Vicki Swier - Academia.edu (original) (raw)
Papers by Vicki Swier
Cytogenetic and Genome Research, 2009
volved heterochromatic additions, centric fusions, tandem fusions, pericentric inversions, as wel... more volved heterochromatic additions, centric fusions, tandem fusions, pericentric inversions, as well as the addition of interstitial DNA not identified by chromosome paints or C-banding. The hypothesis that the ancestral karyotype for this complex had a diploid number of 52, a fundamental number of 52, and a G-band pattern of which most, if not all are similar to that present in modern day S. hispidus fails to be rejected. This hypothesis remains viable as an explanation of chromosomal evolution in Sigmodontine rodents.
Journal of Heredity, May 16, 2012
We studied the chromosomal distribution of telomere repeats (TTAGGG) n in 8 species of Sigmodon (... more We studied the chromosomal distribution of telomere repeats (TTAGGG) n in 8 species of Sigmodon (cotton rats) using chromosome paints fluorescent in situ hybridization (FISH) from Sigmodon hispidus. In 2 species with the proposed primitive karyotype for the genus, telomere repeats were restricted to telomeric sites. But in the other 6 species that include 3 with proposed primitive karyotypes and 3 with highly rearranged karyotypes, telomere repeats were found on both telomeric sites and within interstitial telomeric sites (ITSs). To explain the distribution of ITS in Sigmodon, we gather data from C-bands, silver nitrate staining, G-bands, and chromosomal paint data from previous published studies. We did find some correlation with ITS and heterochromatin, euchromatic chromosomal rearrangements, and nucleolar organizing regions. No one type of chromosomal structure explains all ITS in Sigmodon. Multiple explanations and mechanisms for movement of intragenomic sequences are required to explain ITS in this genus. We rejected the hypothesis that age of a lineage correlates with the presence of ITS using divergence time estimate analyses. This multigene phylogeny places species with ITS (S. arizonae, S. fulviventer, S. hispidus, S. mascotensis, S. ochrognathus, and S. toltecus) in the clade with a species without ITS (S. hirsutus). Lineages with ITS (S. arizonae and S. mascotensis) arose independently from a lineage absent of ITS (S. hirsutus) around 0.67 to 0.83 Ma. The rearranged karyotypes of S. mascotensis and S. arizonae appear to be an independently derived autapomorphic characters, supporting a fast rate of chromosomal changes that vary among species.
Scientific Reports, Mar 29, 2023
Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pe... more Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pediatric disease, with symptom development leading to clinical diagnosis. Early diagnosis and effective tracking of disease progression are required for treatment. We hypothesize that brain volumetry is valuable in identifying CLN2 disease at an early stage and tracking disease progression in a genetically modified miniswine model. CLN2 R208X/R208X miniswine and wild type controls were evaluated at 12-and 17-months of age, correlating to early and late stages of disease progression. Magnetic resonance imaging (MRI) T1-and T2-weighted data were acquired. Total intercranial, gray matter, cerebrospinal fluid, white matter, caudate, putamen, and ventricle volumes were calculated and expressed as proportions of the intracranial volume. The brain regions were compared between timepoints and cohorts using Gardner-Altman plots, mean differences, and confidence intervals. At an early stage of disease, the total intracranial volume (− 9.06 cm 3), gray matter (− 4.37% 95 CI − 7.41; − 1.83), caudate (− 0.16%, 95 CI − 0.24; − 0.08) and putamen (− 0.11% 95 CI − 0.23; − 0.02) were all notably smaller in CLN2 R208X/R208X miniswines versus WT, while cerebrospinal fluid was larger (+ 3.42%, 95 CI 2.54; 6.18). As the disease progressed to a later stage, the difference between the gray matter (− 8.27%, 95 CI − 10.1; − 5.56) and cerebrospinal fluid (+ 6.88%, 95 CI 4.31; 8.51) continued to become more pronounced, while others remained stable. MRI brain volumetry in this miniswine model of CLN2 disease is sensitive to early disease detection and longitudinal change monitoring, providing a valuable tool for pre-clinical treatment development and evaluation. Abbreviations CLN2 Late-infantile neuronal ceroid lipofuscinosis type 2 MRI Magnetic resonance imaging GM Gray matter WM White matter CSF Cerebrospinal fluid ICV Intracranial volume WT Wild type (control) CI Confidence interval SubC Mictochondrial ATP synthase subunit c Batten disease, or neuronal ceroid lipofuscinoses, is a group of neurodegenerative diseases in which mutations in 13-14 different genes can cause issues with a lysosome's capability to recycle or process molecules. All forms of Batten disease show similar symptoms but are caused by different gene mutations 1,2. The late-infantile neuronal
Journal of Mammalogy, Apr 16, 2010
Nucleotide sequences from 94 individuals representing the Oryzomys palustris complex (O. palustri... more Nucleotide sequences from 94 individuals representing the Oryzomys palustris complex (O. palustris and O. couesi) were examined to assess phylogenetic relationships and taxonomic boundaries. Sequence data from the entire mitochondrial cytochrome-b (Cytb; 1,143 base pairs [bp]), a portion of exon 1 of the nuclear interphotoreceptor retinoid-binding protein (1,266 bp), and intron 2 of the alcohol dehydrogenase 1 (580 bp) genes were analyzed using phylogenetic methods (maximum parsimony and Bayesian inference). In the Cytb analysis, individuals recognized as O. palustris and O. couesi formed reciprocally monophyletic clades supporting their recognition as species; however, additional phylogenetically informative groups were present within each of the 2 nominate clades. In addition, levels of genetic divergence within the currently recognized taxa exceeded values normally associated with intraspecies variation. Together, the phylogenetic and genetic divergence data imply that consideration should be given to recognizing 4 additional species in this complex.
