The integration of proteomics data with biological knowledge is a recent trend in bioinformatics. A lot of biological information is available and is spread on different sources and encoded in ...different ontologies (e.g. Gene Ontology). Annotating existing protein data with biological information may enable the use (and the development) of algorithms that use biological ontologies as framework to mine annotated data. Recently many methodologies and algorithms that use ontologies to extract knowledge from data, as well as to analyse ontologies themselves have been proposed and applied to other fields. Conversely, the use of such annotations for the analysis of protein data is a relatively novel research area that is currently becoming more and more central in research. Existing approaches span from the definition of the similarity among genes and proteins on the basis of the annotating terms, to the definition of novel algorithms that use such similarities for mining protein data on a proteome-wide scale. This work, after the definition of main concept of such analysis, presents a systematic discussion and comparison of main approaches. Finally, remaining challenges, as well as possible future directions of research are presented.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inhibition of phosphodiesterase 9 (PDE9) has been reported to enhance rodent cognitive function and may represent a potential novel approach to improving cognitive dysfunction in Alzheimer's disease. ...PF-04447943, (6-(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo3,4-dpyrimidin-4-one), a recently described PDE9 inhibitor, was found to have high affinity (Ki of 2.8, 4.5 and 18 nM) for human, rhesus and rat recombinant PDE9 respectively and high selectivity for PDE9 versus PDEs1-8 and 10-11. PF-04447943 significantly increased neurite outgrowth and synapse formation (as indicated by increased synapsin 1 expression) in cultured hippocampal neurons at low (30-100 nM) but not high (300-1000 nM) concentrations. PF-04447943 significantly facilitated hippocampal slice LTP evoked by a weak tetanic stimulus at a concentration of 100 nM but failed to affect response to the weak tetanus at either 30 or 300 nM, or the LTP produced by a theta burst stimulus. Systemic administration of PF-04447943 (1-30 mg/kg p.o.) dose-dependently increased cGMP in the cerebrospinal fluid 30 min after administration indicating target engagement in the CNS of rats. PF-04447943 (1-3 mg/kg p.o.) significantly improved cognitive performance in three rodent cognition assays (mouse Y maze spatial recognition memory model of natural forgetting, mouse social recognition memory model of natural forgetting and rat novel object recognition with a scopolamine deficit). When administered at a dose of 3 mg/kg p.o., which improved performance in novel object recognition, PF-04447943 significantly increased phosphorylated but not total GluR1 expression in rat hippocampal membranes. Collectively these data indicate that PF-04447943 is a potent, selective brain penetrant PDE9 inhibitor that increased indicators of hippocampal synaptic plasticity and improved cognitive function in a variety of cognition models in both rats and mice. Results with PF-04447943 are consistent with previously published findings using a structurally diverse PDE9 inhibitor, BAY73-6199, and further support the suggestion that PDE9 inhibition may represent a novel approach to the palliative remediation of cognitive dysfunction.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Non-alcoholic fatty liver disease (NAFLD) is a relevant public health matter in Western countries. The pathogenetic link between visceral fat, insulin resistance (IR) and NAFLD has been reported in ...literature. However, there are contradictions on the changes of adipokine levels in serum related to the presence of NAFLD. The aim of the present study was to evaluate the serum concentrations of a selected set of adipokines, that is, adiponectin, leptin, resistin and the pro-inflammatory cytokine interleukin-6 (IL-6) in overweight patients, and to clarify their relationship with NAFLD.
Fasting serum levels of adipokines were determined in 42 consecutive overweight patients and in 25 lean controls. The degree of ultrasound (US) liver steatosis was graded according to the Hamaguchi score.
Liver steatosis was detected in 33 patients (78%) by US examination. Twelve patients with elevated transaminases levels showed significantly higher values of IR, leptin and resistin levels (P<0.05). Patients with steatosis presented a significantly higher leptin and a lower adiponectin levels (P<0.05) than controls. A significant inverse correlation was found between US steatosis progression and adiponectin and resistin levels (p<0.05). Considering the multiple logistic regression, adiponectin and leptin were good predictors to detect the presence of steatosis (p<0.05).
