Science.gov

Sample records for primate lentivirus replication

  1. High frequency of genetic recombination is a common feature of primate lentivirus replication.

    PubMed

    Chen, Jianbo; Powell, Douglas; Hu, Wei-Shau

    2006-10-01

    Recent studies indicate that human immunodeficiency virus type 1 (HIV-1) recombines at exceedingly high rates, approximately 1 order of magnitude more frequently than simple gammaretroviruses such as murine leukemia virus and spleen necrosis virus. We hypothesize that this high frequency of genetic recombination is a common feature of primate lentiviruses. Alternatively, it is possible that HIV-1 is unique among primate lentiviruses in possessing high recombination rates. Among other primate lentiviruses, only the molecular mechanisms of HIV-2 replication have been extensively studied. There are reported differences between the replication mechanisms of HIV-1 and those of HIV-2, such as preferences for RNA packaging in cis and properties of reverse transcriptase and RNase H activities. These biological disparities could lead to differences in recombination rates between the two viruses. Currently, HIV-1 is the only primate lentivirus in which recombination rates have been measured. To test our hypothesis, we established recombination systems to measure the recombination rates of two other primate lentiviruses, HIV-2 and simian immunodeficiency virus from African green monkeys (SIVagm), in one round of viral replication. We determined that, for markers separated by 588, 288, and 90 bp, HIV-2 recombined at rates of 7.4%, 5.5%, and 2.4%, respectively, whereas SIVagm recombined at rates of 7.8%, 5.6%, and 2.7%, respectively. These high recombination rates are within the same range as the previously measured HIV-1 recombination rates. Taken together, our results indicate that HIV-1, HIV-2, and SIVagm all possess high recombination frequencies; hence, the high recombination potential is most likely a common feature of primate lentivirus replication.

  2. Understanding restriction factors and intrinsic immunity: insights and lessons from the primate lentiviruses

    PubMed Central

    Kirmaier, Andrea; Krupp, Annabel; Johnson, Welkin E

    2014-01-01

    Primate lentiviruses include the HIVs, HIV-1 and HIV-2; the SIVs, which are endemic to more than 40 species of nonhuman primates in Africa; and SIVmac, an AIDS-causing pathogen that emerged in US macaque colonies in the 1970s. Because of the worldwide spread of HIV and AIDS, primate lentiviruses have been intensively investigated for more than 30 years. Research on these viruses has played a leading role in the discovery and characterization of intrinsic immunity, and in particular the identification of several antiviral effectors (also known as restriction factors) including APOBEC3G, TRIM5α, BST-2/tetherin and SAMHD1. Comparative studies of the primate lentiviruses and their hosts have proven critical for understanding both the evolutionary significance and biological relevance of intrinsic immunity, and the role intrinsic immunity plays in governing viral host range and interspecies transmission of viruses in nature. PMID:26543491

  3. Inhibition of lentivirus replication by aqueous extracts of Prunella vulgaris

    PubMed Central

    Brindley, Melinda A; Widrlechner, Mark P; McCoy, Joe-Ann; Murphy, Patricia; Hauck, Cathy; Rizshsky, Ludmila; Nikolau, Basil; Maury, Wendy

    2009-01-01

    Background Various members of the mint family have been used historically in Chinese and Native American medicine. Many of these same family members, including Prunella vulgaris, have been reported to have anti-viral activities. To further characterize the anti-lentiviral activities of P. vulgaris, water and ethanol extractions were tested for their ability to inhibit equine infectious anemia virus (EIAV) replication. Results Aqueous extracts contained more anti-viral activity than did ethanol extracts, displaying potent anti-lentiviral activity against virus in cell lines as well as in primary cell cultures with little to no cellular cytotoxicity. Time-of-addition studies demonstrated that the extracts were effective when added during the first four h of the viral life cycle, suggesting that the botanical constituents were targeting the virion itself or early entry events. Further analysis revealed that the extracts did not destroy EIAV virion integrity, but prevented viral particles from binding to the surface of permissive cells. Modest levels of anti-EIAV activity were also detected when the cells were treated with the extracts prior to infection, indicating that anti-EIAV botanical constituents could interact with both viral particles and permissive cells to interfere with infectivity. Size fractionation of the extract demonstrated that eight of the nine fractions generated from aqueous extracts displayed anti-viral activity. Separation of ethanol soluble and insoluble compounds in the eight active fractions revealed that ethanol-soluble constituents were responsible for the anti-viral activity in one fraction whereas ethanol-insoluble constituents were important for the anti-viral activity in two of the other fractions. In three of the five fractions that lost activity upon sub-fractionation, anti-viral activity was restored upon reconstitution of the fractions, indicating that synergistic anti-viral activity is present in several of the fractions. Conclusion

  4. Evolutionary and Functional Analysis of Old World Primate TRIM5 Reveals the Ancient Emergence of Primate Lentiviruses and Convergent Evolution Targeting a Conserved Capsid Interface

    PubMed Central

    McCarthy, Kevin R.; Kirmaier, Andrea; Autissier, Patrick; Johnson, Welkin E.

    2015-01-01

    The widespread distribution of lentiviruses among African primates, and the lack of severe pathogenesis in many of these natural reservoirs, are taken as evidence for long-term co-evolution between the simian immunodeficiency viruses (SIVs) and their primate hosts. Evidence for positive selection acting on antiviral restriction factors is consistent with virus-host interactions spanning millions of years of primate evolution. However, many restriction mechanisms are not virus-specific, and selection cannot be unambiguously attributed to any one type of virus. We hypothesized that the restriction factor TRIM5, because of its unique specificity for retrovirus capsids, should accumulate adaptive changes in a virus-specific fashion, and therefore, that phylogenetic reconstruction of TRIM5 evolution in African primates should reveal selection by lentiviruses closely related to modern SIVs. We analyzed complete TRIM5 coding sequences of 22 Old World primates and identified a tightly-spaced cluster of branch-specific adaptions appearing in the Cercopithecinae lineage after divergence from the Colobinae around 16 million years ago. Functional assays of both extant TRIM5 orthologs and reconstructed ancestral TRIM5 proteins revealed that this cluster of adaptations in TRIM5 specifically resulted in the ability to restrict Cercopithecine lentiviruses, but had no effect (positive or negative) on restriction of other retroviruses, including lentiviruses of non-Cercopithecine primates. The correlation between lineage-specific adaptations and ability to restrict viruses endemic to the same hosts supports the hypothesis that lentiviruses closely related to modern SIVs were present in Africa and infecting the ancestors of Cercopithecine primates as far back as 16 million years ago, and provides insight into the evolution of TRIM5 specificity. PMID:26291613

  5. Primate lentiviruses are differentially inhibited by interferon-induced transmembrane proteins

    PubMed Central

    Qian, Jin; Le Duff, Yann; Wang, Yimeng; Pan, Qinghua; Ding, Shilei; Zheng, Yi-Min; Liu, Shan-Lu; Liang, Chen

    2015-01-01

    Interferon-induced transmembrane (IFITM) proteins inhibit the entry of a large number of viruses. Not surprisingly, many viruses are refractory to this inhibition. In this study, we report that different strains of HIV and SIV are inhibited by human IFITM proteins to various degrees, with SIV of African green monkeys (SIVAGM) being mostly restricted by human IFITM2. Interestingly, SIVAGM is as much inhibited by human IFITM2 as by IFITM3 of its own host African green monkeys. Our data further demonstrate that the entry of SIVAGM is impaired by human IFITM2 and that this inhibition is overcome by the cholesterol-binding compound amphotericin B that also overcomes IFITM inhibition of influenza A viruses. These results suggest that IFITM proteins exploit similar mechanisms to inhibit the entry of both pH-independent primate lentiviruses and the pH-dependent influenza A viruses. PMID:25463599

  6. Ovine lentivirus is macrophagetropic and does not replicate productively in T lymphocytes.

    PubMed Central

    Gorrell, M D; Brandon, M R; Sheffer, D; Adams, R J; Narayan, O

    1992-01-01

    The lentiviruses of sheep, goats, and horses cause chronic multiorgan disease in which macrophages are highly permissive for viral replication. Monocytes, which mature into macrophages, are thought to be latently infected with lentivirus, but the extent to which other leukocytes are infected is unknown. Dendritic cells have not been studied separately from monocytes and T-cell subsets have not been examined in previous attempts to identify infected cells in peripheral blood mononuclear cells (PBMC). We found no evidence of T-cell tropism using an animal-passaged, pathogenic ovine lentivirus. Phytohemagglutinin-stimulated infectious PBMC produced 20-fold less virus than differentiated macrophages, and cocultivation of infectious PBMC with fresh, uninfected phytohemagglutinin blasts did not facilitate virus replication. Furthermore, central lymph cells, the best in vivo source of purified lymphocytes, lacked virus and did not yield virus upon in vitro cultivation. In contrast, cultivated blood-derived macrophages were highly permissive for viral replication. To identify the latently infected PBMC, PBMC from infected sheep were selectively depleted of monocytes and B cells by passage over nylon wool and then of nonadherent cells bearing CD4, CD8, T19, gamma delta T-cell receptor, CD45RA, or major histocompatibility complex class II antigens by panning. Removal of adherent monocytes and B cells or of adherent cells and the three major T-cell subsets (CD4+, CD8+, T19+) did not decrease the infectivity of PBMC. The richest sources of infected cells in fresh PBMC were CD45RA+ and major histocompatibility complex class II+ nonadherent cells, which are three characteristics of dendritic cells. Thus, the dendritic cell, and not the monocyte or the CD4+ cell, is probably the predominant infected cell type in blood. Images PMID:1348546

  7. The Potency of Nef-Mediated SERINC5 Antagonism Correlates with the Prevalence of Primate Lentiviruses in the Wild.

    PubMed

    Heigele, Anke; Kmiec, Dorota; Regensburger, Kerstin; Langer, Simon; Peiffer, Lukas; Stürzel, Christina M; Sauter, Daniel; Peeters, Martine; Pizzato, Massimo; Learn, Gerald H; Hahn, Beatrice H; Kirchhoff, Frank

    2016-09-14

    The cellular factor serine incorporator 5 (SERINC5) impairs HIV-1 infectivity but is antagonized by the viral Nef protein. We analyzed the anti-SERINC5 activity of Nef proteins across primate lentiviruses and examined whether SERINC5 represents a barrier to cross-species transmissions and/or within-species viral spread. HIV-1, HIV-2, and SIV Nefs counteract human, ape, monkey, and murine SERINC5 orthologs with similar potency. However, HIV-1 Nefs are more active against SERINC5 than HIV-2 Nefs, and chimpanzee SIV (SIVcpz) Nefs are more potent than those of their monkey precursors. Additionally, Nefs of HIV and most SIVs rely on the dileucine motif in the C-terminal loop for anti-SERINC5 activity, while the Nef from colobus SIV (SIVcol) evolved different inhibitory mechanisms. We also found a significant correlation between anti-SERINC5 potency and the SIV prevalence in the respective ape and monkey species. Thus, Nef-mediated SERINC5 antagonism may determine the ability of primate lentiviruses to spread within natural hosts. PMID:27631701

  8. Development of an Equine-Tropic Replication-Competent Lentivirus Assay for Equine Infectious Anemia Virus-Based Lentiviral Vectors

    PubMed Central

    Bannister, Richard; Leroux-Carlucci, Marie A.; Evans, Nerys E.; Miskin, James E.; Mitrophanous, Kyriacos A.

    2012-01-01

    Abstract The release of lentiviral vectors for clinical use requires the testing of vector material, production cells, and, if applicable, ex vivo-transduced cells for the presence of replication-competent lentivirus (RCL). Vectors derived from the nonprimate lentivirus equine infectious anemia virus (EIAV) have been directly administered to patients in several clinical trials, with no toxicity observed to date. Because EIAV does not replicate in human cells, and because putative RCLs derived from vector components within human vector production cells would most likely be human cell-tropic, we previously developed an RCL assay using amphotropic murine leukemia virus (MLV) as a surrogate positive control and human cells as RCL amplification/indicator cells. Here we report an additional RCL assay that tests for the presence of theoretical “equine-tropic” RCLs. This approach provides further assurance of safety by detecting putative RCLs with an equine cell-specific tropism that might not be efficiently amplified by the human cell-based RCL assay. We tested the ability of accessory gene-deficient EIAV mutant viruses to replicate in a highly permissive equine cell line to direct our choice of a suitable EIAV-derived positive control. In addition, we report for the first time the mathematical rationale for use of the Poisson distribution to calculate minimal infectious dose of positive control virus and for use in monitoring assay positive/spike control failures in accumulating data sets. No RCLs have been detected in Good Manufacturing Practice (GMP)-compliant RCL assays to date, further demonstrating that RCL formation is highly unlikely in contemporary minimal lentiviral vector systems. PMID:23121195

  9. Sustained inhibition of hepatitis B virus replication in vivo using RNAi-activating lentiviruses.

    PubMed

    Ivacik, D; Ely, A; Ferry, N; Arbuthnot, P

    2015-02-01

    Chronic infection with hepatitis B virus (HBV) puts individuals at high risk for complicating cirrhosis and liver cancer, but available treatment to counter the virus rarely eliminates infection. Although harnessing RNA interference (RNAi) to silence HBV genes has shown the potential, achieving efficient and durable silencing of viral genes remains an important goal. Here we report on the propagation of lentiviral vectors (LVs) that successfully deliver HBV-targeting RNAi activators to liver cells. Mono- and tricistronic artificial primary microRNAs (pri-miRs) derived from pri-miR-31, placed under transcriptional control of the liver-specific modified murine transthyretin (mTTR) promoter, caused efficient inhibition of HBV replication markers. The tricistronic cassette was capable of silencing a mutant viral target and the effects were observed without disrupting the function of an endogenous miR (miR-16). The mTTR promoter stably expressed a reporter transgene in mouse livers over a study period of 1 year. Good silencing of HBV genes, without evidence of toxicity, was demonstrated following intravenous injection of LVs into neonatal HBV transgenic mice. Collectively, these data indicate that LVs may achieve sustained inhibition of HBV replication that is appealing for their therapeutic use.

  10. Inhibition of Human Immunodeficiency Virus Type 1 Replication in Primary Macrophages by Using Tat- or CCR5-Specific Small Interfering RNAs Expressed from a Lentivirus Vector

    PubMed Central

    Lee, Ming-Ta M.; Coburn, Glen A.; McClure, Myra O.; Cullen, Bryan R.

    2003-01-01

    Although several groups have demonstrated that RNA interference, induced by transfection of small interfering RNA (siRNA) duplexes, can protect cells against a viral challenge in culture, this protection is transient. Here, we describe lentivirus expression vectors that can stably express siRNAs at levels sufficient to block virus replication. We have used these vectors to stably express siRNAs specific for the essential human immunodeficiency virus type 1 (HIV-1) Tat transcription factor or specific for a cellular coreceptor, CCR5, that is required for infection by the majority of primary HIV-1 isolates. These lentivirus vectors are shown to protect cells, including primary macrophages, against HIV-1 infection in culture by inducing selective degradation of their target mRNA species. These data suggest that it should be possible to block the expression of specific viral or cellular genes in vivo by using viral vectors to stably express the appropriate siRNAs. PMID:14581533

  11. Discovery of a lentivirus susceptibility gene in sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ovine lentivirus targets the host immune system and causes persistent retroviral infections affecting millions of sheep worldwide. In primates, lentivirus resistance is attributed to mutant virus coreceptors that are not expressed. In sheep, some animals are resistant to lentivirus infection despit...

  12. Small ruminant lentivirus-induced arthritis: clinicopathologic findings in sheep infected by a highly replicative SRLV B2 genotype.

    PubMed

    Pérez, M; Biescas, E; Reina, R; Glaria, I; Marín, B; Marquina, A; Salazar, E; Álvarez, N; de Andrés, D; Fantova, E; Badiola, J J; Amorena, B; Luján, L

    2015-01-01

    We describe the clinicopathologic features of an arthritis outbreak in sheep induced by small ruminant lentivirus (SRLV), linked to the presence of a new SRLV isolate phylogenetically assigned to caprine arthritis encephalitis virus-like subgroup B2. Thirteen SRLV seropositive Rasa Aragonesa adult ewes were selected from 5 SRLV highly infected flocks (mean seroprevalence, 90.7%) for presenting uni- or bilateral chronic arthritis in the carpal joint. A complete study was performed, including symptomatology, histopathology, immunocytochemistry, immunohistochemistry, in situ hybridization, and microbiology. The carpus was the joint almost exclusively affected, with 10 sheep (76%) showing a moderate increase in carpal joint size (diameter range, 18-20 cm; normal range, 15-16 cm) without signs of locomotion problems and with 3 ewes (23%) showing severe inflammation with marked increase in diameter (21-24 cm), pain at palpation, and abnormal standing position. Grossly, chronic proliferative arthritis was observed in affected joints characterized by an increased thickness of the synovial capsule and synovial membrane proliferation. Microscopically, synovial membrane inflammation and proliferation and hyperplasia of synoviocytes were observed. More positive cases of SLRV infection were detected by immunocytochemistry of articular fluid than of bronchoalveolar lavage fluid. Immunohistochemistry and in situ hybridization also detected positive cells in the subsynovial connective tissue, lung, mediastinal lymph node, mammary gland, and mammary lymph node. All animals were negative for the presence of Mycoplasma or other bacteria in the articular space. The present outbreak likely represents an adaptation of a caprine virus to sheep. Our results underline the importance of the arthritis induced by SRLV in sheep, a clinical form that might be underestimated.

  13. Nonhuman Primate IFITM Proteins Are Potent Inhibitors of HIV and SIV

    PubMed Central

    Wilkins, Jordan; Zheng, Yi-Min; Yu, Jingyou; Liang, Chen

    2016-01-01

    Interferon-induced transmembrane (IFITM) proteins are potent antiviral factors shown to restrict the infection of many enveloped viruses, including HIV. Here we report cloning and characterization of a panel of nonhuman primate IFITMs. We show that, similar to human IFITM, nonhuman primate IFITM proteins inhibit HIV and other primate lentiviruses. While some nonhuman primate IFITM proteins are more potent than human counterparts to inhibit HIV-1, they are generally not effective against HIV-2 similar to that of human IFITMs. Notably, depending on SIV strains and also IFITM species tested, nonhuman primate IFITM proteins exhibit distinct activities against SIVs; no correlation was found to support the notion that IFITM proteins are most active in non-natural primate hosts. Consistent with our recent findings for human IFITMs, nonhuman primate IFITM proteins interact with HIV-1 Env and strongly act in viral producer cells to impair viral infectivity and block cell-to-cell transmission. Accordingly, knockdown of primate IFITM3 increases HIV-1 replication in nohuman primate cells. Interestingly, analysis of DNA sequences of human and nonhuman primate IFITMs suggest that IFITM proteins have been undergoing purifying selection, rather than positive selection typical for cellular restriction factors. Overall, our study reveals some new and unexpected features of IFITMs in restricting primate lentiviruses, which enhances our understanding of virus-host interaction and AIDS pathogenesis. PMID:27257969

  14. Cyclin A Degradation by Primate Cytomegalovirus Protein pUL21a Counters Its Innate Restriction of Virus Replication

    PubMed Central

    Yu, Dong

    2013-01-01

    Cyclin A is critical for cellular DNA synthesis and S phase progression of the cell cycle. Human cytomegalovirus (HCMV) can reduce cyclin A levels and block cellular DNA synthesis, and cyclin A overexpression can repress HCMV replication. This interaction has only been previously observed in HCMV as murine CMV does not downregulate cyclin A, and the responsible viral factor has not been identified. We previously reported that the HCMV protein pUL21a disrupted the anaphase-promoting complex (APC), but a point mutant abrogating this activity did not phenocopy a UL21a-deficient virus, suggesting that pUL21a has an additional function. Here we identified a conserved arginine-x-leucine (RxL) cyclin-binding domain within pUL21a, which allowed pUL21a to interact with cyclin A and target it for proteasome degradation. Homologous pUL21a proteins from both chimpanzee and rhesus CMVs also contained the RxL domain and similarly degraded cyclin A, indicating that this function is conserved in primate CMVs. The RxL point mutation disabled the virus' ability to block cellular DNA synthesis and resulted in a growth defect similar to pUL21a-deficient virus. Importantly, knockdown of cyclin A rescued growth of UL21a-deficient virus. Together, these data show that during evolution, the pUL21a family proteins of primate CMVs have acquired a cyclin-binding domain that targets cyclin A for degradation, thus neutralizing its restriction on virus replication. Finally, the combined proteasome-dependent degradation of pUL21a and its cellular targets suggests that pUL21a may act as a novel suicide protein, targeting its protein cargos for destruction. PMID:24385906

  15. A minimal lentivirus Tat.

    PubMed Central

    Derse, D; Carvalho, M; Carroll, R; Peterlin, B M

    1991-01-01

    Transcriptional regulatory mechanisms found in lentiviruses employ RNA enhancer elements called trans-activation responsive (TAR) elements. These nascent RNA stem-loops are cis-acting targets of virally encoded Tat effectors. Interactions between Tat and TAR increase the processivity of transcription complexes and lead to efficient copying of viral genomes. To study essential elements of this trans activation, peptide motifs from Tats of two distantly related lentiviruses, equine infectious anemia virus (EIAV) and human immunodeficiency virus type 1 (HIV-1), were fused to the coat protein of bacteriophage R17 and tested on the long terminal repeat of EIAV, where TAR was replaced by the R17 operator, the target of the coat protein. This independent RNA-tethering mechanism mapped activation domains of Tats from HIV-1 and EIAV to 47 and 15 amino acids and RNA-binding domains to 10 and 26 amino acids, respectively. Thus, a minimal lentivirus Tat consists of 25 amino acids, of which 15 modify viral transcription and 10 bind to the target RNA stem-loop. Images PMID:1658392

  16. Lentivirus-mediated Bos taurus bta-miR-29b overexpression interferes with bovine viral diarrhoea virus replication and viral infection-related autophagy by directly targeting ATG14 and ATG9A in Madin-Darby bovine kidney cells.

    PubMed

    Fu, Qiang; Shi, Huijun; Ni, Wei; Shi, Mengting; Meng, Luping; Zhang, Hui; Ren, Yan; Guo, Fei; Wang, Pengyan; Qiao, Jun; Jia, Bin; Chen, Chuangfu

    2015-01-01

    MicroRNAs (miRNAs) are a class of short endogenous RNA molecules with the ability to control development, autophagy, apoptosis and the stress response in eukaryotes by pairing with partially complementary sites in the 3' UTRs of targeted genes. Recent studies have demonstrated that miRNAs serve as critical effectors in intricate networks of host-pathogen interactions. Notably, we found that Bos taurus bta-miR-29b (referred to as miR-29b herein) was significantly upregulated >2.3-fold in bovine viral diarrhoea virus (BVDV) strain NADL-infected Madin-Darby bovine kidney (MDBK) cells 6 h post-infection compared with normal MDBK cells. However, the roles of miR-29b in BVDV infection and pathogenesis remain unclear. Here, we report the inhibitory effects of miR-29b on BVDV NADL replication and viral infection-related autophagy. miR-29b overexpression mediated by miRNA precursor-expressing lentivirus resulted in the attenuation of BVDV NADL infection-related autophagy by directly downregulating the intracellular expression levels of two key autophagy-associated proteins, ATG14 and ATG9A. Moreover, ATG14 and ATG9A overexpression rescue not only reversed miR-29b-inhibited autophagy, but also increased BVDV NADL replication. In previous studies, we found that the early stages of autophagy contributed to BVDV NADL replication in MDBK cells and that the inhibition of autophagy repressed BVDV NADL replication, which was also proved in the present study. Collectively, our results establish a novel link between miR-29b and viral replication, and also provide a new pathway for the intimate interaction between host cells and pathogens.

  17. A Primitive Endogenous Lentivirus in a Colugo: Insights into the Early Evolution of Lentiviruses

    PubMed Central

    Han, Guan-Zhu; Worobey, Michael

    2015-01-01

    Lentiviruses infect a wide range of mammal species. Much remains unknown about their deep history and host distribution. Here, we report the discovery of an endogenous lentivirus within the genome of the Sunda flying lemur (Galeopterus variegatus) (which we designate “Galeopterus variegatus endogenous lentivirus” [GvaELV]). We estimate the GvaELV genome invasion to have occurred more than 14 Ma, supporting an ancient origin of the lentivirus clade and an ancient lentiviral infection in colugo. Phylogenetic analyses show that GvaELV is a sister group of all previously known lentiviruses. The GvaELV genome appears to possess some primitive genomic features of a lentivirus, encoding not only a trans-activator of transcription (tat) gene but also two additional putative accessory genes that share no discernible similarity with other lentiviral accessory genes. The discovery of GvaELV provides novel insights into the prehistory and host distribution of lentivirus. PMID:25349288

  18. A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates.

    PubMed

    Sha, Jian; Kirtley, Michelle L; Klages, Curtis; Erova, Tatiana E; Telepnev, Maxim; Ponnusamy, Duraisamy; Fitts, Eric C; Baze, Wallace B; Sivasubramani, Satheesh K; Lawrence, William S; Patrikeev, Igor; Peel, Jennifer E; Andersson, Jourdan A; Kozlova, Elena V; Tiner, Bethany L; Peterson, Johnny W; McWilliams, David; Patel, Snehal; Rothe, Eric; Motin, Vladimir L; Chopra, Ashok K

    2016-07-01

    Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models. PMID:27170642

  19. A Replication-Defective Human Type 5 Adenovirus-Based Trivalent Vaccine Confers Complete Protection against Plague in Mice and Nonhuman Primates.

    PubMed

    Sha, Jian; Kirtley, Michelle L; Klages, Curtis; Erova, Tatiana E; Telepnev, Maxim; Ponnusamy, Duraisamy; Fitts, Eric C; Baze, Wallace B; Sivasubramani, Satheesh K; Lawrence, William S; Patrikeev, Igor; Peel, Jennifer E; Andersson, Jourdan A; Kozlova, Elena V; Tiner, Bethany L; Peterson, Johnny W; McWilliams, David; Patel, Snehal; Rothe, Eric; Motin, Vladimir L; Chopra, Ashok K

    2016-07-01

    Currently, no plague vaccine exists in the United States for human use. The capsular antigen (Caf1 or F1) and two type 3 secretion system (T3SS) components, the low-calcium-response V antigen (LcrV) and the needle protein YscF, represent protective antigens of Yersinia pestis We used a replication-defective human type 5 adenovirus (Ad5) vector and constructed recombinant monovalent and trivalent vaccines (rAd5-LcrV and rAd5-YFV) that expressed either the codon-optimized lcrV or the fusion gene designated YFV (consisting of ycsF, caf1, and lcrV). Immunization of mice with the trivalent rAd5-YFV vaccine by either the intramuscular (i.m.) or the intranasal (i.n.) route provided protection superior to that with the monovalent rAd5-LcrV vaccine against bubonic and pneumonic plague when animals were challenged with Y. pestis CO92. Preexisting adenoviral immunity did not diminish the protective response, and the protection was always higher when mice were administered one i.n. dose of the trivalent vaccine (priming) followed by a single i.m. booster dose of the purified YFV antigen. Immunization of cynomolgus macaques with the trivalent rAd5-YFV vaccine by the prime-boost strategy provided 100% protection against a stringent aerosol challenge dose of CO92 to animals that had preexisting adenoviral immunity. The vaccinated and challenged macaques had no signs of disease, and the invading pathogen rapidly cleared with no histopathological lesions. This is the first report showing the efficacy of an adenovirus-vectored trivalent vaccine against pneumonic plague in mouse and nonhuman primate (NHP) models.

  20. Cell-Associated Transmission of HIV Type 1 and Other Lentiviruses in Small-Animal Models

    PubMed Central

    Moench, Thomas R.

    2014-01-01

    Small-animal models of lentivirus transmission have repeatedly demonstrated transmission by cell-associated virus via vaginal, rectal, and oral routes. The earliest experiments were in the cat/feline immunodeficiency virus model, followed a decade later by successful vaginal transmission of cell-associated human immunodeficiency virus (HIV) in mice bearing transplanted human immune cells. After early unsuccessful attempts at cell-associated transmission in nonhuman primates, renewed investigation in diverse primate models has now confirmed the findings from the cat and humanized mouse models. Improvements in humanized mouse models have made them the preferred small-animal models to study HIV mucosal transmission. They provide complementary systems to nonhuman primate models to aid in the elucidation of the many remaining questions on the mechanism of and means to prevent both cell-associated and cell-free HIV transmission across mucosal barriers. PMID:25414420

  1. Going Wild: Lessons from Naturally Occurring T-Lymphotropic Lentiviruses

    PubMed Central

    VandeWoude, Sue; Apetrei, Cristian

    2006-01-01

    Over 40 nonhuman primate (NHP) species harbor species-specific simian immunodeficiency viruses (SIVs). Similarly, more than 20 species of nondomestic felids and African hyenids demonstrate seroreactivity against feline immunodeficiency virus (FIV) antigens. While it has been challenging to study the biological implications of nonfatal infections in natural populations, epidemiologic and clinical studies performed thus far have only rarely detected increased morbidity or impaired fecundity/survival of naturally infected SIV- or FIV-seropositive versus -seronegative animals. Cross-species transmissions of these agents are rare in nature but have been used to develop experimental systems to evaluate mechanisms of pathogenicity and to develop animal models of HIV/AIDS. Given that felids and primates are substantially evolutionarily removed yet demonstrate the same pattern of apparently nonpathogenic lentiviral infections, comparison of the biological behaviors of these viruses can yield important implications for host-lentiviral adaptation which are relevant to human HIV/AIDS infection. This review therefore evaluates similarities in epidemiology, lentiviral genotyping, pathogenicity, host immune responses, and cross-species transmission of FIVs and factors associated with the establishment of lentiviral infections in new species. This comparison of consistent patterns in lentivirus biology will expose new directions for scientific inquiry for understanding the basis for virulence versus avirulence. PMID:17041142

  2. [Analysis of the biological effect of city smog extract. III. Comparative investigations on the effect of city smog extracts on cell replication and DNA-synthesis of kidney cells in vitro from the primate Cercopithecus aethiops (author's transl)].

    PubMed

    Manojlovic, N; Seemayer, N; de Ruiter, N; Weisz, H; Bauer, S

    1978-08-01

    We analysed the cytotoxic effect of city smog extracts from a heavy industrialized area using kidney cell cultures from the primate Cercopithecus aethiops.--Using logarithmically growing cell cultures we determined cell replication and the rate of DNA-synthesis after incorporation of 3H-thymidine.--In presence of city smog extracts we found a dose dependent reduction of cell replication and of DNA-synthesis. In presence of high concentrations (BP-aquivalent 0.25-0.5 microgram/ml) of city smog extract we found no increase in cell number over a period of 72 h. Under the same conditions hardly any DNA-synthesis was detected.--In presence of middle and low concentrations of city smog extract a dose- and time-dependent increase in cell number and rate of DNA-synthesis was detected.

  3. Absence of MutSβ leads to the formation of slipped-DNA for CTG/CAG contractions at primate replication forks.

    PubMed

    Slean, Meghan M; Panigrahi, Gagan B; Castel, Arturo López; Pearson, August B; Tomkinson, Alan E; Pearson, Christopher E

    2016-06-01

    Typically disease-causing CAG/CTG repeats expand, but rare affected families can display high levels of contraction of the expanded repeat amongst offspring. Understanding instability is important since arresting expansions or enhancing contractions could be clinically beneficial. The MutSβ mismatch repair complex is required for CAG/CTG expansions in mice and patients. Oddly, by unknown mechanisms MutSβ-deficient mice incur contractions instead of expansions. Replication using CTG or CAG as the lagging strand template is known to cause contractions or expansions respectively; however, the interplay between replication and repair leading to this instability remains unclear. Towards understanding how repeat contractions may arise, we performed in vitro SV40-mediated replication of repeat-containing plasmids in the presence or absence of mismatch repair. Specifically, we separated repair from replication: Replication mediated by MutSβ- and MutSα-deficient human cells or cell extracts produced slipped-DNA heteroduplexes in the contraction- but not expansion-biased replication direction. Replication in the presence of MutSβ disfavoured the retention of replication products harbouring slipped-DNA heteroduplexes. Post-replication repair of slipped-DNAs by MutSβ-proficient extracts eliminated slipped-DNAs. Thus, a MutSβ-deficiency likely enhances repeat contractions because MutSβ protects against contractions by repairing template strand slip-outs. Replication deficient in LigaseI or PCNA-interaction mutant LigaseI revealed slipped-DNA formation at lagging strands. Our results reveal that distinct mechanisms lead to expansions or contractions and support inhibition of MutSβ as a therapeutic strategy to enhance the contraction of expanded repeats. PMID:27155933

  4. Coevolutionary dynamics between tribe Cercopithecini tetherins and their lentiviruses

    PubMed Central

    Takeuchi, Junko S.; Ren, Fengrong; Yoshikawa, Rokusuke; Yamada, Eri; Nakano, Yusuke; Kobayashi, Tomoko; Matsuda, Kenta; Izumi, Taisuke; Misawa, Naoko; Shintaku, Yuta; Wetzel, Katherine S.; Collman, Ronald G.; Tanaka, Hiroshi; Hirsch, Vanessa M.; Koyanagi, Yoshio; Sato, Kei

    2015-01-01

    Human immunodeficiency virus, a primate lentivirus (PLV), causes AIDS in humans, whereas most PLVs are less or not pathogenic in monkeys. These notions suggest that the co-evolutionary process of PLVs and their hosts associates with viral pathogenicity, and therefore, that elucidating the history of virus-host co-evolution is one of the most intriguing topics in the field of virology. To address this, recent studies have focused on the interplay between intrinsic anti-viral proteins, such as tetherin, and viral antagonists. Through an experimental-phylogenetic approach, here we investigate the co-evolutionary interplay between tribe Cercopithecini tetherin and viral antagonists, Nef and Vpu. We reveal that tribe Cercopithecini tetherins are positively selected, possibly triggered by ancient Nef-like factor(s). We reconstruct the ancestral sequence of tribe Cercopithecini tetherin and demonstrate that all Nef proteins are capable of antagonizing ancestral Cercopithecini tetherin. Further, we consider the significance of evolutionary arms race between tribe Cercopithecini and their PLVs. PMID:26531727

  5. Evolutionary Analyses Suggest a Function of MxB Immunity Proteins Beyond Lentivirus Restriction

    PubMed Central

    Mitchell, Patrick S.; Young, Janet M.; Emerman, Michael; Malik, Harmit S.

    2015-01-01

    Viruses impose diverse and dynamic challenges on host defenses. Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts. The myxovirus resistance (Mx) genes encode interferon-inducible GTPases that constitute a major arm of the cell-autonomous defense against viral infection. Unlike the broad antiviral activity of MxA, primate MxB was recently shown to specifically inhibit lentiviruses including HIV-1. We carried out detailed evolutionary analyses to investigate whether genetic conflict with lentiviruses has shaped MxB evolution in primates. We found strong evidence for diversifying selection in the MxB N-terminal tail, which contains molecular determinants of MxB anti-lentivirus specificity. However, we found no overlap between previously-mapped residues that dictate lentiviral restriction and those that have evolved under diversifying selection. Instead, our findings are consistent with MxB having a long-standing and important role in the interferon response to viral infection against a broader range of pathogens than is currently appreciated. Despite its critical role in host innate immunity, we also uncovered multiple functional losses of MxB during mammalian evolution, either by pseudogenization or by gene conversion from MxA genes. Thus, although the majority of mammalian genomes encode two Mx genes, this apparent stasis masks the dramatic effects that recombination and diversifying selection have played in shaping the evolutionary history of Mx genes. Discrepancies between our study and previous publications highlight the need to account for recombination in analyses of positive selection, as well as the importance of using sequence datasets with appropriate depth of divergence. Our study also illustrates that evolutionary analyses of antiviral gene families are critical towards understanding molecular principles that govern host-virus interactions and

  6. Evolutionary Analyses Suggest a Function of MxB Immunity Proteins Beyond Lentivirus Restriction.

    PubMed

    Mitchell, Patrick S; Young, Janet M; Emerman, Michael; Malik, Harmit S

    2015-12-01

    Viruses impose diverse and dynamic challenges on host defenses. Diversifying selection of codons and gene copy number variation are two hallmarks of genetic innovation in antiviral genes engaged in host-virus genetic conflicts. The myxovirus resistance (Mx) genes encode interferon-inducible GTPases that constitute a major arm of the cell-autonomous defense against viral infection. Unlike the broad antiviral activity of MxA, primate MxB was recently shown to specifically inhibit lentiviruses including HIV-1. We carried out detailed evolutionary analyses to investigate whether genetic conflict with lentiviruses has shaped MxB evolution in primates. We found strong evidence for diversifying selection in the MxB N-terminal tail, which contains molecular determinants of MxB anti-lentivirus specificity. However, we found no overlap between previously-mapped residues that dictate lentiviral restriction and those that have evolved under diversifying selection. Instead, our findings are consistent with MxB having a long-standing and important role in the interferon response to viral infection against a broader range of pathogens than is currently appreciated. Despite its critical role in host innate immunity, we also uncovered multiple functional losses of MxB during mammalian evolution, either by pseudogenization or by gene conversion from MxA genes. Thus, although the majority of mammalian genomes encode two Mx genes, this apparent stasis masks the dramatic effects that recombination and diversifying selection have played in shaping the evolutionary history of Mx genes. Discrepancies between our study and previous publications highlight the need to account for recombination in analyses of positive selection, as well as the importance of using sequence datasets with appropriate depth of divergence. Our study also illustrates that evolutionary analyses of antiviral gene families are critical towards understanding molecular principles that govern host-virus interactions and

  7. Detailed analysis of the promoter activity of an attenuated lentivirus.

    PubMed

    Blatti-Cardinaux, Laure; Sanjosé, Leticia; Zahno, Marie-Luise; Zanoni, Reto; Reina, Ramses; Bertoni, Giuseppe

    2016-07-01

    In spite of an eradication campaign that eliminated clinical cases of caprine arthritis encephalitis virus-induced arthritis in the Swiss goat population, seroconversions are still observed. In the affected flocks, viruses belonging mainly to the small ruminant lentivirus A4 subtype are regularly isolated. These viruses are considered attenuated, except in the mammary gland, where high viral loads and histopathological lesions have been observed. We previously characterized and sequenced such field isolates, detecting several potentially attenuating mutations in their LTR. Here we present a detailed analysis of the promoter activity of these genetic elements, which was comparable to those of virulent isolates. An AP-1 binding site was shown to be crucial for promoter activity in reporter gene assays and also in the context of a replicating molecular clone. Other sites, such as AML(vis) and a conserved E-box, appeared to be less crucial. Analysis of a unique AP-4 site showed a clear discrepancy between results obtained with reporter gene assays and those with mutated viruses. Within the limits of this in vitro study, we did not find evidence pointing to the LTR as the genetic correlate of attenuation for these viruses. Finally, the limited replication of SRLV A4 in mammary cell culture could not explain the suggested mammary tropism. In contrast, and in view of the abundance of macrophages in the mammary gland, it is the striking replication capacity of SRLV A4 in these cells, unaffected by all LTR mutations tested, which may explain the apparent mammary tropism of these viruses.

  8. Detailed analysis of the promoter activity of an attenuated lentivirus.

    PubMed

    Blatti-Cardinaux, Laure; Sanjosé, Leticia; Zahno, Marie-Luise; Zanoni, Reto; Reina, Ramses; Bertoni, Giuseppe

    2016-07-01

    In spite of an eradication campaign that eliminated clinical cases of caprine arthritis encephalitis virus-induced arthritis in the Swiss goat population, seroconversions are still observed. In the affected flocks, viruses belonging mainly to the small ruminant lentivirus A4 subtype are regularly isolated. These viruses are considered attenuated, except in the mammary gland, where high viral loads and histopathological lesions have been observed. We previously characterized and sequenced such field isolates, detecting several potentially attenuating mutations in their LTR. Here we present a detailed analysis of the promoter activity of these genetic elements, which was comparable to those of virulent isolates. An AP-1 binding site was shown to be crucial for promoter activity in reporter gene assays and also in the context of a replicating molecular clone. Other sites, such as AML(vis) and a conserved E-box, appeared to be less crucial. Analysis of a unique AP-4 site showed a clear discrepancy between results obtained with reporter gene assays and those with mutated viruses. Within the limits of this in vitro study, we did not find evidence pointing to the LTR as the genetic correlate of attenuation for these viruses. Finally, the limited replication of SRLV A4 in mammary cell culture could not explain the suggested mammary tropism. In contrast, and in view of the abundance of macrophages in the mammary gland, it is the striking replication capacity of SRLV A4 in these cells, unaffected by all LTR mutations tested, which may explain the apparent mammary tropism of these viruses. PMID:27114068

  9. The Role of the Antiviral APOBEC3 Gene Family in Protecting Chimpanzees against Lentiviruses from Monkeys

    PubMed Central

    Etienne, Lucie; Bibollet-Ruche, Frederic; Sudmant, Peter H.; Wu, Lily I.; Hahn, Beatrice H.; Emerman, Michael

    2015-01-01

    Cross-species transmissions of viruses from animals to humans are at the origin of major human pathogenic viruses. While the role of ecological and epidemiological factors in the emergence of new pathogens is well documented, the importance of host factors is often unknown. Chimpanzees are the closest relatives of humans and the animal reservoir at the origin of the human AIDS pandemic. However, despite being regularly exposed to monkey lentiviruses through hunting, chimpanzees are naturally infected by only a single simian immunodeficiency virus, SIVcpz. Here, we asked why chimpanzees appear to be protected against the successful emergence of other SIVs. In particular, we investigated the role of the chimpanzee APOBEC3 genes in providing a barrier to infection by most monkey lentiviruses. We found that most SIV Vifs, including Vif from SIVwrc infecting western-red colobus, the chimpanzee’s main monkey prey in West Africa, could not antagonize chimpanzee APOBEC3G. Moreover, chimpanzee APOBEC3D, as well as APOBEC3F and APOBEC3H, provided additional protection against SIV Vif antagonism. Consequently, lentiviral replication in primary chimpanzee CD4+ T cells was dependent on the presence of a lentiviral vif gene that could antagonize chimpanzee APOBEC3s. Finally, by identifying and functionally characterizing several APOBEC3 gene polymorphisms in both common chimpanzees and bonobos, we found that these ape populations encode APOBEC3 proteins that are uniformly resistant to antagonism by monkey lentiviruses. PMID:26394054

  10. Good CoP, bad CoP? Interrogating the immune responses to primate lentiviral vaccines.

    PubMed

    Klasse, Per Johan; Moore, John P

    2012-10-01

    Correlates of protection (CoPs) against infection by primate lentiviruses remain undefined. Modest protection against HIV-1 was observed in one human vaccine trial, whereas previous trials and vaccine-challenge experiments in non-human primates have yielded inconsistent but intriguing results. Although high levels of neutralizing antibodies are known to protect macaques from mucosal and intravenous viral challenges, antibody or other adaptive immune responses associated with protection might also be mere markers of innate immunity or susceptibility. Specific strategies for augmenting the design of both human trials and animal experiments could help to identify mechanistic correlates of protection and clarify the influences of confounding factors. Robust protection may, however, require the combined actions of immune responses and other host factors, thereby limiting what inferences can be drawn from statistical associations. Here, we discuss how to analyze immune protection against primate lentiviruses, and how host factors could influence both the elicitation and effectiveness of vaccine-induced responses.

  11. Primate archaeology.

    PubMed

    Haslam, Michael; Hernandez-Aguilar, Adriana; Ling, Victoria; Carvalho, Susana; de la Torre, Ignacio; DeStefano, April; Du, Andrew; Hardy, Bruce; Harris, Jack; Marchant, Linda; Matsuzawa, Tetsuro; McGrew, William; Mercader, Julio; Mora, Rafael; Petraglia, Michael; Roche, Hélène; Visalberghi, Elisabetta; Warren, Rebecca

    2009-07-16

    All modern humans use tools to overcome limitations of our anatomy and to make difficult tasks easier. However, if tool use is such an advantage, we may ask why it is not evolved to the same degree in other species. To answer this question, we need to bring a long-term perspective to the material record of other members of our own order, the Primates.

  12. Generation of a molecular clone of an attenuated lentivirus, a first step in understanding cytopathogenicity and virulence.

    PubMed

    Blatti-Cardinaux, Laure; Pisoni, Giuliano; Stoffel, Michael H; Zanoni, Reto; Zahno, Marie-Luise; Bertoni, Giuseppe

    2016-01-01

    Small ruminant lentiviruses infect goats and sheep, inducing clinical disease in a minority of infected animals. Following an eradication campaign, clinical cases may disappear in a population. The complete elimination of these lentiviruses is however difficult to achieve and the spreading of less virulent strains often parallels the elimination of their virulent counterparts. Here, we characterized three such strains isolated from a flock in the post-eradication phase. We completely sequenced their genomes, showing that one of the isolates was most probably the product of a recombination event between the other two viruses. By comparing the sequences of these isolates with those of virulent strains, we found evidence that particular LTR mutations may explain their attenuated phenotype. Finally, we constructed an infectious molecular clone representative of these viruses, analyzing its replication characteristics in different target cells. This clone will permit us to explore the molecular correlates of cytopathogenicity and virulence.

  13. Structural insight into equine lentivirus receptor 1.

    PubMed

    Qian, Lei; Han, Xiaodong; Liu, Xinqi

    2015-05-01

    Equine lentivirus receptor 1 (ELR1) has been identified as a functional cellular receptor for equine infectious anemia virus (EIAV). Herein, recombinant ELR1 and EIAV surface glycoprotein gp90 were respectively expressed in Drosophila melanogaster S2 cells, and purified to homogeneity by Ni-NTA affinity chromatography and gel filtration chromatography. Gel filtration chromatography and analytical ultracentrifugation (AUC) analyses indicated that both ELR1 and gp90 existed as individual monomers in solution and formed a complex with a stoichiometry of 1:1 when mixed. The structure of ELR1 was first determined with the molecular replacement method, which belongs to the space group P42 21 2 with one molecule in an asymmetric unit. It contains eight antiparallel β-sheets, of which four are in cysteine rich domain 1 (CRD1) and two are in CRD2 and CRD3, respectively. Alignment of ELR1 with HVEM and CD134 indicated that Tyr61, Leu70, and Gly72 in CRD1 of ELR1 are important residues for binding to gp90. Isothermal titration calorimetry (ITC) experiments further confirmed that Leu70 and Gly72 are the critical residues.

  14. A Single Nucleotide Polymorphism in Human APOBEC3C Enhances Restriction of Lentiviruses

    PubMed Central

    Wittkopp, Cristina J.; Adolph, Madison B.; Wu, Lily I.; Chelico, Linda; Emerman, Michael

    2016-01-01

    Humans express seven human APOBEC3 proteins, which can inhibit viruses and endogenous retroelements through cytidine deaminase activity. The seven paralogs differ in the potency of their antiviral effects, as well as in their antiviral targets. One APOBEC3, APOBEC3C, is exceptional as it has been found to only weakly block viruses and endogenous retroelements compared to other APOBEC3s. However, our positive selection analyses suggest that APOBEC3C has played a role in pathogen defense during primate evolution. Here, we describe a single nucleotide polymorphism in human APOBEC3C, a change from serine to isoleucine at position 188 (I188) that confers potent antiviral activity against HIV-1. The gain-of-function APOBEC3C SNP results in increased enzymatic activity and hypermutation of target sequences when tested in vitro, and correlates with increased dimerization of the protein. The I188 is widely distributed in human African populations, and is the ancestral primate allele, but is not found in chimpanzees or gorillas. Thus, while other hominids have lost activity of this antiviral gene, it has been maintained, or re-acquired, as a more active antiviral gene in a subset of humans. Taken together, our results suggest that APOBEC3C is in fact involved in protecting hosts from lentiviruses. PMID:27732658

  15. Abrogation of attenuated lentivirus-induced protection in rhesus macaques by administration of depo-provera before intravaginal challenge with simian immunodeficiency virus mac239.

    PubMed

    Abel, Kristina; Rourke, Tracy; Lu, Ding; Bost, Kristen; McChesney, Michael B; Miller, Christopher J

    2004-11-01

    In nonhuman primate models of acquired immunodeficiency syndrome, live attenuated lentiviruses provide the most reliable protection from systemic and mucosal challenge with pathogenic simian immunodeficiency virus (SIV). Although live attenuated lentiviruses may never be used in humans because of safety concerns, understanding the nature of the protective immune mechanisms induced by live attenuated vaccines in primate models will be useful for developing other vaccine approaches. Approximately 60% of rhesus macaques immunized with nonpathogenic simian-human immunodeficiency virus (SHIV) strain 89.6 are protected from infection or clinical disease after intravaginal (IVAG) challenge with pathogenic SIVmac239. The goal of the present study was to determine whether administration of Depo-Provera before IVAG challenge with SIV decreases the protective efficacy of infection with SHIV89.6. The rate of protection after IVAG challenge with SIVmac239 was significantly lower (P<.05), and the acute postchallenge plasma viral RNA levels were significantly higher (P<.006), in Depo-Provera-treated, SHIV89.6-immunized macaques than in Depo-Provera-naive, SHIV89.6-immunized macaques. In the primate model of sexual transmission of human immunodeficiency virus, treatment with progesterone before IVAG challenge with a pathogenic virus can decrease the efficacy of a model "vaccine."

  16. Viral evolution in deep time: lentiviruses and mammals.

    PubMed

    Gifford, Robert J

    2012-02-01

    Lentiviruses are a distinctive genus of retroviruses that cause chronic, persistent infections in mammals, including humans. The emergence of pandemic HIV type-1 (HIV-1) infection during the late 20th century shaped a view of lentiviruses as 'modern' viruses. However, recent research has revealed an entirely different perspective, elucidating aspects of an evolutionary relationship with mammals that extends across many millions of years. Such deep evolutionary history is likely to be typical of many host-virus systems, fundamentally underpinning their interactions in the present day. For this reason, establishing the deep history of virus and host interaction is key to developing a fully informed approach to tackling viral diseases. Here, I use the example of lentiviruses to illustrate how paleovirological, geographic and genetic calibrations allow observations of virus and host interaction across a wide range of temporal and spatial scales to be integrated into a coherent ecological and evolutionary framework. PMID:22197521

  17. Interspecific transmission of small ruminant lentiviruses from goats to sheep.

    PubMed

    Souza, Thiago S de; Pinheiro, Raymundo R; Costa, Joselito N; Lima, Carla C V de; Andrioli, Alice; Azevedo, Dalva A A de; Santos, Vanderlan W S dos; Araújo, Juscilânia F; Sousa, Ana Lídia M de; Pinheiro, Danielle N S; Fernandes, Flora M C; Costa Neto, Antonio O

    2015-01-01

    This study was conducted in order to evaluate the transmission of caprine lentivirus to sheep using different experimental groups. The first one (colostrum group) was formed by nine lambs receiving colostrum from goats positive for small ruminant lentiviruses (SRLV). The second group (milk group) was established by nine lambs that received milk of these goats. Third was a control group, consisting of lambs that suckled colostrum and milk of negative mothers. Another experimental group (contact group) was formed by eight adult sheep, confined with two naturally infected goats. The groups were monitored by immunoblotting (IB), enzyme-linked immunosorbent assay (ELISA), agar gel immunodiffusion (AGID) and nested polymerase chain reaction (nPCR). All lambs that suckled colostrum and milk of infected goats and six sheep of the contact group had positive results in the nPCR, although seroconversion was detected only in three of the exposed animals, with no clinical lentiviruses manifestation, in 720 days of observation. There was a close relationship between viral sequences obtained from infected animals and the prototype CAEV-Cork. Thus, it was concluded that SRLV can be transmitted from goats to sheep, however, the degree of adaptation of the virus strain to the host species probably interferes with the infection persistence and seroconversion rate. PMID:26413072

  18. Interspecific transmission of small ruminant lentiviruses from goats to sheep

    PubMed Central

    de Souza, Thiago S.; Pinheiro, Raymundo R.; Costa, Joselito N.; de Lima, Carla C.V.; Andrioli, Alice; de Azevedo, Dalva A.A.; dos Santos, Vanderlan W.S.; Araújo, Juscilânia F.; de Sousa, Ana Lídia M.; Pinheiro, Danielle N.S.; Fernandes, Flora M.C.; Costa, Antonio O.

    2015-01-01

    This study was conducted in order to evaluate the transmission of caprine lentivirus to sheep using different experimental groups. The first one (colostrum group) was formed by nine lambs receiving colostrum from goats positive for small ruminant lentiviruses (SRLV). The second group (milk group) was established by nine lambs that received milk of these goats. Third was a control group, consisting of lambs that suckled colostrum and milk of negative mothers. Another experimental group (contact group) was formed by eight adult sheep, confined with two naturally infected goats. The groups were monitored by immunoblotting (IB), enzyme-linked immunosorbent assay (ELISA), agar gel immunodiffusion (AGID) and nested polymerase chain reaction (nPCR). All lambs that suckled colostrum and milk of infected goats and six sheep of the contact group had positive results in the nPCR, although seroconversion was detected only in three of the exposed animals, with no clinical lentiviruses manifestation, in 720 days of observation. There was a close relationship between viral sequences obtained from infected animals and the prototype CAEV-Cork. Thus, it was concluded that SRLV can be transmitted from goats to sheep, however, the degree of adaptation of the virus strain to the host species probably interferes with the infection persistence and seroconversion rate. PMID:26413072

  19. Microarrays of lentiviruses for gene function screens in immortalized and primary cells.

    PubMed

    Bailey, Steve N; Ali, Siraj M; Carpenter, Anne E; Higgins, Caitlin O; Sabatini, David M

    2006-02-01

    Here we describe lentivirus-infected cell microarrays for the high-throughput screening of gene function in mammalian cells. To create these arrays, we cultured mammalian cells on glass slides 'printed' with lentiviruses pseudotyped as vesicular stomatitis virus glycoprotein, which encode short hairpin RNA or cDNA. Cells that land on the printed 'features' become infected with lentivirus, creating a living array of stably transduced cell clusters within a monolayer of uninfected cells. The small size of the features of the microarrays (300 microm in diameter) allows high-density spotting of lentivirus, permitting thousands of distinct parallel infections on a single glass slide. Because lentiviruses have a wide cellular tropism, including primary cells, lentivirus-infected cell microarrays can be used as a platform for high-throughput screening in a variety of cell types. PMID:16432521

  20. The origin of lentivirus research: Maedi-visna virus.

    PubMed

    Thormar, Halldor

    2013-01-01

    Maedi and visna are contagious sheep diseases which were introduced into Iceland in 1933 by imported sheep of Karakul breed. Maedi, a slowly progressing pneumonia, and the central nervous system disease visna were shown to be transmissible in sheep and most likely caused by a virus. In 1957, visna virus was isolated in tissue culture from sheep brain and maedi virus was isolated the following year from sheep lungs. Both viruses showed similar cytopathic effect in tissue culture. Electron microscope studies of ultrathin sections from visna virus infected cells demonstrated spherical particles, 70-100 nm in diameter, which were formed by budding from the cell membrane. Later studies showed identical particles in maedi virus infected cultures. These, and several other comparative studies, strongly indicated that maedi and visna were caused by strains of the same virus, later named maedi-visna virus (MVV). Comparative studies in tissue culture suggested that MVV was related to RNA tumor viruses of animals, the oncornaviruses. This was later supported by the finding that MVV is an RNA virus. A few months after reverse transcriptase was demonstrated in oncornaviruses, the enzyme was also found in MVV virions. Thus, MVV was classified as a retrovirus together with the oncornaviruses. However, MVV is not oncogenic in vivo or in vitro and was in 1975 placed in a subgroup of retroviruses named lentiviruses, which cause cytopathic effect in vitro and slowly progressing inflammatory disease in animals, but are nononcogenic. In the early 1980s, the causative agent of AIDS was found to be a non-oncogenic retrovirus and was classified as a lentivirus. Thus, HIV became the first human lentivirus. PMID:23278353

  1. Envelope residue 375 substitutions in simian–human immunodeficiency viruses enhance CD4 binding and replication in rhesus macaques

    PubMed Central

    Li, Hui; Wang, Shuyi; Kong, Rui; Ding, Wenge; Lee, Fang-Hua; Parker, Zahra; Kim, Eunlim; Learn, Gerald H.; Hahn, Paul; Policicchio, Ben; Brocca-Cofano, Egidio; Deleage, Claire; Hao, Xingpei; Chuang, Gwo-Yu; Gorman, Jason; Gardner, Matthew; Lewis, Mark G.; Hatziioannou, Theodora; Santra, Sampa; Apetrei, Cristian; Pandrea, Ivona; Alam, S. Munir; Liao, Hua-Xin; Shen, Xiaoying; Tomaras, Georgia D.; Farzan, Michael; Chertova, Elena; Keele, Brandon F.; Estes, Jacob D.; Lifson, Jeffrey D.; Doms, Robert W.; Montefiori, David C.; Haynes, Barton F.; Sodroski, Joseph G.; Kwong, Peter D.; Hahn, Beatrice H.; Shaw, George M.

    2016-01-01

    Most simian–human immunodeficiency viruses (SHIVs) bearing envelope (Env) glycoproteins from primary HIV-1 strains fail to infect rhesus macaques (RMs). We hypothesized that inefficient Env binding to rhesus CD4 (rhCD4) limits virus entry and replication and could be enhanced by substituting naturally occurring simian immunodeficiency virus Env residues at position 375, which resides at a critical location in the CD4-binding pocket and is under strong positive evolutionary pressure across the broad spectrum of primate lentiviruses. SHIVs containing primary or transmitted/founder HIV-1 subtype A, B, C, or D Envs with genotypic variants at residue 375 were constructed and analyzed in vitro and in vivo. Bulky hydrophobic or basic amino acids substituted for serine-375 enhanced Env affinity for rhCD4, virus entry into cells bearing rhCD4, and virus replication in primary rhCD4 T cells without appreciably affecting antigenicity or antibody-mediated neutralization sensitivity. Twenty-four RMs inoculated with subtype A, B, C, or D SHIVs all became productively infected with different Env375 variants—S, M, Y, H, W, or F—that were differentially selected in different Env backbones. Notably, SHIVs replicated persistently at titers comparable to HIV-1 in humans and elicited autologous neutralizing antibody responses typical of HIV-1. Seven animals succumbed to AIDS. These findings identify Env–rhCD4 binding as a critical determinant for productive SHIV infection in RMs and validate a novel and generalizable strategy for constructing SHIVs with Env glycoproteins of interest, including those that in humans elicit broadly neutralizing antibodies or bind particular Ig germ-line B-cell receptors. PMID:27247400

  2. Primate photopigments and primate color vision.

    PubMed

    Jacobs, G H

    1996-01-23

    The past 15 years have brought much progress in our understanding of several basic features of primate color vision. There has been particular success in cataloging the spectral properties of the cone photopigments found in retinas of a number of primate species and in elucidating the relationship between cone opsin genes and their photopigment products. Direct studies of color vision show that there are several modal patterns of color vision among groupings of primates: (i) Old World monkeys, apes, and humans all enjoy trichromatic color vision, although the former two groups do not seem prone to the polymorphic variations in color vision that are characteristic of people; (ii) most species of New World monkeys are highly polymorphic, with individual animals having any of several types of dichromatic or trichromatic color vision; (iii) less is known about color vision in prosimians, but evidence suggests that at least some diurnal species have dichromatic color vision; and (iv) some nocturnal primates may lack color vision completely. In many cases the photopigments and photopigment gene arrangements underlying these patterns have been revealed and, as a result, hints are emerging about the evolution of color vision among the primates. PMID:8570598

  3. Primate photopigments and primate color vision.

    PubMed Central

    Jacobs, G H

    1996-01-01

    The past 15 years have brought much progress in our understanding of several basic features of primate color vision. There has been particular success in cataloging the spectral properties of the cone photopigments found in retinas of a number of primate species and in elucidating the relationship between cone opsin genes and their photopigment products. Direct studies of color vision show that there are several modal patterns of color vision among groupings of primates: (i) Old World monkeys, apes, and humans all enjoy trichromatic color vision, although the former two groups do not seem prone to the polymorphic variations in color vision that are characteristic of people; (ii) most species of New World monkeys are highly polymorphic, with individual animals having any of several types of dichromatic or trichromatic color vision; (iii) less is known about color vision in prosimians, but evidence suggests that at least some diurnal species have dichromatic color vision; and (iv) some nocturnal primates may lack color vision completely. In many cases the photopigments and photopigment gene arrangements underlying these patterns have been revealed and, as a result, hints are emerging about the evolution of color vision among the primates. PMID:8570598

  4. Expanding possibilities for intervention against small ruminant lentiviruses through genetic marker-assisted selective breeding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Small ruminant lentiviruses include members that infect sheep (ovine lentivirus [OvLV]; also known as ovine progressive pneumonia virus/maedi-visna virus) and goats (caprine arthritis encephalitis virus [CAEV]). Breed differences in seroprevalence and proviral concentration of OvLV had suggested a s...

  5. Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ovine lentiviruses cause incurable, progressive, lymphoproliferative diseases that affect millions of sheep worldwide. Genetic variation in the ovine transmembrane protein 154 gene (TMEM154) has been recently associated with lentivirus infections in U.S. sheep. Sheep with the two most common TMEM1...

  6. Replicating nucleosomes

    PubMed Central

    Ramachandran, Srinivas; Henikoff, Steven

    2015-01-01

    Eukaryotic replication disrupts each nucleosome as the fork passes, followed by reassembly of disrupted nucleosomes and incorporation of newly synthesized histones into nucleosomes in the daughter genomes. In this review, we examine this process of replication-coupled nucleosome assembly to understand how characteristic steady-state nucleosome landscapes are attained. Recent studies have begun to elucidate mechanisms involved in histone transfer during replication and maturation of the nucleosome landscape after disruption by replication. A fuller understanding of replication-coupled nucleosome assembly will be needed to explain how epigenetic information is replicated at every cell division. PMID:26269799

  7. Property in Nonhuman Primates

    ERIC Educational Resources Information Center

    Brosnan, Sarah F.

    2011-01-01

    Property is rare in most nonhuman primates, most likely because their lifestyles are not conducive to it. Nonetheless, just because these species do not frequently maintain property does not mean that they lack the propensity to do so. Primates show respect for possession, as well as behaviors related to property, such as irrational decision…

  8. Raptors and primate evolution.

    PubMed

    McGraw, W Scott; Berger, Lee R

    2013-01-01

    Most scholars agree that avoiding predators is a central concern of lemurs, monkeys, and apes. However, given uncertainties about the frequency with which primates actually become prey, the selective importance of predation in primate evolution continues to be debated. Some argue that primates are often killed by predators, while others maintain that such events are relatively rare. Some authors have contended that predation's influence on primate sociality has been trivial; others counter that predation need not occur often to be a powerful selective force. Given the challenges of documenting events that can be ephemeral and irregular, we are unlikely ever to amass the volume of systematic, comparative data we have on such topics as feeding, social dynamics, or locomotor behavior. Nevertheless, a steady accumulation of field observations, insight gained from natural experiments, and novel taphonomic analyses have enhanced understanding of how primates interact with several predators, especially raptors, the subject of this review. PMID:24347501

  9. Designing, Packaging, and Delivery of High Titer CRISPR Retro and Lentiviruses via Stereotaxic Injection.

    PubMed

    Fricano-Kugler, Catherine J; Williams, Michael R; Salinaro, Julia R; Li, Meijie; Luikart, Bryan

    2016-01-01

    Replication defective lentiviruses or retroviruses are capable of stably integrating transgenes into the genome of an infected host cell. This technique has been widely used to encode fluorescent proteins, opto- or chemo-genetic controllers of cell activity, or heterologous expression of human genes in model organisms. These viruses have also successfully been used to deliver recombinases to relevant target sites in transgenic animals, or even deliver small hairpin or micro RNAs in order to manipulate gene expression. While these techniques have been fruitful, they rely on transgenic animals (recombinases) or frequently lack high efficacy and specificity (shRNA/miRNA). In contrast, the CRISPR/Cas system uses an exogenous Cas nuclease which targets specific sites in an organism's genome via an exogenous guide RNA in order to induce double stranded breaks in DNA. These breaks are then repaired by non-homologous end joining (NHEJ), producing insertion and deletion (indel) mutations that can result in deleterious missense or nonsense mutations. This manuscript provides detailed methods for the design, production, injection, and validation of single lenti/retro virus particles that can stably transduce neurons to express a fluorescent reporter, Cas9, and sgRNAs to knockout genes in a model organism. PMID:27285851

  10. Designing, Packaging, and Delivery of High Titer CRISPR Retro and Lentiviruses via Stereotaxic Injection

    PubMed Central

    Fricano-Kugler, Catherine J.; Williams, Michael R.; Salinaro, Julia R.; Li, Meijie; Luikart, Bryan

    2016-01-01

    Replication defective lentiviruses or retroviruses are capable of stably integrating transgenes into the genome of an infected host cell. This technique has been widely used to encode fluorescent proteins, opto- or chemo-genetic controllers of cell activity, or heterologous expression of human genes in model organisms. These viruses have also successfully been used to deliver recombinases to relevant target sites in transgenic animals, or even deliver small hairpin or micro RNAs in order to manipulate gene expression. While these techniques have been fruitful, they rely on transgenic animals (recombinases) or frequently lack high efficacy and specificity (shRNA/miRNA). In contrast, the CRISPR/Cas system uses an exogenous Cas nuclease which targets specific sites in an organism's genome via an exogenous guide RNA in order to induce double stranded breaks in DNA. These breaks are then repaired by non-homologous end joining (NHEJ), producing insertion and deletion (indel) mutations that can result in deleterious missense or nonsense mutations. This manuscript provides detailed methods for the design, production, injection, and validation of single lenti/retro virus particles that can stably transduce neurons to express a fluorescent reporter, Cas9, and sgRNAs to knockout genes in a model organism. PMID:27285851

  11. Reduced Lentivirus Susceptibility in Sheep with TMEM154 Mutations

    PubMed Central

    Heaton, Michael P.; Clawson, Michael L.; Chitko-Mckown, Carol G.; Leymaster, Kreg A.; Smith, Timothy P. L.; Harhay, Gregory P.; White, Stephen N.; Herrmann-Hoesing, Lynn M.; Mousel, Michelle R.; Lewis, Gregory S.; Kalbfleisch, Theodore S.; Keen, James E.; Laegreid, William W.

    2012-01-01

    Visna/Maedi, or ovine progressive pneumonia (OPP) as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a genome-wide association study with 50,614 markers. A single SNP was identified in the ovine transmembrane protein (TMEM154) that exceeded genome-wide significance (unadjusted p-value 3×10−9). Sanger sequencing of the ovine TMEM154 coding region identified six missense and two frameshift deletion mutations in the predicted signal peptide and extracellular domain. Two TMEM154 haplotypes encoding glutamate (E) at position 35 were associated with infection while a third haplotype with lysine (K) at position 35 was not. Haplotypes encoding full-length E35 isoforms were analyzed together as genetic risk factors in a multi-breed, matched case-control design, with 61 pairs of 4-year-old ewes. The odds of infection for ewes with one copy of a full-length TMEM154 E35 allele were 28 times greater than the odds for those without (p-value<0.0001, 95% CI 5–1,100). In a combined analysis of nine cohorts with 2,705 sheep from Nebraska, Idaho, and Iowa, the relative risk of infection was 2.85 times greater for sheep with a full-length TMEM154 E35 allele (p-value<0.0001, 95% CI 2.36–3.43). Although rare, some sheep were homozygous for TMEM154 deletion mutations and remained uninfected despite a lifetime of significant exposure. Together, these findings indicate that TMEM154 may play a central role in ovine lentivirus infection and removing sheep with the most susceptible genotypes may help eradicate OPP and protect flocks from reinfection. PMID:22291605

  12. Lentivirus-expressed siRNA vectors against Alzheimer disease.

    PubMed

    Peng, Kevin A; Masliah, Eliezer

    2010-01-01

    Amyloid precursor protein (APP) has been implicated in the pathogenesis of Alzheimer disease, and the accumulation of APP products ultimately leads to the familiar histopathological and clinical manifestations associated with this most common form of dementia. A protein that has been shown to promote APP accumulation is beta-secretase (beta-site APP cleaving enzyme 1, or BACE1), which is increased in the cerebrospinal fluid in those affected with Alzheimer disease. Through in vivo studies using APP transgenic mice, we demonstrated that decreasing the expression of BACE1 via lentiviral vector delivery of BACE1 siRNA has the potential for significantly reducing the cleavage of APP, accumulation of these products, and consequent neurodegeneration. As such, lentiviral-expressed siRNA against BACE1 is a therapeutic possibility in the treatment of Alzheimer disease. We detail the use of lentivirus-expressed siRNA as a method to ameliorate Alzheimer disease neuropathology in APP transgenic mice.

  13. [Lentivirus Delivery of the Short Hairpin RNA Targeting NDV P Gene Inhibits Production of the Newcastle Disease Virus in Chicken Embryo Fibroblasts and Chicken Embryos].

    PubMed

    Yang, Shaohua; Xu, Chuantian; Zhang, Lin; Huang, Yanyan; Huang, Qinghua; Hu, Beixia; Zhang, Xiumei

    2016-01-01

    Small interfering ribonucleic acid (siRNA)-induced RNA degradation can inhibit viral infection, and has been investigated extensively for its efficacy as antiviral therapy. The potential therapeutic role of lentiviral-mediated short hairpin ribonucleic acid (shRNA) to Newcastle disease virus (NDV) replication in vivo has been explored less often. We constructed two recombinant lentiviral vectors containing shRNA against the phosphoprotein (P) of the NDV, RNAi-341 and RNAi-671. Recombinant shRNA lentivirus vectors were co-transfected into 293T cells, along with helper plasmids, to package the recombinant shRNA lentivirus. Lentivirus-based shRNAs were titrated and transduced into NDV-susceptible chicken embryo fibroblasts (CEFs) and chick embryos. Antiviral activity against the NDV strain was evaluated by virus titration and real-time reverse transcription-polymerase chain reaction. RNAi-341 and RNAi-671 strongly suppressed transient expression of a FLAG-tagged P fusion protein in 293T cells. RNAi-341 and RNAi-671 NDV reduced virus titers by 66.6-fold and 30.6-fold, respectively, in CEFs 16 h after infection. RNAi-341 and RNAi-671 reduced virus titers in specific pathogen-free chick embryos by 99% and 98%, respectively, 48 h after infection. Both shRNAs inhibited accumulation of not only P-gene mRNA, but also nucleocapsid, M-, F-, HN-, and L-gene mRNA. RNAi-341 silenced P-gene mRNA more potently than RNAi-671. These results suggest that shRNAs silencing the P gene had substantial antiviral properties and inhibited NDV replication in CEFs and chick embryos. PMID:27295882

  14. [Lentivirus Delivery of the Short Hairpin RNA Targeting NDV P Gene Inhibits Production of the Newcastle Disease Virus in Chicken Embryo Fibroblasts and Chicken Embryos].

    PubMed

    Yang, Shaohua; Xu, Chuantian; Zhang, Lin; Huang, Yanyan; Huang, Qinghua; Hu, Beixia; Zhang, Xiumei

    2016-01-01

    Small interfering ribonucleic acid (siRNA)-induced RNA degradation can inhibit viral infection, and has been investigated extensively for its efficacy as antiviral therapy. The potential therapeutic role of lentiviral-mediated short hairpin ribonucleic acid (shRNA) to Newcastle disease virus (NDV) replication in vivo has been explored less often. We constructed two recombinant lentiviral vectors containing shRNA against the phosphoprotein (P) of the NDV, RNAi-341 and RNAi-671. Recombinant shRNA lentivirus vectors were co-transfected into 293T cells, along with helper plasmids, to package the recombinant shRNA lentivirus. Lentivirus-based shRNAs were titrated and transduced into NDV-susceptible chicken embryo fibroblasts (CEFs) and chick embryos. Antiviral activity against the NDV strain was evaluated by virus titration and real-time reverse transcription-polymerase chain reaction. RNAi-341 and RNAi-671 strongly suppressed transient expression of a FLAG-tagged P fusion protein in 293T cells. RNAi-341 and RNAi-671 NDV reduced virus titers by 66.6-fold and 30.6-fold, respectively, in CEFs 16 h after infection. RNAi-341 and RNAi-671 reduced virus titers in specific pathogen-free chick embryos by 99% and 98%, respectively, 48 h after infection. Both shRNAs inhibited accumulation of not only P-gene mRNA, but also nucleocapsid, M-, F-, HN-, and L-gene mRNA. RNAi-341 silenced P-gene mRNA more potently than RNAi-671. These results suggest that shRNAs silencing the P gene had substantial antiviral properties and inhibited NDV replication in CEFs and chick embryos.

  15. Antiviral CD8+ T cells in the genital tract control viral replication and delay progression to AIDS after vaginal SIV challenge in rhesus macaques immunized with virulence attenuated SHIV 89.6

    PubMed Central

    Genescà, M.; McChesney, M.B.; Miller, C.J.

