| charge detection mass spectrometry identifies preferred non-icosahedral polymorphs in the self-assembly of woodchuck hepatitis virus capsids. | woodchuck hepatitis virus (whv) is prone to aberrant assembly in vitro and can form a broad distribution of oversized particles. characterizing aberrant assembly products is challenging because they are both large and heterogeneous. in this work, charge detection mass spectrometry (cdms) is used to measure the distribution of whv assembly products. cdms is a single-particle technique where the masses of individual ions are determined from simultaneous measurement of each ion's charge and m/z (ma ... | 2016 | 26151485 |
| infection patterns induced in naive adult woodchucks by virions of woodchuck hepatitis virus collected during either the acute or chronic phase of infection. | the infectivity of hepadnavirus virions produced during either acute or chronic stages of infection was compared by testing the ability of the virions of woodchuck hepatitis virus (whv) to induce productive acute infection in naive adult woodchucks. serum whv collected during acute infection was compared to virions harvested from whv-infected woodchucks during either (i) early chronic infection, when whv-induced hepatocellular carcinoma (hcc) was not yet developed, or (ii) late chronic infection ... | 2015 | 26063428 |
| systemic gene delivery following intravenous administration of aav9 to fetal and neonatal mice and late-gestation nonhuman primates. | several acute monogenic diseases affect multiple body systems, causing death in childhood. the development of novel therapies for such conditions is challenging. however, improvements in gene delivery technology mean that gene therapy has the potential to treat such disorders. we evaluated the ability of the aav9 vector to mediate systemic gene delivery after intravenous administration to perinatal mice and late-gestation nonhuman primates (nhps). titer-matched single-stranded (ss) and self-comp ... | 2015 | 26062602 |
| capacity of a natural strain of woodchuck hepatitis virus, whvny, to induce acute infection in naive adult woodchucks. | woodchuck hepatitis virus (whv) is often used as surrogate to study mechanism of hbv infection. currently, most infections are conducted using strains whv7 or whv8 that have very high sequence identity. this study focused on natural strain whvny that is more genetically distant from whv7. three naive adult woodchucks inoculated with whvny developed productive acute infection with long lasting viremia. however, only one of two woodchucks infected with whv7 at the same multiplicity demonstrated pr ... | 2015 | 25979221 |
| characterization and genotyping of the drb1 gene of the major histocompatibility complex (mhc) in the marmota monax, animal model of hepatitis b. | the major histocompatibility complex (mhc)-containing genes are among the most polymorphic in vertebrates. mhc genes code for proteins that are critical in the immune system response. in this study, the polymorphism of the second exon of the mhc class ii drb gene was characterized in the eastern woodchuck (marmota monax). woodchucks chronically infected with the woodchuck hepatitis virus (whv) represent the best available animal model for the study of chronic hepatitis b infection in humans. in ... | 2015 | 25458311 |
| universal real-time pcr-based assay for lentiviral titration. | lentiviral vectors are efficient vehicles for stable gene transfer in both dividing and non-dividing cells. this feature among others makes lentiviral vectors a powerful tool in molecular research. however, the use of lentiviruses in research studies and clinical trials requires a precise and validated titration method. in this study, we describe a qpcr-based approach for estimation of lentiviral vector titer (plv-thm-gfp). the use of wpre (woodchuck hepatitis virus posttranscriptional regulator ... | 2015 | 25370825 |
| [construction of recombinant baculovirus vectors started by ef1alpha]. | to improve the transduction efficiency of baculovirus and exogenous gene expression level, we chose a mammalian cell-specific promoter-human extension factor 1alpha promoter (ef1-alpha), used virus pseudotyped tools--truncated vessicular stomatitis virus protein g (vsv-ged), added woodchuck hepatitis virus post-transcriptional regulatory element (wpre) and adenovirus inverted terminal repeats (itrs). | 2014 | 25272818 |
| novel woodchuck hepatitis virus (whv) transgene mouse models show sex-dependent whv replicative activity and development of spontaneous immune responses to whv proteins. | the woodchuck model is an informative model for studies on hepadnaviral infection. in this study, woodchuck hepatitis virus (whv) transgenic (tg) mouse models based on c57bl/6 mice were established to study the pathogenesis associated with hepadnaviral infection. two lineages of whv tg mice, harboring the whv wild-type genome (lineage 1217) and a mutated whv genome lacking surface antigen (lineage 1281), were generated. whv replication intermediates were detected by southern blotting. dna vaccin ... | 2014 | 24257601 |
| rnai induces innate immunity through multiple cellular signaling pathways. | our previous results showed that the knockdown of woodchuck hepatitis virus (whv) by rna interference (rnai) led to upregulation of interferon stimulated genes (isgs) in primary hepatocytes. in the present study, we tested the hypothesis that the cellular signaling pathways recognizing rna molecules may be involved the isg stimulation by rnai. | 2013 | 23700487 |
| adenoviral and adeno-associated viral vectors-mediated neuronal gene transfer to cardiovascular control regions of the rat brain. | viral vectors have been utilized extensively to introduce genetic material into the central nervous system. in order to investigate gene functions in cardiovascular control regions of rat brain, we applied wpre (woodchuck hepatitis virus post-transcriptional regulatory element) enhanced-adenoviral (ad) and adeno-assoicated virus (aav) type 2 vectors to mediate neuronal gene delivery to the paraventricular nucleus of the hypothalamus, the nucleus tractus solitarius and the rostral ventrolateral m ... | 2013 | 23569423 |
