Beyond the human genome: microbes, metaphors and what it means to be human in an interconnected post-genomic world

Four years after the completion of the Human Genome Project, the US National Institutes for Health launched the Human Microbiome Project on 19 December 2007. Using metaphor analysis, this article investigates reporting in English-language newspapers on advances in microbiomics from 2003 onwards, when the word “microbiome” was first used. This research was said to open up a “new frontier” and was conceived as a “second human genome project”, this time focusing on the genomes of microbes that inhabit and populate humans rather than focusing on the human genome itself. The language used by scientists and by the journalists who reported on their research employed a type of metaphorical framing that was very different from the hyperbole surrounding the decipherment of the “book of life”. Whereas during the HGP genomic successes had been mainly framed as being based on a unidirectional process of reading off information from a passive genetic or genomic entity, the language employed to discuss advances in microbiomics frames genes, genomes and life in much more active and dynamic ways.

Epigenetics and alternative splicing

Dissertação de Mestrado, Oncobiologia: Mecanismos Moleculares do Cancro, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

Systematic Improvement of Density Functionals through Parameter-Free Hybridization Schemes

It is suggested here that the ultimate accuracy of DFT methods arises from the type of hybridization scheme followed. This idea can be cast into a mathematical formulation utilizing an integrand connecting the noninteracting and the interacting particle system. We consider two previously developed models for it, dubbed as HYB0 and QIDH, and assess a large number of exchange-correlation functionals against the AE6, G2/148, and S22 reference data sets. An interesting consequence of these hybridization schemes is that the error bars, including the standard deviation, are found to markedly decrease with respect to the density-based (nonhybrid) case. This improvement is substantially better than variations due to the underlying density functional used. We thus finally hypothesize about the universal character of the HYB0 and QIDH models.

Development of an innovative non rule-based energy management strategy for a Hybrid Electric Vehicle, structured for predictive driving controls based on external information knowledge

Recently, the interest of the automotive market for hybrid vehicles has increased due to the more restrictive pollutants emissions legislation and to the necessity of decreasing the fossil fuel consumption, since such solution allows a consistent improvement of the vehicle global efficiency. The term hybridization regards the energy flow in the powertrain of a vehicle: a standard vehicle has, usually, only one energy source and one energy tank; instead, a hybrid vehicle has at least two energy sources. In most cases, the prime mover is an internal combustion engine (ICE) while the auxiliary energy source can be mechanical, electrical, pneumatic or hydraulic. It is expected from the control unit of a hybrid vehicle the use of the ICE in high efficiency working zones and to shut it down when it is more convenient, while using the EMG at partial loads and as a fast torque response during transients. However, the battery state of charge may represent a limitation for such a strategy. That’s the reason why, in most cases, energy management strategies are based on the State Of Charge, or SOC, control. Several studies have been conducted on this topic and many different approaches have been illustrated. The purpose of this dissertation is to develop an online (usable on-board) control strategy in which the operating modes are defined using an instantaneous optimization method that minimizes the equivalent fuel consumption of a hybrid electric vehicle. The equivalent fuel consumption is calculated by taking into account the total energy used by the hybrid powertrain during the propulsion phases. The first section presents the hybrid vehicles characteristics. The second chapter describes the global model, with a particular focus on the energy management strategies usable for the supervisory control of such a powertrain. The third chapter shows the performance of the implemented controller on a NEDC cycle compared with the one obtained with the original control strategy.

Label-free oligonucleotide biosensor based on dual-peak long period fiber grating

We report the simplification and development of biofunctionalization methodology based on one-step 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC)-mediated reaction. The dual-peak long period grating (dLPG) has been demonstrated its inherent ultrahigh sensitivity to refractive index (RI), achieving 50-fold improvement in RI sensitivity over a standard LPG sensor used in low RI range. With the simple and efficient immobilization of unmodified oligonucleotides on sensor surface, dLPG-based biosensor has been used to monitor the hybridization of complementary oligonucleotides showing a detectable oligonucleotide concentration of 4 nM with the advantages of label-free, real-time, and ultrahigh sensitivity.

