Growth characterization of CHO DP-12 cell lines with different high passage histories

Heinrich C, Timo W, Christina K, Northoff S, Noll T. Growth characterization of CHO DP-12 cell lines with different high passage histories. In: Hansjörg H, ed. BMC Proceedings. BMC Proceedings. Vol 5. BioMed Central; 2011

Community Service Learning Packet

This learning packet contains a set of exercises designed to stimulate the student\u27s thinking about their community and the value of community service. It begins with a personal definition of the word community. From this definition, the student then gathers information about the school community. Hopefully, by attending school club meetings students will increase their sense of belonging and learn about options for volunteering at their campus. The notion that young people are selfish and hedonistic is examined in a section about stereotypes and biased news reporting. To break up the worksheet sequence two movie assignment guides are provided, where students view stories of compassion or caring and documentaries about youth performing volunteer service

HIV-1 Tat causes cognitive deficits and selective loss of parvalbumin, somatostatin, and neuronal nitric oxide synthase expressing hippocampal CA1 interneuron subpopulations

Memory deficits are characteristic of HIV-associated neurocognitive disorders (HAND) and co-occur with hippocampal pathology. The HIV-1 transactivator of transcription (Tat), a regulatory protein, plays a significant role in these events, but the cellular mechanisms involved are poorly understood. Within the hippocampus, diverse populations of interneurons form complex networks; even subtle disruptions can drastically alter synaptic output, resulting in behavioral dysfunction. We hypothesized that HIV-1 Tat would impair cognitive behavior and injure specific hippocampal interneuron subtypes. Male transgenic mice that inducibly expressed HIV-1 Tat (or non-expressing controls) were assessed for cognitive behavior or had hippocampal CA1 subregions evaluated via interneuron subpopulation markers. Tat exposure decreased spatial memory in a Barnes maze and mnemonic performance in a novel object recognition test. Tat reduced the percentage of neurons expressing neuronal nitric oxide synthase (nNOS) without neuropeptide Y immunoreactivity in the stratum pyramidale and the stratum radiatum, parvalbumin in the stratum pyramidale, and somatostatin in the stratum oriens, which are consistent with reductions in interneuron-specific interneuron type 3 (IS3), bistratified, and oriens-lacunosum-moleculare interneurons, respectively. The findings reveal that an interconnected ensemble of CA1 nNOS-expressing interneurons, the IS3 cells, as well as subpopulations of parvalbumin- and somatostatin-expressing interneurons are preferentially vulnerable to HIV-1 Tat. Importantly, the susceptible interneurons form a microcircuit thought to be involved in feedback inhibition of CA1 pyramidal cells and gating of CA1 pyramidal cell inputs. The identification of vulnerable CA1 hippocampal interneurons may provide novel insight into the basic mechanisms underlying key functional and neurobehavioral deficits associated with HAND

[68Ga]-DOTATOC-PET/CT for meningioma IMRT treatment planning

<p>Abstract</p> <p>Purpose</p> <p>The observation that human meningioma cells strongly express somatostatin receptor (SSTR 2) was the rationale to analyze retrospectively in how far DOTATOC PET/CT is helpful to improve target volume delineation for intensity modulated radiotherapy (IMRT).</p> <p>Patients and Methods</p> <p>In 26 consecutive patients with preferentially skull base meningioma, diagnostic magnetic resonance imaging (MRI) and planning-computed tomography (CT) was complemented with data from [⁶⁸Ga]-DOTA-D Phe¹-Tyr³-Octreotide (DOTATOC)-PET/CT. Image fusion of PET/CT, diagnostic computed tomography, MRI and radiotherapy planning CT as well as target volume delineation was performed with OTP-Masterplan^®. Initial gross tumor volume (GTV) definition was based on MRI data only and was secondarily complemented with DOTATOC-PET information. Irradiation was performed as EUD based IMRT, using the Hyperion Software package.</p> <p>Results</p> <p>The integration of the DOTATOC data led to additional information concerning tumor extension in 17 of 26 patients (65%). There were major changes of the clinical target volume (CTV) which modify the PTV in 14 patients, minor changes were realized in 3 patients. Overall the GTV-MRI/CT was larger than the GTV-PET in 10 patients (38%), smaller in 13 patients (50%) and almost the same in 3 patients (12%). Most of the adaptations were performed in close vicinity to bony skull base structures or after complex surgery. Median GTV based on MRI was 18.1 cc, based on PET 25.3 cc and subsequently the CTV was 37.4 cc. Radiation planning and treatment of the DOTATOC-adapted volumes was feasible.</p> <p>Conclusion</p> <p>DOTATOC-PET/CT information may strongly complement patho-anatomical data from MRI and CT in cases with complex meningioma and is thus helpful for improved target volume delineation especially for skull base manifestations and recurrent disease after surgery.</p