Journal of Virology, Dec 15, 2005
A large percentage of the repetitive elements in mammalian genomes are retroelements, which have ... more A large percentage of the repetitive elements in mammalian genomes are retroelements, which have been moved primarily by LINE-1 retrotransposons and endogenous retroviruses. Although LINE-1 elements have remained active throughout the mammalian radiation, specific groups of endogenous retroviruses generally remain active for comparatively shorter periods of time. Identification of an unusual extinction of LINE-1 activity in a group of South American rodents has opened a window for examination of the interplay in mammalian genomes between these ubiquitous retroelements. In the course of a search for any type of repetitive sequences whose copy numbers have substantially changed in Oryzomys palustris, a species that has lost LINE-1 activity, versus Sigmodon hispidus, a closely related species retaining LINE-1 activity, we have identified an endogenous retrovirus family differentially amplified in these two species. Analysis of three full-length, recently transposed copies, called mysTR elements, revealed gag, pro, and pol coding regions containing stop codons which may have accumulated either before or after retrotransposition. Isolation of related sequences in S. hispidus and the LINE-1 active outgroup species, Peromyscus maniculatus, by PCR of a pro-pol region has allowed determination of copy numbers in each species. Unusually high copy numbers of approximately 10,000 in O. palustris versus 1,000 in S. hispidus and 4,500 in the more distantly related P. maniculatus leave open the question of whether there is a connection between endogenous retrovirus activity and LINE-1 inactivity. Nevertheless, these independent expansions of mysTR represent recent amplifications of this endogenous retrovirus family to unprecedented levels.
Neurotherapeutics, Sep 13, 2022
Scientific Reports, Mar 29, 2023
Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pe... more Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pediatric disease, with symptom development leading to clinical diagnosis. Early diagnosis and effective tracking of disease progression are required for treatment. We hypothesize that brain volumetry is valuable in identifying CLN2 disease at an early stage and tracking disease progression in a genetically modified miniswine model. CLN2 R208X/R208X miniswine and wild type controls were evaluated at 12-and 17-months of age, correlating to early and late stages of disease progression. Magnetic resonance imaging (MRI) T1-and T2-weighted data were acquired. Total intercranial, gray matter, cerebrospinal fluid, white matter, caudate, putamen, and ventricle volumes were calculated and expressed as proportions of the intracranial volume. The brain regions were compared between timepoints and cohorts using Gardner-Altman plots, mean differences, and confidence intervals. At an early stage of disease, the total intracranial volume (− 9.06 cm 3), gray matter (− 4.37% 95 CI − 7.41; − 1.83), caudate (− 0.16%, 95 CI − 0.24; − 0.08) and putamen (− 0.11% 95 CI − 0.23; − 0.02) were all notably smaller in CLN2 R208X/R208X miniswines versus WT, while cerebrospinal fluid was larger (+ 3.42%, 95 CI 2.54; 6.18). As the disease progressed to a later stage, the difference between the gray matter (− 8.27%, 95 CI − 10.1; − 5.56) and cerebrospinal fluid (+ 6.88%, 95 CI 4.31; 8.51) continued to become more pronounced, while others remained stable. MRI brain volumetry in this miniswine model of CLN2 disease is sensitive to early disease detection and longitudinal change monitoring, providing a valuable tool for pre-clinical treatment development and evaluation. Abbreviations CLN2 Late-infantile neuronal ceroid lipofuscinosis type 2 MRI Magnetic resonance imaging GM Gray matter WM White matter CSF Cerebrospinal fluid ICV Intracranial volume WT Wild type (control) CI Confidence interval SubC Mictochondrial ATP synthase subunit c Batten disease, or neuronal ceroid lipofuscinoses, is a group of neurodegenerative diseases in which mutations in 13-14 different genes can cause issues with a lysosome's capability to recycle or process molecules. All forms of Batten disease show similar symptoms but are caused by different gene mutations 1,2. The late-infantile neuronal
Mouse models of CLN3 Batten disease, a rare lysosomal storage disorder with no cure, have improve... more Mouse models of CLN3 Batten disease, a rare lysosomal storage disorder with no cure, have improved our understanding of CLN3 biology and therapeutics through their ease of use and a consistent display of cellular pathology. However, the translatability of murine models is limited by disparities in anatomy, body size, life span, and inconsistent, subtle behavior deficits that can be difficult to detect in CLN3 mutant mouse models, limiting their utility in preclinical studies. Here we present a longitudinal characterization of a novel miniswine model of CLN3 disease that recapitulates the most common human pathogenic variant, an exon 7-8 deletion (CLN3Δex7/8). Progressive pathology and neuron loss is observed in various regions of the CLN3Δex7/8 miniswine brain and retina. Additionally, mutant miniswine present with vision impairment and motor abnormalities, similar to deficits seen in human patients. Taken together, the CLN3Δex7/8 miniswine model shows consistent and progressive Bat...
