Effect of Glycosylation on the in Vivo Circulating Half-Life of Ribonuclease

The circulating half-lives of the four isozymes of bovine pancreatic ribonuclease (RNases A, B, C, and D) have been determined in normal and in nephrectomized rats. The isozymes differ only in their glycosyl content. While A contains no sugars, B has a simple oligosaccharide (GlcNAc, Man,+), and C and D each have a complex oligosaccharide (GlcNAc, Man,., Gal, Fuc NeuAc%, and GlcNAc, Mans Gal, Fuc NeuAc,, respectively) attached to Asn-34 of the polypeptide chain. All four isozymes were cleared rapidly in normal rats (t,,, = 2 to 3 min), as expected on the basis of the established role of the kidneys in removing low molecular weight proteins from circulation. In nephrectomized rats, however, a much slower clearance was observed, thus permitting the evaluation of the role of the carbohydrate chains in the catabolism of the isozymes. The clearance curves can be analyzed in terms of two processes, a rapid initial one, shown to represent the equilibration of the injected enzyme into extravascular space, and a second one which is interpreted as the catabolic clearance of the enzyme. The half-life of the RNase isozymes was calculated from this second process and found to be in the range 528 to 577 min for RNase A, 15 min for RNase B, 681 to 862 min for RNase C, and 839 to 941 min for RNase D. The rapidly cleared RNase B was treated with cu-mannosidase to remove 3 of the 4 mannosyl residues, leaving only a trisaccharide (GlcNAc,-PMan) attached to the protein. The half-life of this RNase B derivative was found to be in the range 616 to 733 min. From these results it is concluded (a) that the addition of complex oligosaccharides to a protein does not have any significant direct effect on its circulating half-life (RNases C and D compared to RNase A), and (b) that in the rat there exists a mechanism for clearing glycoproteins based on specific recognition of exposed oc-mannosyl residues (RNase B compared to the other isozymes and to cY-mannosidase-treated RNase B)

Certain Aspects of Amino Acid Nutrition in Lactic Acid Bacteria

Chemistr

CENSORS: A Combined EIS-NVSS Survey Of Radio Sources. I. Sample definition, radio data and optical identifications

A new sample of radio sources, with the designated name CENSORS (A Combined EIS-NVSS Survey Of Radio Sources), has been defined by combining the NRAO VLA Sky Survey (NVSS) at 1.4 GHz with the ESO Imaging Survey (EIS) Patch D, a 3 by 2 degree region of sky centred at 09 51 36.0, -21 00 00 (J2000). New radio observations of 199 NVSS radio sources with NVSS flux densities S(1.4GHz) > 7.8mJy are presented, and compared with the EIS I-band imaging observations which reach a depth of I~23; optical identifications are obtained for over two-thirds of the ~150 confirmed radio sources within the EIS field. The radio sources have a median linear size of 6 arcseconds, consistent with the trend for lower flux density radio sources to be less extended. Other radio source properties, such as the lobe flux density ratios, are consistent with those of brighter radio source samples. From the optical information, 30-40% of the sources are expected to lie at redshifts z >~ 1.5. One of the key goals of this survey is to accurately determine the high redshift evolution of the radio luminosity function. These radio sources are at the ideal flux density level to achieve this goal; at redshifts z~2 they have luminosities which are around the break of the luminosity function and so provide a much more accurate census of the radio source population at those redshifts than the existing studies of extreme, high radio power sources. Other survey goals include investigating the dual--population unification schemes for radio sources, studying the radio luminosity dependence of the evolution of radio source environments, and understanding the radio power dependence of the K-z relation for radio galaxies.Comment: Accepted for publication in MNRAS. 28 pages plus 36 reduced resolution jpeg figures. A postscript version with full resolution figures included in the text is available from http://www.roe.ac.uk/~pnb/censors.ps.g

Causality and the Entropy-Complexity Plane: Robustness and Missing Ordinal Patterns

We deal here with the issue of determinism versus randomness in time series. One wishes to identify their relative weights in a given time series. Two different tools have been advanced in the literature to such effect, namely, i) the "causal" entropy-complexity plane [Rosso et al. Phys. Rev. Lett. 99 (2007) 154102] and ii) the estimation of the decay rate of missing ordinal patterns [Amig\'o et al. Europhys. Lett. 79 (2007) 50001, and Carpi et al. Physica A 389 (2010) 2020-2029]. In this work we extend the use of these techniques to address the analysis of deterministic finite time series contaminated with additive noises of different degree of correlation. The chaotic series studied here was via the logistic map (r = 4) to which we added correlated noise (colored noise with f-k Power Spectrum, 0 {\leq} k {\leq} 2) of varying amplitudes. In such a fashion important insights pertaining to the deterministic component of the original time series can be gained. We find that in the entropy-complexity plane this goal can be achieved without additional computations.Comment: submitted to Physica