Exploring novel targeted therapeutic strategies against Acute Myeloid Leukemia cells based on inhibition of bromodomain proteins and CDC20 activity

Acute myeloid leukemia (AML) is a haematological malignancies arising from the accumulation of undifferentiated myeloid progenitors with an uncontrolled proliferation. The genomic landscape of AML revealed that the disease is characterized by high level of heterogeneity and is subjected to clonal evolution driven by selective pressure of chemotherapy. In this study, we investigated the therapeutic effects of the inhibition of BRD4 and CDC20 in vitro and ex vivo. We demonstrated that inhibition of BRD4 with GSK1215101A in AML cell lines was effective under hypoxia. It induced the activation of antioxidant response both, at transcriptomic and metabolomic levels, driven by enrichment of NRF2 pathway under normoxic and hypoxic condition. Moreover, the combined treatment with Omaveloxolone, a drug inducing NRF2 activation and NF-κB inhibition, potentiated the effects on apoptosis and colony forming capacity of stem progenitor cells. Lastly, gene expression profiling data revealed that combination treatment induced major changes in genes related to cell cycle, together with enrichment of cell differentiation pathways and negative regulation of WNT, in normoxia and hypoxia. Regarding CDC20, we observed its up-regulation in AML patients. Treatment with two different inhibitors, Apcin and proTAME, was effective in primary AML cells and in AML cell lines, through induction of apoptosis and mitotic arrest. The lack of correlation between proliferation markers and CDC20 levels in AML cell subpopulations supports the idea of alternative CDC20 functions, independent from its essential role during mitosis. CDC20-KD experiments conducted in AML cell lines revealed a mild effect on apoptosis induction, but no significant change in cell cycle progression. In summary, these results allowed the identification of a new strategy combination to improve the effects of BRD4 inhibition on LSC residing in the BM hypoxic niche, and provide some new evidence regarding the potential role of CDC20 as a new target for AML treatment.

Moving toward stock units identification based on spatial population structure of marine species in the Mediterranean Sea and adjacent waters through multidisciplinary and holistic approaches for the sustainability of fisheries resources

Investigating stock identity of marine species in a multidisciplinary holistic approach can reveal patterns of complex spatial population structure and signatures of potential local adaptation. The population structure of common sole (Solea solea) in the Mediterranean Sea was delineated using genomic and otolith data, including single nucleotide polymorphisms (SNPs) markers and otolith data. SNPs were correlated with environmental and spatial variables to evaluate the impact of these features on the actual genetic population structure. Integrated holistic approach was applied to combine the tracers with different spatio-temporal scales. SNPs data was also used to illustrate the population structure of European hake (Merluccius merluccius) within the Alboran Sea, extending into the neighboring Mediterranean Sea and Atlantic Ocean. The aim was to identify patterns of neutral and potential adaptive genetic variation by applying seascape genomic framework. Results from both genetic and otolith data suggested significant divergence among putative populations of common sole, confirming a clear separation between Western, Adriatic Sea and Eastern Mediterranean Sea. Evidence of fine-scale population structure in the Western Mediterranean Sea was observed at outlier loci level and in the Adriatic. Our study not only indicates that separation among Mediterranean sole population is led primarily by neutral processes, but it also suggests the presence of local adaptation influenced by environmental and spatial factors. The holistic approach by considering the spatio-temporal scales of variation confirmed that the same pattern of separation between these geographical sites is currently occurring and has occurred for many generations. Results showed the occurrence of population structure in Merluccius merluccius by detecting westward–eastward differentiation among populations and distinct subgroups at a fine geographical scale using outlier SNPs. These results enhance the knowledge of the population structure of commercially relevant species to support the application of spatial stock assessment models, including a redefinition of fishery management units.

Applied genomics to monitor the genetic diversity and integrity of honey bee (Apis mellifera) populations and define sustainable strategies to benefit the beekeeping sector

Honey bees are considered keystone species in ecosystem, the effect of harmful pesticides for the honey bees, the action of extreme climatic waves and their consequence on honey bees health can cause the loss of many colonies which could contribute to the reduction of the effective population size and incentive the use of non-autochthonous queens to replace dead colonies. Over the last decades, the use of non-ligustica bee subspecies in Italy has increased and together with the mentioned phenomena exposed native honey bees to hybridization, laeding to a dramatic loss of genetic erosion and admixture. Healthy genetic diversity within honey bee populations is critical to provide tolerance and resistance to current and future threatening. Nowadays it is urgent to design strategies for the conservation of local subspecies and their valorisation on a productive scale. In this Thesis we applied genomics tool for the analysis of the genetic diversity and the genomic integrity of honey bee populations in Italy are described. In this work mtDNA based methods are presented using honey bee DNA or honey eDNA as source of information of the genetic diversity of A. mellifera at different level. Taken together, the results derived from these studies should enlarge the knowledge of the genetic diversity and integrity of the honey bee populations in Italy, filling the gap of information necessary to design efficient conservation programmes. Furthermore, the methods presented in these works will provide a tool for the honey authentication to sustain and valorise beekeeping products and sector against frauds.