Cross-cultural adaptation of the PatientDoctor Relationship Questionnaire (PDRQ-9) in Brazil

OBJETIVO: Descrever o processo de adaptação transcultural do Patient-Doctor Relationship Questionnaire (PDRQ-9), além de comparar a concordância entre duas diferentes formas de aplicação. MÉTODOS: Estudo transversal, com 133 usuários adultos de uma Unidade Básica de Saúde de Porto Alegre, RS. O PDRQ-9 foi respondido pelos participantes de maneira autoaplicada e por meio de entrevista. O instrumento também foi validado por entrevista, utilizando os dados de 628 participantes da Pesquisa de Avaliação do Programa Mais Médicos, um estudo transversal com amostra sistemática de Unidades Básicas de Saúde em todas as regiões do Brasil. Foram realizadas avaliações de equivalência semântica, conceitual e de itens, análise fatorial e avaliação da fidedignidade. RESULTADOS: Todos os itens apresentaram carga fatorial &gt; 0,5 nos diferentes métodos de aplicação e populações na análise fatorial. Foi encontrado alfa de Cronbach de 0,94 no método autoaplicado. A aplicação por meio de entrevista encontrou alfa de Cronbach de 0,95 e 0,94 nas duas amostras diferentes. A utilização do PDRQ-9 por meio de entrevista ou de maneira autoaplicada foi considerada equivalente. CONCLUSÕES: A adaptação transcultural do PDRQ-9 no Brasil replicou a estrutura fatorial encontrada no estudo original, com alta consistência interna. O instrumento poderá ser utilizado como uma nova dimensão na avaliação da qualidade do cuidado em saúde em pesquisas clínicas, na avaliação de serviços e em saúde pública, na gestão em saúde e na formação profissional. Novos estudos poderão ampliar a avaliação de outras propriedades do instrumento, bem como seu comportamento em diferentes populações e contextos.OBJECTIVE: To describe the process of cross-cultural adaptation of the Patient-Doctor Relationship Questionnaire (PDRQ-9), as well as compare the agreement between two different types of application. METHODS: This is a cross-sectional study with 133 adult users of a Primary Health Service in Porto Alegre, State of Rio Grande do Sul, Brazil. The PDRQ-9 was answered by the participants as a self-administered questionnaire and in an interview. The instrument was also validated by interview, using data from 628 participants of the Mais Médicos Program Evaluation Research, which is a cross-sectional study with a systematic sample of Primary Care Services in all regions of Brazil. We evaluated the semantic, conceptual, and item equivalence, as well as factor analysis and reliability. RESULTS: All items presented factor loading &gt; 0.5 in the different methods of application and populations in the factor analysis. We found Cronbach’s alpha of 0.94 in the self-administered method. We found Cronbach’s alpha of 0.95 and 0.94 in the two different samples in the interview application. The use of PDRQ-9 with an interview or self-administered was considered equivalent. CONCLUSIONS: The cross-cultural adaptation of the PDRQ-9 in Brazil replicated the factorial structure found in the original study, with high internal consistency. The instrument can be used as a new dimension in the evaluation of the quality of health care in clinical research, in the evaluation of services and public health, in health management, and in professional training. Further studies can evaluate other properties of the instrument, as well as its behavior in different populations and contexts