Hormonal control of tryptic enzyme activity in Atlantic cod larvae (Gadus morhua): Involvement of cholecystokinin during ontogeny and diurnal rhythm

Highlights • We describe the ontogenetic development of CCK and tryptic enzyme activity in larval cod • CCK is known to play a key role in regulating digestive processes • CCK concentrations increased during ontogeny suggesting a growing role in regulating digestive processes • A short-term experiment reveals a feedback mechanism between CCK and tryptic enzyme activity • Cod larvae have limited regulatory and digestive capacity to handle several meals in a short period The ontogenetic development of the gut hormone cholecystokinin (CCK) and the key proteolytic enzyme trypsin was described in Atlantic cod larvae (Gadus morhua) from first-feeding until 38 days post first-feeding (dpff). CCK is known to play a major role in the endocrine control of digestive processes in mammals and adult fish, but its regulatory role in the larval stages of marine fish is largely unknown. Only small amounts of CCK were found in the body (excluding head) in cod larvae at first-feeding, but CCK levels increased exponentially with development, suggesting a more pronounced role of CCK during ontogeny. Tryptic enzyme activity increased slightly until a standard length of ca. 8 mm (approx. 33 days dpff) with a significant increase in larvae larger than 8 mm standard length, indicating limited digestive capacity in the early stages. To entangle the short-term feedback mechanism between CCK and tryptic enzyme activity, we conducted a 12 hour feeding experiment at 21 dpff. Cod larvae receiving only algae revealed a noticeable response in tryptic enzyme activity within two hours in the morning, whereas larvae fed algae and rotifers at the same time showed a slightly delayed response up to four hours. Tryptic enzyme activity remained low in the group receiving only algae as well as the two fed groups in the afternoon. No reaction in tryptic enzyme activity was observed in larvae that received a second meal of rotifers in the afternoon, indicating limited regulatory and digestive capacity to handle several meals in a short period. CCK levels remained relatively constant throughout the day but increased in the afternoon in all three groups when tryptic enzyme activity was low, suggesting that a negative feedback mechanism between CCK and tryptic enzyme activity is present in larval cod at least from 21 dpff

Combining Structure and Sequence Information Allows Automated Prediction of Substrate Specificities within Enzyme Families

An important aspect of the functional annotation of enzymes is not only the type of reaction catalysed by an enzyme, but also the substrate specificity, which can vary widely within the same family. In many cases, prediction of family membership and even substrate specificity is possible from enzyme sequence alone, using a nearest neighbour classification rule. However, the combination of structural information and sequence information can improve the interpretability and accuracy of predictive models. The method presented here, Active Site Classification (ASC), automatically extracts the residues lining the active site from one representative three-dimensional structure and the corresponding residues from sequences of other members of the family. From a set of representatives with known substrate specificity, a Support Vector Machine (SVM) can then learn a model of substrate specificity. Applied to a sequence of unknown specificity, the SVM can then predict the most likely substrate. The models can also be analysed to reveal the underlying structural reasons determining substrate specificities and thus yield valuable insights into mechanisms of enzyme specificity. We illustrate the high prediction accuracy achieved on two benchmark data sets and the structural insights gained from ASC by a detailed analysis of the family of decarboxylating dehydrogenases. The ASC web service is available at http://asc.informatik.uni-tuebingen.de/

RNA-Seq analysis reveals new evidence for inflammation-related changes in aged kidney

Age-related dysregulated inflammation plays an essential role as a major risk factor underlying the pathophysiological aging process. To better understand how inflammatory processes are related to aging at the molecular level, we sequenced the transcriptome of young and aged rat kidney using RNA-Seq to detect known genes, novel genes, and alternative splicing events that are differentially expressed. By comparing young (6 months of age) and old (25 months of age) rats, we detected 722 up-regulated genes and 111 down-regulated genes. In the aged rats, we found 32 novel genes and 107 alternatively spliced genes. Notably, 6.6% of the up-regulated genes were related to inflammation (P < 2.2 ?? 10-16, Fisher exact t-test); 15.6% were novel genes with functional protein domains (P = 1.4 ?? 10-5); and 6.5% were genes showing alternative splicing events (P = 3.3 ?? 10-4). Based on the results of pathway analysis, we detected the involvement of inflammation-related pathways such as cytokines (P = 4.4 ?? 10-16), which were found up-regulated in the aged rats. Furthermore, an up-regulated inflammatory gene analysis identified the involvement of transcription factors, such as STAT4, EGR1, and FOSL1, which regulate cancer as well as inflammation in aging processes. Thus, RNA changes in these pathways support their involvement in the pro-inflammatory status during aging. We propose that whole RNA-Seq is a useful tool to identify novel genes and alternative splicing events by documenting broadly implicated inflammation-related genes involved in aging processesclos

