AIM To establish a rotavirus(RV)-induced diarrhea model using RV SA11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of RV infection and evaluation of candidate vaccines.METHODS Neona...AIM To establish a rotavirus(RV)-induced diarrhea model using RV SA11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of RV infection and evaluation of candidate vaccines.METHODS Neonatal rhesus monkeys with an average age of 15-20 d and an average weight of 500 g ± 150 g received intragastric administration of varying doses of SA11 RV( 107 PFUs/mL, 106 PFUs/mL, or 105 PFUs/mL, 10 mL/animal) to determine whether the SA11 strain can effectively infect these animals by observing their clinical symptoms, fecal shedding of virus antigen by ELISA, distribution of RV antigen in the organs by immunofluorescence, variations of viral RNA load in the organs by qRT-PCR, histopathological changes in the small intestine by HE staining, and apoptosis of small intestinal epithelial cells by TUNEL assay.RESULTS The RV monkey model showed typical clinical diarrhea symptoms in the 108 PFUs SA11 group, where we observed diarrhea 1-4 d post infection(dpi) and viral antigen shed in the feces from 1-7 dpi. RV was found in jejunal epithelial cells. We observed a viral load of approximately 5.85 × 103 copies per 100 mg in the jejunum at 2 dpi, which was increased to 1.09 × 105 copies per 100 mg at 3 dpi. A relatively high viral load was also seen in mesenteric lymph nodes at 2 dpi and 3 dpi. The following histopathological changes were observed in the small intestine following intragastric administration of SA11 RV: vacuolization, edema, and atrophy. Apoptosis in the jejunal villus epithelium was also detectable at 3 dpi.CONCLUSION Our results indicate that we have successfully established a RV SA11 strain diarrhea model in neonatal rhesus monkeys. Future studies will elucidate the mechanisms underlying the pathogenesis of RV infection, and we will use the model to evaluate the protective effect of candidate vaccines.展开更多
We study a generalization of the vertex cover problem. For a given graph with weights on the vertices and an integer k, we aim to find a subset of the vertices with minimum total weight, so that at least k edges in th...We study a generalization of the vertex cover problem. For a given graph with weights on the vertices and an integer k, we aim to find a subset of the vertices with minimum total weight, so that at least k edges in the graph are covered. The problem is called the k-partial vertex cover problem. There are some 2-approximation algorithms for the problem. In the paper we do not improve on the approximation ratios of the previous algorithms, but we derive an iterative rounding algorithm. We present our technique in two algorithms. The first is an iterative rounding algorithm and gives a(2 +Q OPT)-approximation for the k-partial vertex cover problem where Q is the largest finite weight in the problem definition and OP T is the optimal value for the instance. The second algorithm uses the first as a subroutine and achieves an approximation ratio of 2.展开更多
Human visual acuity is anatomically determined by the retinal fovea.The ontogenetic development of the fovea can be seriously hindered by oculocutaneous albinism(OCA),which is characterized by a disorder of melanin sy...Human visual acuity is anatomically determined by the retinal fovea.The ontogenetic development of the fovea can be seriously hindered by oculocutaneous albinism(OCA),which is characterized by a disorder of melanin synthesis.Although people of all ethnic backgrounds can be affected,no efficient treatments for OCA have been developed thus far,due partly to the lack of effective animal models.Rhesus macaques are genetically homologous to humans and,most importantly,exhibit structures of the macula and fovea that are similar to those of humans;thus,rhesus macaques present special advantages in the modeling and study of human macular and foveal diseases.In this study,we identified rhesus macaque models with clinical characteristics consistent with those of OCA patients according to observations of ocular behavior,fundus examination,and optical coherence tomography.Genomic sequencing revealed a biallelic p.L312I mutation in TYR and a homozygous p.S788L mutation in OCA2,both of which were further confirmed to affect melanin biosynthesis via in vitro assays.These rhesus macaque models of OCA will be useful animal resources for studying foveal development and for preclinical trials of new therapies for OCA.展开更多
