Hybrid zones provide insights into the evolution of reproductive isolation. Sexual selection can contribute to the evolution of reproductive barriers, but it remains poorly understood how sexual ...traits impact gene flow in secondary contact. Here, we show that a recently evolved suite of sexual traits that function in male-male competition mediates gene flow between two lineages of wall lizards (Podarcis muralis). Gene flow was relatively low and asymmetric in the presence of exaggerated male morphology and coloration compared to when the lineages share the ancestral phenotype. Putative barrier loci were enriched in genomic regions that were highly differentiated between the two lineages and showed low concordance between the transects. The exception was a consistently low genetic exchange around ATXN1, a gene that modulates social behavior. We suggest that this gene may contribute to the male mate preferences that are known to cause lineage-assortative mating in this species. Although female choice modulates the degree of reproductive isolation in a variety of taxa, wall lizards demonstrate that both male-male competition and male mate choice can contribute to the extent of gene flow between lineages.
The aim of this qualitative study was to clarify how terminally ill elderly patients in acute wards perceive the end of life and what are their needs and wishes regarding care. The patients, despite ...their advanced illness, wished to be treated actively and hoped for more conversations with doctors about active care. They were content with their daily care but evaluated the care in light of the great workload of the nurses, forgiving them for not having time to talk to individual patients. They had specific modest wishes, but were reluctant to express even these because of concern about troubling their caregivers. We conclude that death remained a distant abstraction for these patients with a terminal prognosis. The challenge is to create an intimate caring atmosphere, where the issues related to dying may be elaborated in interaction and the last wishes expressed in a safe atmosphere.
Strongly selected characters can be transferred from one lineage to another with limited genetic exchange, resulting in asymmetric introgression and a mosaic genome in the receiving population. ...However, systems are rarely sufficiently well studied to link the pattern of introgression to its underlying process. Male common wall lizards in western Italy exhibit exaggeration of a suite of sexually selected characters that make them outcompete males from a distantly related lineage that lack these characters. This results in asymmetric hybridization and adaptive introgression of the suite of characters following secondary contact. We developed genomewide markers to infer the demographic history of gene flow between different genetic lineages, identify the spread of the sexually selected syndrome, and test the prediction that introgression should be asymmetric and heterogeneous across the genome. Our results show that secondary contact was accompanied by gene flow in both directions across most of the genome, but with approximately 3% of the genome showing highly asymmetric introgression in the predicted direction. Demographic simulations reveal that this asymmetric gene flow is more recent than the initial secondary contact, and the data suggest that the exaggerated male sexual characters originated within the Italian lineage and subsequently spread throughout this lineage before eventually reaching the contact zone. These results demonstrate that sexual selection can cause a suite of characters to spread throughout both closely and distantly related lineages with limited gene flow across the genome at large.
The membrane-bound enzyme cytochrome c oxidase is responsible for cell respiration in aerobic organisms and conserves free energy from O2reduction into an electrochemical proton gradient by coupling ...the redox reaction to proton-pumping across the membrane. O2reduction produces water at the bimetallic heme a3/ CuBactive site next to a hydrophobic cavity deep within the membrane. Water molecules in this cavity have been suggested to play an important role in the proton-pumping mechanism. Here, we show by molecular dynamics simulations that the conserved arginine/heme a3Δ-propionate ion pair provides a gate, which exhibits reversible thermal opening that is governed by the redox state and the water molecules in the cavity. An important role of this gate in the proton-pumping mechanism is supported by site-directed mutagenesis experiments. Transport of the product water out of the enzyme must be rigidly controlled to prevent water-mediated proton leaks that could compromise the proton-pumping function. Exit of product water is observed through the same arginine/propionate gate, which provides an explanation for the observed extraordinary spatial specificity of water expulsion from the enzyme.