Atherosclerosis, 2016
as monocytes, key drivers of plaque inflammation, have been reported to accumulate remnant choles... more as monocytes, key drivers of plaque inflammation, have been reported to accumulate remnant cholesterol, enhancing migratory capacity, we assessed the phenotype of circulating monocytes. Methods: We performed 18fluorodeoxyglucose positron emission tomography with computed tomography (18 F-FDG PET/CT) imaging in patients with familial dysbetalipoproteinemia (FD) compared with matched healthy controls. Furthermore, we performed monocyte characterization studies. Results: We included 14 FD patients (age 61±8, 64% male) and 14 controls (age 58±6, 64% male). FD patients had a significant higher total cholesterol, remnant cholesterol and plasma triglycerides. 18 F-FDG uptake in the arterial wall was significantly increased in FD patients compared with controls (carotid target-to-background-ratio: 2,03±0,39 versus 1,62±0,29, p<0.001). Furthermore, monocyte count was significantly increased and characterization showed higher surface expression of adhesion markers CD18, CD11b and CD11c. Assessment of lipid accumulation showed an increase in percentage of monocytes with lipid droplets and a concomitant increase in number of lipid droplets. Conclusions: FD patients have increased arterial wall inflammation and are characterized by an inflammatory phenotype of circulating monocytes, which accumulated larger amounts of lipids. These findings indicate an important inflammatory component to the atherogenicity of remnant cholesterol, contributing to its relationship with increased CVD risk.
We studied the chromosomal distribution of telomere repeats (TTAGGG)n in 8 species of Sigmodon (c... more We studied the chromosomal distribution of telomere repeats (TTAGGG)n in 8 species of Sigmodon (cotton rats) using chromosome paints fluorescent in situ hybridization (FISH) from Sigmodon hispidus. In 2 species with the proposed primitive karyotype for the genus, telomere repeats were restricted to telomeric sites. But in the other 6 species that include 3 with proposed primitive karyotypes and 3 with highly rearranged karyotypes, telomere repeats were found on both telomeric sites and within interstitial telomeric sites (ITSs). To explain the distribution of ITS in Sigmodon, we gather data from C-bands, silver nitrate staining, G-bands, and chromosomal paint data from previous published studies. We did find some correlation with ITS and heterochromatin, euchromatic chromosomal rearrangements, and nucleolar organizing regions. No one type of chromosomal structure explains all ITS in Sigmodon. Multiple explanations and mechanisms for movement of intragenomic sequences are required to...
Montserrat is one of several volcanic islands in the archipelago that have been created by the su... more Montserrat is one of several volcanic islands in the archipelago that have been created by the subduction of the Atlantic tectonic plate beneath the Caribbean plate. Most of these islands are dominated by andesitic stratovolcanoes (steep-sided symmetrical cones) that are the result of explosive eruptions and extensive pyroclastic flows that generate a cone composed of alternating layers of volcanic debris. Stratovolcanoes are quite different from the gently sloping shield volcanoes, such as those in Hawaii, which are typically nonexplosive and which produce fluid lavas that can flow great distances from active vents. There are three volcanic massifs on Montserrat-Silver Hills in the north, Centre Hills, and, largest and youngest, the Soufrière Hills, which occupy the southern half of the island (fig. 11.2). Due to its location on a fault line, earthquakes are not uncommon on Montserrat, with several periods of activity reported from the 1890s, 1930s, and 1960s (e.g., Perret 1939). Renewed seismic activity and pyroclastic flows from the Soufrière Hills volcano, which began in 1995, have progressively reduced the eastern and western flanks of the volcano to an ecological wasteland and have buried much of the southern half of the island under varying amounts of volcanic ash. Figure 11.1. Map of the Lesser Antilles showing the position of Montserrat (16°45′N, 62°10′W).