| baculovirus vector as an avian influenza vaccine: hemagglutinin expression and presentation augment the vaccine immunogenicity. | baculovirus simultaneously displaying and expressing the avian influenza virus (aiv) hemagglutinin (ha) protein can induce potent anti-ha humoral and cellular immune responses. based on the hypothesis that improving the antigen expression and presentation can further boost the aiv vaccine efficacies, we first constructed a baculoviral vector (bac-haw) with ha gene fused with the woodchuck hepatitis virus post-transcriptional regulatory element (wpre) near its 3' end and expressed under the contr ... | 2013 | 23313887 |
| a simple and effective method to generate lentiviral vectors for ex vivo gene delivery to mature human peripheral blood lymphocytes. | human ex vivo gene therapy protocols have been used successfully to treat a variety of genetic disorders, infectious diseases, and cancer. murine oncoretroviruses (specifically, gammaretroviruses) have served as the primary gene delivery vehicles for these trials. however, in some cases, such vectors have been associated with insertional mutagenesis. as a result, alternative vector platforms such as lentiviral vectors (lvvs) are being developed. lvvs may provide advantages compared with gammaret ... | 2012 | 22515320 |
| impact of age at administration, lysosomal storage, and transgene regulatory elements on aav2/8-mediated rat liver transduction. | liver-directed gene transfer is being investigated for the treatment of systemic or liver-specific diseases. recombinant vectors based on adeno-associated virus serotype 8 (aav2/8) efficiently transduce liver cells allowing long term transgene expression after a single administration in animal models and in patients.we evaluated the impact on aav2/8-mediated rat liver transduction of the following variables: i) age at vector administration, ii) presence of lysosomal storage in liver cells, and i ... | 2012 | 22428010 |
| the woodchuck hepatitis b virus infection model for the evaluation of hbv therapies and vaccine therapies. | studies focused on the understanding of the molecular mechanisms involved in recovery or progression to chronicity of hbv may take advantage of natural and experimental models that mimic its properties. this is also of relevance for associated diseases such as cirrhosis and hepatocellulocarcinoma. the eastern woodchuck (marmota monax) infected by the hepadnavirus woodchuck hepatitis b virus (whv) has been applied as a predictive model to support development of new hbv vaccines, antivirals, immun ... | 2010 | 22822718 |
| immune modulation by genetic modification of dendritic cells with lentiviral vectors. | our work over the past eight years has focused on the use of hiv-1 lentiviral vectors (lentivectors) for the genetic modification of dendritic cells (dcs) to control their functions in immune modulation. dcs are key professional antigen presenting cells which regulate the activity of most effector immune cells, including t, b and nk cells. their genetic modification provides the means for the development of targeted therapies towards cancer and autoimmune disease. we have been modulating with le ... | 2013 | 23726846 |
| codon optimization and woodchuck hepatitis virus posttranscriptional regulatory element enhance the immune responses of dna vaccines against infectious bursal disease virus in chickens. | the present study was undertaken to evaluate the protective efficacy of dna vaccines against infectious bursal disease virus (ibdv) in chickens and to determine whether codon optimization and the woodchuck hepatitis virus posttranscriptional regulatory element (wpre) could improve the immunogenicity of the dna vaccines. the vp2, vp243 and codon-optimized vp243 genes of ibdv were cloned into pcaggs vector, and designated as pcagvp2, pcagvp243 and pcagoptivp243, respectively. plasmids pcagwvp243 a ... | 2013 | 23631937 |
| protection of chickens against reticuloendotheliosis virus infection by dna vaccination. | the present study was undertaken to evaluate the ability of dna vaccination to protect chickens against reticuloendotheliosis virus (rev) infection and to determine whether codon optimization and the woodchuck hepatitis virus posttranscriptional regulatory element (wpre) could improve the immunogenicity of the dna vaccines. the wild-type and codon-optimized gp90 genes of rev were cloned into pcaggs vector, and designated as pcaggp90 and pcagoptigp90, respectively. plasmids pcagwgp90 and pcagwopt ... | 2013 | 23764274 |
| sensitivity of primary fibroblasts in culture to atmospheric oxygen does not correlate with species lifespan. | differences in the way human and mouse fibroblasts experience senescence in culture had long puzzled researchers. while senescence of human cells is mediated by telomere shortening, parrinello et al. demonstrated that senescence of mouse cells is caused by extreme oxygen sensitivity. it was hypothesized that the striking difference in oxygen sensitivity between mouse and human cells explains their different rates of aging. to test if this hypothesis is broadly applicable, we cultured cells from ... | 2016 | 27163160 |
| palivizumab epitope-displaying virus-like particles protect rodents from rsv challenge. | respiratory syncytial virus (rsv) is the most common cause of serious viral bronchiolitis in infants, young children, and the elderly. currently, there is not an fda-approved vaccine available for rsv, though the mab palivizumab is licensed to reduce the incidence of rsv disease in premature or at-risk infants. the palivizumab epitope is a well-characterized, approximately 24-aa helix-loop-helix structure on the rsv fusion (f) protein (f254-277). here, we genetically inserted this epitope and mu ... | 2015 | 25751145 |
| molecular determinants of gs-9620-dependent tlr7 activation. | gs-9620 is an orally administered agonist of toll-like receptor (tlr)7 currently being evaluated in clinical studies for the treatment of chronic hbv and hiv patients. gs-9620 has shown antiviral efficacy in preclinical models of chronic hepadnavirus infection in woodchuck as well as chimpanzee. however, the molecular determinants of gs-9620-dependent activation of tlr7 are not well defined. the studies presented here elucidate gs-9620 subcellular distribution and characterize its molecular inte ... | 2016 | 26784926 |
| foreign gene expression and induction of antibody response by recombinant fowl adenovirus-9-based vectors with exogenous promoters. | fowl adenoviruses (fadvs) are promising vectors for poultry vaccines and gene therapy. the commonly used human cytomegalovirus (cmv) promoter in recombinant fadv-9 viruses (recfadv-9s) leads to foreign gene expression that elicits an antibody response. despite its strength, studies have shown that the cmv promoter is prone to silencing by methylation hampering the in vivo application of vectors containing this promoter. therefore, to improve our virus vector system and circumvent potential limit ... | 2017 | 28780115 |
| preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of js-001, a programmed cell death protein-1 (pd-1) monoclonal antibody. | js-001 is the first monoclonal antibody (mab) against programmed cell death protein-1 (pd-1) approved by the china food and drug administration (cfda) into the clinical trails. to date, however, no pre-clinical pharmacological and pharmacokinetic (pk) data are available. in this study, we investigated the efficacy of js-001 and conducted a preclinical pk study, including the monitoring of anti-drug antibodies (adas). we found that js-001 specifically bound to pd-1 antigen with an ec50 of 21 nmol ... | 2017 | 28317872 |
| initial sites of hepadnavirus integration into host genome in human hepatocytes and in the woodchuck model of hepatitis b-associated hepatocellular carcinoma. | hepatitis b virus (hbv) and the closely related woodchuck hepatitis virus (whv) are potent carcinogens that trigger development of primary hepatocellular carcinoma (hcc). the initial sites of hepadnavirus-host genome integration, their diversity and kinetics of formation can be central to virus persistence and the initiation and progression of hcc. to recognize the nature of the very early virus-host interactions, we explored de novo infection of human hepatocyte-like heparg cells with authentic ... | 2017 | 28414318 |
| dysfunction of pla2g6 and cyp2c44-associated network signals imminent carcinogenesis from chronic inflammation to hepatocellular carcinoma. | little is known about how chronic inflammation contributes to the progression of hepatocellular carcinoma (hcc), especially the initiation of cancer. to uncover the critical transition from chronic inflammation to hcc and the molecular mechanisms at a network level, we analyzed the time-series proteomic data of woodchuck hepatitis virus/c-myc mice and age-matched wt-c57bl/6 mice using our dynamical network biomarker (dnb) model. dnb analysis indicated that the 5th month after birth of transgenic ... | 2017 | 28655161 |
| modifying scent-marking behavior to reduce woodchuck damage to fruit trees. | woodchucks (marmota monax) damage fruit trees by gnawing on main stems during scent marking, a behavior unrelated to feeding. i tested whether damage could be reduced by providing alternative sites for scent marking or by applying predator odor to trees. nearly all hardwood stakes supplied as alternative sites for scent marking were used, and the elapsed time from activation of a burrow until onset of damage to an adjacent tree was significantly greater for sites with stakes. however, the mean l ... | 1991 | 27755676 |
| identification of volatile components of bobcat (lynx rufus) urine. | bobcat (lynx rufus) urine reduces scent-marking activity of woodchucks (marmota monax) and feeding activity of snowshoe hares (lepus americanus) and deer (odocoileus virginianus, o. hemionus). in order to identify the semiochemicals responsible for these behavior modifications, a dichloromethane extract of the bobcat urine was analyzed by gc-ms. among the known compounds identified in the extract are phenol, indole, dimethyl sulfone, and 3-mercapto-3-methylbutanol. compounds for which spectrosco ... | 1991 | 24258737 |
| improved microrna suppression by wpre-linked tough decoy microrna sponges. | our genes are post-transcriptionally regulated by micrornas (mirnas) inducing translational suppression and degradation of targeted mrnas. strategies to inhibit mirnas in a spatiotemporal manner in a desired cell type or tissue, or at a desired developmental stage, can be crucial for understanding mirna function and for pushing forward mirna suppression as a feasible rationale for genetic treatment of disease. for such purposes, rna polymerase ii (rna pol ii)-transcribed tough decoy (tud) mirna ... | 2017 | 28487381 |
| signs observed among animal species infected with raccoon rabies variant virus, massachusetts, usa, 1992-2010. | we analyzed signs occurring among domestic and wild terrestrial animal species infected with raccoon rabies variant virus (rrv) in massachusetts, 1992-2010. the clinical sign of aggression was significantly associated with rabid stray cats (odds ratio, or = 2.3) and rrv affected major wild terrestrial animal species individually, which included raccoons (or = 2.8), skunks (or = 8.0), gray foxes (or = 21.3), red foxes (or = 10.4), woodchucks (or = 4.7) and coyotes (or = 27.6). while aggression is ... | 2011 | 26486623 |
| growth of the eye lens: i. weight accumulation in multiple species. | to examine the accumulation of wet and/or dry weight in the ocular lens as a function of age in different species. | 2014 | 24715758 |
| suspected hepadnavirus association with a hepatocellular carcinoma in a black-tailed prairie dog (cynomys ludovicianus). | hepatocellular carcinomas are the most commonly reported neoplasm of black-tailed prairie dogs (cynomys ludovicianus). in several other closely related sciuridae species, infection with species-specific hepadnaviruses is associated with the development of these tumours, but such a hepadnavirus has not yet been identified in any prairie dog species, although its presence has been hypothesized previously. an adult prairie dog was humanely destroyed due to progressive illness and the identification ... | 2017 | 29169624 |
| toll-like receptor 7 agonist gs-9620 induces prolonged inhibition of hbv via a type i interferon-dependent mechanism. | gs-9620, an oral agonist of toll-like receptor 7 (tlr7), is in clinical development for the treatment of chronic hepatitis b (chb). gs-9620 was previously shown to induce prolonged suppression of serum viral dna and antigens in the woodchuck and chimpanzee models of chb. here we investigated the molecular mechanisms that contribute to the antiviral response to gs-9620 using in vitro models of hepatitis b virus (hbv) infection. | 2017 | 29247725 |
| anti-hbv response to toll-like receptor 7 agonist gs-9620 is associated with intrahepatic aggregates of t cells and b cells. | gs-9620, an oral agonist of toll-like receptor 7 (tlr7), is in clinical development for the treatment of chronic hepatitis b (chb). gs-9620 was previously shown to induced prolonged suppression of serum viral dna and antigens in the chimpanzee and woodchuck models of chb. here we investigated the immunomodulatory mechanisms underlying these antiviral effects. | 2017 | 29247724 |
