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1.
Am Nat ; 198(2): 295-309, 2021 08.
Article in English | MEDLINE | ID: mdl-34260872

ABSTRACT

AbstractTransitions between sexual and unisexual reproductive modes have significant consequences for the evolutionary trajectories of species. These transitions have occurred numerous times in vertebrates and are frequently mediated by hybridization events. Triploid unisexual vertebrates are thought to arise through hybridization between individuals of a diploid unisexual lineage and a sexual species, although additional evidence that confirms this mechanism is needed in numerous groups. North American whiptail lizards (Aspidoscelis) are notable for being one of the largest radiations of unisexual vertebrates, and the most diverse group of Aspidoscelis includes numerous triploid lineages that have no known diploid unisexual ancestors. This pattern of "missing" ancestors may result from the short evolutionary life span of unisexual lineages or the selective advantages of polyploidy, or it could suggest that alternative mechanisms of triploid formation are operating in nature. We leverage genomic, morphological, and karyotypic data to describe a new diploid unisexual whiptail and show that it is likely the unisexual progenitor of an extant triploid lineage, A. opatae. We also resolve patterns of polyploidization within the A. sexlineatus species group and test predictions about the phenotypic outcomes of hybridization.


Subject(s)
Lizards , Animals , Biological Evolution , Diploidy , Humans , Lizards/genetics , Mexico , Polyploidy
2.
Chem Sci ; 11(40): 10939-10944, 2020 Sep 30.
Article in English | MEDLINE | ID: mdl-34094343

ABSTRACT

The recent natural product isolates spiroviolene and spirograterpene A are two relatively non-functionalized linear triquinane terpenes with a large number of structural homologies. Nevertheless, three significant areas of structural disparity exist based on their original assignments, one of which implies a key stereochemical divergence early in their respective biosyntheses. Herein, using two known bicyclic ketone intermediates, a core Pd-catalyzed Heck cyclization sequence, and several chemoselective transformations, we describe concise total syntheses of both natural product targets and propose that the structure of spiroviolene should be reassigned. As a result, these natural products possess greater homology than previously anticipated.

3.
Chem Sci ; 11(8): 2175-2180, 2019 Dec 26.
Article in English | MEDLINE | ID: mdl-34123308

ABSTRACT

Despite the proven value in utilizing pyrone dienes to create molecular complexity via Diels-Alder reactions with varied dienophiles, few examples of effective catalytic, asymmetric variants of this process have been developed. Herein, we show that the use of Jørgensen-Hayashi-type catalysts can convert an array of α,ß-unsaturated aldehydes into chiral dienamines that can formally add in a Diels-Alder fashion to a number of electron-deficient pyrones of the coumalate-type to generate optically active [2.2.2]-bicyclic lactones. In most cases, the reactions proceed with good to excellent diastereo- and enantiocontrol (up to 99% ee). Models to explain that stereoselectivity, as well as several additional transformations of the resultant products, are also presented.

4.
PLoS One ; 7(5): e37539, 2012.
Article in English | MEDLINE | ID: mdl-22624047

ABSTRACT

Following influenza infection, natural killer (NK) cells function as interim effectors by suppressing viral replication until CD8 T cells are activated, proliferate, and are mobilized within the respiratory tract. Thus, NK cells are an important first line of defense against influenza virus. Here, in a murine model of influenza, we show that virally-induced IL-15 facilitates the trafficking of NK cells into the lung airways. Blocking IL-15 delays NK cell entry to the site of infection and results in a disregulated control of early viral replication. By the same principle, viral control by NK cells can be therapeutically enhanced via intranasal administration of exogenous IL-15 in the early days post influenza infection. In addition to controlling early viral replication, this IL-15-induced mobilization of NK cells to the lung airways has important downstream consequences on adaptive responses. Primarily, depletion of responding NK1.1+ NK cells is associated with reduced immigration of influenza-specific CD8 T cells to the site of infection. Together this work suggests that local deposits of IL-15 in the lung airways regulate the coordinated innate and adaptive immune responses to influenza infection and may represent an important point of immune intervention.


Subject(s)
Immunity, Innate/immunology , Interleukin-15/immunology , Killer Cells, Natural/immunology , Orthomyxoviridae Infections/immunology , Respiratory System/immunology , Animals , Bronchoalveolar Lavage , Cell Movement/drug effects , Cell Movement/immunology , Flow Cytometry , Interleukin-15/pharmacology , Killer Cells, Natural/drug effects , Mice , Mice, Inbred C57BL , Respiratory System/virology
5.
J Immunol ; 186(1): 174-82, 2011 Jan 01.
Article in English | MEDLINE | ID: mdl-21098221

