THE INSTITUTE OF PLEA BARGAINING IN GEORGIA

Since 2004, a completely new institution for the legal system of Georgia was introduced and actively used in the criminal law on the legislative level, which has changed the traditional procedural course of reviewing criminal cases. This institution is plea bargaining i.e. the bargaining between the prosecution and defence when it is possible the court to reach the verdict without reviewing the case thoroughly. In the article are reviewed new statutes of the Criminal Procedural Code of Georgia as well as the statistical analysis of jurisprudence. Special emphasis is made on the Institute of plea agreement as one of the most significant changes in the criminal proceedings

The peroxin PEX14 of Neurospora crassa is essential for the biogenesis of both glyoxysomes and Woronin bodies

In the filamentous fungus Neurospora crassa, glyoxysomes and Woronin bodies coexist in the same cell. Because several glyoxysomal matrix proteins and also HEX1, the dominant protein of Woronin bodies, possess typical peroxisomal targeting signals, the question arises as to how protein targeting to these distinct yet related types of microbodies is achieved. Here we analyzed the function of the Neurospora ortholog of PEX14, an essential component of the peroxisomal import machinery. PEX14 interacted with both targeting signal receptors and was localized to glyoxysomes but was virtually absent from Woronin bodies. Nonetheless, a pex14 Delta mutant not only failed to grow on fatty acids because of a defect in glyoxysomal beta-oxidation but also suffered from cytoplasmic bleeding, indicative of a defect in Woronin body-dependent septal pore plugging. Inspection of pex14 Delta mutant hyphae by fluorescence and electron microscopy indeed revealed the absence of Woronin bodies. When these cells were subjected to subcellular fractionation, HEX1 was completely mislocalized to the cytosol. Expression of GFP-HEX1 in wild-type mycelia caused the staining of Woronin bodies and also of glyoxysomes in a targeting signal-dependent manner. Our data support the view that Woronin bodies emerge from glyoxysomes through import of HEX1 and subsequent fission

Reevaluation of the role of Pex1 and dynamin-related proteins in peroxisome membrane biogenesis

A recent model for peroxisome biogenesis postulates that peroxisomes form de novo continuously in wild-type cells by heterotypic fusion of endoplasmic reticulum–derived vesicles containing distinct sets of peroxisomal membrane proteins. This model proposes a role in vesicle fusion for the Pex1/Pex6 complex, which has an established role in matrix protein import. The growth and division model proposes that peroxisomes derive from existing peroxisomes. We tested these models by reexamining the role of Pex1/Pex6 and dynamin-related proteins in peroxisome biogenesis. We found that induced depletion of Pex1 blocks the import of matrix proteins but does not affect membrane protein delivery to peroxisomes; markers for the previously reported distinct vesicles colocalize in pex1 and pex6 cells; peroxisomes undergo continued growth if ission is blocked. Our data are compatible with the established primary role of the Pex1/Pex6 complex in matrix protein import and show that peroxisomes in Saccharomyces cerevisiae multiply mainly by growth and division

Negative Correlation between Expression Level and Evolutionary Rate of Long Intergenic Noncoding RNAs

Mammalian genomes contain numerous genes for long noncoding RNAs (lncRNAs). The functions of the lncRNAs remain largely unknown but their evolution appears to be constrained by purifying selection, albeit relatively weakly. To gain insights into the mode of evolution and the functional range of the lncRNA, they can be compared with much better characterized protein-coding genes. The evolutionary rate of the protein-coding genes shows a universal negative correlation with expression: highly expressed genes are on average more conserved during evolution than the genes with lower expression levels. This correlation was conceptualized in the misfolding-driven protein evolution hypothesis according to which misfolding is the principal cost incurred by protein expression. We sought to determine whether long intergenic ncRNAs (lincRNAs) follow the same evolutionary trend and indeed detected a moderate but statistically significant negative correlation between the evolutionary rate and expression level of human and mouse lincRNA genes. The magnitude of the correlation for the lincRNAs is similar to that for equal-sized sets of protein-coding genes with similar levels of sequence conservation. Additionally, the expression level of the lincRNAs is significantly and positively correlated with the predicted extent of lincRNA molecule folding (base-pairing), however, the contributions of evolutionary rates and folding to the expression level are independent. Thus, the anticorrelation between evolutionary rate and expression level appears to be a general feature of gene evolution that might be caused by similar deleterious effects of protein and RNA misfolding and/or other factors, for example, the number of interacting partners of the gene product

Biogenesis of microbodies in the filamentous fungus Neurospora crassa\textit {Neurospora crassa}