Work environments implementation for genomic reporting and analytics

A global italian pharmaceutical company has to provide two work environments that favor different needs. The environments will allow to develop solutions in a controlled, secure and at the same time in an independent manner on a state-of-the-art enterprise cloud platform. The need of developing two different environments is dictated by the needs of the working units. Indeed, the first environment is designed to facilitate the creation of application related to genomics, therefore, designed more for data-scientists. This environment is capable of consuming, producing, retrieving and incorporating data, furthermore, will support the most used programming languages for genomic applications (e.g., Python, R). The proposal was to obtain a pool of ready-togo Virtual Machines with different architectures to provide best performance based on the job that needs to be carried out. The second environment has more of a traditional trait, to obtain, via ETL (Extract-Transform-Load) process, a global datamodel, resembling a classical relational structure. It will provide major BI operations (e.g., analytics, performance measure, reports, etc.) that can be leveraged both for application analysis or for internal usage. Since, both architectures will maintain large amounts of data regarding not only pharmaceutical informations but also internal company informations, it would be possible to digest the data by reporting/ analytics tools and also apply data-mining, machine learning technologies to exploit intrinsic informations. The thesis work will introduce, proposals, implementations, descriptions of used technologies/platforms and future works of the above discussed environments.

[almost An Autobiography: A Study Of Social Scientists In Health Based On The Lattes Curriculum].

Among the various ways of adopting the biographical approach, we used the curriculum vitaes (CVs) of Brazilian researchers who work as social scientists in health as our research material. These CVs are part of the Lattes Platform of CNPq - the National Council for Scientific and Technological Development, which includes Research and Institutional Directories. We analyzed 238 CVs for this study. The CVs contain, among other things, the following information: professional qualifications, activities and projects, academic production, participation in panels for the evaluation of theses and dissertations, research centers and laboratories and a summarized autobiography. In this work there is a brief review of the importance of autobiography for the social sciences, emphasizing the CV as a form of autobiographical practice. We highlight some results, such as it being a group consisting predominantly of women, graduates in social sciences, anthropology, sociology or political science, with postgraduate degrees. The highest concentration of social scientists is located in Brazil's southern and southeastern regions. In some institutions the main activities of social scientists are as teachers and researchers with great thematic diversity in research.

Phylogenetics, Ancestral State Reconstruction, And A New Infrafamilial Classification Of The Pantropical Ochnaceae (medusagynaceae, Ochnaceae S.str., Quiinaceae) Based On Five Dna Regions.

Ochnaceae s.str. (Malpighiales) are a pantropical family of about 500 species and 27 genera of almost exclusively woody plants. Infrafamilial classification and relationships have been controversial partially due to the lack of a robust phylogenetic framework. Including all genera except Indosinia and Perissocarpa and DNA sequence data for five DNA regions (ITS, matK, ndhF, rbcL, trnL-F), we provide for the first time a nearly complete molecular phylogenetic analysis of Ochnaceae s.l. resolving most of the phylogenetic backbone of the family. Based on this, we present a new classification of Ochnaceae s.l., with Medusagynoideae and Quiinoideae included as subfamilies and the former subfamilies Ochnoideae and Sauvagesioideae recognized at the rank of tribe. Our data support a monophyletic Ochneae, but Sauvagesieae in the traditional circumscription is paraphyletic because Testulea emerges as sister to the rest of Ochnoideae, and the next clade shows Luxemburgia+Philacra as sister group to the remaining Ochnoideae. To avoid paraphyly, we classify Luxemburgieae and Testuleeae as new tribes. The African genus Lophira, which has switched between subfamilies (here tribes) in past classifications, emerges as sister to all other Ochneae. Thus, endosperm-free seeds and ovules with partly to completely united integuments (resulting in an apparently single integument) are characters that unite all members of that tribe. The relationships within its largest clade, Ochnineae (former Ochneae), are poorly resolved, but former Ochninae (Brackenridgea, Ochna) are polyphyletic. Within Sauvagesieae, the genus Sauvagesia in its broad circumscription is polyphyletic as Sauvagesia serrata is sister to a clade of Adenarake, Sauvagesia spp., and three other genera. Within Quiinoideae, in contrast to former phylogenetic hypotheses, Lacunaria and Touroulia form a clade that is sister to Quiina. Bayesian ancestral state reconstructions showed that zygomorphic flowers with adaptations to buzz-pollination (poricidal anthers), a syncarpous gynoecium (a near-apocarpous gynoecium evolved independently in Quiinoideae and Ochninae), numerous ovules, septicidal capsules, and winged seeds with endosperm are the ancestral condition in Ochnoideae. Although in some lineages poricidal anthers were lost secondarily, the evolution of poricidal superstructures secured the maintenance of buzz-pollination in some of these genera, indicating a strong selective pressure on keeping that specialized pollination system.

