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molecular characterization of pro-inflammatory cytokines interleukin-1β and interleukin-8 in asian elephant (elephas maximus).interleukin (il)-1β and il-8 are pro-inflammatory cytokines produced primarily by monocytes and macrophages in response to a variety of microbial and nonmicrobial agents. as yet, no molecular data have been reported for il-1β and il-8 of the asian elephant. in the present study, we have cloned and sequenced the cdna encoding il-1β and il-8 of the asian elephant. the open reading frame (orf) of asian elephant il-1β is 789 bp in length, encoded a propeptide of 263 amino acid polypeptide. the predi ...201626849252
how chimpanzees integrate sensory information to select figs.figs are keystone resources that sustain chimpanzees when preferred fruits are scarce. many figs retain a green(ish) colour throughout development, a pattern that causes chimpanzees to evaluate edibility on the basis of achromatic accessory cues. such behaviour is conspicuous because it entails a succession of discrete sensory assessments, including the deliberate palpation of individual figs, a task that requires advanced visuomotor control. these actions are strongly suggestive of domain-speci ...201627274803
pre-columbian monkey tools.stone tools reveal worldwide innovations in human behaviour over the past three million years [1]. however, the only archaeological report of pre-modern non-human animal tool use comes from three western chimpanzee (pan troglodytes verus) sites in côte d'ivoire, aged between 4.3 and 1.3 thousand years ago (kya) [2]. this anthropocentrism limits our comparative insight into the emergence and development of technology, weakening our evolutionary models [3]. here, we apply archaeological techniques ...201627404235
the stable isotope ecology of pan in uganda and beyond.stable isotope analysis has long been used to study the dietary ecology of living and fossil primates, and there has been increasing interest in using stable isotopes to study primate habitat use and anthropogenic impacts on non-human primates. here, we examine the stable carbon and nitrogen isotope compositions of chimpanzees (pan troglodytes) from seven communities in uganda across a continuum of habitat structure (closed to more open) and access to anthropogenic resources (no reliance to heav ...201627188271
complex processing of prickly pear cactus (opuntia sp.) by free-ranging long-tailed macaques: preliminary analysis for hierarchical organisation.complex food-processing techniques by gorillas, chimpanzees, and orangutans have allowed comparisons of complex hierarchical cognition between great apes and humans. here, we analyse preliminary observations of free-ranging long-tailed macaques (macaca fascicularis) (n = 3) in thailand processing opuntia sp. cactus fruits. from our observations, we suggest that there is potential to extend the analyses of hierarchical cognition to old world monkeys. we found that the macaques used six behavioura ...201626921023
ravens attribute visual access to unseen competitors.recent studies purported to demonstrate that chimpanzees, monkeys and corvids possess a basic theory of mind, the ability to attribute mental states like seeing to others. however, these studies remain controversial because they share a common confound: the conspecific's line of gaze, which could serve as an associative cue. here, we show that ravens corvus corax take into account the visual access of others, even when they cannot see a conspecific. specifically, we find that ravens guard their ...201626835849
territorial and land-use rights perspectives on human-chimpanzee-elephant coexistence in west africa (guinea, guinea-bissau, senegal, nineteenth to twenty-first centuries).the first part of this article compares the distribution of chimpanzee and elephant populations in reaction to human territorial dynamics of west african trade in parts of nineteenth century guinea, guinea-bissau and senegal. it answers for this specific region the question of whether present-day situations of close chimpanzee-human spatial proximity are stable or only temporary phenomena in long-term processes of environmental change, and shows that conservation policies centred on either of th ...201627038218
primary bone microanatomy records developmental aspects of life history in catarrhine primates.a central challenge in human origins research is to understand how evolution has shaped modern human life history. as fossilized remains of our ancestors provide the only direct evidence for life history evolution, efforts to reconstruct life history in paleontological contexts have focused on hard tissues, particularly on dental development. however, among investigators of other vertebrate groups, there is a long tradition of examining primary bone microstructure to decipher growth rates and ma ...201626989017