Distribution, Roost Site Selection and Food Habits of bats in Eastern South Dakota
Resumen The karyotype of Peromyscus grandis (Rodentia:
PLOS ONE
Genetically modified swine disease models are becoming increasingly important for studying molecu... more Genetically modified swine disease models are becoming increasingly important for studying molecular, physiological and pathological characteristics of human disorders. Given the limited history of these model systems, there remains a great need for proven molecular reagents in swine tissue. Here, to provide a resource for neurological models of disease, we validated antibodies by immunohistochemistry for use in examining central nervous system (CNS) markers in a recently developed miniswine model of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant tumor predisposition disorder stemming from mutations in NF1, a gene that encodes the Ras-GTPase activating protein neurofibromin. Patients classically present with benign neurofibromas throughout their bodies and can also present with neurological associated symptoms such as chronic pain, cognitive impairment, and behavioral abnormalities. As validated antibodies for immunohistochemistry applications are particularly difficult to find for swine models of neurological disease, we present immunostaining validation of antibodies implicated in glial inflammation (CD68), oligodendrocyte development (NG2, O4 and Olig2), and neuron differentiation and neurotransmission (doublecortin, GAD67, and tyrosine hydroxylase) by examining cellular localization and brain region specificity. Additionally, we confirm the utility of anti-GFAP, anti-Iba1, and anti-MBP antibodies, previously validated in swine, by testing their immunoreactivity across multiple brain regions in mutant NF1 samples. These immunostaining protocols for CNS markers provide a useful resource to the scientific community, furthering the utility of genetically modified miniswine for translational and clinical applications.
Vitamin D functions as a potent immunomodulator by interacting with many immune cells however, it... more Vitamin D functions as a potent immunomodulator by interacting with many immune cells however, its role in regulating inflammation in the epicardial adipose tissue (EAT) is unclear. In the EAT of atherosclerotic microswine that were fed with deficient, sufficient or supplemented levels of vitamin D, we evaluated the phenotype of the macrophages. Vitamin D treatment was continued for 12 months and serum 25(OH)D levels were measured regularly. Infiltration of M1/M2 macrophage was investigated by immunostaining for CCR7 and CD206, respectively in conjunction with a pan macrophage marker CD14. Significant difference in the number of CCR7+ cells was observed in the EAT from vitamin D-deficient swine compared to vitamin D-sufficient or -supplemented swine. Expression of CD206 correlated with high levels of serum 25(OH)D indicating a significant increase in M2 macrophages in the EAT of vitamin D-supplemented compared to -deficient swine. These findings suggest that vitamin D-deficiency exa...
From May 2000 to August 2002, a study was conducted to document the distribution of bats in South... more From May 2000 to August 2002, a study was conducted to document the distribution of bats in South Dakota east of the Missouri River. During the summers of 2000, 2001, and 2002, mist netting and acoustic sampling (Anabat system) were conducted at 35 sites, including state parks, state recreation areas, and national wildlife refuges. Seven species of bat were recorded from this region: Myotis septentrional is, Myotis lucifugus, Myotis ciliolabrum, Eptesicus fus cits, Lasionycteris noctivagans, Lmiunis borealis, and Lasiurus cinereus. Distribution maps and species accounts were compiled for the seven species using data from the summers of 2000, 2001, and 2002 in addition to data from literature records and voucher records.
Genetically modified porcine disease models are becoming increasingly important for studying mole... more Genetically modified porcine disease models are becoming increasingly important for studying molecular, physiological and pathological characteristics of human disorders. Given their limited history, there remains a great need for proven reagents in swine tissue. To provide a resource for neurological models of disease, we validated antibodies by immunohistochemistry for use in examining central nervous system (CNS) markers. To validate these tools in a relevant model, we utilized a recently developed miniswine model of neurofibromatosis type 1 (NF1). NF1 is a tumor predisposition disorder, presenting with different type of tumors. Additionally, neurological associated symptomologies may include chronic pain, cognitive impairment, and behavioral abnormalities, making this miniswine model an ideal candidate for validating CNS-relevant antibodies. We validate antibodies implicated in glial inflammation (CD68), oligodendrocyte development (NG2, O4, Olig2, and myelin PLP), and neuron di...