Systems-Level Modeling of Cancer-Fibroblast Interaction

Cancer cells interact with surrounding stromal fibroblasts during tumorigenesis, but the complex molecular rules that govern these interactions remain poorly understood thus hindering the development of therapeutic strategies to target cancer stroma. We have taken a mathematical approach to begin defining these rules by performing the first large-scale quantitative analysis of fibroblast effects on cancer cell proliferation across more than four hundred heterotypic cell line pairings. Systems-level modeling of this complex dataset using singular value decomposition revealed that normal tissue fibroblasts variably express at least two functionally distinct activities, one which reflects transcriptional programs associated with activated mesenchymal cells, that act either coordinately or at cross-purposes to modulate cancer cell proliferation. These findings suggest that quantitative approaches may prove useful for identifying organizational principles that govern complex heterotypic cell-cell interactions in cancer and other contexts

ProphNet: A generic prioritization method through propagation of information

This article has been published as part of BMC Bioinformatics Volume 15 Supplement 1, 2014: Integrated Bio-Search: Selected Works from the 12th International Workshop on Network Tools and Applications in Biology (NETTAB 2012).[Background] Prioritization methods have become an useful tool for mining large amounts of data to suggest promising hypotheses in early research stages. Particularly, network-based prioritization tools use a network representation for the interactions between different biological entities to identify novel indirect relationships. However, current network-based prioritization tools are strongly tailored to specific domains of interest (e.g. gene-disease prioritization) and they do not allow to consider networks with more than two types of entities (e.g. genes and diseases). Therefore, the direct application of these methods to accomplish new prioritization tasks is limited.[Results] This work presents ProphNet, a generic network-based prioritization tool that allows to integrate an arbitrary number of interrelated biological entities to accomplish any prioritization task. We tested the performance of ProphNet in comparison with leading network-based prioritization methods, namely rcNet and DomainRBF, for gene-disease and domain-disease prioritization, respectively. The results obtained by ProphNet show a significant improvement in terms of sensitivity and specificity for both tasks. We also applied ProphNet to disease-gene prioritization on Alzheimer, Diabetes Mellitus Type 2 and Breast Cancer to validate the results and identify putative candidate genes involved in these diseases.[Conclusions] ProphNet works on top of any heterogeneous network by integrating information of different types of biological entities to rank entities of a specific type according to their degree of relationship with a query set of entities of another type. Our method works by propagating information across data networks and measuring the correlation between the propagated values for a query and a target sets of entities. ProphNet is available at: http://genome2.ugr.es/prophnet webcite. A Matlab implementation of the algorithm is also available at the website.This work was part of projects P08-TIC-4299 of J. A., Sevilla and TIN2009-13489 of DGICT, Madrid. It was also supported by Plan Propio de Investigación, University of Granada

Mobile application user behavior in the developing countries : a survey in Iran

Mobile applications are increasingly presented by service providers to fulfill the users’ tendency for mobility and access to services from anywhere and anytime; thereby, service platforms and a long range of tasks from banking to gaming are enabled by this technology. Although different companies offer a growing number of mobile services for potential users, only a few of them become popular and are perceived to be useful from the users’ viewpoint. The purpose of this research is to investigate the factors, which directly or indirectly influence mobile applications’ adoption by users. In other words, this study investigates the decision making process of users considering different factors such as subjective norms, attitude, perception and quality. Employing analytical approach in the literature review led to the development of a comprehensive model covering influential factors from different theories such as TPB and TAM as well as system quality, information and service quality approach. Incidentally, 39 hypotheses were developed and classified into nine different groups based on the originated theories. The model and hypotheses were tested by a sample of 1348 potential mobile application users in Iran and the data were analyzed through structural equation modeling techniques. Different internal and external variables were investigated, among which the effect of satisfaction on intention to recommend, the trace of trust on subjective norms and the influence of perceived ease of use on perceived behavioral control were more potent. In addition to offering a few suggestions for mobile application providers and marketers, this research proposes an integrated model of influential variables from different perspectives for scholars