Malignant gliomas are associated with high mortality due to infiltrative growth, recurrence, and malignant progression. Even with the most efficient therapy combinations, median survival of the ...glioblastoma multiforme (grade 4) patients is less than 15 months. Therefore, new treatment approaches are urgently needed. We describe here identification of a novel homing peptide that recognizes tumor vessels and invasive tumor satellites in glioblastomas. We demonstrate successful brain tumor imaging using radiolabeled peptide in whole-body SPECT/CT imaging. Peptide-targeted delivery of chemotherapeutics prolonged the lifespan of mice bearing invasive brain tumors and significantly reduced the number of tumor satellites compared with the free drug. Moreover, we identified mammary-derived growth inhibitor (MDGI/H-FABP/FABP3) as the interacting partner for our peptide on brain tumor tissue. MDGI was expressed in human brain tumor specimens in a grade-dependent manner and its expression positively correlated with the histologic grade of the tumor, suggesting MDGI as a novel marker for malignant gliomas.
Background: The growth of life-sustaining medical technology and greater attention to medical care at the end of life have provoked interest in issues related to advance care planning. Objective: To ...investigate how having a living will (LW), resuscitation preferences, health condition, and life attitudes are related in home-dwelling elderly people. Methods: In a cross-sectional descriptive study, detailed assessments were made of 378 home-dwelling elderly individuals participating in a cardiovascular prevention study (DEBATE Study). The participants were inquired about a preexistence of a written document (LW) concerning life-sustaining care, preferences of cardiopulmonary resuscitation (CPR) in their current situation, and attitudes towards life. General health, physical and cognitive functioning, the presence of depression, and quality of life were also assessed. Results: Forty-four of the 378 participants (12%) had a LW. As compared with those without one (n = 334), there were more women 82% (36/44) vs. 63% (210/334) and widows 57% (25/44) vs. 41% (135/334) among those with a LW. They were also more educated and considered their health to be better. Despite having a LW, 46% (20/44) of them preferred CPR in their current condition, a proportion not statistically different from the 58% (194/334) of the individuals without a LW. In the whole sample, 39% (149/378) of the individuals preferred to forgo CPR. As compared with those preferring CPR, they were older, more often women, and widowed. Participants preferring to forgo CPR had a poorer quality of life, were more lonely, and showed signs of depression more often than those preferring CPR. The preference to forgo CPR was related to attitudes towards life regardless of physical or cognitive functioning. Conclusions: Having a LW does not reduce the reported preference of CPR which is related more to current mental status and life attitudes. In-depth assessment of the patient’s preferences should be performed in any comprehensive care plan.
Abstract
The Mediterranean Basin has experienced extensive change in geology and climate over the past six million years. Yet, the relative importance of key geological events for the distribution ...and genetic structure of the Mediterranean fauna remains poorly understood. Here, we use population genomic and phylogenomic analyses to establish the evolutionary history and genetic structure of common wall lizards (Podarcis muralis). This species is particularly informative because, in contrast to other Mediterranean lizards, it is widespread across the Iberian, Italian, and Balkan Peninsulas, and in extra-Mediterranean regions. We found strong support for six major lineages within P. muralis, which were largely discordant with the phylogenetic relationship of mitochondrial DNA. The most recent common ancestor of extant P. muralis was likely distributed in the Italian Peninsula, and experienced an “Out-of-Italy” expansion following the Messinian salinity crisis (∼5 Mya), resulting in the differentiation into the extant lineages on the Iberian, Italian, and Balkan Peninsulas. Introgression analysis revealed that both inter- and intraspecific gene flows have been pervasive throughout the evolutionary history of P. muralis. For example, the Southern Italy lineage has a hybrid origin, formed through admixture between the Central Italy lineage and an ancient lineage that was the sister to all other P. muralis. More recent genetic differentiation is associated with the onset of the Quaternary glaciations, which influenced population dynamics and genetic diversity of contemporary lineages. These results demonstrate the pervasive role of Mediterranean geology and climate for the evolutionary history and population genetic structure of extant species.
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