Noise Minimization in Eukaryotic Gene Expression

All organisms have elaborate mechanisms to control rates of protein production. However, protein production is also subject to stochastic fluctuations, or “noise.” Several recent studies in Saccharomyces cerevisiae and Escherichia coli have investigated the relationship between transcription and translation rates and stochastic fluctuations in protein levels, or more generally, how such randomness is a function of intrinsic and extrinsic factors. However, the fundamental question of whether stochasticity in protein expression is generally biologically relevant has not been addressed, and it remains unknown whether random noise in the protein production rate of most genes significantly affects the fitness of any organism. We propose that organisms should be particularly sensitive to variation in the protein levels of two classes of genes: genes whose deletion is lethal to the organism and genes that encode subunits of multiprotein complexes. Using an experimentally verified model of stochastic gene expression in S. cerevisiae, we estimate the noise in protein production for nearly every yeast gene, and confirm our prediction that the production of essential and complex-forming proteins involves lower levels of noise than does the production of most other genes. Our results support the hypothesis that noise in gene expression is a biologically important variable, is generally detrimental to organismal fitness, and is subject to natural selection

Rapid and Highly Informative Diagnostic Assay for H5N1 Influenza Viruses

A highly discriminative and information-rich diagnostic assay for H5N1 avian influenza would meet immediate patient care needs and provide valuable information for public health interventions, e.g., tracking of new and more dangerous variants by geographic area as well as avian-to-human or human-to-human transmission. In the present study, we have designed a rapid assay based on multilocus nucleic acid sequencing that focuses on the biologically significant regions of the H5N1 hemagglutinin gene. This allows the prediction of viral strain, clade, receptor binding properties, low- or high-pathogenicity cleavage site and glycosylation status. H5 HA genes were selected from nine known high-pathogenicity avian influenza subtype H5N1 viruses, based on their diversity in biologically significant regions of hemagglutinin and/or their ability to cause infection in humans. We devised a consensus pre-programmed pyrosequencing strategy, which may be used as a faster, more accurate alternative to de novo sequencing. The available data suggest that the assay described here is a reliable, rapid, information-rich and cost-effective approach for definitive diagnosis of H5N1 avian influenza. Knowledge of the predicted functional sequences of the HA will enhance H5N1 avian influenza surveillance efforts

Rapid and Highly Informative Diagnostic Assay for H5N1 Influenza Viruses

A highly discriminative and information-rich diagnostic assay for H5N1 avian influenza would meet immediate patient care needs and provide valuable information for public health interventions, e.g., tracking of new and more dangerous variants by geographic area as well as avian-to-human or human-to-human transmission. In the present study, we have designed a rapid assay based on multilocus nucleic acid sequencing that focuses on the biologically significant regions of the H5N1 hemagglutinin gene. This allows the prediction of viral strain, clade, receptor binding properties, low- or high-pathogenicity cleavage site and glycosylation status. H5 HA genes were selected from nine known high-pathogenicity avian influenza subtype H5N1 viruses, based on their diversity in biologically significant regions of hemagglutinin and/or their ability to cause infection in humans. We devised a consensus pre-programmed pyrosequencing strategy, which may be used as a faster, more accurate alternative to de novo sequencing. The available data suggest that the assay described here is a reliable, rapid, information-rich and cost-effective approach for definitive diagnosis of H5N1 avian influenza. Knowledge of the predicted functional sequences of the HA will enhance H5N1 avian influenza surveillance efforts

Gene-culture coevolution and sex ratios:The effects of infanticide, sex-selective abortion, sex, selection, and sex-biased parental investment on the evolution of sex ratios

The evolutionary consequences of culturally transmitted practices that cause differential mortality between the sexes, thereby distorting the sex ratio (e.g., female infanticide and sex-selective abortion), are explored using dynamic models of gene-culture coevolution. We investigate how a preference for the sex of offspring may affect the selection of genes distorting the primary sex ratio. Sex-dependent differences in mortality have been predicted to select for a male- or female-biased primary sex ratio, to have no effect, or to favor either under different circumstances. We find that when a mating pair's behavior modifies mortality rates in favor of one sex, but does not change the number of offspring produced in the mating, the primary sex ratio will evolve a bias against the favored sex However, when the total number of offspring of a mating pair is significantly seduced as a consequence of their prejudice, the primary sex ratio will evolve to favor the preferred sex. These results hold irrespective of whether the sex ratio is distorted by the mother's, the father's or the individual's own autosomal genes. The use of dynamic models of gene-culture coevolution allows us to explore the evolution of alleles which distort the sex ratio, as well as the final equilibrium states of the system. Gene-culture interactions can provide equilibria different from those in purely genetic systems, slow the approach to these equilibria by orders of magnitude, and move the primary (PSR) and the adult sex ratio (ASR) away from any stable equilibrium for hundreds of generations.</p

A gene-culture model of human handedness

A model of handedness incorporating both genetic and cultural processes is proposed, based on an evolutionary analysis, and maximum-likelihood estimates of its parameters are generated. This model has the characteristics that (i) no genetic variation underlies variation in handedness, and (ii) variation in handedness among humans is the results of a combination of cultural and developmental factors, but (iii) a genetic influence remains since handedness is a facultative trait. The model fits the data from 17 studies of handedness in families and 14 studies of handedness in monozygotic and dizygotic twins. This model has the additional advantages that it can explain why monozygotic and dizygotic twins and siblings have similar concordance rates, and no hypothetical selection regimes are required to explain the persistence of left handedness.</p

Retinal Changes in Patients with Common Mental Disorders (Anxiety Disorders, Unipolar Depression, OCD, and PTSD): A Protocol for a Scoping Review

This review aims to provide an overview of the evidence available in the scientific literature regarding retinal changes associated with Common Mental Disorders (CMDs; i.e., anxiety disorders, unipolar Depression, obsessive-compulsive disorder, and post-traumatic stress disorder). To achieve this, the retinal alterations linked to CMDs will be investigated. This includes the methods used to identify these changes; the occurrence of specific alterations associated with one or more diagnoses or subsets of symptoms; and ultimately, whether there is any influence between the duration of evolution or the severity of symptoms in retinal alterations. the search strategy will be refined and applied to the following databases: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, PsycINFO and Embase