Data-driven identification of structural alerts for mitigating the risk of drug-induced human liver injuries

El presente trabajo propone, tomando como eje los postulados de Iuri Lotman acerca de la memoria, una lectura de la novela Los pichiciegos (1984), del escritor argentino Rodolfo Enrique Fogwill (1941-2010). Escrito en paralelo a la guerra de las Malvinas, este relato pone en cuestión la narrativa oficial de la guerra y problematiza, en clave literaria, las tensiones entre memoria y ficción en la construcción de un acontecimiento relevante de la historia latinoamericana. De este modo, nuestro trabajo propone un abordaje, desde el campo de la semiótica de la cultura, de las complejas relaciones entre memoria y ficción.From the perspective of Iuri Lotman´s concept about memory, this paper propose a reading of Los pichiciegos, novel that wrote by the Argentinian author Rodolfo Enrique Fogwill (1941-2010). Written at the same moment of Falklans War happens, this story calls into question the official narrative of the war and discuss, in literary key, boundaries between memory and fiction on contemporary Latin-American history. Thus, from the field of Cultural Semiotics, our work proposes an approach of the complex relationship between memory and fiction in Los Pichiciegos.Aquest treball proposa, prenent com a eix els postulats de Iuri Lotman sobre la memòria, una lectura de la novel·la Los pichiciegos (1984), de l'escriptor argentí Rodolfo Enrique Fogwill (1941-2010). Escrit en paral·lel a la guerra de les Malvines, aquest relat posa en qüestió la narrativa oficial de la guerra i problematitza, en clau literària, les tensions entre memòria i ficció en construir un esdeveniment rellevant de la història llatinoamericana. D'aquesta manera, el nostre treball proposa un abordatge, des del camp de la semiòtica de la cultura, de les complexes relacions entre memòria i ficció

Influence of Protein Abundance on High-Throughput Protein-Protein Interaction Detection

Experimental protein-protein interaction (PPI) networks are increasingly being exploited in diverse ways for biological discovery. Accordingly, it is vital to discern their underlying natures by identifying and classifying the various types of deterministic (specific) and probabilistic (nonspecific) interactions detected. To this end, we have analyzed PPI networks determined using a range of high-throughput experimental techniques with the aim of systematically quantifying any biases that arise from the varying cellular abundances of the proteins. We confirm that PPI networks determined using affinity purification methods for yeast and Eschericia coli incorporate a correlation between protein degree, or number of interactions, and cellular abundance. The observed correlations are small but statistically significant and occur in both unprocessed (raw) and processed (high-confidence) data sets. In contrast, the yeast two-hybrid system yields networks that contain no such relationship. While previously commented based on mRNA abundance, our more extensive analysis based on protein abundance confirms a systematic difference between PPI networks determined from the two technologies. We additionally demonstrate that the centrality-lethality rule, which implies that higher-degree proteins are more likely to be essential, may be misleading, as protein abundance measurements identify essential proteins to be more prevalent than nonessential proteins. In fact, we generally find that when there is a degree/abundance correlation, the degree distributions of nonessential and essential proteins are also disparate. Conversely, when there is no degree/abundance correlation, the degree distributions of nonessential and essential proteins are not different. However, we show that essentiality manifests itself as a biological property in all of the yeast PPI networks investigated here via enrichments of interactions between essential proteins. These findings provide valuable insights into the underlying natures of the various high-throughput technologies utilized to detect PPIs and should lead to more effective strategies for the inference and analysis of high-quality PPI data sets

Bio-inspired Design and Fabrication of Super-Strong and Multifunctional Carbon Nanotube Composites

Carbon nanotubes (CNTs) are ideal scaffolds to design and architect high-performance composites at high CNT volume fractions. In these composites, the CNT alignment determines the level of aggregation and the structure morphology, and thus the load transfer efficiency between neighboring CNTs. Here, we discuss two major solutions to produce high-volume fraction CNT composites, namely the layer-by-layer stacking of aligned CNT sheets and the stretching of entangled CNT webs (networks). As inspired by the growth procedure of natural composites, the aggregation of CNTs can be well controlled during the assembling process. As a result, the CNTs can be highly packed, aligned, and importantly unaggregated, with the impregnated polymers acting as interfacial adhesion or mortars to build up the composite structure. The CNT/bismaleimide composites can yield a super-high tensile strength up to 6.27–6.94 GPa and a modulus up to 315 GPa

Identification of tissue-specific cis-regulatory modules based on interactions between transcription factors

