Sexual conflict maintains variation at an insecticide resistance locus

Background: The maintenance of genetic variation through sexually antagonistic selection is controversial, partly because specific sexually-antagonistic alleles have not been identified. The Drosophila DDT resistance allele (DDT-R) is an exception. This allele increases female fitness, but simultaneously decreases male fitness, and it has been suggested that this sexual antagonism could explain why polymorphism was maintained at the locus prior to DDT use. We tested this possibility using a genetic model and then used evolving fly populations to test model predictions. Results: Theory predicted that sexual antagonism is able to maintain genetic variation at this locus, hence explaining why DDT-R did not fix prior to DDT use despite increasing female fitness, and experimentally evolving fly populations verified theoretical predictions. Conclusions: This demonstrates that sexually antagonistic selection can maintain genetic variation and explains the DDT-R frequencies observed in nature

Matrix metalloproteinases (MMP-2,9) and their tissue inhibitors (TIMP-1,2) as novel markers of stress response and atherogenesis in children with chronic kidney disease (CKD) on conservative treatment

The system of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) may play a key role in atherogenesis of chronic kidney disease (CKD) patients by its impact on matrix accumulation. Connections with inflammation, stress, or endothelial dysfunction are also probable. However, the data on correlations between these parameters in CKD patients are scarce in adults and absent in children. The aim of our study was to evaluate serum concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2, as well as their correlations with markers of stress response (Hsp90-α, anti-Hsp60), endothelial dysfunction (sE-selectin), and inflammation (high-sensitivity C-reactive protein) in CKD children treated conservatively. Thirty-seven patients were divided into two groups according to the CKD stage (gr.CKDI, 19 children with CKD stages 2–3; gr.CKDII, 18 subjects with CKD stages 4–5). Twenty-four age-matched healthy subjects served as controls. Serum concentrations of MMP-2, MMP-9, TIMP-1, TIMP-2, Hsp90-α, anti-Hsp60, and sE-selectin were assessed by ELISA. Median values of MMP-2, MMP-9, TIMP-1, and TIMP-2 were significantly higher in all CKD children vs. controls and were increased in patients with CKD stages 4–5 vs. CKD stages 2–3. Hsp90-α, anti-Hsp60, sE-selectin, and glomerular filtration rate predicted the values of MMPs and TIMPs. Chronic kidney disease in children is characterized by MMP/TIMP system dysfunction, aggravated by the progression of renal failure. Correlations between examined parameters, heat shock proteins, and markers of endothelial damage suggest the possibility of MMP/TIMP application as indicators of stress response and atherogenesis in children with CKD on conservative treatment

Contrasting Patterns of Transposable Element Insertions in Drosophila Heat-Shock Promoters

The proximal promoter regions of heat-shock genes harbor a remarkable number of P transposable element (TE) insertions relative to both positive and negative control proximal promoter regions in natural populations of Drosophila melanogaster. We have screened the sequenced genomes of 12 species of Drosophila to test whether this pattern is unique to these populations. In the 12 species' genomes, transposable element insertions are no more abundant in promoter regions of single-copy heat-shock genes than in promoters with similar or dissimilar architecture. Also, insertions appear randomly distributed across the promoter region, whereas insertions clustered near the transcription start site in promoters of single-copy heat-shock genes in D. melanogaster natural populations. Hsp70 promoters exhibit more TE insertions per promoter than all other genesets in the 12 species, similarly to in natural populations of D. melanogaster. Insertions in the Hsp70 promoter region, however, cluster away from the transcription start site in the 12 species, but near it in natural populations of D. melanogaster. These results suggest that D. melanogaster heat-shock promoters are unique in terms of their interaction with transposable elements, and confirm that Hsp70 promoters are distinctive in TE insertions across Drosophila

Copy Number Variation and Transposable Elements Feature in Recent, Ongoing Adaptation at the Cyp6g1 Locus

The increased transcription of the Cyp6g1 gene of Drosophila melanogaster, and consequent resistance to insecticides such as DDT, is a widely cited example of adaptation mediated by cis-regulatory change. A fragment of an Accord transposable element inserted upstream of the Cyp6g1 gene is causally associated with resistance and has spread to high frequencies in populations around the world since the 1940s. Here we report the existence of a natural allelic series at this locus of D. melanogaster, involving copy number variation of Cyp6g1, and two additional transposable element insertions (a P and an HMS-Beagle). We provide evidence that this genetic variation underpins phenotypic variation, as the more derived the allele, the greater the level of DDT resistance. Tracking the spatial and temporal patterns of allele frequency changes indicates that the multiple steps of the allelic series are adaptive. Further, a DDT association study shows that the most resistant allele, Cyp6g1-[BP], is greatly enriched in the top 5% of the phenotypic distribution and accounts for ∼16% of the underlying phenotypic variation in resistance to DDT. In contrast, copy number variation for another candidate resistance gene, Cyp12d1, is not associated with resistance. Thus the Cyp6g1 locus is a major contributor to DDT resistance in field populations, and evolution at this locus features multiple adaptive steps occurring in rapid succession

Whisker Movements Reveal Spatial Attention: A Unified Computational Model of Active Sensing Control in the Rat