| optimized lentiviral transduction of human amniotic mesenchymal stromal cells. | mesenchymal stromal cells are excellent candidates for regenerative medicine since they are multipotent, easy to isolate, can be expanded to obtain clinically relevant numbers and are immunoprivileged. stable genetic modification with viral vectors can improve mesenchymal stromal cell function and enhance their therapeutic potential. however, standard viral vectors achieve sub-optimal transduction efficiency with a single infection. on the other hand, multiple transduction cycles or antibiotic-b ... | 2018 | 29155015 |
| peromyscus leucopus mouse brain transcriptome response to powassan virus infection. | powassan virus (powv) is a tick-borne flavivirus responsible for life-threatening encephalitis in north america and some regions of russia. the ticks that have been reported to transmit the virus belong to the ixodes species, and they feed on small-to-medium-sized mammals, such as peromyscus leucopus mice, skunks, and woodchucks. we previously developed a p. leucopus mouse model of powv infection, and the model is characterized by a lack of clinical signs of disease following intraperitoneal or ... | 2017 | 29147886 |
| activity of nucleic acid polymers in rodent models of hbv infection. | nucleic acid polymers (naps) block the release of hbsag from infected hepatocytes. these compounds have been previously shown to have the unique ability to eliminate serum surface antigen in dhbv-infected pekin ducks and achieve multilog reduction of hbsag or hbsag loss in patients with chronic hbv infection and hbv/hdv coinfection. in ducks and humans, the blockage of hbsag release by naps occurs by the selective targeting of the assembly and/or secretion of subviral particles (svps). the clini ... | 2018 | 29126900 |
| protective efficacy of an il-12-expressing baculoviral malaria vaccine. | interleukin-12 (il-12) plays an important role in antigen-specific adaptive immunity against plasmodium sporozoites, and this requirement allows for a new approach to developing an effective malaria vaccine. in this study, we examined whether il-12 could enhance protective efficacy of a baculovirus-based malaria vaccine. for this aim, a baculoviral vector expressing murine il-12 (mil-12) under the control of cmv promoter (bes-mil-12-spider) and a baculoviral vector expressing plasmodium falcipar ... | 2017 | 29072334 |
| the use of the woodchuck as an animal model for evaluation of transarterial embolization. | there are many shortcomings of current animal models as surrogates of hepatocellular carcinoma that handicap preclinical testing of embolization agents. the present study explores the feasibility of using the woodchuck (marmota monax) as an animal model for the testing of novel embolization agents. four woodchucks underwent magnetic resonance imaging, angiography, and left lobar hepatic artery particle embolization. percutaneous access, arteriography, and lobar embolization were successful in al ... | 2017 | 28941521 |
| groundhog day for rodent models of acute lung injury: clear relevance or renewed debate? | | 2017 | 28762770 |
| groundhog day again? you be the judge: commentary on an article by carlos a. higuera, md, et al.: "synovial fluid cell count for diagnosis of chronic periprosthetic hip infection". | | 2017 | 28463930 |
| do you believe in groundhogs? | | 2016 | 27648866 |
| david oliver: groundhog days for doctors. | | 2016 | 27590196 |
| correction: intrahepatic transcriptional signature associated with response to interferon-α treatment in the woodchuck model of chronic hepatitis b. | | 2016 | 27022978 |
| analysis of the carrot and stick policy of repeal of the sustainable growth rate formula: the good, the bad, and the ugly. | the balanced budget act which became law in 1997 was designed to help stem the increasing in costs of healthcare. the sustainable growth rate (sgr) formula was incorporated into that law as a method of helping balance the budget through a complex formula tying reimbursement to the growth in the economy. soon after its inception, the flawed nature of the formula, linking the balancing of the federal budget to physician professional fees was realized. congress has provided multiple short-term fixe ... | 2015 | 26000675 |
| elusive "doc fix": groundhog day 2015 for sustainable growth rate (sgr). | in summary, the sgr continues to hang like damocles sword over physicians. to understand health care needs, we need to separate basic health care needs from economic mandates, and health insurance from health care coverage. the sgr flux represents another meaningful uncertainty to this health care conundrum. | 2015 | 25794208 |
| real-time in vivo characterization of primary liver tumors with diffuse optical spectroscopy during percutaneous needle interventions: feasibility study in woodchucks. | this study presents the first in vivo real-time optical tissue characterization during image-guided percutaneous intervention using near-infrared diffuse optical spectroscopy sensing at the tip of a needle. the goal of this study was to indicate transition boundaries from healthy tissue to tumors, namely, hepatic carcinoma, based on the real-time feedback derived from the optical measurements. | 2015 | 25783227 |
| myocardial ischemic protection in natural mammalian hibernation. | hibernating myocardium is an important clinical syndrome protecting the heart with chronic myocardial ischemia, named for its assumed resemblance to hibernating mammals in winter. however, the effects of myocardial ischemic protection have never been studied in true mammalian hibernation, which is a unique strategy for surviving extreme winter environmental stress. the goal of this investigation was to test the hypothesis that ischemic stress may also be protected in woodchucks as they hibernate ... | 2015 | 25613166 |
| forelimb muscle architecture and myosin isoform composition in the groundhog (marmota monax). | scratch-digging mammals are commonly described as having large, powerful forelimb muscles for applying high force to excavate earth, yet studies quantifying the architectural properties of the musculature are largely unavailable. to further test hypotheses about traits that represent specializations for scratch-digging, we quantified muscle architectural properties and myosin expression in the forelimb of the groundhog (marmota monax), a digger that constructs semi-complex burrows. architectural ... | 2015 | 25452499 |
