Editing autoreactive TCR enables efficient positive selection

Allelic exclusion is inefficient at the TCRalpha locus, allowing a sizeable portion of T cells to carry two functional TCRs. The potential danger of dual TCR expression is a rescue of autoreactive TCRs during selection in the thymus and subsequent development of autoimmunity. In this study, we examine the reason(s) for replacing an autoreactive TCR and for allowing the survival of cells carrying two TCRs. We compared development of TCR transgenic CD4(+)CD8(-) thymocytes in the presence or absence of MHC class II autoantigen that does not induce deletion of thymocytes. Contrary to the expected negative effect of the presence of autoantigen, approximately 100% more CD4(+)CD8(-) thymocytes were found in the presence of MHC class II autoantigen than in the neutral background. A further increase in the strength of autoantigenic signal via expression of a human CD4 transgene led to an additional increase in the numbers of CD4(+)CD8(-) thymocytes. Thus, editing autoreactive TCR results in more efficient positive selection, and this may be both a reason and a reward for risking autoimmunity.     

Isolation and characterization of highly liganded protein from brewer's barley grain

Two basic proteins, HLP-1 and HLP-2, were isolated from brewer's barley grain (Hordeum vulgare L.) and characterized as glycoproteins with molecular masses of 16 and 13 kDa and pI values of 7.4 and 8.8, respectively. They could bind sugars, metal ions, and both hydrophobic and hydrophylic molecules of low molecular mass. These characteristics may be related to their potential plant-protecting role.     

Metabolic response of cerambycid beetle (Morimus funereus) larvae to starvation and food quality

The response of xylophagous Morimus funereus larvae to a direct change of diet demonstrated that the larvae from nutrient-poor substrates, e.g. oak, are very sensitive to such a change. Depending on dietary protein quality and quantity, an increase of proteolytic activity, i.e. an intensified protein metabolism accompanied by changes in body mass gain, was observed. At the same time, amylolytic activity was usually decreased. In the larvae reared on Robert's diet, sensitivity to the switch in diet was lower at the level of proteolytic enzymes that remained at the control level, while amylolytic activity was elevated. If the switch to a new diet was preceded by 7-day-starvation that disturbed nutritional homeostasis, the response of the larvae was similar to that recorded upon a direct switch only after short-term feeding (24 h) upon starvation. Differences in the response to changes in the diet of the larvae from nature, those reared under laboratory conditions and those of different physiological status could be ascribed to plasticity in the expression of the genes coding for proteases and their isoenzymes, as well as to the multi-functionality of some neurosecretory neurons, synthetic products that participate in the regulation of digestive enzyme activities.     

PCR-RFLPs within the lactate dehydrogenase (LDH-A) gene of the domestic pigeon (Columba livia var. domestica)

A total of 45 racing pigeons were genotyped using PCR-RFLP method. PCR product of the LDH-A gene was amplified according to the Long-PCR procedure. The amplification products were digested with restriction enzymes. PCR-RFLPs for two restriction enzymes, HaeIII and NlaIV, were observed. Two pairs of alleles LDH-A(A) and LDH-A(B) for LDH-A-NlaIV polymorphism and LDH-A(C) and LDH-A(D) for LDH-A-HaeIII polymorphism were detected in the homozygous and heterozygous states. Frequencies of alleles were as follows: A - 0.622, B - 0.378 and C - 0.256, D - 0.744.     

A Bayesian framework for combining gene predictions

MOTIVATION: Gene identification and gene discovery in new genomic sequences is one of the most timely computational questions addressed by bioinformatics scientists. This computational research has resulted in several systems that have been used successfully in many whole-genome analysis projects. As the number of such systems grows the need for a rigorous way to combine the predictions becomes more essential. RESULTS: In this paper we provide a Bayesian network framework for combining gene predictions from multiple systems. The framework allows us to treat the problem as combining the advice of multiple experts. Previous work in the area used relatively simple ideas such as majority voting. We introduce, for the first time, the use of hidden input/output Markov models for combining gene predictions. We apply the framework to the analysis of the Adh region in Drosophila that has been carefully studied in the context of gene finding and used as a basis for the GASP competition. The main challenge in combination of gene prediction programs is the fact that the systems are relying on similar features such as cod on usage and as a result the predictions are often correlated. We show that our approach is promising to improve the prediction accuracy and provides a systematic and flexible framework for incorporating multiple sources of evidence into gene prediction systems.     

The biomechanics of standing and balancing in paralyzed people

Prolonged immobilization results in several physiological problems. It has been demonstrated that standing exercises can ameliorate many of these problems. Standing exercises can be performed efficiently with the help of functional electrical stimulation (FES). A novel robotic mechanism which aids the unsupported standing of paraplegics, providing balancing exercise has been developed. The balancing strategy is based on voluntary activity of the paraplegic's upper body and artificially controlled stiffness in the ankles.     

The influence of amino acid side chains on water binding to the copper(II) in bis(N,N-dimethyl-L-alpha-isoleucinato)-copper(II): an EPR and molecular mechanics study

Simulations were done of the electron paramagnetic resonance (EPR) spectra for bis(N,N-dimethyl-L-alpha-isoleucinato)copper(II) dissolved in deuterated methanol as a function of temperature. They indicated different behaviour of the complex below and above 300 degrees K. The effect was examined by the conformational analysis of the copper(II) complex with a new molecular mechanics force field.     

Requirements for the localization of p130 Cas to Z-lines in cardiac myocytes

The vertebrate heart responds to hemodynamic load with the enlargement of postmitotic, terminally differentiated cardiac myocytes. Such hypertrophic changes are characterized by alterations in sarcomeric organization and gene expression. Previously, we established a role for a nonreceptor tyrosine kinase, focal adhesion kinase, in signaling the changes in cytoskeletal organization associated with hypertrophy. Here, we report on data supporting a key role for p130Cas in this process. In neonatal cardiac myocytes FAK, Cas and paxillin are located in sarcomeric Z-lines, suggesting that the Z-line is an important signaling locus in these cells. The expression of different Cas mutants results in a nearly complete loss of sarcomeric organization in these myocytes. Moreover, expression of the C-terminal focal adhesion-targeting domain of FAK both disrupted sarcomeric organization and interfered with the localization of endogenous Cas to Z-lines. These findings suggest that the association of FAK and Cas and the preservation of multiple protein-interaction motifs of Cas are required for the correct assembly of sarcomeres in cardiac myocytes.     

Apoptotic pathways: involvement of lysosomal proteases

Apoptosis or programmed cell death is the major mechanism used by multicellular organisms to remove infected, excessive and potentially dangerous cells. Cysteine proteases from the caspase family play a crucial role in the process. However, there is increasing evidence that lysosomal proteases are also involved in apoptosis. In this review various lysosomal proteases and their potential contribution to propagation of apoptosis are discussed.