the fecal virome of south and central american children with diarrhea includes small circular dna viral genomes of unknown origin.viral metagenomics of feces collected from 58 peruvian children with unexplained diarrhea revealed several small circular ssdna genomes. two genomes related to sequences previously reported in feces from chimpanzees and other mammals and recently named smacoviruses were characterized and then detected by pcr in 1.7 % (1/58) and 19 % (11/58) of diarrheal samples, respectively. another three genomes from a distinct small circular ssdna viral group provisionally called pecoviruses encoded cap and r ...201626780893
do domestic dogs (canis lupus familiaris) perceive the delboeuf illusion?in the last decade, visual illusions have been repeatedly used as a tool to compare visual perception among species. several studies have investigated whether non-human primates perceive visual illusions in a human-like fashion, but little attention has been paid to other mammals, and sensitivity to visual illusions has been never investigated in the dog. here, we studied whether domestic dogs perceive the delboeuf illusion. in human and non-human primates, this illusion creates a misperception ...201627999956
exploring the evolutionary origins of overimitation: a comparison across domesticated and non-domesticated canids.when learning from others, human children tend to faithfully copy - or 'overimitate' - the actions of a demonstrator, even when these actions are irrelevant for solving the task at hand. we investigate whether domesticated dogs (canis familiaris) and dingoes (canis dingo) share this tendency to overimitate in three experiments. in experiment 1, dogs and dingoes had the opportunity to solve a puzzle after watching an ostensive demonstrator who used both a relevant action and an irrelevant action. ...201627659592
mammals consumed by bonobos (pan paniscus): new data from the iyondji forest, tshuapa, democratic republic of the congo.findings of regional variations in the behavioral patterns of non-human primates have led to the vigorous study of animal traditions (or culture), which contribute to a biological understanding of diversity in human cultures. although our knowledge of behavioral variations of the bonobo (pan paniscus) is limited compared with its sister species, the chimpanzee (p. troglodytes), variations in the prey of this species have been reported across study sites. this study describes evidence of mammals ...201626968409
accuracy of human and veterinary point-of-care glucometers for use in rhesus macaques (macaca mulatta), sooty mangabeys (cercocebus atys), and chimpanzees (pan troglodytes).handheld, point-of-care glucometers are commonly used in nhp for clinical and research purposes, but whether these devices are appropriate for use in nhp is unknown. other animal studies indicate that glucometers should be species-specific, given differences in glucose distribution between rbc and plasma; in addition, hct and sampling site (venous compared with capillary) influence glucometer readings. therefore, we compared the accuracy of 2 human and 2 veterinary glucometers at various hct ran ...201627177571
functional analysis of the upstream regulatory region of chicken mir-17-92 cluster.mir-17-92 cluster plays important roles in cell proliferation, differentiation, apoptosis, animal development and tumorigenesis. the transcriptional regulation of mir-17-92 cluster has been extensively studied in mammals, but not in birds. to date, avian mir-17-92 cluster genomic structure has not been fully determined. the promoter location and sequence of mir-17-92 cluster have not been determined, due to the existence of a genomic gap sequence upstream of mir-17-92 cluster in all the birds wh ...201627531611
mutation/snp analysis in ef-hand calcium binding domain of mitochondrial ca[formula: see text] uptake 1 gene in bipolar disorder patients.calcium signaling is important for synaptic plasticity, generation of brain rhythms, regulating neuronal excitability, data processing and cognition. impairment in calcium homeostasis contributed to the development of psychiatric disorders such as bipolar disorder (bp). mcu is the most important calcium transporter in mitochondria inner membrane responsible for influx of ca[formula: see text]. micu1 is linked with mcu and has two canonical ef hands that are vital for its activity and regulates m ...201627297032
evaluation of oasis qsar models using toxcast™ in vitro estrogen and androgen receptor binding data and application in an integrated endocrine screening approach.integrative testing strategies (itss) for potential endocrine activity can use tiered in silico and in vitro models. each component of an its should be thoroughly assessed.201627152837