| is it groundhog day? | | 2014 | 25397656 |
| groundhog day: airway narrowing, deep inspirations, and asthma. | | 2014 | 25317460 |
| indigenous health: radical hope or groundhog day? | | 2014 | 24938331 |
| the effect of fasting on pet imaging of hepatocellular carcinoma. | the clinical utility of positron emission tomography (pet) imaging for liver cancer applications is not clearly defined either for diagnosis or treatment assessment. previous clinical studies demonstrated that fluorodeoxyglucose (fdg) did not show uptake in some hepatocellular carcinoma (hcc) while acetate showed uptake. pre-imaging fasting is required for clinical pet imaging with fdg. no studies were done to confirm the effect of fasting on acetate uptake in hcc for pet imaging. we investigate ... | 2013 | 24683497 |
| what a woodchuck could chuck. | | 2014 | 24651779 |
| in vitro characterization of uptake mechanism of l-[methyl-(3)h]-methionine in hepatocellular carcinoma. | methionine (met) could be a useful imaging biomarker for the diagnosis of hepatocellular carcinoma (hcc), as demonstrated by pet imaging with l-[methyl-(11)c]-met. in hcc cells, protein synthesis mainly contributes to radiopharmaceutical uptake. in contrast, lipid synthesis via the phosphatidylethanolamine (pe) methylation pathway is the major metabolic route of l-[methyl-(11)c]-met in normal hepatocytes, which contributes to the background contrast observed in pet images. however, the mechanism ... | 2014 | 24488484 |
| effect of body mass on hibernation strategies of woodchucks (marmota monax). | the benefits of mammalian hibernation have been well documented. however, the physiological and ecological costs of torpor have been emphasized only recently as part of a hibernation-optimization hypothesis. this hypothesis predicts that hibernators with greater availability of energy minimize costs of torpor by less frequent utilization of torpor and by maintaining higher body temperatures (t(b)) during torpor. in order to further examine the relationship between body mass and other parameters ... | 2014 | 24345658 |
| proteomic mechanisms of cardioprotection during mammalian hibernation in woodchucks, marmota monax. | mammalian hibernation is a unique strategy for winter survival in response to limited food supply and harsh climate, which includes resistance to cardiac arrhythmias. we previously found that hibernating woodchucks (marmota monax) exhibit natural resistance to ca2+ overload-related cardiac dysfunction and nitric oxide (no)-dependent vasodilation, which maintains myocardial blood flow during hibernation. since the cellular/molecular mechanisms mediating the protection are less clear, the goal of ... | 2013 | 23855383 |
| adenocarcinoma of the dorsal glands in 2 european ground squirrels (spermophilus citellus). | olfactory communication is an important aspect of the biology of ground squirrels; accordingly, some of their integumentary glands are associated with scent-marking behavior. although reports of neoplasms in ground squirrels are limited, the literature on tumors in this family of rodents is extensive, with hepatocellular carcinomas in woodchucks and fibromas in squirrels being the 2 most common neoplasms. apocrine gland tumors occur frequently in domestic animals such as cats and dogs but to our ... | 2012 | 23043780 |
| prostate cancer-specific and potent antitumor effect of a dd3-controlled oncolytic virus harboring the pten gene. | prostate cancer is a major health problem for men in western societies. here we report a prostate cancer-specific targeting gene-viro-therapy (ctgvt-pca), in which pten was inserted into a dd3-controlled oncolytic viral vector (ov) to form ad.dd3.e1a.e1b(δ55)-(pten) or, briefly, ad.dd3.d55-pten. the woodchuck post-transcriptional element (wpre) was also introduced at the downstream of the e1a coding sequence, resulting in much higher expression of the e1a gene. dd3 is one of the most prostate ca ... | 2012 | 22509396 |
| groundhog day. | | 2011 | 21476469 |
| groundhog day versus alice in wonderland, red herrings versus swedish fishes, and hopefully something constructive: a reply to comments. | in this reply to the comments on our original article, we identify common themes and respond to some specific issues that appear to be at the core of the debate over the evidence for "generation me." in particular, we point out that generational studies have both applied and theoretical consequences and echo the sentiment that developmental considerations are likely to be more important than generational considerations when thinking about the attributes of today's young people. we also acknowled ... | 2010 | 26162068 |
| efficient visual search of videos cast as text retrieval. | we describe an approach to object retrieval which searches for and localizes all the occurrences of an object in a video, given a query image of the object. the object is represented by a set of viewpoint invariant region descriptors so that recognition can proceed successfully despite changes in viewpoint, illumination and partial occlusion. the temporal continuity of the video within a shot is used to track the regions in order to reject those that are unstable. efficient retrieval is achieved ... | 2009 | 19229077 |
| medical groundhog days. | | 2008 | 19032463 |
| groundhog day. | i think i have cliché phobia. the symptoms are a feeling of acute despair, pursed lips and grinding teeth. it happens every time i hear nurses complain in the media about the pay rise. | 2007 | 28091084 |
| anti-lymphoproliferative activity of alpha-2-macroglobulin in the plasma of hibernating 13-lined ground squirrels and woodchucks. | plasma from hibernating (hib) woodchucks (marmota monax) or 13-lined ground squirrels (ictidomys tridecemlineatus) suppressed (3)h-thymidine uptake in mouse spleen cell cultures stimulated with concanavalin a (cona); plasma from non-hibernating animals were only slightly inhibitory. maximum inhibition occurred when hib plasma was added to the cultures prior to cona. after hplc size exclusion chromatography of the hib ground squirrel plasma, a single fraction (fraction-14) demonstrated inhibitory ... | 2014 | 25113962 |