    2009-01-01

    Genescà M, McChesney MB, Miller CJ (Center for Comparative Medicine and California National Primate Research Center, University of California, Davis, CA, USA). Antiviral CD8+ T cells in the genital tract control viral replication and delay progression to AIDS after vaginal SIV challenge in rhesus macaques immunized with virulence attenuated SHIV 89.6 (Review). The recently failed clinical efficacy trial of an acquired immunodeficiency syndrome (AIDS) vaccine that elicits antiviral CD8+ T-cell responses has emphasized the challenge of producing an effective vaccine against human immunodeficiency virus (HIV). In the simian immunodeficiency virus (SIV)/rhesus monkey model of AIDS, live-attenuated lentivirus ‘vaccines’ provide the best protection from uncontrolled viral replication and clinical disease after pathogenic SIV challenge. This review summarizes a recent series of studies in which we show that after vaginal SIV challenge of rhesus macaques immunized with an attenuated lentivirus protection from uncontrolled viral replication is primarily mediated by CD8+ T cells in the vaginal mucosa. Immunization with a chimeric simian/human immunodeficiency virus (SHIV) results in a systemic infection that induces a moderate population of SIV-specific CD8+ and CD4+ T cells with cytolytic potential in the vaginal mucosa. Depletion of CD8+ T cells at the time of SIV challenge completely abrogates the protection mediated by prior infection with attenuated SHIV. Further after vaginal SIV challenge, the only significant expansion of SIV-specific T cells occurs in the vagina in these animals. No significant expansion of T-cell responses was observed in systemic lymphoid tissues. Thus, the presence of SIV-specific CD8+ T cells in the vagina on the day of vaginal SIV challenge and a modest expansion of local effector T cells is sufficient to stop uncontrolled SIV replication. It seems that T-cell based vaccine strategies that can elicit mucosal effector CD8+ T

  16. Inhibition of choroidal neovascularization by lentivirus-mediated PEDF gene transfer in rats

    PubMed Central

    Yu, Ya-Jie; Mo, Bin; Liu, Lu; Yue, Yan-Kun; Yue, Chang-Li; Liu, Wu

    2016-01-01

    AIM To evaluate the effects of lentivirus-mediated pigment epithelium-derived factor (PEDF) gene transfer performed in treatment of rats with established choroidal neovascularization (CNV), and investigates the mechanism by which PEDF inhibits CNV in rats. METHODS Brown Norway (BN) rats (n=204) were induced by exposure to a laser, and then randomly assigned to 3 groups: no treatment; treatments with intravitreal injection of lentivirus-PEDF-green fluorescent protein (GFP) or lentivirus-control GFP (free fluorescent protein). Following induction and treatment, the CNV tissue was assessed for form, size and vessel leakage by fluorescein fundus angiography (FFA), optical coherence tomography (OCT), histopathology, and examination of choroidal flat mounts. VEGF, Flk-1, and PEDF expression were evaluated by real-time polymerase chain reaction (PCR) and Western blot. RESULTS A stable laser-induced rat model of CNV was successfully established, and used to demonstrate lentivirus-mediated PEDG gene transfer by intravitreal injection. Expression of green fluorescence labelled PEDF was observed in the retina up to 28d after injection. An intravitreal injection of lentivirus-PEDF-GFP at 7d led to a significant reduction in the size, thickness and area of CNV showed by FFA, OCT and choroidal flat mounts. PEDF was up-regulated while VEGF and Flk-1 were down-regulated in the lentivirus-PEDF-GFP group. The differences in VEGF and Flk-1 expression in the control and lentivirus-PEDF groups at 7, 14, 21 and 28d after laser induction were all statistically significant. CONCLUSION Lentivirus-mediated PEDF gene transfer is effective for use in treatment of laser-induced CNV, and PEDF exerts its therapeutic effects by inhibiting expression of VEGF and Flk-1. PMID:27588264

  17. Altering α-dystroglycan receptor affinity of LCMV pseudotyped lentivirus yields unique cell and tissue tropism

    PubMed Central

    2011-01-01

    Background The envelope glycoprotein of lymphocytic choriomeningitis virus (LCMV) can efficiently pseudotype lentiviral vectors. Some strains of LCMV exploit high affinity interactions with α-dystroglycan (α-DG) to bind to cell surfaces and subsequently fuse in low pH endosomes. LCMV strains with low α-DG affinity utilize an unknown receptor and display unique tissue tropisms. We pseudotyped non-primate feline immunodeficiency virus (FIV) vectors using LCMV derived glycoproteins with high or low affinity to α-DG and evaluated their properties in vitro and in vivo. Methods We pseudotyped FIV with the LCMV WE54 strain envelope glycoprotein and also engineered a point mutation in the WE54 envelope glycoprotein (L260F) to diminish α-DG affinity and direct binding to alternate receptors. We hypothesized that this change would alter in vivo tissue tropism and enhance gene transfer to neonatal animals. Results In mice, hepatic α- and β-DG expression was greatest at the late gestational and neonatal time points. When displayed on the surface of the FIV lentivirus the WE54 L260F mutant glycoprotein bound weakly to immobilized α-DG. Additionally, LCMV WE54 pseudotyped FIV vector transduction was neutralized by pre-incubation with soluble α-DG, while the mutant glycoprotein pseudotyped vector was not. In vivo gene transfer in adult mice with either envelope yielded low transduction efficiencies in hepatocytes following intravenous delivery. In marked contrast, neonatal gene transfer with the LCMV envelopes, and notably with the FIV-L260F vector, conferred abundant liver and lower level cardiomyocyte transduction as detected by luciferase assays, bioluminescent imaging, and β-galactosidase staining. Conclusions These results suggest that a developmentally regulated receptor for LCMV is expressed abundantly in neonatal mice. LCMV pseudotyped vectors may have applications for neonatal gene transfer. Abbreviations Armstrong 53b (Arm53b); baculovirus Autographa

  18. Neurologic Disease in Captive Lions (Panthera leo) with Low-Titer Lion Lentivirus Infection▿

    PubMed Central

    Brennan, Greg; Podell, Michael D.; Wack, Raymund; Kraft, Susan; Troyer, Jennifer L.; Bielefeldt-Ohmann, Helle; VandeWoude, Sue

    2006-01-01

    Lion lentivirus (LLV; also known as feline immunodeficiency virus of lion, Panthera leo [FIVPle]) is present in free-ranging and captive lion populations at a seroprevalence of up to 100%; however, clinical signs are rarely reported. LLV displays up to 25% interclade sequence diversity, suggesting that it has been in the lion population for some time and may be significantly host adapted. Three captive lions diagnosed with LLV infection displayed lymphocyte subset alterations and progressive behavioral, locomotor, and neuroanatomic abnormalities. No evidence of infection with other potential neuropathogens was found. Antemortem electrodiagnostics and radiologic imaging indicated a diagnosis consistent with lentiviral neuropathy. PCR was used to determine a partial lentiviral genomic sequence and to quantify the proviral burden in eight postmortem tissue specimens. Phylogenetic analysis demonstrated that the virus was consistent with the LLV detected in other captive and free-ranging lions. Despite progressive neurologic signs, the proviral load in tissues, including several regions of the brain, was low; furthermore, gross and histopathologic changes in the brain were minimal. These findings suggest that the symptoms in these animals resulted from nonspecific encephalopathy, similar to human immunodeficiency virus, FIV, and simian immunodeficiency virus (SIV) neuropathies, rather than a direct effect of active viral replication. The association of neuropathy and lymphocyte subset alterations with chronic LLV infection suggests that long-term LLV infection can have detrimental effects for the host, including death. This is similar to reports of aged sootey mangabeys dying from diseases typically associated with end-stage SIV infection and indicates areas for further research of lentiviral infections of seemingly adapted natural hosts, including mechanisms of host control and viral adaptation. PMID:17005739

  19. Development and validation of puma (Felis concolor) cytokine and lentivirus real-time PCR detection systems.

    PubMed

    Sondgeroth, Kerry; Leutenegger, Christian; Vandewoude, Sue

    2005-04-01

    Studies of immune correlates of disease outcome associate humoral immune response mediated by T-helper 2 cytokines (IL-4, IL-10) with more virulent disease relative to a cell-mediated response driven by T-helper 1 cytokines (IL-2, IFN-gamma), particularly in viral and other intra-cellular infections. Specifically, the kinetics of both human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV) infection are closely associated with Type 1 versus Type 2 cytokine profiles. Puma (Felis concolor) lentivirus (PLV) is closely related to FIV, but based on phylogenetic and clinical studies, is more ancient and less pathogenic. The aims of this study were to validate feline real-time PCR primer/probe systems for puma cytokines and PLV as sensitive, quantitative assays for use in investigations of PLV pathogenicity. We demonstrate that primer/probe systems for IL-4, IL-10, IFN-gamma, TNF-alpha, GAPDH, and the pol region of PLV-1695 amplify puma cytokines and PLV-1695 with high amplification efficiency and sensitivity. Detection of PLV-1695 provirus in experimentally inoculated domestic cats proved to be of equivalent sensitivity, specificity, and positive and negative predictive value to co-culture of one million peripheral blood mononuclear cells (PBMC). Evaluation of cytokine induction during naturally occurring PLV infection will allow insight into mechanisms of host control associated with apathogenic infection. In addition, determination of viral loads during different stages of PLV infection or in different tissues from domestic cats or pumas will further elucidate capacity of these viruses to replicate and establish infection.

  20. The presence of small ruminant lentiviruses in Mexican Pelibuey sheep.

    PubMed

    Sánchez, José H; Martínez, Humberto A; García, María M; Garrido, Germán; Gómez, Luis; Aguilar, José A; de Andrés, Damián F; Reina, Ramsés; Ramírez, Hugo

    2016-11-01

    The transmission frequency of small ruminant lentiviruses (SRLVs) through the placenta is controversial and may be associated with breed susceptibility. In Mexico, SRLV infections in sheep have been poorly studied. This work explores the presence of antibodies and proviral DNA in Mexican Pelibuey sheep. Enzyme-linked immunosorbent assays (ELISAs; three commercial kits and two on the basis of synthetic peptides) and polymerase chain reaction (PCR; amplifying the long terminal repeat and gag segments) were performed to diagnose SRLV infection in 25 adult Pelibuey ewes with an average age of 2.5 years and 32 fetuses with gestational ages ranging from 40 to 90 days without clinical signs of SRLV. Two of the three commercial ELISAs and the synthetic peptide-based ones were positive for SRLV antibody detection in 28% and 24% of the ewes, respectively, whereas none of the fetuses were positive by any of the ELISAs. By PCR, 31% of the ewes and, interestingly, two fetuses were positive. Characteristic SRLV lesions were not found in the fetal and/or ewe tissues, including those with positive PCR results. These findings demonstrate the susceptibility of Pelibuey sheep to SRLV infection and the low transmission frequency through the placenta. PMID:27461580

  1. The presence of small ruminant lentiviruses in Mexican Pelibuey sheep.

    PubMed

    Sánchez, José H; Martínez, Humberto A; García, María M; Garrido, Germán; Gómez, Luis; Aguilar, José A; de Andrés, Damián F; Reina, Ramsés; Ramírez, Hugo

    2016-11-01

    The transmission frequency of small ruminant lentiviruses (SRLVs) through the placenta is controversial and may be associated with breed susceptibility. In Mexico, SRLV infections in sheep have been poorly studied. This work explores the presence of antibodies and proviral DNA in Mexican Pelibuey sheep. Enzyme-linked immunosorbent assays (ELISAs; three commercial kits and two on the basis of synthetic peptides) and polymerase chain reaction (PCR; amplifying the long terminal repeat and gag segments) were performed to diagnose SRLV infection in 25 adult Pelibuey ewes with an average age of 2.5 years and 32 fetuses with gestational ages ranging from 40 to 90 days without clinical signs of SRLV. Two of the three commercial ELISAs and the synthetic peptide-based ones were positive for SRLV antibody detection in 28% and 24% of the ewes, respectively, whereas none of the fetuses were positive by any of the ELISAs. By PCR, 31% of the ewes and, interestingly, two fetuses were positive. Characteristic SRLV lesions were not found in the fetal and/or ewe tissues, including those with positive PCR results. These findings demonstrate the susceptibility of Pelibuey sheep to SRLV infection and the low transmission frequency through the placenta.

  2. A naturally occurring bovine APOBEC3 confers resistance to bovine lentiviruses: implication for the co-evolution of bovids and their lentiviruses

    PubMed Central

    Yamada, Eri; Yoshikawa, Rokusuke; Nakano, Yusuke; Misawa, Naoko; Kobayashi, Tomoko; Ren, Fengrong; Izumi, Taisuke; Miyazawa, Takayuki; Koyanagi, Yoshio; Sato, Kei

    2016-01-01

    Mammals have co-evolved with lentiviruses for a long time. As evidence, viral infectivity factor (Vif), encoded by lentiviruses, antagonizes the anti-viral action of cellular APOBEC3 of their hosts. Here, we address the co-evolutionary dynamics of bovine APOBEC3 and the following two bovine lentiviruses: bovine immunodeficiency virus (BIV) and Jembrana disease virus (JDV). We determined the sequences of three APOBEC3 genes of bovids belonging to the genera Bos and Bison and showed that bovine APOBEC3Z3 is under a strong positive selection. We found that APOBEC3Z3 of gaur, a bovid in the genus Bos, acquired resistance to JDV Vif-mediated degradation after diverging from the other bovids through conversion of the structural composition of the loop 1 domain. Interestingly, the resistance of gaur APOBEC3Z3 can be attributed to the positive selection of residue 62. This study provides the first evidence, suggesting that a co-evolutionary arms race between bovids and lentiviruses occurred in Asia. PMID:27665724

  3. What Is a Primate?

    ERIC Educational Resources Information Center

    McGee, Elizabeth

    2003-01-01

    Describes a series of hands-on experiments that engage students in hypothesis testing and promotes active learning of the concepts of evolution and adaptation. Laboratory exercises demonstrate how features of the hands and eyes distinguish primates from other mammals. (SOE)

  4. In Vivo Replication Capacity Rather Than In Vitro Macrophage Tropism Predicts Efficiency of Vaginal Transmission of Simian Immunodeficiency Virus or Simian/Human Immunodeficiency Virus in Rhesus Macaques

    PubMed Central

    Miller, Christopher J.; Marthas, Marta; Greenier, Jennifer; Lu, Ding; Dailey, Peter J.; Lu, Yichen

    1998-01-01

    We used the rhesus macaque model of heterosexual human immunodeficiency virus (HIV) transmission to test the hypothesis that in vitro measures of macrophage tropism predict the ability of a primate lentivirus to initiate a systemic infection after intravaginal inoculation. A single atraumatic intravaginal inoculation with a T-cell-tropic molecular clone of simian immunodeficiency virus (SIV), SIVmac239, or a dualtropic recombinant molecular clone of SIV, SIVmac239/1A11/239, or uncloned dualtropic SIVmac251 or uncloned dualtropic simian/human immunodeficiency virus (SHIV) 89.6-PD produced systemic infection in all rhesus macaques tested. However, vaginal inoculation with a dualtropic molecular clone of SIV, SIVmac1A11, resulted in transient viremia in one of two rhesus macaques. It has previously been shown that 12 intravaginal inoculations with SIVmac1A11 resulted in infection of one of five rhesus macaques (M. L. Marthas, C. J. Miller, S. Sutjipto, J. Higgins, J. Torten, B. L. Lohman, R. E. Unger, H. Kiyono, J. R. McGhee, P. A. Marx, and N. C. Pedersen, J. Med. Primatol. 21:99–107, 1992). In addition, SHIV HXBc2, which replicates in monkey macrophages, does not infect rhesus macaques following multiple vaginal inoculations, while T-cell-tropic SHIV 89.6 does (Y. Lu, P. B. Brosio, M. Lafaile, J. Li, R. G. Collman, J. Sodroski, and C. J. Miller, J. Virol. 70:3045–3050, 1996). These results demonstrate that in vitro measures of macrophage tropism do not predict if a SIV or SHIV will produce systemic infection after intravaginal inoculation of rhesus macaques. However, we did find that the level to which these viruses replicate in vivo after intravenous inoculation predicts the outcome of intravaginal inoculation with each virus. PMID:9525652

  5. Replicating vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Early work on fish immunology and disease resistance demonstrated fish (like animals and humans) that survived infection were typically resistant to re-infection with the same pathogen. The concepts of resistance upon reinfection lead to the research and development of replicating (live) vaccines in...

  6. Lentivirus-mediated Gene Transfer in Hematopoietic Stem Cells Is Impaired in SHIV-infected, ART-treated Nonhuman Primates

    PubMed Central

    Younan, Patrick M; Peterson, Christopher W; Polacino, Patricia; Kowalski, John P; Obenza, Willimark; Miller, Hannah W; Milless, Brian P; Gafken, Phil; DeRosa, Stephen C; Hu, Shiu-Lok; Kiem, Hans-Peter

    2015-01-01

    Recent studies have demonstrated that genetically modified hematopoietic stem cells (HSCs) can reduce HIV viremia. We have developed an HIV/AIDS-patient model in Simian/human immunodeficiency virus (SHIV)-infected pigtailed macaques that are stably suppressed on antiretroviral therapy (ART: raltegravir, emtricitabine and tenofovir). Following SHIV infection and ART, animals undergo autologous HSC transplantation (HSCT) with lentivirally transduced cluster of differentiation (CD)34+ cells expressing the mC46 anti-HIV fusion protein. We show that SHIV+, ART-treated animals had very low gene marking levels after HSCT. Pretransduction CD34+ cells contained detectable levels of all three ART drugs, likely contributing to the low gene transfer efficiency. Following HSCT recovery and the cessation of ART, plasma viremia rebounded, indicating that myeloablative total body irradiation cannot completely eliminate viral reservoirs after autologous HSCT. The kinetics of recovery following autologous HSCT in SHIV+, ART-treated macaques paralleled those observed following transplantation of control animals. However, T-cell subset analyses demonstrated a high percentage of C-C chemokine receptor 5 (CCR5)-expressing CD4+ T-cells after HSCT. These data suggest that an extended ART interruption time may be required for more efficient lentiviral transduction. To avoid complications associated with ART interruption in the context of high percentages of CD4+CCR5+T-cells after HSCT, the use of vector systems not impaired by the presence of residual ART may also be beneficial. PMID:25648264

  7. Lentivirus-mediated Gene Transfer in Hematopoietic Stem Cells Is Impaired in SHIV-infected, ART-treated Nonhuman Primates.

    PubMed

    Younan, Patrick M; Peterson, Christopher W; Polacino, Patricia; Kowalski, John P; Obenza, Willimark; Miller, Hannah W; Milless, Brian P; Gafken, Phil; DeRosa, Stephen C; Hu, Shiu-Lok; Kiem, Hans-Peter

    2015-05-01

    Recent studies have demonstrated that genetically modified hematopoietic stem cells (HSCs) can reduce HIV viremia. We have developed an HIV/AIDS-patient model in Simian/human immunodeficiency virus (SHIV)-infected pigtailed macaques that are stably suppressed on antiretroviral therapy (ART: raltegravir, emtricitabine and tenofovir). Following SHIV infection and ART, animals undergo autologous HSC transplantation (HSCT) with lentivirally transduced cluster of differentiation (CD)34(+) cells expressing the mC46 anti-HIV fusion protein. We show that SHIV(+), ART-treated animals had very low gene marking levels after HSCT. Pretransduction CD34(+) cells contained detectable levels of all three ART drugs, likely contributing to the low gene transfer efficiency. Following HSCT recovery and the cessation of ART, plasma viremia rebounded, indicating that myeloablative total body irradiation cannot completely eliminate viral reservoirs after autologous HSCT. The kinetics of recovery following autologous HSCT in SHIV(+), ART-treated macaques paralleled those observed following transplantation of control animals. However, T-cell subset analyses demonstrated a high percentage of C-C chemokine receptor 5 (CCR5)-expressing CD4(+) T-cells after HSCT. These data suggest that an extended ART interruption time may be required for more efficient lentiviral transduction. To avoid complications associated with ART interruption in the context of high percentages of CD4(+)CCR5(+)T-cells after HSCT, the use of vector systems not impaired by the presence of residual ART may also be beneficial.

  8. Lentivirus-mediated Gene Transfer in Hematopoietic Stem Cells Is Impaired in SHIV-infected, ART-treated Nonhuman Primates.

    PubMed

    Younan, Patrick M; Peterson, Christopher W; Polacino, Patricia; Kowalski, John P; Obenza, Willimark; Miller, Hannah W; Milless, Brian P; Gafken, Phil; DeRosa, Stephen C; Hu, Shiu-Lok; Kiem, Hans-Peter

    2015-05-01

    Recent studies have demonstrated that genetically modified hematopoietic stem cells (HSCs) can reduce HIV viremia. We have developed an HIV/AIDS-patient model in Simian/human immunodeficiency virus (SHIV)-infected pigtailed macaques that are stably suppressed on antiretroviral therapy (ART: raltegravir, emtricitabine and tenofovir). Following SHIV infection and ART, animals undergo autologous HSC transplantation (HSCT) with lentivirally transduced cluster of differentiation (CD)34(+) cells expressing the mC46 anti-HIV fusion protein. We show that SHIV(+), ART-treated animals had very low gene marking levels after HSCT. Pretransduction CD34(+) cells contained detectable levels of all three ART drugs, likely contributing to the low gene transfer efficiency. Following HSCT recovery and the cessation of ART, plasma viremia rebounded, indicating that myeloablative total body irradiation cannot completely eliminate viral reservoirs after autologous HSCT. The kinetics of recovery following autologous HSCT in SHIV(+), ART-treated macaques paralleled those observed following transplantation of control animals. However, T-cell subset analyses demonstrated a high percentage of C-C chemokine receptor 5 (CCR5)-expressing CD4(+) T-cells after HSCT. These data suggest that an extended ART interruption time may be required for more efficient lentiviral transduction. To avoid complications associated with ART interruption in the context of high percentages of CD4(+)CCR5(+)T-cells after HSCT, the use of vector systems not impaired by the presence of residual ART may also be beneficial. PMID:25648264

  9. Mutations in Ovis aries TMEM154 are associated with lower small ruminant lentivirus proviral concentration in one sheep flock

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Small ruminant lentivirus (SRLV), also called ovine progressive pneumonia virus or maedi-visna, is present in 24% of U.S. sheep. Like human immunodeficiency virus, SRLV is a macrophage-tropic lentivirus that causes lifelong infection. The production impacts from SRLV are due to a range of disease sy...

  10. Deletion variant near ZNF389 is associated with control of ovine lentivirus in multiple flocks of sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ovine lentivirus (OvLV) is a macrophage-tropic lentivirus found in many countries that causes interstitial pneumonia, mastitis, arthritis and cachexia in sheep. There is no preventive vaccine and no cure, but breed differences suggest marker-assisted selective breeding might improve odds of infectio...

  11. Differential Cellular Tropism of Lentivirus and Adeno-Associated Virus in the Brain of Cynomolgus Monkey

    PubMed Central

    An, Heeyoung; Cho, Doo-Wan; Lee, Seung Eun; Yang, Young-Su

    2016-01-01

    Many researchers are using viruses to deliver genes of interest into the brains of laboratory animals. However, certain target brain cells are not easily infected by viruses. Moreover, the differential tropism of different viruses in monkey brain is not well established. We investigated the cellular tropism of lentivirus and adeno-associated virus (AAV) toward neuron and glia in the brain of cynomolgus monkeys (Macaca fascularis). Lentivirus and AAV were injected into putamen of the monkey brain. One month after injection, monkeys were sacrificed, and then the presence of viral infection by expression of reporter fluorescence proteins was examined. Tissues were sectioned and stained with NeuN and GFAP antibodies for identifying neuronal cells or astrocytes, respectively, and viral reporter GFP-expressing cells were counted. We found that while lentivirus infected mostly astrocytes, AAV infected neurons at a higher rate than astrocytes. Moreover, astrocytes showed reactiveness when cells were infected by virus, likely due to virus-mediated neuroinflammation. The Sholl analysis was done to compare the hypertrophy of infected and uninfected astrocytes by virus. The lentivirus infected astrocytes showed negligible hypertrophy whereas AAV infected astrocytes showed significant changes in morphology, compared to uninfected astrocytes. In the brain of cynomolgus monkey, lentivirus shows tropism for astrocytes over neurons without much reactivity in astrocytes, whereas AAV shows tropism for neurons over glial cells with a significant reactivity in astrocytes. We conclude that AAV is best-suited for gene delivery to neurons, whereas lentivirus is the best choice for gene delivery to astrocytes in the brain of cynomolgus monkeys. PMID:26924933

  12. A lion lentivirus related to feline immunodeficiency virus: epidemiologic and phylogenetic aspects.

    PubMed Central

    Brown, E W; Yuhki, N; Packer, C; O'Brien, S J

    1994-01-01

    Feline immunodeficiency virus (FIV) is a novel lentivirus that is genetically homologous and functionally analogous to the human AIDS viruses, human immunodeficiency virus types 1 and 2. FIV causes immunosuppression in domestic cats by destroying the CD4 T-lymphocyte subsets in infected hosts. A serological survey of over 400 free-ranging African and Asian lions (Panthera leo) for antibodies to FIV revealed endemic lentivirus prevalence with an incidence of seropositivity as high as 90%. A lion lentivirus (FIV-Ple) was isolated by infection of lion lymphocytes in vitro. Seroconversion was documented in two Serengeti lions, and discordance of mother-cub serological status argues against maternal transmission (in favor of horizontal spread) as a major route of infection among lions. A phylogenetic analysis of cloned FIV-Ple pol gene sequences from 27 lions from four African populations (from the Serengeti reserve, Ngorongoro Crater, Lake Manyara, and Kruger Park) revealed remarkably high intra- and interindividual genetic diversity at the sequence level. Three FIV-Ple phylogenetic clusters or clades were resolved with phenetic, parsimony, and likelihood analytical procedures. The three clades, which occurred not only together in the same population but throughout Africa, were as divergent from each other as were homologous pol sequences of lentivirus isolated from distinct feline species, i.e., puma and domestic cat. The FIV-Ple clades, however, were more closely related to each other than to other feline lentiviruses (monophyletic for lion species), suggesting that the ancestors of FIV-Ple evolved in allopatric (geographically isolated) lion populations that converged recently. To date, there is no clear evidence of FIV-Ple-associated pathology, raising the possibility of a historic genetic accommodation of the lion lentivirus and its host leading to a coevolved host-parasite symbiosis (or commensalism) in the population similar to that hypothesized for endemic

  13. The primate seahorse rhythm.

    PubMed

    Campos, L M G; Cruz-Rizzolo, Roelf J; Pinato, L

    2015-07-10

    The main Zeitgeber, the day-night cycle, synchronizes the central oscillator which determines behaviors rhythms as sleep-wake behavior, body temperature, the regulation of hormone secretion, and the acquisition and processing of memory. Thus, actions such as acquisition, consolidation, and retrieval performed in the hippocampus are modulated by the circadian system and show a varied dependence on light and dark. To investigate changes in the hippocampus' cellular mechanism invoked by the day and night in a diurnal primate, this study analyzed the expression of PER2 and the calcium binding proteins (CaBPs) calbindin, calretinin and parvalbumin in the hippocampus of Sapajus apella, a diurnal primate, at two different time points, one during the day and one during the dark phase. The PER2 protein expression peaked at night in the antiphase described for the suprachiasmatic nucleus (SCN) of the same primate, indicating that hippocampal cells can present independent rhythmicity. This hippocampal rhythm was similar to that presented by diurnal but not nocturnal rodents. The CaBPs immunoreactivity also showed day/night variations in the cell number and in the cell morphology. Our findings provide evidence for the claim that the circadian regulation in the hippocampus may involve rhythms of PER2 and CaBPs expression that may contribute to the adaptation of this species in events and activities relevant to the respective periods.

  14. Evaluation of a combinatorial RNAi lentivirus vector targeting foot-and-mouth disease virus in vitro and in vivo

    PubMed Central

    ZHANG, XIAOXI; ZHENG, HAIXUE; XU, MINJUN; ZHOU, YU; LI, XIANGPING; YANG, FAN; LIU, QINGYOU; SHI, DESHUN

    2015-01-01

    Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals, which leads to serious economical losses. FMDV is not adequately controlled by vaccination or biosecurity measures. To generate genetically modified FMDV-resistant animals, a combinatorial expression cassette producing three short hairpin (sh) RNAs was constructed using the lentivirus (LV) vector, LV-3shRNA. The three shRNAs were expressed under the regulation of DNA polymerase III promoters from a buffalo and a bovine source, with one targeted to the non-structural protein 3B, and the other two targeted to the viral polymerase protein 3D of FMDV, respectively. The role of LV-3shRNA in the inhibition of the replication of FMDV was determined in BHK-21 cells and in suckling mice. The results revealed that LV-3shRNA reduced viral growth 3-fold (24 h post-infection) when the cells were challenged with 107-times the tissue culture infective dose (TCID50)/ml of O serotype FMDV. The suckling mice pretreated with LV-3shRNA were completely protected on administration of 5-times the dose of FMDV otherwise sufficient to kill 50% of the experimental animals (LD50). These results demonstrated that the LV-mediated dual expression of three FMDV-specific shRNAs provided a novel strategy towards combating FMDV, which facilitates the permanent introduction of novel disease-resistance traits into the buffalo and bovine genomes in the future. PMID:26323462

  15. Maturation of adult beta-cells revealed using a Pdx1/insulin dual-reporter lentivirus.

    PubMed

    Szabat, Marta; Luciani, Dan S; Piret, James M; Johnson, James D

    2009-04-01

    The enigmatic process of beta-cell maturation has significant implications for diabetes pathogenesis, and potential diabetes therapies. This study examined the dynamics and heterogeneity of insulin and pancreatic duodenal homeobox (Pdx)-1 gene expression in adult beta-cells. Insulin and Pdx1 expression were monitored in human and mouse islet cells and MIN6 cells using a Pdx1-monomeric red fluorescent protein/insulin-enhanced green fluorescent protein dual-reporter lentivirus. The majority of fluorescent cells were highly positive for both Pdx1 and insulin. Cells expressing Pdx1 but little or no insulin (Pdx1(+)/Ins(low)) comprised 15-25% of the total population. Time-lapse imaging demonstrated that Pdx1(+)/Ins(low) primary beta-cells and MIN6 cells could convert to Pdx1(+)/Ins(+) cells without cell division. Genes involved in the mature beta-cell phenotype (Glut2, MafA) were expressed at higher levels in Pdx1(+)/Ins(+) cells relative to Pdx1(+)/Ins(low) cells. Conversely, genes implicated in early beta-cell development (MafB, Nkx2.2) were enriched in Pdx1(+)/Ins(low) cells. Sorted Pdx1(+)/Ins(low) MIN6 cells had a higher replication rate and secreted less insulin relative to double-positive cells. Long-term phenotype tracking of Pdx1(+)/Ins(low) cells showed two groups, one that matured into Pdx1(+)/Ins(+) cells and one that remained immature. These results demonstrate that adult beta-cells pass through distinct maturation states, which is consistent with previously observed heterogeneity in insulin and Pdx1 expression in adult beta-cells. At a given time, a proportion of adult beta-cells share similar characteristics to functionally immature embryonic beta-cell progenitors. The maturation of adult beta-cells recapitulates development in that Pdx1 expression precedes the robust expression of insulin and other mature beta-cell genes. These results have implications for harnessing the maturation process for therapeutic purposes. PMID:19095744

  16. Genetic testing for TMEM154 mutations associated with lentivirus susceptibility in sheep

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In sheep, small ruminant lentiviruses cause an incurable, progressive, lymphoproliferative disease that affect millions of animals worldwide. Known as ovine progressive pneumonia virus (OPPV) in the U.S., and Visna/Maedi virus (VMV) elsewhere, these viruses reduce an animal’s health, productivity, ...

  17. Brains, Genes and Primates

    PubMed Central

    Belmonte, Juan Carlos Izpisua; Callaway, Edward M.; Churchland, Patricia; Caddick, Sarah J.; Feng, Guoping; Homanics, Gregg E.; Lee, Kuo-Fen; Leopold, David A.; Miller, Cory T.; Mitchell, Jude F.; Mitalipov, Shoukhrat; Moutri, Alysson R.; Movshon, J. Anthony; Okano, Hideyuki; Reynolds, John H.; Ringach, Dario; Sejnowski, Terrence J.; Silva, Afonso C.; Strick, Peter L.; Wu, Jun; Zhang, Feng

    2015-01-01

    One of the great strengths of the mouse model is the wide array of genetic tools that have been developed. Striking examples include methods for directed modification of the genome, and for regulated expression or inactivation of genes. Within neuroscience, it is now routine to express reporter genes, neuronal activity indicators and opsins in specific neuronal types in the mouse. However, there are considerable anatomical, physiological, cognitive and behavioral differences between the mouse and the human that, in some areas of inquiry, limit the degree to which insights derived from the mouse can be applied to understanding human neurobiology. Several recent advances have now brought into reach the goal of applying these tools to understanding the primate brain. Here we describe these advances, consider their potential to advance our understanding of the human brain and brain disorders, discuss bioethical considerations, and describe what will be needed to move forward. PMID:25950631

  18. Ethics of primate use

    NASA Astrophysics Data System (ADS)

    Prescott, M. J.

    2010-11-01

    This article provides an overview of the ethical issues raised by the use of non-human primates (NHPs) in research involving scientific procedures which may cause pain, suffering, distress or lasting harm. It is not an exhaustive review of the literature and views on this subject, and it does not present any conclusions about the moral acceptability or otherwise of NHP research. Rather the aim has been to identify the ethical issues involved and to provide guidance on how these might be addressed, in particular by carefully examining the scientific rationale for NHP use, implementing fully the 3Rs principle of Russell and Burch (1959) and applying a robust "harm-benefit assessment" to research proposals involving NHPs.

  19. Captivity humanizes the primate microbiome

    PubMed Central

    Vangay, Pajau; Huang, Hu; Ward, Tonya; Hillmann, Benjamin M.; Al-Ghalith, Gabriel A.; Travis, Dominic A.; Long, Ha Thang; Tuan, Bui Van; Minh, Vo Van; Cabana, Francis; Nadler, Tilo; Toddes, Barbara; Murphy, Tami; Glander, Kenneth E.; Johnson, Timothy J.; Knights, Dan

    2016-01-01

    The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome. PMID:27573830

  20. Captivity humanizes the primate microbiome.

    PubMed

    Clayton, Jonathan B; Vangay, Pajau; Huang, Hu; Ward, Tonya; Hillmann, Benjamin M; Al-Ghalith, Gabriel A; Travis, Dominic A; Long, Ha Thang; Tuan, Bui Van; Minh, Vo Van; Cabana, Francis; Nadler, Tilo; Toddes, Barbara; Murphy, Tami; Glander, Kenneth E; Johnson, Timothy J; Knights, Dan

    2016-09-13

    The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome. PMID:27573830

  1. Leopard predation and primate evolution.

    PubMed

    Zuberbühler, Klaus; Jenny, David

    2002-12-01

    Although predation is an important driving force of natural selection its effects on primate evolution are still not well understood, mainly because little is known about the hunting behaviour of the primates' various predators. Here, we present data on the hunting behaviour of the leopard (Panthera pardus), a major primate predator in the Tai; forest of Ivory Coast and elsewhere. Radio-tracking data showed that forest leopards primarily hunt for monkeys on the ground during the day. Faecal analyses confirmed that primates accounted for a large proportion of the leopards' diet and revealed in detail the predation pressure exerted on the eight different monkey and one chimpanzee species. We related the species-specific predation rates to various morphological, behavioural and demographic traits that are usually considered adaptations to predation (body size, group size, group composition, reproductive behaviour, and use of forest strata). Leopard predation was most reliably associated with density, suggesting that leopards hunt primates according to abundance. Contrary to predictions, leopard predation rates were not negatively, but positively, related to body size, group size and the number of males per group, suggesting that predation by leopards did not drive the evolution of these traits in the predicted way. We discuss these findings in light of some recent experimental data and suggest that the principal effect of leopard predation has been on primates' cognitive evolution.

  2. Captivity humanizes the primate microbiome.

    PubMed

    Clayton, Jonathan B; Vangay, Pajau; Huang, Hu; Ward, Tonya; Hillmann, Benjamin M; Al-Ghalith, Gabriel A; Travis, Dominic A; Long, Ha Thang; Tuan, Bui Van; Minh, Vo Van; Cabana, Francis; Nadler, Tilo; Toddes, Barbara; Murphy, Tami; Glander, Kenneth E; Johnson, Timothy J; Knights, Dan

    2016-09-13

    The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome.

  3. Sponge-mediated Lentivirus Delivery to Acute and Chronic Spinal Cord Injuries

    PubMed Central

    Thomas, Aline M.; Palma, Jaime L.; Shea, Lonnie D.

    2015-01-01

    The environment within the spinal cord after injury, which changes in the progression from the acute to chronic stages, limits the extent of regeneration. The delivery of inductive factors to promote regeneration following spinal cord injury has been promising, yet, few strategies are have are versatile to allow delivery during acute or chronic injury that would facilitate screening of candidate therapies. This report investigates the intrathecal delivery of lentiviruses for long-term expression of regenerative factors. Lentivirus-filled sponges were inserted into the intrathecal space surrounding the spinal cord, with transgene expression observed within multiple cell types that persists for 12 weeks for both intact and injured spinal cord, without any apparent damage to the spinal cord tissue. Sponges loaded with lentivirus encoding for Sonic hedgehog (Shh) were investigated for acute (delivered at 0 weeks) and chronic (at 4 weeks) injuries, and for multiple locations relative to the injury. In an acute model, sponges placed directly above the injury increased oligodendrocyte and decreased astrocyte presence. Sponges placed caudal to the injury had reduced impact on oligodendrocytes and astrocytes in the injury. In a chronic model, sponges increased oligodendrocyte and decreased astrocyte presence. Furthermore, the effect of Shh was shown to be mediated in part by reduction of Bmp signaling, monitored with an Msx2-sensitive reporter vector. The implantation of lentivirus-loaded biomaterials intrathecally provides the opportunity to induce the expression of a factor at a specified time without entering the spinal cord, and has the potential to promote gene delivery within the spinal cord, which can influence the extent of regeneration. PMID:25724274

  4. Sponge-mediated lentivirus delivery to acute and chronic spinal cord injuries.

    PubMed

    Thomas, Aline M; Palma, Jaime L; Shea, Lonnie D

    2015-04-28

    The environment within the spinal cord after injury, which changes in the progression from the acute to chronic stages, limits the extent of regeneration. The delivery of inductive factors to promote regeneration following spinal cord injury has been promising, yet, few strategies are versatile to allow delivery during acute or chronic injury that would facilitate screening of candidate therapies. This report investigates the intrathecal delivery of lentiviruses for long-term expression of regenerative factors. Lentivirus-filled sponges were inserted into the intrathecal space surrounding the spinal cord, with transgene expression observed within multiple cell types that persists for 12 weeks for both intact and injured spinal cord, without any apparent damage to the spinal cord tissue. Sponges loaded with lentivirus encoding for Sonic hedgehog (Shh) were investigated for acute (delivered at 0 weeks) and chronic (at 4 weeks) injuries, and for multiple locations relative to the injury. In an acute model, sponges placed directly above the injury increased oligodendrocyte and decreased astrocyte presence. Sponges placed caudal to the injury had reduced impact on oligodendrocytes and astrocytes in the injury. In a chronic model, sponges increased oligodendrocyte and decreased astrocyte presence. Furthermore, the effect of Shh was shown to be mediated in part by reduction of Bmp signaling, monitored with an Msx2-sensitive reporter vector. The implantation of lentivirus-loaded biomaterials intrathecally provides the opportunity to induce the expression of a factor at a specified time without entering the spinal cord, and has the potential to promote gene delivery within the spinal cord, which can influence the extent of regeneration.

  5. Expanding Possibilities for Intervention against Small Ruminant Lentiviruses through Genetic Marker-Assisted Selective Breeding

    PubMed Central

    White, Stephen N.; Knowles, Donald P.

    2013-01-01

    Small ruminant lentiviruses include members that infect sheep (ovine lentivirus [OvLV]; also known as ovine progressive pneumonia virus/maedi-visna virus) and goats (caprine arthritis encephalitis virus [CAEV]). Breed differences in seroprevalence and proviral concentration of OvLV had suggested a strong genetic component in susceptibility to infection by OvLV in sheep. A genetic marker test for susceptibility to OvLV has been developed recently based on the TMEM154 gene with validation data from over 2,800 sheep representing nine cohorts. While no single genotype has been shown to have complete resistance to OvLV, consistent association in thousands of sheep from multiple breeds and management conditions highlight a new strategy for intervention by selective breeding. This genetic marker-assisted selection (MAS) has the potential to be a useful addition to existing viral control measures. Further, the discovery of multiple additional genomic regions associated with susceptibility to or control of OvLV suggests that additional genetic marker tests may be developed to extend the reach of MAS in the future. This review will cover the strengths and limitations of existing data from host genetics as an intervention and outline additional questions for future genetic research in sheep, goats, small ruminant lentiviruses, and their host-pathogen interactions. PMID:23771240

  6. Lentivirus-mediated Knockdown of HDAC1 Uncovers Its Role in Esophageal Cancer Metastasis and Chemosensitivity

    PubMed Central

    Song, Min; He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

    2016-01-01

    Histone deacetylationase 1 (HDAC1) is ubiquitously expressed in various cell lines and tissues and play an important role of regulation gene expression. Overexpression of HDAC1 has been observed in various types of cancers, which indicated that it might be a target for cancer therapy. To test HDAC1 inhibition for cancer treatment, the gene expression of HDAC1 was knockdown mediated by a lentivirus system. Our data showed the gene expression of HDAC1 could be efficiently knockdown by RNAi mediated by lentivirus in esophageal carcinoma EC109 cells. Knockdown of HDAC1 led to significant decrease of cell growth and altered cell cycle distribution. The result of transwell assay showed that the numbers of cells travelled through the micropore membrane was significantly decreased as HDAC1 expression was knockdown. Moreover, HDAC1 knockdown inhibited the migration of EC109 cells as determining by scratch test. Additionally, enhancement of cisplatin-stimulated apoptosis was detected by HDAC1 knockdown. Our data suggested inhibition of HDAC1 expression by lentivirus mediated shRNA might be further applied for esophageal cancer chemotherapy. PMID:27698906

  7. Bridges delivering neurotrophin encoding lentivirus enhance regeneration following spinal cord injury

    PubMed Central

    Tuinstra, Hannah M; Aviles, Misael O.; Shin, Seungjin; Holland, Samantha J.; Zelivyanskaya, Marina L.; Fast, Alan; Ko, Sarah; Margul, Daniel J.; Bartels, Anne K.; Boehler, Ryan M.; Cummings, Brian J.; Anderson, Aileen J.; Shea, Lonnie D.

    2011-01-01

    Therapeutic strategies following spinal cord injury must address the multiple barriers that limit regeneration. Multiple channel bridges have been developed that stabilize the injury following implantation and provide physical guidance for regenerating axons. These bridges have now been employed as a vehicle for localized delivery of lentivirus. Implantation of lentivirus loaded multiple channel bridges produced transgene expression that persisted for at least 4 weeks. Expression was maximal at the implant at the earliest time point, and decreased with increasing time of implantation, as well as rostral and caudal to the bridge. Immunohistochemical staining indicated transduction of macrophages, Schwann cells, fibroblasts, and astrocytes within the bridge and adjacent tissue. Subsequently, the delivery of lentivirus encoding the neurotrophic factors NT3 or BDNF significantly increased the extent of axonal growth into the bridge relative to empty scaffolds. In addition to promoting axon growth, the induced expression of neurotrophic factors led to myelination of axons within the channels of the bridge, where the number of myelinated axons was significantly enhanced relative to control. Combining gene delivery with biomaterials to provide physical guidance and create a permissive environment can provide a platform to enhance axonal growth and promote regeneration. PMID:22130565

  8. Lentivirus-mediated Knockdown of HDAC1 Uncovers Its Role in Esophageal Cancer Metastasis and Chemosensitivity

    PubMed Central

    Song, Min; He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

    2016-01-01

    Histone deacetylationase 1 (HDAC1) is ubiquitously expressed in various cell lines and tissues and play an important role of regulation gene expression. Overexpression of HDAC1 has been observed in various types of cancers, which indicated that it might be a target for cancer therapy. To test HDAC1 inhibition for cancer treatment, the gene expression of HDAC1 was knockdown mediated by a lentivirus system. Our data showed the gene expression of HDAC1 could be efficiently knockdown by RNAi mediated by lentivirus in esophageal carcinoma EC109 cells. Knockdown of HDAC1 led to significant decrease of cell growth and altered cell cycle distribution. The result of transwell assay showed that the numbers of cells travelled through the micropore membrane was significantly decreased as HDAC1 expression was knockdown. Moreover, HDAC1 knockdown inhibited the migration of EC109 cells as determining by scratch test. Additionally, enhancement of cisplatin-stimulated apoptosis was detected by HDAC1 knockdown. Our data suggested inhibition of HDAC1 expression by lentivirus mediated shRNA might be further applied for esophageal cancer chemotherapy.

  9. Evaluation of a combinatorial RNAi lentivirus vector targeting foot-and-mouth disease virus in vitro and in vivo.

    PubMed

    Zhang, Xiaoxi; Zheng, Haixue; Xu, Minjun; Zhou, Yu; Li, Xiangping; Yang, Fan; Liu, Qingyou; Shi, Deshun

    2015-11-01

    Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven‑hoofed animals, which leads to serious economical losses. FMDV is not adequately controlled by vaccination or biosecurity measures. To generate genetically modified FMDV‑resistant animals, a combinatorial expression cassette producing three short hairpin (sh)RNAs was constructed using the lentivirus (LV) vector, LV‑3shRNA. The three shRNAs were expressed under the regulation of DNA polymerase III promoters from a buffalo and a bovine source, with one targeted to the non‑structural protein 3B, and the other two targeted to the viral polymerase protein 3D of FMDV, respectively. The role of LV‑3shRNA in the inhibition of the replication of FMDV was determined in BHK‑21 cells and in suckling mice. The results revealed that LV‑3shRNA reduced viral growth 3‑fold (24 h post‑infection) when the cells were challenged with 107‑times the tissue culture infective dose (TCID50)/ml of O serotype FMDV. The suckling mice pretreated with LV‑3shRNA were completely protected on administration of 5‑times the dose of FMDV otherwise sufficient to kill 50% of the experimental animals (LD50). These results demonstrated that the LV‑mediated dual expression of three FMDV‑specific shRNAs provided a novel strategy towards combating FMDV, which facilitates the permanent introduction of novel disease-resistance traits into the buffalo and bovine genomes in the future.

  10. Hepatocyte innervation in primates

    PubMed Central

    1977-01-01

    The efferent innervation and some characteristics of nerve fibers of the liver lobule in the tree shrew, a primate, are described. Nerve endings on hepatocytes were encountered regularly and were determined to be efferent adrenergic nerves. Transmission electron microscopy revealed nerve endings and varicosities in close apposition to the hepatocytes adjacent to the connective tissue of the triads as well as within the liver lobule in the space of Disse. Fluorescence microscopy indicated the existence of adrenergic nerves with a similar distribution. Autoradiography of the avid uptake of exogenous [3H]norepinephrine indicated that all intralobular nerves are potentially norepinephrinergic (adrenergic). Chemical sympathectomy with 6-OH-dopamine resulted in the degeneration of all intralobular liver nerve fibers as revealed by fluorescence microscopy and electron microscopy. Substantial regeneration occurred after 60-90 days but was not completed by that time. Some nerves were also observed in close association with von Kupffer cells and endothelial cells. The functional significance of the efferent liver innervation is discussed. PMID:406265

  11. Lack of neutralizing antibodies to caprine arthritis-encephalitis lentivirus in persistently infected goats can be overcome by immunization with inactivated Mycobacterium tuberculosis.

    PubMed Central

    Narayan, O; Sheffer, D; Griffin, D E; Clements, J; Hess, J

    1984-01-01

    The pathogenesis of the persistent progressive diseases of sheep (visna-maedi) and goats (arthritis-encephalitis) is dependent on continuous replication of the causative lentiviruses. One subgroup of these viruses, Icelandic visna virus, accomplishes this form of replication by undergoing antigenic mutation. Mutant viruses arising late in the infection escape neutralization by antibodies directed to the parental virus. In contrast, we show here that viruses obtained from persistently infected sheep and goats with natural disease in this country do not induce virus-neutralizing antibodies, although antibodies to virus core proteins were produced. The lack of neutralizing antibodies was not overcome by hyperimmunization of animals with concentrated preparations of live or inactivated virus. Thus, failure to produce these specific antibodies was not due to lack of sufficient antigen or interference with the immune response because of the ability of these viruses to infect macrophages. The hyporesponsive state, however, was overcome by immunization of animals with virus and large amounts of inactivated Mycobacterium tuberculosis. Induction of agglutinating and neutralizing antibodies by this method was probably due to a unique form of antigen processing by macrophages activated by M. tuberculosis. Neutralizing antibodies were produced for the first time against the caprine arthritis-encephalitis virus by this method. These antibodies have similar biological properties to those induced by Icelandic visna virus. They belong to the immunoglobulin G1 subclass, they are effective against a narrow range of caprine arthritis-encephalitis viruses, and they identify (for the first time) antigenic variants among these caprine agents. PMID:6319735

  12. Replication fork collapse at replication terminator sequences.

    PubMed

    Bidnenko, Vladimir; Ehrlich, S Dusko; Michel, Bénédicte

    2002-07-15

    Replication fork arrest is a source of genome re arrangements, and the recombinogenic properties of blocked forks are likely to depend on the cause of blockage. Here we study the fate of replication forks blocked at natural replication arrest sites. For this purpose, Escherichia coli replication terminator sequences Ter were placed at ectopic positions on the bacterial chromosome. The resulting strain requires recombinational repair for viability, but replication forks blocked at Ter are not broken. Linear DNA molecules are formed upon arrival of a second round of replication forks that copy the DNA strands of the first blocked forks to the end. A model that accounts for the requirement for homologous recombination for viability in spite of the lack of chromosome breakage is proposed. This work shows that natural and accidental replication arrests sites are processed differently.

  13. No need to replace an "anomalous" primate (Primates) with an "anomalous" bear (Carnivora, Ursidae).

    PubMed

    Gutiérrez, Eliécer E; Pine, Ronald H

    2015-01-01

    By means of mitochondrial 12S rRNA sequencing of putative "yeti", "bigfoot", and other "anomalous primate" hair samples, a recent study concluded that two samples, presented as from the Himalayas, do not belong to an "anomalous primate", but to an unknown, anomalous type of ursid. That is, that they match 12S rRNA sequences of a fossil Polar Bear (Ursusmaritimus), but neither of modern Polar Bears, nor of Brown Bears (Ursusarctos), the closest relative of Polar Bears, and one that occurs today in the Himalayas. We have undertaken direct comparison of sequences; replication of the original comparative study; inference of phylogenetic relationships of the two samples with respect to those from all extant species of Ursidae (except for the Giant Panda, Ailuropodamelanoleuca) and two extinct Pleistocene species; and application of a non-tree-based population aggregation approach for species diagnosis and identification. Our results demonstrate that the very short fragment of the 12S rRNA gene sequenced by Sykes et al. is not sufficiently informative to support the hypotheses provided by these authors with respect to the taxonomic identity of the individuals from which these sequences were obtained. We have concluded that there is no reason to believe that the two samples came from anything other than Brown Bears. These analyses afforded an opportunity to test the monophyly of morphologically defined species and to comment on both their phylogenetic relationships and future efforts necessary to advance our understanding of ursid systematics.

  14. No need to replace an "anomalous" primate (Primates) with an "anomalous" bear (Carnivora, Ursidae).

    PubMed

    Gutiérrez, Eliécer E; Pine, Ronald H

    2015-01-01

    By means of mitochondrial 12S rRNA sequencing of putative "yeti", "bigfoot", and other "anomalous primate" hair samples, a recent study concluded that two samples, presented as from the Himalayas, do not belong to an "anomalous primate", but to an unknown, anomalous type of ursid. That is, that they match 12S rRNA sequences of a fossil Polar Bear (Ursusmaritimus), but neither of modern Polar Bears, nor of Brown Bears (Ursusarctos), the closest relative of Polar Bears, and one that occurs today in the Himalayas. We have undertaken direct comparison of sequences; replication of the original comparative study; inference of phylogenetic relationships of the two samples with respect to those from all extant species of Ursidae (except for the Giant Panda, Ailuropodamelanoleuca) and two extinct Pleistocene species; and application of a non-tree-based population aggregation approach for species diagnosis and identification. Our results demonstrate that the very short fragment of the 12S rRNA gene sequenced by Sykes et al. is not sufficiently informative to support the hypotheses provided by these authors with respect to the taxonomic identity of the individuals from which these sequences were obtained. We have concluded that there is no reason to believe that the two samples came from anything other than Brown Bears. These analyses afforded an opportunity to test the monophyly of morphologically defined species and to comment on both their phylogenetic relationships and future efforts necessary to advance our understanding of ursid systematics. PMID:25829853

  15. The malignant primate?

    PubMed

    de Grouchy, J

    1991-01-01

    Speciation and carcinogenesis result from genomic instability at the gametic or at the somatic levels. After an infinity of trials they occur, by chromosome rearrangements, in single individuals or in single cells and evolve by similar chromosomal or clonal evolutions. Loss of heterozygosity for the first event is essential in both processes: in evolution, a chromosomal rearrangement, a pericentric inversion or a Robertsonian fusion, must become homozygous to ensure a reproductive barrier for a new species; Knudson's two-event sequence is a similar situation in cancer. Position effect is equally important: we have shown overexpression of the SOD1 gene in the orangutan phylum probably by an intrachromosomal rearrangement; the t(9;22) in CML acts by typical position effect. Parental imprinting underlies the evolution of genome function and the unset of certain cancers. Evolution and malignancy are interweaved by viruses and oncogenes since the dawn of life. Cancer uses its intelligence to expand and to destroy the other tissues, using subtle metabolic pathways and a variety of tricks to metastasize other cells. It always wins but saws the branch on which it sits. Mankind also grows exponentially, killing thousands of other species, poisoning the oceans and soft waters, polluting the atmosphere, all for his egoistic needs. Man also travels and metastasizes other Earths. He modifies his genome or that of other species, and develops new technologies for his reproduction. He can destroy the planet in an eyeblink. To be or not to be the malignant primate, that will be the dilemma for the 21st Century. PMID:1809219

  16. APOBEC3G polymorphism as a selective barrier to cross-species transmission and emergence of pathogenic SIV and AIDS in a primate host.

    PubMed

    Krupp, Annabel; McCarthy, Kevin R; Ooms, Marcel; Letko, Michael; Morgan, Jennifer S; Simon, Viviana; Johnson, Welkin E

    2013-01-01

    Cellular restriction factors, which render cells intrinsically resistant to viruses, potentially impose genetic barriers to cross-species transmission and emergence of viral pathogens in nature. One such factor is APOBEC3G. To overcome APOBEC3G-mediated restriction, many lentiviruses encode Vif, a protein that targets APOBEC3G for degradation. As with many restriction factor genes, primate APOBEC3G displays strong signatures of positive selection. This is interpreted as evidence that the primate APOBEC3G locus reflects a long-term evolutionary "arms-race" between retroviruses and their primate hosts. Here, we provide direct evidence that APOBEC3G has functioned as a barrier to cross-species transmission, selecting for viral resistance during emergence of the AIDS-causing pathogen SIVmac in captive colonies of Asian macaques in the 1970s. Specifically, we found that rhesus macaques have multiple, functionally distinct APOBEC3G alleles, and that emergence of SIVmac and simian AIDS required adaptation of the virus to evade APOBEC3G-mediated restriction. Our evidence includes the first comparative analysis of APOBEC3G polymorphism and function in both a reservoir and recipient host species (sooty mangabeys and rhesus macaques, respectively), and identification of adaptations unique to Vif proteins of the SIVmac lineage that specifically antagonize rhesus APOBEC3G alleles. By demonstrating that interspecies variation in a known restriction factor selected for viral counter-adaptations in the context of a documented case of cross-species transmission, our results lend strong support to the evolutionary "arms-race" hypothesis. Importantly, our study confirms that APOBEC3G divergence can be a critical determinant of interspecies transmission and emergence of primate lentiviruses, including viruses with the potential to infect and spread in human populations.

  17. A Molecular Phylogeny of Living Primates

    PubMed Central

    Perelman, Polina; Johnson, Warren E.; Roos, Christian; Seuánez, Hector N.; Horvath, Julie E.; Moreira, Miguel A. M.; Kessing, Bailey; Pontius, Joan; Roelke, Melody; Rumpler, Yves; Schneider, Maria Paula C.; Silva, Artur; O'Brien, Stephen J.; Pecon-Slattery, Jill

    2011-01-01

    Comparative genomic analyses of primates offer considerable potential to define and understand the processes that mold, shape, and transform the human genome. However, primate taxonomy is both complex and controversial, with marginal unifying consensus of the evolutionary hierarchy of extant primate species. Here we provide new genomic sequence (∼8 Mb) from 186 primates representing 61 (∼90%) of the described genera, and we include outgroup species from Dermoptera, Scandentia, and Lagomorpha. The resultant phylogeny is exceptionally robust and illuminates events in primate evolution from ancient to recent, clarifying numerous taxonomic controversies and providing new data on human evolution. Ongoing speciation, reticulate evolution, ancient relic lineages, unequal rates of evolution, and disparate distributions of insertions/deletions among the reconstructed primate lineages are uncovered. Our resolution of the primate phylogeny provides an essential evolutionary framework with far-reaching applications including: human selection and adaptation, global emergence of zoonotic diseases, mammalian comparative genomics, primate taxonomy, and conservation of endangered species. PMID:21436896

  18. Retinal connectivity and primate vision

    PubMed Central

    Lee, Barry B.; Martin, Paul R.; Grünert, Ulrike

    2012-01-01

    The general principles of retinal organization are now well known. It may seem surprising that retinal organization in the primate, which has a complex visual behavioral repertoire, appears relatively simple. In this review, we primarily consider retinal structure and function in primate species. Photoreceptor distribution and connectivity are considered as are connectivity in the outer and inner retina. One key issue is the specificity of retinal connections; we suggest that the retina shows connectional specificity but this is seldom complete, and we consider here the functional consequences of imprecise wiring. Finally, we consider how retinal systems can be linked to psychophysical descriptions of different channels, chromatic and luminance, which are proposed to exist in the primate visual system. PMID:20826226

  19. Lentivirus IL-10 gene therapy down-regulates IL-17 and attenuates mouse orthotopic lung allograft rejection.

    PubMed

    Hirayama, S; Sato, M; Loisel-Meyer, S; Matsuda, Y; Oishi, H; Guan, Z; Saito, T; Yeung, J; Cypel, M; Hwang, D M; Medin, J A; Liu, M; Keshavjee, S

    2013-06-01

    The purpose of the study was to examine the effect of lentivirus-mediated IL-10 gene therapy to target lung allograft rejection in a mouse orthotopic left lung transplantation model. IL-10 may regulate posttransplant immunity mediated by IL-17. Lentivirus-mediated trans-airway luciferase gene transfer to the donor lung resulted in persistent luciferase activity up to 6 months posttransplant in the isograft (B6 to B6); luciferase activity decreased in minor-mismatched allograft lungs (B10 to B6) in association with moderate rejection. Fully MHC-mismatched allograft transplantation (BALB/c to B6) resulted in severe rejection and complete loss of luciferase activity. In minor-mismatched allografts, IL-10-encoding lentivirus gene therapy reduced the acute rejection score compared with the lentivirus-luciferase control at posttransplant day 28 (3.0 ± 0.6 vs. 2.0 ± 0.6 (mean ± SD); p = 0.025; n = 6/group). IL-10 gene therapy also significantly reduced gene expression of IL-17, IL-23, and retinoic acid-related orphan receptor (ROR)-γt without affecting levels of IL-12 and interferon-γ (IFN-γ). Cells expressing IL-17 were dramatically reduced in the allograft lung. In conclusion, lentivirus-mediated IL-10 gene therapy significantly reduced expression of IL-17 and other associated genes in the transplanted allograft lung and attenuated posttransplant immune responses after orthotopic lung transplantation. PMID:23601206

  20. Cytoplasmic Viral Replication Complexes

    PubMed Central

    den Boon, Johan A.; Diaz, Arturo; Ahlquist, Paul

    2010-01-01

    Many viruses that replicate in the cytoplasm compartmentalize their genome replication and transcription in organelle-like structures that enhance replication efficiency and protection from host defenses. In particular, recent studies with diverse positive-strand RNA viruses have further elucidated the ultrastructure of membrane-bounded RNA replication complexes and their close coordination with virion assembly and budding. The structure, function and assembly of some positive-strand RNA virus replication complexes have parallels and potential evolutionary links with the replicative cores of double-strand RNA virus and retrovirus virions, and more general similarities with the replication factories of cytoplasmic DNA viruses. PMID:20638644

  1. Evolution of Puma Lentivirus in Bobcats (Lynx rufus) and Mountain Lions (Puma concolor) in North America

    PubMed Central

    Bevins, Sarah N.; Serieys, Laurel E. K.; Vickers, Winston; Logan, Ken A.; Aldredge, Mat; Boydston, Erin E.; Lyren, Lisa M.; McBride, Roy; Roelke-Parker, Melody; Pecon-Slattery, Jill; Troyer, Jennifer L.; Riley, Seth P.; Boyce, Walter M.; Crooks, Kevin R.; VandeWoude, Sue

    2014-01-01

    ABSTRACT Mountain lions (Puma concolor) throughout North and South America are infected with puma lentivirus clade B (PLVB). A second, highly divergent lentiviral clade, PLVA, infects mountain lions in southern California and Florida. Bobcats (Lynx rufus) in these two geographic regions are also infected with PLVA, and to date, this is the only strain of lentivirus identified in bobcats. We sequenced full-length PLV genomes in order to characterize the molecular evolution of PLV in bobcats and mountain lions. Low sequence homology (88% average pairwise identity) and frequent recombination (1 recombination breakpoint per 3 isolates analyzed) were observed in both clades. Viral proteins have markedly different patterns of evolution; sequence homology and negative selection were highest in Gag and Pol and lowest in Vif and Env. A total of 1.7% of sites across the PLV genome evolve under positive selection, indicating that host-imposed selection pressure is an important force shaping PLV evolution. PLVA strains are highly spatially structured, reflecting the population dynamics of their primary host, the bobcat. In contrast, the phylogeography of PLVB reflects the highly mobile mountain lion, with diverse PLVB isolates cocirculating in some areas and genetically related viruses being present in populations separated by thousands of kilometers. We conclude that PLVA and PLVB are two different viral species with distinct feline hosts and evolutionary histories. IMPORTANCE An understanding of viral evolution in natural host populations is a fundamental goal of virology, molecular biology, and disease ecology. Here we provide a detailed analysis of puma lentivirus (PLV) evolution in two natural carnivore hosts, the bobcat and mountain lion. Our results illustrate that PLV evolution is a dynamic process that results from high rates of viral mutation/recombination and host-imposed selection pressure. PMID:24741092

  2. Evolution of puma lentivirus in bobcats (Lynx rufus) and mountain lions (Puma concolor) in North America.

    PubMed

    Lee, Justin S; Bevins, Sarah N; Serieys, Laurel E K; Vickers, Winston; Logan, Ken A; Aldredge, Mat; Boydston, Erin E; Lyren, Lisa M; McBride, Roy; Roelke-Parker, Melody; Pecon-Slattery, Jill; Troyer, Jennifer L; Riley, Seth P; Boyce, Walter M; Crooks, Kevin R; VandeWoude, Sue

    2014-07-01

    Mountain lions (Puma concolor) throughout North and South America are infected with puma lentivirus clade B (PLVB). A second, highly divergent lentiviral clade, PLVA, infects mountain lions in southern California and Florida. Bobcats (Lynx rufus) in these two geographic regions are also infected with PLVA, and to date, this is the only strain of lentivirus identified in bobcats. We sequenced full-length PLV genomes in order to characterize the molecular evolution of PLV in bobcats and mountain lions. Low sequence homology (88% average pairwise identity) and frequent recombination (1 recombination breakpoint per 3 isolates analyzed) were observed in both clades. Viral proteins have markedly different patterns of evolution; sequence homology and negative selection were highest in Gag and Pol and lowest in Vif and Env. A total of 1.7% of sites across the PLV genome evolve under positive selection, indicating that host-imposed selection pressure is an important force shaping PLV evolution. PLVA strains are highly spatially structured, reflecting the population dynamics of their primary host, the bobcat. In contrast, the phylogeography of PLVB reflects the highly mobile mountain lion, with diverse PLVB isolates cocirculating in some areas and genetically related viruses being present in populations separated by thousands of kilometers. We conclude that PLVA and PLVB are two different viral species with distinct feline hosts and evolutionary histories. Importance: An understanding of viral evolution in natural host populations is a fundamental goal of virology, molecular biology, and disease ecology. Here we provide a detailed analysis of puma lentivirus (PLV) evolution in two natural carnivore hosts, the bobcat and mountain lion. Our results illustrate that PLV evolution is a dynamic process that results from high rates of viral mutation/recombination and host-imposed selection pressure. PMID:24741092

  3. Effects of lentivirus mediated STAT3 silencing on human chronic myeloid leukemia cells and leukemia mice

    PubMed Central

    Jia, Xinyan; Yang, Wenzhong; Han, Jia; Xiong, Hong

    2014-01-01

    Objective: To investigate the effects of lentivirus mediated STAT3 silencing on human chronic myeloid leukemia cells (K562) and the growth of chronic myeloid leukemia mice as well as to explore the potential mechanisms. Methods: Unbtreated K562 cells (CON), blank lentivirus transfected K562 cells (NC) and K562 cells expressing STAT3 siRNA (STAT3 siRNA) were injected into SCID mice to establish the chronic myeloid leukemia model in mice. The growth, peripheral white blood cell count and spleen index in these mice were determined. Results: In vitro experiment showed, when compared with control group, the interference efficiency of STAT3 expression was as high as 97.5% in K562 cells. Western blot assay revealed that the expression of c-Myc, Bcl-xL and Cyclin D1 reduced by 17.01%, 7.3% and 6.82%, respectively, showing significant difference when compared with control group (P < 0.01). These findings were consistent with those from fluorescence quantitative PCR. In vivo experiment showed the body weight of mice reduced progressively and the peripheral white blood cell count increased gradually in control group, accompanied by dragging hind limbs and progressive enlargement of the spleen. The body weight remained unchanged, peripheral white blood cell count reduced gradually and the spleen did not enlarge in mice treated with STAT3 siRNA expressing cells. Conclusion: Lentivirus mediated STAT3 silencing may inhibit the expression of its downstream genes (c-Myc, Bcl-xL and Cyclin D1) related to cell proliferation, apoptosis and cycle to suppress the malignant biological behaviors, and STAT3 silencing also inhibit the leukemogenic potency of K562 cells in mice. PMID:25550912

  4. Evolution of puma lentivirus in bobcats (Lynx rufus) and mountain lions (Puma concolor) in North America.

    PubMed

    Lee, Justin S; Bevins, Sarah N; Serieys, Laurel E K; Vickers, Winston; Logan, Ken A; Aldredge, Mat; Boydston, Erin E; Lyren, Lisa M; McBride, Roy; Roelke-Parker, Melody; Pecon-Slattery, Jill; Troyer, Jennifer L; Riley, Seth P; Boyce, Walter M; Crooks, Kevin R; VandeWoude, Sue

    2014-07-01

    Mountain lions (Puma concolor) throughout North and South America are infected with puma lentivirus clade B (PLVB). A second, highly divergent lentiviral clade, PLVA, infects mountain lions in southern California and Florida. Bobcats (Lynx rufus) in these two geographic regions are also infected with PLVA, and to date, this is the only strain of lentivirus identified in bobcats. We sequenced full-length PLV genomes in order to characterize the molecular evolution of PLV in bobcats and mountain lions. Low sequence homology (88% average pairwise identity) and frequent recombination (1 recombination breakpoint per 3 isolates analyzed) were observed in both clades. Viral proteins have markedly different patterns of evolution; sequence homology and negative selection were highest in Gag and Pol and lowest in Vif and Env. A total of 1.7% of sites across the PLV genome evolve under positive selection, indicating that host-imposed selection pressure is an important force shaping PLV evolution. PLVA strains are highly spatially structured, reflecting the population dynamics of their primary host, the bobcat. In contrast, the phylogeography of PLVB reflects the highly mobile mountain lion, with diverse PLVB isolates cocirculating in some areas and genetically related viruses being present in populations separated by thousands of kilometers. We conclude that PLVA and PLVB are two different viral species with distinct feline hosts and evolutionary histories. Importance: An understanding of viral evolution in natural host populations is a fundamental goal of virology, molecular biology, and disease ecology. Here we provide a detailed analysis of puma lentivirus (PLV) evolution in two natural carnivore hosts, the bobcat and mountain lion. Our results illustrate that PLV evolution is a dynamic process that results from high rates of viral mutation/recombination and host-imposed selection pressure.

  5. Highly Efficient Generation of Transgenic Sheep by Lentivirus Accompanying the Alteration of Methylation Status

    PubMed Central

    Liu, Chenxi; Wang, Liqin; Li, Wenrong; Zhang, Xuemei; Tian, Yongzhi; Zhang, Ning; He, Sangang; Chen, Tong; Huang, Juncheng; Liu, Mingjun

    2013-01-01

    Background Low efficiency of gene transfer and silence of transgene expression are the critical factors hampering the development of transgenic livestock. Recently, transfer of recombinant lentivirus has been demonstrated to be an efficient transgene delivery method in various animals. However, the lentiviral transgenesis and the methylation status of transgene in sheep have not been well addressed. Methodology/Principle Findings EGFP transgenic sheep were generated by injecting recombinant lentivirus into zygotes. Of the 13 lambs born, 8 carried the EGFP transgene, and its chromosomal integration was identified in all tested tissues. Western blotting showed that GFP was expressed in all transgenic founders and their various tissues. Analysis of CpG methylation status of CMV promoter by bisulfate sequencing unraveled remarkable variation of methylation levels in transgenic sheep. The average methylation levels ranged from 37.6% to 79.1% in the transgenic individuals and 34.7% to 83% in the tested tissues. Correlative analysis of methylation status with GFP expression revealed that the GFP expression level was inversely correlated with methylation density. The similar phenomenon was also observed in tested tissues. Transgene integration determined by Southern blotting presented multiple integrants ranging from 2 to 6 copies in the genome of transgenic sheep. Conclusions/Significance Injection of lentiviral transgene into zygotes could be a promising efficient gene delivery system to generate transgenic sheep and achieved widespread transgene expression. The promoter of integrants transferred by lentiviral vector was subjected to dramatic alteration of methylation status and the transgene expression level was inversely correlative with promoter methylation density. Our work illustrated for the first time that generation of transgenic sheep by injecting recombinant lentivirus into zygote could be an efficient tool to improve sheep performance by genetic modification

  6. Recombinant small ruminant lentivirus subtype B1 in goats and sheep of imported breeds in Mexico.

    PubMed

    Ramírez, H; Glaria, I; de Andrés, X; Martínez, H A; Hernández, M M; Reina, R; Iráizoz, E; Crespo, H; Berriatua, E; Vázquez, J; Amorena, B; de Andrés, D

    2011-10-01

    Nucleotide sequences of small ruminant lentiviruses (SRLVs) were determined in sheep and goats, including progeny of imported animals, on a farm in Mexico. On the basis of gag-pol, pol, env and LTR sequences, SRLVs were assigned to the B1 subgroup, which comprises caprine arthritis-encephalitis virus (CAEV)-like prototype sequences mainly from goats. In comparison with CAEV-like env sequences of American and French origin, two putative recombination events were identified within the V3-V4 and V4-V5 regions of the env gene of a full length SRLV sequence (FESC-752) derived from a goat on the farm.

  7. Assessing anxiety in nonhuman primates.

    PubMed

    Coleman, Kristine; Pierre, Peter J

    2014-01-01

    Anxiety can be broadly described as a psychological state in which normally innocuous environmental stimuli trigger negative emotional expectations. Human anxiety disorders are multidimensional and may be organic or acquired, situational or pervasive. The broad ranging nature of the anxiety phenotype speaks to the need for models that identify its various components and root causes to develop effective clinical treatments. The cross-species comparative approach to modeling anxiety disorders in animals aims to understand mechanisms that both contribute to and modulate anxiety. Nonhuman primate models provide an important bridge from nonprimate model systems because of the complexity of nonhuman primates' biobehavioral capacities and their commonalities with human emotion. The broad goal of this review is to provide an overview of various procedures available to study anxiety in the nonhuman primate, with a focus on the behavioral aspects of anxiety. Commonly used methods covered in this review include assessing animals in their home environment or in response to an ethologically relevant threat, associative conditioning and startle response tests, and cognitive bias tests. We also discuss how these procedures can help veterinarians and researchers care for captive nonhuman primates.

  8. Enrichment and aggression in primates.

    PubMed

    Honess, P E; Marin, C M

    2006-01-01

    There is considerable evidence that primates housed under impoverished conditions develop behavioural abnormalities, including, in the most extreme example, self-harming behaviour. This has implications for all contexts in which primates are maintained in captivity from laboratories to zoos since by compromising the animals' psychological well-being and allowing them to develop behavioural abnormalities their value as appropriate educational and research models is diminished. This review examines the extensive body of literature documenting attempts to improve living conditions with a view to correcting behavioural abnormalities and housing primates in such a way that they are encouraged to exhibit a more natural range and proportion of behaviours, including less self-directed and social aggression. The results of housing, feeding, physical, sensory and social enrichment efforts are examined with specific focus on their effect on aggressive behaviour and variation in their use and efficacy. It is concluded that while inappropriate or poorly distributed enrichment may encourage aggressive competition, enrichment that is species, sex, age and background appropriate can dramatically reduce aggression, can eliminate abnormal behaviour and substantially improve the welfare of primates maintained in captivity.

  9. Pathogenesis of Varicelloviruses in primates

    PubMed Central

    Ouwendijk, Werner J.D.; Verjans, Georges M.G.M.

    2014-01-01

    Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation. PMID:25255989

  10. Neuroethology of primate social behavior.

    PubMed

    Chang, Steve W C; Brent, Lauren J N; Adams, Geoffrey K; Klein, Jeffrey T; Pearson, John M; Watson, Karli K; Platt, Michael L

    2013-06-18

    A neuroethological approach to human and nonhuman primate behavior and cognition predicts biological specializations for social life. Evidence reviewed here indicates that ancestral mechanisms are often duplicated, repurposed, and differentially regulated to support social behavior. Focusing on recent research from nonhuman primates, we describe how the primate brain might implement social functions by coopting and extending preexisting mechanisms that previously supported nonsocial functions. This approach reveals that highly specialized mechanisms have evolved to decipher the immediate social context, and parallel circuits have evolved to translate social perceptual signals and nonsocial perceptual signals into partially integrated social and nonsocial motivational signals, which together inform general-purpose mechanisms that command behavior. Differences in social behavior between species, as well as between individuals within a species, result in part from neuromodulatory regulation of these neural circuits, which itself appears to be under partial genetic control. Ultimately, intraspecific variation in social behavior has differential fitness consequences, providing fundamental building blocks of natural selection. Our review suggests that the neuroethological approach to primate behavior may provide unique insights into human psychopathology.

  11. Worldwide prevalence of lentivirus infection in wild feline species: epidemiologic and phylogenetic aspects.

    PubMed

    Olmsted, R A; Langley, R; Roelke, M E; Goeken, R M; Adger-Johnson, D; Goff, J P; Albert, J P; Packer, C; Laurenson, M K; Caro, T M

    1992-10-01

    The natural occurrence of lentiviruses closely related to feline immunodeficiency virus (FIV) in nondomestic felid species is shown here to be worldwide. Cross-reactive antibodies to FIV were common in several free-ranging populations of large cats, including East African lions and cheetahs of the Serengeti ecosystem and in puma (also called cougar or mountain lion) populations throughout North America. Infectious puma lentivirus (PLV) was isolated from several Florida panthers, a severely endangered relict puma subspecies inhabiting the Big Cypress Swamp and Everglades ecosystems in southern Florida. Phylogenetic analysis of PLV genomic sequences from disparate geographic isolates revealed appreciable divergence from domestic cat FIV sequences as well as between PLV sequences found in different North American locales. The level of sequence divergence between PLV and FIV was greater than the level of divergence between human and certain simian immunodeficiency viruses, suggesting that the transmission of FIV between feline species is infrequent and parallels in time the emergence of HIV from simian ancestors.

  12. Novel antimicrobial peptides derived from human immunodeficiency virus type 1 and other lentivirus transmembrane proteins.

    PubMed Central

    Tencza, S B; Douglass, J P; Creighton, D J; Montelaro, R C; Mietzner, T A

    1997-01-01

    We have previously described a conserved set of peptides derived from lentiviral envelope transmembrane proteins that are similar to the natural antimicrobial peptides cecropins and magainins in overall structure but bear no sequence homology to them or other members of their class. We describe here an evaluation of the antimicrobial properties of these virally derived peptides, designated lentivirus lytic peptides (LLPs). The results of this study demonstrate that they are potent and selective antibacterial peptides: the prototype sequence, LLP1, is bactericidal to both gram-positive and gram-negative organisms at micromolar concentrations in 10 mM phosphate buffer. Furthermore, LLP1 kills bacteria quite rapidly, causing a 1,000-fold reduction in viable organisms within 50 s. Peptides corresponding to sequences from three lentivirus envelope proteins were synthesized and characterized. Several of these peptides are selective, killing bacteria at concentrations 50- to 100-fold lower than those required to lyse erythrocytes. Development of antimicrobial agents based on these peptides may lead to improved therapeutics for the management of a variety of infectious diseases. PMID:9371339

  13. Evolution of puma lentivirus in bobcats (Lynx rufus) and mountain lions (Puma concolor) in North America

    USGS Publications Warehouse

    Lee, Justin S.; Bevins, Sarah N.; Serieys, Laurel E.K.; Vickers, Winston; Logan, Ken A.; Aldredge, Mat; Boydston, Erin E.; Lyren, Lisa M.; McBride, Roy; Roelke-Parker, Melody; Pecon-Slattery, Jill; Troyer, Jennifer L.; Riley, Seth P.; Boyce, Walter M.; Crooks, Kevin R.; VandeWoude, Sue

    2014-01-01

    Mountain lions (Puma concolor) throughout North and South America are infected with puma lentivirus clade B (PLVB). A second, highly divergent lentiviral clade, PLVA, infects mountain lions in southern California and Florida. Bobcats (Lynx rufus) in these two geographic regions are also infected with PLVA, and to date, this is the only strain of lentivirus identified in bobcats. We sequenced full-length PLV genomes in order to characterize the molecular evolution of PLV in bobcats and mountain lions. Low sequence homology (88% average pairwise identity) and frequent recombination (1 recombination breakpoint per 3 isolates analyzed) were observed in both clades. Viral proteins have markedly different patterns of evolution; sequence homology and negative selection were highest in Gag and Pol and lowest in Vif and Env. A total of 1.7% of sites across the PLV genome evolve under positive selection, indicating that host-imposed selection pressure is an important force shaping PLV evolution. PLVA strains are highly spatially structured, reflecting the population dynamics of their primary host, the bobcat. In contrast, the phylogeography of PLVB reflects the highly mobile mountain lion, with diverse PLVB isolates cocirculating in some areas and genetically related viruses being present in populations separated by thousands of kilometers. We conclude that PLVA and PLVB are two different viral species with distinct feline hosts and evolutionary histories.

