Search results for "Key"
showing 10 items of 1962 documents
Disease–Genes Must Guide Data Source Integration in the Gene Prioritization Process
2019
One of the main issues in detecting the genes involved in the etiology of genetic human diseases is the integration of different types of available functional relationships between genes. Numerous approaches exploited the complementary evidence coded in heterogeneous sources of data to prioritize disease-genes, such as functional profiles or expression quantitative trait loci, but none of them to our knowledge posed the scarcity of known disease-genes as a feature of their integration methodology. Nevertheless, in contexts where data are unbalanced, that is, where one class is largely under-represented, imbalance-unaware approaches may suffer a strong decrease in performance. We claim that …
Scientific Reports
2019
Anthropogenic climate change ranks among the major global-scale threats to modern biodiversity. Extinction risks are known to increase via the interactions between rapid climatic alterations and environmentally-sensitive species traits that fail to adapt to those changes. Accumulating evidence reveals the influence of ecophysiological, ecological and phenological factors as drivers underlying demographic collapses that lead to population extinctions. However, the extent to which life-history traits influence population responses to climate change remains largely unexplored. The emerging 'cul-de-sac hypothesis' predicts that reptilian viviparity ('live-bearing' reproduction), a 'key innovati…
Bioequivalence decision for nanoparticular iron complex drugs for parenteral administration based on their disposition
2017
Although parenteral iron products have been established to medicinal use decades before, their structure and pharmacokinetic properties are not fully characterized yet. With its' second reflection paper on intravenous iron-based nano-colloidal products (EMA/CHMP/SWP/620008/2012) the European Medicine Agency provided an extensive catalogue of methods for quality, non-clinical and pharmacokinetic studies for the comparison of nano-sized iron products to an originator (EMA, 2015). For iron distribution studies, the reflection paper assumed the use of rodents. In our tests, we used a turkey fetus model to investigate time dependent tissue concentrations in pharmacological and toxicological rele…
Pharmacokinetics and Pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in Mice and Non-human Primates
2016
Locked nucleic acid (LNA) oligonucleotides have been successfully used to efficiently inhibit endogenous small noncoding RNAs in vitro and in vivo. We previously demonstrated that the direct miR-221 inhibition by the novel 13-mer LNA-i-miR-221 induces significant antimyeloma activity and upregulates canonical miR-221 targets in vitro and in vivo. To evaluate the LNA-i-miR-221 pharmacokinetics and pharmacodynamics, novel assays for oligonucleotides quantification in NOD.SCID mice and Cynomolgus monkeys (Macaca fascicularis) plasma, urine and tissues were developed. To this aim, a liquid chromatography/mass spectrometry method, after solid-phase extraction, was used for the detection of LNA-i…
Application of modern computer algebra systems in food formulations and development: A case study
2017
Abstract Background Nutritional security determines the level of public health within a population while inadequate nutrition is one of the major factors in development of various health problems. This can be alleviated with sufficient and affordable access to currently available or newly designed nutritious foods. Scope and approach Formulation of new foods can be very costly, so methods able to lower design expanses are of utmost importance to the industry. Hence, the purpose of this work was to rationalize utilization of modern computerized algebraic systems (CAS) in solving traditional problems for formulating food mixtures by food combinatoric principles (FCP). Key findings and conclus…
Comparative Performance of Linear Multielectrode Probes and Single-Tip Electrodes for Intracortical Microstimulation and Single-Neuron Recording in M…
2017
Intracortical microstimulation (ICMS) is one of the most widely employed techniques for providing causal evidence of the relationship between neuronal activity and specific motor, perceptual, or even cognitive functions. In recent years, several new types of linear multielectrode silicon probes have been developed, allowing researchers to sample neuronal activity at different depths along the same cortical site simultaneously and with high spatial precision. Nevertheless, silicon multielectrode probes have been rarely employed for ICMS studies and, more importantly, it is unknown whether and to what extent they can be used for combined recording and stimulation experiments. Here, we address…
High-Performance Biocomputing in Synthetic Biology-Integrated Transcriptional and Metabolic Circuits
2019
Biocomputing uses molecular biology parts as the hardware to implement computational devices. By following pre-defined rules, often hard-coded into biological systems, these devices are able to process inputs and return outputs-thus computing information. Key to the success of any biocomputing endeavor is the availability of a wealth of molecular tools and biological motifs from which functional devices can be assembled. Synthetic biology is a fabulous playground for such purpose, offering numerous genetic parts that allow for the rational engineering of genetic circuits that mimic the behavior of electronic functions, such as logic gates. A grand challenge, as far as biocomputing is concer…
Molecular Biology of Atherosclerotic Ischemic Strokes
2020
Among the causes of global death and disability, ischemic stroke (also known as cerebral ischemia) plays a pivotal role, by determining the highest number of worldwide mortality, behind cardiomyopathies, affecting 30 million people. The etiopathogenetic burden of a cerebrovascular accident could be brain ischemia (~80%) or intracranial hemorrhage (~20%). The most common site when ischemia occurs is the one is perfused by middle cerebral arteries. Worse prognosis and disablement consequent to brain damage occur in elderly patients or affected by neurological impairment, hypertension, dyslipidemia, and diabetes. Since, in the coming years, estimates predict an exponential increase of people w…
Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency
2016
International audience; N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal…
Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders
2018
International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 1…