Model for comparative analysis of antigen receptor repertoires

In modern molecular biology one of the standard ways of analyzing a vertebrate immune system is to sequence and compare the counts of specific antigen receptor clones (either immunoglobulins or T-cell receptors) derived from various tissues under different experimental or clinical conditions. The resulting statistical challenges are difficult and do not fit readily into the standard statistical framework of contingency tables primarily due to the serious under-sampling of the receptor populations. This under-sampling is caused, on one hand, by the extreme diversity of antigen receptor repertoires maintained by the immune system and, on the other, by the high cost and labor intensity of the receptor data collection process. In most of the recent immunological literature the differences across antigen receptor populations are examined via non-parametric statistical measures of the species overlap and diversity borrowed from ecological studies. While this approach is robust in a wide range of situations, it seems to provide little insight into the underlying clonal size distribution and the overall mechanism differentiating the receptor populations. As a possible alternative, the current paper presents a parametric method that adjusts for the data under-sampling as well as provides a unifying approach to a simultaneous comparison of multiple receptor groups by means of the modern statistical tools of unsupervised learning. The parametric model is based on a flexible multivariate Poisson-lognormal distribution and is seen to be a natural generalization of the univariate Poisson-lognormal models used in the ecological studies of biodiversity patterns. The procedure for evaluating a model's fit is described along with the public domain software developed to perform the necessary diagnostics. The model-driven analysis is seen to compare favorably vis a vis traditional methods when applied to the data from T-cell receptors in transgenic mice populations.     

Magnesium and cell energetics in plants under anoxia

Stress conditions (e.g. anoxia) frequently result in a decrease of [ATP] and in an increase of [ADP] and [AMP], with a concomitant increase of [Mg(2+)] and other cations, e.g. Ca(2+). The elevation of [Mg(2+)] is linked to the shift in the apparent equilibrium of adenylate kinase. As a result, enzymes that use Mg(2+) as a cofactor are activated, Ca(2+) activates calcium-dependent signalling pathways, and PP(i) can serve as an alternative energy source in its active form of MgPP(i) or Mg2PP(i). Under anoxic conditions in plants, an important source of PP(i) may come as a result of combined reactions of PK (pyruvate kinase) and PPDK (pyruvate, phosphate dikinase). The PP(i) formed in the PPDK/PK cycle ignites glycolysis in conditions of low [ATP] by involving PP(i)-dependent reactions. This saves ATP and makes metabolism under stress conditions more energy efficient.     

Elevated level of Wnt5a protein in localized prostate cancer tissue is associated with better outcome

Background

Wnt5a is a non-canonical secreted glycoprotein of the Wnt family that plays an important role in cancer development and progression. Previous studies report that Wnt5a is upregulated in prostate cancer and suggested that Wnt5a affects migration and invasion of prostate tumor cell. This study aimed to evaluate the prognostic value of Wnt5a protein expression in prostate cancer tissue and its potential to predict outcome after radical prostatectomy in patients with localized prostate cancer.

Methodology and Results

Immunohistochemical analysis of a tissue microarray containing prostate specimens of 503 patients with localized prostate cancer showed significantly higher Wnt5a protein expression in cancer compared to benign cores from the same patients (p<0.0001). Patients with high expression of Wnt5a protein had significantly better outcome in terms of time to biochemical recurrence compared to patients with low expression levels (p = 0.001, 95%CI 1.361–3.570, Hazard''s ratio 2.204). A combination of high Wnt5a expression with low levels of Ki-67 or androgen receptor expression had even better outcome compared to all other groups. Furthermore, we found that Wnt5a expression significantly correlated with VEGF and with Ki-67 and androgen receptor expression, although not highly significant. In vitro, we demonstrated that recombinant Wnt5a decreased invasion of 22Rv1 and DU145 cells and that siRNA knockdown of endogenous Wnt5a protein led to increased invasion of 22Rv1 and LNCaP cells.

Conclusion

We demonstrate that preserved overexpression of Wnt5a protein in patients with localized prostate cancer predicts a favorable outcome after surgery. This finding together with our in vitro data demonstrating the ability of Wnt5a to impair the invasive properties of prostate cancer cells, suggests a tumor suppressing effect of Wnt5a in localized prostate cancer. These results indicate that Wnt5a can be used as a predictive marker and that it also is a plausible therapeutic target for treatment of localized prostate cancer.     

Autumn-winter diet overlap of fallow, red, and roe deer in forest ecosystems, Southern Poland

The wild population of fallow deer in Central Europe has grown considerably over the last decade. However, information on feeding habits of this alien species in relation to the indigenous red deer or roe deer, in areas of their co-occurrence, is scarce. A prevailing view maintains that their food-niches are distinct, although direct comparative studies have not been carried out. Therefore, the aim of the research was to compare the diets of fallow, red, and roe deer feeding in the same habitat. Research was based on the rumen contents of 242 animals hunted in the autumn-winter season in the forests of Southern Poland. The analyses demonstrated that fallow deer are moderate grazers in such conditions and eat more graminoids in comparison to red or roe deer (36.4% vs. 16.1% or 5.5%, respectively). On the other hand, it feeds on less browse (17.2% vs. 41.4%) or dwarf shrubs (8.4% vs. 19.0%) than red deer, and on less bramble (10.9% vs. 34.6%) or forbs (4.0% vs. 7.6%) in comparison to roe deer (P=0.05). Although the diets of the three deer species differ in terms of the proportion of each food type in their diet, overlapping of their food-niches is high (52.6%).     