Cytogenetic and Genome Research, 2009
volved heterochromatic additions, centric fusions, tandem fusions, pericentric inversions, as wel... more volved heterochromatic additions, centric fusions, tandem fusions, pericentric inversions, as well as the addition of interstitial DNA not identified by chromosome paints or C-banding. The hypothesis that the ancestral karyotype for this complex had a diploid number of 52, a fundamental number of 52, and a G-band pattern of which most, if not all are similar to that present in modern day S. hispidus fails to be rejected. This hypothesis remains viable as an explanation of chromosomal evolution in Sigmodontine rodents.
Journal of Heredity, May 16, 2012
We studied the chromosomal distribution of telomere repeats (TTAGGG) n in 8 species of Sigmodon (... more We studied the chromosomal distribution of telomere repeats (TTAGGG) n in 8 species of Sigmodon (cotton rats) using chromosome paints fluorescent in situ hybridization (FISH) from Sigmodon hispidus. In 2 species with the proposed primitive karyotype for the genus, telomere repeats were restricted to telomeric sites. But in the other 6 species that include 3 with proposed primitive karyotypes and 3 with highly rearranged karyotypes, telomere repeats were found on both telomeric sites and within interstitial telomeric sites (ITSs). To explain the distribution of ITS in Sigmodon, we gather data from C-bands, silver nitrate staining, G-bands, and chromosomal paint data from previous published studies. We did find some correlation with ITS and heterochromatin, euchromatic chromosomal rearrangements, and nucleolar organizing regions. No one type of chromosomal structure explains all ITS in Sigmodon. Multiple explanations and mechanisms for movement of intragenomic sequences are required to explain ITS in this genus. We rejected the hypothesis that age of a lineage correlates with the presence of ITS using divergence time estimate analyses. This multigene phylogeny places species with ITS (S. arizonae, S. fulviventer, S. hispidus, S. mascotensis, S. ochrognathus, and S. toltecus) in the clade with a species without ITS (S. hirsutus). Lineages with ITS (S. arizonae and S. mascotensis) arose independently from a lineage absent of ITS (S. hirsutus) around 0.67 to 0.83 Ma. The rearranged karyotypes of S. mascotensis and S. arizonae appear to be an independently derived autapomorphic characters, supporting a fast rate of chromosomal changes that vary among species.
Scientific Reports, Mar 29, 2023
Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pe... more Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pediatric disease, with symptom development leading to clinical diagnosis. Early diagnosis and effective tracking of disease progression are required for treatment. We hypothesize that brain volumetry is valuable in identifying CLN2 disease at an early stage and tracking disease progression in a genetically modified miniswine model. CLN2 R208X/R208X miniswine and wild type controls were evaluated at 12-and 17-months of age, correlating to early and late stages of disease progression. Magnetic resonance imaging (MRI) T1-and T2-weighted data were acquired. Total intercranial, gray matter, cerebrospinal fluid, white matter, caudate, putamen, and ventricle volumes were calculated and expressed as proportions of the intracranial volume. The brain regions were compared between timepoints and cohorts using Gardner-Altman plots, mean differences, and confidence intervals. At an early stage of disease, the total intracranial volume (− 9.06 cm 3), gray matter (− 4.37% 95 CI − 7.41; − 1.83), caudate (− 0.16%, 95 CI − 0.24; − 0.08) and putamen (− 0.11% 95 CI − 0.23; − 0.02) were all notably smaller in CLN2 R208X/R208X miniswines versus WT, while cerebrospinal fluid was larger (+ 3.42%, 95 CI 2.54; 6.18). As the disease progressed to a later stage, the difference between the gray matter (− 8.27%, 95 CI − 10.1; − 5.56) and cerebrospinal fluid (+ 6.88%, 95 CI 4.31; 8.51) continued to become more pronounced, while others remained stable. MRI brain volumetry in this miniswine model of CLN2 disease is sensitive to early disease detection and longitudinal change monitoring, providing a valuable tool for pre-clinical treatment development and evaluation. Abbreviations CLN2 Late-infantile neuronal ceroid lipofuscinosis type 2 MRI Magnetic resonance imaging GM Gray matter WM White matter CSF Cerebrospinal fluid ICV Intracranial volume WT Wild type (control) CI Confidence interval SubC Mictochondrial ATP synthase subunit c Batten disease, or neuronal ceroid lipofuscinoses, is a group of neurodegenerative diseases in which mutations in 13-14 different genes can cause issues with a lysosome's capability to recycle or process molecules. All forms of Batten disease show similar symptoms but are caused by different gene mutations 1,2. The late-infantile neuronal
Journal of Mammalogy, Apr 16, 2010
Nucleotide sequences from 94 individuals representing the Oryzomys palustris complex (O. palustri... more Nucleotide sequences from 94 individuals representing the Oryzomys palustris complex (O. palustris and O. couesi) were examined to assess phylogenetic relationships and taxonomic boundaries. Sequence data from the entire mitochondrial cytochrome-b (Cytb; 1,143 base pairs [bp]), a portion of exon 1 of the nuclear interphotoreceptor retinoid-binding protein (1,266 bp), and intron 2 of the alcohol dehydrogenase 1 (580 bp) genes were analyzed using phylogenetic methods (maximum parsimony and Bayesian inference). In the Cytb analysis, individuals recognized as O. palustris and O. couesi formed reciprocally monophyletic clades supporting their recognition as species; however, additional phylogenetically informative groups were present within each of the 2 nominate clades. In addition, levels of genetic divergence within the currently recognized taxa exceeded values normally associated with intraspecies variation. Together, the phylogenetic and genetic divergence data imply that consideration should be given to recognizing 4 additional species in this complex.
