Sherrie Clark | Virginia Tech (original) (raw)

Papers by Sherrie Clark

Pharmaceutics

Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, d... more Pancreatic tumors can be resistant to drug penetration due to high interstitial fluid pressure, dense stroma, and disarrayed vasculature. Ultrasound-induced cavitation is an emerging technology that may overcome many of these limitations. Low-intensity ultrasound, coupled with co-administered cavitation nuclei consisting of gas-stabilizing sub-micron scale SonoTran Particles, is effective at increasing therapeutic antibody delivery to xenograft flank tumors in mouse models. Here, we sought to evaluate the effectiveness of this approach in situ using a large animal model that mimics human pancreatic cancer patients. Immunocompromised pigs were surgically engrafted with human Panc-1 pancreatic ductal adenocarcinoma (PDAC) tumors in targeted regions of the pancreas. These tumors were found to recapitulate many features of human PDAC tumors. Animals were intravenously injected with the common cancer therapeutics Cetuximab, gemcitabine, and paclitaxel, followed by infusion with SonoTran ...

Animal, 2016

The objective was to determine the effects of immunization against gonadotropin-releasing hormone... more The objective was to determine the effects of immunization against gonadotropin-releasing hormone on reproductive characteristics in boars. A total of 72 boars were used in a randomized design with three treatments: single immunization (SI) (10 weeks of age) or double immunization (DI) (10 and 15 weeks of age) with Improvest® and intact controls (no Improvest®; CNT) (n=24/group). At 10, 15, 20, 25 and 40 weeks of age, blood was collected and serum harvested to evaluate testosterone concentrations. Testosterone concentrations were less for DI boars compared with CNT boars and SI boars at 20 and 25 weeks (P<0.001), but not at 40 weeks of age. At week 25, 18 pigs (n=6/group) were sacrificed and testes were removed, weighed and measured, and seminiferous tubules were examined and scored using histological slides of testes parenchyma. A sample of neck fat was assessed for boar taint aroma. All testicular measurements and weights and seminiferous tubule scores were less for DI boars co...

aPigs with daily fecal scores of ≥2 were considered diarrheic. Fecal consistency was sco... more aPigs with daily fecal scores of ≥2 were considered diarrheic. Fecal consistency was scored as follows: 0, normal; 1, pasty; 2, semiliquid; and 3, liquid.bFor durations of diarrhea and virus shedding, if no diarrhea or virus shedding until the euthanasia day (PCD7), the duration (days) were recorded as 0 and the onset (days) were as 8 for statistical analysis.cMean cumulative score calculation included all the pigs in each group.dStandard error of the mean.eFFU, fluorescent focus forming units. Geometric mean peak titers were calculated among pigs that shed virus.*Fisher's exact test or ** Kruskal-Wallis rank sum test was used for comparisons. Different letters indicate significant differences among treatment groups (p<0.05), while shared letters indicate no significant difference.</p

Proceedings of the National Academy of Sciences

Hepatitis E virus (HEV) is an important but understudied zoonotic virus causing both acute and ch... more Hepatitis E virus (HEV) is an important but understudied zoonotic virus causing both acute and chronic viral hepatitis. A proportion of HEV-infected individuals also developed neurological diseases such as Guillain–Barré syndrome, neuralgic amyotrophy, encephalitis, and myelitis, although the mechanism remains unknown. In this study, by using an in vitro blood–brain barrier (BBB) model, we first investigated whether HEV can cross the BBB and whether the quasi-enveloped HEV virions are more permissible to the BBB than the nonenveloped virions. We found that both quasi-enveloped and nonenveloped HEVs can similarly cross the BBB and that addition of proinflammatory cytokine tumor necrosis factor alpha (TNF-α) has no significant effect on the ability of HEV to cross the BBB in vitro. To explore the possible mechanism of HEV entry across the BBB, we tested the susceptibility of human brain microvascular endothelial cells lining the BBB to HEV infection and showed that brain microvascular...