| dental pathology of the hoary marmot (marmota caligata), groundhog (marmota monax) and alaska marmot (marmota broweri). | museum specimens (maxillae and mandibles) of the three marmot species occurring in alaska (marmota caligata [n = 108 specimens], marmota monax [n = 30] and marmota broweri [n = 24]) were examined macroscopically according to predefined criteria. there were 71 specimens (43.8%) from female animals, 69 (42.6%) from male animals and 22 (13.6%) from animals of unknown sex. the ages of animals ranged from neonatal to adult, with 121 young adults (74.4%) and 41 adults (25.3%) included, and 168 exclude ... | 2017 | 27908555 |
| exploring the bone proteome to help explain altered bone remodeling and preservation of bone architecture and strength in hibernating marmots. | periods of physical inactivity increase bone resorption and cause bone loss and increased fracture risk. however, hibernating bears, marmots, and woodchucks maintain bone structure and strength, despite being physically inactive for prolonged periods annually. we tested the hypothesis that bone turnover rates would decrease and bone structural and mechanical properties would be preserved in hibernating marmots (marmota flaviventris). femurs and tibias were collected from marmots during hibernati ... | 2017 | 27617358 |
| groundhog day. | | 2010 | 20210115 |
| differential gene expression of caenorhabditis elegans grown on unmethylated sterols or 4alpha-methylsterols. | transcriptional profiles of caenorhabditis elegans grown on unmethylated sterols (desmss) or on 4alpha-methylsterols (4mss) were compared using microarrays. thirty-four genes were upregulated and 2 were downregulated>2-fold by growth on 4mss, including 13 cuticle collagen (col) genes, 1 cuticulin gene (cut-1), 2 groundhog-like (grl) genes, and 1 groundhog gene (grd-4); col-36 and grl-20 were increased 12- and 19-fold, respectively. fifteen of these 17 genes have been assigned to metabolic mounta ... | 2007 | 17277379 |
| revisiting groundhog day (1993): cinematic depiction of mutative process. | | 2006 | 16997731 |
| the surviving sepsis guidelines: not another "groundhog day". | | 2004 | 15241108 |
| groundhog day: cause and effect and the primary importance of the finite population induced by randomization. | the logical structure that enables randomized clinical trials to establish cause and effect is reviewed. statisticians have a major role to define this structure clearly and to help clinicians apply statistical inference in ways directly related to their trials. scientific importance of establishing limited cause and effect should be accented rather than inferences to generalized populations beyond the scope of a trial's actual random sampling. authors of clinical reports should clearly define t ... | 2002 | 12413233 |
| caenorhabditis elegans has scores of hedgehog-related genes: sequence and expression analysis. | previously, we have described novel families of genes, warthog (wrt) and groundhog (grd), in caenorhabditis elegans. they are related to hedgehog (hh) through the carboxy-terminal autoprocessing domain (called hog or hint). a comprehensive survey revealed 10 genes with hog/hint modules in c. elegans. five of these are associated with a wart domain in wrt genes, and three with multiple copies of the ground domain in grd genes. both the wart domain and the ground domain occur also in genes encodin ... | 1999 | 10523520 |
| warthog and groundhog, novel families related to hedgehog. | | 1996 | 8805384 |
| animal models for the study of hepatitis b virus infection. | even with an effective vaccine, an estimated 240 million people are chronically infected with hepatitis b virus (hbv) worldwide. current antiviral therapies, including interferon and nucleot(s)ide analogues, rarely cure chronic hepatitis b. animal models are very crucial for understanding the pathogenesis of chronic hepatitis b and developing new therapeutic drugs or strategies. hbv can only infect humans and chimpanzees, with the use of chimpanzees in hbv research strongly restricted. thus, mos ... | 2018 | 29511142 |
| safety and efficacy of anti-pd-l1 therapy in the woodchuck model of hbv infection. | immune clearance of hepatitis b virus (hbv) is characterized by broad and robust antiviral t cell responses, while virus-specific t cells in chronic hepatitis b (chb) are rare and exhibit immune exhaustion that includes programmed-death-1 (pd-1) expression on virus-specific t cells. thus, an immunotherapy able to expand and activate virus-specific t cells may have therapeutic benefit for chb patients. like hbv-infected patients, woodchucks infected with woodchuck hepatitis virus (whv) can have i ... | 2018 | 29444087 |
| tlr7 agonist increases responses of hepatitis b virus-specific t cells and natural killer cells in patients with chronic hepatitis b treated with nucleos(t)ide analogues. | the oral toll-like receptor (tlr) 7 agonist gs-9620 has antiviral effects in woodchuck and chimpanzee models of chronic hepatitis b virus (hbv) infection. we investigated, in a clinical trial, the capacity of this agent to reconstitute protective immunity in patients with chronic hbv infection. | 2018 | 29378197 |
| experimental infection of marmota monax with a novel hepatitis a virus. | to establish an animal model for the newly identified marmota himalayana hepatovirus, mhhav, so as to develop a better understanding of the infection of hepatitis a viruses. five experimental woodchucks (marmota monax) were inoculated intravenously with the purified mhhav from wild woodchuck feces. one animal injected with pbs was defined as a control. feces and blood were routinely collected. after the animals were subjected to necropsy, different tissues were collected. the presence of viral r ... | 2018 | 29387970 |
| the role of mammalian reservoir hosts in tick-borne flavivirus biology. | small-to-medium sized mammals and large animals are lucrative sources of blood meals for ixodid ticks that transmit life-threatening tick-borne flaviviruses (tbfvs). tbfvs have been isolated from various organs obtained from wild-caught myodes and apodemus species in europe and asia. thus, these rodents are well-established reservoirs of tbfvs. wild-caught peromyscus species have demonstrated seropositivity against powassan virus, the only tbfv known to circulate in north america, suggesting tha ... | 2018 | 30234026 |