Journal of Virology, Dec 15, 2005
A large percentage of the repetitive elements in mammalian genomes are retroelements, which have ... more A large percentage of the repetitive elements in mammalian genomes are retroelements, which have been moved primarily by LINE-1 retrotransposons and endogenous retroviruses. Although LINE-1 elements have remained active throughout the mammalian radiation, specific groups of endogenous retroviruses generally remain active for comparatively shorter periods of time. Identification of an unusual extinction of LINE-1 activity in a group of South American rodents has opened a window for examination of the interplay in mammalian genomes between these ubiquitous retroelements. In the course of a search for any type of repetitive sequences whose copy numbers have substantially changed in Oryzomys palustris, a species that has lost LINE-1 activity, versus Sigmodon hispidus, a closely related species retaining LINE-1 activity, we have identified an endogenous retrovirus family differentially amplified in these two species. Analysis of three full-length, recently transposed copies, called mysTR elements, revealed gag, pro, and pol coding regions containing stop codons which may have accumulated either before or after retrotransposition. Isolation of related sequences in S. hispidus and the LINE-1 active outgroup species, Peromyscus maniculatus, by PCR of a pro-pol region has allowed determination of copy numbers in each species. Unusually high copy numbers of approximately 10,000 in O. palustris versus 1,000 in S. hispidus and 4,500 in the more distantly related P. maniculatus leave open the question of whether there is a connection between endogenous retrovirus activity and LINE-1 inactivity. Nevertheless, these independent expansions of mysTR represent recent amplifications of this endogenous retrovirus family to unprecedented levels.
Neurotherapeutics, Sep 13, 2022
Scientific Reports, Mar 29, 2023
Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pe... more Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease (Batten disease) is a rare pediatric disease, with symptom development leading to clinical diagnosis. Early diagnosis and effective tracking of disease progression are required for treatment. We hypothesize that brain volumetry is valuable in identifying CLN2 disease at an early stage and tracking disease progression in a genetically modified miniswine model. CLN2 R208X/R208X miniswine and wild type controls were evaluated at 12-and 17-months of age, correlating to early and late stages of disease progression. Magnetic resonance imaging (MRI) T1-and T2-weighted data were acquired. Total intercranial, gray matter, cerebrospinal fluid, white matter, caudate, putamen, and ventricle volumes were calculated and expressed as proportions of the intracranial volume. The brain regions were compared between timepoints and cohorts using Gardner-Altman plots, mean differences, and confidence intervals. At an early stage of disease, the total intracranial volume (− 9.06 cm 3), gray matter (− 4.37% 95 CI − 7.41; − 1.83), caudate (− 0.16%, 95 CI − 0.24; − 0.08) and putamen (− 0.11% 95 CI − 0.23; − 0.02) were all notably smaller in CLN2 R208X/R208X miniswines versus WT, while cerebrospinal fluid was larger (+ 3.42%, 95 CI 2.54; 6.18). As the disease progressed to a later stage, the difference between the gray matter (− 8.27%, 95 CI − 10.1; − 5.56) and cerebrospinal fluid (+ 6.88%, 95 CI 4.31; 8.51) continued to become more pronounced, while others remained stable. MRI brain volumetry in this miniswine model of CLN2 disease is sensitive to early disease detection and longitudinal change monitoring, providing a valuable tool for pre-clinical treatment development and evaluation. Abbreviations CLN2 Late-infantile neuronal ceroid lipofuscinosis type 2 MRI Magnetic resonance imaging GM Gray matter WM White matter CSF Cerebrospinal fluid ICV Intracranial volume WT Wild type (control) CI Confidence interval SubC Mictochondrial ATP synthase subunit c Batten disease, or neuronal ceroid lipofuscinoses, is a group of neurodegenerative diseases in which mutations in 13-14 different genes can cause issues with a lysosome's capability to recycle or process molecules. All forms of Batten disease show similar symptoms but are caused by different gene mutations 1,2. The late-infantile neuronal
Mouse models of CLN3 Batten disease, a rare lysosomal storage disorder with no cure, have improve... more Mouse models of CLN3 Batten disease, a rare lysosomal storage disorder with no cure, have improved our understanding of CLN3 biology and therapeutics through their ease of use and a consistent display of cellular pathology. However, the translatability of murine models is limited by disparities in anatomy, body size, life span, and inconsistent, subtle behavior deficits that can be difficult to detect in CLN3 mutant mouse models, limiting their utility in preclinical studies. Here we present a longitudinal characterization of a novel miniswine model of CLN3 disease that recapitulates the most common human pathogenic variant, an exon 7-8 deletion (CLN3Δex7/8). Progressive pathology and neuron loss is observed in various regions of the CLN3Δex7/8 miniswine brain and retina. Additionally, mutant miniswine present with vision impairment and motor abnormalities, similar to deficits seen in human patients. Taken together, the CLN3Δex7/8 miniswine model shows consistent and progressive Bat...
