The genetic control of growth rate: a systems biology study in yeast.

BACKGROUND: Control of growth rate is mediated by tight regulation mechanisms in all free-living organisms since long-term survival depends on adaptation to diverse environmental conditions. The yeast, Saccharomyces cerevisiae, when growing under nutrient-limited conditions, controls its growth rate via both nutrient-specific and nutrient-independent gene sets. At slow growth rates, at least, it has been found that the expression of the genes that exert significant control over growth rate (high flux control or HFC genes) is not necessarily regulated by growth rate itself. It has not been determined whether the set of HFC genes is the same at all growth rates or whether it is the same in conditions of nutrient limitation or excess. RESULTS: HFC genes were identified in competition experiments in which a population of hemizygous diploid yeast deletants were grown at, or close to, the maximum specific growth rate in either nutrient-limiting or nutrient-sufficient conditions. A hemizygous mutant is one in which one of any pair of homologous genes is deleted in a diploid, These HFC genes divided into two classes: a haploinsufficient (HI) set, where the hemizygous mutants grow slower than the wild type, and a haploproficient (HP) set, which comprises hemizygotes that grow faster than the wild type. The HI set was found to be enriched for genes involved in the processes of gene expression, while the HP set was enriched for genes concerned with the cell cycle and genome integrity. CONCLUSION: A subset of growth-regulated genes have HFC characteristics when grown in conditions where there are few, or no, external constraints on the rate of growth that cells may attain. This subset is enriched for genes that participate in the processes of gene expression, itself (i.e. transcription and translation). The fact that haploproficiency is exhibited by mutants grown at the previously determined maximum rate implies that the control of growth rate in this simple eukaryote represents a trade-off between the selective advantages of rapid growth and the need to maintain the integrity of the genome.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The approximability of the String Barcoding problem

The String Barcoding (SBC) problem, introduced by Rash and Gusfield (RECOMB, 2002), consists in finding a minimum set of substrings that can be used to distinguish between all members of a set of given strings. In a computational biology context, the given strings represent a set of known viruses, while the substrings can be used as probes for an hybridization experiment via microarray. Eventually, one aims at the classification of new strings (unknown viruses) through the result of the hybridization experiment. In this paper we show that SBC is as hard to approximate as Set Cover. Furthermore, we show that the constrained version of SBC (with probes of bounded length) is also hard to approximate. These negative results are tight

The study of metaphor as part of Critical Discourse Analysis

This article discusses how the study of metaphoric and more generally, figurative language use contributes to critical discourse analysis (CDA). It shows how cognitive linguists’ recognition of metaphor as a fundamental means of concept- and argument-building can add to CDA's account of meaning constitution in the social context. It then discusses discrepancies between the early model of conceptual metaphor theory and empirical data and argues that discursive-pragmatic factors as well as sociolinguistic variation have to be taken into account in order to make cognitive analyses more empirically and socially relevant. In conclusion, we sketch a modified cognitive approach informed by Relevance Theory within CDA

Protecting Against Address Space Layout Randomization (ASLR) Compromises and Return-to-Libc Attacks Using Network Intrusion Detection Systems

Writable XOR eXecutable (W XOR X) and Address Space Layout Randomisation (ASLR), have elevated the understanding necessary to perpetrate buffer overflow exploits [1]. However, they have not proved to be a panacea [1] [2] [3] and so other mechanisms such as stack guards and prelinking have been introduced. In this paper we show that host based protection still does not offer a complete solution. To demonstrate, we perform an over the network brute force return-to-libc attack against a pre-forking concurrent server to gain remote access to W XOR X and ASLR. We then demonstrate that deploying a NIDS with appropriate signatures can detect this attack efficiently

Growth control of the eukaryote cell: a systems biology study in yeast.