| surveys for ticks on wildlife hosts and in the environment at asian longhorned tick (haemaphysalis longicornis)-positive sites in virginia and new jersey, 2018. | haemaphysalis longicornis, the asian longhorned tick (alt), is native to eastern asia, but it has become invasive in several countries, including australia, new zealand and recently in the eastern united states (us). to identify wild mammal and avian host species in the us, we conducted active wildlife surveillance in two states with known alt infestations (virginia and new jersey). in addition, we conducted environmental surveys in both states. these surveillance efforts resulted in detection o ... | 2020 | 32639639 |
| a glance at the gut microbiota of five experimental animal species through fecal samples. | experimental animals including the ferret, marmoset, woodchuck, mini pig, and tree shrew have been used in biomedical research. however, their gut microbiota have not been fully investigated. in this study, the gut microbiota of these five experimental animals were analyzed with 16s rrna sequencing. the phyla firmicutes, bacteroidetes, and fusobacteria were present in the gut microbiota of all the species. specific phyla were present in different animals: proteobacteria in the ferret, tenericute ... | 2020 | 33024229 |
| animal models for the study of human hepatitis b and d virus infection: new insights and progress. | hepatitis b virus (hbv) is a member of the hepadnaviridae family and infects hepatocytes, leading to liver pathology in acutely and chronically infected individuals. co-infection with hepatitis d virus (hdv), which requires the surface proteins of hbv to replicate, can exacerbate this disease progression. thus, the >250 million people living with chronic hbv infection, including 13 million co-infected with hdv, would significantly benefit from an effective and affordable curative treatment. anim ... | 2020 | 32758525 |
| innate and adaptive immunity associated with resolution of acute woodchuck hepatitis virus infection in adult woodchucks. | viral and/or host factors that are directly responsible for the acute versus chronic outcome of hepatitis b virus (hbv) infection have not been identified yet. information on immune response during the early stages of hbv infection in humans is mainly derived from blood samples of patients with acute hepatitis b (ahb), which are usually obtained after the onset of clinical symptoms. features of intrahepatic immune response in these patients are less studied due to the difficulty of obtaining mul ... | 2019 | 31869393 |
| ati-2173, a novel liver-targeted non-chain-terminating nucleotide for hepatitis b virus cure regimens. | ati-2173 is a novel liver-targeted molecule designed to deliver the 5'-monophosphate of clevudine for the treatment of chronic hepatitis b infection. unlike other nucleos(t)ides, the active clevudine-5'-triphosphate is a noncompetitive, non-chain-terminating inhibitor of hepatitis b virus (hbv) polymerase that delivers prolonged reduction of viremia in both a woodchuck hbv model and in humans for up to 6 months after cessation of treatment. however, long-term clevudine treatment was found to exh ... | 2020 | 32540975 |
| extensive distribution of the lyme disease bacterium, borrelia burgdorferi sensu lato, in multiple tick species parasitizing avian and mammalian hosts across canada. | lyme disease, caused by the spirochetal bacterium, borrelia burgdorferi sensu lato (bbsl), is typically transmitted by hard-bodied ticks (acari: ixodidae). whenever this tick-borne zoonosis is mentioned in medical clinics and emergency rooms, it sparks a firestorm of controversy. denial often sets in, and healthcare practitioners dismiss the fact that this pathogenic spirochetosis is present in their area. for distribution of bbsl across canada, we conducted a 4-year, tick⁻host study (2013⁻2016) ... | 2018 | 30424543 |
| tv-circrgpd6 nanoparticle suppresses breast cancer stem cell-mediated metastasis via the mir-26b/yaf2 axis. | metastatic tumor is a major contributor to death caused by breast cancer. however, effective and targeted therapy for metastatic breast cancer remains to be developed. initially, we exploited a feasible biological rationale of the association between metastatic status and tumor-initiating properties in metastatic breast cancer stem cells (bcscs). further, we explored that circular rna ranbp2-like and grip domain-containing protein 6 (circrgpd6) regulates the maintenance of stem cell-like charact ... | 2020 | 32950105 |
| characterization of seasonal pharmacokinetic variability in woodchucks. | the eastern woodchuck (marmota monax) is a hibernating species extensively used as an in vivo efficacy model for chronic human hepatitis b virus infection. under laboratory conditions, woodchucks develop a pseudohibernation condition; thus, the pharmacokinetics (pk) of small-molecule therapeutics may be affected by the seasonal change. the seasonal pk of four probe compounds were characterized over 12 months in seven male and nine female laboratory-maintained woodchucks. these compounds were sel ... | 2020 | 32892154 |
| zika virus-like particle (vlp) vaccine displaying envelope (e) protein cd loop antigen elicits protective and specific immune response in a murine model. | zika virus (zikv) is a mosquito-borne flavivirus associated with congenital zika syndrome (czs), reflecting a wide range of congenital abnormalities in fetuses and infants infected with zikv before birth. zikv infections have also been associated with the neurological autoimmune disorder known as guillian-barré syndrome (gbs). to date, no vaccines or antiviral strategies are licensed for zikv. we used rational design to develop a novel zikv vaccine candidate using a woodchuck hepatitis core anti ... | 2020 | 32736711 |
| dynamics of hepatitis b virus capsid protein dimer regulate assembly through an allosteric network. | while there is an effective vaccine for human hepatitis b virus (hbv), 257 million people have chronic infections for which there is no cure. the assembly process for the viral capsid is a potential therapeutic target. in order to understand the capsid assembly process, we investigated the dimeric building blocks of the capsid. to understand what blocks assembly, we took advantage of an assembly incompetent mutant dimer, cp149-y132a, located in the interdimer interface. this mutation leads to ch ... | 2020 | 32662972 |
| diverse virus and host-dependent mechanisms influence the systemic and intrahepatic immune responses in the woodchuck model of hepatitis b. | woodchuck infected with woodchuck hepatitis virus (whv) represents the pathogenically nearest model of hepatitis b and associated hepatocellular carcinoma (hcc). this naturally occurring animal model also is highly valuable for development and preclinical evaluation of new anti-hbv agents and immunotherapies against chronic hepatitis (ch) b and hcc. studies in this system uncovered a number of molecular and immunological processes which contribute or likely contribute to the immunopathogenesis o ... | 2020 | 32536912 |