Atherosclerosis, 2016
as monocytes, key drivers of plaque inflammation, have been reported to accumulate remnant choles... more as monocytes, key drivers of plaque inflammation, have been reported to accumulate remnant cholesterol, enhancing migratory capacity, we assessed the phenotype of circulating monocytes. Methods: We performed 18fluorodeoxyglucose positron emission tomography with computed tomography (18 F-FDG PET/CT) imaging in patients with familial dysbetalipoproteinemia (FD) compared with matched healthy controls. Furthermore, we performed monocyte characterization studies. Results: We included 14 FD patients (age 61±8, 64% male) and 14 controls (age 58±6, 64% male). FD patients had a significant higher total cholesterol, remnant cholesterol and plasma triglycerides. 18 F-FDG uptake in the arterial wall was significantly increased in FD patients compared with controls (carotid target-to-background-ratio: 2,03±0,39 versus 1,62±0,29, p<0.001). Furthermore, monocyte count was significantly increased and characterization showed higher surface expression of adhesion markers CD18, CD11b and CD11c. Assessment of lipid accumulation showed an increase in percentage of monocytes with lipid droplets and a concomitant increase in number of lipid droplets. Conclusions: FD patients have increased arterial wall inflammation and are characterized by an inflammatory phenotype of circulating monocytes, which accumulated larger amounts of lipids. These findings indicate an important inflammatory component to the atherogenicity of remnant cholesterol, contributing to its relationship with increased CVD risk.
We studied the chromosomal distribution of telomere repeats (TTAGGG)n in 8 species of Sigmodon (c... more We studied the chromosomal distribution of telomere repeats (TTAGGG)n in 8 species of Sigmodon (cotton rats) using chromosome paints fluorescent in situ hybridization (FISH) from Sigmodon hispidus. In 2 species with the proposed primitive karyotype for the genus, telomere repeats were restricted to telomeric sites. But in the other 6 species that include 3 with proposed primitive karyotypes and 3 with highly rearranged karyotypes, telomere repeats were found on both telomeric sites and within interstitial telomeric sites (ITSs). To explain the distribution of ITS in Sigmodon, we gather data from C-bands, silver nitrate staining, G-bands, and chromosomal paint data from previous published studies. We did find some correlation with ITS and heterochromatin, euchromatic chromosomal rearrangements, and nucleolar organizing regions. No one type of chromosomal structure explains all ITS in Sigmodon. Multiple explanations and mechanisms for movement of intragenomic sequences are required to...
Montserrat is one of several volcanic islands in the archipelago that have been created by the su... more Montserrat is one of several volcanic islands in the archipelago that have been created by the subduction of the Atlantic tectonic plate beneath the Caribbean plate. Most of these islands are dominated by andesitic stratovolcanoes (steep-sided symmetrical cones) that are the result of explosive eruptions and extensive pyroclastic flows that generate a cone composed of alternating layers of volcanic debris. Stratovolcanoes are quite different from the gently sloping shield volcanoes, such as those in Hawaii, which are typically nonexplosive and which produce fluid lavas that can flow great distances from active vents. There are three volcanic massifs on Montserrat-Silver Hills in the north, Centre Hills, and, largest and youngest, the Soufrière Hills, which occupy the southern half of the island (fig. 11.2). Due to its location on a fault line, earthquakes are not uncommon on Montserrat, with several periods of activity reported from the 1890s, 1930s, and 1960s (e.g., Perret 1939). Renewed seismic activity and pyroclastic flows from the Soufrière Hills volcano, which began in 1995, have progressively reduced the eastern and western flanks of the volcano to an ecological wasteland and have buried much of the southern half of the island under varying amounts of volcanic ash. Figure 11.1. Map of the Lesser Antilles showing the position of Montserrat (16°45′N, 62°10′W).