<p>Abstract</p> <p>Background</p> <p>Evolutionary conservation has been used successfully to help identify cis-acting DNA regions that are important in regulating tissue-specific gene expression. Motivated by increasing evidence that some DNA regulatory regions are not evolutionary conserved, we have developed an approach for cis-regulatory region identification that does not rely upon evolutionary sequence conservation.</p> <p>Results</p> <p>The conservation-independent approach is based on an empirical potential energy between interacting transcription factors (TFs). In this analysis, the potential energy is defined as a function of the number of TF interactions in a genomic region and the strength of the interactions. By identifying sets of interacting TFs, the analysis locates regions enriched with the binding sites of these interacting TFs. We applied this approach to 30 human tissues and identified 6232 putative cis-regulatory modules (CRMs) regulating 2130 tissue-specific genes. Interestingly, some genes appear to be regulated by different CRMs in different tissues. Known regulatory regions are highly enriched in our predicted CRMs. In addition, DNase I hypersensitive sites, which tend to be associated with active regulatory regions, significantly overlap with the predicted CRMs, but not with more conserved regions. We also find that conserved and non-conserved CRMs regulate distinct gene groups. Conserved CRMs control more essential genes and genes involved in fundamental cellular activities such as transcription. In contrast, non-conserved CRMs, in general, regulate more non-essential genes, such as genes related to neural activity.</p> <p>Conclusion</p> <p>These results demonstrate that identifying relevant sets of binding motifs can help in the mapping of DNA regulatory regions, and suggest that non-conserved CRMs play an important role in gene regulation.</p

BTLA/HVEM Signaling: Milestones in Research and Role in Chronic Hepatitis B Virus Infection

B- and T-lymphocyte attenuator (BTLA) is an immune-regulatory receptor, similar to CTLA-4 and PD-1, and is mainly expressed on B-, T-, and all mature lymphocyte cells. Herpes virus entry mediator (HVEM)-BTLA plays a critical role in immune tolerance and immune responses which are areas of intense research. However, the mechanisms of the BTLA and the BTLA/HVEM signaling pathway in human diseases remain unclear. This review describes the research milestones of BTLA and HVEM in chronological order and their role in chronic HBV infection

TiGER: A database for tissue-specific gene expression and regulation

<p>Abstract</p> <p>Background</p> <p>Understanding how genes are expressed and regulated in different tissues is a fundamental and challenging question. However, most of currently available biological databases do not focus on tissue-specific gene regulation.</p> <p>Results</p> <p>The recent development of computational methods for tissue-specific combinational gene regulation, based on transcription factor binding sites, enables us to perform a large-scale analysis of tissue-specific gene regulation in human tissues. The results are stored in a web database called TiGER (Tissue-specific Gene Expression and Regulation). The database contains three types of data including tissue-specific gene expression profiles, combinatorial gene regulations, and cis-regulatory module (CRM) detections. At present the database contains expression profiles for 19,526 UniGene genes, combinatorial regulations for 7,341 transcription factor pairs and 6,232 putative CRMs for 2,130 RefSeq genes.</p> <p>Conclusion</p> <p>We have developed and made publicly available a database, TiGER, which summarizes and provides large scale data sets for tissue-specific gene expression and regulation in a variety of human tissues. This resource is available at <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>.</p

MnOx-SiO2系ナノ粒子の免疫療法および他療法との併用療法への応用

早大学位記番号:新9263博士(工学)早稲田大

Effect of passive finger exercises on grip strength and the ability to perform activities of daily living for older people with dementia: a 12-week randomized controlled trial

Background: Dementia adds burden to society. As it is not curable, physical exercise activities are optimal to improve the physical strength and quality-of-life of people with dementia. Aim: Design, implementation, and examination of a set of passive finger exercises and their effects on improving grip strength and activities of daily living (ADL) for older people with dementia. Methods: Forty older people with dementia were recruited and randomly allocated into an experimental group and a control group, each with 20 people. The control group received routine nursing care. In addition to this, the experimental group received 25-minutes of passive finger exercises every day for 12 weeks. The health outcomes measured were grip strength and ADL, before and after the intervention. Grip strength was assessed by electrical hand muscle dynamometer. ADL were assessed with Barthel index. Results: Although there was no effect on grip strength, passive finger exercises led to significant improvements in urinary control, defecation function, and overall ADL in comparison with the control group. Implications for practice: Passive finger exercises can be integrated into physical exercise programs for older people with dementia to improve their urinary control, defecation function, and ADL

Analysis of regulatory network topology reveals functionally distinct classes of microRNAs

MicroRNAs (miRNAs) negatively regulate the expression of target genes at the post-transcriptional level. Little is known about the crosstalk between miRNAs and transcription factors (TFs). Here we provide data suggesting that the interaction patterns between TFs and miRNAs can influence the biological functions of miRNAs. From this global survey, we find that a regulated feedback loop, in which two TFs regulate each other and one miRNA regulates both of the factors, is the most significantly overrepresented network motif. Mathematical modeling shows that the miRNA in this motif stabilizes the feedback loop to resist environmental perturbation, providing one mechanism to explain the robustness of developmental programs that is contributed by miRNAs. Furthermore, on the basis of a network motif profile analysis, we demonstrate the existence of two classes of miRNAs with distinct network topological properties. The first class of miRNAs is regulated by a large number of TFs, whereas the second is regulated by only a few TFs. The differential expression level of the two classes of miRNAs in embryonic developmental stages versus adult tissues suggests that the two classes may have fundamentally different biological functions. Our results demonstrate that the TFs and miRNAs extensively interact with each other and the biological functions of miRNAs may be wired in the regulatory network topology