PubMed | Montpellier University, University of Zürich, The Jackson Laboratory, Leibniz Institute for Zoo and Wildlife Research and 21 more.
Type: Journal Article | Journal: Molecular biology and evolution | Year: 2016
A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether selfish genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.
Rettenmund C.,University of Wisconsin - Madison |
Sladky K.K.,University of Wisconsin - Madison |
Rodriguez D.,University of Wisconsin - Madison |
Rodriguez D.,Louisiana State University |
And 4 more authors.
Journal of Zoo and Wildlife Medicine | Year: 2010
Pulmonary carcinoma was diagnosed in an 18-year-old captive female great horned owl (Bubo virginianus). The owl presented with a history of progressive weakness and sudden onset of frank blood in the droppings. On physical examination, the owl had multiple white to yellow plaques in the oral cavity, decreased air sac sounds on the right side, dyspnea (during manual restraint), and reduced pectoral musculature. Whole-body radiographs revealed obliteration of the right-sided air sacs, a soft tissue plaque/density in the left caudal thoracic air sac, soft tissue opacity over the coelomic organs, and increased medullary opacity in the distal right humerus. The owl died during anesthetic recovery, and the body was submitted for necropsy. Although the clinical signs, physical examination results, radiographic signs, and gross pathology supported a diagnosis of mycotic infection, such as aspergillosis, histopathology confirmed pulmonary carcinoma with metastases to the air sacs and humerus. Copyright 2010 by American Association of Zoo Veterinarians.
Ma X.,Chinese University of Hong Kong |
Cheng K.-T.,U.S. National Institutes of Health |
Wong C.-O.,Chinese University of Hong Kong |
Wong C.-O.,University of Texas Health Science Center at Houston |
And 4 more authors.
Cell Calcium | Year: 2011
There is controversy as to whether TRP channels participate in mediating store-operated current (I SOC) and store-operated Ca 2+ entry (SOCE). Our recent study has demonstrated that TRPC1 forms heteromeric channels with TRPV4 in vascular endothelial cells and that Ca 2+ store depletion enhances the vesicle trafficking of heteromeric TRPV4-C1 channels, causing insertion of more channels into the plasma membrane in vascular endothelial cells. In the present study, we determined whether the enhanced TRPV4-C1 insertion to the plasma membrane could contribute to SOCE and I SOC. We found that thapsigargin-induced SOCE was much lower in aortic endothelial cells derived from trpv4 -/- or trpc1 -/- knockout mice when compared to that of wild-type mice. In human umbilical vein endothelial cells (HUVECs), thapsigargin-induced SOCE was markedly reduced by knocking down the expression of TRPC1 and/or TRPV4 with respective siRNAs. Brefeldin A, a blocker of vesicular translocation, inhibited the SOCE. These results suggest that an enhanced vesicular trafficking of heteromeric TRPV4-C1 channels contributes to SOCE in vascular endothelial cells. Vascular tension studies suggest that such an enhanced trafficking of TRPV4-C1 channels may play a role in thapsigargin-induced vascular relaxation in rat small mesenteric arteries. © 2011 Elsevier Ltd.
Lowe J.M.,National Institute of Environmental science |
Menendez D.,National Institute of Environmental science |
Bushel P.R.,Biostatistics Branch |
Shatz M.,National Institute of Environmental science |
And 5 more authors.