Computable visually observed phenotype ontological framework for plants

Background

Gene regulatory networks have an essential role in every process of life. In this regard, the amount of genome-wide time series data is becoming increasingly available, providing the opportunity to discover the time-delayed gene regulatory networks that govern the majority of these molecular processes.

Results

This paper aims at reconstructing gene regulatory networks from multiple genome-wide microarray time series datasets. In this sense, a new model-free algorithm called GRNCOP2 (Gene Regulatory Network inference by Combinatorial OPtimization 2), which is a significant evolution of the GRNCOP algorithm, was developed using combinatorial optimization of gene profile classifiers. The method is capable of inferring potential time-delay relationships with any span of time between genes from various time series datasets given as input. The proposed algorithm was applied to time series data composed of twenty yeast genes that are highly relevant for the cell-cycle study, and the results were compared against several related approaches. The outcomes have shown that GRNCOP2 outperforms the contrasted methods in terms of the proposed metrics, and that the results are consistent with previous biological knowledge. Additionally, a genome-wide study on multiple publicly available time series data was performed. In this case, the experimentation has exhibited the soundness and scalability of the new method which inferred highly-related statistically-significant gene associations.

Conclusions

A novel method for inferring time-delayed gene regulatory networks from genome-wide time series datasets is proposed in this paper. The method was carefully validated with several publicly available data sets. The results have demonstrated that the algorithm constitutes a usable model-free approach capable of predicting meaningful relationships between genes, revealing the time-trends of gene regulation.     

Expression of glucose transporters in cancers

It has been known for 80 years that cancer cell growth in an energy-related process supported by an increased glucose metabolism. This phenomenon suggests a need for a corresponding increased uptake of glucose across the plasma membrane through an enhancement in the glucose transporter proteins, SGLT proteins as well as GLUT proteins. The results of many studies have demonstrated that the expression of glucose transporters, especially GLUT1, is increased in a variety of malignancies. GLUT1 overexpression has been found to be associated with tumor progression. It was found that GLUT1 overexpression is associated with poor overall survival in various malignant tumors.     

Pseudomonas silesiensis sp. nov. strain A3T isolated from a biological pesticide sewage treatment plant and analysis of the complete genome sequence

Microorganisms classified in to the Pseudomonas genus are a ubiquitous bacteria inhabiting variety of environmental niches and have been isolated from soil, sediment, water and different parts of higher organisms (plants and animals). Members of this genus are known for their metabolic versatility and are able to utilize different chemical compounds as a source of carbon, nitrogen or phosphorus, which makes them an interesting microorganism for bioremediation or bio-transformation. Moreover, Pseudomonas sp. has been described as a microorganism that can easily adapt to new environmental conditions due to its resistance to the presence of high concentrations of heavy metals or chemical pollution. Here we present the isolation and analysis of Pseudomonas silesiensis sp. nov. strain A3^T isolated from peaty soil used in a biological wastewater treatment plant exploited by a pesticide packaging company. Phylogenetic MLSA analysis of 4 housekeeping genes (16S rRNA, gyrB, rpoD and rpoB), complete genome sequence comparison (ANIb, Tetranucleotide identity, digital DDH), FAME analysis, and other biochemical tests indicate the A3^T strain (type strain PCM 2856^T = DSM 103370^T) differs significantly from the closest relative species and therefore represents a new species within the Pseudomonas genus. Moreover, bioinformatic analysis of the complete sequenced genome showed that it consists of 6,823,539 bp with a 59.58 mol% G + C content and does not contain any additional plasmids. Genome annotation predicted the presence of 6066 genes, of which 5875 are coding proteins and 96 are RNA genes.     

Cloning and characterization of several cDNAs for UDP-glucose pyrophosphorylase from barley (Hordeum vulgare) tissues

Eleven cDNA clones encoding UDP-glucose pyrophosphorylase (UGPase) have been isolated from cDNA libraries prepared from seed embryo, seed endosperm and leaves of barley (Hordeum vulgare L.). The sequences were identical, with the exception of positioning of the poly(A) tail; at least five clones with different polyadenylation sites were found. For a putative full-length cDNA [1775 nucleotides (nt) plus polyadenylation tail], isolated from an embryo cDNA library, an open reading frame of 1419 nt encodes a protein of 473 amino acids (aa) of 51.6 kDa. An alignment of the derived aa sequence with other UGPases has revealed high identity to UGPases from eukaryotic tissues, but not from bacteria. Within the aa sequence, no homology was found to a UDP-glucose-binding motif that has been postulated for a family of glucosyl transferases. The derived aa sequence of UGPase contains three putative N-glycosylation sites and has a highly conserved positioning of five Lys residues, previously shown to be critical for catalysis and substrate binding of potato tuber UGPase. A possible role for N-glycosylation in the intracellular targeting of UGPase is discussed.