  14. Generation and analysis of lentivirus expressing a 2A peptide-linked bicistronic fluorescent construct.

    PubMed

    Huss, David; Lansford, Rusty

    2014-12-01

    This weeklong protocol for making and testing lentivirus has been used in the Advanced Topics in Molecular Neuroscience (ATMN) lecture and laboratory course at Cold Spring Harbor Laboratory (CSHL) for nearly a decade. Lentiviruses are derived from HIV-1 and are ideal vehicles for the delivery of multiple genes of interest into target cells. In this protocol, 2A peptide-linked sequences are used to create a bicistronic lentiviral construct containing a ubiquitous promoter (chick β actin with a cytomegalovirus [CMV] early enhancer) driving dual expression of two fluorescent proteins (FP): H2B-Cerulean (a nuclear-localized blue FP) and Dendra2 (a photoactivatable green FP that converts to red after exposure to UV light). Polymerase chain reaction (PCR) amplification of the bicistronic insert is followed by subcloning into a lentiviral vector and transfection into a packaging cell line. The resulting viral supernatants can be used to prepare concentrated stocks and infect cells for imaging via epifluorescent and confocal microscopy. PMID:25447284

  15. Worldwide prevalence of lentivirus infection in wild feline species: epidemiologic and phylogenetic aspects.

    PubMed

    Olmsted, R A; Langley, R; Roelke, M E; Goeken, R M; Adger-Johnson, D; Goff, J P; Albert, J P; Packer, C; Laurenson, M K; Caro, T M

    1992-10-01

    The natural occurrence of lentiviruses closely related to feline immunodeficiency virus (FIV) in nondomestic felid species is shown here to be worldwide. Cross-reactive antibodies to FIV were common in several free-ranging populations of large cats, including East African lions and cheetahs of the Serengeti ecosystem and in puma (also called cougar or mountain lion) populations throughout North America. Infectious puma lentivirus (PLV) was isolated from several Florida panthers, a severely endangered relict puma subspecies inhabiting the Big Cypress Swamp and Everglades ecosystems in southern Florida. Phylogenetic analysis of PLV genomic sequences from disparate geographic isolates revealed appreciable divergence from domestic cat FIV sequences as well as between PLV sequences found in different North American locales. The level of sequence divergence between PLV and FIV was greater than the level of divergence between human and certain simian immunodeficiency viruses, suggesting that the transmission of FIV between feline species is infrequent and parallels in time the emergence of HIV from simian ancestors. PMID:1382145

  16. Computer retina that models the primate retina

    NASA Astrophysics Data System (ADS)

    Shah, Samir; Levine, Martin D.

    1994-06-01

    At the retinal level, the strategies utilized by biological visual systems allow them to outperform machine vision systems, serving to motivate the design of electronic or `smart' sensors based on similar principles. Design of such sensors in silicon first requires a model of retinal information processing which captures the essential features exhibited by biological retinas. In this paper, a simple retinal model is presented, which qualitatively accounts for the achromatic information processing in the primate cone system. The model exhibits many of the properties found in biological retina such as data reduction through nonuniform sampling, adaptation to a large dynamic range of illumination levels, variation of visual acuity with illumination level, and enhancement of spatio temporal contrast information. The model is validated by replicating experiments commonly performed by electrophysiologists on biological retinas and comparing the response of the computer retina to data from experiments in monkeys. In addition, the response of the model to synthetic images is shown. The experiments demonstrate that the model behaves in a manner qualitatively similar to biological retinas and thus may serve as a basis for the development of an `artificial retina.'

  17. Surveying genome replication

    PubMed Central

    Kearsey, Stephen

    2002-01-01

    Two recent studies have added microarrays to the toolkit used to analyze the origins of replication in yeast chromosomes, providing a fuller picture of how genomic DNA replication is organized. PMID:12093380

  18. CCR5 Gene Editing of Resting CD4+ T Cells by Transient ZFN Expression From HIV Envelope Pseudotyped Nonintegrating Lentivirus Confers HIV-1 Resistance in Humanized Mice

    PubMed Central

    Yi, Guohua; Choi, Jang Gi; Bharaj, Preeti; Abraham, Sojan; Dang, Ying; Kafri, Tal; Alozie, Ogechika; Manjunath, Manjunath N; Shankar, Premlata

    2014-01-01

    CCR5 disruption by zinc finger nucleases (ZFNs) is a promising method for HIV-1 gene therapy. However, successful clinical translation of this strategy necessitates the development of a safe and effective method for delivery into relevant cells. We used non-integrating lentivirus (NILV) for transient expression of ZFNs and pseudotyped the virus with HIV-envelope for targeted delivery to CD4+ T cells. Both activated and resting primary CD4+ T cells transduced with CCR5-ZFNs NILV showed resistance to HIV-1 infection in vitro. Furthermore, NILV transduced resting CD4+ T cells from HIV-1 seronegative individuals were resistant to HIV-1 challenge when reconstituted into NOD-scid IL2rγc null (NSG) mice. Likewise, endogenous virus replication was suppressed in NSG mice reconstituted with CCR5-ZFN–transduced resting CD4+ T cells from treatment naïve as well as ART-treated HIV-1 seropositive patients. Taken together, NILV pseudotyped with HIV envelope provides a simple and clinically viable strategy for HIV-1 gene therapy. PMID:25268698

  19. Replicating repetitive DNA.

    PubMed

    Tognetti, Silvia; Speck, Christian

    2016-05-27

    The function and regulation of repetitive DNA, the 'dark matter' of the genome, is still only rudimentarily understood. Now a study investigating DNA replication of repetitive centromeric chromosome segments has started to expose a fascinating replication program that involves suppression of ATR signalling, in particular during replication stress. PMID:27230530

  20. Underground hibernation in a primate.

    PubMed

    Blanco, Marina B; Dausmann, Kathrin H; Ranaivoarisoa, Jean F; Yoder, Anne D

    2013-01-01

    Hibernation in mammals is a remarkable state of heterothermy wherein metabolic rates are reduced, core body temperatures reach ambient levels, and key physiological functions are suspended. Typically, hibernation is observed in cold-adapted mammals, though it has also been documented in tropical species and even primates, such as the dwarf lemurs of Madagascar. Western fat-tailed dwarf lemurs are known to hibernate for seven months per year inside tree holes. Here, we report for the first time the observation that eastern dwarf lemurs also hibernate, though in self-made underground hibernacula. Hence, we show evidence that a clawless primate is able to bury itself below ground. Our findings that dwarf lemurs can hibernate underground in tropical forests draw unforeseen parallels to mammalian temperate hibernation. We expect that this work will illuminate fundamental information about the influence of temperature, resource limitation and use of insulated hibernacula on the evolution of hibernation.

  1. Optogenetics in the nonhuman primate

    PubMed Central

    Han, Xue

    2013-01-01

    The nonhuman primate brain, the model system closest to the human brain, plays a critical role in our understanding of neural computation, cognition, and behavior. The continued quest to crack the neural codes in the monkey brain would be greatly enhanced with new tools and technologies that can rapidly and reversibly control the activities of desired cells at precise times during specific behavioral states. Recent advances in adapting optogenetic technologies to monkeys have enabled precise control of specific cells or brain regions at the millisecond timescale, allowing for the investigation of the causal role of these neural circuits in this model system. Validation of optogenetic technologies in monkeys also represents a critical preclinical step on the translational path of new generation cell-type-specific neural modulation therapies. Here, I discuss the current state of the application of optogenetics in the nonhuman primate model system, highlighting the available genetic, optical and electrical technologies, and their limitations and potentials. PMID:22341328

  2. Primate Experiments on SLS-1

    NASA Technical Reports Server (NTRS)

    Aochi, J.

    1985-01-01

    Experiments to study how certain body systems are affected by the space environment are described. These experiments are to be conducted on space shuttle flights. How weightlessness affects two body systems of primates are the prime concern. Thermoregulation and fluid and electrolyte homeostasis are the two systems concerned. The thermoregulation project will provide data on how body temperature and circadian rhythms are affected in a weightlessness environment and the homeostasis in fluids and electrolyte levels will address the problem of body fluid shifts.

  3. Genome-Wide association identifies multiple genomic regions associated with susceptibility to and control of ovine lentivirus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Like human immunodeficiency virus (HIV), ovine lentivirus (OvLV) is macrophage-tropic and causes lifelonginfection. OvLV infects one quarter of U.S. sheep and induces pneumonia and body condition wasting. There is no vaccine to prevent OvLV infection and no cost-effective treatment for i...

  4. Genetic subgroup of small ruminant lentiviruses that infects sheep homozygous for TMEM154 frameshift deletion mutation A4delta53

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Small Ruminant Lentivirus (SRLV) infections of sheep are influenced by genetics on both the host and pathogen sides. Genetic variation in the ovine transmembrane 154 (TMEM154) gene associates with infection susceptibility, and distinct SRLV genetic subtypes infect sheep in association with their TM...

  5. Soils, time, and primate paleoenvironments

    USGS Publications Warehouse

    Bown, T.M.; Kraus, M.J.

    1993-01-01

    Soils are the skin of the earth. From both poles to the equator, wherever rocks or sediment are exposed at the surface, soils are forming through the physical and chemical action of climate and living organisms. The physical attributes (color, texture, thickness) and chemical makeup of soils vary considerably, depending on the composition of the parent material and other variables: temperature, rainfall and soil moisture, vegetation, soil fauna, and the length of time that soil-forming processes have been at work. United States soil scientists1 have classified modern soils into ten major groups and numerous subgroups, each reflecting the composition and architecture of the soils and, to some extent, the processes that led to their formation. The physical and chemical processes of soil formation have been active throughout geologic time; the organic processes have been active at least since the Ordovician.2 Consequently, nearly all sedimentary rocks that were deposited in nonmarine settings and exposed to the elements contain a record of ancient, buried soils or paleosols. A sequence of these rocks, such as most ancient fluvial (stream) deposits, provides a record of soil paleoenvironments through time. Paleosols are also repositories of the fossils of organisms (body fossils) and the traces of those organisms burrowing, food-seeking, and dwelling activities (ichnofossils). Indeed, most fossil primates are found in paleosols. Careful study of ancient soils gives new, valuable insights into the correct temporal reconstruction of the primate fossil record and the nature of primate paleoenvironments. ?? 1993 Wiley-Liss, Inc.

  6. Serendipitous insights involving nonhuman primates.

    PubMed

    Morton, William R; Swindler, Kathryn

    2005-01-01

    Serendipity is discussed as a form of controlled chaos, a phenomenon in a class with synchronicity and other actions affecting research in terms of theory versus observation (e.g., "optional stopping"). Serendipity is a fundamental aspect of basic research, a profitable and normal outcome in the context of "informed observation." The serendipitous finding fits into the following pattern: it is unanticipated, anomalous, and strategic. All observations that have meaning must fit into some context in the observer's mind or suggest a revolutionary new context. It is critically important to maintain access to the resources provided by established primate centers and similar laboratories to capitalize in a timely way on serendipitous findings and to benefit from valuable discoveries made in more directly targeted development investments. Examples are given of serendipitous insights gained in experimentation and observation relative to nonhuman primate research, including both broad and narrow topics. Genomics, which uses comparison-based strategies and capitalizes on the DNA sequences of genetic information, presents what might seem the basis for endless serendipity because nonhuman primates are likely to share most genes present in the human genome. Other topics discussed include infant behavior, birth periodicity, leprosy, cystic fibrosis, environmental enrichment, endocrinology, drug development, and the rapidly expanding study of infectious diseases and pathogen-based bioterrorism. PMID:16179742

  7. Assessing Anxiety in Nonhuman Primates

    PubMed Central

    Coleman, Kristine; Pierre, Peter J.

    2014-01-01

    Anxiety can be broadly described as a psychological state in which normally innocuous environmental stimuli trigger negative emotional expectations. Human anxiety disorders are multidimensional and may be organic or acquired, situational or pervasive. The broad ranging nature of the anxiety phenotype speaks to the need for models that identify its various components and root causes to develop effective clinical treatments. The cross-species comparative approach to modeling anxiety disorders in animals aims to understand mechanisms that both contribute to and modulate anxiety. Nonhuman primate models provide an important bridge from nonprimate model systems because of the complexity of nonhuman primates’ biobehavioral capacities and their commonalities with human emotion. The broad goal of this review is to provide an overview of various procedures available to study anxiety in the nonhuman primate, with a focus on the behavioral aspects of anxiety. Commonly used methods covered in this review include assessing animals in their home environment or in response to an ethologically relevant threat, associative conditioning and startle response tests, and cognitive bias tests. We also discuss how these procedures can help veterinarians and researchers care for captive nonhuman primates. PMID:25225310

  8. Production, purification and titration of a lentivirus-based vector for gene delivery purposes.

    PubMed

    Nasri, Masoud; Karimi, Ali; Allahbakhshian Farsani, Mehdi

    2014-12-01

    Viral vectors are valuable tools to deliver genetic materials into cells. Vectors derived from human immunodeficiency virus type 1 are being widely used for gene delivery, mainly because they are able to transduce both dividing and non-dividing cells which leads to stable and long term gene expression. In addition, these types of vectors are safe, with low toxicity, high stability and cell type specificity. Therefore, this work was aimed to produce lentivirus-based vector using a three-plasmid system. To produce this system, the eGFP marker gene was cloned into the plasmid pWPXLd. Subsequently, this vector plasmid, along with packaging plasmids, psPAX2 and envelope plasmid, pMD2.G, was co-transfected into packaging cell line (293T) using calcium phosphate method. 48 h post transfection, the constructed viral vector was harvested, purified and concentrated and stored at -80 °C for next experiments. The titration of the vector was carried out, using ELISA, flowcytometry, and fluorescent microscopy. Finally, transduction of HEK-293T, CHO, HepG2, MCF-7, MEFs and Jurkat cell lines was carried out with indicated cell numbers and multiplicities of infections of the vector in the presence of polybrene. Using this system, high titer lentivirus at titers of up to 2 × 10(8) transducing units/ml (TU/ml) was successfully generated and its transduction efficacy was improved by seven to over 20-fold in various cell types. We demonstrate the applicability of this vector for the efficient transduction of dividing and non-dividing cells, including HEK-293T, CHO, HepG2, MCF-7, MEFs and Jurkat cell line. Transduction efficiency yielded titers of (6.3 ± 1.2) 10(5) TU/ml. Furthermore, lentivirus transferred transgene was expressed at high level in the target cells and expression was followed until 90 days after transduction. Thus, the vector generated in this work, might be able to deliver the transgene into a wide range of mammalian cells.

  9. Ecology and evolution of primate colour vision.

    PubMed

    Vorobyev, Misha

    2004-07-01

    More than one hundred years ago, Grant Allen suggested that colour vision in primates, birds and insects evolved as an adaptation for foraging on colourful advertisements of plants--fruits and flowers. Recent studies have shown that well developed colour vision appeared long before fruits and flowers evolved. Thus, colour vision is generally beneficial for many animals, not only for those eating colourful food. Primates are the only placental mammals that have trichromatic colour vision. This may indicate either that trichromacy is particularly useful for primates or that primates are unique among placental mammals in their ability to utilise the signals of three spectrally distinct types of cones or both. Because fruits are an important component of the primate diet, primate trichromacy could have evolved as a specific adaptation for foraging on fruits. Alternatively, primate trichromacy could have evolved as an adaptation for many visual tasks. Comparative studies of mammalian eyes indicate that primates are the only placental mammals that have in their retina a pre-existing neural machinery capable of utilising the signals of an additional spectral type of cone. Thus, the failure of non-primate placental mammals to evolve trichromacy can be explained by constraints imposed on the wiring of retinal neurones. PMID:15312027

  10. Ecology and evolution of primate colour vision.

    PubMed

    Vorobyev, Misha

    2004-07-01

    More than one hundred years ago, Grant Allen suggested that colour vision in primates, birds and insects evolved as an adaptation for foraging on colourful advertisements of plants--fruits and flowers. Recent studies have shown that well developed colour vision appeared long before fruits and flowers evolved. Thus, colour vision is generally beneficial for many animals, not only for those eating colourful food. Primates are the only placental mammals that have trichromatic colour vision. This may indicate either that trichromacy is particularly useful for primates or that primates are unique among placental mammals in their ability to utilise the signals of three spectrally distinct types of cones or both. Because fruits are an important component of the primate diet, primate trichromacy could have evolved as a specific adaptation for foraging on fruits. Alternatively, primate trichromacy could have evolved as an adaptation for many visual tasks. Comparative studies of mammalian eyes indicate that primates are the only placental mammals that have in their retina a pre-existing neural machinery capable of utilising the signals of an additional spectral type of cone. Thus, the failure of non-primate placental mammals to evolve trichromacy can be explained by constraints imposed on the wiring of retinal neurones.

  11. Secondary expansion of the transient subplate zone in the developing cerebrum of human and nonhuman primates.

    PubMed

    Duque, Alvaro; Krsnik, Zeljka; Kostović, Ivica; Rakic, Pasko

    2016-08-30

    The subplate (SP) was the last cellular compartment added to the Boulder Committee's list of transient embryonic zones [Bystron I, Blakemore C, Rakic P (2008) Nature Rev Neurosci 9(2):110-122]. It is highly developed in human and nonhuman primates, but its origin, mode, and dynamics of development, resolution, and eventual extinction are not well understood because human postmortem tissue offers only static descriptive data, and mice cannot serve as an adequate experimental model for the distinct regional differences in primates. Here, we take advantage of the large and slowly developing SP in macaque monkey to examine the origin, settling pattern, and subsequent dispersion of the SP neurons in primates. Monkey embryos exposed to the radioactive DNA replication marker tritiated thymidine ([(3)H]dT, or TdR) at early embryonic ages were killed at different intervals postinjection to follow postmitotic cells' positional changes. As expected in primates, most SP neurons generated in the ventricular zone initially migrate radially, together with prospective layer 6 neurons. Surprisingly, mostly during midgestation, SP cells become secondarily displaced and widespread into the expanding SP zone, which becomes particularly wide subjacent to the association cortical areas and underneath the summit of its folia. We found that invasion of monoamine, basal forebrain, thalamocortical, and corticocortical axons is mainly responsible for this region-dependent passive dispersion of the SP cells. Histologic and immunohistochemical comparison with the human SP at corresponding fetal ages indicates that the same developmental events occur in both primate species. PMID:27503885

  12. Secondary expansion of the transient subplate zone in the developing cerebrum of human and nonhuman primates.

    PubMed

    Duque, Alvaro; Krsnik, Zeljka; Kostović, Ivica; Rakic, Pasko

    2016-08-30

    The subplate (SP) was the last cellular compartment added to the Boulder Committee's list of transient embryonic zones [Bystron I, Blakemore C, Rakic P (2008) Nature Rev Neurosci 9(2):110-122]. It is highly developed in human and nonhuman primates, but its origin, mode, and dynamics of development, resolution, and eventual extinction are not well understood because human postmortem tissue offers only static descriptive data, and mice cannot serve as an adequate experimental model for the distinct regional differences in primates. Here, we take advantage of the large and slowly developing SP in macaque monkey to examine the origin, settling pattern, and subsequent dispersion of the SP neurons in primates. Monkey embryos exposed to the radioactive DNA replication marker tritiated thymidine ([(3)H]dT, or TdR) at early embryonic ages were killed at different intervals postinjection to follow postmitotic cells' positional changes. As expected in primates, most SP neurons generated in the ventricular zone initially migrate radially, together with prospective layer 6 neurons. Surprisingly, mostly during midgestation, SP cells become secondarily displaced and widespread into the expanding SP zone, which becomes particularly wide subjacent to the association cortical areas and underneath the summit of its folia. We found that invasion of monoamine, basal forebrain, thalamocortical, and corticocortical axons is mainly responsible for this region-dependent passive dispersion of the SP cells. Histologic and immunohistochemical comparison with the human SP at corresponding fetal ages indicates that the same developmental events occur in both primate species.

  13. The epidemiology of lion lentivirus infection among a population of free-ranging lions (Panthera leo) in the Kruger National Park, South Africa.

    PubMed

    Adams, H; van Vuuren, M; Bosman, A-M; Keet, D; New, J; Kennedy, M

    2009-09-01

    Feline immunodeficiency virus is a lentivirus of domestic cats that causes significant lifelong infection. Infection with this or similar lentiviruses has been detected in several nondomestic feline species, including African lions (Panthera leo). Although lion lentivirus (FIVple) infection is endemic in certain lion populations in eastern and southern Africa, little is known about its pathogenic effects or its epidemiological impact in free-ranging lions. This report describes the epidemiological investigation of lentivirus positivity of free-ranging lions in the Kruger National Park, South Africa. A nested polymerase chain reaction assay for virus detection was performed on all whole blood samples collected. In addition, serum samples were tested for cross-reactive antibodies to domestic feline lentivirus antigens and to puma lentivirus synthetic envelope peptide antigen. The results were analysed in conjunction with epidemiological data to provide a descriptive epidemiological study on lion lentivirus infection in a free-ranging population of lions. The overall prevalence of lentivirus infection was 69%, with a prevalence of 41% in the north of the park, and 80% in the south. Adult males had the highest prevalence when combining the factors of sex and age: 94%. The lowest prevalences were found among juveniles, with male juveniles at 29%. Adults were 5.58 times more likely to test positive for FIVple than juveniles, with adult males being 35 times more likely to be test positive for FIVple compared with juvenile males. This research represents the 1st epidemiological study of the lion lentivirus among free-ranging lions in the Kruger National Park.

  14. Lentivirus-Mediated knockdown of tectonic family member 1 inhibits medulloblastoma cell proliferation

    PubMed Central

    Jing, Junjie; Wang, Chengfeng; Liang, Qinchuan; Zhao, Yang; Zhao, Qingshuang; Wang, Shousen; Ma, Jie

    2015-01-01

    Tectonic family member 1 (TCTN1) encodes a member of the tectonic family which are evolutionarily conserved secreted and transmembrane proteins, involving in a diverse variety of developmental processes. It has been demonstrated that tectonics expressed in regions that participate in Hedgehog (Hh) signaling during mouse embryonic development and was imperative for Hh-mediated patterning of the ventral neural tube. However, the expression and regulation of tectonics in human tumor is still not clear. In this study, shRNA-expressing lentivirus was constructed to knockdown TCTN1 in medulloblastoma cell line Daoy. The results showed that knockdown of TCTN1 inhibited cell proliferation and colony formation in Daoy cell line, also caused cell cycle arrest at the G2/M boundary. Taken all together, our data suggest that TCTN1 might play an important role in the progression of medulloblastoma. PMID:26550235

  15. Experimental design for stable genetic manipulation in mammalian cell lines: lentivirus and alternatives.

    PubMed

    Shearer, Robert F; Saunders, Darren N

    2015-01-01

    The use of third-generation lentiviral vectors is now commonplace in most areas of basic biology. These systems provide a fast, efficient means for modulating gene expression, but experimental design needs to be carefully considered to minimize potential artefacts arising from off-target effects and other confounding factors. This review offers a starting point for those new to lentiviral-based vector systems, addressing the main issues involved with the use of lentiviral systems in vitro and outlines considerations which should be taken into account during experimental design. Factors such as selecting an appropriate system and controls, and practical titration of viral transduction are important considerations for experimental design. We also briefly describe some of the more recent advances in genome editing technology. TALENs and CRISPRs offer an alternative to lentivirus, providing endogenous gene editing with reduced off-target effects often at the expense of efficiency.

  16. Omega-1 knockdown in Schistosoma mansoni eggs by lentivirus transduction reduces granuloma size in vivo

    PubMed Central

    Hagen, Jana; Young, Neil D.; Every, Alison L.; Pagel, Charles N.; Schnoeller, Corinna; Scheerlinck, Jean-Pierre Y.; Gasser, Robin B.

    2014-01-01

    Schistosomiasis, one of the most important neglected tropical diseases worldwide, is caused by flatworms (blood flukes or schistosomes) that live in the bloodstream of humans. The hepatointestinal form of this debilitating disease results from a chronic infection with Schistosoma mansoni or Schistosoma japonicum. No vaccine is available to prevent schistosomiasis, and treatment relies predominantly on the use of a single drug, praziquantel. In spite of considerable research effort over the years, very little is known about the complex in vivo events that lead to granuloma formation and other pathological changes during infection. Here we use, for the first time, a lentivirus-based transduction system to deliver microRNA-adapted short hairpin RNAs (shRNAmirs) into the parasite to silence and explore selected protein-encoding genes of S. mansoni implicated in the disease process. This gene-silencing system has potential to be used for functional genomic–phenomic studies of a range of socioeconomically important pathogens. PMID:25400038

  17. Small ruminant lentivirus proviral sequences from wild ibexes in contact with domestic goats.

    PubMed

    Erhouma, Esadk; Guiguen, François; Chebloune, Yahia; Gauthier, Dominique; Lakhal, Laila Mselli; Greenland, Timothy; Mornex, Jean François; Leroux, Caroline; Alogninouwa, Théodore

    2008-06-01

    Small ruminant lentiviruses (SRLV) are widespread amongst domesticated goats and sheep worldwide, but have not been clearly identified in wild small ruminants, where they might constitute an animal health risk through contamination from local domesticates. SRLV proviruses from three ibexes from the French Alps are described and sequences from their gag gene and long terminal repeats (LTRs) were compared with sequences from local goats and goat/ibex hybrids. The ibex and hybrid proviruses formed a closely related group with <2 % nucleotide difference. Their LTRs were clearly distinct from those of local goats or reference SRLV sequences; however, their gag sequences resembled those from one local goat and reference sequences from caprine arthritis encephalitis virus rather than visna/maedi virus. One SRLV-positive ibex from a distant site shared similarities with the other ibexes studied in both its gag and LTR sequences, suggesting that a distinct SRLV population could circulate in some wild ibex populations. PMID:18474564

  18. Production and Concentration of Lentivirus for Transduction of Primary Human T Cells.

    PubMed

    Kennedy, Alan; Cribbs, Adam P

    2016-01-01

    Lentiviral vectors have emerged as efficient tools for investigating T cell biology through their ability to efficiently deliver transgene expression into both dividing and nondividing cells. Such lentiviral vectors have the potential to infect a wide variety of cell types. However, despite this advantage, the ability to transduce primary human T cells remains challenging and methods to achieve efficient gene transfer are often time consuming and expensive. We describe a method for generating lentivirus that is simple to perform and does not require the purchase of non-standard equipment to transduce primary human T cells. Therefore, we provide an optimized protocol that is easy to implement and allow transduction with high efficiency and reproducibility. PMID:27317175

  19. Lentivirus-mediated downregulation of MAT2B inhibits cell proliferation and induces apoptosis in melanoma.

    PubMed

    Lei, Yu; Zhang, Bo; Zhang, Yaohua; Zhao, Yuan; Sun, Jingying; Zhang, Xuejun; Yang, Sen

    2016-09-01

    Malignant melanoma is the most lethal of skin cancers and its pathogenesis is complex and heterogeneous. The efficacy of conventional therapeutic regimens for melanoma remains limited. Thus, it is important to explore novel effective therapeutic targets in the treatment of melanoma. The MAT2B gene encodes for the regulatory subunit of methionine adenosyltransferase (MAT). Recent studies have suggested that MAT2B may have functional roles other than modulating catalytic activity of MAT. In order to identify the roles of MAT2B in the tumorigenesis of malignant melanoma, we compared MAT2B expression profile in melanoma tissues with that in benign nevus samples. We employed lentivirus-mediated RNAi to downregulate the expression of MAT2B in malignant melanoma cell lines (A375 and Mel-RM), and investigated the effects of MAT2B on cell growth, colony-formation ability and apoptosis in vitro, as well as tumor growth of a xenograft model in vivo. The expression levels of BCL2 and XAF1 proteins, which were closely related to tumor cell apoptosis, were analyzed by western blot analysis. Our data showed that MAT2B was elevated in both primary and metastatic melanoma tissues compared with benign nevus samples. Lentivirus-mediated downregulation of MAT2B suppressed cell growth, colony formation and induced apoptosis in A375 and Mel-RM cell lines in vitro, affected protein expression of BCL2 and XAF1, extended the transplanted tumor growth in vivo. These results indicated that MAT2B was critical in the proliferation of melanoma cells and tumorigenicity. It may be considered as a potential anti-melanoma therapeutic target. PMID:27573889

  20. Risk factors associated with small ruminant lentivirus infection in eastern Poland sheep flocks.

    PubMed

    Junkuszew, Andrzej; Dudko, Paulina; Bojar, Wiktor; Olech, Monika; Osiński, Zbigniew; Gruszecki, Tomasz M; Kania, Monika Greguła; Kuźmak, Jacek; Czerski, Grzegorz

    2016-05-01

    An analysis of the risk factors for ovine lentivirus infection was performed in sheep flocks located throughout the central-eastern region of Poland. Here, we report the infection details for 98 flocks with a total of 6470 ewes, 15 sheep breeds. The identification of infected animals and a review of the epidemiological status of each flock were based on an evaluation of serological tests performed on collected blood serum samples. Blood for examination was obtained from 2925 ewes of the 98 flocks under observation. Specific antibodies for Maedi Visna Virus (MVV) were detected via ELISA. Data illustrating the conditions at each sheep farm were obtained through questionnaires completed by farmers, as well as observations, measurements, and breeding records that were available. These observations were used to assess risk factors contributing to small ruminant lentivirus (SRLV) infection in sheep flocks. It was found that both sheep flock size and the type of management system had a significant effect on the increased risk of lentiviral infection. In addition, we demonstrate that there is a significant (p<0.0001) relationship between the occurrence of mastitis (OR 2.01, CI: 1.55-2.61) and diarrhea (OR 4.22, CI: 3.30-5.39) with SRLV infection in the observed sheep. Additionally, the infection rate of the animals translated directly to an impaired physical condition. Notably, the risk of infection could potentially be reduced if sheep producers are further acquainted with SRLV detection and invoke a control program based on diagnostic tests. Moreover, marketing approval should be granted for solely SRLV-seronegative animals.

  1. The evolution of replicators.

    PubMed Central

    Szathmáry, E

    2000-01-01

    Replicators of interest in chemistry, biology and culture are briefly surveyed from a conceptual point of view. Systems with limited heredity have only a limited evolutionary potential because the number of available types is too low. Chemical cycles, such as the formose reaction, are holistic replicators since replication is not based on the successive addition of modules. Replicator networks consisting of catalytic molecules (such as reflexively autocatalytic sets of proteins, or reproducing lipid vesicles) are hypothetical ensemble replicators, and their functioning rests on attractors of their dynamics. Ensemble replicators suffer from the paradox of specificity: while their abstract feasibility seems to require a high number of molecular types, the harmful effect of side reactions calls for a small system size. No satisfactory solution to this problem is known. Phenotypic replicators do not pass on their genotypes, only some aspects of the phenotype are transmitted. Phenotypic replicators with limited heredity include genetic membranes, prions and simple memetic systems. Memes in human culture are unlimited hereditary, phenotypic replicators, based on language. The typical path of evolution goes from limited to unlimited heredity, and from attractor-based to modular (digital) replicators. PMID:11127914

  2. Enhanced Viral Replication by Cellular Replicative Senescence

    PubMed Central

    Kim, Ji-Ae; Seong, Rak-Kyun

    2016-01-01

    Cellular replicative senescence is a major contributing factor to aging and to the development and progression of aging-associated diseases. In this study, we sought to determine viral replication efficiency of influenza virus (IFV) and Varicella Zoster Virus (VZV) infection in senescent cells. Primary human bronchial epithelial cells (HBE) or human dermal fibroblasts (HDF) were allowed to undergo numbers of passages to induce replicative senescence. Induction of replicative senescence in cells was validated by positive senescence-associated β-galactosidase staining. Increased susceptibility to both IFV and VZV infection was observed in senescent HBE and HDF cells, respectively, resulting in higher numbers of plaque formation, along with the upregulation of major viral antigen expression than that in the non-senescent cells. Interestingly, mRNA fold induction level of virus-induced type I interferon (IFN) was attenuated by senescence, whereas IFN-mediated antiviral effect remained robust and potent in virus-infected senescent cells. Additionally, we show that a longevity-promoting gene, sirtuin 1 (SIRT1), has antiviral role against influenza virus infection. In conclusion, our data indicate that enhanced viral replication by cellular senescence could be due to senescence-mediated reduction of virus-induced type I IFN expression. PMID:27799874

  3. Non-human primate models of SIV infection and CNS neuropathology.

    PubMed

    Williams, Kenneth; Lackner, Andrew; Mallard, Jaclyn

    2016-08-01

    Non-human primate models of AIDS and neuroAIDS are the premiere model of HIV infection of the CNS and neuropathogenesis. This review discusses current SIV infection models of neuroAIDS emphasizing findings in the last two years. Consistent in these findings is the interplay between host factors that regulate immune responses to virus and viral replication. Several rapid models of AIDS with consistent CNS pathogenesis exist, each of which modulates by antibody treatment or viruses that cause rapid immune suppression and replicate well in macrophages. Consistent in all of these models are data underscoring the importance of monocyte and macrophage activation, infection and accumulation in the CNS. PMID:27544476

  4. Bion 11 mission: primate experiments

    NASA Technical Reports Server (NTRS)

    Ilyin, E. A.; Korolkov, V. I.; Skidmore, M. G.; Viso, M.; Kozlovskaya, I. B.; Grindeland, R. E.; Lapin, B. A.; Gordeev, Y. V.; Krotov, V. P.; Fanton, J. W.; Bielitzki, J. T.; Golov, V. K.; Magedov, V. S.; Hines, J. W.

    2000-01-01

    A summary is provided of the major operations required to conduct the wide range of primate experiments on the Bion 11 mission, which flew for 14 days beginning December 24, 1996. Information is given on preflight preparations, including flight candidate selection and training; attachment and implantation of bioinstrumentation; flight and ground experiment designs; onboard life support and test systems; ground and flight health monitoring; flight monkey selection and transport to the launch site; inflight procedures and data collection; postflight examinations and experiments; and assessment of results.

  5. Bion 11 mission: primate experiments.

    PubMed

    Ilyin, E A; Korolkov, V I; Skidmore, M G; Viso, M; Kozlovskaya, I B; Grindeland, R E; Lapin, B A; Gordeev, Y V; Krotov, V P; Fanton, J W; Bielitzki, J T; Golov, V K; Magedov, V S; Hines, J W

    2000-01-01

    A summary is provided of the major operations required to conduct the wide range of primate experiments on the Bion 11 mission, which flew for 14 days beginning December 24, 1996. Information is given on preflight preparations, including flight candidate selection and training; attachment and implantation of bioinstrumentation; flight and ground experiment designs; onboard life support and test systems; ground and flight health monitoring; flight monkey selection and transport to the launch site; inflight procedures and data collection; postflight examinations and experiments; and assessment of results.

  6. Natural Single-Nucleotide Variations in the HIV-1 Genomic SA1prox Region Can Alter Viral Replication Ability by Regulating Vif Expression Levels

    PubMed Central

    Nomaguchi, Masako; Doi, Naoya; Sakai, Yosuke; Ode, Hirotaka; Iwatani, Yasumasa; Matsumoto, Yui; Miyazaki, Yasuyuki; Masuda, Takao

    2016-01-01

    forces behind mutual evolution. The interplay of cellular APOBEC3G and viral Vif proteins is a typical example. Here, we demonstrate that naturally occurring single-nucleotide variations in the proximal region of splicing acceptor 1 (SA1prox) of the HIV-1 genome frequently alter Vif expression levels, thereby modulating viral replication potential in cells with various ABOBEC3G levels. The results of the present study reveal a previously unidentified and important way for HIV-1 to compete with APOBEC3G restriction by regulating its Vif expression levels. We propose that SA1prox plays a regulatory role in Vif counteraction against APOBEC3G in order to contribute to HIV-1 replication and evolution, and this may be applicable to other primate lentiviruses. PMID:26912631

  7. Pseudotypes of vesicular stomatitis virus with the envelope properties of mammalian and primate retroviruses.

    PubMed

    Schnitzer, T J; Weiss, R A; Zavada, J

    1977-09-01

    By employing improved techniques it has been possible to produce and characterize a representative spectrum of mammalian and primate retrovirus pseudotypes of vesicular stomatitis virus (VSV). Selection of appropriate cell lines for both the production and subsequent detection of the VSV pseudotypes has been the most important factor in permitting their demonstration. The host range for penetration of these retrovirus pseudotypes of VSV has been defined and found to differ from that reported for the replication of the corresponding retroviruses. Additionally, retroviruses having an identical host range for replication were distinguishable by differences in their host range for penetration, implying that restriction of replication may be occurring by different mechanisms. Studies of the plaque-forming efficiency of retrovirus pseudotypes of VSV in cell lines nonpermissive for replication of the corresponding retroviruses permitted a distinction to be made between the restriction of replication occurring as a consequence of postpenetration events and that occurring as a consequence of a block of penetration itself. The demonstration of primate retrovirus pseudotypes of VSV permits the use of VSV as a probe for the detection of this group of viruses. PMID:197255

  8. Noninvasive Test for Tuberculosis Detection among Primates

    PubMed Central

    Mugisha, Lawrence; Shoyama, Fernanda Miyagaki; O’Malley, Melanie J.; Flynn, JoAnne L.; Asiimwe, Benon; Travis, Dominic A.; Singer, Randall S.; Sreevatsan, Srinand

    2015-01-01

    Traditional testing methods have limited epidemiologic studies of tuberculosis among free-living primates. PCR amplification of insertion element IS6110 of Mycobacterium tuberculosis from fecal samples was evaluated as a noninvasive screening test for tuberculosis in primates. Active tuberculosis was detected among inoculated macaques and naturally exposed chimpanzees, demonstrating the utility of this test. PMID:25695329

  9. Who Needs Replication?

    ERIC Educational Resources Information Center

    Porte, Graeme

    2013-01-01

    In this paper, the editor of a recent Cambridge University Press book on research methods discusses replicating previous key studies to throw more light on their reliability and generalizability. Replication research is presented as an accepted method of validating previous research by providing comparability between the original and replicated…

  10. Lentivirus delivery of IL-10 to promote and sustain macrophage polarization towards an anti-inflammatory phenotype.

    PubMed

    Boehler, R M; Kuo, R; Shin, S; Goodman, A G; Pilecki, M A; Gower, R M; Leonard, J N; Shea, L D

    2014-06-01

    Gene delivery from biomaterials can create an environment that promotes and guides tissue formation. However, the immune response induced upon biomaterial implantation can be detrimental to tissue regeneration. Macrophages play a central role in mediating early phases of this response, and functional "polarization" of macrophages towards M1 (inflammatory) or M2 (anti-inflammatory) phenotypes may bias the local immune state at the implant site. Since gene delivery from biomaterial scaffolds can confer transgene expression in macrophages in vivo, we investigated whether transduction of macrophages with an IL-10 encoding lentivirus can (1) induce macrophage polarization toward an M2 phenotype even in an pro-inflammatory environment, and (2) prevent a shift in polarization from M2 to M1 following exposure to pro-inflammatory stimuli. IL-10 lentivirus delivery to pre-polarized M1 macrophages reduced TNF-α production 1.5-fold when compared to cells treated with either a control virus or a bolus delivery of recombinant IL-10 protein. IL-10 lentivirus delivery to naïve macrophages reduced the amount of TNF-α produced following an inflammatory challenge by 2.5-fold compared to cells treated with both the control virus and recombinant IL-10. At a mechanistic level, IL-10 lentivirus delivery mediated sustained reduction in NF-κB activation and, accordingly, reduced transcription of TNF-α. In sum, lentiviral delivery of IL-10 to macrophages represents a promising strategy for directing and sustaining macrophage polarization towards an M2 phenotype in order to promote local immune responses that facilitate tissue engineering.

  11. Toll Like Receptor 9 (TLR9) Polymorphism G520R in Sheep Is Associated with Seropositivity for Small Ruminant Lentivirus

    PubMed Central

    Sarafidou, Theologia; Stamatis, Costas; Kalozoumi, Georgia; Spyrou, Vassiliki; Fthenakis, George C.; Billinis, Charalambos; Mamuris, Zissis

    2013-01-01

    Infectious diseases of sheep are of major economic importance causing direct and indirect losses. Among the major sheep infectious agents are Small Ruminant Lentivirus, Chlamydophila abortus and Mycobacterium avium subsp. paratuberculosis infections, mainly due to their worldwide distribution and economic impact that they cause. Based on the differential susceptibility to infectious diseases between and within breeds and on the recent findings regarding the putative involvement of TLR9 in disease susceptibility, the aim of this study was to evaluate the levels of nucleotide variation of TLR9 and its mediator MyD88 in three sheep flocks originated from different breeds and assess their possible association with seropositivity/seronegativity for different infectious agents. The analysis indicated that the change of G to R at codon 520 of TLR9 polypeptide shows a significant association with Small Ruminant Lentivirus seropositivity. This amino-acid substitution, which can result in polarity change, might influence structure and function of LRR17, interfering with ligand binding and thus could be used in studies investigating susceptibility/resistance to Small Ruminant Lentivirus infections in sheep. PMID:23691111

  12. Cellular Chaperonin CCTγ Contributes to Rabies Virus Replication during Infection

    PubMed Central

    Zhang, Jinyang; Wu, Xiaopeng; Zan, Jie; Wu, Yongping; Ye, Chengjin; Ruan, Xizhen

    2013-01-01

    Rabies, as the oldest known infectious disease, remains a serious threat to public health worldwide. The eukaryotic cytosolic chaperonin TRiC/CCT complex facilitates the folding of proteins through ATP hydrolysis. Here, we investigated the expression, cellular localization, and function of neuronal CCTγ during neurotropic rabies virus (RABV) infection using mouse N2a cells as a model. Following RABV infection, 24 altered proteins were identified by using two-dimensional electrophoresis and mass spectrometry, including 20 upregulated proteins and 4 downregulated proteins. In mouse N2a cells infected with RABV or cotransfected with RABV genes encoding nucleoprotein (N) and phosphoprotein (P), confocal microscopy demonstrated that upregulated cellular CCTγ was colocalized with viral proteins N and P, which formed a hollow cricoid inclusion within the region around the nucleus. These inclusions, which correspond to Negri bodies (NBs), did not form in mouse N2a cells only expressing the viral protein N or P. Knockdown of CCTγ by lentivirus-mediated RNA interference led to significant inhibition of RABV replication. These results demonstrate that the complex consisting of viral proteins N and P recruits CCTγ to NBs and identify the chaperonin CCTγ as a host factor that facilitates intracellular RABV replication. This work illustrates how viruses can utilize cellular chaperonins and compartmentalization for their own benefit. PMID:23637400

  13. Adenovirus DNA Replication

    PubMed Central

    Hoeben, Rob C.; Uil, Taco G.

    2013-01-01

    Adenoviruses have attracted much attention as probes to study biological processes such as DNA replication, transcription, splicing, and cellular transformation. More recently these viruses have been used as gene-transfer vectors and oncolytic agents. On the other hand, adenoviruses are notorious pathogens in people with compromised immune functions. This article will briefly summarize the basic replication strategy of adenoviruses and the key proteins involved and will deal with the new developments since 2006. In addition, we will cover the development of antivirals that interfere with human adenovirus (HAdV) replication and the impact of HAdV on human disease. PMID:23388625

  14. Recombination and Replication

    PubMed Central

    Syeda, Aisha H.; Hawkins, Michelle; McGlynn, Peter

    2014-01-01

    The links between recombination and replication have been appreciated for decades and it is now generally accepted that these two fundamental aspects of DNA metabolism are inseparable: Homologous recombination is essential for completion of DNA replication and vice versa. This review focuses on the roles that recombination enzymes play in underpinning genome duplication, aiding replication fork movement in the face of the many replisome barriers that challenge genome stability. These links have many conserved features across all domains of life, reflecting the conserved nature of the substrate for these reactions, DNA. PMID:25341919

  15. Oligocene primates from China reveal divergence between African and Asian primate evolution.

    PubMed

    Ni, Xijun; Li, Qiang; Li, Lüzhou; Beard, K Christopher

    2016-05-01

    Profound environmental and faunal changes are associated with climatic deterioration during the Eocene-Oligocene transition (EOT) roughly 34 million years ago. Reconstructing how Asian primates responded to the EOT has been hindered by a sparse record of Oligocene primates on that continent. Here, we report the discovery of a diverse primate fauna from the early Oligocene of southern China. In marked contrast to Afro-Arabian Oligocene primate faunas, this Asian fauna is dominated by strepsirhines. There appears to be a strong break between Paleogene and Neogene Asian anthropoid assemblages. Asian and Afro-Arabian primate faunas responded differently to EOT climatic deterioration, indicating that the EOT functioned as a critical evolutionary filter constraining the subsequent course of primate evolution across the Old World. PMID:27151861

  16. The Automated Primate Research Laboratory (APRL)

    NASA Technical Reports Server (NTRS)

    Pace, N.; Smith, G. D.

    1972-01-01

    A description is given of a self-contained automated primate research laboratory to study the effects of weightlessness on subhuman primates. Physiological parameters such as hemodynamics, respiration, blood constituents, waste, and diet and nutrition are analyzed for abnormalities in the simulated space environment. The Southeast Asian pig-tailed monkey (Macaca nemistrina) was selected for the experiments owing to its relative intelligence and learning capacity. The objective of the program is to demonstrate the feasibility of a man-tended primate space flight experiment.

  17. Influence of small ruminant lentivirus infection on cheese yield in goats.

    PubMed

    Nowicka, Dorota; Czopowicz, Michał; Bagnicka, Emilia; Rzewuska, Magdalena; Strzałkowska, Nina; Kaba, Jarosław

    2015-02-01

    Three-year cohort study was carried out to investigate the influence of small ruminant lentivirus (SRLV) infection on cheese yield in goats. For this purpose records of milk yield, milk composition and cheese yield were collected in a dairy goat herd. Cheese yield was recorded as the amount of fresh cheese obtained from 1 kg milk. All goats were serologically tested for SRLV infection twice a year. The analysis included 247 records in total (71 for seropositive and 176 from seronegative individuals) and was carried out with the use of the four-level hierarchical linear model (α = 0·05). SRLV infection proved to be a statistically significant independent factor reducing cheese yield (P = 0·013)--when other covariates were held constant cheese yield was reduced by 4·6 g per each 1 kg milk in an infected goat compared with an uninfected goat. Other statistically significant covariates positively associated with cheese yield were protein contents, fat contents and the 3rd stage of lactation (P < 0·001 for all).

  18. Post-entry blockade of small ruminant lentiviruses by wild ruminants.

    PubMed

    Sanjosé, Leticia; Crespo, Helena; Blatti-Cardinaux, Laure; Glaria, Idoia; Martínez-Carrasco, Carlos; Berriatua, Eduardo; Amorena, Beatriz; De Andrés, Damián; Bertoni, Giuseppe; Reina, Ramses

    2016-01-06

    Small ruminant lentivirus (SRLV) infection causes losses in the small ruminant industry due to reduced animal production and increased replacement rates. Infection of wild ruminants in close contact with infected domestic animals has been proposed to play a role in SRLV epidemiology, but studies are limited and mostly involve hybrids between wild and domestic animals. In this study, SRLV seropositive red deer, roe deer and mouflon were detected through modified ELISA tests, but virus was not successfully amplified using a set of different PCRs. Apparent restriction of SRLV infection in cervids was not related to the presence of neutralizing antibodies. In vitro cultured skin fibroblastic cells from red deer and fallow deer were permissive to the SRLV entry and integration, but produced low quantities of virus. SRLV got rapidly adapted in vitro to blood-derived macrophages and skin fibroblastic cells from red deer but not from fallow deer. Thus, although direct detection of virus was not successfully achieved in vivo, these findings show the potential susceptibility of wild ruminants to SRLV infection in the case of red deer and, on the other hand, an in vivo SRLV restriction in fallow deer. Altogether these results may highlight the importance of surveilling and controlling SRLV infection in domestic as well as in wild ruminants sharing pasture areas, and may provide new natural tools to control SRLV spread in sheep and goats.

  19. Production and neurotropism of lentivirus vectors pseudotyped with lyssavirus envelope glycoproteins.

    PubMed

    Desmaris, N; Bosch, A; Salaün, C; Petit, C; Prévost, M C; Tordo, N; Perrin, P; Schwartz, O; de Rocquigny, H; Heard, J M

    2001-08-01

    We investigated the production efficiency and the gene transfer capacity in the central nervous system of HIV-1-based vectors pseudotyped with either the G protein of the Mokola lyssaviruses (MK-G), a neurotropic virus causing rabies disease, or the vesiculo-stomatitis G protein (VSV-G). Both envelopes induced syncitia in cell cultures. They were incorporated into vector particles and mature virions were observed by electron microscopy. Vector production was two- to sixfold more efficient with VSV-G than with MK-G. For equivalent amounts of physical particles, vector titration was 5- to 25-fold higher with VSV-G than with MK-G pseudotypes on cultured cells, and in vivo gene expression in mouse brain was more intense. Thus, VSV-G pseudotypes were produced more efficiently and were more infectious than MK-G pseudotypes. Tropism for brain cells was analyzed by intrastriatal injections in rats. Both pseudotypes preferentially transduced neurons (70-90% of transduced cells). Retrograde axonal transport was investigated by instilling vector suspensions in the rat nasal cavity. Both pseudotypes were efficiently transported to olfactive neuron bodies. Thus, although coating HIV-1 particles with rabdhovirus envelope glycoproteins enables them to enter neuronal cells efficiently, pseudotyping is not sufficient to confer the powerful neurotropism of lyssaviruses to lentivirus vectors.

  20. Determinants of effective lentivirus-driven microRNA expression in vivo

    PubMed Central

    Mishima, Takuya; Sadovsky, Elena; Gegick, Margaret E.; Sadovsky, Yoel

    2016-01-01

    Manipulation of microRNA (miRNA) levels, including overexpression of mature species, has become an important biological tool, even motivating miRNA-based therapeutics. To assess key determinants of miRNA overexpression in a mammalian system in vivo, we sought to bypass the laborious generation of a transgenic animal by exploiting placental trophoblast-specific gene manipulation using lentiviral vectors, which has been instrumental in elucidating trophoblast biology. We examined the impact of several key components of miRNA stem loops and their flanking sequences on the efficiency of mature miRNA expression in vivo. By combining established and novel approaches for miRNA expression, we engineered lentivirus-driven miRNA expression plasmids, which we tested in the mouse placenta. We found that reverse sense inserts minimized single-strand splicing and degradation, and that maintaining longer, poly-A-containing arms flanking the miRNA stem-loop markedly enhanced transgenic miRNA expression. Additionally, we accomplished overexpression of diverse mammalian, drosophila, or C. elegans miRNAs, either based on native context or using a “cassette” replacement of the mature miRNA sequence. Together, we have identified primary miRNA sequences that are paramount for effective expression of mature miRNAs, and validated their role in mice. Principles established by our findings may guide the design of efficient miRNA vectors for in vivo use. PMID:27627961

  1. Post-entry blockade of small ruminant lentiviruses by wild ruminants.

    PubMed

    Sanjosé, Leticia; Crespo, Helena; Blatti-Cardinaux, Laure; Glaria, Idoia; Martínez-Carrasco, Carlos; Berriatua, Eduardo; Amorena, Beatriz; De Andrés, Damián; Bertoni, Giuseppe; Reina, Ramses

    2016-01-01

    Small ruminant lentivirus (SRLV) infection causes losses in the small ruminant industry due to reduced animal production and increased replacement rates. Infection of wild ruminants in close contact with infected domestic animals has been proposed to play a role in SRLV epidemiology, but studies are limited and mostly involve hybrids between wild and domestic animals. In this study, SRLV seropositive red deer, roe deer and mouflon were detected through modified ELISA tests, but virus was not successfully amplified using a set of different PCRs. Apparent restriction of SRLV infection in cervids was not related to the presence of neutralizing antibodies. In vitro cultured skin fibroblastic cells from red deer and fallow deer were permissive to the SRLV entry and integration, but produced low quantities of virus. SRLV got rapidly adapted in vitro to blood-derived macrophages and skin fibroblastic cells from red deer but not from fallow deer. Thus, although direct detection of virus was not successfully achieved in vivo, these findings show the potential susceptibility of wild ruminants to SRLV infection in the case of red deer and, on the other hand, an in vivo SRLV restriction in fallow deer. Altogether these results may highlight the importance of surveilling and controlling SRLV infection in domestic as well as in wild ruminants sharing pasture areas, and may provide new natural tools to control SRLV spread in sheep and goats. PMID:26738942

  2. Efficient generation of transgenic mice by lentivirus-mediated modification of spermatozoa.

    PubMed

    Chandrashekran, Anil; Sarkar, Rupa; Thrasher, Adrian; Fraser, Scott E; Dibb, Nicholas; Casimir, Colin; Winston, Robert; Readhead, Carol

    2014-02-01

    Transgenic technologies conventionally rely on the oocyte as a substrate for genetic modification. Owing to their accessibility, however, male germ cells, including mature sperm, have material advantages for use in transgenesis. Here we have exploited lentiviruses to generate transgenic animals via the male germline. When pseudotyped lentiviral vectors encoding green fluorescent protein (GFP) were incubated with mouse spermatozoa, these sperm were highly successful in producing transgenics. Lentivirally transduced mouse spermatozoa were used in in vitro fertilization (IVF) studies, and when followed by embryo transfer, ≥ 42% of founders were found to be transgenic for GFP. Inverse PCR strategy for integration site analysis demonstrated integration of at least 1 or 2 copies of GFP in the transgenics, mapping to different chromosomes. GFP expression was detected in a wide range of murine tissues, including testis and the transgene was stably transmitted to a third generation of transgenic animals. This relatively simple, yet highly efficient, technique for generating transgenic animals by transducing spermatozoa with lentiviral vectors in vitro is a powerful tool for the study of fertilization/preimplantation development, vertical viral gene transmission, gene function and regulation, and epigenetic inheritance. PMID:24297703

  3. Influence of small ruminant lentivirus infection on cheese yield in goats.

    PubMed

    Nowicka, Dorota; Czopowicz, Michał; Bagnicka, Emilia; Rzewuska, Magdalena; Strzałkowska, Nina; Kaba, Jarosław

    2015-02-01

    Three-year cohort study was carried out to investigate the influence of small ruminant lentivirus (SRLV) infection on cheese yield in goats. For this purpose records of milk yield, milk composition and cheese yield were collected in a dairy goat herd. Cheese yield was recorded as the amount of fresh cheese obtained from 1 kg milk. All goats were serologically tested for SRLV infection twice a year. The analysis included 247 records in total (71 for seropositive and 176 from seronegative individuals) and was carried out with the use of the four-level hierarchical linear model (α = 0·05). SRLV infection proved to be a statistically significant independent factor reducing cheese yield (P = 0·013)--when other covariates were held constant cheese yield was reduced by 4·6 g per each 1 kg milk in an infected goat compared with an uninfected goat. Other statistically significant covariates positively associated with cheese yield were protein contents, fat contents and the 3rd stage of lactation (P < 0·001 for all). PMID:25499464

  4. Determinants of effective lentivirus-driven microRNA expression in vivo.

    PubMed

    Mishima, Takuya; Sadovsky, Elena; Gegick, Margaret E; Sadovsky, Yoel

    2016-01-01

    Manipulation of microRNA (miRNA) levels, including overexpression of mature species, has become an important biological tool, even motivating miRNA-based therapeutics. To assess key determinants of miRNA overexpression in a mammalian system in vivo, we sought to bypass the laborious generation of a transgenic animal by exploiting placental trophoblast-specific gene manipulation using lentiviral vectors, which has been instrumental in elucidating trophoblast biology. We examined the impact of several key components of miRNA stem loops and their flanking sequences on the efficiency of mature miRNA expression in vivo. By combining established and novel approaches for miRNA expression, we engineered lentivirus-driven miRNA expression plasmids, which we tested in the mouse placenta. We found that reverse sense inserts minimized single-strand splicing and degradation, and that maintaining longer, poly-A-containing arms flanking the miRNA stem-loop markedly enhanced transgenic miRNA expression. Additionally, we accomplished overexpression of diverse mammalian, drosophila, or C. elegans miRNAs, either based on native context or using a "cassette" replacement of the mature miRNA sequence. Together, we have identified primary miRNA sequences that are paramount for effective expression of mature miRNAs, and validated their role in mice. Principles established by our findings may guide the design of efficient miRNA vectors for in vivo use. PMID:27627961

  5. Feline immunodeficiency virus and puma lentivirus in Florida panthers (Puma concolor coryi): epidemiology and diagnostic issues.

    PubMed

    Miller, D L; Taylor, S K; Rotstein, D S; Pough, M B; Barr, M C; Baldwin, C A; Cunningham, M; Roelke, M; Ingram, D

    2006-04-01

    This study documents the seroprevalence of feline immunodeficiency virus (FIV) and puma lentivirus (PLV) in free-ranging and captive Florida panthers (Puma concolor coryi) (n = 51) and translocated Texas cougars (P. concolor stanleyana) (n = 10) from 1985 to 1998. The sera were tested for anti-FIV antibodies by enzyme-linked immunosorbent assay (ELISA) and Western blot tests. The ELISAs were read kinetically (KELA) and the sera were retrospectively examined by PLV peptide ELISA. Eleven panthers and one cougar were positive by KELA; 4 panthers and 4 cougars were equivocal; 35 panthers and 5 cougars were negative; and 1 panther had no data. Seven of the 11 KELA-positive panthers were also positive by Western blot tests and all but one were positive by PLV peptide ELISA. Ten KELA-negative and Western blot-negative cats, were positive by PLV peptide ELISA. KELA results varied within cats from one sample period to the next, but PLV peptide ELISA results were consistent. Territorial sympatry and mating behaviour, noted from radiotelemetry location data on the cats, may have contributed to viral transmission between seropositive animals. These findings suggest that Florida panthers and the introduced Texas cougars have been exposed to FIV and/or PLV.

  6. Retroviral Infections in Sheep and Goats: Small Ruminant Lentiviruses and Host Interaction

    PubMed Central

    Larruskain, Amaia; Jugo, Begoña M.

    2013-01-01

    Small ruminant lentiviruses (SRLV) are members of the Retrovirus family comprising the closely related Visna/Maedi Virus (VMV) and the Caprine Arthritis-Encephalitis Virus (CAEV), which infect sheep and goats. Both infect cells of the monocyte/macrophage lineage and cause lifelong infections. Infection by VMV and CAEV can lead to Visna/Maedi (VM) and Caprine Arthritis-Encephalitis (CAE) respectively, slow progressive inflammatory diseases primarily affecting the lungs, nervous system, joints and mammary glands. VM and CAE are distributed worldwide and develop over a period of months or years, always leading to the death of the host, with the consequent economic and welfare implications. Currently, the control of VM and CAE relies on the control of transmission and culling of infected animals. However, there is evidence that host genetics play an important role in determining Susceptibility/Resistance to SRLV infection and disease progression, but little work has been performed in small ruminants. More research is necessary to understand the host-SRLV interaction. PMID:23965529

  7. Lentivirus-mediated silencing of MPHOSPH8 inhibits MTC proliferation and enhances apoptosis

    PubMed Central

    LI, PEIYONG; YANG, WEIPING; SHEN, BAIYONG; LI, HONGWEI; YAN, JIQI

    2016-01-01

    Thyroid carcinoma (TC) is the most common malignancy of the endocrine organs, and its incidence rate has steadily increased over the last decade. For medullary thyroid cancer (MTC), a type of TC, a high mortality rate has been reported. In previous studies, M-phase phosphoprotein 8 (MPHOSPH8) displayed an elevated expression in various human carcinoma cells. Thus, MPHOSPH8 may be a sensitive biomarker that could be used for the diagnosis and follow-up of MTC. In the present study, plasmids of RNA interference targeting the MPHOSPH8 gene were constructed. Once these lentiviruses targeting MPHOSPH8 were transfected into the MTC cell line TT, cell viability and proliferation were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometry was used to assess the cell cycle distribution and apoptosis. The expression levels of MPHOSPH8 were detected by reverse transcription quantitative-polymerase chain reaction and western blot analyses. Depletion of MPHOSPH8 significantly inhibited cell proliferation. Furthermore, knockdown of MPHOSPH8 in TT cells led to G0/G1 phase cell cycle arrest and apoptosis. The results of the present study suggest that MPHOSPH8 promotes cell proliferation and may be a potential target for anticancer therapy of MTC. PMID:27313751

  8. Modeling DNA Replication.

    ERIC Educational Resources Information Center

    Bennett, Joan

    1998-01-01

    Recommends the use of a model of DNA made out of Velcro to help students visualize the steps of DNA replication. Includes a materials list, construction directions, and details of the demonstration using the model parts. (DDR)

  9. Abiotic self-replication.

    PubMed

    Meyer, Adam J; Ellefson, Jared W; Ellington, Andrew D

    2012-12-18

    The key to the origins of life is the replication of information. Linear polymers such as nucleic acids that both carry information and can be replicated are currently what we consider to be the basis of living systems. However, these two properties are not necessarily coupled. The ability to mutate in a discrete or quantized way, without frequent reversion, may be an additional requirement for Darwinian evolution, in which case the notion that Darwinian evolution defines life may be less of a tautology than previously thought. In this Account, we examine a variety of in vitro systems of increasing complexity, from simple chemical replicators up to complex systems based on in vitro transcription and translation. Comparing and contrasting these systems provides an interesting window onto the molecular origins of life. For nucleic acids, the story likely begins with simple chemical replication, perhaps of the form A + B → T, in which T serves as a template for the joining of A and B. Molecular variants capable of faster replication would come to dominate a population, and the development of cycles in which templates could foster one another's replication would have led to increasingly complex replicators and from thence to the initial genomes. The initial genomes may have been propagated by RNA replicases, ribozymes capable of joining oligonucleotides and eventually polymerizing mononucleotide substrates. As ribozymes were added to the genome to fill gaps in the chemistry necessary for replication, the backbone of a putative RNA world would have emerged. It is likely that such replicators would have been plagued by molecular parasites, which would have been passively replicated by the RNA world machinery without contributing to it. These molecular parasites would have been a major driver for the development of compartmentalization/cellularization, as more robust compartments could have outcompeted parasite-ridden compartments. The eventual outsourcing of metabolic

  10. Abiotic self-replication.

    PubMed

    Meyer, Adam J; Ellefson, Jared W; Ellington, Andrew D

    2012-12-18

    The key to the origins of life is the replication of information. Linear polymers such as nucleic acids that both carry information and can be replicated are currently what we consider to be the basis of living systems. However, these two properties are not necessarily coupled. The ability to mutate in a discrete or quantized way, without frequent reversion, may be an additional requirement for Darwinian evolution, in which case the notion that Darwinian evolution defines life may be less of a tautology than previously thought. In this Account, we examine a variety of in vitro systems of increasing complexity, from simple chemical replicators up to complex systems based on in vitro transcription and translation. Comparing and contrasting these systems provides an interesting window onto the molecular origins of life. For nucleic acids, the story likely begins with simple chemical replication, perhaps of the form A + B → T, in which T serves as a template for the joining of A and B. Molecular variants capable of faster replication would come to dominate a population, and the development of cycles in which templates could foster one another's replication would have led to increasingly complex replicators and from thence to the initial genomes. The initial genomes may have been propagated by RNA replicases, ribozymes capable of joining oligonucleotides and eventually polymerizing mononucleotide substrates. As ribozymes were added to the genome to fill gaps in the chemistry necessary for replication, the backbone of a putative RNA world would have emerged. It is likely that such replicators would have been plagued by molecular parasites, which would have been passively replicated by the RNA world machinery without contributing to it. These molecular parasites would have been a major driver for the development of compartmentalization/cellularization, as more robust compartments could have outcompeted parasite-ridden compartments. The eventual outsourcing of metabolic

  11. DNA replication origins.

    PubMed

    Leonard, Alan C; Méchali, Marcel

    2013-10-01

    The onset of genomic DNA synthesis requires precise interactions of specialized initiator proteins with DNA at sites where the replication machinery can be loaded. These sites, defined as replication origins, are found at a few unique locations in all of the prokaryotic chromosomes examined so far. However, replication origins are dispersed among tens of thousands of loci in metazoan chromosomes, thereby raising questions regarding the role of specific nucleotide sequences and chromatin environment in origin selection and the mechanisms used by initiators to recognize replication origins. Close examination of bacterial and archaeal replication origins reveals an array of DNA sequence motifs that position individual initiator protein molecules and promote initiator oligomerization on origin DNA. Conversely, the need for specific recognition sequences in eukaryotic replication origins is relaxed. In fact, the primary rule for origin selection appears to be flexibility, a feature that is modulated either by structural elements or by epigenetic mechanisms at least partly linked to the organization of the genome for gene expression.

  12. Replication of lightweight mirrors

    NASA Astrophysics Data System (ADS)

    Chen, Ming Y.; Matson, Lawrence E.; Lee, Heedong; Chen, Chenggang

    2009-08-01

    The fabrication of lightweight mirror assemblages via a replication technique offers great potential for eliminating the high cost and schedule associated with the grinding and polishing steps needed for conventional glass or SiC mirrors. A replication mandrel is polished to an inverse figure shape and to the desired finish quality. It is then, coated with a release layer, the appropriate reflective layer, and followed by a laminate for coefficient of thermal expansion (CTE) tailorability and strength. This optical membrane is adhered to a mirror structural substrate with a low shrinkage, CTE tailored adhesive. Afterwards, the whole assembly is separated from the mandrel. The mandrel is then cleaned and reused for the next replication run. The ultimate goal of replication is to preserve the surface finish and figure of the optical membrane upon its release from the mandrel. Successful replication requires a minimization of the residual stresses within the optical coating stack, the curing stresses from the adhesive and the thermal stress resulting from CTE mismatch between the structural substrate, the adhesive, and the optical membrane. In this paper, the results on replicated trials using both metal/metal and ceramic/ceramic laminates adhered to light weighted structural substrates made from syntactic foams (both inorganic and organic) will be discussed.

  13. Biokinetics of Plutonium in Nonhuman Primates.

    PubMed

    Poudel, Deepesh; Guilmette, Raymond A; Gesell, Thomas F; Harris, Jason T; Brey, Richard R

    2016-10-01

    A major source of data on metabolism, excretion and retention of plutonium comes from experimental animal studies. Although old world monkeys are one of the closest living relatives to humans, certain physiological differences do exist between these nonhuman primates and humans. The objective of this paper was to describe the metabolism of plutonium in nonhuman primates using the bioassay and retention data obtained from macaque monkeys injected with plutonium citrate. A biokinetic model for nonhuman primates was developed by adapting the basic model structure and adapting the transfer rates described for metabolism of plutonium in adult humans. Significant changes to the parameters were necessary to explain the shorter retention of plutonium in liver and skeleton of the nonhuman primates, differences in liver to bone partitioning ratio, and significantly higher excretion of plutonium in feces compared to that in humans. PMID:27575347

  14. Polyomaviruses of Nonhuman Primates: Implications for Research

    PubMed Central

    Simon, Meredith A

    2008-01-01

    Polyomaviruses are a family of small nonenveloped DNA viruses that infect birds and mammals. At least 7 nonhuman primate polyomaviruses that occur in macaques, African green monkeys, marmosets baboons, and chimpanzees have been described, as well as 4 polyomaviruses that occur in humans. Simian virus 40 (SV40), which infects macaques, was the first nonhuman primate polyomavirus identified as a contaminant of early polio vaccines. Primate polyomaviruses cause inapparent primary infections but persist in the host and can cause severe disease in situations of immunocompromise. This review describes the primate polyomaviruses, and the diseases associated with the viruses of macaques. In macaques, the greatest current concerns are the potential confounding of study results by polyomavirus infections and the zoonotic potential of SV40. PMID:19793457

  15. Exposure to Nonhuman Primates in Rural Cameroon

    PubMed Central

    Prosser, A. Tassy; Carr, Jean K.; Tamoufe, Ubald; Mpoudi-Ngole, Eitel; Torimiro, J. Ndongo; LeBreton, Matthew; McCutchan, Francine E.; Birx, Deborah L.; Burke, Donald S.

    2004-01-01

    Exposure to nonhuman primates has led to the emergence of important diseases, including Ebola hemorrhagic fever, AIDS, and adult T-cell leukemia. To determine the extent of exposure to nonhuman primates, persons were examined in 17 remote villages in Cameroon that represented three habitats (savanna, gallery forest, and lowland forest). Questionnaire data were collected to assess whether persons kept wild animal pets; hunted and butchered wild game; had experienced bites, scratches, or injuries from live animals; or had been injured during hunting or butchering. While all villages had substantial exposure to nonhuman primates, higher rates of exposure were seen in lowland forest sites. The study demonstrates that exposure is not limited to small groups of hunters. A high percentage of rural villagers report exposure to nonhuman primate blood and body fluids and risk acquiring infectious diseases. PMID:15663844

  16. Biokinetics of Plutonium in Nonhuman Primates.

    PubMed

    Poudel, Deepesh; Guilmette, Raymond A; Gesell, Thomas F; Harris, Jason T; Brey, Richard R

    2016-10-01

    A major source of data on metabolism, excretion and retention of plutonium comes from experimental animal studies. Although old world monkeys are one of the closest living relatives to humans, certain physiological differences do exist between these nonhuman primates and humans. The objective of this paper was to describe the metabolism of plutonium in nonhuman primates using the bioassay and retention data obtained from macaque monkeys injected with plutonium citrate. A biokinetic model for nonhuman primates was developed by adapting the basic model structure and adapting the transfer rates described for metabolism of plutonium in adult humans. Significant changes to the parameters were necessary to explain the shorter retention of plutonium in liver and skeleton of the nonhuman primates, differences in liver to bone partitioning ratio, and significantly higher excretion of plutonium in feces compared to that in humans.

  17. The use of nonhuman primates in space

    NASA Technical Reports Server (NTRS)

    Simmonds, R. C. (Editor); Bourne, G. H. (Editor)

    1977-01-01

    Space related biomedical research involving nonhuman primates is reviewed. The scientific assets of various species and the instruments used for monitoring physiological processes during long duration experimentations are described.

  18. Correlates of body mass evolution in primates.

    PubMed

    Soligo, Christophe

    2006-07-01

    Body mass is undoubtedly central to the overall adaptive profile of any organism. Despite this, very little is known of what forces drive evolutionary changes in body mass and, consequently, shape patterns of body mass distribution exhibited by animal radiations. The search for factors that may influence evolutionary processes in general frequently focuses on environmental parameters such as climate change or interspecific competition. With respect to body mass, there is also the suggestion that evolutionary lineages may follow an inherent trend toward increased body mass, known as Cope's rule. The present paper investigates whether overall directional trends of body mass change, or correlations between patterns of body mass evolution and environmental factors have influenced the evolution of body mass in plesiadapiforms and primates. Analyses of the global fossil record of plesiadapiforms and primates suggest that the former did indeed follow an overall trend toward increased body mass compatible with the predictions of Cope's rule. In contrast, neither primates as a whole, nor a number of individual primate radiations (Adapiformes, Omomyiformes, and Anthropoidea), show any indication of overall directional patterns of body mass change. No correlations of primate body mass change with either the latitudinal distribution of fossil species, or with estimates of global temperature trends, were found. There is evidence, however, that direct competition between omomyiforms and adapiforms (the two main primate radiations known from the Paleogene) influenced processes of body mass evolution in omomyiforms.

  19. Ontogeny of the nasopalatine duct in primates.

    PubMed

    Shimp, Kristin L; Bhatnagar, Kunwar P; Bonar, Christopher J; Smith, Timothy D

    2003-09-01

    Ecological explanations have been put forward to account for the precocious or delayed development of patency in ducts leading to the vomeronasal organ (VNO) in certain mammals. Perinatal function may be related, in part, to the patency or fusion of the vomeronasal and nasopalatine (NPD) ducts. However, few studies have focused on NPD development in primates, which generally have a prolonged period of dependence during infancy. In this study we examined 24 prenatal primates and 13 neonatal primates, and a comparative sample of fetal mice and insectivores. In embryonic and early fetal Microcebus murinus, the NPD was completely fused, whereas in fetuses of later stages the duct was partially fused or completely patent. M. myoxinus of all stages demonstrated some degree of NPD fusion. In all other prenatal primates, the NPD was fused to some extent. Four prenatal insectivores (Tenrec ecaudatus) showed some degree of NPD fusion. In Mus musculus at 19 days gestation, the NPD was patent, although the anatomically separate VNO duct was fused. T. ecaudatus and most of the neonatal primates revealed complete NPD patency. An exception was Saguinus geoffroyi, which exhibited fusion of the NPD near the VNO opening. These observations may relate to differences in perinatal VNO function. The differences noted in our study suggest that M. murinus and M. myoxinus may differ in perinatal VNO functionality and perhaps in related behavior. Observations of neonatal primates suggest that NPD patency may be relatively common at birth and could serve other purposes in addition to being an access route for VNO stimuli.

  20. Forest structure drives global diversity of primates.

    PubMed

    Gouveia, Sidney F; Villalobos, Fabricio; Dobrovolski, Ricardo; Beltrão-Mendes, Raone; Ferrari, Stephen F

    2014-11-01

    Geographic gradients in the species richness of non-human primates have traditionally been attributed to the variation in forest productivity (related to precipitation levels), although an all-inclusive, global-scale analysis has never been conducted. We perform a more comprehensive test on the role of precipitation and biomass production and propose an alternative hypothesis - the variation in vertical structure of forest habitats as measured by forest canopy height - in determining primate species richness on a global scale. Considering the potential causal relationships among precipitation, productivity and forest structure, we arranged these variables within a path framework to assess their direct and indirect associations with the pattern of primate species richness using structural equation modelling. The analysis also accounted for the influence of spatial autocorrelation in the relationships and assessed possible historical differences among biogeographical regions. The path coefficients indicate that forest canopy height (used as a proxy for vertical forest structure) is a better predictor of primate species richness than either precipitation or productivity on both global and continental scales. The only exception was Asia, where precipitation prevailed, albeit independently from productivity or forest structure. The influence of spatially structured processes varied markedly among biogeographical regions. Our results challenge the traditional rainfall-based viewpoint in favour of forest distribution and structure as primary drivers of primate species richness, which aggregate potential effects from both climatic factors and habitat complexity. These findings may support predictions of the impact of forest removal on primate species richness.

  1. Modeling DNA Replication Intermediates

    SciTech Connect

    Broyde, S.; Roy, D.; Shapiro, R.