Our data support the concept that adipokine level changes are closely linked with IR. In addition, serum adiponectin and leptin levels may be used as diagnostic markers to determine the presence of NAFLD in overweight patients.
Mass-Spectrometry (MS) based biological analysis is a powerful approach for discovering novel biomarkers or identifying patterns and associations in biological samples. Each value of a spectrum is ...composed of two measurements, m/Z (mass to charge ratio) and intensity. Even if data produced by mass spectrometers contains potentially huge amount of information, data are often affected by errors and noise due to sample preparation and instrument approximation. Preprocessing consists of (possibly) eliminating noise from spectra and identifying significant values (peaks). Preprocessing techniques need to be applied before performing analysis: cleaned spectra may then be analyzed by using data mining techniques or can be compared with known spectra in databases. This paper surveys different techniques for spectra preprocessing, working either on a single spectrum, or on an entire data set. We analyze preprocessing techniques aiming to correct intensity and m/Z values in order to: (i) reduce noise, (ii) reduce amount of data, and (iii) make spectra comparable.
Full text
Available for:
FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
We demonstrate optical orientation in Ge/SiGe quantum wells and study their spin properties. The ultrafast electron transfer from the center of the Brillouin zone to its edge allows us to achieve ...high spin polarizations and to resolve the spin dynamics of holes and electrons. The circular polarization degree of the direct gap photoluminescence exceeds the theoretical bulk limit, yielding ∼37% and ∼85% for transitions with heavy and light holes states, respectively. The spin lifetime of holes at the top of the valence band is estimated to be ∼0.5 ps and it is governed by transitions between light and heavy hole states. Electrons at the bottom of the conduction band, on the other hand, have a spin lifetime that exceeds 5 ns below 150 K. Theoretical analysis of the spin relaxation indicates that phonon-induced intervalley scattering dictates the spin lifetime of electrons.
Full text
Available for:
CMK, CTK, FMFMET, IJS, NUK, PNG, UM
The analysis of mass spectrometry proteomics data requires the composition of different software tools devoted to the loading, management, preprocessing, mining, and visualization of spectra data. ...This paper proposes the use of ontologies to guide the composition of preprocessing and data mining tools and describes the approach through MS-Analyzer, a software tool for the integrated management, preprocessing and mining of spectra data on the Grid.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Microarray is a key technology in genomics and is increasingly used in molecular biology as well as in molecular medicine and clinical applications. The availability of different microarray types and ...vendors and the increasing number of samples forming microarray studies pose new challenges in the management and analysis of microarray data. The paper recalls main microarray types and goals and discusses the most important challenges in microarray management and analysis, including the following issues. Heterogeneity in microarray data format requires the application of different preprocessing and annotation tools and the use of different, vendor-specific, preprocessing libraries. Multiplicity of microarray types (e.g. gene expression, SNPs and miRNA arrays, to cite a few) requires the application of different analysis tools. The application of various preprocessing steps produces a number of different files for each study, such as raw, preprocessed, annotated and eventually filtered data, that must be managed and stored properly. Finally, the increasing volume of microarray data due to the use of large sets of samples poses further challenges for the storage of such data. Finally, some emerging directions to face such challenges are also described.
The combined use of mass spectrometry and data mining is a novel approach in proteomic pattern analysis for discovering novel biomarkers or identifying patterns and associations in proteomic ...profiles. Data produced by mass spectrometers are affected by errors and noise due to sample preparation and instrument approximation, so different preprocessing techniques need to be applied before analysis is conducted. We survey different techniques for spectra preprocessing, and we present a first design of a software tool that allows the preprocessing, management and analysis of mass spectrometry data on the Grid.
PDF