Cancer Research | Year: 2014
Macrophages are sentinel immune cells that survey the tissue microenvironment, releasing cytokines in response to both exogenous insults and endogenous events such as tumorigenesis. Macrophages mediate tumor surveillance and therapy-induced tumor regression; however, tumor-Associated macrophages (TAM) and their products may also promote tumor progression. Whereas NF-κB is prominent in macrophage-initiated inflammatory responses, little is known about the role of p53 in macrophage responses to environmental challenge, including chemotherapy or in TAMs. Here, we report that NF-κB and p53, which generally have opposing effects in cancer cells, coregulate induction of proinflammatory genes in primary human monocytes and macrophages. Using Nutlin-3 as a tool, we demonstrate that p53 and NF-κB rapidly and highly induce interleukin (IL)-6 by binding to its promoter. Transcriptome analysis revealed global p53/NF-κB co-regulation of immune response genes, including several chemokines, which effectively induced human neutrophil migration. In addition, we show that p53, activated by tumor cell paracrine factors, induces high basal levels of macrophage IL-6 in a TAM model system [tumor-conditioned macrophages (TCM)]. Compared with normal macrophages, TCMs exhibited higher p53 levels, enhanced p53 binding to the IL-6 promoter, and reduced IL-6 levels upon p53 inhibition. Taken together, we describe a mechanism by which human macrophages integrate signals through p53 and NF-κB to drive proinflammatory cytokine induction. Our results implicate a novel role for macrophage p53 in conditioning the tumor microenvironment and suggest a potential mechanism by which p53-Activating chemotherapeutics, acting upon p53-sufficient macrophages and precursor monocytes, may indirectly impact tumors lacking functional p53. © 2014 American Association for Cancer Research.
Rider L.G.,National Institute of Environmental science |
Danko K.,Debrecen University |
Miller F.W.,National Institute of Environmental science
Current Opinion in Rheumatology | Year: 2014
Purpose of review: Clinical registries and biorepositories have proven extremely useful in many studies of diseases, especially rare diseases. Given their rarity and diversity, the idiopathic inflammatory myopathies, or myositis syndromes, have benefited from individual researchers' collections of cohorts of patients. Major efforts are being made to establish large registries and biorepositories that will allow many additional studies to be performed that were not possible before. Here, we describe the registries developed by investigators and patient support groups that are currently available for collaborative research purposes. Recent findings: We have identified 46 myositis research registries, including many with biorepositories, which have been developed for a wide variety of purposes and have resulted in great advances in understanding the range of phenotypes, clinical presentations, risk factors, pathogenic mechanisms, outcome assessment, therapeutic responses, and prognoses. These are now available for collaborative use to undertake additional studies. Two myositis patient registries have been developed for research, and myositis patient support groups maintain demographic registries with large numbers of patients available to be contacted for potential research participation. Summary: Investigator-initiated myositis research registries and biorepositories have proven extremely useful in understanding many aspects of these rare and diverse autoimmune diseases. These registries and biorepositories, in addition to those developed by myositis patient support groups, deserve continued support to maintain the momentum in this field as they offer major opportunities to improve understanding of the pathogenesis and treatment of these diseases in cost-effective ways. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Hong S.,University of Seoul |
Choi I.,University of Seoul |
Lim B.J.,National Institute of Environmental Science |
Kim H.,University of Seoul
Sensors (Switzerland) | Year: 2012
In Korea, more than 80% of municipal wastewater treatment plants (WWTPs) with capacities of 500 m3·d-1 or more are capable of removing nitrogen from wastewater through biological nitrification and denitrification processes. Normally, these biological processes show excellent performance, but if a toxic chemical is present in the influent to a WWTP, the biological processes (especially, the nitrification process) may be affected and fail to function normally; nitrifying bacteria are known very vulnerable to toxic substances. Then, the toxic compound as well as the nitrogen in wastewater may be discharged into a receiving water body without any proper treatment. Moreover, it may take significant time for the process to return back its normal state. In this study, a DO- and pH-based strategy to identify potential nitrification inhibition was developed to detect early the inflow of toxic compounds to a biological nitrogen removal process. This strategy utilizes significant changes observed in the oxygen uptake rate and the pH profiles of the mixed liquor when the activity of nitrifying bacteria is inhibited. Using the strategy, the toxicity from test wastewater with 2.5 mg·L-1 Hg2+, 0.5 mg·L-1 allythiourea, or 0.25 mg·L-1 chloroform could be successfully detected. © 2012 by the authors; licensee MDPI, Basel, Switzerland.