Assessing multilocus introgression patterns: a case study on the mouse X chromosome in central Europe

Multilocus hybrid zone (HZ) studies predate genomics by decades. The power of early methods is becoming apparent and now large datasets are commonplace. Relating introgression along a chromosome to evolutionary process is challenging: although reduced introgression regions may indicate speciation genes, this pattern may be obscured by asymmetric introgression of linked invasive genes. Further, HZ movement may form salients and leave islands in its wake. Barton's concordance was proposed 24 years ago for assessing introgression where geographic patterns are complex. The geographic axis of introgression is replaced with the hybrid index. We compare this, a recently proposed genomic clines approach, and two-dimensional (2D) geographic analyses, for 24 X chromosome loci of 2873 mice from the central-European house mouse HZ. In 2D, 14 loci show linear contact, seven precisely matching previous studies. Four show introgression islands to the east of the zone, suggesting past westward zone movement, two show westward salients. Barton's concordance both recovers and refines this information. A region of reduced introgression on the central X is supported, despite X centromere-proximal male-biased westward introgression matching a westward 2D geographic salient. Genomic clines results are consistent regarding introgression asymmetries, but otherwise more difficult to interpret. Evidence for genetic conflict is discussed.     

Inference of selection and stochastic effects in the house mouse hybrid zone

We explored the transition of 13 X-linked markers across two separate portions of the house mouse hybrid zone, asking whether such a comparison can distinguish the effects of selection from random factors. A heuristic search in the likelihood landscape revealed more complex likelihood profiles for data sampled in two-dimensional (2D) space relative to data sampled along a linear transect. Randomized resampling of localities analyzed for individual loci showed that deletion of sites away from the zone center can decrease cline width estimates whereas deletion of sites close to the center can significantly increase the width estimates. Deleting localities for all loci resulted in wider clines if the number of samples from the center was limited. The results suggest that, given the great variation in width estimates resulting from inclusion/exclusion of sampling sites, the geographic sampling design is important in hybrid zone studies and that our inferences should take into account measures of uncertainty such as support intervals. The comparison of the two transects indicates cline widths are narrower for loci in the central part of the X chromosome, suggesting selection is stronger in this region and genetic incompatibilities may have at least partly common architecture in the house mouse hybrid zone.     

Protocadherin 9 inhibits epithelial–mesenchymal transition and cell migration through activating GSK-3β in hepatocellular carcinoma

Protocadherin 9 (PCDH9) was found frequently lost in hepatocellular carcinoma (HCC). Here we investigated the role of PCDH9 in the development of HCC. We confirmed that PCDH9 was down-regulated in HCC tissues and cell lines compared with the adjacent non-tumor tissues. PCDH9 downregulation was significantly associated with malignant portal vein invasion of HCC patients. Gain- and loss-of-function studies revealed that downregulation of PCDH9 facilitated tumor cell migration and epithelial–mesenchymal transition (EMT). We identified PCDH9 as a novel regulator of EMT by increasing the activity of GSK-3β and inhibiting Snail1, indicating its potential therapeutic value for reducing metastasis of HCC.     

Multilocus phylogeography and morphology give insights into the recent evolution of a Mexican endemic songbird: Vireo hypochryseus

We used multilocus phylogeographic analyses, morphometric measurements, and environmental niche models (ENMs) to analyze the recent evolution of the golden vireo Vireo hypochryseus, a Mexican endemic species. Vireo hypochryseus is made up of two phylogeographically structured mitochondrial DNA clades that probably diverged 132 000 yr ago. One clade comprised individuals from mainland Sinaloa and the Tres Marías islands in the northwest, and the other included individuals from the remaining range of the species. This marked phylogeographic structure contrasts with the low genetic structure reported for temperate North American vireos. The nuclear DNA markers also showed some geographic differences in allele frequency, but did not exhibit a clear phylogeographic structure. The morphometric analyses suggested a decreasing north to south cline, with the largest individuals located in the Tres Marías islands. The ENMs did not support a scenario of geographic fragmentation of the environmental conditions of the area in which V. hypochryseus has inhabited over the last 130 000 yr. However, a model of isolation by resistance based on the actual configuration of climatic conditions in western Mexico did explain a major proportion of both the mitochondrial DNA distances and the differences in size, while a model of isolation by distance explain a low proportion of such differences. Therefore, the recent history of V. hypochryseus was likely shaped by historical habitat fragmentation due to fluctuating environmental conditions in the mainland that produced a phylogeographic print, and natural selection on morphological traits in the insular population, suggesting an active diversification of endemic lineages in the Mexican dry forest.     

Effects of potassium deficiency and replacement of potassium by sodium on sugar beet plants

Two sugar beet (Beta vulgaris L.) genotypes were cultivated at different K⁺/Na⁺ concentration in nutrient solutions (mM, 3/0 (control groups), 0.03/2.97 (K-Na replacement groups), and 0.03/0 (K deficiency groups)) to investigate the effects of potassium deficiency and replacement of potassium by sodium on plant growth and to explore how sodium can compensate for a lack of potassium. After 22 days of growth were determined: (i) dry weights of leaves, stems, and roots, (ii) the Na⁺ and K⁺ contents, (iii) MDA level, (iv) the activities of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX), and (v) the level of free amino acids. Potassium deficit inhibited plant growth, decreased the K⁺ content in leaves and roots, activated GPX and SOD, suppressed CAT activity, and increased the content of most amino acids. In K-Na replacement groups, the effects of K⁺ deficiency, including changes in the MDA level, antioxidant enzyme activities, and the level of free amino acids, were alleviated, but the degree of recovery did not reach the values characteristic for the control groups. Based on these results, we concluded that low potassium could lead to the inhibition of seedling growth, oxidative damage, and amino acid accumulation. While sodium was able to substitute potassium to a large extent, it cannot fulfil potassium fundamental role as an essential nutrient in sugar beet.     