In dieser Arbeit sollte die Biogenese von Microbodies in dem filamentösen Hyphenpilz $\textit {Neurospora crassa}$ untersucht werden. Im Speziellen sollten die molekularen Grundlagen für den selektiven Matrixproteinimport in Microbodies (Glyoxysomen und Woronin bodies) untersucht werden. Unter anderem wurde untersucht, ob beide Organellen die typische peroxisomale Importmaschinerie aufweisen. Da das PEX14 Protein ein essentieller Bestandteil der Matrixproteinimportmaschinerie ist, wurde dessen subzelluläre Lokalisation näher analysiert. In einem weiteren Teilaspekt dieser Arbeit wurde ein zu PEX14 teilweise homologes Protein untersucht. Dessen Charakterisierung sollte Aufschluß darüber geben, ob es am Matrixproteinimport beteiligt ist und Hinweise auf die Funktion liefern. Zur Identifizierung von Microbody-Proteinen wurden diese Organellen aufgereinigt und ihre Proteinzusammensetzung über MS bestimmt. Die identifizierten Proteine wurden $\textit {in silico}$ analysiert und ausgewählte näher charakterisiert.Our goal was to study the biogenesis of microbodies in filamentous fungus $\textit {Neurospora crassa}$, in particular to elucidate the molecular mechanisms of the selective import of matrix proteins into the two distinct types of microbodies, glyoxysomes and Woronin bodies. It was addressed whether both organelles depend on the typical peroxisomal import machinery. Therefore, our primary target was the determination of the subcellular localization of PEX14 protein since it is an essential member of the matrix protein import machinery. Part II is about a protein similar to PEX14. Thorough characterization should clarify whether it is also involved in peroxisome biogenesis and acts independently from PEX14. For better understanding of microbody functions, their proteomic analysis was done. Organelles were purified and their protein composition was determined by mass-spectrometry. This allowed the identification of novel proteins involved in the microbody biogenesis. Bioinformatic analysis of the identified proteins in combination with a characterization of some of them should increase our knowledge on the function of these organelles

Generalized portrait of cancer metabolic pathways inferred from a list of genes overexpressed

More than half a century from postulated Warburg theory of cancer cells origin, a question of changed metabolism in cancer is again taking the central place. Generalized picture of cancer metabolism was replaced by analysis of signaling and oncogenes in each type of cancer for several decades. However, now empowered with wealth of knowledge about tumor suppressors, oncogenes, and signaling pathways, reprogramming of cellular metabolism (e.g., increased glycolysis to respiration ratio in cancer cells) reemerged as an important element of cancer progression. To analyze level of expression of various proteins including metabolic enzymes across various cancers we used dbEST and Unigene data. We delineated a list of genes that are overexpressed in different types of cancer. We also grouped overexpressed enzymes into KEGG pathways and analyzed adjacent pathways to describe enzymatic reactions that take place in cancer cells and to identify major players that are abundant in cancer protein machinery. Glycolysis/gluconeogenesis and oxidative phosphorylation are the most abundant pathways although several other pathways are enriched in genes from our list. Ubiquitously overexpressed genes could be marked as nonspecific cancer-associated genes when analyzing genes that are overexpressed in certain types of cancer. Thus the list of overexpressed genes may be a useful tool for cancer research

Conservation of the Exon-Intron Structure of Long Intergenic Non-Coding RNA Genes in Eutherian Mammals

The abundance of mammalian long intergenic non-coding RNA (lincRNA) genes is high, yet their functions remain largely unknown. One possible way to study this important question is to use large-scale comparisons of various characteristics of lincRNA with those of protein-coding genes for which a large body of functional information is available. A prominent feature of mammalian protein-coding genes is the high evolutionary conservation of the exon-intron structure. Comparative analysis of putative intron positions in lincRNA genes from various mammalian genomes suggests that some lincRNA introns have been conserved for over 100 million years, thus the primary and/or secondary structure of these molecules is likely to be functionally important

The Vast, Conserved Mammalian lincRNome

<div><p>We compare the sets of experimentally validated long intergenic non-coding (linc)RNAs from human and mouse and apply a maximum likelihood approach to estimate the total number of lincRNA genes as well as the size of the conserved part of the lincRNome. Under the assumption that the sets of experimentally validated lincRNAs are random samples of the lincRNomes of the corresponding species, we estimate the total lincRNome size at approximately 40,000 to 50,000 species, at least twice the number of protein-coding genes. We further estimate that the fraction of the human and mouse euchromatic genomes encoding lincRNAs is more than twofold greater than the fraction of protein-coding sequences. Although the sequences of most lincRNAs are much less strongly conserved than protein sequences, the extent of orthology between the lincRNomes is unexpectedly high, with 60 to 70% of the lincRNA genes shared between human and mouse. The orthologous mammalian lincRNAs can be predicted to perform equivalent functions; accordingly, it appears likely that thousands of evolutionarily conserved functional roles of lincRNAs remain to be characterized.</p> </div