Beauty\u27s Eyes

https://digitalcommons.library.umaine.edu/mmb-vp/5837/thumbnail.jp

DNA methylation changes in response to neoadjuvant chemotherapy are associated with breast cancer survival

Background: Locally advanced breast cancer is a heterogeneous disease with respect to response to neoadjuvant chemotherapy (NACT) and survival. It is currently not possible to accurately predict who will benefit from the specific types of NACT. DNA methylation is an epigenetic mechanism known to play an important role in regulating gene expression and may serve as a biomarker for treatment response and survival. We investigated the potential role of DNA methylation as a prognostic marker for long-term survival (> 5 years) after NACT in breast cancer. Methods: DNA methylation profiles of pre-treatment (n = 55) and post-treatment (n = 75) biopsies from 83 women with locally advanced breast cancer were investigated using the Illumina HumanMethylation450 BeadChip. The patients received neoadjuvant treatment with epirubicin and/or paclitaxel. Linear mixed models were used to associate DNA methylation to treatment response and survival based on clinical response to NACT (partial response or stable disease) and 5-year survival, respectively. LASSO regression was performed to identify a risk score based on the statistically significant methylation sites and Kaplan–Meier curve analysis was used to estimate survival probabilities using ten years of survival follow-up data. The risk score developed in our discovery cohort was validated in an independent validation cohort consisting of paired pre-treatment and post-treatment biopsies from 85 women with locally advanced breast cancer. Patients included in the validation cohort were treated with either doxorubicin or 5-FU and mitomycin NACT. Results: DNA methylation patterns changed from before to after NACT in 5-year survivors, while no significant changes were observed in non-survivors or related to treatment response. DNA methylation changes included an overall loss of methylation at CpG islands and gain of methylation in non-CpG islands, and these changes affected genes linked to transcription factor activity, cell adhesion and immune functions. A risk score was developed based on four methylation sites which successfully predicted long-term survival in our cohort (p = 0.0034) and in an independent validation cohort (p = 0.049). Conclusion: Our results demonstrate that DNA methylation patterns in breast tumors change in response to NACT. These changes in DNA methylation show potential as prognostic biomarkers for breast cancer survival.publishedVersio

Analysis and annotation of DNA methylation in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips

Aim: Nonhuman primates are essential for research on many human diseases. The Infinium Human Methylation450/EPIC BeadChips are popular tools for the study of the methylation state across the human genome at affordable cost. Methods: We performed a precise evaluation and re-annotation of the BeadChip probes for the analysis of genome-wide DNA methylation patterns in rhesus macaques and African green monkeys through in silico analyses combined with functional validation by pyrosequencing. Results: Up to 165,847 of the 450K and 261,545 probes of the EPIC BeadChip can be reliably used. The annotation files are provided in a format compatible with a variety of standard bioinformatic pipelines. Conclusion: Our study will facilitate high-throughput DNA methylation analyses in Macaca mulatta and Chlorocebus sabaeus.Host-parasite interactio

A General Framework for Interrogation of mRNA Stability Programs Identifies RNA-Binding Proteins that Govern Cancer Transcriptomes

Widespread remodeling of the transcriptome is a signature of cancer; however, little is known about the post-transcriptional regulatory factors, including RNA-binding proteins (RBPs) that regulate mRNA stability, and the extent to which RBPs contribute to cancer-associated pathways. Here, by modeling the global change in gene expression based on the effect of sequence-specific RBPs on mRNA stability, we show that RBP-mediated stability programs are recurrently deregulated in cancerous tissues. Particularly, we uncovered several RBPs that contribute to the abnormal transcriptome of renal cell carcinoma (RCC), including PCBP2, ESRP2, and MBNL2. Modulation of these proteins in cancer cell lines alters the expression of pathways that are central to the disease and highlights RBPs as driving master regulators of RCC transcriptome. This study presents a framework for the screening of RBP activities based on computational modeling of mRNA stability programs in cancer and highlights the role of post-transcriptional gene dysregulation in RCC. Perron et al. develop a computational approach that models the functional activity of RBPs in individual cancer samples by monitoring their associated RNA stability programs. Applying this method to renal cell carcinoma transcriptomes, the authors identify RBPs that enhance cancer-associated pathways including hypoxia and cell cycle

Brain state stability during working memory is explained by network control theory, modulated by dopamine D1/D2 receptor function, and diminished in schizophrenia

Dynamical brain state transitions are critical for flexible working memory but the network mechanisms are incompletely understood. Here, we show that working memory entails brainwide switching between activity states. The stability of states relates to dopamine D1 receptor gene expression while state transitions are influenced by D2 receptor expression and pharmacological modulation. Schizophrenia patients show altered network control properties, including a more diverse energy landscape and decreased stability of working memory representations

Disfunção pré-frontoparietal durante o processamento de informação visuoauditiva em pacientes idosos com esquizofrenia crônica e efeitos da medicação