Journal of the Mechanical Behavior of Biomedical Materials

MNCs were stained freshly without in vitro stimulation. The frequenci... more MNCs were stained freshly without in vitro stimulation. The frequencies of Tregs were expressed as the percentages among gated MNCs (A, top panel). The absolute numbers of Tregs per tissue were calculated based on the frequencies of Tregs and the total number of MNCs isolated from each tissue (A, bottom panel). The frequencies of IL−10+ or TGF−β+ Tregs were expressed as the percentages of IL−10+ or TGF−β+ cells among the Tregs (B). Data are presented as mean number or frequency ± standard error of the mean (n = 4–9). See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094504#pone-0094504-g002" target="_blank">Fig. 2</a> legend for statistical analysis.</p

Number of pigs in non-HGM group and HGM groups at beginning of study and at euthanasia o... more Number of pigs in non-HGM group and HGM groups at beginning of study and at euthanasia on PID 28 and PCD 7.</p

After VirHRV challenge, pigs were monitored for 7 days for incidence of diarrhea, fecal ... more After VirHRV challenge, pigs were monitored for 7 days for incidence of diarrhea, fecal score and virus shedding. Data are presented as mean ± standard error of the mean (n = 12 for AttHRV group; n = 4 for HGM+AttHRV group). The sign “*” in (A) indicates significant difference between groups (Kruskal–Wallis test, p<0.05). LGG amounts at different time points were determined by strain-specific real-time PCR and are presented as mean counts/ml ± standard error of the mean (n = 7–10 for fecal samples and n = 3–6 for large intestinal content samples). The sign “*” in (B) indicates significant differences between groups at the same time points and the symbol “Δ” indicates significant increases in LGG numbers compared to PID 5 for the same group (Kruskal–Wallis test, p<0.05).</p

MNCs were stimulated with semi-purified AttHRV antigen in vitro for 1... more MNCs were stimulated with semi-purified AttHRV antigen in vitro for 17 hrs. Brefeldin A was added for the last 5 hrs to block secretion of cytokines produced by the T cells. HRV-specific IFN-γ producing CD4+ and CD8+ T cells was detected by intracellular staining and flow cytometry as we previously described <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0094504#pone.0094504-Yuan5" target="_blank">[16]</a>. The frequencies of IFN−γ+CD4+/CD8+ T cells were expressed as percentages among total CD3+ T cells (A and B, middle panel). All mean frequencies are reported after subtraction of the background frequencies. The absolute numbers of CD3+CD4+/CD8+ cells and IFN−γ+CD3+CD4+/CD8+ cells per tissue (A and B, top and bottom panels) were calculated based on the frequencies of CD3+CD4+/CD8+ cells and IFN−γ+CD3+CD4+/CD8+ cells, respectively, and the total number of MNCs isolated from each tissue. Data are presented as mean number or frequency ± standard error of the mean (n = 4–12). The sign “*” indicates the significant difference between groups (Kruskal–Wallis test, p<0.05).</p

Table S1. Summary of off-targeting comparison for RAG2. Target gene (RAG2) guide sequence compare... more Table S1. Summary of off-targeting comparison for RAG2. Target gene (RAG2) guide sequence compared to potential off-target sequence. Location on chromosome, intron or exon region and presence of PAM site is indicated. Table S2. Summary of off-targeting comparison for IL2RG. Target gene (IL2RG) guide sequence compared to potential off-target sequence. Location on chromosome, intron or exon region and presence of PAM site is indicated. Table S3. Summary of off-targeting comparison for Ig heavy chain. Target gene (Ig heavy chain) guide sequence compared to potential off-target sequence. Location on chromosome, intron or exon region and presence of PAM site is indicated. Table S4. Summary of off-targeting comparison for SCD5. Target gene (SCD5) guide sequence compared to potential off-target sequence. Location on chromosome, intron or exon region and presence of PAM site is indicated. Table S5. Summary of off-targeting results for RAG2. Five pigs were tested for each potential off-targe...

The primers used in this study. (PDF 54Â kb)

Journal of Swine Health and Production, 2020

Materials and methods: Weanlings (n = 144) were allocated to a 2 × 2 × 2 factorial ar rangement ... more Materials and methods: Weanlings (n = 144) were allocated to a 2 × 2 × 2 factorial ar rangement of treatments (6 pens/treatment, 3 pigs/pen). Factors were size (large or small), 100 mg intramuscular iron doses (birth or birth and weaning), and dietary copper (14.2 or 250 ppm). Average daily gain (ADG), feed intake (ADFI), and gain to feed ratio were determined for 49 days. Blood was sampled at weaning and days 7 and 49. Results: Hemoglobin (P < .001) and he matocrit (P = .002) at weaning were less in large pigs. Pigs receiving two doses of iron had greater hemoglobin (P = .05) and hema tocrit (P = .04). Hemoglobin (P = .03) and hematocrit (P = .03) were greater in pigs fed the control diet. In large pigs only, body weights at day 49 were greater (P = .05) for individuals receiving two doses of iron. The interaction between number of iron doses and diet affected many growth measures in cluding ADG (P = .02) and ADFI (P = .04) for the overall trial. In all cases, performance wa...