Sperm Morphology in Two House Mouse Subspecies: Do Wild-Derived Strains and Wild Mice Tell the Same Story?

Being subject to intense post-copulatory selection, sperm size is a principal determining component of male fitness. Although previous studies have presented comparative sperm size data at higher taxonomic levels, information on the evolution of sperm size within species is generally lacking. Here, we studied two house mouse subspecies, Mus musculus musculus and Mus musculus domesticus, which undergo incipient speciation. We measured four sperm dimensions from cauda epididymis smears of 28 wild-caught mice of both subspecies. As inbred mouse strains are frequently used as proxies for exploring evolutionary processes, we further studied four wild-derived inbred strains from each subspecies. The subspecies differed significantly in terms of sperm head length and midpiece length, and these differences were consistent for wild mice and wild-derived strains pooled over genomes. When the inbred strains were analyzed individually, however, their strain-specific values were in some cases significantly shifted from subspecies-specific values derived from wild mice. We conclude that: (1) the size of sperm components differ in the two house mouse subspecies studied, and that (2) wild-derived strains reflect this natural polymorphism, serving as a potential tool to identify the genetic variation driving these evolutionary processes. Nevertheless, we suggest that more strains should be used in future experiments to account for natural variation and to avoid confounding results due to reduced variability and/or founder effect in the individual strains.     

Mapping Cortical Thickness of the Patients with Unilateral End-Stage Open Angle Glaucoma on Planar Cerebral Cortex Maps

Purpose

To estimate and compare cerebral cortex thickness in patients with unilateral end-stage glaucoma with that of age-matched individuals with unaffected vision.

Methods

14 patients with unilateral end-stage primary open angle glaucoma (POAG) and 12 age-matched control individuals with no problems with vision were selected for the study based on detailed ophthalmic examination. For each participant 3D high-resolution structural brain T1-weighted magnetization prepared MR images were acquired on a 3.0 T scanner. Brain cortex thickness was estimated using the FreeSurfer image analysis environment. After warping of subjects'' cortical surfaces to FreeSurfer common space, differences between POAG and control groups were inferred at the group analysis level with the General Linear Model.

Results

The analysis performed revealed local thinning in the visual cortex areas in the POAG group. Statistically significant differences form 600 mm² clusters located in the Brodmann area BA19 in the left and right hemisphere.

Conclusion

Unilateral vision loss due to end-stage neuropathy from POAG is associated with significant thinning of cortical areas employed in vision.     

Relationship between Aldosterone and the Metabolic Syndrome in Patients with Obstructive Sleep Apnea Hypopnea Syndrome: Effect of Continuous Positive Airway Pressure Treatment

Background

Metabolic syndrome (MS) occurs frequently in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). We hypothesized that aldosterone levels are elevated in OSAHS and associated with the presence of MS.

Methods

We studied 66 patients with OSAHS (33 with MS and 33 without MS) and 35 controls. The occurrence of the MS was analyzed according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) clinical criteria. Measurements of plasma renin activity (PRA), aldosterone, aldosterone:PRA ratio, creatinine, glucose, triglycerides, cholesterol and HDL cholesterol were obtained at baseline and after CPAP treatment.

Results

Aldosterone levels were associated with the severity of OSAHS and higher than controls (p = 0.046). Significant differences in aldosterone levels were detected between OSAHS patients with and without MS (p = 0.041). A significant reduction was observed in the aldosterone levels in patients under CPAP treatment (p = 0.012).

Conclusion

This study shows that aldosterone levels are elevated in OSAHS in comparison to controls, and that CPAP therapy reduces aldosterone levels. It also shows that aldosterone levels are associated with the presence of metabolic syndrome, suggesting that aldosterone excess might predispose or aggravate the metabolic and cardiovascular complications of OSAHS.

Trial registration

The study is not a randomized controlled trial and was not registered.

What is the key question?

Are aldosterone levels elevated in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS), and associated with the presence of metabolic syndrome (MS)?

What is the bottom line?

Current data indicate that OSAHS is highly associated with MS. The underlying mechanistic links between OSAHS and MS are not well delineated to date.There is a close relationship between the Renin-Angiotensin-Aldosterone system and hypertension, and recent evidence involves aldosterone in the pathogenesis of MS.

Why read on?

These findings show that aldosterone levels are elevated in OSAHS in comparison to controls, and continuous positive airway pressure (CPAP) therapy reduces aldosterone levels. They also show that aldosterone levels are associated with the presence of metabolic syndrome, suggesting a potential role of aldosterone excess in the development of metabolic and cardiovascular complications in patients with OSAHS.

What is the bottom line?

Current data indicate that OSAHS is highly associated with MS. The underlying mechanistic links between OSAHS and MS are not well delineated to date.There is a close relationship between the Renin-Angiotensin-Aldosterone system and hypertension, and recent evidence involves aldosterone in the pathogenesis of MS.

Why read on?

These findings show that aldosterone levels are elevated in OSAHS in comparison to controls, and continuous positive airway pressure (CPAP) therapy reduces aldosterone levels. They also show that aldosterone levels are associated with the presence of metabolic syndrome, suggesting a potential role of aldosterone excess in the development of metabolic and cardiovascular complications in patients with OSAHS.