic ability.