Iron deficiency anemia can develop rapidly in suckling pigs because little iron is stored in the ... more Iron deficiency anemia can develop rapidly in suckling pigs because little iron is stored in the newborn animal; sow colostrum and milk have relatively insignificant iron concentrations; and modern genotypes have the capacity for extremely rapid growth rates. To prevent anemia, it is a standard industry practice to provide supplemental iron to newborn pigs, with intramuscular injections of 100 to 200 mg iron dextran common (Almond et al., 2017). Recent research, however, has demonstrated that many pigs, particularly the largest, fastest-growing animals in a litter, are iron deficient at weaning despite having received iron supplementation during the first week of life (Bhattarai and Nielsen, 2015a; Perri et al., 2016). Anemic pigs at weaning have slower growth rates during the nursery phase of production (Bhattarai and Nielson, 2015b; Perri et al., 2016). An additional iron treatment at weaning could be important, particularly for nursery pigs that consume diets supplemented with ph...

Journal of Swine Health and Production, 2019

Materials and methods: Weaned pigs (n = 144) were allocated to treatments in a 2 × 2 × 2 factoria... more Materials and methods: Weaned pigs (n = 144) were allocated to treatments in a 2 × 2 × 2 factorial arrangement (6 pens/ treatment, 3 pigs/pen), with factors being pig size (large or small); number of 100 mg iron dextran doses (1 [birth] or 2 [birth and wean ing]); and dietary zinc (100 or 2000 ppm). Average daily gain (ADG), feed intake (ADFI), and gain to feed ratio (G:F) were determined. Blood samples were collected at weaning and 7 and 49 days postweaning. Results: Anemia (hemoglobin < 9.0 g/dL) at weaning tended to be greater (P = .07) for large pigs and hemoglobin (P = .02) and hematocrit (P = .05) were greater in small pigs. Hematology was largely unaffected by number of iron doses or diet. Large pigs displayed greater ADG (P < .001) but poorer G:F (P = .002). Zincsupplemented pigs had greater (P = .002) ADG and G:F from day 0 to 21. From day 22 to 49, G:F (P = .005) was greater for controls. Over all, zinc tended to increase ADFI in large (P = .09) but not small (P ...

The objective was to determine the effects of immunocastration (Improvest) on reproductive charac... more The objective was to determine the effects of immunocastration (Improvest) on reproductive characteristics in boars. Seventy-two boars were used in a randomized design with three treatments: single injection (SI) or double injection (DI) of Improvest, and intact controls (no Improvest; CNT) (n = 24/group). At wk 10, 15, 20, 25, and 40, blood was collected and serum harvested to evaluate testosterone concentrations via RIA. At wk 25, 18 pigs (n = 6/ group) were sacrificed and testes were removed, weighed, and measured. Libido was assessed at 32, 36, 47, 60, and 63+ wk of age (1 to 5; 1 = no libido; 5 = high libido) and semen collected beyond 60 wk of age. Testosterone concentrations were less for DI boars compared to CNT boars and SI boars at 20 and 25 wk of age (P < 0.001), but not different at 40 wk of age. All testicular measurements and weight were less for DI boars compared to SI and CNT boars (P < 0.001). There was no treatment effect on libido between 32 to 63+ wk of age...

Ursus, 2017

Abstract: Herniation of viscera induced by medical intervention has been described in carnivores... more Abstract: Herniation of viscera induced by medical intervention has been described in carnivores, yet occurrence of hernias causing wild carnivore mortality, including in bears, remains unknown. We describe an inguinal hernia, intestinal entrapment and rupture, and peritonitis causing mortality in a male American black bear (Ursus americanus). In the autumn of 2014, a free-ranging, adult bear was housed at Virginia Tech's Black Bear Research Center. After 13 days in captivity, the bear showed signs of lethargy and intermittent inappetence consistent with the onset of hibernating behaviors. However, the bear suddenly displayed rapid deterioration and died before medical assistance could be provided. During necropsy examination, a devitalized portion of small intestine was found entrapped in the left inguinal ring. An intestinal perforation was evident near the entrapment area, which caused a subsequent peritonitis. To our knowledge this is the first report of bear mortality due ...