基金the CAMS Initiative for Innovative Medicine,No.2016-I2M-1-019National Natural Science Foundation of China,No.31700154+4 种基金Major Science and Technology Special Project of Yunnan Province(Biomedicine),No.2018ZF006Science and Technology Project of Yunnan Province-general program,No.2016FB034Science and Technology Innovation Team Project of Kunming,No.2016-2-R-07674the Project of National Nonprofit Scientific Institutes Basic Scientific Service Fee,No.2016ZX310179-4Science and Technology Project of Yunnan Province,Key New Product Development,No.2014BC008
文摘AIM To establish a rotavirus(RV)-induced diarrhea model using RV SA11 in neonatal rhesus monkeys for the study of the pathogenic and immune mechanisms of RV infection and evaluation of candidate vaccines.METHODS Neonatal rhesus monkeys with an average age of 15-20 d and an average weight of 500 g ± 150 g received intragastric administration of varying doses of SA11 RV( 107 PFUs/mL, 106 PFUs/mL, or 105 PFUs/mL, 10 mL/animal) to determine whether the SA11 strain can effectively infect these animals by observing their clinical symptoms, fecal shedding of virus antigen by ELISA, distribution of RV antigen in the organs by immunofluorescence, variations of viral RNA load in the organs by qRT-PCR, histopathological changes in the small intestine by HE staining, and apoptosis of small intestinal epithelial cells by TUNEL assay.RESULTS The RV monkey model showed typical clinical diarrhea symptoms in the 108 PFUs SA11 group, where we observed diarrhea 1-4 d post infection(dpi) and viral antigen shed in the feces from 1-7 dpi. RV was found in jejunal epithelial cells. We observed a viral load of approximately 5.85 × 103 copies per 100 mg in the jejunum at 2 dpi, which was increased to 1.09 × 105 copies per 100 mg at 3 dpi. A relatively high viral load was also seen in mesenteric lymph nodes at 2 dpi and 3 dpi. The following histopathological changes were observed in the small intestine following intragastric administration of SA11 RV: vacuolization, edema, and atrophy. Apoptosis in the jejunal villus epithelium was also detectable at 3 dpi.CONCLUSION Our results indicate that we have successfully established a RV SA11 strain diarrhea model in neonatal rhesus monkeys. Future studies will elucidate the mechanisms underlying the pathogenesis of RV infection, and we will use the model to evaluate the protective effect of candidate vaccines.
基金Supported by the National Natural Science Foundation of China(No.11201021)
文摘We study a generalization of the vertex cover problem. For a given graph with weights on the vertices and an integer k, we aim to find a subset of the vertices with minimum total weight, so that at least k edges in the graph are covered. The problem is called the k-partial vertex cover problem. There are some 2-approximation algorithms for the problem. In the paper we do not improve on the approximation ratios of the previous algorithms, but we derive an iterative rounding algorithm. We present our technique in two algorithms. The first is an iterative rounding algorithm and gives a(2 +Q OPT)-approximation for the k-partial vertex cover problem where Q is the largest finite weight in the problem definition and OP T is the optimal value for the instance. The second algorithm uses the first as a subroutine and achieves an approximation ratio of 2.
基金This study was supported by the Natural Science Foundation of China(81522014,81970838)the National Key Research and Development Program of China(2017YFA0105300)+3 种基金the Zhejiang Provincial Natural Science Foundation of China(LQ17H120005)China Postdoctoral Science Foundation(2017M620235)the CAMS Innovation Fund for Medical Sciences(CIFMS,2016-I2M-2-001)the Chinese Institute for Brain Research,Beijing(CIBR,Z18110000151800).
文摘Human visual acuity is anatomically determined by the retinal fovea.The ontogenetic development of the fovea can be seriously hindered by oculocutaneous albinism(OCA),which is characterized by a disorder of melanin synthesis.Although people of all ethnic backgrounds can be affected,no efficient treatments for OCA have been developed thus far,due partly to the lack of effective animal models.Rhesus macaques are genetically homologous to humans and,most importantly,exhibit structures of the macula and fovea that are similar to those of humans;thus,rhesus macaques present special advantages in the modeling and study of human macular and foveal diseases.In this study,we identified rhesus macaque models with clinical characteristics consistent with those of OCA patients according to observations of ocular behavior,fundus examination,and optical coherence tomography.Genomic sequencing revealed a biallelic p.L312I mutation in TYR and a homozygous p.S788L mutation in OCA2,both of which were further confirmed to affect melanin biosynthesis via in vitro assays.These rhesus macaque models of OCA will be useful animal resources for studying foveal development and for preclinical trials of new therapies for OCA.
