Sequence-based prediction of protein-protein interactions by means of codon usage

A new approach based on similarity in codon usage is used to predict protein-protein interactions

Genome-wide computational identification of functional RNA elements in Trypanosoma brucei

<p>Abstract</p> <p>Background</p> <p>Post-transcriptional regulation of gene expression is the dominant regulatory mechanism in trypanosomatids as their mRNAs are transcribed from polycistronic units. A few <it>cis</it>-acting RNA elements in 3'-untranslated regions of mRNAs have been identified in trypanosomatids, which affect the mRNA stability or translation rate in different life stages of these parasites. Other functional RNAs (fRNAs) also play essential roles in these organisms. However, there has been no genome-wide analysis for identification of fRNAs in trypanosomatids.</p> <p>Results</p> <p>Functional RNAs, including non-coding RNAs (ncRNAs) and <it>cis</it>-acting RNA elements involved in post-transcriptional gene regulation, were predicted based on two independent computational analyses of the genome of <it>Trypanosoma brucei</it>. In the first analysis, the predicted candidate ncRNAs were identified based on conservation with the related trypanosomatid <it>Leishmania braziliensis</it>. This prediction had a substantially low estimated false discovery rate, and a considerable number of the predicted ncRNAs represented novel classes with unknown functions. In the second analysis, we identified a number of function-specific regulatory motifs, based on which we devised a classifier that can be used for homology-independent function prediction in <it>T. brucei</it>.</p> <p>Conclusion</p> <p>This first genome-wide analysis of fRNAs in trypanosomatids restricts the search space of experimental approaches and, thus, can significantly expedite the process of characterization of these elements. Our classifier for function prediction based on <it>cis</it>-acting regulatory elements can also, in combination with other methods, provide the means for homology-independent annotation of trypanosomatid genomes.</p

Taking U out, with two nucleases?

BACKGROUND: REX1 and REX2 are protein components of the RNA editing complex (the editosome) and function as exouridylylases. The exact roles of REX1 and REX2 in the editosome are unclear and the consequences of the presence of two related proteins are not fully understood. Here, a variety of computational studies were performed to enhance understanding of the structure and function of REX proteins in Trypanosoma and Leishmania species. RESULTS: Sequence analysis and homology modeling of the Endonuclease/Exonuclease/Phosphatase (EEP) domain at the C-terminus of REX1 and REX2 highlights a common active site shared by all EEP domains. Phylogenetic analysis indicates that REX proteins contain a distinct subfamily of EEP domains. Inspection of three-dimensional models of the EEP domain in Trypanosoma brucei REX1 and REX2, and Leishmania major REX1 suggests variations of previously characterized key residues likely to be important in catalysis and determining substrate specificity. CONCLUSION: We have identified features of the REX EEP domain that distinguish it from other family members and hence subfamily specific determinants of catalysis and substrate binding. The results provide specific guidance for experimental investigations about the role(s) of REX proteins in RNA editing

Identification of novel components of Trypanosoma brucei editosomes

The editosome is a multiprotein complex that catalyzes the insertion and deletion of uridylates that occurs during RNA editing in trypanosomatids. We report the identification of nine novel editosome proteins in Trypanosoma brucei. They were identified by mass spectrometric analysis of functional editosomes that were purified by serial ion exchange/gel permeation chromatography, immunoaffinity chromatography specific to the TbMP63 editosome protein, or tandem affinity purification based on a tagged RNA editing ligase. The newly identified proteins have ribonuclease and/or RNA binding motifs suggesting nuclease function for at least some of these. Five of the proteins are interrelated, as are two others, and one is related to four previously identified editosome proteins. The implications of these findings are discussed

Systematic discovery of structural elements governing stability of mammalian messenger RNAs.

Decoding post-transcriptional regulatory programs in RNA is a critical step towards the larger goal of developing predictive dynamical models of cellular behaviour. Despite recent efforts, the vast landscape of RNA regulatory elements remains largely uncharacterized. A long-standing obstacle is the contribution of local RNA secondary structure to the definition of interaction partners in a variety of regulatory contexts, including--but not limited to--transcript stability, alternative splicing and localization. There are many documented instances where the presence of a structural regulatory element dictates alternative splicing patterns (for example, human cardiac troponin T) or affects other aspects of RNA biology. Thus, a full characterization of post-transcriptional regulatory programs requires capturing information provided by both local secondary structures and the underlying sequence. Here we present a computational framework based on context-free grammars and mutual information that systematically explores the immense space of small structural elements and reveals motifs that are significantly informative of genome-wide measurements of RNA behaviour. By applying this framework to genome-wide human mRNA stability data, we reveal eight highly significant elements with substantial structural information, for the strongest of which we show a major role in global mRNA regulation. Through biochemistry, mass spectrometry and in vivo binding studies, we identified human HNRPA2B1 (heterogeneous nuclear ribonucleoprotein A2/B1, also known as HNRNPA2B1) as the key regulator that binds this element and stabilizes a large number of its target genes. We created a global post-transcriptional regulatory map based on the identity of the discovered linear and structural cis-regulatory elements, their regulatory interactions and their target pathways. This approach could also be used to reveal the structural elements that modulate other aspects of RNA behaviour

An ant-based rate allocation algorithm for media streaming in peer to peer networks: extension to multiple sessions and dynamic networks