    1997-06-01

    While there is now available a great deal of information on double stranded DNA from X-ray crystallography, high resolution NMR and computer modeling, very little is known about structures that are representative of the DNA core of replication intermediates. DNA replication occurs at a single strand/double strand junction and bulged out intermediates near the junction can lead to frameshift mutations. The single stranded domains are particularly challenging. Our interest is focused on strategies for modeling the DNA of these types of replication intermediates. Modeling such structures presents special problems in addressing the multiple minimum problem and in treating the electrostatic component of the force field. We are testing a number of search strategies for locating low energy structures of these types and we are also investigating two different distance dependent dielectric functions in the coulombic term of the force field. We are studying both unmodified DNA and DNA damaged by aromatic amines, carcinogens present in the environment in tobacco smoke, barbecued meats and automobile exhaust. The nature of the structure adopted by the carcinogen modified DNA at the replication fork plays a key role in determining whether the carcinogen will cause a mutation during replication that can initiate the carcinogenic process. In the present work results are presented for unmodified DNA.

  2. Lentivirus-mediated PGC-1α overexpression protects against traumatic spinal cord injury in rats.

    PubMed

    Hu, Jianzhong; Lang, Ye; Zhang, Tao; Ni, Shuangfei; Lu, Hongbin

    2016-07-22

    Peroxisome proliferator-activated receptor-γ coactivator-1 alpha (PGC-1α) is a crucial neuronal regulator in the brain. However, its role in the spinal cord and the underlying regulating mechanisms remain poorly understood. Our previous study demonstrated that PGC-1α is significantly down-regulated following acute spinal cord injury (SCI) in rats. The current study aimed to explore the effects of PGC-1α overexpression on the injured spinal cord by establishing a contusive SCI model in adult Sprague-Dawley rats, followed by immediate intraspinal injection of lentiviral vectors at rostral and caudal sites 3mm from the lesion epicenter. Hindlimb motor function was monitored using the Basso-Beattie-Bresnahan Locomotor Rating Scale (BBB scores), and cords were collected. Transfection efficiency analysis showed that lentivirus successfully induced enhanced PGC-1α expression. This resulted in attenuated apoptotic changes and a greater number of surviving spinal neurons, as determined by transmission electron microscopy and Nissl staining, respectively. Western blot and immunofluorescence analyses revealed increased growth-associated protein 43 and 5-hydroxytryptamine expression, two key markers of axonal regeneration. Importantly, BBB scores showed improved hindlimb motor functional recovery. Moreover, quantitative real-time polymerase chain reaction analysis demonstrated significantly inhibited RhoA, ROCK1, and ROCK2 mRNA expression, revealing a potential mechanism of PGC-1α overexpression following traumatic SCI. Altogether, these results suggest that gene delivery of PGC-1α exerts a significant neuroprotective effect following traumatic SCI, which could serve as a promising treatment for repair of the injured cord, and RhoA-ROCK pathway inhibition may partially underlie this neuroprotection. PMID:27132229

  3. Low proviral small ruminant lentivirus load as biomarker of natural restriction in goats.

    PubMed

    Crespo, Helena; Bertolotti, Luigi; Proffiti, Margherita; Cascio, Paolo; Cerruti, Fulvia; Acutis, Pier Luigi; de Andrés, Damián; Reina, Ramsés; Rosati, Sergio

    2016-08-30

    Small ruminant lentiviruses (SRLV) globally affect welfare and production of sheep and goats and are mainly controlled through elimination of infected animals, independently of the viral kinetics within the single animal. Control programs are based on highly sensitive serological tests, however the existence of low antibody responders leads to the permanent presence of seronegative infected animals in the flock, thus perpetuating the infection. On the other hand, long-term non-progressors show a detectable antibody response not indicative of a shedding animal, suggesting immune contention of infection. In this study, we analyse two goat populations within the same herd, harbouring low or high proviral SRLV loads respectively, both showing a robust antibody response. In vivo findings were confirmed in vitro since fibroblastic cell lines obtained from one high and one low proviral load representative goats, showed respectively a high and a faint production of virus upon infection with reference and field circulating SRLV strains. Differences in virus production were relieved when strain CAEV-Co was used for experimental infection. We analysed LTR promoter activity, proviral load, entry step and production of virus and viral proteins. Intriguingly, proteasomal activity was higher in fibroblasts from low proviral load animals and proteasome inhibition increased viral production in both cell lines, suggesting the implication of active proteasome-dependent restriction factors. Among them, we analysed relative expression and sequences of TRIM5α, APOBEC3 (Z1, Z2, Z3 and Z2-Z3) and BST-2 (Tetherin) and found a global antiviral status in low proviral carriers that may confer protection against viral shedding and disease onset. PMID:27527777

  4. Small ruminant lentivirus genetic subgroups associate with sheep TMEM154 genotypes

    PubMed Central

    2013-01-01

    Small ruminant lentiviruses (SRLVs) are prevalent in North American sheep and a major cause of production losses for the U.S. sheep industry. Sheep susceptibility to SRLV infection is influenced by genetic variation within the ovine transmembrane 154 gene (TMEM154). Animals with either of two distinct TMEM154 haplotypes that both encode glutamate at position 35 of the protein (E35) are at greater risk of SRLV infection than those homozygous with a lysine (K35) haplotype. Prior to this study, it was unknown if TMEM154 associations with infection are influenced by SRLV genetic subgroups. Accordingly, our goals were to characterize SRLVs naturally infecting sheep from a diverse U.S. Midwestern flock and test them for associations with TMEM154 E35K genotypes. Two regions of the SRLV genome were targeted for proviral amplification, cloning, sequence analysis, and association testing with TMEM154 E35K genotypes: gag and the transmembrane region of env. Independent analyses of gag and env sequences showed that they clustered in two subgroups (1 and 2), they were distinct from SRLV subtypes originating from Europe, and that subgroup 1 associated with hemizygous and homozygous TMEM154 K35 genotypes and subgroup 2 with hemi- and homozygous E35 genotypes (gag p < 0.001, env p = 0.01). These results indicate that SRLVs in the U.S. have adapted to infect sheep with specific TMEM154 E35K genotypes. Consequently, both host and SRLV genotypes affect the relative risk of SRLV infection in sheep. PMID:23895262

  5. A Polytropic Caprine Arthritis Encephalitis Virus Promoter Isolated from Multiple Tissues from a Sheep with Multisystemic Lentivirus-Associated Inflammatory Disease

    PubMed Central

    Adedeji, Adeyemi O.; Barr, Bradd; Gomez-Lucia, Esperanza; Murphy, Brian

    2013-01-01

    Caprine arthritis encephalitis virus (CAEV) is a lentivirus that infects both goats and sheep and is closely related to maedi-visna virus that infects sheep; collectively, these viruses are known as small ruminant lentiviruses (SRLV). Infection of goats and sheep with SRLV typically results in discrete inflammatory diseases which include arthritis, mastitis, pneumonia or encephalomyelitis. SRLV-infected animals concurrently demonstrating lentivirus-associated lesions in tissues of lung, mammary gland, joint synovium and the central nervous system are either very rare or have not been reported. Here we describe a novel CAEV promoter isolated from a sheep with multisystemic lentivirus-associated inflammatory disease including interstitial pneumonia, mastitis, polyarthritis and leukomyelitis. A single, novel SRLV promoter was cloned and sequenced from five different anatomical locations (brain stem, spinal cord, lung, mammary gland and carpal joint synovium), all of which demonstrated lesions characteristic of lentivirus associated inflammation. This SRLV promoter isolate was found to be closely related to CAEV promoters isolated from goats in northern California and other parts of the world. The promoter was denoted CAEV-ovine-MS (multisystemic disease); the stability of the transcription factor binding sites within the U3 promoter sequence are discussed. PMID:23955501

  6. Primate genotyping via high resolution melt analysis: rapid and reliable identification of color vision status in wild lemurs.

    PubMed

    Jacobs, Rachel L; Spriggs, Amanda N; MacFie, Tammie S; Baden, Andrea L; Irwin, Mitchell T; Wright, Patricia C; Louis, Edward E; Lawler, Richard R; Mundy, Nicholas I; Bradley, Brenda J

    2016-10-01

    Analyses of genetic polymorphisms can aid our understanding of intra- and interspecific variation in primate sociality, ecology, and behavior. Studies of primate opsin genes are prime examples of this, as single nucleotide variants (SNVs) in the X-linked opsin gene underlie variation in color vision. For primate species with polymorphic trichromacy, genotyping opsin SNVs can generally indicate whether individual primates are red-green color-blind (denoted homozygous M or homozygous L) or have full trichromatic color vision (heterozygous ML). Given the potential influence of color vision on behavior and fitness, characterizing the color vision status of study subjects is becoming commonplace for many primate field projects. Such studies traditionally involve a multi-step sequencing-based method that can be costly and time-consuming. Here we present a new reliable, rapid, and relatively inexpensive method for characterizing color vision in primate populations using high resolution melt analysis (HRMA). Using lemurs as a case study, we characterized variation at exons 3 and/or 5 of the X-linked opsin gene for 87 individuals representing nine species. We scored opsin genotypes and color vision status using both traditional sequencing-based methods as well as our novel melting-curve based HRMA protocol. For each species, the melting curves of varying genotypes (homozygous M, homozygous L, heterozygous ML) differed in melting temperature and/or shape. Melting curves for each sample were consistent across replicates, and genotype-specific melting curves were consistent across DNA sources (blood vs. feces). We show that opsin genotypes can be quickly and reliably scored using HRMA once lab-specific reference curves have been developed based on known genotypes. Although the protocol presented here focuses on genotyping lemur opsin loci, we also consider the larger potential for applying this approach to various types of genetic studies of primate populations. PMID:27271303

  7. Primate genotyping via high resolution melt analysis: rapid and reliable identification of color vision status in wild lemurs.

    PubMed

    Jacobs, Rachel L; Spriggs, Amanda N; MacFie, Tammie S; Baden, Andrea L; Irwin, Mitchell T; Wright, Patricia C; Louis, Edward E; Lawler, Richard R; Mundy, Nicholas I; Bradley, Brenda J

    2016-10-01

    Analyses of genetic polymorphisms can aid our understanding of intra- and interspecific variation in primate sociality, ecology, and behavior. Studies of primate opsin genes are prime examples of this, as single nucleotide variants (SNVs) in the X-linked opsin gene underlie variation in color vision. For primate species with polymorphic trichromacy, genotyping opsin SNVs can generally indicate whether individual primates are red-green color-blind (denoted homozygous M or homozygous L) or have full trichromatic color vision (heterozygous ML). Given the potential influence of color vision on behavior and fitness, characterizing the color vision status of study subjects is becoming commonplace for many primate field projects. Such studies traditionally involve a multi-step sequencing-based method that can be costly and time-consuming. Here we present a new reliable, rapid, and relatively inexpensive method for characterizing color vision in primate populations using high resolution melt analysis (HRMA). Using lemurs as a case study, we characterized variation at exons 3 and/or 5 of the X-linked opsin gene for 87 individuals representing nine species. We scored opsin genotypes and color vision status using both traditional sequencing-based methods as well as our novel melting-curve based HRMA protocol. For each species, the melting curves of varying genotypes (homozygous M, homozygous L, heterozygous ML) differed in melting temperature and/or shape. Melting curves for each sample were consistent across replicates, and genotype-specific melting curves were consistent across DNA sources (blood vs. feces). We show that opsin genotypes can be quickly and reliably scored using HRMA once lab-specific reference curves have been developed based on known genotypes. Although the protocol presented here focuses on genotyping lemur opsin loci, we also consider the larger potential for applying this approach to various types of genetic studies of primate populations.

  8. Avian Retroviral Replication

    PubMed Central

    Justice, James; Beemon, Karen L.

    2013-01-01

    Avian retroviruses have undergone intense study since the beginning of the 20th century. They were originally identified as cancer-inducing filterable agents in chicken neoplasms. Since their discovery, the study of these simple retroviruses has contributed greatly to our understanding of retroviral replication and cancer. Avian retroviruses are continuing to evolve and have great economic importance in the poultry industry worldwide. The aim of this review is to provide a broad overview of the genome, pathology, and replication of avian retroviruses. Notable gaps in our current knowledge are highlighted, and areas where avian retroviruses differ from other retrovirus are also emphasized. PMID:24011707

  9. Replicated Composite Optics Development

    NASA Technical Reports Server (NTRS)

    Engelhaupt, Darell

    1997-01-01

    Advanced optical systems for applications such as grazing incidence Wolter I x-ray mirror assemblies require extraordinary mirror surfaces in ten-ns of fine surface finish and figure. The impeccable mirror surface is on the inside of the rotational mirror form. One practical method of producing devices with these requirements is to first fabricate an exterior surface for the optical device then replicate that surface to have the inverse component with lightweight characteristics. The replicate optic is not better than the master or mandrel from which it is made. This task is a continuance of previous studies to identify methods and materials for forming these extremely low roughness optical components.

  10. Construction of p66Shc gene interfering lentivirus vectors and its effects on alveolar epithelial cells apoptosis induced by hyperoxia

    PubMed Central

    Zhang, Chan; Dong, Wen-Bin; Zhao, Shuai; Li, Qing-Ping; Kang, Lan; Lei, Xiao-Ping; Guo, Lin; Zhai, Xue-Song

    2016-01-01

    Background The aim of this study is to observe the inhibitive effects of p66Shc gene interfering lentivirus vectors on the expression of p66Shc, and to explore its effects on alveolar epithelial cells apoptosis induced by hyperoxia. Methods The gene sequences were cloned into the pLenR-GPH-shRNA lentiviral vector, which was selected by Genebank searches. The pLenR-GPH-shRNA and lentiviral vector packaging plasmid mix were cotransfected into 293T cells to package lentiviral particles. Culture virus supernatant was harvested, and then the virus titer was determined by serial dilution assay. A549 cells were transduced with the constructed lentiviral vectors, and real-time polymerase chain reaction (RT-PCR) and Western blot were used to evaluate p66Shc expression. This study is divided into a control group, a hyperoxia group, an A549-p66ShcshRNA hyperoxia group, and a negative lentivirus group. Cell apoptosis was detected by flow cytometry after 24 hours; the expression of X-linked inhibitor of apoptosis protein (XIAP) and caspase-9 were detected by immunohistochemistry assay. The production of reactive oxygen species and cellular mitochondria membrane potential (ΔΨm) were determined by fluorescence microscopy. Results We successfully established the p66Shc gene interfering lentivirus vectors, A549-p66ShcshRNA. The A549-p66ShcshRNA was transfected into alveolar epithelial cells, and the inhibitive effects on the expression of p66Shc were observed. Both RT-PCR and Western blot demonstrated downregulation of p66Shc expression in A549 cells. In the A549-p66ShcshRNA hyperoxia group, we found dampened oxidative stress. A549-p66ShcshRNA can cause p66Shc gene silencing, reduce mitochondrial reactive oxygen species generation, reduce membrane potential decrease, reduce the apoptosis of A549 cells, and reduce alveolar epithelial cell injury, while the lentiviral empty vector group had no such changes. Conclusion p66Shc gene interfering lentivirus vector can affect the

  11. Replication of clinical measles virus strains in hispid cotton rats.

    PubMed

    Wyde, P R; Moore-Poveda, D K; Daley, N J; Oshitani, H

    1999-05-01

    An alternative model to nonhuman primates to study measles virus (MV) pathogenesis, to evaluate potential MV vaccines, or to screen for potential antivirals effective against this virus is highly desirable. The laboratory-adapted Edmonston strain of MV has been reported to replicate in the lungs of hispid cotton rats following intranasal inoculation, immunosuppress infected animals, and disseminate widely from the lungs, making these animals a candidate model. However, clinical MV strains have generally not been found to grow in these animals, limiting the utility and acceptance of this model. In the present studies we demonstrate reproducible replication of several clinical MV strains in hispid cotton rats. As with the Edmonston strain, leukocytes appear to be the primary target cells of these viruses following intranasal inoculation, and extrapulmonary dissemination is common. It is also demonstrated that prior MV infection or immunization of test animals with MV vaccine prevents pulmonary tract infection. These findings should make the MV-cotton rat model more acceptable.

  12. Cellular senescence in aging primates.

    PubMed

    Herbig, Utz; Ferreira, Mark; Condel, Laura; Carey, Dee; Sedivy, John M

    2006-03-01

    The aging of organisms is characterized by a gradual functional decline of all organ systems. Mammalian somatic cells in culture display a limited proliferative life span, at the end of which they undergo an irreversible cell cycle arrest known as replicative senescence. Whether cellular senescence contributes to organismal aging has been controversial. We investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent fibroblasts increases exponentially in the skin of aging baboons, reaching >15% of all cells in very old individuals. In addition, the same cells contain activated ataxia-telangiectasia mutated kinase and heterochromatinized nuclei, confirming their senescent status. PMID:16456035

  13. Replicated spectrographs in astronomy

    NASA Astrophysics Data System (ADS)

    Hill, Gary J.

    2014-06-01

    As telescope apertures increase, the challenge of scaling spectrographic astronomical instruments becomes acute. The next generation of extremely large telescopes (ELTs) strain the availability of glass blanks for optics and engineering to provide sufficient mechanical stability. While breaking the relationship between telescope diameter and instrument pupil size by adaptive optics is a clear path for small fields of view, survey instruments exploiting multiplex advantages will be pressed to find cost-effective solutions. In this review we argue that exploiting the full potential of ELTs will require the barrier of the cost and engineering difficulty of monolithic instruments to be broken by the use of large-scale replication of spectrographs. The first steps in this direction have already been taken with the soon to be commissioned MUSE and VIRUS instruments for the Very Large Telescope and the Hobby-Eberly Telescope, respectively. MUSE employs 24 spectrograph channels, while VIRUS has 150 channels. We compare the information gathering power of these replicated instruments with the present state of the art in more traditional spectrographs, and with instruments under development for ELTs. Design principles for replication are explored along with lessons learned, and we look forward to future technologies that could make massively-replicated instruments even more compelling.

  14. Human Mitochondrial DNA Replication

    PubMed Central

    Holt, Ian J.; Reyes, Aurelio

    2012-01-01

    Elucidation of the process of DNA replication in mitochondria is in its infancy. For many years, maintenance of the mitochondrial genome was regarded as greatly simplified compared to the nucleus. Mammalian mitochondria were reported to lack all DNA repair systems, to eschew DNA recombination, and to possess but a single DNA polymerase, polymerase γ. Polγ was said to replicate mitochondrial DNA exclusively via one mechanism, involving only two priming events and a handful of proteins. In this “strand-displacement model,” leading strand DNA synthesis begins at a specific site and advances approximately two-thirds of the way around the molecule before DNA synthesis is initiated on the “lagging” strand. Although the displaced strand was long-held to be coated with protein, RNA has more recently been proposed in its place. Furthermore, mitochondrial DNA molecules with all the features of products of conventional bidirectional replication have been documented, suggesting that the process and regulation of replication in mitochondria is complex, as befits a genome that is a core factor in human health and longevity. PMID:23143808

  15. SIMS Replications in Ontario.

    ERIC Educational Resources Information Center

    Russell, Howard

    Replication of the Second International Mathematics Study (SIMS) in Ontario, Canada, is described and assessed. The curriculum and testing program covers numerical methods, geometry, and algebra. Whereas classical studies focused on mean scores of a system's students and on percentages of teachers for opportunity to learn (OTL), SIMS aggregates…

  16. Sperm Morphology Assessment in Captive Neotropical Primates.

    PubMed

    Swanson, W F; Valle, R R; Carvalho, F M; Arakaki, P R; Rodas-Martínez, A Z; Muniz, Japc; García-Herreros, M

    2016-08-01

    The main objective of this study was to evaluate sperm morphology in four neotropical primate species to compare the sperm morphological traits and the sperm morphometric parameters as a basis for establishing normative sperm standards for each species. Data from 80 ejaculates collected from four primate species, Callithrix jacchus, Callimico goeldii, Alouatta caraya and Ateles geoffroyi, were analysed for detection of sperm morphological alterations using subjective World Health Organization (WHO-2010) standards and Sperm Deformity Index (SDI) criteria, objective computer-assisted sperm morphometry analysis (CASMA) and subpopulation sperm determination (SSD) methods. There were multiple differences (p < 0.01) observed among primate species in values obtained from WHO-2010, SDI, CASMA and SSD sperm analysis methods. In addition, multiple significant positive and negative correlations were observed between the sperm morphological traits (SDI, Sperm Deformity Index Head Defects, Sperm Deformity Index Midpiece Defects, Sperm Deformity Index Tail Defects, Normal Sperm, Head Defects, Midpiece Defects and Tail Defects) and the sperm morphometric parameters (SSD, Area (A), Perimeter (P), Length (L), Width (W), Ellipticity, Elongation and Rugosity) (p ≤ 0.046). In conclusion, our findings using different evaluation methods indicate that pronounced sperm morphological variation exists among these four neotropical primate species. Because of the strong relationship observed among morphological and morphometric parameters, these results suggest that application of objective analysis methods could substantially improve the reliability of comparative studies and help to establish valid normative sperm values for neotropical primates. PMID:27260333

  17. Ancient single origin for Malagasy primates.

    PubMed Central

    Yoder, A D; Cartmill, M; Ruvolo, M; Smith, K; Vilgalys, R

    1996-01-01

    We report new evidence that bears decisively on a long-standing controversy in primate systematics. DNA sequence data for the complete cytochrome b gene, combined with an expanded morphological data set, confirm the results of a previous study and again indicate that all extant Malagasy lemurs originated from a single common ancestor. These results, as well as those from other genetic studies, call for a revision of primate classifications in which the dwarf and mouse lemurs are placed within the Afro-Asian lorisiforms. The phylogenetic results, in agreement with paleocontinental data, indicate an African origin for the common ancestor of lemurs and lorises (the Strepsirrhini). The molecular data further suggest the surprising conclusion that lemurs began evolving independently by the early Eocene at the latest. This indicates that the Malagasy primate lineage is more ancient than generally thought and places the split between the two strepsirrhine lineages well before the appearance of known Eocene fossil primates. We conclude that primate origins were marked by rapid speciation and diversification sometime before the late Paleocene. Images Fig. 1 Fig. 2 PMID:8643538

  18. Primate energy expenditure and life history

    PubMed Central

    Pontzer, Herman; Raichlen, David A.; Gordon, Adam D.; Schroepfer-Walker, Kara K.; Hare, Brian; O’Neill, Matthew C.; Muldoon, Kathleen M.; Dunsworth, Holly M.; Wood, Brian M.; Isler, Karin; Burkart, Judith; Irwin, Mitchell; Shumaker, Robert W.; Lonsdorf, Elizabeth V.; Ross, Stephen R.

    2014-01-01

    Humans and other primates are distinct among placental mammals in having exceptionally slow rates of growth, reproduction, and aging. Primates’ slow life history schedules are generally thought to reflect an evolved strategy of allocating energy away from growth and reproduction and toward somatic investment, particularly to the development and maintenance of large brains. Here we examine an alternative explanation: that primates’ slow life histories reflect low total energy expenditure (TEE) (kilocalories per day) relative to other placental mammals. We compared doubly labeled water measurements of TEE among 17 primate species with similar measures for other placental mammals. We found that primates use remarkably little energy each day, expending on average only 50% of the energy expected for a placental mammal of similar mass. Such large differences in TEE are not easily explained by differences in physical activity, and instead appear to reflect systemic metabolic adaptation for low energy expenditures in primates. Indeed, comparisons of wild and captive primate populations indicate similar levels of energy expenditure. Broad interspecific comparisons of growth, reproduction, and maximum life span indicate that primates’ slow metabolic rates contribute to their characteristically slow life histories. PMID:24474770

  19. Sperm Morphology Assessment in Captive Neotropical Primates.

    PubMed

    Swanson, W F; Valle, R R; Carvalho, F M; Arakaki, P R; Rodas-Martínez, A Z; Muniz, Japc; García-Herreros, M

    2016-08-01

    The main objective of this study was to evaluate sperm morphology in four neotropical primate species to compare the sperm morphological traits and the sperm morphometric parameters as a basis for establishing normative sperm standards for each species. Data from 80 ejaculates collected from four primate species, Callithrix jacchus, Callimico goeldii, Alouatta caraya and Ateles geoffroyi, were analysed for detection of sperm morphological alterations using subjective World Health Organization (WHO-2010) standards and Sperm Deformity Index (SDI) criteria, objective computer-assisted sperm morphometry analysis (CASMA) and subpopulation sperm determination (SSD) methods. There were multiple differences (p < 0.01) observed among primate species in values obtained from WHO-2010, SDI, CASMA and SSD sperm analysis methods. In addition, multiple significant positive and negative correlations were observed between the sperm morphological traits (SDI, Sperm Deformity Index Head Defects, Sperm Deformity Index Midpiece Defects, Sperm Deformity Index Tail Defects, Normal Sperm, Head Defects, Midpiece Defects and Tail Defects) and the sperm morphometric parameters (SSD, Area (A), Perimeter (P), Length (L), Width (W), Ellipticity, Elongation and Rugosity) (p ≤ 0.046). In conclusion, our findings using different evaluation methods indicate that pronounced sperm morphological variation exists among these four neotropical primate species. Because of the strong relationship observed among morphological and morphometric parameters, these results suggest that application of objective analysis methods could substantially improve the reliability of comparative studies and help to establish valid normative sperm values for neotropical primates.

  20. Neocortex size predicts deception rate in primates.

    PubMed Central

    Byrne, Richard W.; Corp, Nadia

    2004-01-01

    Human brain organization is built upon a more ancient adaptation, the large brain of simian primates: on average, monkeys and apes have brains twice as large as expected for mammals of their size, principally as a result of neocortical enlargement. Testing the adaptive benefit of this evolutionary specialization depends on finding an association between brain size and function in primates. However, most cognitive capacities have been assessed in only a restricted range of species under laboratory conditions. Deception of conspecifics in social circumstances is an exception, because a corpus of field data is available that encompasses all major lines of the primate radiation. We show that the use of deception within the primates is well predicted by the neocortical volume, when observer effort is controlled for; by contrast, neither the size of the rest of the brain nor the group size exert significant effects. These findings are consistent with the hypothesis that neocortical expansion has been driven by social challenges among the primates. Complex social manipulations such as deception are thought to be based upon rapid learning and extensive social knowledge; thus, learning in social contexts may be constrained by neocortical size. PMID:15306289

  1. Direct hippocampal injection of pseudo lentivirus-delivered nerve growth factor gene rescues the damaged cognitive function after traumatic brain injury in the rat.

    PubMed

    Lin, Yong; Wan, Jie-qing; Gao, Guo-yi; Pan, Yao-hua; Ding, Sheng-hao; Fan, Yi-ling; Wang, Yong; Jiang, Ji-yao

    2015-11-01

    Traumatic brain injury (TBI) treatment is a long-term process and requires repeated medicine administration, which, however, can cause high expense, infection, and hemorrhage to patients. To investigate how a long-term expression of nerve growth factor (Ngf) gene affects the injured hippocampus function post-TBI, in this study, a pseudo lentivirus carrying the β-Ngf fusion gene, with green fluorescence protein (GFP) gene, was constructed to show the gene expression and its ability of protecting cells from oxidative damage in vitro. Then, the pseudo lentivirus-carried β-Ngf fusion gene was directly injected into the injured brain to evaluate its influence on the injured hippocampus function post-TBI in vivo. We found that the expression of the pseudo lentivirus-delivered β-Ngf fusion gene lasted more than four-week after the cell transduction and the encoded β-NGF fusion protein could induce the neuron-like PC12 cell differentiation. Moreover, the hippocampal injection of the pseudo lentivirus-carried β-Ngf fusion gene sped the injured cognitive function recovery of the rat subjected to TBI. Together, our findings indicate that the long-term expression of the β-Ngf fusion gene, delivered by the pseudo lentivirus, can promote the neurite outgrowth of the neuron-like cells and protect the cells from the oxidative damage in vitro, and that the direct and single dose hippocampal injection of the pseudo lentivirus-carried β-Ngf fusion gene is able to rescue the hippocampus function after the TBI in the rat.

  2. Direct hippocampal injection of pseudo lentivirus-delivered nerve growth factor gene rescues the damaged cognitive function after traumatic brain injury in the rat.

    PubMed

    Lin, Yong; Wan, Jie-qing; Gao, Guo-yi; Pan, Yao-hua; Ding, Sheng-hao; Fan, Yi-ling; Wang, Yong; Jiang, Ji-yao

    2015-11-01

    Traumatic brain injury (TBI) treatment is a long-term process and requires repeated medicine administration, which, however, can cause high expense, infection, and hemorrhage to patients. To investigate how a long-term expression of nerve growth factor (Ngf) gene affects the injured hippocampus function post-TBI, in this study, a pseudo lentivirus carrying the β-Ngf fusion gene, with green fluorescence protein (GFP) gene, was constructed to show the gene expression and its ability of protecting cells from oxidative damage in vitro. Then, the pseudo lentivirus-carried β-Ngf fusion gene was directly injected into the injured brain to evaluate its influence on the injured hippocampus function post-TBI in vivo. We found that the expression of the pseudo lentivirus-delivered β-Ngf fusion gene lasted more than four-week after the cell transduction and the encoded β-NGF fusion protein could induce the neuron-like PC12 cell differentiation. Moreover, the hippocampal injection of the pseudo lentivirus-carried β-Ngf fusion gene sped the injured cognitive function recovery of the rat subjected to TBI. Together, our findings indicate that the long-term expression of the β-Ngf fusion gene, delivered by the pseudo lentivirus, can promote the neurite outgrowth of the neuron-like cells and protect the cells from the oxidative damage in vitro, and that the direct and single dose hippocampal injection of the pseudo lentivirus-carried β-Ngf fusion gene is able to rescue the hippocampus function after the TBI in the rat. PMID:26285082

  3. Autophagy during early stages contributes to bovine viral diarrhea virus replication in MDBK cells.

    PubMed

    Fu, Qiang; Shi, Huijun; Zhang, Hui; Ren, Yan; Guo, Fei; Qiao, Jun; Jia, Bin; Wang, Pengyan; Chen, Chuangfu

    2014-10-01

    Autophagy (or autophagocytosis) is an essential and precise control process by which cells degrade unnecessary or dysfunctional cellular components or organelles in the cytoplasm in response to nutrient depletion, exogenous pathogens, or other stimuli. This process results in the removal of damaged or surplus organelles and macromolecular complexes via a lysosome-dependent mechanism. Bovine viral diarrhea virus (BVDV) is a ssRNA virus of the Flaviviridae family (genus Pestivirus). BVDV infection results in major economic losses due to poor reproductive performance and poor calf performance in cattle herds. In our previous studies, we have shown that BVDV NADL infection significantly increases autophagy in MDBK cells. To further define the interactions between autophagy and BVDV infection, we investigated the effects of autophagy on the replication of BVDV NADL. The findings showed that autophagy was inhibited by treatment with 3-methyladenine (3-MA) or wortmannin and that the knockdown of LC3 and Beclin1 using lentivirus-mediated RNA interference (RNAi) suppressed BVDV NADL replication. In contrast, the findings showed the replication of BVDV NADL was significantly increased by treatment with the autophagy inducer rapamycin within 18 h post-infection (pi). However, the mRNA levels of BVDV NADL 5'UTRs showed a downward trend after 18 h pi, and this effect was reversed by chloroquine treatment. Therefore, we inferred that infection with BVDV NADL increases autophagy, which in turn favors BVDV NADL replication at early stages.

  4. Convergent evolution in primates and an insectivore

    SciTech Connect

    Boffelli, Dario; Cheng, Jan-Fang; Rubin, Edward M.

    2003-04-16

    The cardiovascular risk factor apolipoprotein(a) (apo(a)) has a puzzling distribution among mammals, its presence being limited to a subset of primates and a member of the insectivore lineage, the hedgehog. To explore the evolutionary history of apo(a), we performed extensive genomic sequence comparisons of multiple species with and without an apo(a) gene product, such as human, baboon, hedgehog, lemurand mouse. This analysis indicated that apo(a) arose independently in a subset of primates, including baboon and human, and an insectivore, the hedgehog, and was not simply lost by species lacking it. The similar structural domains shared by the hedgehog and primate apo(a) indicate that they were formed by a unique molecular mechanism involving the convergent evolution of paralogous genes in these distantspecies.

  5. Progress with nonhuman primate embryonic stem cells.

    PubMed

    Wolf, Don P; Kuo, Hung-Chih; Pau, K-Y Francis; Lester, Linda

    2004-12-01

    Embryonic stem cells hold potential in the fields of regenerative medicine, developmental biology, tissue regeneration, disease pathogenicity, and drug discovery. Embryonic stem (ES) cell lines are now available in primates, including man, rhesus, and cynomologous monkeys. Monkey ES cells serve as invaluable clinically relevant models for studies that can't be conducted in humans because of practical or ethical limitations, or in rodents because of differences in physiology and anatomy. Here, we review the current status of nonhuman primate research with ES cells, beginning with a description of their isolation, characterization, and availability. Substantial limitations still plague the use of primate ES cells, such as their required growth on feeder layers, poor cloning efficiency, and restricted availability. The ability to produce homogenous populations of both undifferentiated as well as differentiated phenotypes is an important challenge, and genetic approaches to achieving these objectives are discussed. Finally, safety, efficiency, and feasibility issues relating to the transplantation of ES-derived cells are considered.

  6. Protopithecus: rediscovering the first fossil primate.

    PubMed

    Hartwig, W C

    1995-01-01

    The earliest discoveries of extinct primates and humans profoundly affected the course of evolutionary theory as a scientific model for explaining life and its diversity through time. The absence of such fossils in the early nineteenth century provided important negative evidence to the competing French intellectual schools of Lamarckian evolutionism and Cuvierian catastrophism. Indeed, the first recognition of extinct primates fell serendipitously between the death of Cuvier in 1832 and the revolutionary writings of Darwin in 1859. Largely unknown to history, however, is that four different European scholars, working on three continents, independently discovered and recognized extinct primates within a few months of each other in 1836. The first of these to be formally named, Protopithecus, is ironically the least well known despite being the largest monkey ever discovered in the western hemisphere. The reasons for this forgotten first discovery reflect a general unawareness of South American mammals, and propagation of misinterpretation at a critical time in the history of primatology.

  7. Primate color vision: a comparative perspective.

    PubMed

    Jacobs, Gerald H

    2008-01-01

    Thirty years ago virtually everything known about primate color vision derived from psychophysical studies of normal and color-defective humans and from physiological investigations of the visual system of the macaque monkey, the most popular of human surrogates for this purpose. The years since have witnessed much progress toward the goal of understanding this remarkable feature of primate vision. Among many advances, investigations focused on naturally occurring variations in color vision in a wide range of nonhuman primate species have proven to be particularly valuable. Results from such studies have been central to our expanding understanding of the interrelationships between opsin genes, cone photopigments, neural organization, and color vision. This work is also yielding valuable insights into the evolution of color vision.

  8. The ecology of primate material culture.

    PubMed

    Koops, Kathelijne; Visalberghi, Elisabetta; van Schaik, Carel P

    2014-11-01

    Tool use in extant primates may inform our understanding of the conditions that favoured the expansion of hominin technology and material culture. The 'method of exclusion' has, arguably, confirmed the presence of culture in wild animal populations by excluding ecological and genetic explanations for geographical variation in behaviour. However, this method neglects ecological influences on culture, which, ironically, may be critical for understanding technology and thus material culture. We review all the current evidence for the role of ecology in shaping material culture in three habitual tool-using non-human primates: chimpanzees, orangutans and capuchin monkeys. We show that environmental opportunity, rather than necessity, is the main driver. We argue that a better understanding of primate technology requires explicit investigation of the role of ecological conditions. We propose a model in which three sets of factors, namely environment, sociality and cognition, influence invention, transmission and retention of material culture.

  9. Genetic correlates of the evolving primate brain

    PubMed Central

    Vallender, Eric J.

    2012-01-01

    The tremendous shifts in the size, structure, and function of the brain during primate evolution are ultimately caused by changes at the genetic level. Understanding what these changes are and how they effect the phenotypic changes observed lies at the heart of understanding evolutionary change. This chapter focuses on understanding the genetic basis of primate brain evolution, considering the substrates and mechanisms through which genetic change occurs. It also discusses the implications that our current understandings and tools have for what we have already discovered and where our studies will head in the future. While genetic and genomic studies have identified many regions undergoing positive selection during primate evolution, the findings are certainly not exhaustive and functional relevance remains to be confirmed. Nevertheless, a strong foundation has been built upon which future studies will emerge. PMID:22230621

  10. Lipoprotein(a): nonhuman primate models.

    PubMed

    Makino, K; Scanu, A M

    1991-09-01

    Lipoprotein(a) [Lp(a)] is a low density lipoprotein which has apo(a) disulfide-linked to apoB100. Apo(a) has recently been shown to have a striking homology with plasminogen, a knowledge that has stimulated a lot of interest in the mechanism of atherogenicity and thrombogenicity of this lipoprotein particle. Several studies have documented the presence of Lp(a) in nonhuman primates with particular reference to the rhesus monkeys and baboons. The Lp(a) of rhesus monkey is structurally very similar to that of humans, except for the absence of kringle V and the amino acid composition of the catalytic region. The Lp(a) of nonhuman primates, like their human counterparts, exhibit a wide range of interindividual plasma levels and also a wide size polymorphism of apo(a). Nonhuman primates appear to represent a good model for the study of the structure and biology of Lp(a).

  11. Compartmentalization of prokaryotic DNA replication.

    PubMed

    Bravo, Alicia; Serrano-Heras, Gemma; Salas, Margarita

    2005-01-01

    It becomes now apparent that prokaryotic DNA replication takes place at specific intracellular locations. Early studies indicated that chromosomal DNA replication, as well as plasmid and viral DNA replication, occurs in close association with the bacterial membrane. Moreover, over the last several years, it has been shown that some replication proteins and specific DNA sequences are localized to particular subcellular regions in bacteria, supporting the existence of replication compartments. Although the mechanisms underlying compartmentalization of prokaryotic DNA replication are largely unknown, the docking of replication factors to large organizing structures may be important for the assembly of active replication complexes. In this article, we review the current state of this subject in two bacterial species, Escherichia coli and Bacillus subtilis, focusing our attention in both chromosomal and extrachromosomal DNA replication. A comparison with eukaryotic systems is also presented.

  12. The use of medicinal plants by primates: A missing link?

    PubMed

    Newton, P

    1991-09-01

    There is growing evidence that some species of wild nonhuman primate, especially chimpanzees, take herbal and clay medicines to treat and prevent disease. Such a primate pharmacopoeia may be a missing link in our understanding of the relationship between primate foraging and ranging strategies and plant chemistry; not all plant secondary compounds may be deleterious to the consumer. Just as study of traditional herbal medicines has yielded powerful drugs, so primate medicines may hint at drugs useful in treating human disease.

  13. Body weight, diet and home range area in primates.

    PubMed

    Milton, K; May, M L

    1976-02-12

    Primates show a strong positive relationship between body weight and home range area. Dietary habits also influence home range area. Folivorous primates occupy smaller home range areas for their body weight than do frugivores and omnivores. Primates generally require smaller home range area per individual than solitary terrestrial mammals, but primates living in social groups have much larger total home range than individual solitary mammals. This trend may necessitate higher expenditures of energy in food-gathering or modifications in movement patterns.

  14. Learning about primates' learning, language, and cognition

    NASA Technical Reports Server (NTRS)

    Rumbaugh, Duane M.

    1992-01-01

    Results are presented of many years of research on the methods of teaching primates the language and cognitive skills which were long considered to be unteachable to particular species of primates. It was found that chimpanzee subjects could not only learn a number of 'stock sentences' but to use them in variations and several combinations for the purpose of solving various problems. Apes placed in different rooms could be taught to communicate via computer, and collaborate with each other on doing specific tasks. Contrary to expectations, young rhesus monkeys proved to be able to learn as much as the chimpanzee species.

  15. Mouse-Based Research on Quiescent Primate Malaria Parasites.

    PubMed

    Markus, Miles B

    2016-04-01

    Mice engrafted with primate tissue make two important plasmodial dormancy-related questions researchable. The first is concerned with whether latent merozoites in the lymphatic system can give rise to relapse-like, recurrent malaria in primates. The second is that genetic evidence of hypnozoite activation as the source of relapsing primate malaria can be looked for.

  16. Small ruminant lentiviruses in Jordan: evaluation of sheep and goat serological response using recombinant and peptide antigens.

    PubMed

    Tolari, Francesco; Al-Ramadneh, Wafa'a; Mazzei, Maurizio; Carrozza, Maria Luisa; Forzan, Mario; Bandecchi, Patrizia; Grego, Elena; Rosati, Sergio

    2013-08-01

    Small ruminant lentiviruses infect sheep and goats worldwide, causing chronic progressive diseases and relevant economic losses. Disease eradication and prevention is mostly based on serological testing. The goal of this research was to investigate the presence of the small ruminant lentiviruses (SRLVs) in Jordan and to characterize the serological response in sheep and goat populations. A panel of sera were collected from flocks located in Northern Jordan and Jordan Valley. The samples were tested using three ELISA assays: a commercially available ELISA based on p25 recombinant protein and transmembrane peptide derived from British maedi-visna virus (MVV) EV1 strain, an ELISA based on P16-P25 recombinant protein derived from two Italian strains representative of MVV- and caprine arthritis encephalitis virus (CAEV)-like SRLVs, and an ELISA based on SU5 peptide from the same two Italian isolates. The results indicate that both MVV- and CAEV-like strains are present in Jordan and that the majority of the viruses circulating among sheep and goat populations belong to the MVV-like genotype.

  17. Heparin-chitosan nanoparticle functionalization of porous poly(ethylene glycol) hydrogels for localized lentivirus delivery of angiogenic factors.

    PubMed

    Thomas, Aline M; Gomez, Andrew J; Palma, Jaime L; Yap, Woon Teck; Shea, Lonnie D

    2014-10-01

    Hydrogels have been extensively used for regenerative medicine strategies given their tailorable mechanical and chemical properties. Gene delivery represents a promising strategy by which to enhance the bioactivity of the hydrogels, though the efficiency and localization of gene transfer have been challenging. Here, we functionalized porous poly(ethylene glycol) hydrogels with heparin-chitosan nanoparticles to retain the vectors locally and enhance lentivirus delivery while minimizing changes to hydrogel architecture and mechanical properties. The immobilization of nanoparticles, as compared to homogeneous heparin and/or chitosan, is essential to lentivirus immobilization and retention of activity. Using this gene-delivering platform, we over-expressed the angiogenic factors sonic hedgehog (Shh) and vascular endothelial growth factor (Vegf) to promote blood vessel recruitment to the implant site. Shh enhanced endothelial recruitment and blood vessel formation around the hydrogel compared to both Vegf-delivering and control hydrogels. The nanoparticle-modified porous hydrogels for delivering gene therapy vectors can provide a platform for numerous regenerative medicine applications. PMID:25023395

  18. Heparin-chitosan nanoparticle functionalization of porous poly(ethylene glycol) hydrogels for localized lentivirus delivery of angiogenic factors

    PubMed Central

    Thomas, Aline M.; Gomez, Andrew J.; Palma, Jaime L.; Yap, Woon Teck

    2014-01-01

    Hydrogels have been extensively used for regenerative medicine strategies given their tailorable mechanical and chemical properties. Gene delivery represents a promising strategy by which to enhance the bioactivity of the hydrogels, though the efficiency and localization of gene transfer have been challenging. Here, we functionalized porous poly(ethylene glycol) hydrogels with heparin-chitosan nanoparticles to retain the vectors locally and enhance lentivirus delivery while minimizing changes to hydrogel architecture and mechanical properties. The immobilization of nanoparticles, as compared to homogeneous heparin and/or chitosan, is essential to lentivirus immobilization and retention of activity. Using this gene-delivering platform, we over-expressed the angiogenic factors sonic hedgehog (Shh) and vascular endothelial growth factor (Vegf) to promote blood vessel recruitment to the implant site. Shh enhanced endothelial recruitment and blood vessel formation around the hydrogel compared to both Vegf-delivering and control hydrogels. The nanoparticle-modified porous hydrogels for delivering gene therapy vectors can provide a platform for numerous regenerative medicine applications. PMID:25023395

  19. Down-regulating HIF-1α by lentivirus-mediated shRNA for therapy of triple negative breast cancer.

    PubMed

    Li, Shuang; Wei, Qingzhu; Li, Qin; Zhang, Bin; Xiao, Qiang

    2015-01-01

    Hypoxia is associated with poor response to treatment in various cancers. Hypoxia inducible factor 1 (HIF-1) is a major transcription factor that mediates adaptation of cancer cells to a hypoxic environment and regulates many genes that are involved in key cellular functions, including cell immortalization, stem cell maintenance, autocrine growth/survival, angiogenesis, invasion/metastasis, and resistance to chemotherapy. HIF-1α has been considered as an attractive therapeutic target for cancer treatment, but there is limited success in this research field. In the present study, we designed a recombinant lentivirus containing HIF-1α siRNA, developed stably transfected cell lines, and tested the anticancer effects of the siRNA on cancer cells in vitro and in vivo. Our results indicated that the stable downregulation of HIF-1α reversed chemoresistance, inhibited proliferation, migration and invasion of cancer cells, and slowed down the tumor growth in breast cancer xenograft models. In conclusion, the recombinant lentivirus containing HIF-1α siRNA provides a new avenue for developing novel therapy for triple negative breast cancer.

  20. Replicators, lineages, and interactors.

    PubMed

    Taylor, Daniel J; Bryson, Joanna J

    2014-06-01

    The target article argues that whole groups can act as interactors in an evolutionary process. We believe that Smaldino's discussion would be advanced by a more thorough analysis of the appropriate replicators and lineages for this model. We show that cultural evolution is necessarily a separate process from cultural group selection, and we also illustrate that the two processes may influence each other as demonstrated by an agent-based model of communicating food-processing skills. PMID:24970423

  1. Differential regulation of NF-κB-mediated proviral and antiviral host gene expression by primate lentiviral Nef and Vpu proteins.

    PubMed

    Sauter, Daniel; Hotter, Dominik; Van Driessche, Benoît; Stürzel, Christina M; Kluge, Silvia F; Wildum, Steffen; Yu, Hangxing; Baumann, Bernd; Wirth, Thomas; Plantier, Jean-Christophe; Leoz, Marie; Hahn, Beatrice H; Van Lint, Carine; Kirchhoff, Frank

    2015-02-01

    NF-κB is essential for effective transcription of primate lentiviral genomes and also activates antiviral host genes. Here, we show that the early protein Nef of most primate lentiviruses enhances NF-κB activation. In contrast, the late protein Vpu of HIV-1 and its simian precursors inhibits activation of NF-κB, even in the presence of Nef. Although this effect of Vpu did not correlate with its ability to interact with β-TrCP, it involved the stabilization of IκB and reduced nuclear translocation of p65. Interestingly, however, Vpu did not affect casein kinase II-mediated phosphorylation of p65. Lack of Vpu was associated with increased NF-κB activation and induction of interferon and interferon-stimulated genes (ISGs) in HIV-1-infected T cells. Thus, HIV-1 and its simian precursors employ Nef to boost NF-κB activation early during the viral life cycle to initiate proviral transcription, while Vpu is used to downmodulate NF-κB-dependent expression of ISGs at later stages.

  2. Generation and characterization of a breast carcinoma model by PyMT overexpression in mammary epithelial cells of tree shrew, an animal close to primates in evolution.

    PubMed

    Ge, Guang-Zhe; Xia, Hou-Jun; He, Bao-Li; Zhang, Hai-Lin; Liu, Wen-Jing; Shao, Ming; Wang, Chun-Yan; Xiao, Ji; Ge, Fei; Li, Fu-Bing; Li, Yi; Chen, Ceshi

    2016-02-01

    The tree shrew is becoming an attractive experimental animal model for human breast cancer owing to a closer relationship to primates/humans than rodents. Tree shrews are superior to classical primates because tree shrew are easier to manipulate, maintain and propagate. It is required to establish a high-efficiency tree shrew breast cancer model for etiological research and drug assessment. Our previous studies suggest that 7,12-dimethylbenz(a)anthracene (DMBA) and medroxyprogesterone acetate (MPA) induce breast tumors in tree shrews with a low frequency (<50%) and long latency (∼ 7-month), making these methods less than ideal. We induced mammary tumors in tree shrew (Tupaia belangeri chinensis) by injection of lentivirus expressing the PyMT oncogene into mammary ducts of 22 animals. Most tree shrews developed mammary tumors with a latency of about three weeks, and by 7 weeks all injected tree shrews had developed mammary tumors. Among these, papillary carcinoma is the predominant tumor type. One case showed lymph node and lung metastasis. Interestingly, the expression levels of phosphorylated AKT, ERK and STAT3 were elevated in 41-68% of PyMT-induced mammary tumors, but not all tumors. Finally, we observed that the growth of PyMT-induced tree shrew mammary tumors was significantly inhibited by Cisplatin and Epidoxorubicin. PyMT-induced tree shrew mammary tumor model may be suitable for further breast cancer research and drug development, due to its high efficiency and short latency.

  3. A New Replicator: A theoretical framework for analysing replication

    PubMed Central

    2010-01-01

    Background Replicators are the crucial entities in evolution. The notion of a replicator, however, is far less exact than the weight of its importance. Without identifying and classifying multiplying entities exactly, their dynamics cannot be determined appropriately. Therefore, it is importance to decide the nature and characteristics of any multiplying entity, in a detailed and formal way. Results Replication is basically an autocatalytic process which enables us to rest on the notions of formal chemistry. This statement has major implications. Simple autocatalytic cycle intermediates are considered as non-informational replicators. A consequence of which is that any autocatalytically multiplying entity is a replicator, be it simple or overly complex (even nests). A stricter definition refers to entities which can inherit acquired changes (informational replicators). Simple autocatalytic molecules (and nests) are excluded from this group. However, in turn, any entity possessing copiable information is to be named a replicator, even multicellular organisms. In order to deal with the situation, an abstract, formal framework is presented, which allows the proper identification of various types of replicators. This sheds light on the old problem of the units and levels of selection and evolution. A hierarchical classification for the partition of the replicator-continuum is provided where specific replicators are nested within more general ones. The classification should be able to be successfully applied to known replicators and also to future candidates. Conclusion This paper redefines the concept of the replicator from a bottom-up theoretical approach. The formal definition and the abstract models presented can distinguish between among all possible replicator types, based on their quantity of variable and heritable information. This allows for the exact identification of various replicator types and their underlying dynamics. The most important claim is that

  4. Complexity transmission during replication

    PubMed Central

    Davis, Brian K.

    1979-01-01

    The transmission of complexity during DNA replication has been investigated to clarify the significance of this molecular property in a deterministic process. Complexity was equated with the amount of randomness within an ordered molecular structure and measured by the entropy of a posteriori probabilities for discrete (monomer sequences, atomic bonds) and continuous (torsion angle sequences) structural parameters in polynucleotides, proteins, and ligand molecules. A theoretical analysis revealed that sequence complexity decreases during transmission from DNA to protein. It was also found that sequence complexity limits the attainable complexity in the folding of a polypeptide chain and that a protein cannot interact with a ligand moiety of higher complexity. The analysis indicated, furthermore, that in any deterministic molecular process a cause possesses more complexity than its effect. This outcome broadly complies with Curie's symmetry principle. Results from an analysis of an extensive set of experimental data are presented; they corroborate these findings. It is suggested, therefore, that complexity governs the direction of order—order molecular transformations. Two biological implications are (i) replication of DNA in a stepwise, repetitive manner by a polymerase appears to be a necessary consequence of structural constraints imposed by complexity, and (ii) during evolution, increases in complexity had to involve a nondeterministic mechanism. This latter requirement apparently applied also to development of the first replicating system on earth. PMID:287070

  5. Can grey parrots (Psittacus erithacus) succeed on a "complex" foraging task failed by nonhuman primates (Pan troglodytes, Pongo abelii, Sapajus apella) but solved by wrasse fish (Labroides dimidiatus)?

    PubMed

    Pepperberg, Irene M; Hartsfield, Leigh Ann

    2014-08-01

    Linking specific cognitive abilities of nonhuman species on a laboratory task to their evolutionary history-ecological niche can be a fruitful exercise in comparative psychology. Crucial issues, however, are the choice of task, the specific conditions of the task, and possibly the subjects' understanding or interpretation of the task. Salwiczek et al. (2012) compared cleaner wrasse fish (Labroides dimidaitus) to several nonhuman primate species (capuchins, Sapajus paella; chimpanzees, Pan troglodytes; orangutans, Pongo abelii) on a task purportedly related to the ecological demands of the fish, but not necessarily of the nonhuman primates; fish succeeded whereas almost all of the nonhuman primates that were tested failed. We replicated the two-choice paradigm of the task with three Grey parrots (Psittacus erithacus), whose ecology, evolutionary history, and cortical capacity are arguably more like those of nonhuman primates than fish. Greys succeeded at levels more like fish than all the nonhuman primates, suggesting possible alternative explanations for their success. Fish and nonhuman primate subjects also experienced a reversal of the initial conditions to test for generalization: Greys were similarly tested; they performed more like fish and capuchins (who now succeeded) than the apes (who continued to fail).

  6. Nutritional contributions of insects to primate diets: implications for primate evolution.

    PubMed

    Rothman, Jessica M; Raubenheimer, David; Bryer, Margaret A H; Takahashi, Maressa; Gilbert, Christopher C

    2014-06-01

    Insects and other invertebrates form a portion of many living and extinct primate diets. We review the nutritional profiles of insects in comparison with other dietary items, and discuss insect nutrients in relation to the nutritional needs of living primates. We find that insects are incorporated into some primate diets as staple foods whereby they are the majority of food intake. They can also be incorporated as complements to other foods in the diet, providing protein in a diet otherwise dominated by gums and/or fruits, or be incorporated as supplements to likely provide an essential nutrient that is not available in the typical diet. During times when they are very abundant, such as in insect outbreaks, insects can serve as replacements to the usual foods eaten by primates. Nutritionally, insects are high in protein and fat compared with typical dietary items like fruit and vegetation. However, insects are small in size and for larger primates (>1 kg) it is usually nutritionally profitable only to consume insects when they are available in large quantities. In small quantities, they may serve to provide important vitamins and fatty acids typically unavailable in primate diets. In a brief analysis, we found that soft-bodied insects are higher in fat though similar in chitin and protein than hard-bodied insects. In the fossil record, primates can be defined as soft- or hard-bodied insect feeders based on dental morphology. The differences in the nutritional composition of insects may have implications for understanding early primate evolution and ecology.

  7. Disproportional Representation of Primates in the Ecological Literature

    PubMed Central

    Heymann, Eckhard W.; Zinner, Dietmar; Ganzhorn, Jörg U.

    2013-01-01

    We address the question why papers dealing with the ecology of primates are so sparsely represented in the general ecological literature. A literature analyses based on entries in Web of Science and PrimateLit reveals that despite a large number of papers published on primates in general and on the ecology of primates, only a very small fraction of these papers is published in high-ranking international ecological journals. We discuss a number of potential reasons for the disproportion and highlight the problems associated with experimental research on wild primates and constraints on sample size as major issues. PMID:24339882

  8. Olfactory Receptor Patterning in a Higher Primate

    PubMed Central

    Horowitz, Lisa F.; Saraiva, Luis R.; Kuang, Donghui; Yoon, Kyoung-hye

    2014-01-01

    The mammalian olfactory system detects a plethora of environmental chemicals that are perceived as odors or stimulate instinctive behaviors. Studies using odorant receptor (OR) genes have provided insight into the molecular and organizational strategies underlying olfaction in mice. One important unanswered question, however, is whether these strategies are conserved in primates. To explore this question, we examined the macaque, a higher primate phylogenetically close to humans. Here we report that the organization of sensory inputs in the macaque nose resembles that in mouse in some respects, but not others. As in mouse, neurons with different ORs are interspersed in the macaque nose, and there are spatial zones that differ in their complement of ORs and extend axons to different domains in the olfactory bulb of the brain. However, whereas the mouse has multiple discrete band-like zones, the macaque appears to have only two broad zones. It is unclear whether the organization of OR inputs in a rodent/primate common ancestor degenerated in primates or, alternatively became more sophisticated in rodents. The mouse nose has an additional small family of chemosensory receptors, called trace amine-associated receptors (TAARs), which may detect social cues. Here we find that TAARs are also expressed in the macaque nose, suggesting that TAARs may also play a role in human olfactory perception. We further find that one human TAAR responds to rotten fish, suggesting a possible role as a sentinel to discourage ingestion of food harboring pathogenic microorganisms. PMID:25209267

  9. Primacy and recency effects in nonhuman primates.

    PubMed

    Castro, C A; Larsen, T

    1992-10-01

    The reports of primacy and recency memory effects in nonhuman primates have been criticized because they have all used an initiating response. That is, the presentation of the to-be-remembered list of items was always contingent on a response being initiated by the nonhuman primate. It has been argued that this initiating response improves performance for early items in the list, resulting in the occurrence of the primacy effect, independent of any memory processing mechanism. This criticism was addressed in the present study by not using an initiating response prior to the presentation of the list. Nevertheless, both a primacy and a recency effect were observed in all 6 rhesus monkeys evaluated using a serial probe recognition task. Thus, the results are similar to those for humans, in that both primacy and recency effects can be obtained in nonhuman primates. A brief literature review is included, and it is proposed that the primacy and recency effects observed in humans, nonhuman primates, and infraprimates can be explained within the context of the configural-association theory.

  10. Nonhuman primate quarantine: its evolution and practice.

    PubMed

    Roberts, Jeffrey A; Andrews, Kirk

    2008-01-01

    Nonhuman primates (NHPs) are imported to the United States for use in research, domestic breeding, and propagation of endangered populations in zoological gardens. During the past 60 years, individuals responsible for NHP importation programs have observed morbidity and mortality typically associated with infectious disease outbreaks. These outbreaks have included infectious agents such as tuberculosis, Herpesvirus sp., simian hemorrhagic fever, and filovirus infections such as the Ebola and Marburg viruses. Some outbreaks have affected both animal and human populations. These epizootics are attributable to a variety of factors, including increased population density, exposure of naïve populations to new infectious agents, and stress. The practice of quarantining animals arriving in the United States was first applied by individual research programs to improve animal health and ensure the quality of animals entering research programs. The development of government regulations for nonhuman primate quarantine accompanied the recognition that imported NHPs could pose a risk to public health. This article briefly reviews the history of US NHP importation and the factors behind the development of NHP quarantine regulations. The focus is on regulations concerned with infectious disease, public health, and the health of domestic primate colonies. These regulations have had the dual benefit of protecting public health as well as reducing animal morbidity and mortality during importation and quarantine. We review current practices and facilities for nonhuman primate quarantine and identify challenges for the future. PMID:18323577

  11. 42 CFR 71.53 - Nonhuman primates.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... nonhuman primates that is suspected of being yellow fever, monkeypox, or Marburg/Ebola disease. (3... disease that may constitute a threat to public health, the Director may provide for or require examination... be required under other Federal regulations (50 CFR parts 17 and 23) protecting such...

  12. Remarkable ancient divergences amongst neglected lorisiform primates

    PubMed Central

    Nekaris, K. Anne‐Isola; Perkin, Andrew; Bearder, Simon K.; Pimley, Elizabeth R.; Schulze, Helga; Streicher, Ulrike; Nadler, Tilo; Kitchener, Andrew; Zischler, Hans; Zinner, Dietmar; Roos, Christian

    2015-01-01

    Lorisiform primates (Primates: Strepsirrhini: Lorisiformes) represent almost 10% of the living primate species and are widely distributed in sub‐Saharan Africa and South/South‐East Asia; however, their taxonomy, evolutionary history, and biogeography are still poorly understood. In this study we report the largest molecular phylogeny in terms of the number of represented taxa. We sequenced the complete mitochondrial cytochrome b gene for 86 lorisiform specimens, including ∼80% of all the species currently recognized. Our results support the monophyly of the Galagidae, but a common ancestry of the Lorisinae and Perodicticinae (family Lorisidae) was not recovered. These three lineages have early origins, with the Galagidae and the Lorisinae diverging in the Oligocene at about 30 Mya and the Perodicticinae emerging in the early Miocene. Our mitochondrial phylogeny agrees with recent studies based on nuclear data, and supports Euoticus as the oldest galagid lineage and the polyphyletic status of Galagoides. Moreover, we have elucidated phylogenetic relationships for several species never included before in a molecular phylogeny. The results obtained in this study suggest that lorisiform diversity remains substantially underestimated and that previously unnoticed cryptic diversity might be present within many lineages, thus urgently requiring a comprehensive taxonomic revision of this primate group. © 2015 The Linnean Society of London PMID:26900177

  13. Chronic wasting disease agents in nonhuman primates.

    PubMed

    Race, Brent; Meade-White, Kimberly D; Phillips, Katie; Striebel, James; Race, Richard; Chesebro, Bruce

    2014-05-01

    Chronic wasting disease is a prion disease of cervids. Assessment of its zoonotic potential is critical. To evaluate primate susceptibility, we tested monkeys from 2 genera. We found that 100% of intracerebrally inoculated and 92% of orally inoculated squirrel monkeys were susceptible, but cynomolgus macaques were not, suggesting possible low risk for humans.

  14. The Neuroendocrinology of Primate Maternal Behavior

    PubMed Central

    Saltzman, Wendy; Maestripieri, Dario

    2010-01-01

    In nonhuman primates and humans, similar to other mammals, hormones are not strictly necessary for the expression of maternal behavior, but nevertheless influence variation in maternal responsiveness and parental behavior both within and between individuals. A growing number of correlational and experimental studies have indicated that high circulating estrogen concentrations during pregnancy increase maternal motivation and responsiveness to infant stimuli, while effects of prepartum or postpartum estrogens and progestogens on maternal behavior are less clear. Prolactin is thought to play a role in promoting paternal and alloparental care in primates, but little is known about the relationship between this hormone and maternal behavior. High circulating cortisol levels appear to enhance arousal and responsiveness to infant stimuli in young, relatively inexperienced female primates, but interfere with the expression of maternal behavior in older and more experienced mothers. Among neuropeptides and neurotransmitters, preliminary evidence indicates that oxytocin and endogenous opioids affect maternal attachment to infants, including maintenance of contact, grooming, and responses to separation. Brain serotonin affects anxiety and impulsivity, which in turn may affect maternal behaviors such as infant retrieval or rejection of infants’ attempts to make contact with the mother. Although our understanding of the neuroendocrine correlates of primate maternal behavior has grown substantially in the last two decades, very little is known about the mechanisms underlying these effects, e.g., the extent to which these mechanisms may involve changes in perception, emotion, or cognition. PMID:20888383

  15. [Experimental whooping cough of nonhuman primate].

    PubMed

    Kubrava, D T; Medkova, A Iu; Siniashina, L N; Shevtsova, Z V; Matua, A Z; Kondzharia, I G; Barkaia, V S; Elistratova, Zh V; Karataev, G I; Mikvabia, Z Ia; Gintsburg, A L

    2013-01-01

    Despite considerable success in study of Bordetella pertussis virulence factors, pathogenesis of whooping cough, duration of B. pertussis bacteria persistence, types and mechanisms of immune response are still keep underinvestigated. It can be explained by the absence ofadequate experimental animal model for pertussis study. Our study estimates clinical and laboratory parameters of whooping cough in non-human primates of the Old World in the process of intranasan infection by virulent B. pertussis bacteria. Also the duration of B. pertussis bacteria persistence in animals was investigated. 14 animal units of 4 species of non-human primates of the Old World were used for intranasal infection. The examination of infect animals included: visual exploration of nasopharynx, thermometry, clinical and biochemical blood analyses, identification ofB. pertussis, using microbiologic and molecular genetic analyses, estimation of innate and adoptive immune factors. The development of infectious process was accompanied by generation of B. pertussis bacteria, catarrhal inflammation of nasopharyngeal mucosa, leucocytosis, hypoglycemia specific for pertussis, and activation of innate and adaptive immunity for all primates regardless of specie were seen. While repeated experimental infection in primates single bacterial colonies were registered during only first week after challenge. It occurs like the absence of inflammation of nasopharyngeal mucosa and the lack of laboratory marks of whooping cough, recorded after first challenge. The evident booster effect of humoral immunity was observed. As a model for investigation of B. pertussis bacteria persistence and immune response against whooping cough we suggest the usage of rhesus macaque as more available to experiments.

  16. Homeostasis in primates in hyperacceleration fields

    NASA Technical Reports Server (NTRS)

    Fuller, C. A.

    1984-01-01

    Various homeostatic responses of a nonhuman primate, the squirrel monkey (Saimiri sciureus) to acute changes in the acceleration environment were examined. When these animals were exposed to a hyperdynamic field the body temperature was consistently depressed and the animals showed behavioral indications of increased drowsiness. Further, time of day played a significant role in influencing these responses.

  17. Processing Of Visual Information In Primate Brains

    NASA Technical Reports Server (NTRS)

    Anderson, Charles H.; Van Essen, David C.

    1991-01-01

    Report reviews and analyzes information-processing strategies and pathways in primate retina and visual cortex. Of interest both in biological fields and in such related computational fields as artificial neural networks. Focuses on data from macaque, which has superb visual system similar to that of humans. Authors stress concept of "good engineering" in understanding visual system.

  18. Nonhuman primate models in translational regenerative medicine.

    PubMed

    Daadi, Marcel M; Barberi, Tiziano; Shi, Qiang; Lanford, Robert E

    2014-12-01

    Humans and nonhuman primates (NHPs) are similar in size, behavior, physiology, biochemistry, structure and function of organs, and complexity of the immune system. Research on NHPs generates complementary data that bridge translational research from small animal models to humans. NHP models of human disease offer unique opportunities to develop stem cell-based therapeutic interventions that directly address relevant and challenging translational aspects of cell transplantation therapy. These include the use of autologous induced pluripotent stem cell-derived cellular products, issues related to the immune response in autologous and allogeneic setting, pros and cons of delivery techniques in a clinical setting, as well as the safety and efficacy of candidate cell lines. The NHP model allows the assessment of complex physiological, biochemical, behavioral, and imaging end points, with direct relevance to human conditions. At the same time, the value of using primates in scientific research must be carefully evaluated and timed due to expense and the necessity for specialized equipment and highly trained personnel. Often it is more efficient and useful to perform initial proof-of-concept studies for new therapeutics in rodents and/or other species before the pivotal studies in NHPs that may eventually lead to first-in-human trials. In this report, we present how the Southwest National Primate Research Center, one of seven NIH-funded National Primate Research Centers, may help the global community in translating promising technologies to the clinical arena.

  19. E1a promotes c-Myc-dependent replicative stress

    PubMed Central

    Valero, María Llanos; Cimas, Francisco Jose; Arias, Laura; Melgar-Rojas, Pedro; García, Elena; Callejas-Valera, Juan Luis; García-Cano, Jesús; Serrano-Oviedo, Leticia; Ángel de la Cruz-Morcillo, Miguel; Sánchez-Pérez, Isabel; Sánchez-Prieto, Ricardo

    2014-01-01

    The E1a gene from adenovirus is known to be a potent inducer of chemo/radiosensitivity in a wide range of tumors. However, the molecular bases of its radiosensitizer properties are still poorly understood. In an attempt to study this effect, U87MG cells, derived from a radio-resistant tumor as glioblastoma, where infected with lentivirus carrying E1a gene developing an acute sensitivity to ionizing radiation. The induction of radiosensitivity correlated with a marked G2/M phase accumulation and a potent apoptotic response. Our findings demonstrate that c-Myc plays a pivotal role in E1a-associated radiosensitivity through the induction of a replicative stress situation, as our data support by genetic approaches, based in interference and overexpression in U87MG cells. In fact, we present evidence showing that Chk1 is a novel transcriptional target of E1a gene through the effect exerted by this adenoviral protein onto c-Myc. Moreover, c-Myc upregulation also explains the marked phosphorylation of H2AX associated to E1a expression in the absence of DNA damage. Indeed, all these observations were applicable to other experimental models, such as T98G, LN-405 and A172, rendering the same pattern in terms of radiosensitivity, cell cycle distribution, upregulation of Chk1, c-Myc, and phosphorylation pattern of H2AX. In summary, our data propose a novel mechanism to explain how E1a mediates radiosensitivity through the signaling axis E1a→c-Myc→ replicative stress situation. This novel mechanism of E1a-mediated radiosensitivity could be the key to open new possibilities in the current therapy of glioblastoma. PMID:24196438

  20. Predictors of orbital convergence in primates: a test of the snake detection hypothesis of primate evolution.

    PubMed

    Wheeler, Brandon C; Bradley, Brenda J; Kamilar, Jason M

    2011-09-01

    Traditional explanations for the evolution of high orbital convergence and stereoscopic vision in primates have focused on how stereopsis might have aided early primates in foraging or locomoting in an arboreal environment. It has recently been suggested that predation risk by constricting snakes was the selective force that favored the evolution of orbital convergence in early primates, and that later exposure to venomous snakes favored further degrees of convergence in anthropoid primates. Our study tests this snake detection hypothesis (SDH) by examining whether orbital convergence among extant primates is indeed associated with the shared evolutionary history with snakes or the risk that snakes pose for a given species. We predicted that orbital convergence would be higher in species that: 1) have a longer history of sympatry with venomous snakes, 2) are likely to encounter snakes more frequently, 3) are less able to detect or deter snakes due to group size effects, and 4) are more likely to be preyed upon by snakes. Results based on phylogenetically independent contrasts do not support the SDH. Orbital convergence shows no relationship to the shared history with venomous snakes, likelihood of encountering snakes, or group size. Moreover, those species less likely to be targeted as prey by snakes show significantly higher values of orbital convergence. Although an improved ability to detect camouflaged snakes, along with other cryptic stimuli, is likely a consequence of increased orbital convergence, this was unlikely to have been the primary selective force favoring the evolution of stereoscopic vision in primates.

  1. Replication Research and Special Education

    ERIC Educational Resources Information Center

    Travers, Jason C.; Cook, Bryan G.; Therrien, William J.; Coyne, Michael D.

    2016-01-01

    Replicating previously reported empirical research is a necessary aspect of an evidence-based field of special education, but little formal investigation into the prevalence of replication research in the special education research literature has been conducted. Various factors may explain the lack of attention to replication of special education…

  2. Variation in the molecular clock of primates

    PubMed Central

    Moorjani, Priya; Amorim, Carlos Eduardo G.; Arndt, Peter F.; Przeworski, Molly

    2016-01-01

    Events in primate evolution are often dated by assuming a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life history traits, suggesting it should also be found among primates. Motivated by these considerations, we analyze whole genomes from 10 primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs), and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are up to 64% higher in lineages leading from the hominoid–NWM ancestor to NWMs than to apes. Within apes, rates are ∼2% higher in chimpanzees and ∼7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however; in particular, transitions at CpG sites exhibit a more clocklike behavior than do other types, presumably because of their nonreplicative origin. Thus, not only the total rate, but also the mutational spectrum, varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate the human and chimpanzee divergence time is 12.1 million years,​ and the human and gorilla divergence time is 15.1 million years​. PMID:27601674

  3. Variation in the molecular clock of primates.

    PubMed

    Moorjani, Priya; Amorim, Carlos Eduardo G; Arndt, Peter F; Przeworski, Molly

    2016-09-20

    Events in primate evolution are often dated by assuming a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life history traits, suggesting it should also be found among primates. Motivated by these considerations, we analyze whole genomes from 10 primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs), and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are up to 64% higher in lineages leading from the hominoid-NWM ancestor to NWMs than to apes. Within apes, rates are ∼2% higher in chimpanzees and ∼7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however; in particular, transitions at CpG sites exhibit a more clocklike behavior than do other types, presumably because of their nonreplicative origin. Thus, not only the total rate, but also the mutational spectrum, varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate the human and chimpanzee divergence time is 12.1 million years,​ and the human and gorilla divergence time is 15.1 million years​. PMID:27601674

  4. Variation in the molecular clock of primates.

    PubMed

    Moorjani, Priya; Amorim, Carlos Eduardo G; Arndt, Peter F; Przeworski, Molly

    2016-09-20

    Events in primate evolution are often dated by assuming a constant rate of substitution per unit time, but the validity of this assumption remains unclear. Among mammals, it is well known that there exists substantial variation in yearly substitution rates. Such variation is to be expected from differences in life history traits, suggesting it should also be found among primates. Motivated by these considerations, we analyze whole genomes from 10 primate species, including Old World Monkeys (OWMs), New World Monkeys (NWMs), and apes, focusing on putatively neutral autosomal sites and controlling for possible effects of biased gene conversion and methylation at CpG sites. We find that substitution rates are up to 64% higher in lineages leading from the hominoid-NWM ancestor to NWMs than to apes. Within apes, rates are ∼2% higher in chimpanzees and ∼7% higher in the gorilla than in humans. Substitution types subject to biased gene conversion show no more variation among species than those not subject to it. Not all mutation types behave similarly, however; in particular, transitions at CpG sites exhibit a more clocklike behavior than do other types, presumably because of their nonreplicative origin. Thus, not only the total rate, but also the mutational spectrum, varies among primates. This finding suggests that events in primate evolution are most reliably dated using CpG transitions. Taking this approach, we estimate the human and chimpanzee divergence time is 12.1 million years,​ and the human and gorilla divergence time is 15.1 million years​.

  5. Occurrence and distribution of Indian primates

    USGS Publications Warehouse

    Karanth, K.K.; Nichols, J.D.; Hines, J.E.

    2010-01-01

    Global and regional species conservation efforts are hindered by poor distribution data and range maps. Many Indian primates face extinction, but assessments of population status are hindered by lack of reliable distribution data. We estimated the current occurrence and distribution of 15 Indian primates by applying occupancy models to field data from a country-wide survey of local experts. We modeled species occurrence in relation to ecological and social covariates (protected areas, landscape characteristics, and human influences), which we believe are critical to determining species occurrence in India. We found evidence that protected areas positively influence occurrence of seven species and for some species are their only refuge. We found evergreen forests to be more critical for some primates along with temperate and deciduous forests. Elevation negatively influenced occurrence of three species. Lower human population density was positively associated with occurrence of five species, and higher cultural tolerance was positively associated with occurrence of three species. We find that 11 primates occupy less than 15% of the total land area of India. Vulnerable primates with restricted ranges are Golden langur, Arunachal macaque, Pig-tailed macaque, stump-tailed macaque, Phayre's leaf monkey, Nilgiri langur and Lion-tailed macaque. Only Hanuman langur and rhesus macaque are widely distributed. We find occupancy modeling to be useful in determining species ranges, and in agreement with current species ranking and IUCN status. In landscapes where monitoring efforts require optimizing cost, effort and time, we used ecological and social covariates to reliably estimate species occurrence and focus species conservation efforts. ?? Elsevier Ltd.