Spatial attention is most often investigated in the visual modality through measurement of eye movements, with primates, including humans, a widely-studied model. Its study in laboratory rodents, such as mice and rats, requires different techniques, owing to the lack of a visual fovea and the particular ethological relevance of orienting movements of the snout and the whiskers in these animals. In recent years, several reliable relationships have been observed between environmental and behavioural variables and movements of the whiskers, but the function of these responses, as well as how they integrate, remains unclear. Here, we propose a unifying abstract model of whisker movement control that has as its key variable the region of space that is the animal's current focus of attention, and demonstrate, using computer-simulated behavioral experiments, that the model is consistent with a broad range of experimental observations. A core hypothesis is that the rat explicitly decodes the location in space of whisker contacts and that this representation is used to regulate whisker drive signals. This proposition stands in contrast to earlier proposals that the modulation of whisker movement during exploration is mediated primarily by reflex loops. We go on to argue that the superior colliculus is a candidate neural substrate for the siting of a head-centred map guiding whisker movement, in analogy to current models of visual attention. The proposed model has the potential to offer a more complete understanding of whisker control as well as to highlight the potential of the rodent and its whiskers as a tool for the study of mammalian attention

Polo kinase recruitment via the constitutive centromere-associated network at the kinetochore elevates centromeric RNA

The kinetochore, a multi-protein complex assembled on centromeres, is essential to segregate chromosomes during cell division. Deficiencies in kinetochore function can lead to chromosomal instability and aneuploidy-a hallmark of cancer cells. Kinetochore function is controlled by recruitment of regulatory proteins, many of which have been documented, however their function often remains uncharacterized and many are yet to be identified. To identify candidates of kinetochore regulation we used a proteome-wide protein association strategy in budding yeast and detected many proteins that are involved in post-translational modifications such as kinases, phosphatases and histone modifiers. We focused on the Polo-like kinase, Cdc5, and interrogated which cellular components were sensitive to constitutive Cdc5 localization. The kinetochore is particularly sensitive to constitutive Cdc5 kinase activity. Targeting Cdc5 to different kinetochore subcomplexes produced diverse phenotypes, consistent with multiple distinct functions at the kinetochore. We show that targeting Cdc5 to the inner kinetochore, the constitutive centromere-associated network (CCAN), increases the levels of centromeric RNA via an SPT4 dependent mechanism

Autosomal recessive cerebellar ataxias

Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia

The significance of genome-wide transcriptional regulation in the evolution of stress tolerance.

It is widely recognized that stress plays an important role in directing the adaptive adjustment of an organism to changing environments. However, very little is known about the evolution of mechanisms that promote stress-induced variation. Adaptive transcriptional responses have been implicated in the evolution of tolerance to natural and anthropogenic stressors in the environment. Recent technological advances in transcriptomics provide a mechanistic understanding of biological pathways or processes involved in stress-induced phenotypic change. Furthermore, these studies are (semi) quantitative and provide insight into the reaction norms of identified target genes in response to specific stressors. We argue that plasticity in gene expression reaction norms may be important in the evolution of stress tolerance and adaptation to environmental stress. This review highlights the consequences of transcriptional plasticity of stress responses within a single generation and concludes that gene promoters containing a TATA box are more capable of rapid and variable responses than TATA-less genes. In addition, the consequences of plastic transcriptional responses to stress over multiple generations are discussed. Based on examples from the literature, we show that constitutive over expression of specific stress response genes results in stress adapted phenotypes. However, organisms with an innate capacity to buffer stress display plastic transcriptional responses. Finally, we call for an improved integration of the concept of phenotypic plasticity with studies that focus on the regulation of transcription. © Springer Science+Business Media B.V. 2010

Radiostratigraphy and age structure of the Greenland Ice Sheet

©2015. The Authors. Several decades of ice-penetrating radar surveys of the Greenland and Antarctic ice sheets have observed numerous widespread internal reflections. Analysis of this radiostratigraphy has produced valuable insights into ice sheet dynamics and motivates additional mapping of these reflections. Here we present a comprehensive deep radiostratigraphy of the Greenland Ice Sheet from airborne deep ice-penetrating radar data collected over Greenland by The University of Kansas between 1993 and 2013. To map this radiostratigraphy efficiently, we developed new techniques for predicting reflection slope from the phase recorded by coherent radars. When integrated along track, these slope fields predict the radiostratigraphy and simplify semiautomatic reflection tracing. Core-intersecting reflections were dated using synchronized depth-age relationships for six deep ice cores. Additional reflections were dated by matching reflections between transects and by extending reflection-inferred depth-age relationships using the local effective vertical strain rate. The oldest reflections, dating to the Eemian period, are found mostly in the northern part of the ice sheet. Within the onset regions of several fast-flowing outlet glaciers and ice streams, reflections typically do not conform to the bed topography. Disrupted radiostratigraphy is also observed in a region north of the Northeast Greenland Ice Stream that is not presently flowing rapidly. Dated reflections are used to generate a gridded age volume for most of the ice sheet and also to determine the depths of key climate transitions that were not observed directly. This radiostratigraphy provides a new constraint on the dynamics and history of the Greenland Ice Sheet