The Promises and Pitfalls of Genoeconomics

This article reviews existing research at the intersection of genetics and economics, presents some new findings that illustrate the state of genoeconomics research, and surveys the prospects of this emerging field. Twin studies suggest that economic outcomes and preferences, once corrected for measurement error, appear to be about as heritable as many medical conditions and personality traits. Consistent with this pattern, we present new evidence on the heritability of permanent income and wealth. Turning to genetic association studies, we survey the main ways that the direct measurement of genetic variation across individuals is likely to contribute to economics, and we outline the challenges that have slowed progress in making these contributions. The most urgent problem facing researchers in this field is that most existing efforts to find associations between genetic variation and economic behavior are based on samples that are too small to ensure adequate statistical power. This has led to many false positives in the literature. We suggest a number of possible strategies to improve and remedy this problem: (a) pooling data sets, (b) using statistical techniques that exploit the greater information content of many genes jointly, and (c) focusing on economically relevant traits that are most proximate to known biological mechanisms.EconomicsSociolog

Immunoblot analysis of the seroreactivity to recombinant Borrelia burgdorferi sensu lato antigens, including VlsE, in the long-term course of treated patients with Erythema migrans

Objective: We evaluated whether immunoblotting is capable of substantiating the posttreatment clinical assessment of patients with erythema migrans ( EM), the hallmark of early Lyme borreliosis. Methods: In 50 patients, seroreactivity to different antigens of Borrelia burgdorferi sensu lato was analyzed by a recombinant immunoblot test (IB) in consecutive serum samples from a minimum follow-up period of 1 year. Antigens in the IgG test were decorin- binding protein A, internal fragment of p41 (p41i), outer surface protein C (OspC), p39, variable major protein-like sequence expressed (VlsE), p58 and p100; those in the IgM test were p41i, OspC and p39. Immune responses were correlated with clinical and treatment-related parameters. Results: Positive IB results were found in 50% before, in 57% directly after therapy and in 44% by the end of the follow-up for the IgG class, and in 36, 43 and 12% for the IgM class. In acute and convalescence phase sera, VlsE was most immunogenic on IgG testing 60 and 70%), and p41i (46 and 57%) and OspC (40 and 57%) for the IgM class. By the end of the follow-up, only the anti-p41i lgM response was significantly decreased to 24%. Conclusions: No correlation was found between IB results and treatment-related parameters. Thus, immunoblotting does not add to the clinical assessment of EM patients after treatment. Copyright (c) 2008 S. Karger AG, Basel

Cross-cultural adaptation of the Patient-Doctor Relationship Questionnaire (PDRQ-9) in Brazil

OBJECTIVE: To describe the process of cross-cultural adaptation of the Patient-Doctor Relationship Questionnaire (PDRQ-9), as well as compare the agreement between two different types of application. METHODS: This is a cross-sectional study with 133 adult users of a Primary Health Service in Porto Alegre, State of Rio Grande do Sul, Brazil. The PDRQ-9 was answered by the participants as a self-administered questionnaire and in an interview. The instrument was also validated by interview, using data from 628 participants of the Mais Médicos Program Evaluation Research, which is a cross-sectional study with a systematic sample of Primary Care Services in all regions of Brazil. We evaluated the semantic, conceptual, and item equivalence, as well as factor analysis and reliability. RESULTS: All items presented factor loading > 0.5 in the different methods of application and populations in the factor analysis. We found Cronbach's alpha of 0.94 in the self-administered method. We found Cronbach's alpha of 0.95 and 0.94 in the two different samples in the interview application. The use of PDRQ-9 with an interview or self-administered was considered equivalent. CONCLUSIONS: The cross-cultural adaptation of the PDRQ-9 in Brazil replicated the factorial structure found in the original study, with high internal consistency. The instrument can be used as a new dimension in the evaluation of the quality of health care in clinical research, in the evaluation of services and public health, in health management, and in professional training. Further studies can evaluate other properties of the instrument, as well as its behavior in different populations and contexts