  6. Retrovirus infections in non-domestic felids: serological studies and attempts to isolate a lentivirus.

    PubMed

    Lutz, H; Isenbügel, E; Lehmann, R; Sabapara, R H; Wolfensberger, C

    1992-12-01

    An African lioness from the Zoo of Zurich had to be euthanized because of an inoperable tumor. The serum tested negative for feline leukemia virus (FeLV) p27 antigen by enzyme-linked immunosorbent assay (ELISA) but was strongly positive for feline immunodeficiency virus (FIV) antibodies by ELISA and Western blot. When her only offspring and mate were tested for FIV, high antibody titers to FIV were also found in their serum. Lymphocytes were prepared from these two lions on different occasions and co-cultivated with specific pathogen free (SPF) cat lymphocytes in the presence of concanavalin A and recombinant human interleukin-2 (IL-2) for 6 weeks. The cell culture supernatants tested negative for Mg(2+)-dependent reverse transcriptase and FIV p24 by a double antibody sandwich ELISA throughout the culture period. Whole blood and buffy coat cells collected from these two lions were transmitted by intraperitoneal injection into two SPF cats. The two cats did not seroconvert for a period of 11 months nor could reverse transcriptase activity and FIV p24 antigen be demonstrated in the supernatant of several lymphocyte cultures. To determine the importance of lentivirus infections in zoo-kept wild felids, 124 serum samples were obtained from African lions, Indian and Siberian tigers, snow leopards, panthers, cheetahs and other wild cats from nine European zoos. In addition, serum samples collected from 12 Asiatic lions originating from Gir forest in the Indian State of Gujarat were included in this study. The sera were tested for antibodies to FIV, FeLV and feline syncytium-forming virus (FeSFV) by ELISA and Western blot using the respective viruses after gradient purification. In addition, some of the sera were also tested for antibodies to equine infectious anemia virus (EIAV) and Visna-Maedi virus (VMV). Antibodies to FIV were found in 30/53 (57%) of African lions, one of 18 tigers and one of four panthers. All other sera including those collected from the 12 Asiatic

  7. Species-Specific, Postentry Barriers to Primate Immunodeficiency Virus Infection

    PubMed Central

    Hofmann, Wolfgang; Schubert, David; LaBonte, Jason; Munson, Linda; Gibson, Susan; Scammell, Jonathan; Ferrigno, Paul; Sodroski, Joseph

    1999-01-01

    By using replication-defective vectors derived from human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIVmac), and murine leukemia virus (MuLV), all of which were pseudotyped with the vesicular stomatitis virus (VSV) G glycoprotein, the efficiency of postentry, early infection events was examined in target cells of several mammalian species. Titers of HIV-1 vectors were significantly lower than those of SIVmac and MuLV vectors in most cell lines and primary cells from Old World monkeys. By contrast, most New World monkey cells exhibited much lower titers for the SIVmac vector compared with those of the HIV-1 vector. Prosimian cells were resistant to both HIV-1 and SIVmac vectors, although the MuLV vector was able to infect these cells. Cells from other mammalian species were roughly equivalent in susceptibility to the three vectors, with the exception of rabbit cells, which were specifically resistant to the HIV-1 vector. The level of HIV-1 vector expression was very low in transduced cells of rodent, rabbit, cow, and pig origin. Early postentry restriction of primate immunodeficiency virus infection exhibits patterns largely coincident with species borders and applies to diverse cell types within an individual host, suggesting the involvement of species-specific, widely expressed cellular factors. PMID:10559316

  8. Modified toolbox for optogenetics in the nonhuman primate

    PubMed Central

    Dai, Ji; Ozden, Ilker; Brooks, Daniel I.; Wagner, Fabien; May, Travis; Agha, Naubahar S.; Brush, Benjamin; Borton, David; Nurmikko, Arto V.; Sheinberg, David L.

    2015-01-01

    Abstract. Attracted by the appealing advantages of optogenetics, many nonhuman primate labs are attempting to incorporate this technique in their experiments. Despite some reported successes by a few groups, many still find it difficult to develop a reliable way to transduce cells in the monkey brain and subsequently monitor light-induced neuronal activity. Here, we describe a methodology that we have developed and successfully deployed on a regular basis with multiple monkeys. All devices and accessories are easy to obtain and results using these have been proven to be highly replicable. We developed the “in-chair” viral injection system and used tapered and thinner fibers for optical stimulation, which significantly improved the efficacy and reduced tissue damage. With these methods, we have successfully transduced cells in multiple monkeys in both deep and shallow cortical areas. We could reliably obtain neural modulation for months after injection, and no light-induced artifacts were observed during recordings. Further experiments using these methods have shown that optogenetic stimulation can be used to bias spatial attention in a visual choice discrimination task in a way comparable to electrical microstimulation, which demonstrates the potential use of our methods in both fundamental research and clinical applications. PMID:26158011

  9. Renal alterations in feline immunodeficiency virus (FIV)-infected cats: a natural model of lentivirus-induced renal disease changes.

    PubMed

    Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro

    2012-09-01

    Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy. PMID:23170163

  10. Renal Alterations in Feline Immunodeficiency Virus (FIV)-Infected Cats: A Natural Model of Lentivirus-Induced Renal Disease Changes

    PubMed Central

    Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro

    2012-01-01

    Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy. PMID:23170163

  11. New insights for Ets2 function in trophoblast using lentivirus-mediated gene knockdown in trophoblast stem cells.

    PubMed

    Odiatis, C; Georgiades, P

    2010-07-01

    Mouse trophoblast stem (TS) cells represent a unique in vitro system that provides an unlimited supply of TS cells for the study of trophoblast differentiation and TS cell self-renewal. Although the mouse transcription factor Ets2 is required for TS cell self-renewal, its role in this and in TS cell differentiation has not been explored fully, partly due to the early lethality of Ets2 null mice. To address this, we developed a novel lentivirus-based system that resulted in efficient Ets2 knockdown in the overwhelming majority of TS cells. This system enables functional studies in TS cells, especially for genes required for TS cell self-renewal because TS cell derivation using gene-knockout embryos for such genes depends on TS cell self-renewal. Using morphological/morphometric criteria and gene expression analysis, we show that the requirement for Ets2 in self-renewal of TS cells cultured in 'stem cell medium' (SCM) involves maintenance of the expression of genes that inhibit TS cell differentiation in SCM, such as Cdx2 and Esrrb, and preservation of the undifferentiated TS cell morphology. During TS cell differentiation caused by Cdx2/Esrrb downregulation, due to either Ets2 knockdown in SCM or culture in differentiation medium (DM), Ets2 is also required for the promotion of trophoblast giant cell (TGC) and junctional zone trophoblast (JZT) differentiation. This TGC differentiation involves Ets2-dependent expression of Hand1, a gene required for the differentiation of all TGC types. This study uncovers new roles for Ets2 in TS cell self-renewal and differentiation and demonstrates the usefulness of this lentivirus system for gene function studies in TS cells.

  12. Canine size, shape, and bending strength in primates and carnivores.

    PubMed

    Plavcan, J Michael; Ruff, Christopher B

    2008-05-01

    Anthropoid primates are well known for their highly sexually dimorphic canine teeth, with males possessing canines that are up to 400% taller than those of females. Primate canine dimorphism has been extensively documented, with a consensus that large male primate canines serve as weapons for intrasexual competition, and some evidence that large female canines in some species may likewise function as weapons. However, apart from speculation that very tall male canines may be relatively weak and that seed predators have strong canines, the functional significance of primate canine shape has not been explored. Because carnivore canine shape and size are associated with killing style, this group provides a useful comparative baseline for primates. We evaluate primate maxillary canine tooth size, shape and relative bending strength against body size, skull size, and behavioral and demographic measures of male competition and sexual selection, and compare them to those of carnivores. We demonstrate that, relative to skull length and body mass, primate male canines are on average as large as or larger than those of similar sized carnivores. The range of primate female canine sizes embraces that of carnivores. Male and female primate canines are generally as strong as or stronger than those of carnivores. Although we find that seed-eating primates have relatively strong canines, we find no clear relationship between male primate canine strength and demographic or behavioral estimates of male competition or sexual selection, in spite of a strong relationship between these measures and canine crown height. This suggests either that most primate canines are selected to be very strong regardless of variation in behavior, or that primate canine shape is inherently strong enough to accommodate changes in crown height without compromising canine function.

  13. Quantum Replicator Dynamics

    NASA Astrophysics Data System (ADS)

    Guevara Hidalgo, Esteban

    2006-09-01

    We propose quantization relationships which would let us describe and solution problems originated by conflicting or cooperative behaviors among the members of a system from the point of view of quantum mechanical interactions. The quantum version of the replicator dynamics is the equation of evolution of mixed states from quantum statistical mechanics. A system and all its members will cooperate and rearrange its states to improve their present condition. They strive to reach the best possible state for each of them which is also the best possible state for the whole system. This led us to propose a quantum equilibrium in which a system is stable only if it maximizes the welfare of the collective above the welfare of the individual. If it is maximized the welfare of the individual above the welfare of the collective the system gets unstable and eventually it collapses.

  14. SUMO and KSHV Replication

    PubMed Central

    Chang, Pei-Ching; Kung, Hsing-Jien

    2014-01-01

    Small Ubiquitin-related MOdifier (SUMO) modification was initially identified as a reversible post-translational modification that affects the regulation of diverse cellular processes, including signal transduction, protein trafficking, chromosome segregation, and DNA repair. Increasing evidence suggests that the SUMO system also plays an important role in regulating chromatin organization and transcription. It is thus not surprising that double-stranded DNA viruses, such as Kaposi’s sarcoma-associated herpesvirus (KSHV), have exploited SUMO modification as a means of modulating viral chromatin remodeling during the latent-lytic switch. In addition, SUMO regulation allows the disassembly and assembly of promyelocytic leukemia protein-nuclear bodies (PML-NBs), an intrinsic antiviral host defense, during the viral replication cycle. Overcoming PML-NB-mediated cellular intrinsic immunity is essential to allow the initial transcription and replication of the herpesvirus genome after de novo infection. As a consequence, KSHV has evolved a way as to produce multiple SUMO regulatory viral proteins to modulate the cellular SUMO environment in a dynamic way during its life cycle. Remarkably, KSHV encodes one gene product (K-bZIP) with SUMO-ligase activities and one gene product (K-Rta) that exhibits SUMO-targeting ubiquitin ligase (STUbL) activity. In addition, at least two viral products are sumoylated that have functional importance. Furthermore, sumoylation can be modulated by other viral gene products, such as the viral protein kinase Orf36. Interference with the sumoylation of specific viral targets represents a potential therapeutic strategy when treating KSHV, as well as other oncogenic herpesviruses. Here, we summarize the different ways KSHV exploits and manipulates the cellular SUMO system and explore the multi-faceted functions of SUMO during KSHV’s life cycle and pathogenesis. PMID:25268162

  15. SUMO and KSHV Replication.

    PubMed

    Chang, Pei-Ching; Kung, Hsing-Jien

    2014-01-01

    Small Ubiquitin-related MOdifier (SUMO) modification was initially identified as a reversible post-translational modification that affects the regulation of diverse cellular processes, including signal transduction, protein trafficking, chromosome segregation, and DNA repair. Increasing evidence suggests that the SUMO system also plays an important role in regulating chromatin organization and transcription. It is thus not surprising that double-stranded DNA viruses, such as Kaposi's sarcoma-associated herpesvirus (KSHV), have exploited SUMO modification as a means of modulating viral chromatin remodeling during the latent-lytic switch. In addition, SUMO regulation allows the disassembly and assembly of promyelocytic leukemia protein-nuclear bodies (PML-NBs), an intrinsic antiviral host defense, during the viral replication cycle. Overcoming PML-NB-mediated cellular intrinsic immunity is essential to allow the initial transcription and replication of the herpesvirus genome after de novo infection. As a consequence, KSHV has evolved a way as to produce multiple SUMO regulatory viral proteins to modulate the cellular SUMO environment in a dynamic way during its life cycle. Remarkably, KSHV encodes one gene product (K-bZIP) with SUMO-ligase activities and one gene product (K-Rta) that exhibits SUMO-targeting ubiquitin ligase (STUbL) activity. In addition, at least two viral products are sumoylated that have functional importance. Furthermore, sumoylation can be modulated by other viral gene products, such as the viral protein kinase Orf36. Interference with the sumoylation of specific viral targets represents a potential therapeutic strategy when treating KSHV, as well as other oncogenic herpesviruses. Here, we summarize the different ways KSHV exploits and manipulates the cellular SUMO system and explore the multi-faceted functions of SUMO during KSHV's life cycle and pathogenesis. PMID:25268162

  16. Nonhuman primate models of polycystic ovary syndrome

    PubMed Central

    Abbott, David H; Nicol, Lindsey E; Levine, Jon E; Xu, Ning; Goodarzi, Mark O; Dumesic, Daniel A

    2013-01-01

    With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction. PMID:23370180

  17. Nonhuman primate models of polycystic ovary syndrome.

    PubMed

    Abbott, David H; Nicol, Lindsey E; Levine, Jon E; Xu, Ning; Goodarzi, Mark O; Dumesic, Daniel A

    2013-07-01

    With close genomic and phenotypic similarity to humans, nonhuman primate models provide comprehensive epigenetic mimics of polycystic ovary syndrome (PCOS), suggesting early life targeting for prevention. Fetal exposure to testosterone (T), of all nonhuman primate emulations, provides the closest PCOS-like phenotypes, with early-to-mid gestation T-exposed female rhesus monkeys exhibiting adult reproductive, endocrinological and metabolic dysfunctional traits that are co-pathologies of PCOS. Late gestational T exposure, while inducing adult ovarian hyperandrogenism and menstrual abnormalities, has less dysfunctional metabolic accompaniment. Fetal exposures to dihydrotestosterone (DHT) or diethylstilbestrol (DES) suggest androgenic and estrogenic aspects of fetal programming. Neonatal exposure to T produces no PCOS-like outcome, while continuous T treatment of juvenile females causes precocious weight gain and early menarche (high T), or high LH and weight gain (moderate T). Acute T exposure of adult females generates polyfollicular ovaries, while chronic T exposure induces subtle menstrual irregularities without metabolic dysfunction.

  18. Nonhuman primate dermatology: a literature review

    PubMed Central

    Bernstein, Joseph A.; Didier, Peter J.

    2015-01-01

    In general, veterinary dermatologists do not have extensive clinical experience of nonhuman primate (NHP) dermatoses. The bulk of the published literature does not provide an organized evidence-based approach to the NHP dermatologic case. The veterinary dermatologist is left to extract information from both human and veterinary dermatology, an approach that can be problematic as it forces the clinician to make diagnostic and therapeutic decisions based on two very disparate bodies of literature. A more cohesive approach to NHP dermatology – without relying on assumptions that NHP pathology most commonly behaves similarly to other veterinary and human disease – is required. This review of the dermatology of NHP species includes discussions of primary dermatoses, as well as diseases where dermatologic signs represent a significant secondary component, provides a first step towards encouraging the veterinary community to study and report the dermatologic diseases of nonhuman primates. PMID:19490576

  19. Optogenetics in primates: a shining future?

    PubMed

    Gerits, Annelies; Vanduffel, Wim

    2013-07-01

    To understand the functional role of specific neurons in micro- and macro-brain circuitry, health, and disease, it is critical to control their activity precisely. This ambitious goal was first achieved by optogenetics, allowing researchers to increase or decrease neural activity artificially with high temporal and spatial precision. In contrast to the revolution optogenetics engendered in invertebrate and rodent research, only a few studies have reported optogenetic-induced neuronal and behavioral effects in primates. Such studies are nonetheless critical before optogenetics can be applied in a clinical setting. Here, we review the state-of-the-art tools for performing optogenetics in mammals, emphasizing recent neuronal and behavioral results obtained in nonhuman primates.

  20. Induced Pluripotent Stem Cells from Nonhuman Primates.

    PubMed

    Mishra, Anuja; Qiu, Zhifang; Farnsworth, Steven L; Hemmi, Jacob J; Li, Miao; Pickering, Alexander V; Hornsby, Peter J

    2016-01-01

    Induced pluripotent stem cells from nonhuman primates (NHPs) have unique roles in cell biology and regenerative medicine. Because of the relatedness of NHPs to humans, NHP iPS cells can serve as a source of differentiated derivatives that can be used to address important questions in the comparative biology of primates. Additionally, when used as a source of cells for regenerative medicine, NHP iPS cells serve an invaluable role in translational experiments in cell therapy. Reprogramming of NHP somatic cells requires the same conditions as previously established for human cells. However, throughout the process, a variety of modifications to the human cell protocols must be made to accommodate significant species differences.

  1. [Ecotourism disturbances to non-human primates].

    PubMed

    Fan, Peng-Lai; Xiang, Zuo-Fu

    2013-02-01

    In tandem with economic growth and rising living conditions, ecotourism has increasingly gained popularity among the Chinese public. Non-human primates, as charismatic animals and the closest relatives of human beings, have shown a strong affinity in attracting the general public and raising money, and for that reason a variety of monkey parks, valleys, and islands are becoming increasingly popular in China. Though successful in raising a substantial sum of money for the managing agency of a nature reserve, there may be negative impacts on monkey groups used in ecotourism. Here, to establish effective guards for non-human primates involved in ecotourism, we present a review on tourism disturbance and summarize the negative impacts on behavioral patterns, reproduction, and health condition of animals. PMID:23389980

  2. [Ecotourism disturbances to non-human primates].

    PubMed

    Fan, Peng-Lai; Xiang, Zuo-Fu

    2013-02-01

    In tandem with economic growth and rising living conditions, ecotourism has increasingly gained popularity among the Chinese public. Non-human primates, as charismatic animals and the closest relatives of human beings, have shown a strong affinity in attracting the general public and raising money, and for that reason a variety of monkey parks, valleys, and islands are becoming increasingly popular in China. Though successful in raising a substantial sum of money for the managing agency of a nature reserve, there may be negative impacts on monkey groups used in ecotourism. Here, to establish effective guards for non-human primates involved in ecotourism, we present a review on tourism disturbance and summarize the negative impacts on behavioral patterns, reproduction, and health condition of animals.

  3. Relaxin and the control of primate parturition.

    PubMed

    Weiss, Gerson

    2013-01-01

    In primate pregnancy, circulating relaxin, solely a product of the corpus luteum, peaks in the first trimester of pregnancy then declines and levels off for the remainder of pregnancy. Relaxin actions in pregnancy include increasing cervical pro-MMP-1 and pro-MMP-3 and decreasing TIMP-1, changes which soften the cervix. Relaxin, from early pregnancy, increases endometrial natural killer cells, macrophages and neutrophils, blood flow and arterial number. Hyperrelaxinemia correlates with preterm birth.

  4. Molecular evolution of prolactin in primates.

    PubMed

    Wallis, O Caryl; Mac-Kwashie, Akofa O; Makri, Georgia; Wallis, Michael

    2005-05-01

    Pituitary prolactin, like growth hormone (GH) and several other protein hormones, shows an episodic pattern of molecular evolution in which sustained bursts of rapid change contrast with long periods of slow evolution. A period of rapid change occurred in the evolution of prolactin in primates, leading to marked sequence differences between human prolactin and that of nonprimate mammals. We have defined this burst more precisely by sequencing the coding regions of prolactin genes for a prosimian, the slow loris (Nycticebus pygmaeus), and a New World monkey, the marmoset (Callithrix jacchus). Slow loris prolactin is very similar in sequence to pig prolactin, so the episode of rapid change occurred during primate evolution, after the separation of lines leading to prosimians and higher primates. Marmoset prolactin is similar in sequence to human prolactin, so the accelerated evolution occurred before divergence of New World monkeys and Old World monkeys/apes. The burst of change was confined largely to coding sequence (nonsynonymous sites) for mature prolactin and is not marked in other components of the gene sequence. This and the observations that (1) there was no apparent loss of function during the episode of rapid evolution, (2) the rate of evolution slowed toward the basal rate after this burst, and (3) the distribution of substitutions in the prolactin molecule is very uneven support the idea that this episode of rapid change was due to positive adaptive selection. In the slow loris and marmoset there is no evidence for duplication of the prolactin gene, and evidence from another New World monkey (Cebus albifrons) and from the chimpanzee and human genome sequences, suggests that this is the general position in primates, contrasting with the situation for GH genes. The chimpanzee prolactin sequence differs from that of human at two residues and comparison of human and chimpanzee prolactin gene sequences suggests that noncoding regions associated with regulating

  5. Classification and automatic transcription of primate calls.

    PubMed

    Versteegh, Maarten; Kuhn, Jeremy; Synnaeve, Gabriel; Ravaux, Lucie; Chemla, Emmanuel; Cäsar, Cristiane; Fuller, James; Murphy, Derek; Schel, Anne; Dunbar, Ewan

    2016-07-01

    This paper reports on an automated and openly available tool for automatic acoustic analysis and transcription of primate calls, which takes raw field recordings and outputs call labels time-aligned with the audio. The system's output predicts a majority of the start times of calls accurately within 200 milliseconds. The tools do not require any manual acoustic analysis or selection of spectral features by the researcher.

  6. Argentine hemorrhagic fever: a primate model.

    PubMed

    Weissenbacher, M C; Calello, M A; Colillas, O J; Rondinone, S N; Frigerio, M J

    1979-01-01

    Experimental Junin virus infection of a New World primate, Callithrix jacchus, was evaluated. The virus produced anorexia, loss of weight, thrombocytopenia, leukopenia, and hemorrhagic and neurological symptoms and terminated in death. Virus was recovered from urine, blood samples and all tissues taken at autopsy. These preliminary observations show that several aspects of the experimental disease in C. jacchus are quite similar to severe natural Argentine hemorrhagic fever of man.

  7. Classification and automatic transcription of primate calls.

    PubMed

    Versteegh, Maarten; Kuhn, Jeremy; Synnaeve, Gabriel; Ravaux, Lucie; Chemla, Emmanuel; Cäsar, Cristiane; Fuller, James; Murphy, Derek; Schel, Anne; Dunbar, Ewan

    2016-07-01

    This paper reports on an automated and openly available tool for automatic acoustic analysis and transcription of primate calls, which takes raw field recordings and outputs call labels time-aligned with the audio. The system's output predicts a majority of the start times of calls accurately within 200 milliseconds. The tools do not require any manual acoustic analysis or selection of spectral features by the researcher. PMID:27475207

  8. THE KINEMATICS OF PRIMATE MIDFOOT FLEXIBILITY

    PubMed Central

    Greiner, Thomas M.; Ball, Kevin A.

    2015-01-01

    This study describes a unique assessment of primate intrinsic foot joint kinematics based upon bone pin rigid cluster tracking. It challenges the assumption that human evolution resulted in a reduction of midfoot flexibility, which has been identified in other primates as the “midtarsal break.” Rigid cluster pins were inserted into the foot bones of human, chimpanzee, baboon and macaque cadavers. The positions of these bone pins were monitored during a plantarflexion-dorsiflexion movement cycle. Analysis resolved flexion-extension movement patterns and the associated orientation of rotational axes for the talonavicular, calcaneocuboid and lateral cubometatarsal joints. Results show that midfoot flexibility occurs primarily at the talonavicular and cubometatarsal joints. The rotational magnitudes are roughly similar between humans and chimps. There is also a similarity among evaluated primates in the observed rotations of the lateral cubometatarsal joint, but there was much greater rotation observed for the talonavicular joint, which may serve to differentiate monkeys from the hominines. It appears that the capability for a midtarsal break is present within the human foot. A consideration of the joint axes shows that the medial and lateral joints have opposing orientations, which has been associated with a rigid locking mechanism in the human foot. However, the potential for this same mechanism also appears in the chimpanzee foot. These findings demonstrate a functional similarity within the midfoot of the hominines. Therefore, the kinematic capabilities and restrictions for the skeletal linkages of the human foot may not be as unique as has been previously suggested. PMID:25234343

  9. Ecological importance of trichromatic vision to primates.

    PubMed

    Dominy, N J; Lucas, P W

    2001-03-15

    Trichromatic colour vision, characterized by three retinal photopigments tuned to peak wavelengths of approximately 430 nm, approximately 535 nm and approximately 562 nm (refs 1, 2), has evolved convergently in catarrhine primates and one genus of New World monkey, the howlers (genus Alouatta). This uniform capacity to discriminate red-green colours, which is not found in other mammals, has been proposed as advantageous for the long-range detection of either ripe fruits or young leaves (which frequently flush red in the tropics) against a background of mature foliage. Here we show that four trichromatic primate species in Kibale Forest, Uganda, eat leaves that are colour discriminated only by red-greenness, a colour axis correlated with high protein levels and low toughness. Despite their divergent digestive systems, these primates have no significant interspecific differences in leaf colour selection. In contrast, eaten fruits were generally discriminated from mature leaves on both red-green and yellow-blue channels and also by their luminance, with a significant difference between chimpanzees and monkeys in fruit colour choice. Our results implicate leaf consumption, a critical food resource when fruit is scarce, as having unique value in maintaining trichromacy in catarrhines. PMID:11268211

  10. Behavioral abnormalities in captive nonhuman primates.

    PubMed

    Mallapur, Avanti; Choudhury, B C

    2003-01-01

    In this study, we dealt with 11 species of nonhuman primates across 10 zoos in India. We recorded behavior as instantaneous scans between 9 a.m. and 5 p.m. In the study, we segregated behaviors for analyses into abnormal, undesirable, active, and resting. The 4 types of abnormal behavior exhibited included floating limb, self-biting, self-clasping, and stereotypic pacing. In the study, we recorded 2 types of undesirable behavior: autoerotic stimulation and begging. Langurs and group-housed macaques did not exhibit undesirable behaviors. A male lion-tailed macaque and a male gibbon exhibited begging behavior. autoerotic stimulation and self-biting occurred rarely. Males exhibited higher levels of undesirable behavior than did females. Animals confiscated from touring zoos, circuses, and animal traders exhibited higher levels of abnormal behaviors than did animals reared in larger, recognized zoos. The stump-tailed macaque was the only species to exhibit floating limb, autoerotic stimulation, self-biting, and self-clasping. Our results show that rearing experience and group composition influence the proportions of abnormal behavior exhibited by nonhuman primates in captivity. The history of early social and environmental deprivation in these species of captive nonhuman primates probably is critical in the development of behavioral pathologies. Establishing this will require further research.

  11. Emotions, stress, and maternal motivation in primates.

    PubMed

    Maestripieri, Dario

    2011-06-01

    Recent research conducted with nonhuman primates confirms that adaptive emotional processes, such as maternal attraction arousability and maternal anxiety arousability, enhance and sustain female motivation to interact with infants, invest in them, and protect them during the postpartum period. Changes in these emotional processes, and concomitant changes in maternal motivation, facilitate the reduction and eventual termination of maternal investment associated with infant weaning. Although laboratory studies of rodents and socially deprived rhesus monkeys have suggested that nulliparous females are neophobic and find infant stimuli aversive, recent primate research indicates that neophobia or aversion to infant stimuli do not occur in females with normal developmental experience. Furthermore, although some rodent and human studies have shown that lactation is accompanied by physiological hyporesponsiveness to stress, other studies of rodents, nonhuman primates, and humans indicate that mothers are highly vulnerable to stress and that stress-induced dysregulation of emotions can interfere with maternal motivation and parenting behavior. It is possible that some aspects of the emotional and experiential regulation of maternal motivation and parental behavior are different in different mammalian species. However, variation in the environments in which subjects are tested and in their developmental experience may also be responsible for the some discrepancies between the results of different studies.

  12. Phylogenomics of primates and their ancestral populations

    PubMed Central

    Siepel, Adam

    2009-01-01

    Genome assemblies are now available for nine primate species, and large-scale sequencing projects are underway or approved for six others. An explicitly evolutionary and phylogenetic approach to comparative genomics, called phylogenomics, will be essential in unlocking the valuable information about evolutionary history and genomic function that is contained within these genomes. However, most phylogenomic analyses so far have ignored the effects of variation in ancestral populations on patterns of sequence divergence. These effects can be pronounced in the primates, owing to large ancestral effective population sizes relative to the intervals between speciation events. In particular, local genealogies can vary considerably across loci, which can produce biases and diminished power in many phylogenomic analyses of interest, including phylogeny reconstruction, the identification of functional elements, and the detection of natural selection. At the same time, this variation in genealogies can be exploited to gain insight into the nature of ancestral populations. In this Perspective, I explore this area of intersection between phylogenetics and population genetics, and its implications for primate phylogenomics. I begin by “lifting the hood” on the conventional tree-like representation of the phylogenetic relationships between species, to expose the population-genetic processes that operate along its branches. Next, I briefly review an emerging literature that makes use of the complex relationships among coalescence, recombination, and speciation to produce inferences about evolutionary histories, ancestral populations, and natural selection. Finally, I discuss remaining challenges and future prospects at this nexus of phylogenetics, population genetics, and genomics. PMID:19801602

  13. Supercoiling, knotting and replication fork reversal in partially replicated plasmids

    PubMed Central

    Olavarrieta, L.; Martínez-Robles, M. L.; Sogo, J. M.; Stasiak, A.; Hernández, P.; Krimer, D. B.; Schvartzman, J. B.

    2002-01-01

    To study the structure of partially replicated plasmids, we cloned the Escherichia coli polar replication terminator TerE in its active orientation at different locations in the ColE1 vector pBR18. The resulting plasmids, pBR18-TerE@StyI and pBR18-TerE@EcoRI, were analyzed by neutral/neutral two-dimensional agarose gel electrophoresis and electron microscopy. Replication forks stop at the Ter–TUS complex, leading to the accumulation of specific replication intermediates with a mass 1.26 times the mass of non-replicating plasmids for pBR18-TerE@StyI and 1.57 times for pBR18-TerE@EcoRI. The number of knotted bubbles detected after digestion with ScaI and the number and electrophoretic mobility of undigested partially replicated topoisomers reflect the changes in plasmid topology that occur in DNA molecules replicated to different extents. Exposure to increasing concentrations of chloroquine or ethidium bromide revealed that partially replicated topoisomers (CCCRIs) do not sustain positive supercoiling as efficiently as their non-replicating counterparts. It was suggested that this occurs because in partially replicated plasmids a positive ΔLk is absorbed by regression of the replication fork. Indeed, we showed by electron microscopy that, at least in the presence of chloroquine, some of the CCCRIs of pBR18-Ter@StyI formed Holliday-like junction structures characteristic of reversed forks. However, not all the positive supercoiling was absorbed by fork reversal in the presence of high concentrations of ethidium bromide. PMID:11809877

  14. The oldest known primate skeleton and early haplorhine evolution.

    PubMed

    Ni, Xijun; Gebo, Daniel L; Dagosto, Marian; Meng, Jin; Tafforeau, Paul; Flynn, John J; Beard, K Christopher

    2013-06-01

    Reconstructing the earliest phases of primate evolution has been impeded by gaps in the fossil record, so that disagreements persist regarding the palaeobiology and phylogenetic relationships of the earliest primates. Here we report the discovery of a nearly complete and partly articulated skeleton of a primitive haplorhine primate from the early Eocene of China, about 55 million years ago, the oldest fossil primate of this quality ever recovered. Coupled with detailed morphological examination using propagation phase contrast X-ray synchrotron microtomography, our phylogenetic analysis based on total available evidence indicates that this fossil is the most basal known member of the tarsiiform clade. In addition to providing further support for an early dichotomy between the strepsirrhine and haplorhine clades, this new primate further constrains the age of divergence between tarsiiforms and anthropoids. It also strengthens the hypothesis that the earliest primates were probably diurnal, arboreal and primarily insectivorous mammals the size of modern pygmy mouse lemurs.

  15. KSHV Genome Replication and Maintenance

    PubMed Central

    Purushothaman, Pravinkumar; Dabral, Prerna; Gupta, Namrata; Sarkar, Roni; Verma, Subhash C.

    2016-01-01

    Kaposi's sarcoma associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8) is a major etiological agent for multiple severe malignancies in immune-compromised patients. KSHV establishes lifetime persistence in the infected individuals and displays two distinct life cycles, generally a prolonged passive latent, and a short productive or lytic cycle. During latent phase, the viral episome is tethered to the host chromosome and replicates once during every cell division. Latency-associated nuclear antigen (LANA) is a predominant multifunctional nuclear protein expressed during latency, which plays a central role in episome tethering, replication and perpetual segregation of the episomes during cell division. LANA binds cooperatively to LANA binding sites (LBS) within the terminal repeat (TR) region of the viral episome as well as to the cellular nucleosomal proteins to tether viral episome to the host chromosome. LANA has been shown to modulate multiple cellular signaling pathways and recruits various cellular proteins such as chromatin modifying enzymes, replication factors, transcription factors, and cellular mitotic framework to maintain a successful latent infection. Although, many other regions within the KSHV genome can initiate replication, KSHV TR is important for latent DNA replication and possible segregation of the replicated episomes. Binding of LANA to LBS favors the recruitment of various replication factors to initiate LANA dependent DNA replication. In this review, we discuss the molecular mechanisms relevant to KSHV genome replication, segregation, and maintenance of latency. PMID:26870016

  16. Lentivirus-Mediated Knockdown of Astrocyte Elevated Gene-1 Inhibits Growth and Induces Apoptosis through MAPK Pathways in Human Retinoblastoma Cells

    PubMed Central

    Chang, Ying; Li, Bin; Xu, Xiaolin; Shen, Ling; Bai, Haixia; Gao, Fei; Zhang, Zhibao; Jonas, Jost B.

    2016-01-01

    Purpose To explore expression and function of astrocyte elevated gene-1 (AEG-1) in human retinoblastoma (RB). Methods The expression of AEG-1 in histological sections of human RBs and in RB cell lines was examined using immunohistochemical staining and RT-PCR and Western blotting respectively. We knocked down AEG-1 gene levels by AEG-1-siRNA lentivirus transfection of human RB cell lines SO-RB50 and Y79, and using an MTT assay, we assessed the role of AEG-1 on RB cell proliferation. The biological significance of lentivirus transfection induced AEG-1 down-regulation was examined by assessing the apoptosis rate in the transfected RB cells by Annexin V-APC staining and flow cytometry. We additionally measured the expression of Bcl-2, Bax, cleaved-caspase-3 and caspase-3, and the phosphorylation and non-phosphorylation alternation of MAPKs. Results AEG-1 expression was detected to be strongly positive in the histological slides of 35 out of 54 (65%) patients with RB. AEG-1 expression increased significantly (P<0.05) with tumor stage. In the RB cell lines SO-RB50, Y79 and WERI-RB1 as compared with retinal pigment epithelium cells, expression of AEG-1 mRNA and AEG-1 protein was significantly higher. In AEG-1-siRNA lentivirus transfected cell cultures as compared with negative control lentivirus transfected cell cultures, levels of AEG-1 mRNA and of AEG-1 protein (P<0.05) and cell growth rates (P<0.01) were significantly lower, and apoptosis rate (P<0.001), Bax/Bcl-2 ratio and cleaved-caspase-3 protein level were significantly increased. The P-ERK/ERK ratio was significantly decreased in the AEG-1-siRNA lentivirus transfected cell lines. Conclusions Expression of AEG-1 was associated with RB, in histological slides of patients and in cell culture experiments. Lentivirus transfection induced knockdown of AEG-1 had a tumor suppressive effect, potentially by tumor cell apoptosis induction through inhibition of ERK. PMID:26894431

  17. The asymmetry of telomere replication contributes to replicative senescence heterogeneity.

    PubMed

    Bourgeron, Thibault; Xu, Zhou; Doumic, Marie; Teixeira, Maria Teresa

    2015-10-15

    In eukaryotes, the absence of telomerase results in telomere shortening, eventually leading to replicative senescence, an arrested state that prevents further cell divisions. While replicative senescence is mainly controlled by telomere length, the heterogeneity of its onset is not well understood. This study proposes a mathematical model based on the molecular mechanisms of telomere replication and shortening to decipher the causes of this heterogeneity. Using simulations fitted on experimental data obtained from individual lineages of senescent Saccharomyces cerevisiae cells, we decompose the sources of senescence heterogeneity into interclonal and intraclonal components, and show that the latter is based on the asymmetry of the telomere replication mechanism. We also evidence telomere rank-switching events with distinct frequencies in short-lived versus long-lived lineages, revealing that telomere shortening dynamics display important variations. Thus, the intrinsic heterogeneity of replicative senescence and its consequences find their roots in the asymmetric structure of telomeres.

  18. The adaptive value of primate color vision for predator detection.

    PubMed

    Pessoa, Daniel Marques Almeida; Maia, Rafael; de Albuquerque Ajuz, Rafael Cavalcanti; De Moraes, Pedro Zurvaino Palmeira Melo Rosa; Spyrides, Maria Helena Constantino; Pessoa, Valdir Filgueiras

    2014-08-01

    The complex evolution of primate color vision has puzzled biologists for decades. Primates are the only eutherian mammals that evolved an enhanced capacity for discriminating colors in the green-red part of the spectrum (trichromatism). However, while Old World primates present three types of cone pigments and are routinely trichromatic, most New World primates exhibit a color vision polymorphism, characterized by the occurrence of trichromatic and dichromatic females and obligatory dichromatic males. Even though this has stimulated a prolific line of inquiry, the selective forces and relative benefits influencing color vision evolution in primates are still under debate, with current explanations focusing almost exclusively at the advantages in finding food and detecting socio-sexual signals. Here, we evaluate a previously untested possibility, the adaptive value of primate color vision for predator detection. By combining color vision modeling data on New World and Old World primates, as well as behavioral information from human subjects, we demonstrate that primates exhibiting better color discrimination (trichromats) excel those displaying poorer color visions (dichromats) at detecting carnivoran predators against the green foliage background. The distribution of color vision found in extant anthropoid primates agrees with our results, and may be explained by the advantages of trichromats and dichromats in detecting predators and insects, respectively. PMID:24535839

  19. Comparative primate genomics: emerging patterns of genome content and dynamics.

    PubMed

    Rogers, Jeffrey; Gibbs, Richard A

    2014-05-01

    Advances in genome sequencing technologies have created new opportunities for comparative primate genomics. Genome assemblies have been published for various primate species, and analyses of several others are underway. Whole-genome assemblies for the great apes provide remarkable new information about the evolutionary origins of the human genome and the processes involved. Genomic data for macaques and other non-human primates offer valuable insights into genetic similarities and differences among species that are used as models for disease-related research. This Review summarizes current knowledge regarding primate genome content and dynamics, and proposes a series of goals for the near future.

  20. Comparative primate genomics: emerging patterns of genome content and dynamics.

    PubMed

    Rogers, Jeffrey; Gibbs, Richard A

    2014-05-01

    Advances in genome sequencing technologies have created new opportunities for comparative primate genomics. Genome assemblies have been published for various primate species, and analyses of several others are underway. Whole-genome assemblies for the great apes provide remarkable new information about the evolutionary origins of the human genome and the processes involved. Genomic data for macaques and other non-human primates offer valuable insights into genetic similarities and differences among species that are used as models for disease-related research. This Review summarizes current knowledge regarding primate genome content and dynamics, and proposes a series of goals for the near future. PMID:24709753

  1. Comparative primate genomics: emerging patterns of genome content and dynamics

    PubMed Central

    Rogers, Jeffrey; Gibbs, Richard A.

    2014-01-01

    Preface Advances in genome sequencing technologies have created new opportunities for comparative primate genomics. Genome assemblies have been published for several primates, with analyses of several others underway. Whole genome assemblies for the great apes provide remarkable new information about the evolutionary origins of the human genome and the processes involved. Genomic data for macaques and other nonhuman primates provide valuable insight into genetic similarities and differences among species used as models for disease-related research. This review summarizes current knowledge regarding primate genome content and dynamics and offers a series of goals for the near future. PMID:24709753

  2. Why is a landscape perspective important in studies of primates?

    PubMed

    Arroyo-Rodríguez, Víctor; Fahrig, Lenore

    2014-10-01

    With accelerated deforestation and fragmentation through the tropics, assessing the impact that landscape spatial changes may have on biodiversity is paramount, as this information is required to design and implement effective management and conservation plans. Primates are expected to be particularly dependent on the landscape context; yet, our understanding on this topic is limited as the majority of primate studies are at the local scale, meaning that landscape-scale inferences are not possible. To encourage primatologists to assess the impact of landscape changes on primates, and help future studies on the topic, we describe the meaning of a "landscape perspective" and evaluate important assumptions of using such a methodological approach. We also summarize a number of important, but unanswered, questions that can be addressed using a landscape-scale study design. For example, it is still unclear if habitat loss has larger consistent negative effects on primates than habitat fragmentation per se. Furthermore, interaction effects between habitat area and other landscape effects (e.g., fragmentation) are unknown for primates. We also do not know if primates are affected by synergistic interactions among factors at the landscape scale (e.g., habitat loss and diseases, habitat loss and climate change, hunting, and land-use change), or whether landscape complexity (or landscape heterogeneity) is important for primate conservation. Testing for patterns in the responses of primates to landscape change will facilitate the development of new guidelines and principles for improving primate conservation.

  3. The adaptive value of primate color vision for predator detection.

    PubMed

    Pessoa, Daniel Marques Almeida; Maia, Rafael; de Albuquerque Ajuz, Rafael Cavalcanti; De Moraes, Pedro Zurvaino Palmeira Melo Rosa; Spyrides, Maria Helena Constantino; Pessoa, Valdir Filgueiras

    2014-08-01

    The complex evolution of primate color vision has puzzled biologists for decades. Primates are the only eutherian mammals that evolved an enhanced capacity for discriminating colors in the green-red part of the spectrum (trichromatism). However, while Old World primates present three types of cone pigments and are routinely trichromatic, most New World primates exhibit a color vision polymorphism, characterized by the occurrence of trichromatic and dichromatic females and obligatory dichromatic males. Even though this has stimulated a prolific line of inquiry, the selective forces and relative benefits influencing color vision evolution in primates are still under debate, with current explanations focusing almost exclusively at the advantages in finding food and detecting socio-sexual signals. Here, we evaluate a previously untested possibility, the adaptive value of primate color vision for predator detection. By combining color vision modeling data on New World and Old World primates, as well as behavioral information from human subjects, we demonstrate that primates exhibiting better color discrimination (trichromats) excel those displaying poorer color visions (dichromats) at detecting carnivoran predators against the green foliage background. The distribution of color vision found in extant anthropoid primates agrees with our results, and may be explained by the advantages of trichromats and dichromats in detecting predators and insects, respectively.

  4. FKBP8 interact with classical swine fever virus NS5A protein and promote virus RNA replication.

    PubMed

    Li, Helin; Zhang, Chengcheng; Cui, Hongjie; Guo, Kangkang; Wang, Fang; Zhao, Tianyue; Liang, Wulong; Lv, Qizhuang; Zhang, Yanming

    2016-02-01

    The non-structural 5A (NS5A) protein of classical swine fever virus (CSFV) is proven to be involved in viral replication and can also modulate cellular signaling and host cellular responses via to its ability to interact with various cellular proteins. FKBP8 is also reported to promote virus replication. Here, we show that NS5A specifically interacts with FKBP8 through coimmunoprecipitation and GST-pulldown studies. Additionally, confocal microscopy study showed that NS5A and FKBP8 colocalized in the cytoplasm. Overexpression of FKBP8 via the eukaryotic expression plasmid pDsRED N1 significantly promoted viral RNA synthesis. The cells knockdown of FKBP8 by lentivirus-mediated shRNA markedly decreased the virus replication when infected with CSFV. These data suggest that FKBP8 plays a critical role in the viral life cycle, particularly during the virus RNA replication period. The investigation of FKBP8 protein functions may be beneficial for developing new strategies to treat CSFV infection. PMID:26748656

  5. Charter School Replication. Policy Guide

    ERIC Educational Resources Information Center

    Rhim, Lauren Morando

    2009-01-01

    "Replication" is the practice of a single charter school board or management organization opening several more schools that are each based on the same school model. The most rapid strategy to increase the number of new high-quality charter schools available to children is to encourage the replication of existing quality schools. This policy guide…

  6. Validation-based insertional mutagenesis for identification of Nup214 as a host factor for EV71 replication in RD cells

    SciTech Connect

    Wang, Bei; Zhang, XiaoYu; Zhao, Zhendong

    2013-08-02

    Highlights: •We introduced a new mutagenesis strategy named VBIM to the viral research. •This method can identify either host factors or host restriction factors. •Using VBIM system, we identified Nup214 as a host factor for EV71 replication in RD cells. -- Abstract: Lentiviral validation-based insertional mutagenesis (VBIM) is a sophisticated, forward genetic approach that is used for the investigation of signal transduction in mammalian cells. Using VBIM, we conducted function-based genetic screening for host genes that affect enterovirus 71 (EV71) viral replication. This included host factors that are required for the life cycle of EV71 and host restriction factors that inhibit EV71 replication. Several cell clones, resistant to EV71, were produced using EV71 infection as a selection pressure and the nuclear pore protein 214 (Nup214) was identified as a host factor required for EV71 replication. In SD2-2, the corresponding VBIM lentivirus transformed clone, the expression of endogenous Nup214 was significantly down-regulated by the reverse inserted VBIM promoter. After Cre recombinase-mediated excision of the VBIM promoter, the expression of Nup214 recovered and the clone regained sensitivity to the EV71 infection. Furthermore, over-expression of Nup214 in the cells suggested that Nup214 was promoting EV71 replication. Results of this study indicate that a successful mutagenesis strategy has been established for screening host genes related to viral replication.

  7. Measles Vaccination of Nonhuman Primates Provides Partial Protection against Infection with Canine Distemper Virus

    PubMed Central

    de Vries, Rory D.; Ludlow, Martin; Verburgh, R. Joyce; van Amerongen, Geert; Yüksel, Selma; Nguyen, D. Tien; McQuaid, Stephen; Osterhaus, Albert D. M. E.; Duprex, W. Paul

    2014-01-01

    ABSTRACT Measles virus (MV) is being considered for global eradication, which would likely reduce compliance with MV vaccination. As a result, children will grow up without MV-specific immunity, creating a potential niche for closely related animal morbilliviruses such as canine distemper virus (CDV). Natural CDV infection causing clinical signs has never been reported in humans, but recent outbreaks in captive macaques have shown that CDV can cause disease in primates. We studied the virulence and tropism of recombinant CDV expressing enhanced green fluorescent protein in naive and measles-vaccinated cynomolgus macaques. In naive animals CDV caused viremia and fever and predominantly infected CD150+ lymphocytes and dendritic cells. Virus was reisolated from the upper and lower respiratory tracts, but infection of epithelial or neuronal cells was not detectable at the time points examined, and the infections were self-limiting. This demonstrates that CDV readily infects nonhuman primates but suggests that additional mutations are necessary to achieve full virulence in nonnatural hosts. Partial protection against CDV was observed in measles-vaccinated macaques, as demonstrated by accelerated control of virus replication and limited shedding from the upper respiratory tract. While neither CDV infection nor MV vaccination induced detectable cross-reactive neutralizing antibodies, MV-specific neutralizing antibody levels of MV-vaccinated macaques were boosted by CDV challenge infection, suggesting that cross-reactive VN epitopes exist. Rapid increases in white blood cell counts in MV-vaccinated macaques following CDV challenge suggested that cross-reactive cellular immune responses were also present. This study demonstrates that zoonotic morbillivirus infections can be controlled by measles vaccination. IMPORTANCE Throughout history viral zoonoses have had a substantial impact on human health. Given the drive toward global eradication of measles, it is essential to

  8. Comparative analysis of the primate X-inactivation center region and reconstruction of the ancestral primate XIST locus

    PubMed Central

    Horvath, Julie E.; Sheedy, Christina B.; Merrett, Stephanie L.; Diallo, Abdoulaye Banire; Swofford, David L.; NISC Comparative Sequencing Program; Green, Eric D.; Willard, Huntington F.

    2011-01-01

    Here we provide a detailed comparative analysis across the candidate X-Inactivation Center (XIC) region and the XIST locus in the genomes of six primates and three mammalian outgroup species. Since lemurs and other strepsirrhine primates represent the sister lineage to all other primates, this analysis focuses on lemurs to reconstruct the ancestral primate sequences and to gain insight into the evolution of this region and the genes within it. This comparative evolutionary genomics approach reveals significant expansion in genomic size across the XIC region in higher primates, with minimal size alterations across the XIST locus itself. Reconstructed primate ancestral XIC sequences show that the most dramatic changes during the past 80 million years occurred between the ancestral primate and the lineage leading to Old World monkeys. In contrast, the XIST locus compared between human and the primate ancestor does not indicate any dramatic changes to exons or XIST-specific repeats; rather, evolution of this locus reflects small incremental changes in overall sequence identity and short repeat insertions. While this comparative analysis reinforces that the region around XIST has been subject to significant genomic change, even among primates, our data suggest that evolution of the XIST sequences themselves represents only small lineage-specific changes across the past 80 million years. PMID:21518738

  9. Regulating DNA Replication in Plants

    PubMed Central

    Sanchez, Maria de la Paz; Costas, Celina; Sequeira-Mendes, Joana; Gutierrez, Crisanto

    2012-01-01

    Chromosomal DNA replication in plants has requirements and constraints similar to those in other eukaryotes. However, some aspects are plant-specific. Studies of DNA replication control in plants, which have unique developmental strategies, can offer unparalleled opportunities of comparing regulatory processes with yeast and, particularly, metazoa to identify common trends and basic rules. In addition to the comparative molecular and biochemical studies, genomic studies in plants that started with Arabidopsis thaliana in the year 2000 have now expanded to several dozens of species. This, together with the applicability of genomic approaches and the availability of a large collection of mutants, underscores the enormous potential to study DNA replication control in a whole developing organism. Recent advances in this field with particular focus on the DNA replication proteins, the nature of replication origins and their epigenetic landscape, and the control of endoreplication will be reviewed. PMID:23209151

  10. Lentivirus Gene Transfer in Murine Hematopoietic Progenitor Cells Is Compromised by a Delay in Proviral Integration and Results in Transduction Mosaicism and Heterogeneous Gene Expression in Progeny Cells

    PubMed Central

    Mikkola, Hanna; Woods, Niels-Bjarne; Sjögren, Marketa; Helgadottir, Hildur; Hamaguchi, Isao; Jacobsen, Sten-Eirik; Trono, Didier; Karlsson, Stefan

    2000-01-01

    Human immunodeficiency virus type 1-based lentivirus vectors containing the green fluorescent protein (GFP) gene were used to transduce murine Lin− c-kit+ Sca1+ primitive hematopoietic progenitor cells. Following transduction, the cells were plated into hematopoietic progenitor cell assays in methylcellulose and the colonies were scored for GFP positivity. After incubation for 20 h, lentivirus vectors transduced 27.3% ± 6.7% of the colonies derived from unstimulated target cells, but transduction was more efficient when the cells were supported with stem cell factor (SCF) alone (42.0% ± 5.5%) or SCF, interleukin-3 (IL-3), and IL-6 (53.3 ± 1.8%) during transduction. The, vesicular stomatitis virus glycoprotein-pseudotyped MGIN oncoretrovirus control vector required IL-3, IL-6, and SCF for significant transduction (39.3 ± 9.4%). Interestingly, only a portion of the progeny cells within the lentivirus-transduced methylcellulose colonies expressed GFP, in contrast to the homogeneous expression in oncoretrovirus-transduced colonies. Secondary plating of the primary GFP+ lentivirus vector-transduced colonies revealed vector PCR+ GFP+ (42%), vector PCR− GFP− (46%), and vector PCR+ GFP− (13%) secondary colonies, indicating true genetic mosaicism with respect to the viral genome in the progeny cells. The degree of vector mosaicism in individual colonies could be reduced by extending the culture time after transduction and before plating into the clonal progenitor cell assay, indicating a delay in the lentiviral integration process. Furthermore, supplementation with exogenous deoxynucleoside triphosphates during transduction decreased mosaicism within the colonies. Although cytokine stimulation during transduction correlates with higher transduction efficiency, rapid cell division after transduction may result in loss of the viral genome in the progeny cells. Therefore, optimal transduction may require activation without promoting intense cell proliferation prior

  11. Why Primates? The Importance of Nonhuman Primates for Understanding Human Infancy

    ERIC Educational Resources Information Center

    Weiss, Daniel J.; Santos, Laurie R.

    2006-01-01

    We introduce the thematic collection by noting some striking similarities in the cognitive abilities of human infants and nonhuman primates. What are the implications of these similarities for our comprehension of human infant cognition? After providing a brief historical and conceptual background on comparative behavioral research, we discuss how…

  12. Lentivirus-ABCG1 instillation reduces lipid accumulation and improves lung compliance in GM-CSF knock-out mice

    SciTech Connect

    Malur, Anagha; Huizar, Isham; Wells, Greg; Barna, Barbara P.; Malur, Achut G.; Thomassen, Mary Jane

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Lentivirus-ABCG1 reduces lipid accumulation in lungs of GM-CSF knock-out mice. Black-Right-Pointing-Pointer Up-regulation of ABCG1 improves lung function. Black-Right-Pointing-Pointer Upregulation of ABCG1 improves surfactant metabolism. -- Abstract: We have shown decreased expression of the nuclear transcription factor, peroxisome proliferator-activated receptor-gamma (PPAR{gamma}) and the PPAR{gamma}-regulated ATP-binding cassette transporter G1 (ABCG1) in alveolar macrophages from patients with pulmonary alveolar proteinosis (PAP). PAP patients also exhibit neutralizing antibodies to granulocyte-macrophage colony stimulating factor (GM-CSF), an upregulator of PPAR{gamma}. In association with functional GM-CSF deficiency, PAP lung is characterized by surfactant-filled alveolar spaces and lipid-filled alveolar macrophages. Similar pathology characterizes GM-CSF knock-out (KO) mice. We reported previously that intratracheal instillation of a lentivirus (lenti)-PPAR{gamma} plasmid into GM-CSF KO animals elevated ABCG1 and reduced alveolar macrophage lipid accumulation. Here, we hypothesized that instillation of lenti-ABCG1 might be sufficient to decrease lipid accumulation and improve pulmonary function in GM-CSF KO mice. Animals received intratracheal instillation of lenti-ABCG1 or control lenti-enhanced Green Fluorescent Protein (eGFP) plasmids and alveolar macrophages were harvested 10 days later. Alveolar macrophage transduction efficiency was 79% as shown by lenti-eGFP fluorescence. Quantitative PCR analyses indicated a threefold (p = 0.0005) increase in ABCG1 expression with no change of PPAR{gamma} or ABCA1 in alveolar macrophages of lenti-ABCG1 treated mice. ABCG1 was unchanged in control lenti-eGFP and PBS-instilled groups. Oil Red O staining detected reduced intracellular neutral lipid in alveolar macrophages from lenti-ABCG1 treated mice. Extracellular cholesterol and phospholipids were also decreased as shown by

  13. Recombinant lentivirus with enhanced expression of caudal-related homeobox protein 2 inhibits human colorectal cancer cell proliferation in vitro.

    PubMed

    He, Sai; Sun, Xue-Jun; Zheng, Jian-Bao; Qi, Jie; Chen, Nan-Zheng; Wang, Wei; Wei, Guang-Bing; Liu, Dong; Yu, Jun-Hui; Lu, Shao-Ying; Wang, Hui

    2015-08-01

    Caudal-related homeobox protein 2 (CDX2), a tumor suppressor in the adult colon, is overexpressed under a non-cancer specific cytomegalovirus promoter in certain tumor cells; furthermore, non-specific expression of CDX2 may result in aberrant side effects in normal cells. The human telomerase reverse transcriptase (hTERT) promoter is active in the majority of cancer cells but not in normal cells. Hypoxia is a key feature of solid tumors, and targeted genes may be significantly upregulated by five copies of hypoxia-response elements (HREs) under hypoxic conditions. However, the effect of CDX2 overexpression, as controlled by five copies of HREs and the hTERT promoter, on human colorectal cancer (CRC) cell proliferation in vitro remains to be fully elucidated. In the current study, a recombinant lentivirus containing the CDX2 gene under the control of five HREs and the hTERT promoter was generated. An immunofluorescence assay was used to detect CDX2 expression by the 5 HhC lentivirus, whereas an MTT assay was used to detect the effects of CoCl2 on the viability of LoVo cells. Western blot analysis was conducted in order to determine the relative ratios of recombinant CDX2 protein to the internal control β-actin, following 5 HhC/LoVo cell culture under normoxic and hypoxic conditions (100, 200, 300, 400 or 500 µmol/l CoCl2) for 24 h, then for 12, 24 or 36 h with the optimal concentration (300 µmol/l) of CoCl2. Reverse transcription polymerase chain reaction analysis was used to determine the transcription of recombinant CDX2 mRNA following culture of 5 HhC/LoVo cells under normoxic or hypoxic conditions. Finally, a cloning assay was used to detect the proliferative ability of 5 HhC/LoVo and 5 Hh cells. High CDX2 expression was observed in hTERT-positive LoVo cells under hypoxic conditions, an effect which was mimicked by treatment with CoCl2 to inhibit LoVo cell proliferation in vitro. High expression of CDX2 therefore provides a promising strategy for the

  14. The Ethics of Infection Challenges in Primates.

    PubMed

    Barnhill, Anne; Joffe, Steven; Miller, Franklin G

    2016-07-01

    In the midst of the recent Ebola outbreak, scientific developments involving infection challenge experiments on nonhuman primates (NHPs) sparked hope that successful treatments and vaccines may soon become available. Yet these studies pose a stark ethical quandary. On the one hand, they represent an important step in developing novel therapies and vaccines for Ebola and the Marburg virus, with the potential to save thousands of human lives and to protect whole communities from devastation; on the other hand, they intentionally expose sophisticated animals to severe suffering and a high risk of death. Other studies that infect NHPs with a lethal disease in order to test interventions that may prove beneficial for humans pose the same ethical difficulty. Some advocates have argued that all research on primates should be phased out, and ethicists have questioned whether a moral justification of primate research is possible. A 2010 European Union directive banned virtually all research on great apes, and 2013 guidelines from the National Institutes of Health (NIH), based upon recommendations in an influential 2011 Institute of Medicine (IOM) report, eliminated most biomedical research with chimpanzees in the United States. But studies involving other NHPs face no comparable restrictions. Should research on NHPs other than great apes be subject to tighter restrictions than it currently is? In this article, we explore this general question in the context of one particular type of biomedical research: infection challenge studies. We advocate a presumptive prohibition on infection challenge experiments in NHPs, but we also argue that exceptions to this prohibition are permissible, subject to strict substantive and procedural safeguards, when necessary to avert substantial loss of human life or severe morbidity for a substantial number of people. PMID:27417865

  15. The Ethics of Infection Challenges in Primates.

    PubMed

    Barnhill, Anne; Joffe, Steven; Miller, Franklin G

    2016-07-01

    In the midst of the recent Ebola outbreak, scientific developments involving infection challenge experiments on nonhuman primates (NHPs) sparked hope that successful treatments and vaccines may soon become available. Yet these studies pose a stark ethical quandary. On the one hand, they represent an important step in developing novel therapies and vaccines for Ebola and the Marburg virus, with the potential to save thousands of human lives and to protect whole communities from devastation; on the other hand, they intentionally expose sophisticated animals to severe suffering and a high risk of death. Other studies that infect NHPs with a lethal disease in order to test interventions that may prove beneficial for humans pose the same ethical difficulty. Some advocates have argued that all research on primates should be phased out, and ethicists have questioned whether a moral justification of primate research is possible. A 2010 European Union directive banned virtually all research on great apes, and 2013 guidelines from the National Institutes of Health (NIH), based upon recommendations in an influential 2011 Institute of Medicine (IOM) report, eliminated most biomedical research with chimpanzees in the United States. But studies involving other NHPs face no comparable restrictions. Should research on NHPs other than great apes be subject to tighter restrictions than it currently is? In this article, we explore this general question in the context of one particular type of biomedical research: infection challenge studies. We advocate a presumptive prohibition on infection challenge experiments in NHPs, but we also argue that exceptions to this prohibition are permissible, subject to strict substantive and procedural safeguards, when necessary to avert substantial loss of human life or severe morbidity for a substantial number of people.

  16. Trabecular bone structure in the primate wrist.

    PubMed

    Schilling, Ann-Marie; Tofanelli, Sergio; Hublin, Jean-Jacques; Kivell, Tracy L

    2014-05-01

    Trabecular (or cancellous) bone has been shown to respond to mechanical loading throughout ontogeny and thus can provide unique insight into skeletal function and locomotion in comparative studies of living and fossil mammalian morphology. Trabecular bone of the hand may be particularly functionally informative because the hand has more direct contact with the substrate compared with the remainder of the forelimb during locomotion in quadrupedal mammals. This study investigates the trabecular structure within the wrist across a sample of haplorhine primates that vary in locomotor behaviour (and thus hand use) and body size. High-resolution microtomographic scans were collected of the lunate, scaphoid, and capitate in 41 individuals and eight genera (Homo, Gorilla, Pan, Papio, Pongo, Symphalangus, Hylobates, and Ateles). We predicted that particular trabecular parameters would 1) vary across suspensory, quadrupedal, and bipedal primates based on differences in hand use and load, and 2) scale with carpal size following similar allometric patterns found previously in other skeletal elements across a larger sample of mammals and primates. Analyses of variance (trabecular parameters analysed separately) and principal component analyses (trabecular parameters analysed together) revealed no clear functional signal in the trabecular structure of any of the three wrist bones. Instead, there was a large degree of variation within suspensory and quadrupedal locomotor groups, as well as high intrageneric variation within some taxa, particularly Pongo and Gorilla. However, as predicted, Homo sapiens, which rarely use their hands for locomotion and weight support, were unique in showing lower relative bone volume (BV/TV) compared with all other taxa. Furthermore, parameters used to quantify trabecular structure within the wrist scale with size generally following similar allometric patterns found in trabeculae of other mammalian skeletal elements. We discuss the challenges

  17. Stepwise evolution of stable sociality in primates.

    PubMed

    Shultz, Susanne; Opie, Christopher; Atkinson, Quentin D

    2011-11-09

    Although much attention has been focused on explaining and describing the diversity of social grouping patterns among primates, less effort has been devoted to understanding the evolutionary history of social living. This is partly because social behaviours do not fossilize, making it difficult to infer changes over evolutionary time. However, primate social behaviour shows strong evidence for phylogenetic inertia, permitting the use of Bayesian comparative methods to infer changes in social behaviour through time, thereby allowing us to evaluate alternative models of social evolution. Here we present a model of primate social evolution, whereby sociality progresses from solitary foraging individuals directly to large multi-male/multi-female aggregations (approximately 52 million years (Myr) ago), with pair-living (approximately 16 Myr ago) or single-male harem systems (approximately 16 Myr ago) derivative from this second stage. This model fits the data significantly better than the two widely accepted alternatives (an unstructured model implied by the socioecological hypothesis or a model that allows linear stepwise changes in social complexity through time). We also find strong support for the co-evolution of social living with a change from nocturnal to diurnal activity patterns, but not with sex-biased dispersal. This supports suggestions that social living may arise because of increased predation risk associated with diurnal activity. Sociality based on loose aggregation is followed by a second shift to stable or bonded groups. This structuring facilitates the evolution of cooperative behaviours and may provide the scaffold for other distinctive anthropoid traits including coalition formation, cooperative resource defence and large brains.

  18. Adeno-associated virus and lentivirus vectors mediate efficient and sustained transduction of cultured mouse and human dorsal root ganglia sensory neurons.

    PubMed

    Fleming, J; Ginn, S L; Weinberger, R P; Trahair, T N; Smythe, J A; Alexander, I E

    2001-01-01

    Peripheral nervous system (PNS) sensory neurons are directly involved in the pathophysiology of numerous inherited and acquired neurological conditions. Therefore, efficient and stable gene delivery to these postmitotic cells has significant therapeutic potential. Among contemporary vector systems capable of neuronal transduction, only those based on herpes simplex virus have been extensively evaluated in PNS neurons. We therefore investigated the transduction performance of recombinant adeno-associated virus type 2 (AAV) and VSV-G-pseudotyped lentivirus vectors derived from human immunodeficiency virus (HIV-1) in newborn mouse and fetal human dorsal root ganglia (DRG) sensory neurons. In dissociated mouse DRG cultures both vectors achieved efficient transduction of sensory neurons at low multiplicities of infection (MOIs) and sustained transgene expression within a 28-day culture period. Interestingly, the lentivirus vector selectively transduced neurons in murine cultures, in contrast to human cultures, in which Schwann and fibroblast-like cells were also transduced. Recombinant AAV transduced all three cell types in both mouse and human cultures. After direct microinjection of murine DRG explants, maximal transduction efficiencies of 20 and 200 transducing units per neuronal transductant were achieved with AAV and lentivirus vectors, respectively. Most importantly, both vectors achieved efficient and sustained transduction of human sensory neurons in dissociated cultures, thereby directly demonstrating the exciting potential of these vectors for gene therapy applications in the PNS.

  19. Two Influential Primate Classifications Logically Aligned

    PubMed Central

    Franz, Nico M.; Pier, Naomi M.; Reeder, Deeann M.; Chen, Mingmin; Yu, Shizhuo; Kianmajd, Parisa; Bowers, Shawn; Ludäscher, Bertram

    2016-01-01

    Classifications and phylogenies of perceived natural entities change in the light of new evidence. Taxonomic changes, translated into Code-compliant names, frequently lead to name:meaning dissociations across succeeding treatments. Classification standards such as the Mammal Species of the World (MSW) may experience significant levels of taxonomic change from one edition to the next, with potential costs to long-term, large-scale information integration. This circumstance challenges the biodiversity and phylogenetic data communities to express taxonomic congruence and incongruence in ways that both humans and machines can process, that is, to logically represent taxonomic alignments across multiple classifications. We demonstrate that such alignments are feasible for two classifications of primates corresponding to the second and third MSW editions. Our approach has three main components: (i) use of taxonomic concept labels, that is name sec. author (where sec. means according to), to assemble each concept hierarchy separately via parent/child relationships; (ii) articulation of select concepts across the two hierarchies with user-provided Region Connection Calculus (RCC-5) relationships; and (iii) the use of an Answer Set Programming toolkit to infer and visualize logically consistent alignments of these input constraints. Our use case entails the Primates sec. Groves (1993; MSW2–317 taxonomic concepts; 233 at the species level) and Primates sec. Groves (2005; MSW3–483 taxonomic concepts; 376 at the species level). Using 402 RCC-5 input articulations, the reasoning process yields a single, consistent alignment and 153,111 Maximally Informative Relations that constitute a comprehensive meaning resolution map for every concept pair in the Primates sec. MSW2/MSW3. The complete alignment, and various partitions thereof, facilitate quantitative analyses of name:meaning dissociation, revealing that nearly one in three taxonomic names are not reliable across

  20. Biorhythms and space experiments with nonhuman primates

    NASA Technical Reports Server (NTRS)

    Winget, C. M.

    1977-01-01

    Man's response to exposure to spaceflight and weightlessness is expressed in physiological adjustments which involve his health and ability to function. The amplitude and periodicity of fluctuations in biological processes affect various functions and responses to provocative stimuli. Primates and other species are subjected to tests to determine the consequences of an altered biorhythm on work and performance, emotional stability, biomedical evaluation in space, the ability to cope with the unexpected, and susceptibility to infection, toxicity, radiation, drugs, and stress. Factors in the environment or operational setup which can change the physiological baseline must be determined and controlled.

  1. Two Influential Primate Classifications Logically Aligned.

    PubMed

    Franz, Nico M; Pier, Naomi M; Reeder, Deeann M; Chen, Mingmin; Yu, Shizhuo; Kianmajd, Parisa; Bowers, Shawn; Ludäscher, Bertram

    2016-07-01

    Classifications and phylogenies of perceived natural entities change in the light of new evidence. Taxonomic changes, translated into Code-compliant names, frequently lead to name:meaning dissociations across succeeding treatments. Classification standards such as the Mammal Species of the World (MSW) may experience significant levels of taxonomic change from one edition to the next, with potential costs to long-term, large-scale information integration. This circumstance challenges the biodiversity and phylogenetic data communities to express taxonomic congruence and incongruence in ways that both humans and machines can process, that is, to logically represent taxonomic alignments across multiple classifications. We demonstrate that such alignments are feasible for two classifications of primates corresponding to the second and third MSW editions. Our approach has three main components: (i) use of taxonomic concept labels, that is name sec. author (where sec. means according to), to assemble each concept hierarchy separately via parent/child relationships; (ii) articulation of select concepts across the two hierarchies with user-provided Region Connection Calculus (RCC-5) relationships; and (iii) the use of an Answer Set Programming toolkit to infer and visualize logically consistent alignments of these input constraints. Our use case entails the Primates sec. Groves (1993; MSW2-317 taxonomic concepts; 233 at the species level) and Primates sec. Groves (2005; MSW3-483 taxonomic concepts; 376 at the species level). Using 402 RCC-5 input articulations, the reasoning process yields a single, consistent alignment and 153,111 Maximally Informative Relations that constitute a comprehensive meaning resolution map for every concept pair in the Primates sec. MSW2/MSW3. The complete alignment, and various partitions thereof, facilitate quantitative analyses of name:meaning dissociation, revealing that nearly one in three taxonomic names are not reliable across treatments

  2. Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions

    PubMed Central

    Sengupta, Asmita; McConkey, Kim R.; Radhakrishna, Sindhu

    2015-01-01

    Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice. PMID:26536365

  3. Primates, Provisioning and Plants: Impacts of Human Cultural Behaviours on Primate Ecological Functions.

    PubMed

    Sengupta, Asmita; McConkey, Kim R; Radhakrishna, Sindhu

    2015-01-01

    Human provisioning of wildlife with food is a widespread global practice that occurs in multiple socio-cultural circumstances. Provisioning may indirectly alter ecosystem functioning through changes in the eco-ethology of animals, but few studies have quantified this aspect. Provisioning of primates by humans is known to impact their activity budgets, diets and ranging patterns. Primates are also keystone species in tropical forests through their role as seed dispersers; yet there is no information on how provisioning might affect primate ecological functions. The rhesus macaque is a major human-commensal species but is also an important seed disperser in the wild. In this study, we investigated the potential impacts of provisioning on the role of rhesus macaques as seed dispersers in the Buxa Tiger Reserve, India. We studied a troop of macaques which were provisioned for a part of the year and were dependent on natural resources for the rest. We observed feeding behaviour, seed handling techniques and ranging patterns of the macaques and monitored availability of wild fruits. Irrespective of fruit availability, frugivory and seed dispersal activities decreased when the macaques were provisioned. Provisioned macaques also had shortened daily ranges implying shorter dispersal distances. Finally, during provisioning periods, seeds were deposited on tarmac roads that were unconducive for germination. Provisioning promotes human-primate conflict, as commensal primates are often involved in aggressive encounters with humans over resources, leading to negative consequences for both parties involved. Preventing or curbing provisioning is not an easy task as feeding wild animals is a socio-cultural tradition across much of South and South-East Asia, including India. We recommend the initiation of literacy programmes that educate lay citizens about the ill-effects of provisioning and strongly caution them against the practice. PMID:26536365

  4. The unique value of primate models in translational research. Nonhuman primate models of women's health: introduction and overview.

    PubMed

    Shively, Carol A; Clarkson, Thomas B

    2009-09-01

    This special issue of AJP is focused on research using nonhuman primates as models to further the understanding of women's health. Nonhuman primates play a unique role in translational science by bridging the gap between basic and clinical investigations. The use of nonhuman primates in biomedical research challenges our resolve to treat all life as sacred. The scientific community has responded by developing ethical guidelines for the care and the use of primates and clarifying the responsibility of investigators to insure the physical and psychological well-being of nonhuman primates used in research. Preclinical investigations often involve the use of animal models. Rodent models have been the mainstay of biomedical science and have provided enormous insight into the workings of many mammalian systems that have proved applicable to human biological systems. Rodent models are dissimilar to primates in numerous ways, which may limit the generalizability to human biological systems. These limitations are much less likely in nonhuman primates and in Old World primates, in particular, Macaques are useful models for investigations involving the reproductive system, bioenergetics, obesity and diabetes, cardiovascular health, central nervous system function, cognitive and social behavior, the musculoskeletal system, and diseases of aging. This issue considers primate models of polycystic ovary syndrome; diet effects on glycemic control, breast and endometrium; estrogen, reproductive life stage and atherosclerosis; estrogen and diet effects on inflammation in atherogenesis; the neuroprotective effects of estrogen therapy; social stress and visceral obesity; and sex differences in the role of social status in atherogenesis. Unmet research needs in women's health include the use of diets in nonhuman primate studies that are similar to those consumed by human beings, primate models of natural menopause, dementia, hypertension, colon cancer, and frailty in old age, and

  5. Selection of TAR RNA-Binding Chameleon Peptides by Using a Retroviral Replication System

    PubMed Central

    Xie, Baode; Calabro, Valerie; Wainberg, Mark A.; Frankel, Alan D.

    2004-01-01

    The interaction between the arginine-rich motif (ARM) of the human immunodeficiency virus (HIV) Tat protein and TAR RNA is essential for Tat activation and viral replication. Two related lentiviruses, bovine immunodeficiency virus (BIV) and Jembrana disease virus (JDV), also require Tat ARM-TAR interactions to mediate activation, but the viruses have evolved different RNA-binding strategies. Interestingly, the JDV ARM can act as a “chameleon,” adopting both the HIV and BIV TAR binding modes. To examine how RNA-protein interactions may evolve in a viral context and possibly to identify peptides that recognize HIV TAR in novel ways, we devised a retroviral system based on HIV replication to amplify and select for RNA binders. We constructed a combinatorial peptide library based on the BIV Tat ARM and identified peptides that, like the JDV Tat ARM, also function through HIV TAR, revealing unexpected sequence characteristics of an RNA-binding chameleon. The results suggest that a retroviral screening approach may help identify high-affinity TAR binders and may provide new insights into the evolution of RNA-protein interactions. PMID:14722301

  6. Development of payload subsystem-primate mission-Biosatellite program

    NASA Technical Reports Server (NTRS)

    Hall, J. F., Jr.

    1971-01-01

    Design and operation of the primate life support subsystem for the Biosatellite Program as used during the flight of Biosatellite 3 are discussed. Included are preflight changes necessitated by the primate's (a Macaca nemistrina monkey) influence on the initial equipment design.

  7. What Cognitive Representations Support Primate Theory of Mind?

    PubMed

    Martin, Alia; Santos, Laurie R

    2016-05-01

    Much recent work has examined the evolutionary origins of human mental state representations. This work has yielded strikingly consistent results: primates show a sophisticated ability to track the current and past perceptions of others, but they fail to represent the beliefs of others. We offer a new account of the nuanced performance of primates in theory of mind (ToM) tasks. We argue that primates form awareness relations tracking the aspects of reality that other agents are aware of. We contend that these awareness relations allow primates to make accurate predictions in social situations, but that this capacity falls short of our human-like representational ToM. We end by explaining how this new account makes important new empirical predictions about primate ToM.

  8. In Transition: Primate Genomics at a Time of Rapid Change

    PubMed Central

    Rogers, Jeffrey

    2013-01-01

    The field of nonhuman primate genomics is undergoing rapid change and making impressive progress. Exploiting new technologies for DNA sequencing, researchers have generated new whole-genome sequence assemblies for multiple primate species over the past 6 years. In addition, investigations of within-species genetic variation, gene expression and RNA sequences, conservation of non-protein-coding regions of the genome, and other aspects of comparative genomics are moving at an accelerating speed. This progress is opening a wide array of new research opportunities in the analysis of comparative primate genome content and evolution. It also creates new possibilities for the use of nonhuman primates as model organisms in biomedical research. This transition, based on both new technology and the new information being generated in regard to human genetics, provides an important justification for reevaluating the research goals, strategies, and study designs used in primate genetics and genomics. PMID:24174444

  9. Lentivirus transduced interleukin-1 receptor antagonist gene expression in murine bone marrow-derived mesenchymal stem cells in vitro.

    PubMed

    He, Tao; Chi, Guanghao; Tian, Bo; Tang, Tingting; Dai, Kerong

    2015-09-01

    Genetically modified mesenchymal stem cells have been used in attempts to increase the expression of interleukin‑1 receptor antagonist (IL‑1Ra); however, the attempts thus far have been unsuccessful. The aim of the present study was to investigate whether the lentivirus transduced IL‑1Ra gene was able to be stably expressed in murine bone marrow‑derived mesenchymal stem cells (mBMSCs) in vitro. In the present study, third generation lentiviral (Lv) vectors transducing the IL‑1Ra/green fluorescent protein (copGFP) gene were constructed and transfected into mBMSCs to establish the Lv.IL‑1Ra.copGFP/mBMSCs, which were evaluated using fluorescence microscopy, flow cytometry, cell viability analysis using a cell counting kit‑8 kit, Trypan blue staining and an MTT growth kinetics assay. The expression of IL‑1Ra was analyzed using reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that the Lv.IL‑1Ra/copGFP vector was successfully constructed. The mBMSCs exhibited a short proliferation life, however they had good growth kinetics at an early stage and improved viability following efficient transduction of the IL‑1Ra gene. IL‑1Ra was overexpressed following transfection of mBMSCs. In conclusion, lentiviral vector transduced mBMSCs were able to efficiently express exogenous Il‑1Ra under certain conditions and had a marked capacity for proliferation. PMID:26130370

  10. Lentivirus-mediated delivery of sonic hedgehog into the striatum stimulates neuroregeneration in a rat model of Parkinson disease.