Distribution, Roost Site Selection and Food Habits of bats in Eastern South Dakota
Resumen The karyotype of Peromyscus grandis (Rodentia:
PLOS ONE
Genetically modified swine disease models are becoming increasingly important for studying molecu... more Genetically modified swine disease models are becoming increasingly important for studying molecular, physiological and pathological characteristics of human disorders. Given the limited history of these model systems, there remains a great need for proven molecular reagents in swine tissue. Here, to provide a resource for neurological models of disease, we validated antibodies by immunohistochemistry for use in examining central nervous system (CNS) markers in a recently developed miniswine model of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant tumor predisposition disorder stemming from mutations in NF1, a gene that encodes the Ras-GTPase activating protein neurofibromin. Patients classically present with benign neurofibromas throughout their bodies and can also present with neurological associated symptoms such as chronic pain, cognitive impairment, and behavioral abnormalities. As validated antibodies for immunohistochemistry applications are particularly difficult to find for swine models of neurological disease, we present immunostaining validation of antibodies implicated in glial inflammation (CD68), oligodendrocyte development (NG2, O4 and Olig2), and neuron differentiation and neurotransmission (doublecortin, GAD67, and tyrosine hydroxylase) by examining cellular localization and brain region specificity. Additionally, we confirm the utility of anti-GFAP, anti-Iba1, and anti-MBP antibodies, previously validated in swine, by testing their immunoreactivity across multiple brain regions in mutant NF1 samples. These immunostaining protocols for CNS markers provide a useful resource to the scientific community, furthering the utility of genetically modified miniswine for translational and clinical applications.
Vitamin D functions as a potent immunomodulator by interacting with many immune cells however, it... more Vitamin D functions as a potent immunomodulator by interacting with many immune cells however, its role in regulating inflammation in the epicardial adipose tissue (EAT) is unclear. In the EAT of atherosclerotic microswine that were fed with deficient, sufficient or supplemented levels of vitamin D, we evaluated the phenotype of the macrophages. Vitamin D treatment was continued for 12 months and serum 25(OH)D levels were measured regularly. Infiltration of M1/M2 macrophage was investigated by immunostaining for CCR7 and CD206, respectively in conjunction with a pan macrophage marker CD14. Significant difference in the number of CCR7+ cells was observed in the EAT from vitamin D-deficient swine compared to vitamin D-sufficient or -supplemented swine. Expression of CD206 correlated with high levels of serum 25(OH)D indicating a significant increase in M2 macrophages in the EAT of vitamin D-supplemented compared to -deficient swine. These findings suggest that vitamin D-deficiency exa...
From May 2000 to August 2002, a study was conducted to document the distribution of bats in South... more From May 2000 to August 2002, a study was conducted to document the distribution of bats in South Dakota east of the Missouri River. During the summers of 2000, 2001, and 2002, mist netting and acoustic sampling (Anabat system) were conducted at 35 sites, including state parks, state recreation areas, and national wildlife refuges. Seven species of bat were recorded from this region: Myotis septentrional is, Myotis lucifugus, Myotis ciliolabrum, Eptesicus fus cits, Lasionycteris noctivagans, Lmiunis borealis, and Lasiurus cinereus. Distribution maps and species accounts were compiled for the seven species using data from the summers of 2000, 2001, and 2002 in addition to data from literature records and voucher records.
Genetically modified porcine disease models are becoming increasingly important for studying mole... more Genetically modified porcine disease models are becoming increasingly important for studying molecular, physiological and pathological characteristics of human disorders. Given their limited history, there remains a great need for proven reagents in swine tissue. To provide a resource for neurological models of disease, we validated antibodies by immunohistochemistry for use in examining central nervous system (CNS) markers. To validate these tools in a relevant model, we utilized a recently developed miniswine model of neurofibromatosis type 1 (NF1). NF1 is a tumor predisposition disorder, presenting with different type of tumors. Additionally, neurological associated symptomologies may include chronic pain, cognitive impairment, and behavioral abnormalities, making this miniswine model an ideal candidate for validating CNS-relevant antibodies. We validate antibodies implicated in glial inflammation (CD68), oligodendrocyte development (NG2, O4, Olig2, and myelin PLP), and neuron di...