Ihwg-μnir: A Miniaturised Near-infrared Gas Sensor Based On Substrate-integrated Hollow Waveguides Coupled To A Micro-nir-spectrophotometer.

A miniaturised gas analyser is described and evaluated based on the use of a substrate-integrated hollow waveguide (iHWG) coupled to a microsized near-infrared spectrophotometer comprising a linear variable filter and an array of InGaAs detectors. This gas sensing system was applied to analyse surrogate samples of natural fuel gas containing methane, ethane, propane and butane, quantified by using multivariate regression models based on partial least square (PLS) algorithms and Savitzky-Golay 1(st) derivative data preprocessing. The external validation of the obtained models reveals root mean square errors of prediction of 0.37, 0.36, 0.67 and 0.37% (v/v), for methane, ethane, propane and butane, respectively. The developed sensing system provides particularly rapid response times upon composition changes of the gaseous sample (approximately 2 s) due the minute volume of the iHWG-based measurement cell. The sensing system developed in this study is fully portable with a hand-held sized analyser footprint, and thus ideally suited for field analysis. Last but not least, the obtained results corroborate the potential of NIR-iHWG analysers for monitoring the quality of natural gas and petrochemical gaseous products.

Can We Predict The Clinical Outcomes Of Genitourinary Trauma Patients And Offer Them An Evidence-based Support? The Case For Telemedicine Network.

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Iis--integrated Interactome System: A Web-based Platform For The Annotation, Analysis And Visualization Of Protein-metabolite-gene-drug Interactions By Integrating A Variety Of Data Sources And Tools.

High-throughput screening of physical, genetic and chemical-genetic interactions brings important perspectives in the Systems Biology field, as the analysis of these interactions provides new insights into protein/gene function, cellular metabolic variations and the validation of therapeutic targets and drug design. However, such analysis depends on a pipeline connecting different tools that can automatically integrate data from diverse sources and result in a more comprehensive dataset that can be properly interpreted. We describe here the Integrated Interactome System (IIS), an integrative platform with a web-based interface for the annotation, analysis and visualization of the interaction profiles of proteins/genes, metabolites and drugs of interest. IIS works in four connected modules: (i) Submission module, which receives raw data derived from Sanger sequencing (e.g. two-hybrid system); (ii) Search module, which enables the user to search for the processed reads to be assembled into contigs/singlets, or for lists of proteins/genes, metabolites and drugs of interest, and add them to the project; (iii) Annotation module, which assigns annotations from several databases for the contigs/singlets or lists of proteins/genes, generating tables with automatic annotation that can be manually curated; and (iv) Interactome module, which maps the contigs/singlets or the uploaded lists to entries in our integrated database, building networks that gather novel identified interactions, protein and metabolite expression/concentration levels, subcellular localization and computed topological metrics, GO biological processes and KEGG pathways enrichment. This module generates a XGMML file that can be imported into Cytoscape or be visualized directly on the web. We have developed IIS by the integration of diverse databases following the need of appropriate tools for a systematic analysis of physical, genetic and chemical-genetic interactions. IIS was validated with yeast two-hybrid, proteomics and metabolomics datasets, but it is also extendable to other datasets. IIS is freely available online at: http://www.lge.ibi.unicamp.br/lnbio/IIS/.

Cluster Analysis To Identify Elderly People's Profiles: A Healthcare Strategy Based On Frailty Characteristics.

The new social panorama resulting from aging of the Brazilian population is leading to significant transformations within healthcare. Through the cluster analysis strategy, it was sought to describe the specific care demands of the elderly population, using frailty components. Cross-sectional study based on reviewing medical records, conducted in the geriatric outpatient clinic, Hospital de Clínicas, Universidade Estadual de Campinas (Unicamp). Ninety-eight elderly users of this clinic were evaluated using cluster analysis and instruments for assessing their overall geriatric status and frailty characteristics. The variables that most strongly influenced the formation of clusters were age, functional capacities, cognitive capacity, presence of comorbidities and number of medications used. Three main groups of elderly people could be identified: one with good cognitive and functional performance but with high prevalence of comorbidities (mean age 77.9 years, cognitive impairment in 28.6% and mean of 7.4 comorbidities); a second with more advanced age, greater cognitive impairment and greater dependence (mean age 88.5 years old, cognitive impairment in 84.6% and mean of 7.1 comorbidities); and a third younger group with poor cognitive performance and greater number of comorbidities but functionally independent (mean age 78.5 years old, cognitive impairment in 89.6% and mean of 7.4 comorbidities). These data characterize the profile of this population and can be used as the basis for developing efficient strategies aimed at diminishing functional dependence, poor self-rated health and impaired quality of life.