    PubMed

    Zhang, Yi; Dong, Weiren; Guo, Suiqun; Zhao, Shu; He, Suifen; Zhang, Lihua; Tang, Yinjuan; Wang, Haihong

    2014-12-01

    Parkinson disease (PD) is a progressive neurodegenerative disorder in which the nigrostriatal pathway, consisting of dopaminergic neuronal projections from the substantia nigra to the striatum, degenerates. Viral transduction is currently the most promising in vivo strategy for delivery of therapeutic proteins into the brain for treatment of PD. Sonic hedgehog (Shh) is necessary for cell proliferation, differentiation and neuroprotection in the central nervous system. In this study, we investigated the effects of overexpressed N-terminal product of SHH (SHH-N) in a PD model rat. A lentiviral vector containing SHH-N was stereotactically injected into the striatum 24 h after a striatal 6-OHDA lesion. We found that overexpressed SHH-N attenuated behavioral deficits and reduced the loss of dopamine neurons in the substantia nigra and the loss of dopamine fibers in the striatum. In addition, fluoro-ruby-labeled nigrostriatal projections were also repaired. Together, our results demonstrate the feasibility and efficacy of using the strategy of lentivirus-mediated Shh-N delivery to delay nigrostriatal pathway degeneration. This strategy holds the potential for therapeutic application in the treatment of PD.

  11. Lentivirus-mediated PLCγ1 gene short-hairpin RNA suppresses tumor growth and metastasis of human gastric adenocarcinoma.

    PubMed

    Zhang, Bingchang; Wang, Fen; Dai, Lianzhi; Cai, Heguo; Zhan, Yanyan; Gang, Song; Hu, Tianhui; Xia, Chun; Zhang, Bing

    2016-02-16

    Targeted molecular therapy has gradually been a potential solution in cancer therapy. Other authors' and our previous studies have demonstrated that phosphoinositide-specific phospholipase γ (PLCγ) is involved in regulating tumor growth and metastasis. However, the molecular mechanism underlying PLCγ-dependent tumor growth and metastasis of gastric adenocarcinoma and whether PLCγ may be a potential target for tumor therapy in human gastric adenocarcinoma are not yet well determined. Here, we investigated the role of PLCγ inhibition in tumor growth and metastasis of human gastric adenocarcinoma using BGC-823 cell line and a nude mouse tumor xenograft model. The results manifested that the depletion of PLCγ1 by the transduction with lentivirus-mediated PLCγ1 gene short-hairpin RNA (shRNA) vector led to the decrease of tumor growth and metastasis of human gastric adenocarcinoma in vitro and in vivo. Furthermore, the Akt/Bad, Akt/S6, and ERK/Bad signal axes were involved in PLCγ1-mediated tumor growth and metastasis of human gastric adenocarcinoma. Therefore, the abrogation of PLCγ1 signaling by shRNA could efficaciously suppress human gastric adenocarcinoma tumor growth and metastasis, with important implication for validating PLCγ1 as a potential target for human gastric adenocarcinoma. PMID:26811493

  12. Efficacy and safety of myocardial gene transfer of adenovirus, adeno-associated virus and lentivirus vectors in the mouse heart.

    PubMed

    Merentie, M; Lottonen-Raikaslehto, L; Parviainen, V; Huusko, J; Pikkarainen, S; Mendel, M; Laham-Karam, N; Kärjä, V; Rissanen, R; Hedman, M; Ylä-Herttuala, S

    2016-03-01

    Gene therapy is a promising new treatment option for cardiac diseases. For finding the most suitable and safe vector for cardiac gene transfer, we delivered adenovirus (AdV), adeno-associated virus (AAV) and lentivirus (LeV) vectors into the mouse heart with sophisticated closed-chest echocardiography-guided intramyocardial injection method for comparing them with regards to transduction efficiency, myocardial damage, effects on the left ventricular function and electrocardiography (ECG). AdV had the highest transduction efficiency in cardiomyocytes followed by AAV2 and AAV9, and the lowest efficiency was seen with LeV. The local myocardial inflammation and fibrosis in the left ventricle (LV) was proportional to transduction efficiency. AdV caused LV dilatation and systolic dysfunction. Neither of the locally injected AAV serotypes impaired the LV systolic function, but AAV9 caused diastolic dysfunction to some extent. LeV did not affect the cardiac function. We also studied systemic delivery of AAV9, which led to transduction of cardiomyocytes throughout the myocardium. However, also diffuse fibrosis was present leading to significantly impaired LV systolic and diastolic function and pathological ECG changes. Compared with widely used AdV vector, AAV2, AAV9 and LeV were less effective in transducing cardiomyocytes but also less harmful. Local administration of AAV9 was safer and more efficient compared with systemic administration.

  13. Lentivirus-mediated PLCγ1 gene short-hairpin RNA suppresses tumor growth and metastasis of human gastric adenocarcinoma

    PubMed Central

    Zhang, Bingchang; Wang, Fen; Dai, Lianzhi; Cai, Heguo; Zhan, Yanyan; Gang, Song; Hu, Tianhui; Xia, Chun; Zhang, Bing

    2016-01-01

    Targeted molecular therapy has gradually been a potential solution in cancer therapy. Other authors' and our previous studies have demonstrated that phosphoinositide-specific phospholipase γ (PLCγ) is involved in regulating tumor growth and metastasis. However, the molecular mechanism underlying PLCγ-dependent tumor growth and metastasis of gastric adenocarcinoma and whether PLCγ may be a potential target for tumor therapy in human gastric adenocarcinoma are not yet well determined. Here, we investigated the role of PLCγ inhibition in tumor growth and metastasis of human gastric adenocarcinoma using BGC-823 cell line and a nude mouse tumor xenograft model. The results manifested that the depletion of PLCγ1 by the transduction with lentivirus-mediated PLCγ1 gene short-hairpin RNA (shRNA) vector led to the decrease of tumor growth and metastasis of human gastric adenocarcinoma in vitro and in vivo. Furthermore, the Akt/Bad, Akt/S6, and ERK/Bad signal axes were involved in PLCγ1-mediated tumor growth and metastasis of human gastric adenocarcinoma. Therefore, the abrogation of PLCγ1 signaling by shRNA could efficaciously suppress human gastric adenocarcinoma tumor growth and metastasis, with important implication for validating PLCγ1 as a potential target for human gastric adenocarcinoma. PMID:26811493

  14. Targeting CRMP-4 by lentivirus-mediated RNA interference inhibits SW480 cell proliferation and colorectal cancer growth

    PubMed Central

    Chen, Si-Le; Cai, Shi-Rong; Zhang, Xin-Hua; Li, Wen-Feng; Zhai, Er-Tao; Peng, Jian-Jun; Wu, Hui; Chen, Chuang-Qi; Ma, Jin-Ping; Wang, Zhao; He, Yu-Long

    2016-01-01

    The aim of the present study was to investigate the expression level of collapsin response mediator protein 4 (CRMP-4) in human colorectal cancer (CRC) tissue and to evauluate its impact on SW480 cell proliferation, in addition to tumor growth in a mouse xenograft model. Clinical CRC tissue samples were collected to detect the CRMP-4 protein expression levels using western blot and immunohistochemistry analyses. A specific small interfering RNA sequence targeting the CRMP-4 gene (DPYSL3) was constructed and transfected into an SW480 cell line using a lentivirus vector to obtain a stable cell line with low expression of CRMP-4. The effectiveness of the interference was evaluated using western blot and reverse transcription-quantitative polymerase chain reaction, and the cell proliferation was determined using MTT and BrdU colorimetric methods. Tumor growth was assessed by subcutaneously inoculating the constructed cells into BALB/c nude mice. The protein expression levels of CRMP-4 were markedly increased in colon tumor tissue of the human samples. The proliferation of SW480 cells and the tumor growth rate in nude mice of the si-CPMR-4 group were evidently depressed compared with the si-scramble group. Thus, the present results suggest that CRMP-4 may be involved in the pathogenesis of CRC. PMID:27698685

  15. Targeting CRMP-4 by lentivirus-mediated RNA interference inhibits SW480 cell proliferation and colorectal cancer growth

    PubMed Central

    Chen, Si-Le; Cai, Shi-Rong; Zhang, Xin-Hua; Li, Wen-Feng; Zhai, Er-Tao; Peng, Jian-Jun; Wu, Hui; Chen, Chuang-Qi; Ma, Jin-Ping; Wang, Zhao; He, Yu-Long

    2016-01-01

    The aim of the present study was to investigate the expression level of collapsin response mediator protein 4 (CRMP-4) in human colorectal cancer (CRC) tissue and to evauluate its impact on SW480 cell proliferation, in addition to tumor growth in a mouse xenograft model. Clinical CRC tissue samples were collected to detect the CRMP-4 protein expression levels using western blot and immunohistochemistry analyses. A specific small interfering RNA sequence targeting the CRMP-4 gene (DPYSL3) was constructed and transfected into an SW480 cell line using a lentivirus vector to obtain a stable cell line with low expression of CRMP-4. The effectiveness of the interference was evaluated using western blot and reverse transcription-quantitative polymerase chain reaction, and the cell proliferation was determined using MTT and BrdU colorimetric methods. Tumor growth was assessed by subcutaneously inoculating the constructed cells into BALB/c nude mice. The protein expression levels of CRMP-4 were markedly increased in colon tumor tissue of the human samples. The proliferation of SW480 cells and the tumor growth rate in nude mice of the si-CPMR-4 group were evidently depressed compared with the si-scramble group. Thus, the present results suggest that CRMP-4 may be involved in the pathogenesis of CRC.

  16. Production and use of lentivirus to selectively transduce primary oligodendrocyte precursor cells for in vitro myelination assays.

    PubMed

    Peckham, Haley M; Ferner, Anita H; Giuffrida, Lauren; Murray, Simon S; Xiao, Junhua

    2015-01-12

    Myelination is a complex process that involves both neurons and the myelin forming glial cells, oligodendrocytes in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS). We use an in vitro myelination assay, an established model for studying CNS myelination in vitro. To do this, oligodendrocyte precursor cells (OPCs) are added to the purified primary rodent dorsal root ganglion (DRG) neurons to form myelinating co-cultures. In order to specifically interrogate the roles that particular proteins expressed by oligodendrocytes exert upon myelination we have developed protocols that selectively transduce OPCs using the lentivirus overexpressing wild type, constitutively active or dominant negative proteins before being seeded onto the DRG neurons. This allows us to specifically interrogate the roles of these oligodendroglial proteins in regulating myelination. The protocols can also be applied in the study of other cell types, thus providing an approach that allows selective manipulation of proteins expressed by a desired cell type, such as oligodendrocytes for the targeted study of signaling and compensation mechanisms. In conclusion, combining the in vitro myelination assay with lentiviral infected OPCs provides a strategic tool for the analysis of molecular mechanisms involved in myelination.

  17. Impaired Expression of Cytokines as a Result of Viral Infections with an Emphasis on Small Ruminant Lentivirus Infection in Goats

    PubMed Central

    Jarczak, Justyna; Kaba, Jarosław; Reczyńska, Daria; Bagnicka, Emilia

    2016-01-01

    Knowing about the genes involved in immunity, and being able to identify the factors influencing their expressions, helps in gaining awareness of the immune processes. The qPCR method is a useful gene expression analysis tool, but studies on immune system genes are still limited, especially on the caprine immune system. Caprine arthritis encephalitis, a disease caused by small ruminant lentivirus (SRLV), causes economic losses in goat breeding, and there is no therapy against SRLV. The results of studies on vaccines against other viruses are promising. Moreover, the Marker-Assisted Selection strategy against SRLV is possible, as has been shown in sheep breeding. However, there are still many gaps in our knowledge on the caprine immune response to infection. All types of cytokines play pivotal roles in immunity, and SRLV infection influences the expression of many cytokines in different types of cells. This information encouraged the authors to examine the results of studies conducted on SRLV and other viral infections, with an emphasis on the expression of cytokine genes. This review attempts to summarize the results of studies on the expression of cytokines in the context of the SRLV infection. PMID:27399757

  18. Primate vaginal microbiomes exhibit species specificity without universal Lactobacillus dominance

    PubMed Central

    Yildirim, Suleyman; Yeoman, Carl J; Janga, Sarath Chandra; Thomas, Susan M; Ho, Mengfei; Leigh, Steven R; Consortium, Primate Microbiome; White, Bryan A; Wilson, Brenda A; Stumpf, Rebecca M

    2014-01-01

    Bacterial communities colonizing the reproductive tracts of primates (including humans) impact the health, survival and fitness of the host, and thereby the evolution of the host species. Despite their importance, we currently have a poor understanding of primate microbiomes. The composition and structure of microbial communities vary considerably depending on the host and environmental factors. We conducted comparative analyses of the primate vaginal microbiome using pyrosequencing of the 16S rRNA genes of a phylogenetically broad range of primates to test for factors affecting the diversity of primate vaginal ecosystems. The nine primate species included: humans (Homo sapiens), yellow baboons (Papio cynocephalus), olive baboons (Papio anubis), lemurs (Propithecus diadema), howler monkeys (Alouatta pigra), red colobus (Piliocolobus rufomitratus), vervets (Chlorocebus aethiops), mangabeys (Cercocebus atys) and chimpanzees (Pan troglodytes). Our results indicated that all primates exhibited host-specific vaginal microbiota and that humans were distinct from other primates in both microbiome composition and diversity. In contrast to the gut microbiome, the vaginal microbiome showed limited congruence with host phylogeny, and neither captivity nor diet elicited substantial effects on the vaginal microbiomes of primates. Permutational multivariate analysis of variance and Wilcoxon tests revealed correlations among vaginal microbiota and host species-specific socioecological factors, particularly related to sexuality, including: female promiscuity, baculum length, gestation time, mating group size and neonatal birth weight. The proportion of unclassified taxa observed in nonhuman primate samples increased with phylogenetic distance from humans, indicative of the existence of previously unrecognized microbial taxa. These findings contribute to our understanding of host–microbe variation and coevolution, microbial biogeography, and disease risk, and have important

  19. Fallback foods, preferred foods, adaptive zones, and primate origins.

    PubMed

    Rosenberger, Alfred L

    2013-09-01

    Appreciation has grown for the impact of tropical forest seasonality and fallback foods on primate diets, behaviors, and morphology. As critically important resources in times of shortage, seasonal fallback foods may have an outsized role in selecting for form and function while the diversity of preferred plant foods has played an equally prominent role in shaping primate evolution. Here, hypotheses of primate origins are examined in the context of food choice models developed by Marshall and Wrangham [2007] and related to the broader concepts of adaptive zones and radiations. The integrated evolution of primate diet and positional behavior is consistent with a growing reliance on angiosperm products--not prey--as preferred and seasonal fallback foods, temporally and phylogenetically coordinated with evolutionary phases of the angiosperm adaptive radiation. Selection for an incisor oriented but non-specialized heterodont dentition, in contrast with most other orders, attests to the universal role of a highly varied vegetation diet as the primates' primary food resource, with diverse physical properties, phenology and high seasonality. A preference by plesiadapiforms for eating small protein- and lipid-rich seeds may have predisposed the primates and advanced angiosperms to diversify their evolving ecological interdependence, which established the primate adaptive zone and became realized more fully with the rise of the modern euprimate and angiosperm phenotypes. The "narrow niche" hypothesis, a recent challenge to the angiosperm co-evolution hypothesis, is evaluated further. Finally, I note support for visual predation as a core adaptive breakthrough for primates or euprimates remains elusive and problematic, especially considering the theoretical framework provided by the Marshall-Wrangham model, updated evidence of primate feeding habits and the counterpoint lessons of the most successful primate predators, the tarsiiforms.

  20. Primate Socioecology: New Insights from Males

    NASA Astrophysics Data System (ADS)

    Kappeler, Peter M.

    Primate males have only recently returned to the center stage of socioecological research. This review surveys new studies that examine variation in the behavior of adult males and their role in social evolution. It is shown that group size, composition, and social behavior are determined not only by resource distribution, predation risk, and other ecological factors, but that life history traits and social factors, especially those related to sexual coercion, can have equally profound consequences for social systems. This general point is illustrated by examining male behavior at three levels: the evolution of permanent associations between males and females, the causes and consequences of variation in the number of males between group-living species, and the determinants of social relationships within and between the sexes. Direct and indirect evidence reviewed in connection with all three questions indicates that the risk of infanticide has been a pervasive force in primate social evolution. Several areas are identified for future research on male life histories that should contribute to a better understanding of male reproductive strategies and corresponding female counterstrategies.

  1. Short hyperdynamic profiles influence primate temperature regulation

    NASA Technical Reports Server (NTRS)

    Fuller, C. A.; Williams, B. A.

    1982-01-01

    Primates have been shown to be sensitive to hyperdynamic fields. That is, when exposed to + 2Gz, body temperature falls. The purpose of this study was to examine the relative sensitivity of these animals to short centrifugation profiles which mimic the gravitational envelope seen on the Space Shuttle during launch (8 minutes, 2.9 Gz max) and re-entry (19 min, 1.7 Gz max). Four loosely restrained squirrel monkeys, isolated from additional external stimuli, were exposed to these profiles. During launch simulation, the temperatures never fell markedly below control levels. However, subsequent to return to 1G, the recovery phase showed decreases in body temperature in all four animals averaging 0.4 C over the next 10 to 15 minutes. The two animals exposed to the reentry profile showed decreases in body temperature within five minutes of the onset of centrifugation. Maximum fall in body temperature was reached by the end of the centrifugation phase and averaged 0.7 C. Thus, the temperature regulation system of this primate is sensitive to short hyperdynamic field exposures.

  2. Primate pelvic anatomy and implications for birth

    PubMed Central

    Trevathan, Wenda

    2015-01-01

    The pelvis performs two major functions for terrestrial mammals. It provides somewhat rigid support for muscles engaged in locomotion and, for females, it serves as the birth canal. The result for many species, and especially for encephalized primates, is an ‘obstetric dilemma’ whereby the neonate often has to negotiate a tight squeeze in order to be born. On top of what was probably a baseline of challenging birth, locomotor changes in the evolution of bipedalism in the human lineage resulted in an even more complex birth process. Negotiation of the bipedal pelvis requires a series of rotations, the end of which has the infant emerging from the birth canal facing the opposite direction from the mother. This pattern, strikingly different from what is typically seen in monkeys and apes, places a premium on having assistance at delivery. Recently reported observations of births in monkeys and apes are used to compare the process in human and non-human primates, highlighting similarities and differences. These include presentation (face, occiput anterior or posterior), internal and external rotation, use of the hands by mothers and infants, reliance on assistance, and the developmental state of the neonate. PMID:25602069

  3. Hunting, law enforcement, and African primate conservation.

    PubMed

    N'Goran, Paul K; Boesch, Christophe; Mundry, Roger; N'Goran, Eliezer K; Herbinger, Ilka; Yapi, Fabrice A; Kühl, Hjalmar S

    2012-06-01

    Primates are regularly hunted for bushmeat in tropical forests, and systematic ecological monitoring can help determine the effect hunting has on these and other hunted species. Monitoring can also be used to inform law enforcement and managers of where hunting is concentrated. We evaluated the effects of law enforcement informed by monitoring data on density and spatial distribution of 8 monkey species in Taï National Park, Côte d'Ivoire. We conducted intensive surveys of monkeys and looked for signs of human activity throughout the park. We also gathered information on the activities of law-enforcement personnel related to hunting and evaluated the relative effects of hunting, forest cover and proximity to rivers, and conservation effort on primate distribution and density. The effects of hunting on monkeys varied among species. Red colobus monkeys (Procolobus badius) were most affected and Campbell's monkeys (Cercopithecus campbelli) were least affected by hunting. Density of monkeys irrespective of species was up to 100 times higher near a research station and tourism site in the southwestern section of the park, where there is little hunting, than in the southeastern part of the park. The results of our monitoring guided law-enforcement patrols toward zones with the most hunting activity. Such systematic coordination of ecological monitoring and law enforcement may be applicable at other sites.

  4. Social inequalities in health in nonhuman primates.

    PubMed

    Shively, Carol A; Day, Stephen M

    2015-01-01

    Overall health has been linked to socioeconomic status, with the gap between social strata increasing each year. Studying the impact of social position on health and biological functioning in nonhuman primates has allowed researchers to model the human condition while avoiding ethical complexities or other difficulties characteristic of human studies. Using female cynomolgus macaques (Macaca fascicularis), our lab has examined the link between social status and stress for 30 years. Female nonhuman primates are especially sensitive to social stressors which can deleteriously affect reproductive health, leading to harmful consequences to their overall health. Subordinates have lower progesterone concentrations during the luteal phase of menstrual cycle, which is indicative of absence or impairment of ovulation. Subordinate animals receive more aggression, less affiliative attention, and are more likely to exhibit depressive behaviors. They also express higher stress-related biomarkers such as increased heart rates and lower mean cortisol. While no differences in body weight between dominant and subordinate animals are observed, subordinates have lower bone density and more visceral fat than their dominant counterparts. The latter increases risk for developing inflammatory diseases. Differences are also observed in neurological and autonomic function. A growing body of data suggests that diet composition may amplify or diminish physiological stress responses which have deleterious effects on health. More experimental investigation of the health effects of diet pattern is needed to further elucidate these differences in an ongoing search to find realistic and long-term solutions to the declining health of individuals living across the ever widening socioeconomic spectrum.

  5. Social inequalities in health in nonhuman primates

    PubMed Central

    Shively, Carol A.; Day, Stephen M.

    2014-01-01

    Overall health has been linked to socioeconomic status, with the gap between social strata increasing each year. Studying the impact of social position on health and biological functioning in nonhuman primates has allowed researchers to model the human condition while avoiding ethical complexities or other difficulties characteristic of human studies. Using female cynomolgus macaques (Macaca fascicularis), our lab has examined the link between social status and stress for 30 years. Female nonhuman primates are especially sensitive to social stressors which can deleteriously affect reproductive health, leading to harmful consequences to their overall health. Subordinates have lower progesterone concentrations during the luteal phase of menstrual cycle, which is indicative of absence or impairment of ovulation. Subordinate animals receive more aggression, less affiliative attention, and are more likely to exhibit depressive behaviors. They also express higher stress-related biomarkers such as increased heart rates and lower mean cortisol. While no differences in body weight between dominant and subordinate animals are observed, subordinates have lower bone density and more visceral fat than their dominant counterparts. The latter increases risk for developing inflammatory diseases. Differences are also observed in neurological and autonomic function. A growing body of data suggests that diet composition may amplify or diminish physiological stress responses which have deleterious effects on health. More experimental investigation of the health effects of diet pattern is needed to further elucidate these differences in an ongoing search to find realistic and long-term solutions to the declining health of individuals living across the ever widening socioeconomic spectrum. PMID:27589665

  6. Voice cells in the primate temporal lobe.

    PubMed

    Perrodin, Catherine; Kayser, Christoph; Logothetis, Nikos K; Petkov, Christopher I

    2011-08-23

    Communication signals are important for social interactions and survival and are thought to receive specialized processing in the visual and auditory systems. Whereas the neural processing of faces by face clusters and face cells has been repeatedly studied [1-5], less is known about the neural representation of voice content. Recent functional magnetic resonance imaging (fMRI) studies have localized voice-preferring regions in the primate temporal lobe [6, 7], but the hemodynamic response cannot directly assess neurophysiological properties. We investigated the responses of neurons in an fMRI-identified voice cluster in awake monkeys, and here we provide the first systematic evidence for voice cells. "Voice cells" were identified, in analogy to "face cells," as neurons responding at least 2-fold stronger to conspecific voices than to "nonvoice" sounds or heterospecific voices. Importantly, whereas face clusters are thought to contain high proportions of face cells [4] responding broadly to many faces [1, 2, 4, 5, 8-10], we found that voice clusters contain moderate proportions of voice cells. Furthermore, individual voice cells exhibit high stimulus selectivity. The results reveal the neurophysiological bases for fMRI-defined voice clusters in the primate brain and highlight potential differences in how the auditory and visual systems generate selective representations of communication signals. PMID:21835625

  7. Fish cognition: a primate's eye view.

    PubMed

    Bshary, Redouan; Wickler, Wolfgang; Fricke, Hans

    2002-03-01

    We provide selected examples from the fish literature of phenomena found in fish that are currently being examined in discussions of cognitive abilities and evolution of neocortex size in primates. In the context of social intelligence, we looked at living in individualized groups and corresponding social strategies, social learning and tradition, and co-operative hunting. Regarding environmental intelligence, we searched for examples concerning special foraging skills, tool use, cognitive maps, memory, anti-predator behaviour, and the manipulation of the environment. Most phenomena of interest for primatologists are found in fish as well. We therefore conclude that more detailed studies on decision rules and mechanisms are necessary to test for differences between the cognitive abilities of primates and other taxa. Cognitive research can benefit from future fish studies in three ways: first, as fish are highly variable in their ecology, they can be used to determine the specific ecological factors that select for the evolution of specific cognitive abilities. Second, for the same reason they can be used to investigate the link between cognitive abilities and the enlargement of specific brain areas. Third, decision rules used by fish could be used as 'null-hypotheses' for primatologists looking at how monkeys might make their decisions. Finally, we propose a variety of fish species that we think are most promising as study objects.

  8. Primate pelvic anatomy and implications for birth.

    PubMed

    Trevathan, Wenda

    2015-03-01

    The pelvis performs two major functions for terrestrial mammals. It provides somewhat rigid support for muscles engaged in locomotion and, for females, it serves as the birth canal. The result for many species, and especially for encephalized primates, is an 'obstetric dilemma' whereby the neonate often has to negotiate a tight squeeze in order to be born. On top of what was probably a baseline of challenging birth, locomotor changes in the evolution of bipedalism in the human lineage resulted in an even more complex birth process. Negotiation of the bipedal pelvis requires a series of rotations, the end of which has the infant emerging from the birth canal facing the opposite direction from the mother. This pattern, strikingly different from what is typically seen in monkeys and apes, places a premium on having assistance at delivery. Recently reported observations of births in monkeys and apes are used to compare the process in human and non-human primates, highlighting similarities and differences. These include presentation (face, occiput anterior or posterior), internal and external rotation, use of the hands by mothers and infants, reliance on assistance, and the developmental state of the neonate.

  9. Conditioned Sexual Arousal in a Nonhuman Primate

    PubMed Central

    Snowdon, Charles T.; Tannenbaum, Pamela L.; Schultz-Darken, Nancy J.; Ziegler, Toni E.; Ferris, Craig F.

    2010-01-01

    Conditioning of sexual arousal has been demonstrated in several species from fish to humans, but has not been demonstrated in nonhuman primates. Controversy exists over whether nonhuman primates produce pheromones that arouse sexual behavior. Although common marmosets copulate throughout the ovarian cycle and during pregnancy, males exhibit behavioral signs of arousal, demonstrate increased neural activation of anterior hypothalamus and medial preoptic area and have an increase in serum testosterone after exposure to odors of novel ovulating females suggestive of a sexually arousing pheromone. Males also have increased androgens prior to their mate’s ovulation. However, males presented with odors of ovulating females demonstrate activation of many other brain areas associated with motivation, memory and decision making. In this study we demonstrate that male marmosets can be conditioned to a novel, arbitrary odor (lemon) with observation of erections, and increased exploration of the location where they previously experienced a receptive female, and increased scratching in postconditioning test without a female present. This conditioned response was demonstrated up to a week after the end of conditioning trials, a much longer lasting effect of conditioning than reported in studies of other species. These results further suggest that odors of ovulating females are not pheromones, strictly speaking, and that marmoset males may learn specific characteristics of odors of females providing a possible basis for mate identification. PMID:21029736

  10. Social inequalities in health in nonhuman primates.

    PubMed

    Shively, Carol A; Day, Stephen M

    2015-01-01

    Overall health has been linked to socioeconomic status, with the gap between social strata increasing each year. Studying the impact of social position on health and biological functioning in nonhuman primates has allowed researchers to model the human condition while avoiding ethical complexities or other difficulties characteristic of human studies. Using female cynomolgus macaques (Macaca fascicularis), our lab has examined the link between social status and stress for 30 years. Female nonhuman primates are especially sensitive to social stressors which can deleteriously affect reproductive health, leading to harmful consequences to their overall health. Subordinates have lower progesterone concentrations during the luteal phase of menstrual cycle, which is indicative of absence or impairment of ovulation. Subordinate animals receive more aggression, less affiliative attention, and are more likely to exhibit depressive behaviors. They also express higher stress-related biomarkers such as increased heart rates and lower mean cortisol. While no differences in body weight between dominant and subordinate animals are observed, subordinates have lower bone density and more visceral fat than their dominant counterparts. The latter increases risk for developing inflammatory diseases. Differences are also observed in neurological and autonomic function. A growing body of data suggests that diet composition may amplify or diminish physiological stress responses which have deleterious effects on health. More experimental investigation of the health effects of diet pattern is needed to further elucidate these differences in an ongoing search to find realistic and long-term solutions to the declining health of individuals living across the ever widening socioeconomic spectrum. PMID:27589665

  11. DNA recombination: the replication connection.

    PubMed

    Haber, J E

    1999-07-01

    Chromosomal double-strand breaks (DSBs) arise after exposure to ionizing radiation or enzymatic cleavage, but especially during the process of DNA replication itself. Homologous recombination plays a critical role in repair of such DSBs. There has been significant progress in our understanding of two processes that occur in DSB repair: gene conversion and recombination-dependent DNA replication. Recent evidence suggests that gene conversion and break-induced replication are related processes that both begin with the establishment of a replication fork in which both leading- and lagging-strand synthesis occur. There has also been much progress in characterization of the biochemical roles of recombination proteins that are highly conserved from yeast to humans.

  12. Overexpression of the Replicative Helicase in Escherichia coli Inhibits Replication Initiation and Replication Fork Reloading.

    PubMed

    Brüning, Jan-Gert; Myka, Kamila Katarzyna; McGlynn, Peter

    2016-03-27

    Replicative helicases play central roles in chromosome duplication and their assembly onto DNA is regulated via initiators and helicase loader proteins. The Escherichia coli replicative helicase DnaB and the helicase loader DnaC form a DnaB6-DnaC6 complex that is required for loading DnaB onto single-stranded DNA. Overexpression of dnaC inhibits replication by promoting continual rebinding of DnaC to DnaB and consequent prevention of helicase translocation. Here we show that overexpression of dnaB also inhibits growth and chromosome duplication. This inhibition is countered by co-overexpression of wild-type DnaC but not of a DnaC mutant that cannot interact with DnaB, indicating that a reduction in DnaB6-DnaC6 concentration is responsible for the phenotypes associated with elevated DnaB concentration. Partial defects in the oriC-specific initiator DnaA and in PriA-specific initiation away from oriC during replication repair sensitise cells to dnaB overexpression. Absence of the accessory replicative helicase Rep, resulting in increased replication blockage and thus increased reinitiation away from oriC, also exacerbates DnaB-induced defects. These findings indicate that elevated levels of helicase perturb replication initiation not only at origins of replication but also during fork repair at other sites on the chromosome. Thus, imbalances in levels of the replicative helicase and helicase loader can inhibit replication both via inhibition of DnaB6-DnaC6 complex formation with excess DnaB, as shown here, and promotion of formation of DnaB6-DnaC6 complexes with excess DnaC [Allen GC, Jr., Kornberg A. Fine balance in the regulation of DnaB helicase by DnaC protein in replication in Escherichia coli. J. Biol. Chem. 1991;266:22096-22101; Skarstad K, Wold S. The speed of the Escherichia coli fork in vivo depends on the DnaB:DnaC ratio. Mol. Microbiol. 1995;17:825-831]. Thus, there are two mechanisms by which an imbalance in the replicative helicase and its associated

  13. Overexpression of the Replicative Helicase in Escherichia coli Inhibits Replication Initiation and Replication Fork Reloading

    PubMed Central

    Brüning, Jan-Gert; Myka, Kamila Katarzyna; McGlynn, Peter

    2016-01-01

    Replicative helicases play central roles in chromosome duplication and their assembly onto DNA is regulated via initiators and helicase loader proteins. The Escherichia coli replicative helicase DnaB and the helicase loader DnaC form a DnaB6–DnaC6 complex that is required for loading DnaB onto single-stranded DNA. Overexpression of dnaC inhibits replication by promoting continual rebinding of DnaC to DnaB and consequent prevention of helicase translocation. Here we show that overexpression of dnaB also inhibits growth and chromosome duplication. This inhibition is countered by co-overexpression of wild-type DnaC but not of a DnaC mutant that cannot interact with DnaB, indicating that a reduction in DnaB6–DnaC6 concentration is responsible for the phenotypes associated with elevated DnaB concentration. Partial defects in the oriC-specific initiator DnaA and in PriA-specific initiation away from oriC during replication repair sensitise cells to dnaB overexpression. Absence of the accessory replicative helicase Rep, resulting in increased replication blockage and thus increased reinitiation away from oriC, also exacerbates DnaB-induced defects. These findings indicate that elevated levels of helicase perturb replication initiation not only at origins of replication but also during fork repair at other sites on the chromosome. Thus, imbalances in levels of the replicative helicase and helicase loader can inhibit replication both via inhibition of DnaB6–DnaC6 complex formation with excess DnaB, as shown here, and promotion of formation of DnaB6–DnaC6 complexes with excess DnaC [Allen GC, Jr., Kornberg A. Fine balance in the regulation of DnaB helicase by DnaC protein in replication in Escherichia coli. J. Biol. Chem. 1991;266:22096–22101; Skarstad K, Wold S. The speed of the Escherichia coli fork in vivo depends on the DnaB:DnaC ratio. Mol. Microbiol. 1995;17:825–831]. Thus, there are two mechanisms by which an imbalance in the replicative helicase and its

  14. The Biology of Replicative Senescence

    SciTech Connect

    Campisi, J.

    1996-12-04

    Most cells cannot divide indefinitely due to a processtermed cellular or replicative senescence. Replicative senescence appearsto be a fundamental feature of somatic cells, with the exception of mosttumour cells and possibly certain stem cells. How do cells sense thenumber of divisions they have completed? Although it has not yet beencritically tested, the telomere shortening hypothesis is currentlyperhaps the best explanation for a cell division 'counting' mechanism.Why do cells irreversibly cease proliferation after completing a finitenumber of divisions? It is now known that replicative senescence altersthe expression of a few crucial growth-regulatory genes. It is not knownhow these changes in growth-regulatory gene expression are related totelomere shortening in higher eukaryotes. However, lower eukaryotes haveprovided several plausible mechanisms. Finally, what are thephysiological consequences of replicative senescence? Several lines ofevidence suggest that, at least in human cells, replicative senescence isa powerful tumour suppressive mechanism. There is also indirect evidencethat replicative senescence contributes to ageing. Taken together,current findings suggest that, at least in mammals, replicativesenescence may have evolved to curtail tumorigenesis, but may also havethe unselected effect of contributing to age-related pathologies,including cancer.

  15. Gambling primates: reactions to a modified Iowa Gambling Task in humans, chimpanzees and capuchin monkeys.

    PubMed

    Proctor, Darby; Williamson, Rebecca A; Latzman, Robert D; de Waal, Frans B M; Brosnan, Sarah F

    2014-07-01

    Humans will, at times, act against their own economic self-interest, for example, in gambling situations. To explore the evolutionary roots of this behavior, we modified a traditional human gambling task, the Iowa Gambling Task (IGT), for use with chimpanzees, capuchin monkeys and humans. We expanded the traditional task to include two additional payoff structures to fully elucidate the ways in which these primate species respond to differing reward distributions versus overall quantities of rewards, a component often missing in the existing literature. We found that while all three species respond as typical humans do in the standard IGT payoff structure, species and individual differences emerge in our new payoff structures. Specifically, when variance avoidance and reward maximization conflicted, roughly equivalent numbers of apes maximized their rewards and avoided variance, indicating that the traditional payoff structure of the IGT is insufficient to disentangle these competing strategies. Capuchin monkeys showed little consistency in their choices. To determine whether this was a true species difference or an effect of task presentation, we replicated the experiment but increased the intertrial interval. In this case, several capuchin monkeys followed a reward maximization strategy, while chimpanzees retained the same strategy they had used previously. This suggests that individual differences in strategies for interacting with variance and reward maximization are present in apes, but not in capuchin monkeys. The primate gambling task presented here is a useful methodology for disentangling strategies of variance avoidance and reward maximization.

  16. Perceptual considerations in the use of colored photographic and video stimuli to study nonhuman primate behavior.

    PubMed

    Waitt, Corri; Buchanan-Smith, Hannah M

    2006-11-01

    The use of photographs, slides, computerized images, and video to study behavior is increasingly being employed in nonhuman primates. However, since these mediums have been designed to simulate natural coloration for normal trichromatic human vision, they can fail to reproduce color in meaningful and accurate ways for viewers with different visual systems. Given the range of color perception that exists both across and within different species, it is necessary to consider this variation in order to discern the suitability of these mediums for experimental use. Because of the high degree of visual similarity among humans, Old World monkeys, and apes, the use of photographic and video stimuli should be acceptable in terms of replicating naturalistic coloration and making noticeable color manipulations. However, among New World primates and prosimians, there exists a considerable degree of variation in color perceptual abilities depending on the species, sex, and allelic combination of the animals involved. Therefore, the use of these mediums to study behavior is problematic for these species, and should be done with caution. PMID:17044007

  17. Expression Profiles of Vpx/Vpr Proteins Are Co-related with the Primate Lentiviral Lineage

    PubMed Central

    Sakai, Yosuke; Miyake, Ariko; Doi, Naoya; Sasada, Hikari; Miyazaki, Yasuyuki; Adachi, Akio; Nomaguchi, Masako

    2016-01-01

    Viruses of human immunodeficiency virus type 2 (HIV-2) and some simian immunodeficiency virus (SIV) lineages carry a unique accessory protein called Vpx. Vpx is essential or critical for viral replication in natural target cells such as macrophages and T lymphocytes. We have previously shown that a poly-proline motif (PPM) located at the C-terminal region of Vpx is required for its efficient expression in two strains of HIV-2 and SIVmac, and that the Vpx expression levels of the two clones are significantly different. Notably, the PPM sequence is conserved and confined to Vpx and Vpr proteins derived from certain lineages of HIV-2/SIVs. In this study, Vpx/Vpr proteins from diverse primate lentiviral lineages were experimentally and phylogenetically analyzed to obtain the general expression picture in cells. While both the level and PPM-dependency of Vpx/Vpr expression in transfected cells varied among viral strains, each viral group, based on Vpx/Vpr amino acid sequences, was found to exhibit a characteristic expression profile. Moreover, phylogenetic tree analyses on Gag and Vpx/Vpr proteins gave essentially the same results. Taken together, our study described here suggests that each primate lentiviral lineage may have developed a unique expression pattern of Vpx/Vpr proteins for adaptation to its hostile cellular and species environments in the process of viral evolution. PMID:27536295

  18. Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

    PubMed

    Marzi, Andrea; Yoshida, Reiko; Miyamoto, Hiroko; Ishijima, Mari; Suzuki, Yasuhiko; Higuchi, Megumi; Matsuyama, Yukie; Igarashi, Manabu; Nakayama, Eri; Kuroda, Makoto; Saijo, Masayuki; Feldmann, Friederike; Brining, Douglas; Feldmann, Heinz; Takada, Ayato

    2012-01-01

    Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.

  19. Gambling primates: reactions to a modified Iowa Gambling Task in humans, chimpanzees and capuchin monkeys

    PubMed Central

    Williamson, Rebecca A.; Latzman, Robert D.; de Waal, Frans B. M.; Brosnan, Sarah F.

    2014-01-01

    Humans will, at times, act against their own economic self-interest, for example, in gambling situations. To explore the evolutionary roots of this behavior, we modified a traditional human gambling task, the Iowa Gambling Task (IGT), for use with chimpanzees, capuchin monkeys and humans. We expanded the traditional task to include two additional payoff structures to fully elucidate the ways in which these primate species respond to differing reward distributions versus overall quantities of rewards, a component often missing in the existing literature. We found that while all three species respond as typical humans do in the standard IGT payoff structure, species and individual differences emerge in our new payoff structures. Specifically, when variance avoidance and reward maximization conflicted, roughly equivalent numbers of apes maximized their rewards and avoided variance, indicating that the traditional payoff structure of the IGT is insufficient to disentangle these competing strategies. Capuchin monkeys showed little consistency in their choices. To determine whether this was a true species difference or an effect of task presentation, we replicated the experiment but increased the intertrial interval. In this case, several capuchin monkeys followed a reward maximization strategy, while chimpanzees retained the same strategy they had used previously. This suggests that individual differences in strategies for interacting with variance and reward maximization are present in apes, but not in capuchin monkeys. The primate gambling task presented here is a useful methodology for disentangling strategies of variance avoidance and reward maximization. PMID:24504555

  20. Protective efficacy of neutralizing monoclonal antibodies in a nonhuman primate model of Ebola hemorrhagic fever.

    PubMed

    Marzi, Andrea; Yoshida, Reiko; Miyamoto, Hiroko; Ishijima, Mari; Suzuki, Yasuhiko; Higuchi, Megumi; Matsuyama, Yukie; Igarashi, Manabu; Nakayama, Eri; Kuroda, Makoto; Saijo, Masayuki; Feldmann, Friederike; Brining, Douglas; Feldmann, Heinz; Takada, Ayato

    2012-01-01

    Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF. PMID:22558378

  1. Validation-based insertional mutagenesis for identification of Nup214 as a host factor for EV71 replication in RD cells.

    PubMed

    Wang, Bei; Zhang, Xiaoyu; Zhao, Zhendong

    2013-08-01

    Lentiviral validation-based insertional mutagenesis (VBIM) is a sophisticated, forward genetic approach that is used for the investigation of signal transduction in mammalian cells. Using VBIM, we conducted function-based genetic screening for host genes that affect enterovirus 71 (EV71) viral replication. This included host factors that are required for the life cycle of EV71 and host restriction factors that inhibit EV71 replication. Several cell clones, resistant to EV71, were produced using EV71 infection as a selection pressure and the nuclear pore protein 214 (Nup214) was identified as a host factor required for EV71 replication. In SD2-2, the corresponding VBIM lentivirus transformed clone, the expression of endogenous Nup214 was significantly down-regulated by the reverse inserted VBIM promoter. After Cre recombinase-mediated excision of the VBIM promoter, the expression of Nup214 recovered and the clone regained sensitivity to the EV71 infection. Furthermore, over-expression of Nup214 in the cells suggested that Nup214 was promoting EV71 replication. Results of this study indicate that a successful mutagenesis strategy has been established for screening host genes related to viral replication.

  2. Does the mastery of center-embedded linguistic structures distinguish humans from nonhuman primates?

    PubMed

    Perruchet, Pierre; Rey, Arnaud

    2005-04-01

    In a recent Science article, Fitch and Hauser (2004; hereafter, F&H) claimed to have demonstrated that cotton-top tamarins fail to learn an artificial language produced by a phrase structure grammar (Chomsky, 1957) generating center-embedded sentences, whereas adult humans easily learn such a language. We report an experiment replicating the results of F&H in humans but also showing that subjects learned the language without exploiting in any way the center-embedded structure. When the procedure was modified to make the processing of this structure mandatory, the subjects no longer showed evidence of learning. We propose a simple interpretation for the difference in performance observed in F&H's task between humans and tamarins and argue that, beyond the specific drawbacks inherent in F&H's study, researching the source of the inability of nonhuman primates to master language within a framework built around Chomsky's hierarchy of grammars is a conceptual dead end. PMID:16082811

  3. Genomic profiling of host responses to Lassa virus: therapeutic potential from primate to man

    PubMed Central

    Zapata, Juan C; Salvato, Maria S

    2015-01-01

    Lassa virus infection elicits distinctive changes in host gene expression and metabolism. We focus on changes in host gene expression that may be biomarkers that discriminate individual pathogens or may help to provide a prognosis for disease. In addition to assessing mRNA changes, functional studies are also needed to discriminate causes of disease from mechanisms of host resistance. Host responses that drive pathogenesis are likely to be targets for prevention or therapy. Host responses to Lassa or its related arenaviruses have been monitored in cell culture, in animal models of hemorrhagic fever, in Lassa-infected nonhuman primates and, to a limited extent, in infected human beings. Here, we describe results from those studies and discuss potential targets for reducing virus replication and mitigating disease. PMID:25844088

  4. Contributions of Nonhuman Primates to Research on Aging

    PubMed Central

    Didier, E. S.; MacLean, A. G.; Mohan, M.; Didier, P. J.; Lackner, A. A.; Kuroda, M. J.

    2016-01-01

    Aging is the biological process of declining physiologic function associated with increasing mortality rate during advancing age. Humans and higher nonhuman primates exhibit unusually longer average life spans as compared with mammals of similar body mass. Furthermore, the population of humans worldwide is growing older as a result of improvements in public health, social services, and health care systems. Comparative studies among a wide range of organisms that include nonhuman primates contribute greatly to our understanding about the basic mechanisms of aging. Based on their genetic and physiologic relatedness to humans, nonhuman primates are especially important for better understanding processes of aging unique to primates, as well as for testing intervention strategies to improve healthy aging and to treat diseases and disabilities in older people. Rhesus and cynomolgus macaques are the predominant monkeys used in studies on aging, but research with lower nonhuman primate species is increasing. One of the priority topics of research about aging in nonhuman primates involves neurologic changes associated with cognitive decline and neurodegenerative diseases. Additional areas of research include osteoporosis, reproductive decline, caloric restriction, and their mimetics, as well as immune senescence and chronic inflammation that affect vaccine efficacy and resistance to infections and cancer. The purpose of this review is to highlight the findings from nonhuman primate research that contribute to our understanding about aging and health span in humans. PMID:26869153

  5. Historical contingency in the evolution of primate color vision.

    PubMed

    Dominy, Nathaniel J; Svenning, Jens Christian; Li, Wen Hsiung

    2003-01-01

    Primates are unique among eutherian mammals for possessing three types of retinal cone. Curiously, catarrhines, platyrrhines, and strepsirhines share this anatomy to different extents, and no hypothesis has hitherto accounted for this variability. Here we propose that the historical biogeography of figs and arborescent palms accounts for the global variation in primate color vision. Specifically, we suggest that primates invaded Paleogene forests characterized by figs and palms, the fruits of which played a keystone function. Primates not only relied on such resources, but also provided high-quality seed dispersal. In turn, figs and palms lost or simply did not evolve conspicuous coloration, as this conferred little advantage for attracting mammals. We suggest that the abundance and coloration of figs and palms offered a selective advantage to foraging groups with mixed capabilities for chromatic distinction. Climatic cooling at the end of the Eocene and into the Neogene resulted in widespread regional extinction or decimation of palms and (probably) figs. In regions where figs and palms became scarce, we suggest primates evolved routine trichromatic vision in order to exploit proteinaceous young leaves as a replacement resource. A survey of the hue and biogeography of extant figs and palms provides some empirical support. Where these resources are infrequent, primates are routinely trichromatic and consume young leaves during seasonal periods of fruit dearth. These results imply a link between the differential evolution of primate color vision and climatic changes during the Eocene-Oligocene transition.

  6. Fruits, foliage and the evolution of primate colour vision.

    PubMed

    Regan, B C; Julliot, C; Simmen, B; Viénot, F; Charles-Dominique, P; Mollon, J D

    2001-03-29

    Primates are apparently unique amongst the mammals in possessing trichromatic colour vision. However, not all primates are trichromatic. Amongst the haplorhine (higher) primates, the catarrhines possess uniformly trichromatic colour vision, whereas most of the platyrrhine species exhibit polymorphic colour vision, with a variety of dichromatic and trichromatic phenotypes within the population. It has been suggested that trichromacy in primates and the reflectance functions of certain tropical fruits are aspects of a coevolved seed-dispersal system: primate colour vision has been shaped by the need to find coloured fruits amongst foliage, and the fruits themselves have evolved to be salient to primates and so secure dissemination of their seeds. We review the evidence for and against this hypothesis and we report an empirical test: we show that the spectral positioning of the cone pigments found in trichromatic South American primates is well matched to the task of detecting fruits against a background of leaves. We further report that particular trichromatic platyrrhine phenotypes may be better suited than others to foraging for particular fruits under particular conditions of illumination; and we discuss possible explanations for the maintenance of polymorphic colour vision amongst the platyrrhines.

  7. The welfare and suitability of primates kept as pets.

    PubMed

    Soulsbury, Carl D; Iossa, Graziella; Kennell, Sarah; Harris, Stephen

    2009-01-01

    Amid growing concern about keeping exotic species as companion animals, nonhuman primates have been highlighted as inappropriate for private ownership. However, there has been no comprehensive review of the suitability of primates as pets, using a framework such as Schuppli and Fraser's (2000). Schuppli and Fraser incorporate welfare of the individual, of others, and of the environment. This article (a) examines the numbers, origins, ages, and ownership trends of primates kept as pets in the United Kingdom and (b) identifies a number of welfare, health, and environmental concerns. Overall, strong evidence supports the argument that primates are not suitable pets; it is unlikely that the welfare of pet primates can be adequately addressed in normal households. Finally, using unpublished data on complaints and inquiries received by the Royal Society for the Prevention of Cruelty to Animals, the study assesses the degree of public concern about the welfare of primates kept as pets in England and Wales. The article identifies a wide range of concerns about keeping pet primates and concludes that this practice should end.

  8. Evolution of the primate cytochrome c oxidase subunit II gene.

    PubMed

    Adkins, R M; Honeycutt, R L

    1994-03-01

    We examined the nucleotide and amino acid sequence variation of the cytochrome c oxidase subunit II (COII) gene from 25 primates (4 hominoids, 8 Old World monkeys, 2 New World monkeys, 2 tarsiers, 7 lemuriforms, 2 lorisiforms). Marginal support was found for three phylogenetic conclusions: (1) sister-group relationship between tarsiers and a monkey/ape clade, (2) placement of the aye-aye (Daubentonia) sister to all other strepsirhine primates, and (3) rejection of a sister-group relationship of dwarf lemurs (i.e., Cheirogaleus) with lorisiform primates. Stronger support was found for a sister-group relationship between the ring-tail lemur (Lemur catta) and the gentle lemurs (Hapalemur). In congruence with previous studies on COII, we found that the monkeys and apes have undergone a nearly two-fold increase in the rate of amino acid replacement relative to other primates. Although functionally important amino acids are generally conserved among all primates, the acceleration in amino acid replacements in higher primates is associated with increased variation in the amino terminal end of the protein. Additionally, the replacement of two carboxyl-bearing residues (glutamate and aspartate) at positions 114 and 115 may provide a partial explanation for the poor enzyme kinetics in cross-reactions between the cytochromes c and cytochrome c oxidases of higher primates and other mammals. PMID:8006990

  9. Fruits, foliage and the evolution of primate colour vision.

    PubMed

    Regan, B C; Julliot, C; Simmen, B; Viénot, F; Charles-Dominique, P; Mollon, J D

    2001-03-29

    Primates are apparently unique amongst the mammals in possessing trichromatic colour vision. However, not all primates are trichromatic. Amongst the haplorhine (higher) primates, the catarrhines possess uniformly trichromatic colour vision, whereas most of the platyrrhine species exhibit polymorphic colour vision, with a variety of dichromatic and trichromatic phenotypes within the population. It has been suggested that trichromacy in primates and the reflectance functions of certain tropical fruits are aspects of a coevolved seed-dispersal system: primate colour vision has been shaped by the need to find coloured fruits amongst foliage, and the fruits themselves have evolved to be salient to primates and so secure dissemination of their seeds. We review the evidence for and against this hypothesis and we report an empirical test: we show that the spectral positioning of the cone pigments found in trichromatic South American primates is well matched to the task of detecting fruits against a background of leaves. We further report that particular trichromatic platyrrhine phenotypes may be better suited than others to foraging for particular fruits under particular conditions of illumination; and we discuss possible explanations for the maintenance of polymorphic colour vision amongst the platyrrhines. PMID:11316480

  10. Fruits, foliage and the evolution of primate colour vision.

    PubMed Central

    Regan, B C; Julliot, C; Simmen, B; Viénot, F; Charles-Dominique, P; Mollon, J D

    2001-01-01

    Primates are apparently unique amongst the mammals in possessing trichromatic colour vision. However, not all primates are trichromatic. Amongst the haplorhine (higher) primates, the catarrhines possess uniformly trichromatic colour vision, whereas most of the platyrrhine species exhibit polymorphic colour vision, with a variety of dichromatic and trichromatic phenotypes within the population. It has been suggested that trichromacy in primates and the reflectance functions of certain tropical fruits are aspects of a coevolved seed-dispersal system: primate colour vision has been shaped by the need to find coloured fruits amongst foliage, and the fruits themselves have evolved to be salient to primates and so secure dissemination of their seeds. We review the evidence for and against this hypothesis and we report an empirical test: we show that the spectral positioning of the cone pigments found in trichromatic South American primates is well matched to the task of detecting fruits against a background of leaves. We further report that particular trichromatic platyrrhine phenotypes may be better suited than others to foraging for particular fruits under particular conditions of illumination; and we discuss possible explanations for the maintenance of polymorphic colour vision amongst the platyrrhines. PMID:11316480

  11. Biomechanical research of joints: IV. the biohinge of primates

    NASA Astrophysics Data System (ADS)

    Zhang, Renxiang; Yu, Jie; Lan, Zu-yun; Qu, Wen-ji; Zhang, Hong-zi; Zhang, Kui; Zhang, Liang

    1991-04-01

    In this paper moire topography is applied to study the femoral articular facies of the knee of Primates. For compari son with each other of different families of Primates we suggest the comparative targets a y and the grade G of the moire contour fringes on two condyles of knee of Primates and comparative study of the articulation of knee between the Macaca assamensis M cellaud Presbytis phayrei Rhinopithecus roxellanae Hylobates concolor leucogenys Nycticebus concany Gorilla gorilla Anthropopithecus troglodytes Sirnia satyrus and human being are given. The results may be useful reference in the study of Biomechanics Zoology and Anthropology.

  12. Neurobiological roots of language in primate audition: common computational properties.

    PubMed

    Bornkessel-Schlesewsky, Ina; Schlesewsky, Matthias; Small, Steven L; Rauschecker, Josef P

    2015-03-01

    Here, we present a new perspective on an old question: how does the neurobiology of human language relate to brain systems in nonhuman primates? We argue that higher-order language combinatorics, including sentence and discourse processing, can be situated in a unified, cross-species dorsal-ventral streams architecture for higher auditory processing, and that the functions of the dorsal and ventral streams in higher-order language processing can be grounded in their respective computational properties in primate audition. This view challenges an assumption, common in the cognitive sciences, that a nonhuman primate model forms an inherently inadequate basis for modeling higher-level language functions.

  13. The Evolution of Primate Communication and Metacommunication

    PubMed Central

    2016-01-01

    Abstract Against the prior view that primate communication is based only on signal decoding, comparative evidence suggests that primates are able, no less than humans, to intentionally perform or understand impulsive or habitual communicational actions with a structured evaluative nonconceptual content. These signals convey an affordance‐sensing that immediately motivates conspecifics to act. Although humans have access to a strategic form of propositional communication adapted to teaching and persuasion, they share with nonhuman primates the capacity to communicate in impulsive or habitual ways. They are also similarly able to monitor fluency, informativeness and relevance of messages or signals through nonconceptual cues. PMID:27134332

  14. Neurobiological roots of language in primate audition: common computational properties

    PubMed Central

    Bornkessel-Schlesewsky, Ina; Schlesewsky, Matthias; Small, Steven L.; Rauschecker, Josef P.

    2015-01-01

    This paper presents a new perspective on an old question: how does the neurobiology of human language relate to brain systems in nonhuman primates? We argue that higher-order language combinatorics – including sentence and discourse processing – can be situated in a unified, cross-species dorsal-ventral streams architecture for higher auditory processing, and that the functions of the dorsal and ventral streams in higher-order language processing can be grounded in their respective computational properties in primate audition. This view challenges an assumption, common in the cognitive sciences, that a nonhuman primate model forms an inherently inadequate basis for modeling higher-level language functions. PMID:25600585

  15. Neurobiological roots of language in primate audition: common computational properties.

    PubMed

    Bornkessel-Schlesewsky, Ina; Schlesewsky, Matthias; Small, Steven L; Rauschecker, Josef P

    2015-03-01

    Here, we present a new perspective on an old question: how does the neurobiology of human language relate to brain systems in nonhuman primates? We argue that higher-order language combinatorics, including sentence and discourse processing, can be situated in a unified, cross-species dorsal-ventral streams architecture for higher auditory processing, and that the functions of the dorsal and ventral streams in higher-order language processing can be grounded in their respective computational properties in primate audition. This view challenges an assumption, common in the cognitive sciences, that a nonhuman primate model forms an inherently inadequate basis for modeling higher-level language functions. PMID:25600585

  16. Character displacement of Cercopithecini primate visual signals

    PubMed Central

    Allen, William L.; Stevens, Martin; Higham, James P.

    2014-01-01

    Animal visual signals have the potential to act as an isolating barrier to prevent interbreeding of populations through a role in species recognition. Within communities of competing species, species recognition signals are predicted to undergo character displacement, becoming more visually distinctive from each other, however this pattern has rarely been identified. Using computational face recognition algorithms to model primate face processing, we demonstrate that the face patterns of guenons (tribe: Cercopithecini) have evolved under selection to become more visually distinctive from those of other guenon species with whom they are sympatric. The relationship between the appearances of sympatric species suggests that distinguishing conspecifics from other guenon species has been a major driver of diversification in guenon face appearance. Visual signals that have undergone character displacement may have had an important role in the tribe’s radiation, keeping populations that became geographically separated reproductively isolated on secondary contact. PMID:24967517

  17. Isolation of Pancreatic Islets from Nonhuman Primates.

    PubMed

    Berman, Dora M

    2016-01-01

    Nonhuman primates (NHP) constitute a highly relevant pre-clinical animal model to develop strategies for beta cell replacement. The close phylogenetic and immunologic relationship between NHP and humans results in cross-reactivity of various biological agents with NHP cells, as well as a very similar cytoarchitecture between islets from human and NHP that is strikingly different from that observed in rodent islets. The composition and location of endocrine cells in human or NHP islets, randomly distributed and associated with blood vessels, have functional consequences and a predisposition for paracrine interactions. Furthermore, translation of approaches that proved successful in rodent models to the clinic has been limited. Consequently, data collected from NHP studies can form the basis for an IND submission to the FDA. This chapter describes in detail the key aspects for isolation of islets from NHP, from organ procurement up to assessment of islet function, comparing and emphasizing the similarities between isolation procedures for human and NHP islets. PMID:27586422

  18. IACUC Review of Nonhuman Primate Research

    PubMed Central

    Tardif, Suzette D.; Coleman, Kristine; Hobbs, Theodore R.; Lutz, Corrine

    2013-01-01

    This article will detail some of the issues that must be considered as institutional animal care and use committees (IACUCs) review the use of nonhuman primates (NHPs) in research. As large, intelligent, social, long-lived, and non-domesticated animals, monkeys are amongst the most challenging species used in biomedical research and the duties of the IACUC in relation to reviewing research use of these species can also be challenging. Issues of specific concern for review of NHP research protocols that are discussed in this article include scientific justification, reuse, social housing requirements, amelioration of distress, surgical procedures, and humane endpoints. Clear institutional policies and procedures as regards NHP in these areas are critical, and the discussion of these issues presented here can serve as a basis for the informed establishment of such policies and procedures. PMID:24174445

  19. First virtual endocasts of adapiform primates.

    PubMed

    Harrington, Arianna R; Silcox, Mary T; Yapuncich, Gabriel S; Boyer, Doug M; Bloch, Jonathan I

    2016-10-01

    Well-preserved crania of notharctine adapiforms from the Eocene of North America provide the best direct evidence available for inferring neuroanatomy and encephalization in early euprimates (crown primates). Virtual endocasts of the notharctines Notharctus tenebrosus (n = 3) and Smilodectes gracilis (n = 4) from the middle Eocene Bridger formation of Wyoming, and the late Eocene European adapid adapiform Adapis parisiensis (n = 1), were reconstructed from high-resolution X-ray computed tomography (CT) data. While the three species share many neuroanatomical similarities differentiating them from plesiadapiforms (stem primates) and extant euprimates, our sample of N. tenebrosus displays more variation than that of S. gracilis, possibly related to differences in the patterns of cranial sexual dimorphism or within-lineage evolution. Body masses predicted from associated teeth suggest that N. tenebrosus was larger and had a lower encephalization quotient (EQ) than S. gracilis, despite their close relationship and similar inferred ecologies. Meanwhile, body masses predicted from cranial length of the same specimens suggest that the two species were more similar, with overlapping body mass and EQ, although S. gracilis exhibits a range of EQs shifted upwards relative to that of N. tenebrosus. While associated data from other parts of the skeleton are mostly lacking for specimens included in this study, measurements for unassociated postcrania attributed to these species yield body mass and EQ estimates that are also more similar to each other than those based on teeth. Regardless of the body mass prediction method used, results suggest that the average EQ of adapiforms was similar to that of plesiadapiforms, only overlapped the lower quadrant for the range of extant strepsirrhines, and did not overlap with the range of extant haplorhines. However, structural changes evident in these endocasts suggest that early euprimates relied more on vision than olfaction

  20. First virtual endocasts of adapiform primates.

    PubMed

    Harrington, Arianna R; Silcox, Mary T; Yapuncich, Gabriel S; Boyer, Doug M; Bloch, Jonathan I

    2016-10-01

    Well-preserved crania of notharctine adapiforms from the Eocene of North America provide the best direct evidence available for inferring neuroanatomy and encephalization in early euprimates (crown primates). Virtual endocasts of the notharctines Notharctus tenebrosus (n = 3) and Smilodectes gracilis (n = 4) from the middle Eocene Bridger formation of Wyoming, and the late Eocene European adapid adapiform Adapis parisiensis (n = 1), were reconstructed from high-resolution X-ray computed tomography (CT) data. While the three species share many neuroanatomical similarities differentiating them from plesiadapiforms (stem primates) and extant euprimates, our sample of N. tenebrosus displays more variation than that of S. gracilis, possibly related to differences in the patterns of cranial sexual dimorphism or within-lineage evolution. Body masses predicted from associated teeth suggest that N. tenebrosus was larger and had a lower encephalization quotient (EQ) than S. gracilis, despite their close relationship and similar inferred ecologies. Meanwhile, body masses predicted from cranial length of the same specimens suggest that the two species were more similar, with overlapping body mass and EQ, although S. gracilis exhibits a range of EQs shifted upwards relative to that of N. tenebrosus. While associated data from other parts of the skeleton are mostly lacking for specimens included in this study, measurements for unassociated postcrania attributed to these species yield body mass and EQ estimates that are also more similar to each other than those based on teeth. Regardless of the body mass prediction method used, results suggest that the average EQ of adapiforms was similar to that of plesiadapiforms, only overlapped the lower quadrant for the range of extant strepsirrhines, and did not overlap with the range of extant haplorhines. However, structural changes evident in these endocasts suggest that early euprimates relied more on vision than olfaction

  1. Prosocial primates: selfish and unselfish motivations

    PubMed Central

    de Waal, Frans B. M.; Suchak, Malini

    2010-01-01

    Non-human primates are marked by well-developed prosocial and cooperative tendencies as reflected in the way they support each other in fights, hunt together, share food and console victims of aggression. The proximate motivation behind such behaviour is not to be confused with the ultimate reasons for its evolution. Even if a behaviour is ultimately self-serving, the motivation behind it may be genuinely unselfish. A sharp distinction needs to be drawn, therefore, between (i) altruistic and cooperative behaviour with knowable benefits to the actor, which may lead actors aware of these benefits to seek them by acting cooperatively or altruistically and (ii) altruistic behaviour that offers the actor no knowable rewards. The latter is the case if return benefits occur too unpredictably, too distantly in time or are of an indirect nature, such as increased inclusive fitness. The second category of behaviour can be explained only by assuming an altruistic impulse, which—as in humans—may be born from empathy with the recipient's need, pain or distress. Empathy, a proximate mechanism for prosocial behaviour that makes one individual share another's emotional state, is biased the way one would predict from evolutionary theories of cooperation (i.e. by kinship, social closeness and reciprocation). There is increasing evidence in non-human primates (and other mammals) for this proximate mechanism as well as for the unselfish, spontaneous nature of the resulting prosocial tendencies. This paper further reviews observational and experimental evidence for the reciprocity mechanisms that underlie cooperation among non-relatives, for inequity aversion as a constraint on cooperation and on the way defection is dealt with. PMID:20679114

  2. Comparative primate energetics and hominid evolution.

    PubMed

    Leonard, W R; Robertson, M L

    1997-02-01

    There is currently great interest in developing ecological models for investigating human evolution. Yet little attention has been given to energetics, one of the cornerstones of modern ecosystem ecology. This paper examines the ecological correlates of variation in metabolic requirements among extant primate species, and uses this information to draw inferences about the changes in energy demands over the course of human evolution. Data on body size, resting metabolism, and activity budgets for selected anthropoid species and human hunter-gatherers are used to estimate total energy expenditure (TEE). Analyses indicate that relative energy expenditure levels and day ranges are positively correlated with diet quality; that is, more active species tend to consume more energy-rich diets. Human foragers fall at the positive extremes for modern primates in having high expenditure levels, large ranges, and very high quality diets. During hominid evolution, it appears that TEE increased substantially with the emergence of Homo erectus. This increase is partly attributable to larger body size as well as likely increases in day range and activity level. Assuming similar activity budgets for all early hominid species, estimated TEE for H. erectus is 40-45% greater than for the australopithecines. If, however, it is assumed that the evolution of early Homo was also associated with a shift to a more "human-like" foraging strategy, estimated expenditure levels for H. erectus are 80-85% greater than in the australopithecines. Changing patterns of resource distribution associated with the expansion of African savannas between 2.5 and 1.5 mya may been the impetus for a shift in foraging behavior among early members of the genus Homo. Such ecological changes likely would have made animal foods a more attractive resource. Moreover, greater use of animal foods and the resulting higher quality diet would have been important for supporting the larger day ranges and greater energy

  3. The major histocompatibility complex of primates.

    PubMed

    Heise, E R; Cook, D J; Schepart, B S; Manning, C H; McMahan, M R; Chedid, M; Keever, C A

    1987-08-31

    The major histocompatibility complex (MHC) encodes cell surface glycoproteins that function in self-nonself recognition and in allograft rejection. Among primates, the MHC has been well defined only in the human; in the chimpanzee and in two species of macaque monkeys the MHC is less well characterized. Serologic, biochemical and genetic evidence indicates that the basic organization of the MHC linkage group has been phylogenetically conserved. However, the number of genes and their linear relationship on the chromosomes differ between species. Class I MHC loci encode molecules that are the most polymorphic genes known. These molecules are ubiquitous in their tissue distribution and typically are recognized together with nominal antigens by cytotoxic lymphocytes. Class II MHC loci constitute a smaller family of serotypes serving as restricting elements for regulatory T lymphocytes. The distribution of class II antigens is limited mainly to cell types serving immune functions, and their expression is subject to up and down modulation. Class III loci code for components C2, C4 and Factor B (Bf) of the complement system. Interspecies differences in the extent of polymorphism occur, but the significance of this finding in relation to fitness and natural selection is unclear. Detailed information on the structure and regulation of MHC gene expression will be required to understand fully the biologic role of the MHC and the evolutionary relationships between species. Meanwhile, MHC testing has numerous applications to biomedical research, especially in preclinical tissue and organ transplantation studies, the study of disease mechanisms, parentage determination and breeding colony management. In this review, the current status of MHC definition in nonhuman primates will be summarized. Special emphasis is placed on the CyLA system of M. fascicularis which is a major focus in our laboratory. A highly polymorphic cynomolgus MHC has been partially characterized and consists

  4. Early primate evolution in Afro-Arabia.

    PubMed

    Seiffert, Erik R

    2012-11-01

    The peculiar mammalian fauna that inhabited Afro-Arabia during the Paleogene first came to the attention of the scientific community in the early part of the twentieth century, when Andrews1 and Schlosser2 published their landmark descriptions of fossil mammals from the Fayum Depression in northern Egypt. Their studies revealed a highly endemic assemblage of land mammals that included the first known Paleogene records of hyraxes, proboscideans, and anthropoid primates, but which lacked ancestors of many iconic mammalian lineages that are found in Africa today, such as rhinos, zebras, bovids, giraffes, and cats. Over the course of the last century, the Afro-Arabian Paleogene has yielded fossil remains of several other endemic mammalian lineages,3 as well as a diversity of prosimian primates,4 but we are only just beginning to understand how the continent's faunal composition came to be, through ancient processes such as the movement of tectonic plates, changes in climate and sea level, and early phylogenetic splits among the major groups of placental mammals. These processes, in turn, made possible chance dispersal events that were critical in determining the competitive landscape--and, indeed, the survival--of our earliest anthropoid ancestors. Newly discovered fossils indicate that the persistence and later diversification of Anthropoidea was not an inevitable result of the clade's competitive isolation or adaptive superiority, as has often been assumed, but rather was as much due to the combined influences of serendipitous geographic conditions, global cooling, and competition with a group of distantly related extinct strepsirrhines with anthropoid-like adaptations known as adapiforms. Many of the important details of this story would not be known, and could never have been predicted, without the fossil evidence that has recently been unearthed by field paleontologists. PMID:23280921

  5. Microgravity Flight - Accommodating Non-Human Primates

    NASA Technical Reports Server (NTRS)

    Dalton, Bonnie P.; Searby, Nancy; Ostrach, Louis

    1994-01-01

    Spacelab Life Sciences-3 (SLS-3) was scheduled to be the first United States man-tended microgravity flight containing Rhesus monkeys. The goal of this flight as in the five untended Russian COSMOS Bion flights and an earlier American Biosatellite flight, was to understand the biomedical and biological effects of a microgravity environment using the non-human primate as human surrogate. The SLS-3/Rhesus Project and COSMOS Primate-BIOS flights all utilized the rhesus monkey, Macaca mulatta. The ultimate objective of all flights with an animal surrogate has been to evaluate and understand biological mechanisms at both the system and cellular level, thus enabling rational effective countermeasures for future long duration human activity under microgravity conditions and enabling technical application to correction of common human physiological problems within earth's gravity, e.g., muscle strength and reloading, osteoporosis, immune deficiency diseases. Hardware developed for the SLS-3/Rhesus Project was the result of a joint effort with the French Centre National d'Etudes Spatiales (CNES) and the United States National Aeronautics and Space Administration (NASA) extending over the last decade. The flight hardware design and development required implementation of sufficient automation to insure flight crew and animal bio-isolation and maintenance with minimal impact to crew activities. A variety of hardware of varying functional capabilities was developed to support the scientific objectives of the original 22 combined French and American experiments, along with 5 Russian co-investigations, including musculoskeletal, metabolic, and behavioral studies. Unique elements of the Rhesus Research Facility (RRF) included separation of waste for daily delivery of urine and fecal samples for metabolic studies and a psychomotor test system for behavioral studies along with monitored food measurement. As in untended flights, telemetry measurements would allow monitoring of

  6. Lentivirus-mediated knockdown of eukaryotic translation initiation factor 3 subunit D inhibits proliferation of HCT116 colon cancer cells.

    PubMed

    Yu, Xiaojun; Zheng, Bo'an; Chai, Rui

    2014-12-12

    Dysregulation of protein synthesis is emerging as a major contributory factor in cancer development. eIF3D (eukaryotic translation initiation factor 3 subunit D) is one member of the eIF3 (eukaryotic translation initiation factor 3) family, which is essential for initiation of protein synthesis in eukaryotic cells. Acquaintance with eIF3D is little since it has been identified as a dispensable subunit of eIF3 complex. Recently, eIF3D was found to embed somatic mutations in human colorectal cancers, indicating its importance for tumour progression. To further probe into its action in colon cancer, we utilized lentivirus-mediated RNA interference to knock down eIF3D expression in one colon cancer cell line HCT116. Knockdown of eIF3D in HCT116 cells significantly inhibited cell proliferation and colony formation in vitro. Flow cytometry analysis indicated that depletion of eIF3D led to cell-cycle arrest in the G2/M phase, and induced an excess accumulation of HCT116 cells in the sub-G1 phase representing apoptotic cells. Signalling pathways responsible for cell growth and apoptosis have also been found altered after eIF3D silencing, such as AMPKα (AMP-activated protein kinase alpha), Bad, PRAS40 [proline-rich Akt (PKB) substrate of 40 kDa], SAPK (stress-activated protein kinase)/JNK (c-Jun N-terminal kinase), GSK3β and PARP [poly(ADP-ribose) polymerase]. Taken together, these findings suggest that eIF3D might play an important role in colon cancer progression.

  7. Enhancing chemosensitivity in oral squamous cell carcinoma by lentivirus vector-mediated RNA interference targeting EGFR and MRP2

    PubMed Central

    Chen, Ying-Ju; Chen, Shiuan-Yin; Lovel, Ronald; Ku, Yi-Chu; Lai, Yi-Hui; Hung, Chiao-Ling; Li, Yu-Fen; Lu, Yin-Che; Tai, Chien-Kuo

    2016-01-01

    Oral cancer is the eighth most common type of cancer among men worldwide, with an age-standardized rate of 6.3 per 100,000, and is the fourth leading cause of cancer-associated mortality among men in Taiwan. Cisplatin and 5-fluorouracil (5-FU) are two of the most frequently utilized chemotherapy drugs for the treatment of oral cancer. Although oral cancer patients initially benefit from chemotherapy with these drugs, they may develop resistance to them, which worsens their prognosis and reduces survival rates. It has been reported that increased levels of epidermal growth factor receptor (EGFR) and multidrug resistance-associated protein 2 (MRP2) induce drug resistance in numerous types of human cancer. Therefore, the present study employed lentivirus vector-mediated RNA interference (RNAi) in order to target the genes encoding EGFR and MRP2 in the oral squamous cell carcinoma cell line OC2. It was observed that RNAi-mediated downregulation of EGFR or MRP2 increased the sensitivity to 5-FU and cisplatin in OC2 cells. Downregulation of EGFR resulted in significant suppression of OC2 tumor growth following 5-FU administration. However, simultaneous downregulation of the two genes did not further suppress the tumor growth, indicating that MRP2 does not have a significant role in the chemosensitivity of EGFR-downregulated cells to 5-FU. In contrast, downregulation of MRP2 was demonstrated to significantly enhance the therapeutic effects of cisplatin in EGFR-downregulated OC2 tumors. The observation that the expression of MRP2 was positively correlated with the level of cisplatin resistance in cells suggests that RNAi-mediated downregulation of MRP2 may be applicable as a therapeutic approach toward reversing MRP2-dependent cisplatin resistance in oral cancer. PMID:27602148

  8. Characteristics of a thyroid hormone responsive reporter gene transduced into a Xenopus laevis cell line using lentivirus vector.

