Fatty-acid amide hydrolase polymorphisms and post-traumatic stress disorder after penetrating brain injury

The past few years have seen an increase in the clinical awareness of post-traumatic stress disorder (PTSD), one of the most disabling and least understood behavioral disorders. Although the biological bases of PTSD are poorly understood, fatty-acid amide hydrolase (FAAH) activity has been linked with arousability and aversive-memories extinction, that is, two key features of PTSD. In this study, we investigated the association between the FAAH genetic polymorphisms and PTSD development and maintenance. We assessed PTSD frequency in a group of male Vietnam war veterans who suffered combat-related penetrating traumatic brain injury, that is, a relatively homogeneous population regarding the nature of the events that led to PTSD. We showed that rs2295633, a single-nucleotide polymorphism of FAAH, was significantly associated with PTSD diagnosis in subjects without lesions in the ventromedial prefrontal cortex. Moreover, the presence of the C allele was associated with more severe re-experiencing of trauma and more negative reported childhood experiences. In conclusion, our data suggest that FAAH has an important role in PTSD through modulation of aversive memories and point to both a novel therapeutic target and a possible risk marker for this condition

Searching a bitstream in linear time for the longest substring of any given density

Given an arbitrary bitstream, we consider the problem of finding the longest substring whose ratio of ones to zeroes equals a given value. The central result of this paper is an algorithm that solves this problem in linear time. The method involves (i) reformulating the problem as a constrained walk through a sparse matrix, and then (ii) developing a data structure for this sparse matrix that allows us to perform each step of the walk in amortised constant time. We also give a linear time algorithm to find the longest substring whose ratio of ones to zeroes is bounded below by a given value. Both problems have practical relevance to cryptography and bioinformatics.Comment: 22 pages, 19 figures; v2: minor edits and enhancement

Compositional Genome Contexts Affect Gene Expression Control in Sea Urchin Embryo

Gene expression is widely perceived as exclusively controlled by the information contained in cis-regulatory regions. These are built in a modular way, each module being a cluster of binding sites for the transcription factors that control the level, the location and the time at which gene transcription takes place. On the other hand, results from our laboratory have shown that gene expression is affected by the compositional properties (GC levels) of the isochores in which genes are embedded, i.e. the genome context. To clarify how compositional genomic properties affect the way cis-regulatory information is utilized, we have changed the genome context of a GFP-reporter gene containing the complete cis-regulatory region of the gene spdeadringer (spdri), expressed during sea urchin embryogenesis. We have observed that GC levels higher or lower than those found in the natural genome context can alter the reporter expression pattern. We explain this as the result of an interference with the functionality of specific modules in the gene's cis-regulatory region. From these observations we derive the notion that the compositional properties of the genome context can affect cis-regulatory control of gene expression. Therefore although the way a gene works depends on the information contained in its cis-regulatory region, availability of such information depends on the compositional properties of the genomic context

Transcriptome map of mouse isochores

<p>Abstract</p> <p>Background</p> <p>The availability of fully sequenced genomes and the implementation of transcriptome technologies have increased the studies investigating the expression profiles for a variety of tissues, conditions, and species. In this study, using RNA-seq data for three distinct tissues (brain, liver, and muscle), we investigate how base composition affects mammalian gene expression, an issue of prime practical and evolutionary interest.</p> <p>Results</p> <p>We present the transcriptome map of the mouse isochores (DNA segments with a fairly homogeneous base composition) for the three different tissues and the effects of isochores' base composition on their expression activity. Our analyses also cover the relations between the genes' expression activity and their localization in the isochore families.</p> <p>Conclusions</p> <p>This study is the first where next-generation sequencing data are used to associate the effects of both genomic and genic compositional properties to their corresponding expression activity. Our findings confirm previous results, and further support the existence of a relationship between isochores and gene expression. This relationship corroborates that isochores are primarily a product of evolutionary adaptation rather than a simple by-product of neutral evolutionary processes.</p