OBJECTIVES: In first-episode schizophrenia patients, functional magnetic resonance imaging (fMRI) has shown prefronto-parietal dysfunction during acoustic and visual stimulation. The aim of this study was to investigate the prefronto-parietal network in elderly schizophrenia patients using the same paradigm. Additionally, we hypothesized favourable effects on brain activation by the atypical antipsychotic clozapine compared to typical neuroleptics. METHODS: We investigated 18 elderly, chronic schizophrenia patients and 21 elderly healthy controls. Nine schizophrenia patients had been medicated with clozapine and 9 had been receiving typical neuroleptics over decades. In addition to assessments with psychopathological and neuropsychological rating scales we used an acoustic and visual stimulation paradigm in a 1.5 Tesla MRI scanner to investigate BOLD-response in different brain areas. RESULTS: Compared to healthy controls schizophrenia patients showed decreased brain activation in the prefrontal and parietal cortex as well as medial anterior cingulate gyrus compared to healthy controls. In these regions, patients medicated with clozapine showed increased BOLD-response compared to patients treated with typical neuroleptics. DISCUSSION: Our study confirmed prefronto-parietal network disturbances in elderly schizophrenia patients thus pointing to the preservation of brain activation deficits and the influence of neurodevelopmental disturbances in chronic schizophrenia until old-age. CONCLUSION: The atypical antipsychotic clozapine seems to facilitate brain activation even in elderly, chronic schizophrenia patients.OBJETIVOS: Em pacientes com primeiro episódio de esquizofrenia, estudos com ressonância magnética funcional (RMf) têm demonstrado disfunção pré-frontoparietal durante estimulação acústica e visual. O objetivo do presente estudo foi investigar a rede pré-frontoparietal em pacientes idosos com esquizofrenia utilizando o mesmo paradigma. Adicionalmente, foram presumidos efeitos favoráveis na ativação cerebral pelo antipsicótico atípico clozapina em comparação a neurolépticos típicos. MÉTODOS: Foram investigados 18 pacientes com esquizofrenia crônica e 21 controles saudáveis idosos. Nove pacientes com esquizofrenia haviam sido medicados com clozapina e nove haviam recebido neurolépticos típicos por décadas. Concomitantemente às avaliações com escalas psicopatológicas e neuropsicológicas foi utilizado um paradigma de estimulação auditiva e visual em um aparelho de ressonância magnética de 1,5 Tesla para investigar a resposta BOLD em diferentes áreas cerebrais. RESULTADOS: Comparados a controles saudáveis, os pacientes com esquizofrenia apresentaram diminuição na ativação cerebral nos córtices pré-frontal e parietal, assim como no giro do cíngulo anterior medial. Nessas regiões, os pacientes medicados com clozapina apresentaram resposta BOLD aumentada em comparação aos pacientes tratados com neurolépticos típicos. DISCUSSÃO: O presente estudo confirmou a presença de distúrbios na rede pré-frontoparietal em pacientes idosos com esquizofrenia, apontando assim para a preservação de déficits de ativação cerebrais e a influência de distúrbios do desenvolvimento neural em esquizofrenia crônica até a velhice. CONCLUSÃO: O antipsicótico atípico clozapina parece facilitar a ativação de áreas cerebrais mesmo em pacientes idosos com esquizofrenia crônica

Position-dependent effects of locked nucleic acid (LNA) on DNA sequencing and PCR primers

Genomes are becoming heavily annotated with important features. Analysis of these features often employs oligonucleotides that hybridize at defined locations. When the defined location lies in a poor sequence context, traditional design strategies may fail. Locked Nucleic Acid (LNA) can enhance oligonucleotide affinity and specificity. Though LNA has been used in many applications, formal design rules are still being defined. To further this effort we have investigated the effect of LNA on the performance of sequencing and PCR primers in AT-rich regions, where short primers yield poor sequencing reads or PCR yields. LNA was used in three positional patterns: near the 5′ end (LNA-5′), near the 3′ end (LNA-3′) and distributed throughout (LNA-Even). Quantitative measures of sequencing read length (Phred Q30 count) and real-time PCR signal (cycle threshold, C(T)) were characterized using two-way ANOVA. LNA-5′ increased the average Phred Q30 score by 60% and it was never observed to decrease performance. LNA-5′ generated cycle thresholds in quantitative PCR that were comparable to high-yielding conventional primers. In contrast, LNA-3′ and LNA-Even did not improve read lengths or C(T). ANOVA demonstrated the statistical significance of these results and identified significant interaction between the positional design rule and primer sequence

Informe de la atención bucodental en el servicio de odontología de la Villa Olímpica durante los Juegos de la XXV Olimpiada Barcelona 92

Durante la celebración de los Juegos Olirnpicos de Barcelona, la Villa Olirnpica dispuso de un servicio de odontología para la atención de las urgencias odontoestomatológícas que pudieran producirse entre el conJunto de la familia olímpica. Los autores informan de la atención prestada por dicho servicio, siendo de destacar la elevada cantidad de tratamientos efectuados, situándose el servicio entre los más concurridos de la Policlínica Olímpica. Se pone de manifiesto el mal estado bucodental de muchos de los participantes, que contrasta con el teórico estricto control médico a que se ven sometidos la mayor parte de los atleta

Cyclic animation using Partial differential Equations

YesThis work presents an efficient and fast method for achieving cyclic animation using Partial Differential Equations (PDEs). The boundary-value nature associ- ated with elliptic PDEs offers a fast analytic solution technique for setting up a framework for this type of animation. The surface of a given character is thus cre- ated from a set of pre-determined curves, which are used as boundary conditions so that a number of PDEs can be solved. Two different approaches to cyclic ani- mation are presented here. The first consists of using attaching the set of curves to a skeletal system hold- ing the animation for cyclic motions linked to a set mathematical expressions, the second one exploits the spine associated with the analytic solution of the PDE as a driving mechanism to achieve cyclic animation, which is also manipulated mathematically. The first of these approaches is implemented within a framework related to cyclic motions inherent to human-like char- acters, whereas the spine-based approach is focused on modelling the undulatory movement observed in fish when swimming. The proposed method is fast and ac- curate. Additionally, the animation can be either used in the PDE-based surface representation of the model or transferred to the original mesh model by means of a point to point map. Thus, the user is offered with the choice of using either of these two animation repre- sentations of the same object, the selection depends on the computing resources such as storage and memory capacity associated with each particular application