| efficacy of an inhibitor of hepatitis b virus expression in combination with entecavir and interferon-α in woodchucks chronically infected with woodchuck hepatitis virus. | rg7834 is a small-molecule inhibitor of hepatitis b virus (hbv) gene expression that significantly reduces the levels of hepatitis b surface antigen (hbsag) and hbv dna in a humanized liver hbv mouse model. in the current study, we evaluated the potency of rg7834 in the woodchuck model of chronic hbv infection, alone and in combination with entecavir (etv) and/or woodchuck interferon-α (wifn-α). rg7834 reduced woodchuck hepatitis virus (whv) surface antigen (whsag) by a mean of 2.57 log10 from b ... | 2020 | 32490326 |
| nanoparticle uptake in a spontaneous and immunocompetent woodchuck liver cancer model. | there is a tremendous focus on the application of nanomaterials for the treatment of cancer. nonprimate models are conventionally used to assess the biomedical utility of nanomaterials. however, these animals often lack an intact immunological background, and the tumors in these animals do not develop spontaneously. we introduce a preclinical woodchuck hepatitis virus-induced liver cancer model as a platform for nanoparticle (np)-based in vivo experiments. liver cancer development in these out-b ... | 2020 | 32255624 |
| toll-like receptor 8 agonist gs-9688 induces sustained efficacy in the woodchuck model of chronic hepatitis b. | gs-9688 (selgantolimod) is an oral selective small molecule agonist of toll-like receptor 8 (tlr8) in clinical development for the treatment of chronic hepatitis b (chb). in this study, we evaluated the antiviral efficacy of gs-9688 in woodchucks chronically infected with woodchuck hepatitis virus (whv), a hepadnavirus closely related to hepatitis b virus (hbv). whv-infected woodchucks received eight weekly oral doses of vehicle, 1 mg/kg gs-9688 or 3 mg/kg gs-9688. vehicle and 1 mg/kg gs-9688 ha ... | 2020 | 32246499 |
| liver-specific 3d sectioning molds for correlating in vivo ct and mri with tumor histopathology in woodchucks (marmota monax). | to evaluate the spatial registration and correlation of liver and tumor histopathology sections with corresponding in vivo ct and mri using 3d, liver-specific cutting molds in a woodchuck (marmota monax) hepatic tumor model. | 2020 | 32214365 |
| delayed response to proton beam treatment of hepatocellular carcinoma. | hepatocellular carcinoma (hcc) has become one of the leading causes of cancer death worldwide. there has been anecdotal report regarding the effectiveness of proton beam treatment for hcc. in this pre-clinical investigation, the woodchuck model of viral hepatitis infection-induced hcc was used for proton beam treatment experiment. the radiopaque fiducial markers that are biodegradable were injected around the tumor under ultrasound guidance to facilitate positioning in sequential treatments. an ... | 2020 | 32201597 |
| a translational hepatic artery infusion (hai) model for hepatocellular carcinoma in woodchucks. | woodchucks (marmota monax) are a well-accepted animal model for the investigation of spontaneous hepatocellular carcinoma (hcc). as hcc tumors obtain nutrient blood supply exclusively from the hepatic artery, hepatic artery infusion (hai) has been applied to hcc. however, there is a scarcity of experimental animal models to standardize drug regimens and examine novel agents. the purpose of this study was to establish an hai model in woodchucks. | 2020 | 32143057 |
| in-vitro and in-vivo models for hepatitis b cure research. | antiviral therapy for chronic hepatitis b infection is rarely curative, thus research in hbv cure strategies is a priority. drug development and testing has been hampered by the lack of robust cell culture systems and small animal models. this review summarizes existing models for hbv cure research and focuses on recent developments since 2017 until today. | 2020 | 32109910 |
| transarterial chemoembolization in a woodchuck model of hepatocellular carcinoma. | to assess the feasibility of transarterial chemoembolization with drug-eluting embolic (dee) microspheres in a woodchuck model of hepatocellular carcinoma (hcc). | 2020 | 32107125 |
| three steps to cure pulmonary fibrosis. step 1: the runaway train or groundhog day? | | 2020 | 32078782 |
| kinetics of dna damage repair response accompanying initial hepadnavirus-host genomic integration in woodchuck hepatitis virus infection of hepatocyte. | mechanism of initial hepatitis b virus (hbv) integrations and kinetics of dna repair immediately after infection remain essentially unknown impairing understanding of hepadnaviral oncogenesis. wcm260 hepatocytes susceptible to hbv-compatible woodchuck hepatitis virus (whv) were examined from 15 min to 72 h post-infection (p.i.). whv strongly induced reactive oxygen species (ros), transiently inducible nitric oxide (inos) and dna damage from 15 min p.i. all initial whv-host fusions had the head-t ... | 2020 | 32062411 |
| efficient in vivo editing of otc-deficient patient-derived primary human hepatocytes. | genome editing technology has immense therapeutic potential and is likely to rapidly supplant contemporary gene addition approaches. key advantages include the capacity to directly repair mutant loci with resultant recovery of physiological gene expression and maintenance of durable therapeutic effects in replicating cells. in this study, we aimed to repair a disease-causing point mutation in the ornithine transcarbamylase (otc) locus in patient-derived primary human hepatocytes in vivo at thera ... | 2020 | 32039406 |
| designing a therapeutic hepatitis b vaccine to circumvent immune tolerance. | an effective prophylactic hepatitis b virus (hbv) vaccine has long been available but is ineffective for chronic infection. the primary cause of chronic hepatitis b (chb) and greatest impediment for a therapeutic vaccine is the direct and indirect effects of immune tolerance to hbv antigens. the resulting defective cd4+/cd8+ t cell response, poor cytokine production, insufficient neutralizing antibody (nab) and poor response to hbsag vaccination characterize chb infection. the objective of this ... | 2020 | 31809638 |