In this paper, we introduce a novel algorithm for rate allocation in media stream- ing P2P networks where multimedia contents are distributed among network members and streamed toward any requesting peer. The proposed algorithm is based on ant-colony optimization. It is capable of handling network dynamism, which is an inherent property of unstructured P2P networks. Another advantage of our algorithm is its ability to get over uncertainties in network state information, particularly the rate of supplying peers that could happen due to lack of accurate measurements. In addition, the suggested method does not rely on any information about the topology of the network. We have investigated both single and multiple streaming sessions scenarios in which more than one peer is receiving media streams from media providers. We show that the suggested algorithm will reach the maximum achievable rate of the network quite fast. A key feature of the proposed algorithm is its low pass filter property, which makes it discriminate between transient and permanent network changes. If the changes are transient, the algorithm easily and rapidly compensates the temporary losses. In cases where the network changes last longer, the algorithm overcomes losses by employing other nodes that have the media stream available. The rate of adaptation is adjustable and must be carefully determined according to network conditions. Moreover, adaption rate is not constant and varies during the streaming session. This results in uninterrupted services for current users in cases where multiple sessions are present in the network. Finally, since we have assumed that fountain codes are used to encode media streams in the P2P networks, the suggested algorithm does not require the user to receive different parts of the streams according to a predefined order and from a specific list of media suppliers. It suffices that the user gets as many stream chunks as necessary, regardless of their order or the fact that not all the media suppliers have all the parts available. In other words, using fountain codes enables us to overcome a big difficulty of P2P media streaming and that is to receive different parts of media streams according to a specific order

Appraisal of fibroblast viability in different concentration of glucose as mimicry diabetic condition

Diabetes mellitus is a common name for a group of diseases of a much diversified etiopathogenesis, characterized by chronically increased concentration of blood glucose. Diabetes results from alterations of various genes, each having a partial and additive effect. The inheritance pattern is thus complex, and environmental factors play an important role in favoring or delaying the expression of the disease. Diabetes can cause devastating complications, including cardiovascular diseases, kidney failure, and blindness, leg and foot amputations, delay in wound healing, which often result in disability and death. Fibroblast cells play a critical role in wound healing. They are the most common cells of connective tissue in animals. Tissue damage stimulates fibrocystic and induces the mitosis of fibroblasts. Wound healing processes in diabetic patients are so longer and sometimes cause to cut damaged tissue. In this study Fibroblasts were isolated from foreskin and cultured as primary cell culture in different concentrations of glucose (8.8 mmol/l, 13.13 mmol/l, 18.31 mmol/l, 27.7 mmol/l, 37.18 mmol/l, 47.17 mmol/l, 83.24 mmol/l, 124.8 mmol/l and 166.4 mmol/l) for 48h incubation time. Traditionally, the determination of cell growth is done by counting viable cells after staining witha vital dye. Among several approaches have been used in the past, The MTT method of cell determination is most invaluable to cultures which are prepared in multiwall plates. This assay is a sensitive, quantitative and reliable colorimetric assay that measures viability, proliferation and activation of cells. The results of this preliminary study suggest that altered glucose concentrations may affect fibroblast behavior in ways that are important for tissue repair and wound healing. The cells had low level of confluency and viability and in high concentration fibroblast had very low cell division.

Factors Determining Primary Coronary Slow Flow Phenomenon among Opium Users and Non-users: A Case Control Study in Northern Iran

Background: Coronary slow flow phenomenon (CSFP) represents a clinical entity with recurrent chest pain leading to living impairment. The present study aimed to investigate whether opium use correlates with primary CSFP. Methods: This study included Iranian patients with suspected coronary artery disease who underwent myocardial perfusion imaging. Coronary blood flow was measured quantitatively using the thrombolysis in myocardial infarction (TIMI) frame count and slow flow was defined as TIMI grade 2 standard deviations. Age and clinical conditions including diabetes mellitus (DM), hypertension (HTN), hyperlipidemia (HLP), history of chest pain, and opium use were recorded. First, the characteristics of the two groups were compared and then the main analyses were conducted to examine the relationship between CSFP and opium use. Data were analyzed using t test and chi-square test via SPSS 25.0. The significance level was set at P<0.05. Findings: This study was conducted on 44 male patients with documented CSFP who had no stenotic lesions and 134 control group male patients who had normal coronary arteries with normal flow. The mean age was similar in the two groups (54.25 vs.52.69, P=0.474). Two groups were significantly different in terms of history of chest pain (P=0.003), but there was no significant difference in HTN (P=0.084), DM (P=0.284), HLP (P=0.183), smoking (P=0.696), and opium use (P=0.107).  Conclusion: This study indicated that opium use is not associated with primary CSFP

Determination of nutritional requirements of kutum fish (Rutilus frissi kutum) fingerling

Three experiments carried out to determine optimize level of crude protein, lipid and gross energy requirements of Kutum fish (Rutilus frissi kutum) fingerling. A completly randomized design consisted of 4 treatments with triplicates which those was used with four experimental dietary crude protein levels (35, 40. 45 and 50% CP), Four crude lipid levels (8, 12, 16 and 20%) and four gross energy levels (4250, 4500, 4750 and 5000 k cal/kg of diet) being tested separately. Kutum fish fingerling averaging 1067 ± 98 mg,,2378 ± 185 mg, and 1067 ± 143 mg respectively and stocked with density of 20 fish at volum 80 liters. Fish fed with 3% of wet body weight at three times, 9 am, 12 am and 4 pm. The following performance parameters were evaluated final weight, weight gain, feed intake, feed conversion ratio, specific growth rate, protein effieciency ratio and condition factor. Fish fed diets 40% CP, 20% CL and 4500 K Cal/kg Gross energy could meet the nutritional requierments of kutum fish fingerling