    PubMed

    Sugiyama, Shin-Ichiro; Miyoshi, Hiroyuki; Yamauchi, Kiyoshi

    2005-12-01

    We introduced a self-inactivation (SIN) lentivirus vector (LV) into Xenopus laevis cell lines and established a permanent cell line expressing a reporter gene in a 3,5,3'-l-triiodothyronine (T(3)) dependent manner. The SIN LV contained the luciferase gene downstream from the X. laevis T(3)-response elements (TREs) and the SV40 promoter, and the enhanced green fluorescent protein (EGFP) gene downstream from the cytomegalovirus (CMV) promoter. It was integrated into the genome of X. laevis XL58, XTC2, and KR cells. The SIN LV transduced the X. laevis cells as efficiently as mammalian cells; however, the expression of EGFP in the transgene decreased with increasing culture time. A cell clone exhibiting the highest TH-dependent luciferase gene expression (XL58-TRE-Luc clone) was isolated from the EGFP-positive XL58 cell pool and characterized. The minimum effective concentration of T(3) that significantly induced the luciferase gene expression was 10(-11)M in the XL58-TRE-Luc clone. The application of the luciferase gene assay using the permanent XL58-TRE-Luc clone for the screening of thyroid-disrupting chemicals revealed that tetrachlorobisphenol A, at 10(-6)M, had a weak T(3)-agonist activity, whereas trichlorobisphenol A, at 10(-8) - 10(-6)M had a weak T(3)-antagonist activity. Our results indicated that the permanent X. laevis cell line containing a T(3)-response transgene could be used as a bioassay, with small intra-assay variation, for the rapid screening, identification, and characterization of the thyroid-disrupting chemicals. PMID:16102758

  9. Mimiviruses: Replication, Purification, and Quantification.

    PubMed

    Abrahão, Jônatas Santos; Oliveira, Graziele Pereira; Ferreira da Silva, Lorena Christine; Dos Santos Silva, Ludmila Karen; Kroon, Erna Geessien; La Scola, Bernard

    2016-01-01

    The aim of this protocol is to describe the replication, purification, and titration of mimiviruses. These viruses belong to the Mimiviridae family, the first member of which was isolated in 1992 from a cooling tower water sample collected during an outbreak of pneumonia in a hospital in Bradford, England. In recent years, several new mimiviruses have been isolated from different environmental conditions. These giant viruses are easily replicated in amoeba of the Acanthamoeba genus, its natural host. Mimiviruses present peculiar features that make them unique viruses, such as the particle and genome size and the genome's complexity. The discovery of these viruses rekindled discussions about their origin and evolution, and the genetic and structural complexity opened up a new field of study. Here, we describe some methods utilized for mimiviruses replication, purification, and titration. © 2016 by John Wiley & Sons, Inc. PMID:27153385

  10. Replicating systems concepts: Self-replicating lunar factory and demonstration

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Automation of lunar mining and manufacturing facility maintenance and repair is addressed. Designing the factory as an automated, multiproduct, remotely controlled, reprogrammable Lunar Manufacturing Facility capable of constructing duplicates of itself which would themselves be capable of further replication is proposed.

  11. A Replication of Failure, Not a Failure to Replicate

    ERIC Educational Resources Information Center

    Holden, Gary; Barker, Kathleen; Kuppens, Sofie; Rosenberg, Gary; LeBreton, Jonathan

    2015-01-01

    Purpose: The increasing role of systematic reviews in knowledge production demands greater rigor in the literature search process. The performance of the Social Work Abstracts (SWA) database has been examined multiple times over the past three decades. The current study is a replication within this line of research. Method: Issue-level coverage…

  12. Personality and Academic Motivation: Replication, Extension, and Replication

    ERIC Educational Resources Information Center

    Jones, Martin H.; McMichael, Stephanie N.

    2015-01-01

    Previous work examines the relationships between personality traits and intrinsic/extrinsic motivation. We replicate and extend previous work to examine how personality may relate to achievement goals, efficacious beliefs, and mindset about intelligence. Approximately 200 undergraduates responded to the survey with a 150 participants replicating…

  13. Polyamines and Hypusination Are Required for Ebolavirus Gene Expression and Replication

    PubMed Central

    Olsen, Michelle E.; Filone, Claire Marie; Rozelle, Dan; Mire, Chad E.; Agans, Krystle N.; Hensley, Lisa

    2016-01-01

    ABSTRACT Ebolavirus (EBOV) is an RNA virus that is known to cause severe hemorrhagic fever in humans and other primates. EBOV successfully enters and replicates in many cell types. This replication is dependent on the virus successfully coopting a number of cellular factors. Many of these factors are currently unidentified but represent potential targets for antiviral therapeutics. Here we show that cellular polyamines are critical for EBOV replication. We found that small-molecule inhibitors of polyamine synthesis block gene expression driven by the viral RNA-dependent RNA polymerase. Short hairpin RNA (shRNA) knockdown of the polyamine pathway enzyme spermidine synthase also resulted in reduced EBOV replication. These findings led us to further investigate spermidine, a polyamine that is essential for the hypusination of eukaryotic initiation factor 5A (eIF5A). Blocking the hypusination of eIF5A (and thereby inhibiting its function) inhibited both EBOV gene expression and viral replication. The mechanism appears to be due to the importance of hypusinated eIF5A for the accumulation of VP30, an essential component of the viral polymerase. The same reduction in hypusinated eIF5A did not alter the accumulation of other viral polymerase components. This action makes eIF5A function an important gate for proper EBOV polymerase assembly and function through the control of a single virus protein. PMID:27460797

  14. Exploiting replication in distributed systems

    NASA Technical Reports Server (NTRS)

    Birman, Kenneth P.; Joseph, T. A.

    1989-01-01

    Techniques are examined for replicating data and execution in directly distributed systems: systems in which multiple processes interact directly with one another while continuously respecting constraints on their joint behavior. Directly distributed systems are often required to solve difficult problems, ranging from management of replicated data to dynamic reconfiguration in response to failures. It is shown that these problems reduce to more primitive, order-based consistency problems, which can be solved using primitives such as the reliable broadcast protocols. Moreover, given a system that implements reliable broadcast primitives, a flexible set of high-level tools can be provided for building a wide variety of directly distributed application programs.

  15. Parkinson's disease and primate research: past, present, and future

    PubMed Central

    Pereira, E A C; Aziz, T Z

    2006-01-01

    Scientific research involving non‐human primates has contributed towards many advances in medicine and surgery. This review discusses its role in the progress made towards our understanding of Parkinson's disease and its treatment. Established medical treatments like dopamine agonists continue to need primate models to assess their efficacy, safety, and mechanism of action. The recently developed treatment of deep brain stimulation of the subthalamic nucleus required validation in primates before entering the clinic. Controversies surrounding future treatments such as gene therapy show the need for properly evaluated preclinical research using appropriate animal models before progression to clinical trials. Research on primates has played—and continues to play—a crucial part in deepening our understanding of Parkinson's disease, improving current therapies, and developing new treatments that are both safe and effective. In animal research, the “three Rs” of humane technique—reduction, refinement, and replacement—should be adhered to. PMID:16679465

  16. The earliest fossil evidence for sexual dimorphism in primates

    NASA Technical Reports Server (NTRS)

    Krishtalka, Leonard; Stucky, Richard K.; Beard, K. C.

    1990-01-01

    Recently obtained material of the early Eocene primate Notharctus venticolus, including two partial skulls from a single stratigraphic horizon, provides the geologically earliest evidence of sexual dimorphism in canine size and shape in primates and the only unequivocal evidence for such dimorphism in strepsirhines. By analogy with living platyrrhines, these data suggest that Notharctus venticolus may have lived in polygynous social groups characterized by a relatively high level of intermale competition for mates and other limited resources. The anatomy of the upper incisors and related evidence imply that Notharctus is not as closely related to extant lemuriform primates as has been recently proposed. The early Eocene evidence for canine sexual dimorphism reported here, and its occurrence in a nonanthropoid, indicates that in the order Primates such a condition is either primitive or evolved independently more than once.

  17. Comparative Triceps Surae Morphology in Primates: A Review

    PubMed Central

    Hanna, Jandy B.; Schmitt, Daniel

    2011-01-01

    Primate locomotor evolution, particularly the evolution of bipedalism, is often examined through morphological studies. Many of these studies have examined the uniqueness of the primate forelimb, and others have examined the primate hip and thigh. Few data exist, however, regarding the myology and function of the leg muscles, even though the ankle plantar flexors are highly important during human bipedalism. In this paper, we draw together data on the fiber type and muscle mass variation in the ankle plantar flexors of primates and make comparisons to other mammals. The data suggest that great apes, atelines, and lorisines exhibit similarity in the mass distribution of the triceps surae. We conclude that variation in triceps surae may be related to the shared locomotor mode exhibited by these groups and that triceps surae morphology, which approaches that of humans, may be related to frequent use of semiplantigrade locomotion and vertical climbing. PMID:22567288

  18. Light responses of primate and other mammalian cones

    PubMed Central

    Cao, Li-Hui; Luo, Dong-Gen; Yau, King-Wai

    2014-01-01

    Retinal cones are photoreceptors for daylight vision. For lower vertebrates, cones are known to give monophasic, hyperpolarizing responses to light flashes. For primate cones, however, they have been reported to give strongly biphasic flash responses, with an initial hyperpolarization followed by a depolarization beyond the dark level, now a textbook dogma. We have reexamined this primate-cone observation and, surprisingly, found predominantly monophasic cone responses. Correspondingly, we found that primate cones began to adapt to steady light at much lower intensities than previously reported, explainable by a larger steady response to background light for a monophasic than for a biphasic response. Similarly, we have found a monophasic cone response for several other mammalian species. Thus, a monophasic flash response may in fact be the norm for primate and other mammalian cones as for lower-vertebrate cones. This revised information is important for ultimately understanding human retinal signal processing and correlating with psychophysical data. PMID:24550304

  19. The scaling of frontal cortex in primates and carnivores

    PubMed Central

    Bush, Eliot C.; Allman, John M.

    2004-01-01

    Size has a profound effect on the structure of the brain. Many brain structures scale allometrically, that is, their relative size changes systematically as a function of brain size. Here we use independent contrasts analysis to examine the scaling of frontal cortex in 43 species of mammals including 25 primates and 15 carnivores. We find evidence for significant differences in scaling between primates and carnivores. Primate frontal cortex hyperscales relative to the rest of neocortex and the rest of the brain. The slope of frontal cortex contrasts on rest of cortex contrasts is 1.18 (95% confidence interval, 1.06-1.30) for primates, which is significantly greater than isometric. It is also significantly greater than the carnivore value of 0.94 (95% confidence interval, 0.82-1.07). This finding supports the idea that there are substantial differences in frontal cortex structure and development between the two groups. PMID:15007170

  20. Bat hepadnaviruses and the origins of primate hepatitis B viruses.

    PubMed

    Rasche, Andrea; Souza, Breno Frederico de Carvalho Dominguez; Drexler, Jan Felix

    2016-02-01

    The origin of primate HBV (family Hepadnaviridae) is unknown. Hepadnaviruses are ancient pathogens and may have been associated with old mammalian lineages like bats for prolonged time. Indeed, the genetic diversity of bat hepadnaviruses exceeds that of extant hepadnaviruses in other host orders, suggesting a long evolution of hepadnaviruses in bats. Strikingly, a recently detected New World bat hepadnavirus is antigenically related to HBV and can infect human hepatocytes. Together with genetically diverse hepadnaviruses from New World rodents and a non-human primate, these viruses argue for a New World origin of ancestral orthohepadnaviruses. Multiple host switches of bat and primate viruses are evident and bats are likely sources of ancestral hepadnaviruses acquired by primates. PMID:26897577

  1. Light responses of primate and other mammalian cones.

    PubMed

    Cao, Li-Hui; Luo, Dong-Gen; Yau, King-Wai

    2014-02-18

    Retinal cones are photoreceptors for daylight vision. For lower vertebrates, cones are known to give monophasic, hyperpolarizing responses to light flashes. For primate cones, however, they have been reported to give strongly biphasic flash responses, with an initial hyperpolarization followed by a depolarization beyond the dark level, now a textbook dogma. We have reexamined this primate-cone observation and, surprisingly, found predominantly monophasic cone responses. Correspondingly, we found that primate cones began to adapt to steady light at much lower intensities than previously reported, explainable by a larger steady response to background light for a monophasic than for a biphasic response. Similarly, we have found a monophasic cone response for several other mammalian species. Thus, a monophasic flash response may in fact be the norm for primate and other mammalian cones as for lower-vertebrate cones. This revised information is important for ultimately understanding human retinal signal processing and correlating with psychophysical data. PMID:24550304

  2. Primate postcrania from the late middle Eocene of Myanmar

    PubMed Central

    Ciochon, Russell L.; Gingerich, Philip D.; Gunnell, Gregg F.; Simons, Elwyn L.

    2001-01-01

    Fossil primates have been known from the late middle to late Eocene Pondaung Formation of Myanmar since the description of Pondaungia cotteri in 1927. Three additional primate taxa, Amphipithecus mogaungensis, Bahinia pondaungensis and Myanmarpithecus yarshensis, were subsequently described. These primates are represented mostly by fragmentary dental and cranial remains. Here we describe the first primate postcrania from Myanmar, including a complete left humerus, a fragmentary right humerus, parts of left and right ulnae, and the distal half of a left calcaneum, all representing one individual. We assign this specimen to a large species of Pondaungia based on body size and the known geographic distribution and diversity of Myanmar primates. Body weight estimates of Pondaungia range from 4,000 to 9,000 g, based on humeral length, humeral midshaft diameter, and tooth area by using extant primate regressions. The humerus and ulna indicate that Pondaungia was capable of a wide variety of forelimb movements, with great mobility at the shoulder joint. Morphology of the distal calcaneus indicates that the hind feet were mobile at the transverse tarsal joint. Postcrania of Pondaungia present a mosaic of features, some shared in common with notharctine and adapine adapiforms, some shared with extant lorises and cebids, some shared with fossil anthropoids, and some unique. Overall, Pondaungia humeral and calcaneal morphology is most consistent with that of other known adapiforms. It does not support the inclusion of Pondaungia in Anthropoidea. PMID:11438722

  3. The evolution of primate general and cultural intelligence.

    PubMed

    Reader, Simon M; Hager, Yfke; Laland, Kevin N

    2011-04-12

    There are consistent individual differences in human intelligence, attributable to a single 'general intelligence' factor, g. The evolutionary basis of g and its links to social learning and culture remain controversial. Conflicting hypotheses regard primate cognition as divided into specialized, independently evolving modules versus a single general process. To assess how processes underlying culture relate to one another and other cognitive capacities, we compiled ecologically relevant cognitive measures from multiple domains, namely reported incidences of behavioural innovation, social learning, tool use, extractive foraging and tactical deception, in 62 primate species. All exhibited strong positive associations in principal component and factor analyses, after statistically controlling for multiple potential confounds. This highly correlated composite of cognitive traits suggests social, technical and ecological abilities have coevolved in primates, indicative of an across-species general intelligence that includes elements of cultural intelligence. Our composite species-level measure of general intelligence, 'primate g(S)', covaried with both brain volume and captive learning performance measures. Our findings question the independence of cognitive traits and do not support 'massive modularity' in primate cognition, nor an exclusively social model of primate intelligence. High general intelligence has independently evolved at least four times, with convergent evolution in capuchins, baboons, macaques and great apes.

  4. Euarchontan Opsin Variation Brings New Focus to Primate Origins.

    PubMed

    Melin, Amanda D; Wells, Konstans; Moritz, Gillian L; Kistler, Logan; Orkin, Joseph D; Timm, Robert M; Bernard, Henry; Lakim, Maklarin B; Perry, George H; Kawamura, Shoji; Dominy, Nathaniel J

    2016-04-01

    Debate on the adaptive origins of primates has long focused on the functional ecology of the primate visual system. For example, it is hypothesized that variable expression of short- (SWS1) and middle-to-long-wavelength sensitive (M/LWS) opsins, which confer color vision, can be used to infer ancestral activity patterns and therefore selective ecological pressures. A problem with this approach is that opsin gene variation is incompletely known in the grandorder Euarchonta, that is, the orders Scandentia (treeshrews), Dermoptera (colugos), and Primates. The ancestral state of primate color vision is therefore uncertain. Here, we report on the genes (OPN1SW and OPN1LW) that encode SWS1 and M/LWS opsins in seven species of treeshrew, including the sole nocturnal scandentian Ptilocercus lowii. In addition, we examined the opsin genes of the Central American woolly opossum (Caluromys derbianus), an enduring ecological analogue in the debate on primate origins. Our results indicate: 1) retention of ultraviolet (UV) visual sensitivity in C. derbianus and a shift from UV to blue spectral sensitivities at the base of Euarchonta; 2) ancient pseudogenization of OPN1SW in the ancestors of P. lowii, but a signature of purifying selection in those of C. derbianus; and, 3) the absence of OPN1LW polymorphism among diurnal treeshrews. These findings suggest functional variation in the color vision of nocturnal mammals and a distinctive visual ecology of early primates, perhaps one that demanded greater spatial resolution under light levels that could support cone-mediated color discrimination.

  5. Stable carbon and nitrogen isotope enrichment in primate tissues

    PubMed Central

    Carter, Melinda L.; Karpanty, Sarah M.; Zihlman, Adrienne L.; Koch, Paul L.; Dominy, Nathaniel J.

    2010-01-01

    Isotopic studies of wild primates have used a wide range of tissues to infer diet and model the foraging ecologies of extinct species. The use of mismatched tissues for such comparisons can be problematic because differences in amino acid compositions can lead to small isotopic differences between tissues. Additionally, physiological and dietary differences among primate species could lead to variable offsets between apatite carbonate and collagen. To improve our understanding of the isotopic chemistry of primates, we explored the apparent enrichment (ε*) between bone collagen and muscle, collagen and fur or hair keratin, muscle and keratin, and collagen and bone carbonate across the primate order. We found that the mean ε* values of proteinaceous tissues were small (≤1‰), and uncorrelated with body size or phylogenetic relatedness. Additionally, ε* values did not vary by habitat, sex, age, or manner of death. The mean ε* value between bone carbonate and collagen (5.6 ± 1.2‰) was consistent with values reported for omnivorous mammals consuming monoisotopic diets. These primate-specific apparent enrichment values will be a valuable tool for cross-species comparisons. Additionally, they will facilitate dietary comparisons between living and fossil primates. Electronic supplementary material The online version of this article (doi:10.1007/s00442-010-1701-6) contains supplementary material, which is available to authorized users. PMID:20628886

  6. Primate spatial strategies and cognition: introduction to this special issue.

    PubMed

    Garber, Paul A; Dolins, Francine L

    2014-05-01

    Wild primates face significant challenges associated with locating resources that involve learning through exploration, encoding, and recalling travel routes, orienting to single landmarks or landmark arrays, monitoring food availability, and applying spatial strategies that reduce effort and increase efficiency. These foraging decisions are likely to involve tradeoffs between traveling to nearby or distant feeding sites based on expectations of resource productivity, predation risk, the availability of other nearby feeding sites, and individual requirements associated with nutrient balancing. Socioecological factors that affect primate foraging decisions include feeding competition, intergroup encounters, mate defense, and opportunities for food sharing. The nine research papers in this Special Issue, "Primate Spatial Strategies and Cognition," address a series of related questions examining how monkeys, apes, and humans encode, internally represent, and integrate spatial, temporal, and quantity information in efficiently locating and relocating productive feeding sites in both small-scale and large-scale space. The authors use a range of methods and approaches to study wild and captive primates, including computer and mathematical modeling, virtual reality, and detailed examinations of animal movement using GPS and GIS analyses to better understand primate cognitive ecology and species differences in decision-making. We conclude this Introduction by identifying a series of critical questions for future research designed to document species-specific differences in primate spatial cognition.

  7. Eye-Blink Behaviors in 71 Species of Primates

    PubMed Central

    Tada, Hideoki; Omori, Yasuko; Hirokawa, Kumi; Ohira, Hideki; Tomonaga, Masaki

    2013-01-01

    The present study was performed to investigate the associations between eye-blink behaviors and various other factors in primates. We video-recorded 141 individuals across 71 primate species and analyzed the blink rate, blink duration, and “isolated” blink ratio (i.e., blinks without eye or head movement) in relation to activity rhythms, habitat types, group size, and body size factors. The results showed close relationships between three types of eye-blink measures and body size factors. All of these measures increased as a function of body weight. In addition, diurnal primates showed more blinks than nocturnal species even after controlling for body size factors. The most important findings were the relationships between eye-blink behaviors and social factors, e.g., group size. Among diurnal primates, only the blink rate was significantly correlated even after controlling for body size factors. The blink rate increased as the group size increased. Enlargement of the neocortex is strongly correlated with group size in primate species and considered strong evidence for the social brain hypothesis. Our results suggest that spontaneous eye-blinks have acquired a role in social communication, similar to grooming, to adapt to complex social living during primate evolution. PMID:23741522

  8. Nonhuman Primate Models in the Genomic Era: A Paradigm Shift

    PubMed Central

    Vallender, Eric J.; Miller, Gregory M.

    2013-01-01

    Because of their strong similarities to humans across physiologic, developmental, behavioral, immunologic, and genetic levels, nonhuman primates are essential models for a wide spectrum of biomedical research. But unlike other animal models, nonhuman primates possess substantial outbred genetic variation, reducing statistical power and potentially confounding interpretation of results in research studies. Although unknown genetic variation is a hindrance in studies that allocate animals randomly, taking genetic variation into account in study design affords an opportunity to transform the way that nonhuman primates are used in biomedical research. New understandings of how the function of individual genes in rhesus macaques mimics that seen in humans are greatly advancing the rhesus macaques utility as research models, but epistatic interaction, epigenetic regulatory mechanisms, and the intricacies of gene networks limit model development. We are now entering a new era of nonhuman primate research, brought on by the proliferation and rapid expansion of genomic data. Already the cost of a rhesus macaque genome is dwarfed by its purchase and husbandry costs, and complete genomic datasets will inevitably encompass each rhesus macaque used in biomedical research. Advancing this outcome is paramount. It represents an opportunity to transform the way animals are assigned and used in biomedical research and to develop new models of human disease. The genetic and genomic revolution brings with it a paradigm shift for nonhuman primates and new mandates on how nonhuman primates are used in biomedical research. PMID:24174439

  9. A Genome-Wide Landscape of Retrocopies in Primate Genomes.

    PubMed

    Navarro, Fábio C P; Galante, Pedro A F

    2015-08-01

    Gene duplication is a key factor contributing to phenotype diversity across and within species. Although the availability of complete genomes has led to the extensive study of genomic duplications, the dynamics and variability of gene duplications mediated by retrotransposition are not well understood. Here, we predict mRNA retrotransposition and use comparative genomics to investigate their origin and variability across primates. Analyzing seven anthropoid primate genomes, we found a similar number of mRNA retrotranspositions (∼7,500 retrocopies) in Catarrhini (Old Word Monkeys, including humans), but a surprising large number of retrocopies (∼10,000) in Platyrrhini (New World Monkeys), which may be a by-product of higher long interspersed nuclear element 1 activity in these genomes. By inferring retrocopy orthology, we dated most of the primate retrocopy origins, and estimated a decrease in the fixation rate in recent primate history, implying a smaller number of species-specific retrocopies. Moreover, using RNA-Seq data, we identified approximately 3,600 expressed retrocopies. As expected, most of these retrocopies are located near or within known genes, present tissue-specific and even species-specific expression patterns, and no expression correlation to their parental genes. Taken together, our results provide further evidence that mRNA retrotransposition is an active mechanism in primate evolution and suggest that retrocopies may not only introduce great genetic variability between lineages but also create a large reservoir of potentially functional new genomic loci in primate genomes. PMID:26224704

  10. The evolution of primate general and cultural intelligence

    PubMed Central

    Reader, Simon M.; Hager, Yfke; Laland, Kevin N.

    2011-01-01

    There are consistent individual differences in human intelligence, attributable to a single ‘general intelligence’ factor, g. The evolutionary basis of g and its links to social learning and culture remain controversial. Conflicting hypotheses regard primate cognition as divided into specialized, independently evolving modules versus a single general process. To assess how processes underlying culture relate to one another and other cognitive capacities, we compiled ecologically relevant cognitive measures from multiple domains, namely reported incidences of behavioural innovation, social learning, tool use, extractive foraging and tactical deception, in 62 primate species. All exhibited strong positive associations in principal component and factor analyses, after statistically controlling for multiple potential confounds. This highly correlated composite of cognitive traits suggests social, technical and ecological abilities have coevolved in primates, indicative of an across-species general intelligence that includes elements of cultural intelligence. Our composite species-level measure of general intelligence, ‘primate gS’, covaried with both brain volume and captive learning performance measures. Our findings question the independence of cognitive traits and do not support ‘massive modularity’ in primate cognition, nor an exclusively social model of primate intelligence. High general intelligence has independently evolved at least four times, with convergent evolution in capuchins, baboons, macaques and great apes. PMID:21357224

  11. Afrotarsius chatrathi, first tarsiiform primate (? Tarsiidae) from Africa

    USGS Publications Warehouse

    Simons, E.L.; Bown, T.M.

    1985-01-01

    Tarsiiform primates have long been regarded as a Laurasian group, with an extensive fossil record in the Eocene of North America and Europe1-4 and two important but less well-known records from Asia5,6. The only living genus is Tarsius (Tarsiidae), whereas all of the fossil tarsier-like primates are usually placed in the extinct family Omomyidae3. We now report the discovery of Afrotarsius chatrathi from early Oligocene rocks of Fayum Province, Egypt. This is the first known tarsiiform primate from Africa. Compared with fossil primates, the molar tooth morphology of this diminutive prosimian is most similar to that of the European Eocene microchoerine Pseudoloris; however, the closest similarity is to the molars of Tarsius. Because the phylogenetic relationships among living Tarsius and the omomyids remain unclear7,8 and because of the fragmentary nature of the only known specimen of this new primate, allocation of Afrotarsius to either Omomyidae or Tarsiidae is necessarily provisional. As we believe that its molar teeth are more like those of Tarsius than of any omomyids (including Pseudoloris), we tentatively assign the new genus to the extant family Tarsiidae as its only known fossil representative. Recovery of a Tarsius-like primate from Africa suggests that it or its ancestors might have been immigrants from Europe, may have been derived from an unknown Asian stock related to the ancestry of Tarsius, or may have originated in Africa. ?? 1985 Nature Publishing Group.

  12. Covert Reinforcement: A Partial Replication.

    ERIC Educational Resources Information Center

    Ripstra, Constance C.; And Others

    A partial replication of an investigation of the effect of covert reinforcement on a perceptual estimation task is described. The study was extended to include an extinction phase. There were five treatment groups: covert reinforcement, neutral scene reinforcement, noncontingent covert reinforcement, and two control groups. Each subject estimated…

  13. Hyperthermia Stimulates HIV-1 Replication

    PubMed Central

    Roesch, Ferdinand; Meziane, Oussama; Kula, Anna; Nisole, Sébastien; Porrot, Françoise; Anderson, Ian; Mammano, Fabrizio; Fassati, Ariberto; Marcello, Alessandro; Benkirane, Monsef; Schwartz, Olivier

    2012-01-01

    HIV-infected individuals may experience fever episodes. Fever is an elevation of the body temperature accompanied by inflammation. It is usually beneficial for the host through enhancement of immunological defenses. In cultures, transient non-physiological heat shock (42–45°C) and Heat Shock Proteins (HSPs) modulate HIV-1 replication, through poorly defined mechanisms. The effect of physiological hyperthermia (38–40°C) on HIV-1 infection has not been extensively investigated. Here, we show that culturing primary CD4+ T lymphocytes and cell lines at a fever-like temperature (39.5°C) increased the efficiency of HIV-1 replication by 2 to 7 fold. Hyperthermia did not facilitate viral entry nor reverse transcription, but increased Tat transactivation of the LTR viral promoter. Hyperthermia also boosted HIV-1 reactivation in a model of latently-infected cells. By imaging HIV-1 transcription, we further show that Hsp90 co-localized with actively transcribing provirus, and this phenomenon was enhanced at 39.5°C. The Hsp90 inhibitor 17-AAG abrogated the increase of HIV-1 replication in hyperthermic cells. Altogether, our results indicate that fever may directly stimulate HIV-1 replication, in a process involving Hsp90 and facilitation of Tat-mediated LTR activity. PMID:22807676

  14. Comparative primate energetics and hominid evolution.

    PubMed

    Leonard, W R; Robertson, M L

    1997-02-01

    There is currently great interest in developing ecological models for investigating human evolution. Yet little attention has been given to energetics, one of the cornerstones of modern ecosystem ecology. This paper examines the ecological correlates of variation in metabolic requirements among extant primate species, and uses this information to draw inferences about the changes in energy demands over the course of human evolution. Data on body size, resting metabolism, and activity budgets for selected anthropoid species and human hunter-gatherers are used to estimate total energy expenditure (TEE). Analyses indicate that relative energy expenditure levels and day ranges are positively correlated with diet quality; that is, more active species tend to consume more energy-rich diets. Human foragers fall at the positive extremes for modern primates in having high expenditure levels, large ranges, and very high quality diets. During hominid evolution, it appears that TEE increased substantially with the emergence of Homo erectus. This increase is partly attributable to larger body size as well as likely increases in day range and activity level. Assuming similar activity budgets for all early hominid species, estimated TEE for H. erectus is 40-45% greater than for the australopithecines. If, however, it is assumed that the evolution of early Homo was also associated with a shift to a more "human-like" foraging strategy, estimated expenditure levels for H. erectus are 80-85% greater than in the australopithecines. Changing patterns of resource distribution associated with the expansion of African savannas between 2.5 and 1.5 mya may been the impetus for a shift in foraging behavior among early members of the genus Homo. Such ecological changes likely would have made animal foods a more attractive resource. Moreover, greater use of animal foods and the resulting higher quality diet would have been important for supporting the larger day ranges and greater energy

  15. Functional Analysis of the Primate Shoulder

    PubMed Central

    Hohn, Bianca; Scherf, Heike; Schmidt, Manuela; Krause, Cornelia; Witzel, Ulrich

    2010-01-01

    Studies of the shoulder girdle are in most cases restricted to morphological comparisons and rarely aim at elucidating function in a strictly biomechanical sense. To fill this gap, we investigated the basic functional conditions that occur in the shoulder joint and shoulder girdle of primates by means of mechanics. Because most of nonhuman primate locomotion is essentially quadrupedal walking—although on very variable substrates—our analysis started with quadrupedal postures. We identified the mechanical situation at the beginning, middle, and end of the load-bearing stance phase by constructing force parallelograms in the shoulder joint and the scapulo-thoracal connection. The resulting postulates concerning muscle activities are in agreement with electromyographical data in the literature. We determined the magnitude and directions of the internal forces and explored mechanically optimal shapes of proximal humerus, scapula, and clavicula using the Finite Element Method. Next we considered mechanical functions other than quadrupedal walking, such as suspension and brachiation. Quadrupedal walking entails muscle activities and joint forces that require a long scapula, the cranial margin of which has about the same length as the axillary margin. Loading of the hand in positions above the head and suspensory behaviors lead to force flows along the axillary margin and so necessitate a scapula with an extended axillary and a shorter cranial margin. In all cases, the facies glenoidalis is nearly normal to the calculated joint forces. In anterior view, terrestrial monkeys chose a direction of the ground reaction force requiring (moderate) activity of the abductors of the shoulder joint, whereas more arboreal monkeys prefer postures that necessitate activity of the adductors of the forelimb even when walking along branches. The same adducting and retracting muscles are recruited in various forms of suspension. As a mechanical consequence, the scapula is in a more

  16. Transgenic mice support replication of hepatitis delta virus RNA in multiple tissues, particularly in skeletal muscle.

    PubMed Central

    Polo, J M; Jeng, K S; Lim, B; Govindarajan, S; Hofman, F; Sangiorgi, F; Lai, M M

    1995-01-01

    Hepatitis delta virus (HDV) is hepatotropic and frequently causes fulminant hepatitis in both human and nonhuman primate hosts. To understand the molecular basis of HDV tissue tropism and the mechanism of pathogenesis, transgenic mice in which replication-competent HDV dimeric RNA is expressed under the control of either liver-specific or universal transcriptional promoters were developed. The expressed RNA replicated efficiently in the liver and several tissues of nonhepatic origin. Surprisingly, maximal replication of HDV RNA occurred in skeletal muscle and was almost 100-fold greater than in the liver. These findings suggest that the hepatotropism of HDV is most likely a receptor-mediated restriction and that muscle-specific factors may facilitate HDV RNA replication. No evidence of cytopathology was apparent in most of the tissues examined, including the liver, supporting the contention that hepatocellular disease is not mediated by direct cytopathological effects associated with HDV RNA replication and gene expression. However, mild muscle atrophy in some of the transgenic mice was noted. Delta antigen was detected in the nuclei of myocytes. Only the small form, not the large form, of delta antigen was detected, suggesting that the RNA editing event which causes the conversion of delta antigen did not occur in transgenic mice. Furthermore, the 0.8-kb antigenomic RNA species, which is postulated to be the mRNA for delta antigen, was not detected in mice. The preferential replication of HDV RNA in skeletal muscle suggests that HDV RNA replication can be facilitated by certain muscle-specific factors. PMID:7609056

  17. In situ replication techniques: II. Quantitative methodologies for replicate materials.

    PubMed

    Kusy, R P; Whitley, J Q

    1985-01-01

    Because replicate materials have requirements different from those of recording or impression materials, quantitative methodologies were sought using commercial impression materials. Two satisfactory objective techniques resulted, a laser-scattering and a capillary flow test. Using high-resolution gratings to stimulate tooth detail (less than 1 micron), the reproduction quality of 36 two-stage replicas was determined in diffraction, reflection, and in an unblazed state. Using precision bore glass tubes (0.25, 0.5, 1, and 2 mm diameters) to simulate the high-energy surface of enamel, the flow characteristics of nine elastomers (the first stage replicates) and four epoxies (the second stage replicates) were determined at isobaric conditions. Because the laser spot size was relatively large (0.6 mm) and the pressure differential was small (25 mm Hg), both the global resolution and the low shear rate characteristics could be measured. Of the commercial materials tested, Reprosil Light had the best combination of fluidity and resolution, regardless of which positive material was used. Although Permagum Low, Silene Wash, and Xantopren Blue scored high in one of the two tests, none of these materials could compare to Reprosil Light within the context described herein.

  18. Development of a Lentivirus Vector-Based Assay for Non-Destructive Monitoring of Cell Fusion Activity

    PubMed Central

    Neshati, Zeinab; Liu, Jia; Zhou, Guangqian; Schalij, Martin J.; de Vries, Antoine A. F.

    2014-01-01

    Cell-to-cell fusion can be quantified by endowing acceptor and donor cells with latent reporter genes/proteins and activators of these genes/proteins, respectively. One way to accomplish this goal is by using a bipartite lentivirus vector (LV)-based cell fusion assay system in which the cellular fusion partners are transduced with a flippase-activatable Photinus pyralis luciferase (PpLuc) expression unit (acceptor cells) or with a recombinant gene encoding FLPeNLS+, a nuclear-targeted and molecularly evolved version of flippase (donor cells). Fusion of both cell populations will lead to the FLPe-dependent generation of a functional PpLuc gene. PpLuc activity is typically measured in cell lysates, precluding consecutive analysis of one cell culture. Therefore, in this study the PpLuc-coding sequence was replaced by that of Gaussia princeps luciferase (GpLuc), a secretory protein allowing repeated analysis of the same cell culture. In myotubes the spread of FLPeNLS+ may be limited due to its nuclear localization signal (NLS) causing low signal outputs. To test this hypothesis, myoblasts were transduced with LVs encoding either FLPeNLS+ or an NLS-less version of FLPe (FLPeNLS−) and subsequently co-cultured in different ratios with myoblasts containing the FLPe-activatable GpLuc expression cassette. At different times after induction of cell-to-cell fusion the GpLuc activity in the culture medium was determined. FLPeNLS+ and FLPeNLS− both activated the latent GpLuc gene but when the percentage of FLPe-expressing myoblasts was limiting, FLPeNLS+ generally yielded slightly higher signals than FLPeNLS− while at low acceptor-to-donor cell ratios FLPeNLS− was usually superior. The ability of FLPeNLS+ to spread through myofibers and to induce reporter gene expression is thus not limited by its NLS. However, at high FLPe concentrations the presence of the NLS negatively affected reporter gene expression. In summary, a rapid and simple chemiluminescence assay for

  19. Development of a lentivirus vector-based assay for non-destructive monitoring of cell fusion activity.

    PubMed

    Neshati, Zeinab; Liu, Jia; Zhou, Guangqian; Schalij, Martin J; de Vries, Antoine A F

    2014-01-01

    Cell-to-cell fusion can be quantified by endowing acceptor and donor cells with latent reporter genes/proteins and activators of these genes/proteins, respectively. One way to accomplish this goal is by using a bipartite lentivirus vector (LV)-based cell fusion assay system in which the cellular fusion partners are transduced with a flippase-activatable Photinus pyralis luciferase (PpLuc) expression unit (acceptor cells) or with a recombinant gene encoding FLPeNLS+, a nuclear-targeted and molecularly evolved version of flippase (donor cells). Fusion of both cell populations will lead to the FLPe-dependent generation of a functional PpLuc gene. PpLuc activity is typically measured in cell lysates, precluding consecutive analysis of one cell culture. Therefore, in this study the PpLuc-coding sequence was replaced by that of Gaussia princeps luciferase (GpLuc), a secretory protein allowing repeated analysis of the same cell culture. In myotubes the spread of FLPeNLS+ may be limited due to its nuclear localization signal (NLS) causing low signal outputs. To test this hypothesis, myoblasts were transduced with LVs encoding either FLPeNLS+ or an NLS-less version of FLPe (FLPeNLS-) and subsequently co-cultured in different ratios with myoblasts containing the FLPe-activatable GpLuc expression cassette. At different times after induction of cell-to-cell fusion the GpLuc activity in the culture medium was determined. FLPeNLS+ and FLPeNLS- both activated the latent GpLuc gene but when the percentage of FLPe-expressing myoblasts was limiting, FLPeNLS+ generally yielded slightly higher signals than FLPeNLS- while at low acceptor-to-donor cell ratios FLPeNLS- was usually superior. The ability of FLPeNLS+ to spread through myofibers and to induce reporter gene expression is thus not limited by its NLS. However, at high FLPe concentrations the presence of the NLS negatively affected reporter gene expression. In summary, a rapid and simple chemiluminescence assay for quantifying

  20. Physics models of centriole replication.

    PubMed

    Cheng, Kang; Zou, Changhua

    2006-01-01

    Our previous pre-clinic experimental results have showed that the epithelialization can be enhanced by the externally applied rectangular pulsed electrical current stimulation (RPECS). The results are clinically significant for patients, especially for those difficult patients whose skin wounds need long periods to heal. However, the results also raise questions: How does the RPECS accelerate the epithelium cell proliferation? To answer these questions, we have previously developed several models for animal cells, in a view of physics, to explain mechanisms of mitosis and cytokinesis at a cellular level, and separation of nucleotide sequences and the unwinding of a double helix during DNA replication at a bio-molecular level. In this paper, we further model the mechanism of centriole replication during a natural and normal mitosis and cytokinesis to explore the mechanism of epithelialization enhanced with the externally applied RPECS at a bio-molecular level. Our models suggest: (1) Centriole replication is an information flowing. The direction of the information flowing is from centrioles to centrioles based on a cylindrical template of 9 x 3 protein microtubules (MTs) pattern. (2) A spontaneous and strong electromagnetic field (EMF) force is a pushing force that separates a mother and a daughter centrioles in centrosomes or in cells, while a pulling force of interacting fibers and pericentriolar materials delivers new babies. The newly born babies inherit the pattern information from their mother(s) and grow using microtubule fragments that come through the centrosome pores. A daughter centriole is always born and grows along stronger EMF. The EMF mostly determines centrioles positions and plays key role in centriole replication. We also hypothesize that the normal centriole replication could not been disturbed in centrosome in the epithelium cells by our RPECS, because the centrioles have two non-conducting envelope (cell and centrosome membranes), that protect

  1. Sequences flanking the pentanucleotide T-antigen binding sites in the polyomavirus core origin help determine selectivity of DNA replication.

    PubMed Central

    Li, L; Li, B L; Hock, M; Wang, E; Folk, W R

    1995-01-01

    Replication of the genomes of the polyomaviruses requires two virus-specified elements, the cis-acting origin of DNA replication, with its auxiliary DNA elements, and the trans-acting viral large tumor antigen (T antigen). Appropriate interactions between them initiate the assembly of a replication complex which, together with cellular proteins, is responsible for primer synthesis and DNA chain elongation. The organization of cis-acting elements within the origins of the polyomaviruses which replicate in mammalian cells is conserved; however, these origins are sufficiently distinct that the T antigen of one virus may function inefficiently or not at all to initiate replication at the origin of another virus. We have studied the basis for such replication selectivity between the murine polyomavirus T antigen and the primate lymphotropic polyomavirus origin. The murine polyomavirus T antigen is capable of carrying out the early steps of the assembly of an initiation complex at the lymphotropic papovavirus origin, including binding to and deformation of origin sequences in vitro. However, the T antigen inefficiently unwinds the origin, and unwinding is influenced by sequences flanking the T antigen pentanucleotide binding sites on the late side of the viral core origin. These same sequences contribute to the replication selectivity observed in vivo and in vitro, suggesting that the inefficient unwinding is the cause of the replication defect. These observations suggest a mechanism by which origins of DNA replication can evolve replication selectivity and by which the function of diverse cellular origins might be temporally activated during the S phase of the eukaryotic cell cycle. PMID:7494263

  2. Experimental schistosomiasis in primates in Tanzania

    PubMed Central

    Jordan, P.; von Lichtenberg, F.; Goatly, K. D.

    1967-01-01

    Laboratory infection of animals with Schistosoma haematobium is generally unsatisfactory as adult worms invariably inhabit the portal venous system rather than the vesical plexus as in man. However, it was thought that certain primates might prove more valuable for experimental studies of schistosomiasis than the usual laboratory animals. Baboons, Papio anubis, were therefore exposed to cercariae of S. haematobium and the pattern of egg excretion in stools and urine was followed quantitatively. Histological studies of various organs were made and it was found that although eggs were excreted in the faeces, they were also passed in the urine and that tissue changes in the bladder were similar to those found in human infections. It is suggested that the sequelae of S. haematobium infection found in man might develop in baboons and that the animal may be useful for studying their development in the laboratory. ImagesFIG. 3FIG. 8FIG. 11FIG. 4FIG. 10FIG. 9FIG. 6FIG. 7FIG. 5 PMID:4968348

  3. Neurobiological mechanisms of puberty in higher primates.

    PubMed

    Plant, Tony M; Barker-Gibb, Mandi L

    2004-01-01

    Puberty in humans is comprised of two developmental processes; namely, gonadarche and adrenarche. Of the two, gonadarche is fundamentally the most important, and this review examines the neurobiological mechanisms that first prevent, and later trigger, progression into this critically important phase of human development when the ability to first reproduce is established. The review draws extensively upon results obtained by studies of the rhesus monkey (Macaca mulatta), a representative higher primate which, like man, exhibits a postnatal pattern in activity of the hypothalamic-pituitary-gonadal axis that is characterized by a prolonged period of relative quiescence from late infancy until the initiation of the pubertal process. The proximate cause of the prepubertal quiescence in this neuroendocrine axis is the arrest or restraint of the pulsatile mode of hypothalamic GnRH release by a neurobiological brake that holds in check release of this decapeptide, without seeming to down-regulate the transcriptional activity of the gene encoding GnRH (GnRH-I). Thus, if neurogenomes control the onset of gonadarche, they must reside upstream from that of the GnRH neuron. The genetic and physiological factors (with a particular emphasis on leptin) that time the application and duration of the prepubertal brake on GnRH release are also considered.

  4. Stereometrics In Primate Taxonomy And Phylogeny

    NASA Astrophysics Data System (ADS)

    Creel, Norman

    1980-07-01

    Studies of the systematic relationships within the primate taxa Homo, Hylobatidae (lesser apes), Hominoidea (apes and man) and Colobinae (Asian and African leaf monkeys) are described. All are based in large part on multivariate statistical analyses of cranial morphology. Adequate quantification of the frequently complex and subtle differences in the morphology of the animals being compared, as well as the inclusion of statistically adequate samples of as many presumed species or other groups of interest as possible, are essential to the success of such analyses. Two methods of stereometric measurement have been developed to make this possible. In initial studies of the Hylobatidae and the Hominoidea, a simple mechanical device was designed which determines the tri-dimensional coordinates of an anatomical point by measuring an angle and two distances. An improved version was used in an investigation of Subsaharan human crania. In a taxonomic revision of the Colobinae now in progress, crania are photographed in several views with a pair of metric cameras; point coordinates are then measured in a modified stereoplotter and the views rotated mathematically into a single coordinate system. Although stereometrics is only one component in a complex system of analysis, it is an extremely important one. Taxonomic revisions of the described scope and depth could not be carried out with conventional methods of measurement without a much greater commitment of resources, if at all.

  5. Context modulates signal meaning in primate communication

    PubMed Central

    Flack, Jessica C.; de Waal, Frans

    2007-01-01

    A central issue in the evolution of social complexity and the evolution of communication concerns the capacity to communicate about increasingly abstract objects and concepts. Many animals can communicate about immediate behavior, but to date, none have been reported to communicate about behavior during future interactions. In this study, we show that a special, unidirectional, cost-free dominance-related signal used by monkeys (pigtailed macaques: Macaca nemestrina) means submission (immediate behavior) or subordination (pattern of behavior) depending on the context of usage. We hypothesize that to decrease receiver uncertainty that the signal object is subordination, senders shift contextual usage from the conflict context, where the signal evolved, to a peaceful one, in which submission is unwarranted. We predict and find that deceasing receiver uncertainty through peaceful signal exchange facilitates the development of higher quality social relationships: Individuals exchanging the peaceful variant groom and reconcile more frequently and fight less frequently than individuals exchanging signals only in the conflict context or no signals. We rule out alternative hypotheses, including an underlying reciprocity rule, temperament, and proximity effects. Our results suggest that primates can communicate about behavioral patterns when these concern relationship rules. The invention of signals decreasing uncertainty about relationship state is likely to have been critical for the evolution of social complexity and to the emergence of robust power structures that feed down to influence rapidly changing individual behavior. PMID:17244712

  6. Evolutionary pressures on primate intertemporal choice.

    PubMed

    Stevens, Jeffrey R

    2014-07-01

    From finding food to choosing mates, animals must make intertemporal choices that involve fitness benefits available at different times. Species vary dramatically in their willingness to wait for delayed rewards. Why does this variation across species exist? An adaptive approach to intertemporal choice suggests that time preferences should reflect the temporal problems faced in a species's environment. Here, I use phylogenetic regression to test whether allometric factors relating to body size, relative brain size and social group size predict how long 13 primate species will wait in laboratory intertemporal choice tasks. Controlling for phylogeny, a composite allometric factor that includes body mass, absolute brain size, lifespan and home range size predicted waiting times, but relative brain size and social group size did not. These findings support the notion that selective pressures have sculpted intertemporal choices to solve adaptive problems faced by animals. Collecting these types of data across a large number of species can provide key insights into the evolution of decision making and cognition. PMID:24827445

  7. FTIR study of primate color visual pigments

    PubMed Central

    Katayama, Kota; Kandori, Hideki

    2015-01-01

    How do we distinguish colors? Humans possess three color pigments; red-, green-, and blue-sensitive proteins, which have maximum absorbance (λmax) at 560, 530, and 420 nm, respectively, and contribute to normal human trichromatic vision (RGB). Each color pigments consists of a different opsin protein bound to a common chromophore molecule, 11-cis-retinal, whereas different chromophore-protein interactions allow preferential absorption of different colors. However, detailed experimental structural data to explain the molecular basis of spectral tuning of color pigments are lacking, mainly because of the difficulty in sample preparation. We thus started structural studies of primate color visual pigments using low-temperature Fourier-transform infrared (FTIR) spectroscopy, which needs only 0.3 mg protein for a single measurement. Here we report the first structural data of monkey red- (MR) and green- (MG) sensitive pigments, in which the information about the protein, retinal chromophore, and internal water molecules is contained. Molecular mechanism of color discrimination between red and green pigments will be discussed based on the structural data by FTIR spectroscopy. PMID:27493516

  8. FTIR study of primate color visual pigments.

    PubMed

    Katayama, Kota; Kandori, Hideki

    2015-01-01

    How do we distinguish colors? Humans possess three color pigments; red-, green-, and blue-sensitive proteins, which have maximum absorbance (λmax) at 560, 530, and 420 nm, respectively, and contribute to normal human trichromatic vision (RGB). Each color pigments consists of a different opsin protein bound to a common chromophore molecule, 11-cis-retinal, whereas different chromophore-protein interactions allow preferential absorption of different colors. However, detailed experimental structural data to explain the molecular basis of spectral tuning of color pigments are lacking, mainly because of the difficulty in sample preparation. We thus started structural studies of primate color visual pigments using low-temperature Fourier-transform infrared (FTIR) spectroscopy, which needs only 0.3 mg protein for a single measurement. Here we report the first structural data of monkey red- (MR) and green- (MG) sensitive pigments, in which the information about the protein, retinal chromophore, and internal water molecules is contained. Molecular mechanism of color discrimination between red and green pigments will be discussed based on the structural data by FTIR spectroscopy.

  9. Use of a Novel Integrase-Deficient Lentivirus for Targeted Anti-Cancer Therapy With Survivin Promoter-Driven Diphtheria Toxin A

    PubMed Central

    Lin, Baoshun; Gao, Anding; Zhang, Rui; Ma, Hongyu; Shen, Haifeng; Hu, Qiong; Zhang, Hua; Zhao, Meng; Lan, Xiaopeng; Liu, Kuancan

    2015-01-01

    Abstract As an immunotoxin, diphtheria toxin has been widely used in gene therapy and gene function assays for its roles in protein synthesis inhibition, and the aim of our study is to set up a nonintegrating lentiviral system for specific expression of diphtheria toxin A (DTA) used in cancer gene therapy. Here, we established a lentiviral system that could coordinately express fluorescent protein and DTA driven by the cytomegalovirus (CMV) promoter, which is convenient for us to precisely trace the expression of DTA and monitor the process of lentivirus packaging. To achieve safer cancer therapy, we replaced the CMV promoter with the Survivin promoter, a specific promoter that is dramatically activated in cancer tissues and cells, but not in normal tissues and cells, and that will impose greater therapeutic potential because a significant expression difference occurred between these 2 groups. Meanwhile, we obtained integrase-deficient lentivirus (IDLV) after packaging with the integrase mutant, which expresses defective integrase RRK262263264AAH, to minimize the side effects that derived from the insertional mutagenesis of the host genome. Our results suggest that the IDLV system that we generated possesses therapeutic potential in cancers in vitro and in vivo. PMID:26252309

  10. TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts.

    PubMed

    Bernstein, Diana L; Le Lay, John E; Ruano, Elena G; Kaestner, Klaus H

    2015-05-01

    Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator-like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics.

  11. TALE-mediated epigenetic suppression of CDKN2A increases replication in human fibroblasts.

    PubMed

    Bernstein, Diana L; Le Lay, John E; Ruano, Elena G; Kaestner, Klaus H

    2015-05-01

    Current strategies to alter disease-associated epigenetic modifications target ubiquitously expressed epigenetic regulators. This approach does not allow specific genes to be controlled in specific cell types; therefore, tools to selectively target epigenetic modifications in the desired cell type and strategies to more efficiently correct aberrant gene expression in disease are needed. Here, we have developed a method for directing DNA methylation to specific gene loci by conjugating catalytic domains of DNA methyltransferases (DNMTs) to engineered transcription activator-like effectors (TALEs). We demonstrated that these TALE-DNMTs direct DNA methylation specifically to the targeted gene locus in human cells. Further, we determined that minimizing direct nucleotide sequence repeats within the TALE moiety permits efficient lentivirus transduction, allowing easy targeting of primary cell types. Finally, we demonstrated that directed DNA methylation with a TALE-DNMT targeting the CDKN2A locus, which encodes the cyclin-dependent kinase inhibitor p16, decreased CDKN2A expression and increased replication of primary human fibroblasts, as intended. Moreover, overexpression of p16 in these cells reversed the proliferative phenotype, demonstrating the specificity of our epigenetic targeting. Together, our results demonstrate that TALE-DNMTs can selectively target specific genes and suggest that this strategy has potential application for the development of locus-specific epigenetic therapeutics. PMID:25866970

  12. LOGISMOS-B for primates: primate cortical surface reconstruction and thickness measurement

    NASA Astrophysics Data System (ADS)

    Oguz, Ipek; Styner, Martin; Sanchez, Mar; Shi, Yundi; Sonka, Milan

    2015-03-01

    Cortical thickness and surface area are important morphological measures with implications for many psychiatric and neurological conditions. Automated segmentation and reconstruction of the cortical surface from 3D MRI scans is challenging due to the variable anatomy of the cortex and its highly complex geometry. While many methods exist for this task in the context of the human brain, these methods are typically not readily applicable to the primate brain. We propose an innovative approach based on our recently proposed human cortical reconstruction algorithm, LOGISMOS-B, and the Laplace-based thickness measurement method. Quantitative evaluation of our approach was performed based on a dataset of T1- and T2-weighted MRI scans from 12-month-old macaques where labeling by our anatomical experts was used as independent standard. In this dataset, LOGISMOS-B has an average signed surface error of 0.01 +/- 0.03mm and an unsigned surface error of 0.42 +/- 0.03mm over the whole brain. Excluding the rather problematic temporal pole region further improves unsigned surface distance to 0.34 +/- 0.03mm. This high level of accuracy reached by our algorithm even in this challenging developmental dataset illustrates its robustness and its potential for primate brain studies.

  13. Links between genome replication and chromatin landscapes.

    PubMed

    Sequeira-Mendes, Joana; Gutierrez, Crisanto

    2015-07-01

    Post-embryonic organogenesis in plants requires the continuous production of cells in the organ primordia, their expansion and a coordinated exit to differentiation. Genome replication is one of the most important processes that occur during the cell cycle, as the maintenance of genomic integrity is of primary relevance for development. As it is chromatin that must be duplicated, a strict coordination occurs between DNA replication, the deposition of new histones, and the introduction of histone modifications and variants. In turn, the chromatin landscape affects several stages during genome replication. Thus, chromatin accessibility is crucial for the initial stages and to specify the location of DNA replication origins with different chromatin signatures. The chromatin landscape also determines the timing of activation during the S phase. Genome replication must occur fully, but only once during each cell cycle. The re-replication avoidance mechanisms rely primarily on restricting the availability of certain replication factors; however, the presence of specific histone modifications are also revealed as contributing to the mechanisms that avoid re-replication, in particular for heterochromatin replication. We provide here an update of genome replication mostly focused on data from Arabidopsis, and the advances that genomic approaches are likely to provide in the coming years. The data available, both in plants and animals, point to the relevance of the chromatin landscape in genome replication, and require a critical evaluation of the existing views about the nature of replication origins, the mechanisms of origin specification and the relevance of epigenetic modifications for genome replication.

  14. Led by the nose: Olfaction in primate feeding ecology.

    PubMed

    Nevo, Omer; Heymann, Eckhard W

    2015-01-01

    Olfaction, the sense of smell, was a latecomer to the systematic investigation of primate sensory ecology after long years in which it was considered to be of minor importance. This view shifted with the growing understanding of its role in social behavior and the accumulation of physiological studies demonstrating that the olfactory abilities of some primates are on a par with those of olfactory-dependent mammals such as dogs and rodents. Recent years have seen a proliferation of physiological, behavioral, anatomical, and genetic investigations of primate olfaction. These investigations have begun to shed light on the importance of olfaction in the process of food acquisition. However, integration of these works has been limited. It is therefore still difficult to pinpoint large-scale evolutionary scenarios, namely the functions that the sense of smell fulfills in primates' feeding ecology and the ecological niches that favor heavier reliance on olfaction. Here, we review available behavioral and physiological studies of primates in the field or captivity and try to elucidate how and when the sense of smell can help them acquire food. PMID:26267435

  15. Primate Anatomy, Kinematics, and Principles for Humanoid Design

    NASA Technical Reports Server (NTRS)

    Ambrose, Robert O.; Ambrose, Catherine G.

    2004-01-01

    The primate order of animals is investigated for clues in the design of Humanoid Robots. The pursuit is directed with a theory that kinematics, musculature, perception, and cognition can be optimized for specific tasks by varying the proportions of limbs, and in particular, the points of branching in kinematic trees such as the primate skeleton. Called the Bifurcated Chain Hypothesis, the theory is that the branching proportions found in humans may be superior to other animals and primates for the tasks of dexterous manipulation and other human specialties. The primate taxa are defined, contemporary primate evolution hypotheses are critiqued, and variations within the order are noted. The kinematic branching points of the torso, limbs and fingers are studied for differences in proportions across the order, and associated with family and genus capabilities and behaviors. The human configuration of a long waist, long neck, and short arms is graded using a kinematic workspace analysis and a set of design axioms for mobile manipulation robots. It scores well. The re emergence of the human waist, seen in early Prosimians and Monkeys for arboreal balance, but lost in the terrestrial Pongidae, is postulated as benefiting human dexterity. The human combination of an articulated waist and neck will be shown to enable the use of smaller arms, achieving greater regions of workspace dexterity than the larger limbs of Gorillas and other Hominoidea.

  16. Male infanticide leads to social monogamy in primates.

    PubMed

    Opie, Christopher; Atkinson, Quentin D; Dunbar, Robin I M; Shultz, Susanne

    2013-08-13

    Although common in birds, social monogamy, or pair-living, is rare among mammals because internal gestation and lactation in mammals makes it advantageous for males to seek additional mating opportunities. A number of hypotheses have been proposed to explain the evolution of social monogamy among mammals: as a male mate-guarding strategy, because of the benefits of biparental care, or as a defense against infanticidal males. However, comparative analyses have been unable to resolve the root causes of monogamy. Primates are unusual among mammals because monogamy has evolved independently in all of the major clades. Here we combine trait data across 230 primate species with a Bayesian likelihood framework to test for correlated evolution between monogamy and a range of traits to evaluate the competing hypotheses. We find evidence of correlated evolution between social monogamy and both female ranging patterns and biparental care, but the most compelling explanation for the appearance of monogamy is male infanticide. It is only the presence of infanticide that reliably increases the probability of a shift to social monogamy, whereas monogamy allows the secondary adoption of paternal care and is associated with a shift to discrete ranges. The origin of social monogamy in primates is best explained by long lactation periods caused by altriciality, making primate infants particularly vulnerable to infanticidal males. We show that biparental care shortens relative lactation length, thereby reducing infanticide risk and increasing reproductive rates. These phylogenetic analyses support a key role for infanticide in the social evolution of primates, and potentially, humans.

  17. Female reproductive synchrony predicts skewed paternity across primates

    PubMed Central

    Nunn, Charles L.; Schülke, Oliver

    2008-01-01

    Recent studies have uncovered remarkable variation in paternity within primate groups. To date, however, we lack a general understanding of the factors that drive variation in paternity skew among primate groups and across species. Our study focused on hypotheses from reproductive skew theory involving limited control and the use of paternity “concessions” by investigating how paternity covaries with the number of males, female estrous synchrony, and rates of extragroup paternity. In multivariate and phylogenetically controlled analyses of data from 27 studies on 19 species, we found strong support for a limited control skew model, with reproductive skew within groups declining as female reproductive synchrony and the number of males per group increase. Of these 2 variables, female reproductive synchrony explained more of the variation in paternity distributions. To test whether dominant males provide incentives to subordinates to resist matings by extragroup males, that is, whether dominants make concessions of paternity, we derived a novel prediction that skew is lower within groups when threat from outside the group exists. This prediction was not supported as a primary factor underlying patterns of reproductive skew among primate species. However, our approach revealed that if concessions occur in primates, they are most likely when female synchrony is low, as these conditions provide alpha male control of paternity that is assumed by concessions models. Collectively, our analyses demonstrate that aspects of male reproductive competition are the primary drivers of reproductive skew in primates. PMID:19018288

  18. Reproductive aging patterns in primates reveal that humans are distinct

    PubMed Central

    Alberts, Susan C.; Altmann, Jeanne; Brockman, Diane K.; Cords, Marina; Fedigan, Linda M.; Pusey, Anne; Stoinski, Tara S.; Strier, Karen B.; Morris, William F.; Bronikowski, Anne M.

    2013-01-01

    Women rarely give birth after ∼45 y of age, and they experience the cessation of reproductive cycles, menopause, at ∼50 y of age after a fertility decline lasting almost two decades. Such reproductive senescence in mid-lifespan is an evolutionary puzzle of enduring interest because it should be inherently disadvantageous. Furthermore, comparative data on reproductive senescence from other primates, or indeed other mammals, remains relatively rare. Here we carried out a unique detailed comparative study of reproductive senescence in seven species of nonhuman primates in natural populations, using long-term, individual-based data, and compared them to a population of humans experiencing natural fertility and mortality. In four of seven primate species we found that reproductive senescence occurred before death only in a small minority of individuals. In three primate species we found evidence of reproductive senescence that accelerated throughout adulthood; however, its initial rate was much lower than mortality, so that relatively few individuals experienced reproductive senescence before death. In contrast, the human population showed the predicted and well-known pattern in which reproductive senescence occurred before death for many women and its rate accelerated throughout adulthood. These results provide strong support for the hypothesis that reproductive senescence in midlife, although apparent in natural-fertility, natural-mortality populations of humans, is generally absent in other primates living in such populations. PMID:23898189

  19. Male infanticide leads to social monogamy in primates

    PubMed Central

    Opie, Christopher; Atkinson, Quentin D.; Dunbar, Robin I. M.; Shultz, Susanne

    2013-01-01

    Although common in birds, social monogamy, or pair-living, is rare among mammals because internal gestation and lactation in mammals makes it advantageous for males to seek additional mating opportunities. A number of hypotheses have been proposed to explain the evolution of social monogamy among mammals: as a male mate-guarding strategy, because of the benefits of biparental care, or as a defense against infanticidal males. However, comparative analyses have been unable to resolve the root causes of monogamy. Primates are unusual among mammals because monogamy has evolved independently in all of the major clades. Here we combine trait data across 230 primate species with a Bayesian likelihood framework to test for correlated evolution between monogamy and a range of traits to evaluate the competing hypotheses. We find evidence of correlated evolution between social monogamy and both female ranging patterns and biparental care, but the most compelling explanation for the appearance of monogamy is male infanticide. It is only the presence of infanticide that reliably increases the probability of a shift to social monogamy, whereas monogamy allows the secondary adoption of paternal care and is associated with a shift to discrete ranges. The origin of social monogamy in primates is best explained by long lactation periods caused by altriciality, making primate infants particularly vulnerable to infanticidal males. We show that biparental care shortens relative lactation length, thereby reducing infanticide risk and increasing reproductive rates. These phylogenetic analyses support a key role for infanticide in the social evolution of primates, and potentially, humans. PMID:23898180

  20. Grooming reciprocation among female primates: a meta-analysis.

    PubMed

    Schino, Gabriele; Aureli, Filippo

    2008-02-23

    The theory of reciprocal altruism offers an explanation for the evolution of altruistic behaviours among unrelated animals. Among primates, grooming is one of the most common altruistic behaviours. Primates have been suggested to exchange grooming both for itself and for rank-related benefits. While previous meta-analyses have shown that they direct their grooming up the hierarchy and exchange it for agonistic support, no comprehensive evaluation of grooming reciprocation has been made. Here we report on a meta-analysis of grooming reciprocation among female primates based on 48 social groups belonging to 22 different species and 12 genera. The results of this meta-analysis showed that female primates groom preferentially those group mates that groom them most. To the extent allowed by the availability of kinship data, this result holds true when controlling for maternal kinship. These results, together with previous findings, suggest that primates are indeed able to exchange grooming both for itself and for different rank-related benefits.

  1. Led by the nose: Olfaction in primate feeding ecology.

    PubMed

    Nevo, Omer; Heymann, Eckhard W

    2015-01-01

    Olfaction, the sense of smell, was a latecomer to the systematic investigation of primate sensory ecology after long years in which it was considered to be of minor importance. This view shifted with the growing understanding of its role in social behavior and the accumulation of physiological studies demonstrating that the olfactory abilities of some primates are on a par with those of olfactory-dependent mammals such as dogs and rodents. Recent years have seen a proliferation of physiological, behavioral, anatomical, and genetic investigations of primate olfaction. These investigations have begun to shed light on the importance of olfaction in the process of food acquisition. However, integration of these works has been limited. It is therefore still difficult to pinpoint large-scale evolutionary scenarios, namely the functions that the sense of smell fulfills in primates' feeding ecology and the ecological niches that favor heavier reliance on olfaction. Here, we review available behavioral and physiological studies of primates in the field or captivity and try to elucidate how and when the sense of smell can help them acquire food.

  2. Microgravity Flight - Accommodating Non-Human Primates

    NASA Technical Reports Server (NTRS)

    Dalton, Bonnie P.; Searby, Nancy; Ostrach, Louis

    1994-01-01

    Spacelab Life Sciences-3 (SLS-3) was scheduled to be the first United States man-tended microgravity flight containing Rhesus monkeys. The goal of this flight as in the five untended Russian COSMOS Bion flights and an earlier American Biosatellite flight, was to understand the biomedical and biological effects of a microgravity environment using the non-human primate as human surrogate. The SLS-3/Rhesus Project and COSMOS Primate-BIOS flights all utilized the rhesus monkey Macaca mulatta. The ultimate objective of all flights with an animal surrogate has been to evaluate and understand biological mechanisms at both the system and cellular level, thus enabling rational effective countermeasures for future long duration human activity under microgravity conditions and enabling technical application to correction of common human physiological problems within earth's gravity, e.g., muscle strength and reloading, osteoporosis, immune deficiency diseases. Hardware developed for the SLS-3/Rhesus Project was the result of a joint effort with the French Centre National d'Etudes Spatiales (CNES) and the United States National Aeronautics and Space Administration (NASA) extending over the last decade. The flight hardware design and development required implementation of sufficient automation to insure flight crew and animal bio-isolation and maintenance with minimal impact to crew activities. A variety of hardware of varying functional capabilities was developed to support the scientific objectives of the original 22 combined French and American experiments, along with 5 Russian co-investigations, including musculoskeletal, metabolic, and behavioral studies. Unique elements of the Rhesus Research Facility (RRF) included separation of waste for daily delivery of urine and fecal samples for metabolic studies and a psychomotor test system for behavioral studies along with monitored food measurement. As in untended flights, telemetry measurements would allow monitoring of

  3. Microgravity Flight: Accommodating Non-Human Primates

    NASA Technical Reports Server (NTRS)

    Dalton, Bonnie P.; Searby, Nancy; Ostrach, Louis

    1995-01-01

    Spacelab Life Sciences-3 (SLS-3) was scheduled to be the first United States man-tended microgravity flight containing Rhesus monkeys. The goal of this flight as in the five untended Russian COSMOS Bion flights and an earlier American Biosatellite flight, was to understand the biomedical and biological effects of a microgravity environment using the non-human primate as human surrogate. The SLS-3/Rhesus Project and COSMOS Primate-BIOS flights all utilized the rhesus monkey, Macaca mulatta. The ultimate objective of all flights with an animal surrogate has been to evaluate and understand biological mechanisms at both the system and cellular level, thus enabling rational effective countermeasures for future long duration human activity under microgravity conditions and enabling technical application to correction of common human physiological problems within earth's gravity, e.g., muscle strength and reloading, osteoporosis, immune deficiency diseases. Hardware developed for the SLS-3/Rhesus Project was the result of a joint effort with the French Centre National d'Etudes Spatiales (CNES) and the United States National Aeronautics and Space Administration (NASA) extending over the last decade. The flight hardware design and development required implementation of sufficient automation to insure flight crew and animal bio-isolation and maintenance with minimal impact to crew activities. A variety of hardware of varying functional capabilities was developed to support the scientific objectives of the original 22 combined French and American experiments, along with 5 Russian co-investigations, including musculoskeletal, metabolic, and behavioral studies. Unique elements of the Rhesus Research Facility (RRF) included separation of waste for daily delivery of urine and fecal samples for metabolic studies and a psychomotor test system for behavioral studies along with monitored food measurement. As in untended flights, telemetry measurements would allow monitoring of

  4. Evolution of coding microsatellites in primate genomes.

    PubMed

    Loire, Etienne; Higuet, Dominique; Netter, Pierre; Achaz, Guillaume

    2013-01-01

    Microsatellites (SSRs) are highly susceptible to expansions and contractions. When located in a coding sequence, the insertion or the deletion of a single unit for a mono-, di-, tetra-, or penta(nucleotide)-SSR creates a frameshift. As a consequence, one would expect to find only very few of these SSRs in coding sequences because of their strong deleterious potential. Unexpectedly, genomes contain many coding SSRs of all types. Here, we report on a study of their evolution in a phylogenetic context using the genomes of four primates: human, chimpanzee, orangutan, and macaque. In a set of 5,015 orthologous genes unambiguously aligned among the four species, we show that, except for tri- and hexa-SSRs, for which insertions and deletions are frequently observed, SSRs in coding regions evolve mainly by substitutions. We show that the rate of substitution in all types of coding SSRs is typically two times higher than in the rest of coding sequences. Additionally, we observe that although numerous coding SSRs are created and lost by substitutions in the lineages, their numbers remain constant. This last observation suggests that the coding SSRs have reached equilibrium. We hypothesize that this equilibrium involves a combination of mutation, drift, and selection. We thus estimated the fitness cost of mono-SSRs and show that it increases with the number of units. We finally show that the cost of coding mono-SSRs greatly varies from function to function, suggesting that the strength of the selection that acts against them can be correlated to gene functions.

  5. Replication Fork Velocities at Adjacent Replication Origins Are Coordinately Modified during DNA Replication in Human Cells

    PubMed Central

    Conti, Chiara; Saccà, Barbara; Herrick, John; Lalou, Claude; Pommier, Yves

    2007-01-01

    The spatial organization of replicons into clusters is believed to be of critical importance for genome duplication in higher eukaryotes, but its functional organization still remains to be fully clarified. The coordinated activation of origins is insufficient on its own to account for a timely completion of genome duplication when interorigin distances vary significantly and fork velocities are constant. Mechanisms coordinating origin distribution with fork progression are still poorly elucidated, because of technical difficulties of visualizing the process. Taking advantage of a single molecule approach, we delineated and compared the DNA replication kinetics at the genome level in human normal primary and malignant cells. Our results show that replication forks moving from one origin, as well as from neighboring origins, tend to exhibit the same velocity, although the plasticity of the replication program allows for their adaptation to variable interorigin distances. We also found that forks that emanated from closely spaced origins tended to move slower than those associated with long replicons. Taken together, our results indicate a functional role for origin clustering in the dynamic regulation of genome duplication. PMID:17522385

  6. Tarsier-like locomotor specializations in the Oligocene primate Afrotarsius

    PubMed Central

    Rasmussen, D. Tab; Conroy, Glenn C.; Simons, Elwyn L.

    1998-01-01

    Tarsiers and extinct tarsier-like primates have played a central role in views of primate phylogeny and evolution for more than a century. Because of the importance of tarsiers in so many primatological problems, there has been particular interest in questions about the origin of tarsier specializations and the biogeography of early tarsioid radiations. We report on a new fossil of rare Afrotarsius that shows near identity to modern Tarsius in unique specializations of the leg, which provides information about the locomotor behavior and clarifies the phylogenetic position of this previously controversial primate. These specializations constitute evidence that Afrotarsius is a tarsiid, closely related to extant Tarsius; hence, it is now excluded from being a generalized sister taxon to Anthropoidea. PMID:9843978

  7. Convergence of complex cognitive abilities in cetaceans and primates.

    PubMed

    Marino, Lori

    2002-01-01

    What examples of convergence in higher-level complex cognitive characteristics exist in the animal kingdom? In this paper I will provide evidence that convergent intelligence has occurred in two distantly related mammalian taxa. One of these is the order Cetacea (dolphins, whales and porpoises) and the other is our own order Primates, and in particular the suborder anthropoid primates (monkeys, apes, and humans). Despite a deep evolutionary divergence, adaptation to physically dissimilar environments, and very different neuroanatomical organization, some primates and cetaceans show striking convergence in social behavior, artificial 'language' comprehension, and self-recognition ability. Taken together, these findings have important implications for understanding the generality and specificity of those processes that underlie cognition in different species and the nature of the evolution of intelligence.

  8. Primate evolution of the recombination regulator PRDM9.

    PubMed

    Schwartz, Jerrod J; Roach, David J; Thomas, James H; Shendure, Jay

    2014-07-08

    The PRDM9 gene encodes a protein with a highly variable tandem-repeat zinc finger (ZF) DNA-binding domain that plays a key role in determining sequence-specific hotspots of meiotic recombination genome wide. Here we survey the diversity of the PRDM9 ZF domain by sequencing this region in 64 primates from 18 species, revealing 68 unique alleles across all groups. We report ubiquitous positive selection at nucleotide positions corresponding to DNA contact residues and the expansion of ZFs within clades, which confirms the rapid evolution of the ZF domain throughout the primate lineage. Alignment of Neandertal and Denisovan sequences suggests that PRDM9 in archaic hominins was closely related to present-day human alleles that are rare and specific to African populations. In the context of its role in reproduction, our results are consistent with variation in PRDM9 contributing to speciation events in primates.

  9. Primate-specific evolution of an LDLR enhancer

    SciTech Connect

    Wang, Qian-Fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles; Eisen, Michael B.; Cheng, Jan-Fang; Rubin,Edward M.; Boffelli, Dario

    2005-12-01

    Sequence changes in regulatory regions have often been invoked to explain phenotypic divergence among species, but molecular examples of this have been difficult to obtain. In this study we identified an anthropoid primate-specific sequence element that contributed to the regulatory evolution of the low-density lipoprotein receptor. Using a combination of close and distant species genomic sequence comparisons coupled with in vivo and in vitro studies, we found that a functional cholesterol-sensing sequence motif arose and was fixed within a pre-existing enhancer in the common ancestor of anthropoid primates. Our study demonstrates one molecular mechanism by which ancestral mammalian regulatory elements can evolve to perform new functions in the primate lineage leading to human.

  10. DNA replication: enzymology and mechanisms.

    PubMed

    Kelman, Z; O'Donnell, M

    1994-04-01

    Research into the enzymology of DNA replication has seen a multitude of highly significant advances during the past year, in both prokaryotic and eukaryotic systems. The scope of this article is limited to chromosomal replicases and origins of initiation. The multiprotein chromosomal replicases of prokaryotes and eukaryotes appear to be strikingly similar in structure and function, although future work may reveal their differences. Recent developments, elaborating the activation of origins in several systems, have begun to uncover mechanisms of regulation. The enzymology of eukaryotic origins has, until now, been limited to viral systems, but over the past few years, enzymology has caught a grip on the cellular origins of yeast.

  11. Regulated expression of lentivirus-mediated GDNF in human bone marrow-derived mesenchymal stem cells and its neuroprotection on dopaminergic cells in vitro.