Epigenetic regulation of COL15A1 in smooth muscle cell replicative aging and atherosclerosis

Smooth muscle cell (SMC) proliferation is a hallmark of vascular injury and disease. Global hypomethylation occurs during SMC proliferation in culture and in vivo during neointimal formation. Regardless of the programmed or stochastic nature of hypomethylation, identifying these changes is important in understanding vascular disease, as maintenance of a cells' epigenetic profile is essential for maintaining cellular phenotype. Global hypomethylation of proliferating aortic SMCs and concomitant decrease of DNMT1 expression were identified in culture during passage. An epigenome screen identified regions of the genome that were hypomethylated during proliferation and a region containing Collagen, type XV, alpha 1 (COL15A1) was selected by ‘genomic convergence' for characterization. COL15A1 transcript and protein levels increased with passage-dependent decreases in DNA methylation and the transcript was sensitive to treatment with 5-Aza-2′-deoxycytidine, suggesting DNA methylation-mediated gene expression. Phenotypically, knockdown of COL15A1 increased SMC migration and decreased proliferation and Col15a1 expression was induced in an atherosclerotic lesion and localized to the atherosclerotic cap. A sequence variant in COL15A1 that is significantly associated with atherosclerosis (rs4142986, P = 0.017, OR = 1.434) was methylated and methylation of the risk allele correlated with decreased gene expression and increased atherosclerosis in human aorta. In summary, hypomethylation of COL15A1 occurs during SMC proliferation and the consequent increased gene expression may impact SMC phenotype and atherosclerosis formation. Hypomethylated genes, such as COL15A1, provide evidence for concomitant epigenetic regulation and genetic susceptibility, and define a class of causal targets that sit at the intersection of genetic and epigenetic predisposition in the etiology of complex diseas

Oncogenic Neu/ErbB-2 Increases Ets, AP-1, and NF-B-dependent Gene Expression, and Inhibiting Ets Activation Blocks Neu-mediated Cellular Transformation

Overexpression of Neu (ErbB-2/HER2) is found in approximately 20% of breast tumors. Activation of Neu by a point mutation (NeuT) causes constitutive tyrosine kinase activity of this transmembrane receptor and transforming activity in fibroblasts. To identify downstream targets of Neu, we have analyzed the ability of Neu to activate gene expression. Expression of NeuT, but not normal Neu, caused transcriptional activation of Ets, AP-1, or NF-kappaB-dependent reporter genes. Dominant inhibitory Ras or Raf mutants blocked the Neu-mediated transcriptional activation, confirming that Ras signaling pathways were required for this activation. Analysis with Ets2 mutants indicated that activation of Ets2 transcriptional activity mediated by NeuT or oncogenic Ras required phosphorylation of the same Ets2 residue, threonine 72. Cotransfection of dominant inhibitory Ets2 mutants specifically blocked NeuT-mediated activation of Ets-dependent reporter genes. Furthermore, in focus formation assays using NIH 3T3 cells, the transforming activity of NeuT was inhibited 5-fold when NeuT was cotransfected with a dominant negative Ets2 mutant. However, parallel colony formation assays showed that the Ets2 dominant negative mutant did not inhibit the growth of normal cells. Together, these data show that NeuT activates a variety of transcription factor families via the Ras signaling pathway and that Ets activation is required for NeuT-mediated cellular transformation. Thus, downstream targets of Neu, including Ets transcription factors, may be useful points for therapeutic intervention in Neu/ErbB-2-associated cancers