ABSTRACT

The cytokines generated locally in response to infection play an important role in CD8 T cell trafficking, survival, and effector function, rendering these signals prime candidates for immune intervention. In this paper, we show that localized increases in the homeostatic cytokine IL-15 induced by influenza infection is responsible for the migration of CD8 effector T cells to the site of infection. Moreover, intranasal delivery of IL-15-IL-15Rα soluble complexes (IL-15c) specifically restores the frequency of effector T cells lost in the lung airways of IL-15-deficient animals after influenza infection. Exogenous IL-15c quantitatively augments the respiratory CD8 T cell response, and continued administration of IL-15c throughout the contraction phase of the anti-influenza CD8 T cell response magnifies the resultant CD8 T cell memory generated in situ. This treatment extends the ability of these cells to protect against heterologous infection, immunity that typically depreciates over time. Overall, our studies describe what to our knowledge is a new function for IL-15 in attracting effector CD8 T cells to the lung airways and suggest that adjuvanting IL-15 could be used to prolong anti-influenza CD8 T cell responses at mucosal surfaces to facilitate pathogen elimination.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , Cell Movement/immunology , Influenza A Virus, H1N1 Subtype/immunology , Influenza A Virus, H3N2 Subtype/immunology , Interleukin-15/physiology , Lung/immunology , Lung/virology , Orthomyxoviridae Infections/immunology , Animals , CD8-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/virology , Cell Differentiation/immunology , Immunologic Memory , Interleukin-15/biosynthesis , Lung/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Orthomyxoviridae Infections/metabolism , Orthomyxoviridae Infections/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/metabolism , Pneumonia, Viral/prevention & control , Respiratory Tract Infections/immunology , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/virology
6.
Mol Ecol ; 16(5): 1035-54, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17305859

ABSTRACT

We investigated a hybrid zone between two major lineages of fence lizards (Sceloporus cowlesi and Sceloporus tristichus) in the Sceloporus undulatus species complex in eastern Arizona. This zone occurs in an ecotone between Great Basin Grassland and Conifer Woodland habitats. We analysed spatial variation in mtDNA (N=401; 969 bp), chromosomes (N=217), and morphology (N=312; 11 characters) to characterize the hybrid zone and assess species limits. A fine-scale population level phylogenetic analysis refined the boundaries between these species and indicated that four nonsister mtDNA clades (three belonging to S. tristichus and one to S. cowlesi) are sympatric at the centre of the zone. Estimates of cytonuclear disequilibria in the population closest to the centre of the hybrid zone suggest that the S. tristichus clades are randomly mating, but that the S. cowlesi haplotype has a significant nonrandom association with nuclear alleles. Maximum-likelihood cline-fitting analyses suggest that the karyotype, morphology, and dorsal colour pattern clines are all coincident, but the mtDNA cline is skewed significantly to the south. A temporal comparison of cline centres utilizing karyotype data collected in the early 1970s and in 2002 suggests that the cline may have shifted by approximately 1.5 km to the north over a 30-year period. The recent northward expansion of juniper trees into the Little Colorado River Basin resulting from intense cattle overgrazing provides a plausible mechanism for a shifting hybrid zone and the introgression of the mtDNA haplotypes, which appear to be selectively neutral. It is clear that complex interactions are operating simultaneously in this contact zone, including the formation of hybrids between populations within S. tristichus having diagnostic mtDNA, morphology, karyotypes, and dorsal colour patterns, and secondary contact between these and a distantly related yet morphologically cryptic mtDNA lineage (S. cowlesi).


Subject(s)
DNA, Mitochondrial/chemistry , Hybridization, Genetic , Lizards/genetics , Animals , Arizona , Chromosomes , Haplotypes , Karyotyping , Lizards/anatomy & histology , Lizards/physiology , Phylogeny , Sequence Analysis, DNA , Sexual Behavior, Animal
8.
J Morphol ; 201(3): 215-234, 1989 Sep.
Article in English | MEDLINE | ID: mdl-29865675

ABSTRACT

All adult specimens known for Gymnophthalmus underwoodi are females, and their mode of reproduction has been a mystery. In order to rule out the possibility of a bisexual mode of reproduction by means of mating with undiscovered males, hermaphroditism, or sex reversal during ontogeny, we examined hundreds of serial histological sections of complete reproductive tracts from juveniles and adults representing two generations of a lineage raised in captivity. In addition, comparative dissections were performed on other individuals and other species, and reproduction to the F5 generation was documented in laboratory colonies of G. underwoodi established from Trinidad and Surinam stocks. A lineage of three successive generations was produced entirely by individuals that were maintained in isolation from the moment of hatching. All specimens of G. underwoodi proved to be female, with reproductive anatomy identical to that of females of closely related, bisexual species of Gymnophthalmus: G. pleei and G. speciosus. Thus, G. underwoodi is an all-female species that reproduces by means of strict parthenogenesis, in the absence of sperm. As in the macroteiids of the genus Cnemidophorus studied previously, Gymnophthalmus has functional mesonephric kidneys throughout life. G. underwoodi ranks among the smallest amniotes, adults weighing about 1.2 gm and having a body length of 36-43 mm. Data from the laboratory colonies indicate the following: clutch size, 1-4 (X = 2); mean egg size about 9.4 × 6.5 mm (weight, 0.23 gm); development time, up to 61 days or more; hatchling body length, 16-19 mm (X = 18); hatchling tail length, 18-25 mm (X = 22); hatchling weight, 0.09-0.14 gm (X = 0.115); reproduction continuous year round with individuals able to produce successive clutches in less than a month but quiescent periods following reproductive sessions; maturity attainable seven mo after hatching; longevity at least 4 yr and 5 mo; and a dramatic decline occurred in egg viability in successive generations in the laboratory.

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