    PubMed

    Yang, Wei-Hua; Yang, Chun; Xue, Yue-Qiang; Lu, Tao; Reiser, Jakob; Zhao, Li-Ru; Duan, Wei-Ming

    2013-01-01

    Gene regulation remains one of the major challenges for gene therapy in clinical trials. In the present study, we first generated a binary tetracycline-on (Tet-On) system based on two lentivirus vectors, one expressing both human glial cell line-derived neurotrophic factor (hGDNF) and humanized recombinant green fluorescent protein (hrGFP) genes under second-generation tetracycline response element (TRE), and the other expressing the advanced reverse tetracycline-controlled transactivator--rtTA2S-M2 under a human minimal cytomegalovirus immediate early (CMV-IE) promoter. This system allows simultaneous expression of hGDNF and hrGFP genes in the presence of doxycycline (Dox). Human bone marrow-derived mesenchymal stem cells (hMSCs) were transduced with the binary Tet-On lentivirus vectors and characterized in vitro in the presence (On) or absence (Off) of Dox. The expression of hGDNF and hrGFP transgenes in transduced hMSCs was tightly regulated as determined by flow cytometry (FCM), GDNF enzyme-linked immunosorbent assay (ELISA) and quantitative real time-polymerase chain reaction (qRT-PCR). There was a dose-dependent regulation for hrGFP transgene expression. The levels of hGDNF protein in culture medium were correlated with the mean fluorescence intensity (MFI) units of hrGFP. The levels of transgene background expression were very low in the absence of Dox. The treatment of the conditioned medium from cultures of transduced hMSCs in the presence of Dox protected SH-SY5Y cells against 6-hydroxydopamine (6-OHDA) toxicity as determined by cell viability using 3, [4,5-dimethylthiazol-2-yl]-diphenyltetrazolium bromide (MTT) assay. The treatment of the conditioned medium was also found to improve the survival of dopaminergic (DA) neurons of ventral mesencephalic (VM) tissue in serum-free culture conditions as assessed by cell body area, the number of neurites and dendrite branching points, and proportion of tyrosine hydroxylase (TH)-immunoreactive (IR) cells. Our

  12. Euarchontan Opsin Variation Brings New Focus to Primate Origins.

    PubMed

    Melin, Amanda D; Wells, Konstans; Moritz, Gillian L; Kistler, Logan; Orkin, Joseph D; Timm, Robert M; Bernard, Henry; Lakim, Maklarin B; Perry, George H; Kawamura, Shoji; Dominy, Nathaniel J

    2016-04-01

    Debate on the adaptive origins of primates has long focused on the functional ecology of the primate visual system. For example, it is hypothesized that variable expression of short- (SWS1) and middle-to-long-wavelength sensitive (M/LWS) opsins, which confer color vision, can be used to infer ancestral activity patterns and therefore selective ecological pressures. A problem with this approach is that opsin gene variation is incompletely known in the grandorder Euarchonta, that is, the orders Scandentia (treeshrews), Dermoptera (colugos), and Primates. The ancestral state of primate color vision is therefore uncertain. Here, we report on the genes (OPN1SW and OPN1LW) that encode SWS1 and M/LWS opsins in seven species of treeshrew, including the sole nocturnal scandentian Ptilocercus lowii. In addition, we examined the opsin genes of the Central American woolly opossum (Caluromys derbianus), an enduring ecological analogue in the debate on primate origins. Our results indicate: 1) retention of ultraviolet (UV) visual sensitivity in C. derbianus and a shift from UV to blue spectral sensitivities at the base of Euarchonta; 2) ancient pseudogenization of OPN1SW in the ancestors of P. lowii, but a signature of purifying selection in those of C. derbianus; and, 3) the absence of OPN1LW polymorphism among diurnal treeshrews. These findings suggest functional variation in the color vision of nocturnal mammals and a distinctive visual ecology of early primates, perhaps one that demanded greater spatial resolution under light levels that could support cone-mediated color discrimination. PMID:26739880

  13. Primate dietary ecology in the context of food mechanical properties.

    PubMed

    Coiner-Collier, Susan; Scott, Robert S; Chalk-Wilayto, Janine; Cheyne, Susan M; Constantino, Paul; Dominy, Nathaniel J; Elgart, Alison A; Glowacka, Halszka; Loyola, Laura C; Ossi-Lupo, Kerry; Raguet-Schofield, Melissa; Talebi, Mauricio G; Sala, Enrico A; Sieradzy, Pawel; Taylor, Andrea B; Vinyard, Christopher J; Wright, Barth W; Yamashita, Nayuta; Lucas, Peter W; Vogel, Erin R

    2016-09-01

    Substantial variation exists in the mechanical properties of foods consumed by primate species. This variation is known to influence food selection and ingestion among non-human primates, yet no large-scale comparative study has examined the relationships between food mechanical properties and feeding strategies. Here, we present comparative data on the Young's modulus and fracture toughness of natural foods in the diets of 31 primate species. We use these data to examine the relationships between food mechanical properties and dietary quality, body mass, and feeding time. We also examine the relationship between food mechanical properties and categorical concepts of diet that are often used to infer food mechanical properties. We found that traditional dietary categories, such as folivory and frugivory, did not faithfully track food mechanical properties. Additionally, our estimate of dietary quality was not significantly correlated with either toughness or Young's modulus. We found a complex relationship among food mechanical properties, body mass, and feeding time, with a potential interaction between median toughness and body mass. The relationship between mean toughness and feeding time is straightforward: feeding time increases as toughness increases. However, when considering median toughness, the relationship with feeding time may depend upon body mass, such that smaller primates increase their feeding time in response to an increase in median dietary toughness, whereas larger primates may feed for shorter periods of time as toughness increases. Our results emphasize the need for additional studies quantifying the mechanical and chemical properties of primate diets so that they may be meaningfully compared to research on feeding behavior and jaw morphology.

  14. Primate dental ecology: How teeth respond to the environment.

    PubMed

    Cuozzo, Frank P; Ungar, Peter S; Sauther, Michelle L

    2012-06-01

    Teeth are central for the study of ecology, as teeth are at the direct interface between an organism and its environment. Recent years have witnessed a rapid growth in the use of teeth to understand a broad range of topics in living and fossil primate biology. This in part reflects new techniques for assessing ways in which teeth respond to, and interact with, an organism's environment. Long-term studies of wild primate populations that integrate dental analyses have also provided a new context for understanding primate interactions with their environments. These new techniques and long-term field studies have allowed the development of a new perspective-dental ecology. We define dental ecology as the broad study of how teeth respond to, or interact with, the environment. This includes identifying patterns of dental pathology and tooth use-wear, as they reflect feeding ecology, behavior, and habitat variation, including areas impacted by anthropogenic disturbance, and how dental development can reflect environmental change and/or stress. The dental ecology approach, built on collaboration between dental experts and ecologists, holds the potential to provide an important theoretical and practical framework for inferring ecology and behavior of fossil forms, for assessing environmental change in living populations, and for understanding ways in which habitat impacts primate growth and development. This symposium issue brings together experts on dental morphology, growth and development, tooth wear and health, primate ecology, and paleontology, to explore the broad application of dental ecology to questions of how living and fossil primates interact with their environments.

  15. Euarchontan Opsin Variation Brings New Focus to Primate Origins

    PubMed Central

    Melin, Amanda D.; Wells, Konstans; Moritz, Gillian L.; Kistler, Logan; Orkin, Joseph D.; Timm, Robert M.; Bernard, Henry; Lakim, Maklarin B.; Perry, George H.; Kawamura, Shoji; Dominy, Nathaniel J.

    2016-01-01

    Debate on the adaptive origins of primates has long focused on the functional ecology of the primate visual system. For example, it is hypothesized that variable expression of short- (SWS1) and middle-to-long-wavelength sensitive (M/LWS) opsins, which confer color vision, can be used to infer ancestral activity patterns and therefore selective ecological pressures. A problem with this approach is that opsin gene variation is incompletely known in the grandorder Euarchonta, that is, the orders Scandentia (treeshrews), Dermoptera (colugos), and Primates. The ancestral state of primate color vision is therefore uncertain. Here, we report on the genes (OPN1SW and OPN1LW) that encode SWS1 and M/LWS opsins in seven species of treeshrew, including the sole nocturnal scandentian Ptilocercus lowii. In addition, we examined the opsin genes of the Central American woolly opossum (Caluromys derbianus), an enduring ecological analogue in the debate on primate origins. Our results indicate: 1) retention of ultraviolet (UV) visual sensitivity in C. derbianus and a shift from UV to blue spectral sensitivities at the base of Euarchonta; 2) ancient pseudogenization of OPN1SW in the ancestors of P. lowii, but a signature of purifying selection in those of C. derbianus; and, 3) the absence of OPN1LW polymorphism among diurnal treeshrews. These findings suggest functional variation in the color vision of nocturnal mammals and a distinctive visual ecology of early primates, perhaps one that demanded greater spatial resolution under light levels that could support cone-mediated color discrimination. PMID:26739880

  16. Primate dental ecology: How teeth respond to the environment.

    PubMed

    Cuozzo, Frank P; Ungar, Peter S; Sauther, Michelle L

    2012-06-01

    Teeth are central for the study of ecology, as teeth are at the direct interface between an organism and its environment. Recent years have witnessed a rapid growth in the use of teeth to understand a broad range of topics in living and fossil primate biology. This in part reflects new techniques for assessing ways in which teeth respond to, and interact with, an organism's environment. Long-term studies of wild primate populations that integrate dental analyses have also provided a new context for understanding primate interactions with their environments. These new techniques and long-term field studies have allowed the development of a new perspective-dental ecology. We define dental ecology as the broad study of how teeth respond to, or interact with, the environment. This includes identifying patterns of dental pathology and tooth use-wear, as they reflect feeding ecology, behavior, and habitat variation, including areas impacted by anthropogenic disturbance, and how dental development can reflect environmental change and/or stress. The dental ecology approach, built on collaboration between dental experts and ecologists, holds the potential to provide an important theoretical and practical framework for inferring ecology and behavior of fossil forms, for assessing environmental change in living populations, and for understanding ways in which habitat impacts primate growth and development. This symposium issue brings together experts on dental morphology, growth and development, tooth wear and health, primate ecology, and paleontology, to explore the broad application of dental ecology to questions of how living and fossil primates interact with their environments. PMID:22610891

  17. Primate dietary ecology in the context of food mechanical properties.

    PubMed

    Coiner-Collier, Susan; Scott, Robert S; Chalk-Wilayto, Janine; Cheyne, Susan M; Constantino, Paul; Dominy, Nathaniel J; Elgart, Alison A; Glowacka, Halszka; Loyola, Laura C; Ossi-Lupo, Kerry; Raguet-Schofield, Melissa; Talebi, Mauricio G; Sala, Enrico A; Sieradzy, Pawel; Taylor, Andrea B; Vinyard, Christopher J; Wright, Barth W; Yamashita, Nayuta; Lucas, Peter W; Vogel, Erin R

    2016-09-01

    Substantial variation exists in the mechanical properties of foods consumed by primate species. This variation is known to influence food selection and ingestion among non-human primates, yet no large-scale comparative study has examined the relationships between food mechanical properties and feeding strategies. Here, we present comparative data on the Young's modulus and fracture toughness of natural foods in the diets of 31 primate species. We use these data to examine the relationships between food mechanical properties and dietary quality, body mass, and feeding time. We also examine the relationship between food mechanical properties and categorical concepts of diet that are often used to infer food mechanical properties. We found that traditional dietary categories, such as folivory and frugivory, did not faithfully track food mechanical properties. Additionally, our estimate of dietary quality was not significantly correlated with either toughness or Young's modulus. We found a complex relationship among food mechanical properties, body mass, and feeding time, with a potential interaction between median toughness and body mass. The relationship between mean toughness and feeding time is straightforward: feeding time increases as toughness increases. However, when considering median toughness, the relationship with feeding time may depend upon body mass, such that smaller primates increase their feeding time in response to an increase in median dietary toughness, whereas larger primates may feed for shorter periods of time as toughness increases. Our results emphasize the need for additional studies quantifying the mechanical and chemical properties of primate diets so that they may be meaningfully compared to research on feeding behavior and jaw morphology. PMID:27542555

  18. Comparative RNA sequencing reveals substantial genetic variation in endangered primates

    PubMed Central

    Perry, George H.; Melsted, Páll; Marioni, John C.; Wang, Ying; Bainer, Russell; Pickrell, Joseph K.; Michelini, Katelyn; Zehr, Sarah; Yoder, Anne D.; Stephens, Matthew; Pritchard, Jonathan K.; Gilad, Yoav

    2012-01-01

    Comparative genomic studies in primates have yielded important insights into the evolutionary forces that shape genetic diversity and revealed the likely genetic basis for certain species-specific adaptations. To date, however, these studies have focused on only a small number of species. For the majority of nonhuman primates, including some of the most critically endangered, genome-level data are not yet available. In this study, we have taken the first steps toward addressing this gap by sequencing RNA from the livers of multiple individuals from each of 16 mammalian species, including humans and 11 nonhuman primates. Of the nonhuman primate species, five are lemurs and two are lorisoids, for which little or no genomic data were previously available. To analyze these data, we developed a method for de novo assembly and alignment of orthologous gene sequences across species. We assembled an average of 5721 gene sequences per species and characterized diversity and divergence of both gene sequences and gene expression levels. We identified patterns of variation that are consistent with the action of positive or directional selection, including an 18-fold enrichment of peroxisomal genes among genes whose regulation likely evolved under directional selection in the ancestral primate lineage. Importantly, we found no relationship between genetic diversity and endangered status, with the two most endangered species in our study, the black and white ruffed lemur and the Coquerel's sifaka, having the highest genetic diversity among all primates. Our observations imply that many endangered lemur populations still harbor considerable genetic variation. Timely efforts to conserve these species alongside their habitats have, therefore, strong potential to achieve long-term success. PMID:22207615

  19. Assessing flavivirus, lentivirus, and herpesvirus exposure in free-ranging ring-tailed lemurs in southwestern Madagascar.

    PubMed

    Sondgeroth, Kerry; Blitvich, Brad; Blair, Carol; Terwee, Julie; Junge, Randall; Sauther, Michelle; VandeWoude, Sue

    2007-01-01

    The ring-tailed lemur (Lemur catta) is an endangered species found in southwestern Madagascar, and understanding infectious disease susceptibility is an essential step towards the preservation of wild and captive lemur populations. Lemurs are primates that are widely dispersed throughout the island of Madagascar and may serve as hosts or reservoirs for zoonotic infections. The aim of this study was to determine the prevalence of antibodies to West Nile virus (WNV), simian immunodeficiency virus (SIV), and herpes simplex virus type 1 (HSV-1) in a population of free-ranging ring-tailed lemur from the Beza Mahafaly Special Reserve, Madagascar. Samples were collected from 50 animals during field capture studies in June and July 2004 and assayed for presence of viral antibodies during the 12 mo following collection. Forty-seven of the 50 lemurs sampled had antibodies against WNV detectable by epitope-blocking enzyme-linked immunosorbent assay (ELISA). In addition, 50 of 50 samples had titers against WNV ranging from 80 to > or = 1,280 using plaque reduction neutralization test (PRNT(90)). Ten lemurs had antibodies against lentiviral antigens as determined by Western blot analysis. None of the lemurs had antibodies against HSV-1 using ELISA. PMID:17347392

  20. Semi-automated closed system manufacturing of lentivirus gene-modified haematopoietic stem cells for gene therapy

    PubMed Central

    Adair, Jennifer E.; Waters, Timothy; Haworth, Kevin G.; Kubek, Sara P.; Trobridge, Grant D.; Hocum, Jonah D.; Heimfeld, Shelly; Kiem, Hans-Peter

    2016-01-01

    Haematopoietic stem cell (HSC) gene therapy has demonstrated potential to treat many diseases. However, current state of the art requires sophisticated ex vivo gene transfer in a dedicated Good Manufacturing Practices facility, limiting availability. An automated process would improve the availability and standardized manufacture of HSC gene therapy. Here, we develop a novel program for semi-automated cell isolation and culture equipment to permit complete benchtop generation of gene-modified CD34+ blood cell products for transplantation. These cell products meet current manufacturing quality standards for both mobilized leukapheresis and bone marrow, and reconstitute human haematopoiesis in immunocompromised mice. Importantly, nonhuman primate autologous gene-modified CD34+ cell products are capable of stable, polyclonal multilineage reconstitution with follow-up of more than 1 year. These data demonstrate proof of concept for point-of-care delivery of HSC gene therapy. Given the many target diseases for gene therapy, there is enormous potential for this approach to treat patients on a global scale. PMID:27762266

  1. Thermal, Autonomous Replicator Made from Transfer RNA

    NASA Astrophysics Data System (ADS)

    Krammer, Hubert; Möller, Friederike M.; Braun, Dieter

    2012-06-01

    Evolving systems rely on the storage and replication of genetic information. Here we present an autonomous, purely thermally driven replication mechanism. A pool of hairpin molecules, derived from transfer RNA replicates the succession of a two-letter code. Energy is first stored thermally in metastable hairpins. Thereafter, energy is released by a highly specific and exponential replication with a duplication time of 30 s, which is much faster than the tendency to produce false positives in the absence of template. Our experiments propose a physical rather than a chemical scenario for the autonomous replication of protein encoding information in a disequilibrium setting.

  2. Replication of prions in differentiated muscle cells.

    PubMed

    Herbst, Allen; Aiken, Judd M; McKenzie, Debbie

    2014-01-01

    We have demonstrated that prions accumulate to high levels in non-proliferative C2C12 myotubes. C2C12 cells replicate as myoblasts but can be differentiated into myotubes. Earlier studies indicated that C2C12 myoblasts are not competent for prion replication. (1) We confirmed that observation and demonstrated, for the first time, that while replicative myoblasts do not accumulate PrP(Sc), differentiated post-mitotic myotube cultures replicate prions robustly. Here we extend our observations and describe the implication and utility of this system for replicating prions.

  3. Strategic Use of Random Subsample Replication and a Coefficient of Factor Replicability

    ERIC Educational Resources Information Center

    Katzenmeyer, William G.; Stenner, A. Jackson

    1975-01-01

    The problem of demonstrating replicability of factor structure across random variables is addressed. Procedures are outlined which combine the use of random subsample replication strategies with the correlations between factor score estimates across replicate pairs to generate a coefficient of replicability and confidence intervals associated with…

  4. Bare skin, blood and the evolution of primate colour vision.

    PubMed

    Changizi, Mark A; Zhang, Qiong; Shimojo, Shinsuke

    2006-06-22

    We investigate the hypothesis that colour vision in primates was selected for discriminating the spectral modulations on the skin of conspecifics, presumably for the purpose of discriminating emotional states, socio-sexual signals and threat displays. Here we show that, consistent with this hypothesis, there are two dimensions of skin spectral modulations, and trichromats but not dichromats are sensitive to each. Furthermore, the M and L cone maximum sensitivities for routine trichromats are optimized for discriminating variations in blood oxygen saturation, one of the two blood-related dimensions determining skin reflectance. We also show that, consistent with the hypothesis, trichromat primates tend to be bare faced.

  5. Primate-Specific Evolution of an LDLR Enhancer

    SciTech Connect

    Wang, Qian-fei; Prabhakar, Shyam; Wang, Qianben; Moses, Alan M.; Chanan, Sumita; Brown, Myles; Eisen, Michael B.; Cheng, Jan-Fang; Rubin,Edward M.; Boffelli, Dario

    2006-06-28

    Sequence changes in regulatory regions have often beeninvoked to explain phenotypic divergence among species, but molecularexamples of this have been difficult to obtain. In this study, weidentified an anthropoid primate specific sequence element thatcontributed to the regulatory evolution of the LDL receptor. Using acombination of close and distant species genomic sequence comparisonscoupled with in vivo and in vitro studies, we show that a functionalcholesterol-sensing sequence motif arose and was fixed within apre-existing enhancer in the common ancestor of anthropoid primates. Ourstudy demonstrates one molecular mechanism by which ancestral mammalianregulatory elements can evolve to perform new functions in the primatelineage leading to human.

  6. Promoter interference mediated by the U3 region in early-generation HIV-1-derived lentivirus vectors can influence detection of transgene expression in a cell-type and species-specific manner.

    PubMed

    Ginn, Samantha L; Fleming, Jane; Rowe, Peter B; Alexander, Ian E

    2003-08-10

    In a previous study using an early-generation VSV-G-pseudotyped lentivirus vector encoding enhanced green fluorescent protein (EGFP) under the transcriptional control of a human cytomegalovirus (CMV) immediate-early promoter, we examined transduction efficiency in dissociated dorsal root ganglia (DRG) cultures. In cultures of murine origin, transgene expression was observed solely in the sensory neurons with the stromal cell population failing to show evidence of transduction. In contrast, efficient and sustained transduction of both sensory neurons and the stromal cell population was observed in cultures of human origin. Given the widespread use of murine models in preclinical gene therapy studies, in the current study we investigated the basis of this apparent neuron specificity of lentivirus-mediated transduction in murine DRG cultures. The interspecies differences persisted at high multiplicities of infection, and irrespective of whether lentiviral vector stocks were packaged in the presence or absence of human immunodeficiency virus type 1 (HIV-1) accessory proteins. Cell-type specificity of CMV promoter expression, tropism of the VSV-G envelope, and blocks to molecular transduction were also precluded as possible mechanisms, thereby implicating transcriptional repression of the internal heterologous promoter. This promoter interference effect was found to be mediated by cis-acting sequences upstream of the core promoter elements located in the U3 region of the proviral long terminal repeats (LTRs). Deletion of this region, as in late-generation self-inactivating (SIN) lentivirus vectors, relieves this effect. This provides a basis for reevaluating data produced using early-generation U3-bearing lentivirus vectors and for reconciling these with results obtained using more contemporary SIN lentivirus vectors carrying a U3 deletion.

  7. Mathematical modelling of eukaryotic DNA replication.

    PubMed

    Hyrien, Olivier; Goldar, Arach

    2010-01-01

    Eukaryotic DNA replication is a complex process. Replication starts at thousand origins that are activated at different times in S phase and terminates when converging replication forks meet. Potential origins are much more abundant than actually fire within a given S phase. The choice of replication origins and their time of activation is never exactly the same in any two cells. Individual origins show different efficiencies and different firing time probability distributions, conferring stochasticity to the DNA replication process. High-throughput microarray and sequencing techniques are providing increasingly huge datasets on the population-averaged spatiotemporal patterns of DNA replication in several organisms. On the other hand, single-molecule replication mapping techniques such as DNA combing provide unique information about cell-to-cell variability in DNA replication patterns. Mathematical modelling is required to fully comprehend the complexity of the chromosome replication process and to correctly interpret these data. Mathematical analysis and computer simulations have been recently used to model and interpret genome-wide replication data in the yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe, in Xenopus egg extracts and in mammalian cells. These works reveal how stochasticity in origin usage confers robustness and reliability to the DNA replication process. PMID:20205354

  8. How dormant origins promote complete genome replication.

    PubMed

    Blow, J Julian; Ge, Xin Quan; Jackson, Dean A

    2011-08-01

    Many replication origins that are licensed by loading MCM2-7 complexes in G1 are not normally used. Activation of these dormant origins during S phase provides a first line of defence for the genome if replication is inhibited. When replication forks fail, dormant origins are activated within regions of the genome currently engaged in replication. At the same time, DNA damage-response kinases activated by the stalled forks preferentially suppress the assembly of new replication factories, thereby ensuring that chromosomal regions experiencing replicative stress complete synthesis before new regions of the genome are replicated. Mice expressing reduced levels of MCM2-7 have fewer dormant origins, are cancer-prone and are genetically unstable, demonstrating the importance of dormant origins for preserving genome integrity. We review the function of dormant origins, the molecular mechanism of their regulation and their physiological implications.

  9. Cell Cycle Regulation of DNA Replication

    PubMed Central

    Sclafani, R. A.; Holzen, T. M.

    2008-01-01

    Eukaryotic DNA replication is regulated to ensure all chromosomes replicate once and only once per cell cycle. Replication begins at many origins scattered along each chromosome. Except for budding yeast, origins are not defined DNA sequences and probably are inherited by epigenetic mechanisms. Initiation at origins occurs throughout the S phase according to a temporal program that is important in regulating gene expression during development. Most replication proteins are conserved in evolution in eukaryotes and archaea, but not in bacteria. However, the mechanism of initiation is conserved and consists of origin recognition, assembly of pre-replication (pre-RC) initiative complexes, helicase activation, and replisome loading. Cell cycle regulation by protein phosphorylation ensures that pre-RC assembly can only occur in G1 phase, whereas helicase activation and loading can only occur in S phase. Checkpoint regulation maintains high fidelity by stabilizing replication forks and preventing cell cycle progression during replication stress or damage. PMID:17630848

  10. How to securely replicate services

    NASA Technical Reports Server (NTRS)

    Reiter, Michael; Birman, Kenneth

    1992-01-01

    A method is presented for constructing replicated services that retain their availability and integrity despite several servers and clients corrupted by an intruder, in addition to others failing benignly. More precisely, a service is replicated by n servers in such a way that a correct client will accept a correct server's response if, for some prespecified parameter k, at least k servers are correct and fewer than k servers are corrupt. The issue of maintaining causality among client requests is also addressed. A security breach resulting from an intruder's ability to effect a violation of causality in the sequence of requests processed by the service is illustrated. An approach to counter this problem is proposed that requires fewer than k servers to be corrupt and that is live if at least k+b servers are correct, where b is the assumed maximum total number of corrupt servers in any system run. An important and novel feature of these schemes is that the client need not be able to identify or authenticate even a single server. Instead, the client is required only to possess at most two public keys for the service. The practicality of these schemes is illustrated through a discussion of several issues pertinent to their implementation and use, and their intended role in a secure version of the Isis system is also described.

  11. Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein

    PubMed Central

    Staprans, Silvija I.; Barry, Ashley P.; Silvestri, Guido; Safrit, Jeffrey T.; Kozyr, Natalia; Sumpter, Beth; Nguyen, Hanh; McClure, Harold; Montefiori, David; Cohen, Jeffrey I.; Feinberg, Mark B.

    2004-01-01

    Given the dual role of CD4 T cells as both immune effectors and targets for HIV infection, the balance of CD4 versus CD8 T cell-mediated responses induced by candidate AIDS vaccines may be critical in determining postvaccination infection outcomes. An attenuated recombinant varicella-zoster virus vaccine expressing the simian immunodeficiency virus (SIV) envelope (Env) elicited nonneutralizing Env-binding antibodies and little if any cytotoxic T lymphocyte responses in rhesus macaques (Macaca mulatta). After challenge with SIV, Env vaccinees manifested increased levels of SIV replication, more rapid CD4 depletion, and accelerated progression to AIDS compared with controls. Enhanced SIV replication correlated with increased CD4 T cell proliferation soon after SIV challenge, apparently the result of an anamnestic response to SIV antigens. Thus activation of virus-specific CD4 T cells at the time of exposure to a CD4 T cell-tropic lentivirus, in the absence of an effective CD8 response, may enhance virus replication and disease. These data suggest suggest that candidate AIDS vaccines may not simply be either efficacious or neutral; they may also have the potential to be harmful. PMID:15326293

  12. Is the rate of insertion and deletion mutation male biased?: Molecular evolutionary analysis of avian and primate sex chromosome sequences.

    PubMed Central

    Sundström, Hannah; Webster, Matthew T; Ellegren, Hans

    2003-01-01

    The rate of mutation for nucleotide substitution is generally higher among males than among females, likely owing to the larger number of DNA replications in spermatogenesis than in oogenesis. For insertion and deletion (indel) mutations, data from a few human genetic disease loci indicate that the two sexes may mutate at similar rates, possibly because such mutations arise in connection with meiotic crossing over. To address origin- and sex-specific rates of indel mutation we have conducted the first large-scale molecular evolutionary analysis of indels in noncoding DNA sequences from sex chromosomes. The rates are similar on the X and Y chromosomes of primates but about twice as high on the avian Z chromosome as on the W chromosome. The fact that indels are not uncommon on the nonrecombining Y and W chromosomes excludes meiotic crossing over as the main cause of indel mutation. On the other hand, the similar rates on X and Y indicate that the number of DNA replications (higher for Y than for X) is also not the main factor. Our observations are therefore consistent with a role of both DNA replication and recombination in the generation of short insertion and deletion mutations. A significant excess of deletion compared to insertion events is observed on the avian W chromosome, consistent with gradual DNA loss on a nonrecombining chromosome. PMID:12750337

  13. Immune Protection of Nonhuman Primates against Ebola Virus with Single Low-Dose Adenovirus Vectors Encoding Modified GPs

    PubMed Central

    Geisbert, Joan B; Shedlock, Devon J; Xu, Ling; Lamoreaux, Laurie; Custers, Jerome H. H. V; Popernack, Paul M; Yang, Zhi-Yong; Pau, Maria G; Roederer, Mario; Koup, Richard A; Goudsmit, Jaap; Jahrling, Peter B; Nabel, Gary J

    2006-01-01

    Background Ebola virus causes a hemorrhagic fever syndrome that is associated with high mortality in humans. In the absence of effective therapies for Ebola virus infection, the development of a vaccine becomes an important strategy to contain outbreaks. Immunization with DNA and/or replication-defective adenoviral vectors (rAd) encoding the Ebola glycoprotein (GP) and nucleoprotein (NP) has been previously shown to confer specific protective immunity in nonhuman primates. GP can exert cytopathic effects on transfected cells in vitro, and multiple GP forms have been identified in nature, raising the question of which would be optimal for a human vaccine. Methods and Findings To address this question, we have explored the efficacy of mutant GPs from multiple Ebola virus strains with reduced in vitro cytopathicity and analyzed their protective effects in the primate challenge model, with or without NP. Deletion of the GP transmembrane domain eliminated in vitro cytopathicity but reduced its protective efficacy by at least one order of magnitude. In contrast, a point mutation was identified that abolished this cytopathicity but retained immunogenicity and conferred immune protection in the absence of NP. The minimal effective rAd dose was established at 1010 particles, two logs lower than that used previously. Conclusions Expression of specific GPs alone vectored by rAd are sufficient to confer protection against lethal challenge in a relevant nonhuman primate model. Elimination of NP from the vaccine and dose reductions to 1010 rAd particles do not diminish protection and simplify the vaccine, providing the basis for selection of a human vaccine candidate. PMID:16683867

  14. Evolution of activity patterns and chromatic vision in primates: morphometrics, genetics and cladistics.

    PubMed

    Heesy, C P; Ross, C F

    2001-02-01

    Hypotheses for the adaptive origin of primates have reconstructed nocturnality as the primitive activity pattern for the entire order based on functional/adaptive interpretations of the relative size and orientation of the orbits, body size and dietary reconstruction. Based on comparative data from extant taxa this reconstruction implies that basal primates were also solitary, faunivorous, and arboreal. Recently, primates have been hypothesized to be primitively diurnal, based in part on the distribution of color-sensitive photoreceptor opsin genes and active trichromatic color vision in several extant strepsirrhines, as well as anthropoid primates (Tan & Li, 1999 Nature402, 36; Li, 2000 Am. J. phys. Anthrop. Supple.30, 318). If diurnality is primitive for all primates then the functional and adaptive significance of aspects of strepsirrhine retinal morphology and other adaptations of the primate visual system such as high acuity stereopsis, have been misinterpreted for decades. This hypothesis also implies that nocturnality evolved numerous times in primates. However, the hypothesis that primates are primitively diurnal has not been analyzed in a phylogenetic context, nor have the activity patterns of several fossil primates been considered. This study investigated the evolution of activity patterns and trichromacy in primates using a new method for reconstructing activity patterns in fragmentary fossils and by reconstructing visual system character evolution at key ancestral nodes of primate higher taxa. Results support previous studies that reconstruct omomyiform primates as nocturnal. The larger body sizes of adapiform primates confound inferences regarding activity pattern evolution in this group. The hypothesis of diurnality and trichromacy as primitive for primates is not supported by the phylogenetic data. On the contrary, nocturnality and dichromatic vision are not only primitive for all primates, but also for extant strepsirrhines. Diurnality, and

  15. Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates

    PubMed Central

    Pierantoni, Angiolo; Esposito, Maria Luisa; Ammendola, Virginia; Napolitano, Federico; Grazioli, Fabiana; Abbate, Adele; del Sorbo, Mariarosaria; Siani, Loredana; D’Alise, Anna Morena; Taglioni, Alessandra; Perretta, Gemma; Siccardi, Antonio; Soprana, Elisa; Panigada, Maddalena; Thom, Michelle; Scarselli, Elisa; Folgori, Antonella; Colloca, Stefano; Taylor, Geraldine; Cortese, Riccardo; Nicosia, Alfredo; Capone, Stefania; Vitelli, Alessandra

    2015-01-01

    Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV) and Modified Vaccinia Ankara RSV (MVA-RSV) encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity. Because RSV infection is restricted to the respiratory tract, we compared intranasal (IN) and intramuscular (M) administration for safety, immunogenicity, and efficacy in different species. A single IN or IM vaccination completely protected BALB/c mice and cotton rats against RSV replication in the lungs. However, only IN administration could prevent infection in the upper respiratory tract. IM vaccination with MVA-RSV also protected cotton rats from lower respiratory tract infection in the absence of detectable neutralizing antibodies. Heterologous prime boost with PanAd3-RSV and MVA-RSV elicited high neutralizing antibody titers and broad T-cell responses in nonhuman primates. In addition, animals primed in the nose developed mucosal IgA against the F protein. In conclusion, we have shown that our vectored RSV vaccine induces potent cellular and humoral responses in a primate model, providing strong support for clinical testing. PMID:26015988

  16. Self-replication of DNA rings.

    PubMed

    Kim, Junghoon; Lee, Junwye; Hamada, Shogo; Murata, Satoshi; Ha Park, Sung

    2015-06-01

    Biology provides numerous examples of self-replicating machines, but artificially engineering such complex systems remains a formidable challenge. In particular, although simple artificial self-replicating systems including wooden blocks, magnetic systems, modular robots and synthetic molecular systems have been devised, such kinematic self-replicators are rare compared with examples of theoretical cellular self-replication. One of the principal reasons for this is the amount of complexity that arises when you try to incorporate self-replication into a physical medium. In this regard, DNA is a prime candidate material for constructing self-replicating systems due to its ability to self-assemble through molecular recognition. Here, we show that DNA T-motifs, which self-assemble into ring structures, can be designed to self-replicate through toehold-mediated strand displacement reactions. The inherent design of these rings allows the population dynamics of the systems to be controlled. We also analyse the replication scheme within a universal framework of self-replication and derive a quantitative metric of the self-replicability of the rings. PMID:25961509

  17. Self-replication of DNA rings

    NASA Astrophysics Data System (ADS)

    Kim, Junghoon; Lee, Junwye; Hamada, Shogo; Murata, Satoshi; Ha Park, Sung

    2015-06-01

    Biology provides numerous examples of self-replicating machines, but artificially engineering such complex systems remains a formidable challenge. In particular, although simple artificial self-replicating systems including wooden blocks, magnetic systems, modular robots and synthetic molecular systems have been devised, such kinematic self-replicators are rare compared with examples of theoretical cellular self-replication. One of the principal reasons for this is the amount of complexity that arises when you try to incorporate self-replication into a physical medium. In this regard, DNA is a prime candidate material for constructing self-replicating systems due to its ability to self-assemble through molecular recognition. Here, we show that DNA T-motifs, which self-assemble into ring structures, can be designed to self-replicate through toehold-mediated strand displacement reactions. The inherent design of these rings allows the population dynamics of the systems to be controlled. We also analyse the replication scheme within a universal framework of self-replication and derive a quantitative metric of the self-replicability of the rings.

  18. Rolling-circle replication of bacterial plasmids.

    PubMed Central

    Khan, S A

    1997-01-01

    Many bacterial plasmids replicate by a rolling-circle (RC) mechanism. Their replication properties have many similarities to as well as significant differences from those of single-stranded DNA (ssDNA) coliphages, which also replicate by an RC mechanism. Studies on a large number of RC plasmids have revealed that they fall into several families based on homology in their initiator proteins and leading-strand origins. The leading-strand origins contain distinct sequences that are required for binding and nicking by the Rep proteins. Leading-strand origins also contain domains that are required for the initiation and termination of replication. RC plasmids generate ssDNA intermediates during replication, since their lagging-strand synthesis does not usually initiate until the leading strand has been almost fully synthesized. The leading- and lagging-strand origins are distinct, and the displaced leading-strand DNA is converted to the double-stranded form by using solely the host proteins. The Rep proteins encoded by RC plasmids contain specific domains that are involved in their origin binding and nicking activities. The replication and copy number of RC plasmids, in general, are regulated at the level of synthesis of their Rep proteins, which are usually rate limiting for replication. Some RC Rep proteins are known to be inactivated after supporting one round of replication. A number of in vitro replication systems have been developed for RC plasmids and have provided insight into the mechanism of plasmid RC replication. PMID:9409148

  19. Evolutionary Developmental Psychology: Contributions from Comparative Research with Nonhuman Primates

    ERIC Educational Resources Information Center

    Maestripieri, Dario; Roney, James R.

    2006-01-01

    Evolutionary developmental psychology is a discipline that has the potential to integrate conceptual approaches to the study of behavioral development derived from psychology and biology as well as empirical data from humans and animals. Comparative research with animals, and especially with nonhuman primates, can provide evidence of adaptation in…

  20. Adaptive evolution of facial colour patterns in Neotropical primates.

    PubMed

    Santana, Sharlene E; Lynch Alfaro, Jessica; Alfaro, Michael E

    2012-06-01

    The rich diversity of primate faces has interested naturalists for over a century. Researchers have long proposed that social behaviours have shaped the evolution of primate facial diversity. However, the primate face constitutes a unique structure where the diverse and potentially competing functions of communication, ecology and physiology intersect, and the major determinants of facial diversity remain poorly understood. Here, we provide the first evidence for an adaptive role of facial colour patterns and pigmentation within Neotropical primates. Consistent with the hypothesis that facial patterns function in communication and species recognition, we find that species living in smaller groups and in sympatry with a higher number of congener species have evolved more complex patterns of facial colour. The evolution of facial pigmentation and hair length is linked to ecological factors, and ecogeographical rules related to UV radiation and thermoregulation are met by some facial regions. Our results demonstrate the interaction of behavioural and ecological factors in shaping one of the most outstanding facial diversities of any mammalian lineage.

  1. Monkeys, Apes and Other Primates. Young Discovery Library Series.

    ERIC Educational Resources Information Center

    Lucas, Andre

    This book is written for children 5 through 10. Part of a series designed to develop their curiosity, fascinate them and educate them, this volume introduces the primate family, their physiology, and habits. Topics described include: (1) kinds of monkeys, including lemur, chimpanzee, gorilla, squirrel monkey, and marmoset; (2) behaviors when…

  2. Alopecia: Possible Causes and Treatments, Particularly in Captive Nonhuman Primates

    PubMed Central

    Novak, Melinda A; Meyer, Jerrold S

    2009-01-01

    Alopecia (hair loss) occurs in some nonhuman primates housed in captivity and is of concern to colony managers and veterinarians. Here we review the characteristics, potential causes, and treatments for this condition. Although we focus on nonhuman primates, relevant research on other mammalian species is discussed also, due to the relative paucity of studies on alopecia in the primate literature. We first discuss the cycle of hair growth and explain how this cycle can be disrupted to produce alopecia. Numerous factors may be related to hair loss and range from naturally occurring processes (for example, seasonality, aging) to various biologic dysfunctions, including vitamin and mineral imbalances, endocrine disorders, immunologic diseases, and genetic mutations. We also address bacterial and fungal infections, infestation by parasites, and atopic dermatitis as possible causes of alopecia. Finally, we examine the role of psychogenic factors, such as stress. Depending on the presumed cause of the hair loss, various treatment strategies can be pursued. Alopecia in nonhuman primates is a multifaceted disorder with many potential sources. For this reason, appropriate testing for various disease conditions should be completed before alopecia is considered to be related to stress. PMID:19295051

  3. Lifespan of mice and primates correlates with immunoproteasome expression

    PubMed Central

    Pickering, Andrew M.; Lehr, Marcus; Miller, Richard A.

    2015-01-01

    There is large variation in lifespan among different species, and there is evidence that modulation of proteasome function may contribute to longevity determination. Comparative biology provides a powerful tool for identifying genes and pathways that control the rate of aging. Here, we evaluated skin-derived fibroblasts and demonstrate that among primate species, longevity correlated with an elevation in proteasomal activity as well as immunoproteasome expression at both the mRNA and protein levels. Immunoproteasome enhancement occurred with a concurrent increase in other elements involved in MHC class I antigen presentation, including β-2 microglobulin, (TAP1), and TAP2. Fibroblasts from long-lived primates also appeared more responsive to IFN-γ than cells from short-lived primate species, and this increase in IFN-γ responsiveness correlated with elevated expression of the IFN-γ receptor protein IFNGR2. Elevation of immunoproteasome and proteasome activity was also observed in the livers of long-lived Snell dwarf mice and in mice exposed to drugs that have been shown to extend lifespan, including rapamycin, 17-α-estradiol, and nordihydroguaiaretic acid. This work suggests that augmented immunoproteasome function may contribute to lifespan differences in mice and among primate species. PMID:25866968

  4. A review of lateralization of spatial functioning in nonhuman primates.

    PubMed

    Oleksiak, Anna; Postma, Albert; van der Ham, Ineke J M; Klink, P Christiaan; van Wezel, Richard J A

    2011-06-24

    The majority of research on functional cerebral lateralization in primates revolves around vocal abilities, addressing the evolutionary origin of the human language faculty and its predominance in the left hemisphere of the brain. Right hemisphere specialization in spatial cognition is commonly reported in humans. This functional asymmetry is especially evident in the context of the unilateral neglect, a deficit in attention to and awareness of one side of space, that more frequently occurs after right-side rather than left-side brain damage. Since most of the research efforts are concentrated on vocalization in primates, much less is known about the presence or absence of spatial functions lateralization. Obtaining this knowledge can provide insight into the evolutionary aspect of the functionally lateralized brain of Homo sapiens and deliver refinement and validation of the nonhuman primate unilateral neglect model. This paper reviews the literature on functional brain asymmetries in processing spatial information, limiting the search to nonhuman primates, and concludes there is no clear evidence that monkeys process spatial information with different efficiency in the two hemispheres. We suggest that lateralization of spatial cognition in humans represents a relatively new feature on the evolutionary time scale, possibly developed as a by-product of the left hemisphere intrusion of language competence. Further, we argue that the monkey model of hemispatial neglect requires reconsideration. PMID:21059373

  5. Led by the nose: Olfaction in primate feeding ecology

    PubMed Central

    Nevo, Omer; Heymann, Eckhard W

    2015-01-01

    Olfaction, the sense of smell, was a latecomer to the systematic investigation of primate sensory ecology after long years in which it was considered to be of minor importance.1 This view shifted with the growing understanding of its role in social behavior2 and the accumulation of physiological studies demonstrating that the olfactory abilities of some primates are on a par with those of olfactory-dependent mammals such as dogs and rodents.3,4 Recent years have seen a proliferation of physiological, behavioral, anatomical, and genetic investigations of primate olfaction. These investigations have begun to shed light on the importance of olfaction in the process of food acquisition. However, integration of these works has been limited. It is therefore still difficult to pinpoint large-scale evolutionary scenarios, namely the functions that the sense of smell fulfills in primates’ feeding ecology and the ecological niches that favor heavier reliance on olfaction. Here, we review available behavioral and physiological studies of primates in the field or captivity and try to elucidate how and when the sense of smell can help them acquire food. PMID:26267435

  6. Distinct Lineages of Bufavirus in Wild Shrews and Nonhuman Primates.

    PubMed

    Sasaki, Michihito; Orba, Yasuko; Anindita, Paulina D; Ishii, Akihiro; Ueno, Keisuke; Hang'ombe, Bernard M; Mweene, Aaron S; Ito, Kimihito; Sawa, Hirofumi

    2015-07-01

    Viral metagenomic analysis identified a new parvovirus genome in the intestinal contents of wild shrews in Zambia. Related viruses were detected in spleen tissues from wild shrews and nonhuman primates. Phylogenetic analyses showed that these viruses are related to human bufaviruses, highlighting the presence and genetic diversity of bufaviruses in wildlife. PMID:26079728

  7. As Threats of Violence Escalate, Primate Researchers Stand Firm.

    ERIC Educational Resources Information Center

    Schneider, Alison

    1999-01-01

    Scientists doing research on primates are increasingly being subjected to threats and acts of violence from animal rights groups. The intimidation has resulted in many laboratories taking extensive security measures. Some scientists claim, however, that there is no surrogate for animal research in understanding human diseases. There are fears that…

  8. Comparative Analysis of Alu Repeats in Primate Genomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Alu repeats are SINEs (Short intersperse repetitive elements) which enjoy a successful application in genome evolution, population biology, phylogenetics and forensics. Human Alu consensus sequences were widely used as surrogates in nonhuman primate studies with an assumption that all p...

  9. Molecular identification of Entamoeba spp. in captive nonhuman primates.

    PubMed

    Levecke, B; Dreesen, Leentje; Dorny, Pierre; Verweij, Jaco J; Vercammen, Francis; Casaert, Stijn; Vercruysse, Jozef; Geldhof, Peter

    2010-08-01

    This study describes the molecular identification of 520 Entamoeba-positive fecal samples from a large and diverse population of captive nonhuman primates (NHP). The results revealed the presence of Entamoeba histolytica (NHP variant only), E. dispar, E. moshkovskii, E. hartmanni, E. coli, and E. polecki-like organisms. PMID:20573870

  10. Human Quadrupeds, Primate Quadrupedalism, and Uner Tan Syndrome

    PubMed Central

    Shapiro, Liza J.; Cole, Whitney G.; Young, Jesse W.; Raichlen, David A.; Robinson, Scott R.; Adolph, Karen E.

    2014-01-01

    Since 2005, an extensive literature documents individuals from several families afflicted with “Uner Tan Syndrome (UTS),” a condition that in its most extreme form is characterized by cerebellar hypoplasia, loss of balance and coordination, impaired cognitive abilities, and habitual quadrupedal gait on hands and feet. Some researchers have interpreted habitual use of quadrupedalism by these individuals from an evolutionary perspective, suggesting that it represents an atavistic expression of our quadrupedal primate ancestry or “devolution.” In support of this idea, individuals with “UTS” are said to use diagonal sequence quadrupedalism, a type of quadrupedal gait that distinguishes primates from most other mammals. Although the use of primate-like quadrupedal gait in humans would not be sufficient to support the conclusion of evolutionary “reversal,” no quantitative gait analyses were presented to support this claim. Using standard gait analysis of 518 quadrupedal strides from video sequences of individuals with “UTS”, we found that these humans almost exclusively used lateral sequence–not diagonal sequence–quadrupedal gaits. The quadrupedal gait of these individuals has therefore been erroneously described as primate-like, further weakening the “devolution” hypothesis. In fact, the quadrupedalism exhibited by individuals with UTS resembles that of healthy adult humans asked to walk quadrupedally in an experimental setting. We conclude that quadrupedalism in healthy adults or those with a physical disability can be explained using biomechanical principles rather than evolutionary assumptions. PMID:25029457

  11. Voice processing in human and non-human primates

    PubMed Central

    Belin, Pascal

    2006-01-01

    Humans share with non-human primates a number of voice perception abilities of crucial importance in social interactions, such as the ability to identify a conspecific individual from its vocalizations. Speech perception is likely to have evolved in our ancestors on the basis of pre-existing neural mechanisms involved in extracting behaviourally relevant information from conspecific vocalizations (CVs). Studying the neural bases of voice perception in primates thus not only has the potential to shed light on cerebral mechanisms that may be—unlike those involved in speech perception—directly homologous between species, but also has direct implications for our understanding of how speech appeared in humans. In this comparative review, we focus on behavioural and neurobiological evidence relative to two issues central to voice perception in human and non-human primates: (i) are CVs ‘special’, i.e. are they analysed using dedicated cerebral mechanisms not used for other sound categories, and (ii) to what extent and using what neural mechanisms do primates identify conspecific individuals from their vocalizations? PMID:17118926

  12. Nonhuman Primates Prefer Slow Tempos but Dislike Music Overall

    ERIC Educational Resources Information Center

    McDermott, Josh; Hauser, Marc D.

    2007-01-01

    Human adults generally find fast tempos more arousing than slow tempos, with tempo frequently manipulated in music to alter tension and emotion. We used a previously published method [McDermott, J., & Hauser, M. (2004). Are consonant intervals music to their ears? Spontaneous acoustic preferences in a nonhuman primate. Cognition, 94(2), B11-B21]…

  13. Consideration of other primate species as flight animals

    NASA Technical Reports Server (NTRS)

    Bourne, G. H.

    1977-01-01

    The different types of primates which might be used as flight animals are surveyed, and the pros and cons of using them are discussed. Various factors suggest that the most desirable animals for space studies are the rhesus, pig-tailed, Java, and squirrel monkeys. The capuchin monkey has assets for certain types of space experimentation.

  14. A survey of diabetes prevalence in zoo-housed primates.

    PubMed

    Kuhar, C W; Fuller, G A; Dennis, P M

    2013-01-01

    In humans, type II diabetes mellitus is a condition in which the pancreas is capable of producing insulin but cells do not appropriately respond to insulin with an uptake of glucose. While multiple factors are associated with type II diabetes in humans, a high calorie diet and limited exercise are significant risk factors for the development of this disease. Zoo primates, with relatively high caloric density diets and sedentary lifestyles, may experience similar conditions that could predispose them to the development of diabetes. We surveyed all Association of Zoos and Aquariums (AZA) facilities with primates in their collections to determine the prevalence of diabetes, diagnosis and treatment methods, and treatment outcomes. Nearly 30% of responding institutions reported at least one diabetic primate in their current collection. Although the majority of reported cases were in Old World Monkeys (51%), all major taxonomic groups were represented. Females represented nearly 80% of the diagnosed cases. A wide variety of diagnosing, monitoring, and treatment techniques were reported. It is clear from these results diabetes should be considered prominently in decisions relating to diet, weight and activity levels in zoo-housed primates, as well as discussions surrounding animal health and welfare.

  15. Nonhuman primate vocalizations support categorization in very young human infants.

    PubMed

    Ferry, Alissa L; Hespos, Susan J; Waxman, Sandra R

    2013-09-17

    Language is a signature of our species and our primary conduit for conveying the contents of our minds. The power of language derives not only from the exquisite detail of the signal itself but also from its intricate link to human cognition. To acquire a language, infants must identify which signals are part of their language and discover how these signals are linked to meaning. At birth, infants prefer listening to vocalizations of human and nonhuman primates; within 3 mo, this initially broad listening preference is tuned specifically to human vocalizations. Moreover, even at this early developmental point, human vocalizations evoke more than listening preferences alone: they engender in infants a heightened focus on the objects in their visual environment and promote the formation of object categories, a fundamental cognitive capacity. Here, we illuminate the developmental origin of this early link between human vocalizations and cognition. We document that this link emerges from a broad biological template that initially encompasses vocalizations of human and nonhuman primates (but not backward speech) and that within 6 mo this link to cognition is tuned specifically to human vocalizations. At 3 and 4 mo, nonhuman primate vocalizations promote object categorization, mirroring precisely the advantages conferred by human vocalizations, but by 6 mo, nonhuman primate vocalizations no longer exert this advantageous effect. This striking developmental shift illuminates a path of specialization that supports infants as they forge the foundational links between human language and the core cognitive processes that will serve as the foundations of meaning. PMID:24003164

  16. Social drive and the evolution of primate hearing

    PubMed Central

    Ramsier, Marissa A.; Cunningham, Andrew J.; Finneran, James J.; Dominy, Nathaniel J.

    2012-01-01

    The structure and function of primate communication have attracted much attention, and vocal signals, in particular, have been studied in detail. As a general rule, larger social groups emit more types of vocal signals, including those conveying the presence of specific types of predators. The adaptive advantages of receiving and responding to alarm calls are expected to exert a selective pressure on the auditory system. Yet, the comparative biology of primate hearing is limited to select species, and little attention has been paid to the effects of social and vocal complexity on hearing. Here, we use the auditory brainstem response method to generate the largest number of standardized audiograms available for any primate radiation. We compared the auditory sensitivities of 11 strepsirrhine species with and without independent contrasts and show that social complexity explains a significant amount of variation in two audiometric parameters—overall sensitivity and high-frequency limit. We verified the generality of this latter result by augmenting our analysis with published data from nine species spanning the primate order. To account for these findings, we develop and test a model of social drive. We hypothesize that social complexity has favoured enhanced hearing sensitivities, especially at higher frequencies. PMID:22641824

  17. A survey of diabetes prevalence in zoo-housed primates.

    PubMed

    Kuhar, C W; Fuller, G A; Dennis, P M

    2013-01-01

    In humans, type II diabetes mellitus is a condition in which the pancreas is capable of producing insulin but cells do not appropriately respond to insulin with an uptake of glucose. While multiple factors are associated with type II diabetes in humans, a high calorie diet and limited exercise are significant risk factors for the development of this disease. Zoo primates, with relatively high caloric density diets and sedentary lifestyles, may experience similar conditions that could predispose them to the development of diabetes. We surveyed all Association of Zoos and Aquariums (AZA) facilities with primates in their collections to determine the prevalence of diabetes, diagnosis and treatment methods, and treatment outcomes. Nearly 30% of responding institutions reported at least one diabetic primate in their current collection. Although the majority of reported cases were in Old World Monkeys (51%), all major taxonomic groups were represented. Females represented nearly 80% of the diagnosed cases. A wide variety of diagnosing, monitoring, and treatment techniques were reported. It is clear from these results diabetes should be considered prominently in decisions relating to diet, weight and activity levels in zoo-housed primates, as well as discussions surrounding animal health and welfare. PMID:22847472

  18. Human quadrupeds, primate quadrupedalism, and Uner Tan Syndrome.

    PubMed

    Shapiro, Liza J; Cole, Whitney G; Young, Jesse W; Raichlen, David A; Robinson, Scott R; Adolph, Karen E

    2014-01-01

    Since 2005, an extensive literature documents individuals from several families afflicted with "Uner Tan Syndrome (UTS)," a condition that in its most extreme form is characterized by cerebellar hypoplasia, loss of balance and coordination, impaired cognitive abilities, and habitual quadrupedal gait on hands and feet. Some researchers have interpreted habitual use of quadrupedalism by these individuals from an evolutionary perspective, suggesting that it represents an atavistic expression of our quadrupedal primate ancestry or "devolution." In support of this idea, individuals with "UTS" are said to use diagonal sequence quadrupedalism, a type of quadrupedal gait that distinguishes primates from most other mammals. Although the use of primate-like quadrupedal gait in humans would not be sufficient to support the conclusion of evolutionary "reversal," no quantitative gait analyses were presented to support this claim. Using standard gait analysis of 518 quadrupedal strides from video sequences of individuals with "UTS", we found that these humans almost exclusively used lateral sequence-not diagonal sequence-quadrupedal gaits. The quadrupedal gait of these individuals has therefore been erroneously described as primate-like, further weakening the "devolution" hypothesis. In fact, the quadrupedalism exhibited by individuals with UTS resembles that of healthy adult humans asked to walk quadrupedally in an experimental setting. We conclude that quadrupedalism in healthy adults or those with a physical disability can be explained using biomechanical principles rather than evolutionary assumptions.

  19. Therapeutic targeting of replicative immortality

    PubMed Central

    Yaswen, Paul; MacKenzie, Karen L.; Keith, W. Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L.; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S.; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I.; Azmi, Asfar S.; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S. Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-01-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells’ heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. PMID:25869441

  20. Primate phylogenetic relationships and divergence dates inferred from complete mitochondrial genomes

    PubMed Central

    Hodgson, Jason A.; Burrell, Andrew S.; Sterner, Kirstin N.; Raaum, Ryan L.; Disotell, Todd R.

    2014-01-01

    The origins and the divergence times of the most basal lineages within primates have been difficult to resolve mainly due to the incomplete sampling of early fossil taxa. The main source of contention is related to the discordance between molecular and fossil estimates: while there are no crown primate fossils older than 56 Ma, most molecule-based estimates extend the origins of crown primates into the Cretaceous. Here we present a comprehensive mitogenomic study of primates. We assembled 87 mammalian mitochondrial genomes, including 62 primate species representing all the families of the order. We newly sequenced eleven mitochondrial genomes, including eight Old World monkeys and three strepsirrhines. Phylogenetic analyses support a strong topology, confirming the monophyly for all the major primate clades. In contrast to previous mitogenomic studies, the positions of tarsiers and colugos relative to strepsirrhines and anthropoids are well resolved. In order to improve our understanding of how fossil calibrations affect age estimates within primates, we explore the effect of seventeen fossil calibrations across primates and other mammalian groups and we select a subset of calibrations to date our mitogenomic tree. The divergence date estimates of the Strepsirrhine/Haplorhine split support an origin of crown primates in the Late Cretaceous, at around 74 Ma. This result supports a short fuse model of primate origins, whereby relatively little time passed between the origin of the order and the diversification of its major clades. It also suggests that the early primate fossil record is likely poorly sampled. PMID:24583291

  1. Live-Attenuated Measles Virus Vaccine Targets Dendritic Cells and Macrophages in Muscle of Nonhuman Primates

    PubMed Central

    Rennick, Linda J.; de Vries, Rory D.; Carsillo, Thomas J.; Lemon, Ken; van Amerongen, Geert; Ludlow, Martin; Nguyen, D. Tien; Yüksel, Selma; Verburgh, R. Joyce; Haddock, Paula; McQuaid, Stephen; de Swart, Rik L.

    2014-01-01

    virus was formulated according to protocols for production of commercial vaccine virus batches, and was subsequently used to assess viral tropism in nonhuman primates. The virus primarily replicated in professional antigen-presenting cells, which may explain why this LAV is so immunogenic and efficacious. PMID:25473055

  2. Evolutionary molecular cytogenetics of catarrhine primates: past, present and future.

    PubMed

    Stanyon, R; Rocchi, M; Bigoni, F; Archidiacono, N

    2012-01-01

    The catarrhine primates were the first group of species studied with comparative molecular cytogenetics. Many of the fundamental techniques and principles of analysis were initially applied to comparisons in these primates, including interspecific chromosome painting, reciprocal chromosome painting and the extensive use of cloned DNA probes for evolutionary analysis. The definition and importance of chromosome syntenies and associations for a correct cladistics analysis of phylogenomic relationships were first applied to catarrhines. These early chromosome painting studies vividly illustrated a striking conservation of the genome between humans and macaques. Contemporarily, it also revealed profound differences between humans and gibbons, a group of species more closely related to humans, making it clear that chromosome evolution did not follow a molecular clock. Chromosome painting has now been applied to more that 60 primate species and the translocation history has been mapped onto the major taxonomic divisions in the tree of primate evolution. In situ hybridization of cloned DNA probes, primarily BAC-FISH, also made it possible to more precisely map breakpoints with spanning and flanking BACs. These studies established marker order and disclosed intrachromosomal rearrangements. When applied comparatively to a range of primate species, they led to the discovery of evolutionary new centromeres as an important new category of chromosome evolution. BAC-FISH studies are intimately connected to genome sequencing, and probes can usually be assigned to a precise location in the genome assembly. This connection ties molecular cytogenetics securely to genome sequencing, assuring that molecular cytogenetics will continue to have a productive future in the multidisciplinary science of phylogenomics. PMID:22710640

  3. Indices of environmental temperatures for primates in open habitats.

    PubMed

    Hill, Russell A; Weingrill, Tony; Barrett, Louise; Henzi, S Peter; Hill, Russel A; Barrett, Luise

    2004-01-01

    Studies of thermoregulation in primates are under-represented in the literature, although there is sufficient evidence to suggest that temperature represents an important ecological constraint. One of the problems in examining thermoregulation in primates, however, is the difficulty in quantifying the thermal environment, since shade temperatures, solar radiation, humidity and wind speed all serve to alter an animal's 'perceived' temperature. Since animals respond to their perceived temperature, we need methods to account for each of these factors, both individually and collectively, if we are to understand the integrated impact of the thermal environment on primates. Here, we present a review of some thermal indices currently available. Black bulb temperatures can account for the effect of solar radiation, with wind chill equivalent temperatures and the heat index providing quantifiable estimates of the relative impact of wind speed and humidity, respectively. We present three potential indices of the 'perceived environmental temperature' (PET) that account for the combined impact of solar radiation, humidity and wind speed on temperature, and perform a preliminary test of all of the climatic indices against behavioural data from a field study of chacma baboons ( Papio cynocephalus ursinus) at De Hoop Nature Reserve, South Africa. One measure of the perceived environmental temperature, PET2, is an effective thermal index, since it enters the models for feeding and resting behaviour, and also accounts for levels of allogrooming. Solar radiation intensity is an important factor underlying these relationships, although the wind chill equivalent temperature and humidity enter the models for other behaviours. Future studies should thus be mindful of the impact of each of these elements of the thermal environment. A detailed understanding of primate thermoregulation will only come with the development of biophysical models of the thermal characteristics of the species

  4. Indices of environmental temperatures for primates in open habitats.

    PubMed

    Hill, Russell A; Weingrill, Tony; Barrett, Louise; Henzi, S Peter; Hill, Russel A; Barrett, Luise

    2004-01-01

    Studies of thermoregulation in primates are under-represented in the literature, although there is sufficient evidence to suggest that temperature represents an important ecological constraint. One of the problems in examining thermoregulation in primates, however, is the difficulty in quantifying the thermal environment, since shade temperatures, solar radiation, humidity and wind speed all serve to alter an animal's 'perceived' temperature. Since animals respond to their perceived temperature, we need methods to account for each of these factors, both individually and collectively, if we are to understand the integrated impact of the thermal environment on primates. Here, we present a review of some thermal indices currently available. Black bulb temperatures can account for the effect of solar radiation, with wind chill equivalent temperatures and the heat index providing quantifiable estimates of the relative impact of wind speed and humidity, respectively. We present three potential indices of the 'perceived environmental temperature' (PET) that account for the combined impact of solar radiation, humidity and wind speed on temperature, and perform a preliminary test of all of the climatic indices against behavioural data from a field study of chacma baboons ( Papio cynocephalus ursinus) at De Hoop Nature Reserve, South Africa. One measure of the perceived environmental temperature, PET2, is an effective thermal index, since it enters the models for feeding and resting behaviour, and also accounts for levels of allogrooming. Solar radiation intensity is an important factor underlying these relationships, although the wind chill equivalent temperature and humidity enter the models for other behaviours. Future studies should thus be mindful of the impact of each of these elements of the thermal environment. A detailed understanding of primate thermoregulation will only come with the development of biophysical models of the thermal characteristics of the species

  5. The Replication System of Bacteriophage T7.

    PubMed

    Kulczyk, A W; Richardson, C C

    2016-01-01

    The replication system of bacteriophage T7 is remarkable in that the 40,000 nucleotide genome is replicated over 100-fold in a matter of minutes. In order to accomplish this feat T7 has evolved an efficient and economical process for the replication of its DNA. The T7 replisome provides a model system to study DNA replication. Four proteins are sufficient for reconstitution of the functional replication complex, yet the assembled replisome recapitulates all the key features of more complex prokaryotic and eukaryotic systems. In this review, we describe chemical mechanisms employed by individual proteins at the replication fork. Integration of structural, biochemical, and single-molecule data reveals a compelling view on how a nearly 1-MDa molecular machine acts as a unit to synthetize the two antiparallel DNA strands in a coordinated fashion.

  6. Cell-cycle-specific initiation of replication.

    PubMed

    Nordström, K; Austin, S J

    1993-11-01

    The following characteristics are relevant when replication of chromosomes and plasmids is discussed in relation to the cell cycle: the timing or replication, the selection of molecules for replication, and the coordination of multiple initiation events within a single cell cycle. Several fundamentally different methods have been used to study these processes: Meselson-Stahl density-shift experiments, experiments with the so-called 'baby machine', sorting of cells according to size, and flow cytometry. The evidence for precise timing and co-ordination of chromosome replication in Escherichia coli is overwhelming. Similarly, the high-copy-number plasmid ColE1 and the low-copy-number plasmids R1/R100 without any doubt replicate randomly throughout the cell cycle. Data about the low-copy-number plasmids F and P1 are conflicting. This calls for new types of experiments and for a better understanding of how these plasmids control their replication and partitioning.

  7. Did DNA replication evolve twice independently?

    PubMed

    Leipe, D D; Aravind, L; Koonin, E V

    1999-09-01

    DNA replication is central to all extant cellular organisms. There are substantial functional similarities between the bacterial and the archaeal/eukaryotic replication machineries, including but not limited to defined origins, replication bidirectionality, RNA primers and leading and lagging strand synthesis. However, several core components of the bacterial replication machinery are unrelated or only distantly related to the functionally equivalent components of the archaeal/eukaryotic replication apparatus. This is in sharp contrast to the principal proteins involved in transcription and translation, which are highly conserved in all divisions of life. We performed detailed sequence comparisons of the proteins that fulfill indispensable functions in DNA replication and classified them into four main categories with respect to the conservation in bacteria and archaea/eukaryotes: (i) non-homologous, such as replicative polymerases and primases; (ii) containing homologous domains but apparently non-orthologous and conceivably independently recruited to function in replication, such as the principal replicative helicases or proofreading exonucleases; (iii) apparently orthologous but poorly conserved, such as the sliding clamp proteins or DNA ligases; (iv) orthologous and highly conserved, such as clamp-loader ATPases or 5'-->3' exonucleases (FLAP nucleases). The universal conservation of some components of the DNA replication machinery and enzymes for DNA precursor biosynthesis but not the principal DNA polymerases suggests that the last common ancestor (LCA) of all modern cellular life forms possessed DNA but did not replicate it the way extant cells do. We propose that the LCA had a genetic system that contained both RNA and DNA, with the latter being produced by reverse transcription. Consequently, the modern-type system for double-stranded DNA replication likely evolved independently in the bacterial and archaeal/eukaryotic lineages.

  8. Two Immunologically Distinct Human DNA Polymerase α-Primase Subpopulations Are Involved in Cellular DNA Replication

    PubMed Central

    Dehde, Silke; Rohaly, Gabor; Schub, Oliver; Nasheuer, Heinz-Peter; Bohn, Wolfgang; Chemnitz, Jan; Deppert, Wolfgang; Dornreiter, Irena

    2001-01-01

    Metabolic labeling of primate cells revealed the existence of phosphorylated and hypophosphorylated DNA polymerase α-primase (Pol-Prim) populations that are distinguishable by monoclonal antibodies. Cell cycle studies showed that the hypophosphorylated form was found in a complex with PP2A and cyclin E-Cdk2 in G1, whereas the phosphorylated enzyme was associated with a cyclin A kinase in S and G2. Modification of Pol-Prim by PP2A and Cdks regulated the interaction with the simian virus 40 origin-binding protein large T antigen and thus initiation of DNA replication. Confocal microscopy demonstrated nuclear colocalization of hypophosphorylated Pol-Prim with MCM2 in S phase nuclei, but its presence preceded 5-bromo-2′-deoxyuridine (BrdU) incorporation. The phosphorylated replicase exclusively colocalized with the BrdU signal, but not with MCM2. Immunoprecipitation experiments proved that only hypophosphorylated Pol-Prim associated with MCM2. The data indicate that the hypophosphorylated enzyme initiates DNA replication at origins, and the phosphorylated form synthesizes the primers for the lagging strand of the replication fork. PMID:11259605

  9. Comparison of three replication strategies in complex multicellular organisms: Asexual replication, sexual replication with identical gametes, and sexual replication with distinct sperm and egg gametes

    NASA Astrophysics Data System (ADS)

    Tannenbaum, Emmanuel

    2008-01-01

    This paper studies the mutation-selection balance in three simplified replication models. The first model considers a population of organisms replicating via the production of asexual spores. The second model considers a sexually replicating population that produces identical gametes. The third model considers a sexually replicating population that produces distinct sperm and egg gametes. All models assume diploid organisms whose genomes consist of two chromosomes, each of which is taken to be functional if equal to some master sequence, and defective otherwise. In the asexual population, the asexual diploid spores develop directly into adult organisms. In the sexual populations, the haploid gametes enter a haploid pool, where they may fuse with other haploids. The resulting immature diploid organisms then proceed to develop into mature organisms. Based on an analysis of all three models, we find that, as organism size increases, a sexually replicating population can only outcompete an asexually replicating population if the adult organisms produce distinct sperm and egg gametes. A sexual replication strategy that is based on the production of large numbers of sperm cells to fertilize a small number of eggs is found to be necessary in order to maintain a sufficiently low cost for sex for the strategy to be selected for over a purely asexual strategy. We discuss the usefulness of this model in understanding the evolution and maintenance of sexual replication as the preferred replication strategy in complex, multicellular organisms.

  10. Regulation of chromosomal replication in Caulobacter crescentus.

    PubMed

    Collier, Justine

    2012-03-01

    The alpha-proteobacterium Caulobacter crescentus is characterized by its asymmetric cell division, which gives rise to a replicating stalked cell and a non-replicating swarmer cell. Thus, the initiation of chromosomal replication is tightly regulated, temporally and spatially, to ensure that it is coordinated with cell differentiation and cell cycle progression. Waves of DnaA and CtrA activities control when and where the initiation of DNA replication will take place in C. crescentus cells. The conserved DnaA protein initiates chromosomal replication by directly binding to sites within the chromosomal origin (Cori), ensuring that DNA replication starts once and only once per cell cycle. The CtrA response regulator represses the initiation of DNA replication in swarmer cells and in the swarmer compartment of pre-divisional cells, probably by competing with DnaA for binding to Cori. CtrA and DnaA are controlled by multiple redundant regulatory pathways that include DNA methylation-dependent transcriptional regulation, temporally regulated proteolysis and the targeting of regulators to specific locations within the cell. Besides being critical regulators of chromosomal replication, CtrA and DnaA are also master transcriptional regulators that control the expression of many genes, thus connecting DNA replication with other events of the C. crescentus cell cycle.

  11. Precise replication of antireflective nanostructures from biotemplates

    NASA Astrophysics Data System (ADS)

    Gao, Hongjun; Liu, Zhongfan; Zhang, Jin; Zhang, Guoming; Xie, Guoyong

    2007-03-01

    The authors report herein a new type of nanonipple structures on the cicada's eye and the direct structural replication of the complex micro- and nanostructures for potential functional emulation. A two-step direct molding process is developed to replicate these natural micro- and nanostructures using epoxy resin with high fidelity, which demonstrates a general way of fabricating functional nanostructures by direct replication of natural biotemplates via a suitable physicochemical process. Measurements of spectral reflectance showed that this kind of replicated nanostructure has remarkable antireflective property, suggestive of its potential applications to optical devices.

  12. Transcriptional correlates of disease outcome in anticoagulant-treated non-human primates infected with ebolavirus.

    PubMed

    Garamszegi, Sara; Yen, Judy Y; Honko, Anna N; Geisbert, Joan B; Rubins, Kathleen H; Geisbert, Thomas W; Xia, Yu; Hensley, Lisa E; Connor, John H

    2014-01-01

    Ebola virus (EBOV) infection in humans and non-human primates (NHPs) is highly lethal, and there is limited understanding of the mechanisms associated with pathogenesis and survival. Here, we describe a transcriptomic analysis of NHPs that survived lethal EBOV infection, compared to NHPs that did not survive. It has been previously demonstrated that anticoagulant therapeutics increase the survival rate in EBOV-infected NHPs, and that the characteristic transcriptional profile of immune response changes in anticoagulant-treated NHPs. In order to identify transcriptional signatures that correlate with survival following EBOV infection, we compared the mRNA expression profile in peripheral blood mononuclear cells from EBOV-infected NHPs that received anticoagulant treatment, to those that did not receive treatment. We identified a small set of 20 genes that are highly confident predictors and can accurately distinguish between surviving and non-surviving animals. In addition, we identified a larger predictive signature of 238 genes that correlated with disease outcome and treatment; this latter signature was associated with a variety of host responses, such as the inflammatory response, T cell death, and inhibition of viral replication. Notably, among survival-associated genes were subsets of genes that are transcriptionally regulated by (1) CCAAT/enhancer-binding protein alpha, (2) tumor protein 53, and (3) megakaryoblastic leukemia 1 and myocardin-like protein 2. These pathways merit further investigation as potential transcriptional signatures of host immune response to EBOV infection. PMID:25079789

  13. Non-human primate FOG develops with advanced parkinsonism induced by MPTP Treatment.

    PubMed

    Revuelta, Gonzalo J; Uthayathas, Subramaniam; Wahlquist, Amy E; Factor, Stewart A; Papa, Stella M

    2012-10-01

    Freezing of gait (FOG) is a debilitating feature of Parkinson's disease (PD) and other forms of parkinsonism. The anatomical or pathophysiological correlates are poorly understood largely due to the lack of a well-established animal model. Here we studied whether FOG is reproduced in the non-human primate (NHP) model of PD. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys (Genus Macaca, n=29) were examined for the development of FOG, and the leg movements were recorded with accelerometry. The relationships between developing FOG and the animals' characteristics, the MPTP treatments, and the modeled outcomes were determined. In parkinsonian monkeys FOG developed frequently (48%) manifesting similar characteristics to those seen in PD patients. In addition, FOG episodes in the monkey were accompanied by leg trembling with the typical duration (2-10s) and frequency (~7 Hz). The development of NHP FOG was significantly associated with the severity of parkinsonism, as shown by high motor disability scores (≥ 20) and levodopa-induced dyskinesia scores (p=0.01 and p=0.04, respectively). Differences in demographics and MPTP treatments (doses, treatment duration, etc.) had no influence on NHP FOG occurrence, with the exception of gender that showed FOG predominance in males (p=0.03). The unique features of FOG in PD can be replicated in severely parkinsonian macaques, and this represents the first description of a FOG animal model.

  14. Replicative Intermediates of Human Papillomavirus Type 11 in Laryngeal Papillomas: Site of Replication Initiation and Direction of Replication

    NASA Astrophysics Data System (ADS)

    Auborn, K. J.; Little, R. D.; Platt, T. H. K.; Vaccariello, M. A.; Schildkraut, C. L.

    1994-07-01

    We have examined the structures of replication intermediates from the human papillomavirus type 11 genome in DNA extracted from papilloma lesions (laryngeal papillomas). The sites of replication initiation and termination utilized in vivo were mapped by using neutral/neutral and neutral/alkaline two-dimensional agarose gel electrophoresis methods. Initiation of replication was detected in or very close to the upstream regulatory region (URR; the noncoding, regulatory sequences upstream of the open reading frames in the papillomavirus genome). We also show that replication forks proceed bidirectionally from the origin and converge 180circ opposite the URR. These results demonstrate the feasibility of analysis of replication of viral genomes directly from infected tissue.

  15. Replication and Control of Circular Bacterial Plasmids

    PubMed Central

    del Solar, Gloria; Giraldo, Rafael; Ruiz-Echevarría, María Jesús; Espinosa, Manuel; Díaz-Orejas, Ramón

    1998-01-01

    An essential feature of bacterial plasmids is their ability to replicate as autonomous genetic elements in a controlled way within the host. Therefore, they can be used to explore the mechanisms involved in DNA replication and to analyze the different strategies that couple DNA replication to other critical events in the cell cycle. In this review, we focus on replication and its control in circular plasmids. Plasmid replication can be conveniently divided into three stages: initiation, elongation, and termination. The inability of DNA polymerases to initiate de novo replication makes necessary the independent generation of a primer. This is solved, in circular plasmids, by two main strategies: (i) opening of the strands followed by RNA priming (theta and strand displacement replication) or (ii) cleavage of one of the DNA strands to generate a 3′-OH end (rolling-circle replication). Initiation is catalyzed most frequently by one or a few plasmid-encoded initiation proteins that recognize plasmid-specific DNA sequences and determine the point from which replication starts (the origin of replication). In some cases, these proteins also participate directly in the generation of the primer. These initiators can also play the role of pilot proteins that guide the assembly of the host replisome at the plasmid origin. Elongation of plasmid replication is carried out basically by DNA polymerase III holoenzyme (and, in some cases, by DNA polymerase I at an early stage), with the participation of other host proteins that form the replisome. Termination of replication has specific requirements and implications for reinitiation, studies of which have started. The initiation stage plays an additional role: it is the stage at which mechanisms controlling replication operate. The objective of this control is to maintain a fixed concentration of plasmid molecules in a growing bacterial population (duplication of the plasmid pool paced with duplication of the bacterial population

  16. Primates as Predictors of Mammal Community Diversity in the Forest Ecosystems of Madagascar

    PubMed Central

    Muldoon, Kathleen M.; Goodman, Steven M.

    2015-01-01

    The geographic distribution of species is the typical metric for identifying priority areas for conservation. Since most biodiversity remains poorly studied, a subset of charismatic species, such as primates, often stand as surrogates for total biodiversity. A central question is therefore, how effectively do primates predict the pooled species richness of other mammalian taxa? We used lemurs as indicator species to predict total non-primate mammal community richness in the forest ecosyst