BACKGROUND: Cell growth underlies many key cellular and developmental processes, yet a limited number of studies have been carried out on cell-growth regulation. Comprehensive studies at the transcriptional, proteomic and metabolic levels under defined controlled conditions are currently lacking. RESULTS: Metabolic control analysis is being exploited in a systems biology study of the eukaryotic cell. Using chemostat culture, we have measured the impact of changes in flux (growth rate) on the transcriptome, proteome, endometabolome and exometabolome of the yeast Saccharomyces cerevisiae. Each functional genomic level shows clear growth-rate-associated trends and discriminates between carbon-sufficient and carbon-limited conditions. Genes consistently and significantly upregulated with increasing growth rate are frequently essential and encode evolutionarily conserved proteins of known function that participate in many protein-protein interactions. In contrast, more unknown, and fewer essential, genes are downregulated with increasing growth rate; their protein products rarely interact with one another. A large proportion of yeast genes under positive growth-rate control share orthologs with other eukaryotes, including humans. Significantly, transcription of genes encoding components of the TOR complex (a major controller of eukaryotic cell growth) is not subject to growth-rate regulation. Moreover, integrative studies reveal the extent and importance of post-transcriptional control, patterns of control of metabolic fluxes at the level of enzyme synthesis, and the relevance of specific enzymatic reactions in the control of metabolic fluxes during cell growth. CONCLUSION: This work constitutes a first comprehensive systems biology study on growth-rate control in the eukaryotic cell. The results have direct implications for advanced studies on cell growth, in vivo regulation of metabolic fluxes for comprehensive metabolic engineering, and for the design of genome-scale systems biology models of the eukaryotic cell.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Healthcare provider knowledge, attitudes, beliefs, and practices surrounding the prescription of opioids for chronic non-cancer pain in North America: protocol for a mixed-method systematic review

Background Evidence from diverse areas of medicine (e.g., cardiovascular disease, diabetes) indicates that healthcare providers (HCPs) often do not adhere to clinical practice guidelines (CPGs) despite a clear indication to implement recommendations—a phenomenon commonly termed clinical inertia. There are a variety of reasons for clinical inertia, but HCP-related factors (e.g., knowledge, motivation, agreement with guidelines) are the most salient and amenable to intervention aimed to improve adherence. CPGs have been developed to support the safe and effective prescription of opioid medication for the management of chronic non-cancer pain. The extent of physician uptake and adherence to such guidelines is not yet well understood. The purpose of this review is to synthesize the published evidence about knowledge, attitudes, beliefs, and practices that HCPs hold regarding the prescription of opioids for chronic non-cancer pain. Methods An experienced information specialist will perform searches of CINAHL, Embase, MEDLINE, and PsycINFO bibliographic databases. The Cochrane library, PROSPERO, and the Joanna Briggs Institute will be searched for systematic reviews. Searches will be performed from inception to the present. Quantitative and qualitative study designs that report on HCP knowledge, attitudes, beliefs, or practices in North America will be eligible for inclusion. Studies reporting on interventions to improve HCP adherence to opioid prescribing CPGs will also be eligible for inclusion. Two trained graduate-level research assistants will independently screen articles for inclusion, perform data extraction, and perform risk of bias and quality assessment using recommended tools. Confidence in qualitative evidence will be evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation-Confidence in the Evidence from Qualitative Reviews (GRADE-CERQual) approach. Confidence in quantitative evidence will be assessed using the GRADE approach. Discussion The ultimate goal of this work is to support interventions aiming to optimize opioid prescribing practices in order to prevent opioid-related morbidity and mortality without restricting a HCP’s ability to select the most appropriate treatment for an individual patient

Geometric morphometrics defines shape differences in the cortical area map of C57BL/6J and DBA/2J inbred mice

BACKGROUND: We previously described planar areal differences in adult mouse visual, somatosensory, and neocortex that collectively discriminated C57BL/6J and DBA/2J inbred strain identity. Here we use a novel application of established methods of two-dimensional geometric morphometrics to examine shape differences in the cortical area maps of these inbred strains. RESULTS: We used Procrustes superimposition to align a reliable set of landmarks in the plane of the cortical sheet from tangential sections stained for the cytochrome oxidase enzyme. Procrustes superimposition translates landmark configurations to a common origin, scales them to a common size, and rotates them to minimize an estimate of error. Remaining variation represents shape differences. We compared the variation in shape between C57BL/6J and DBA/2J relative to that within each strain using a permutation test of Goodall's F statistic. Significant differences in shape in the posterior medial barrel subfield (PMBSF), as well as differences in shape across primary sensory areas, characterize the cortical area maps of these common inbred, isogenic strains. CONCLUSION: C57BL/6J and DBA/2J have markedly different cortical area maps, in both size and shape. These differences suggest polymorphism in genetic factors underlying cortical specification, even between common isogenic strains. Comparing cortical phenotypes between normally varying inbred mice or between genetically modified mice can identify genetic contributions to cortical specification. Geometric morphometric analysis of shape represents an additional quantitative tool for the study of cortical development, regardless of whether it is studied from phenotype to gene or gene to phenotype