next generation sequencing (ngs) database for tandem repeats with multiple pattern 2°-shaft multicore string matching.next generation sequencing (ngs) technologies have been rapidly applied in biomedical and biological research in recent years. to provide the comprehensive ngs resource for the research, in this paper , we have considered 10 loci/codi/repeats taga, tcat, gaat, agat, agaa, gata, tatc, cttt, tctg and tcta. then we developed the ngs tandem repeat database (tandemrepeatdb) for all the chromosomes of homo sapiens, callithrix jacchus, chlorocebus sabaeus, gorilla gorilla, macaca fascicularis, macaca m ...201626981434
a longitudinal analysis of the effects of age on the blood plasma metabolome in the common marmoset, callithrix jacchus.primates tend to be long-lived for their size with humans being the longest lived of all primates. there are compelling reasons to understand the underlying age-related processes that shape human lifespan. but the very fact of our long lifespan that makes it so compelling, also makes it especially difficult to study. thus, in studies of aging, researchers have turned to non-human primate models, including chimpanzees, baboons, and rhesus macaques. more recently, the common marmoset, callithrix j ...201626805607
female and male life tables for seven wild primate species.we provide male and female census count data, age-specific survivorship, and female age-specific fertility estimates for populations of seven wild primates that have been continuously monitored for at least 29 years: sifaka (propithecus verreauxi) in madagascar; muriqui (brachyteles hypoxanthus) in brazil; capuchin (cebus capucinus) in costa rica; baboon (papio cynocephalus) and blue monkey (cercopithecus mitis) in kenya; chimpanzee (pan troglodytes) in tanzania; and gorilla (gorilla beringei) i ...201626928014
blood transmission studies of prion infectivity in the squirrel monkey (saimiri sciureus): the baxter study.four secondary transmissions of variant creutzfeldt-jakob disease (vcjd) infectivity have been associated with the transfusion of nonleukoreduced red blood cells collected from vcjd patients during the asymptomatic phase of the disease. establishing efficient experimental models for assessing the risk of future transmissions of vcjd infectivity via blood transfusion is of paramount importance in view of a study of archived appendix samples in which the prevalence of asymptomatic vcjd infection i ...201626594017
beyond primates: research protections and animal moral value.should monkeys be used in painful and often deadly infectious disease research that may save many human lives? this is the challenging question that anne barnhill, steven joffe, and franklin g. miller take on in their carefully argued and compelling article "the ethics of infection challenges in primates." the authors offer a nuanced and even-handed position that takes philosophical worries about nonhuman primate moral status seriously and still appreciates the very real value of such research f ...201627417867
complete genome sequence of streptococcus troglodytae tku31 isolated from the oral cavity of a chimpanzee (pan troglodytes).streptococcus troglodytae tku31 was isolated from the oral cavity of a chimpanzee (pan troglodytes) and was found to be the most closely related species of the mutans group streptococci to streptococcus mutans. the complete sequence of tku31 genome consists of a single circular chromosome that is 2,097,874 base pairs long and has a g + c content of 37.18%. it possesses 2082 coding sequences (cdss), 65 trnas and five rrna operons (15 rrnas). two clustered regularly interspaced short palindromic r ...201627921343
strongyloides infections of humans and great apes in dzanga-sangha protected areas, central african republic and in degraded forest fragments in bulindi, uganda.dna sequence analysis was carried out on strongyloides spp. larvae obtained from fecal samples of local humans, a wild western lowland gorilla (gorilla gorilla gorilla) and a central chimpanzee (pan troglodytes troglodytes) inhabiting dzanga-sangha protected areas (dspa), central african republic, and eastern chimpanzees (pan troglodytes schweinfurthii) living in degraded forest fragments on farmland in bulindi, uganda. from humans, both strongyloides fuelleborni and strongyloides stercoralis we ...201627180094
morbid attraction to leopard urine in toxoplasma-infected chimpanzees.parasites are sometimes capable of inducing phenotypic changes in their hosts to improve transmission [1]. toxoplasma gondii, a protozoan that infects a broad range of warm-blooded species, is one example that supports the so-called 'parasite manipulation hypothesis': it induces modifications in rodents' olfactory preferences, converting an innate aversion for cat odor into attraction and probably favoring trophic transmission to feline species, its only definitive hosts [2]. in humans, t. gondi ...201626859275
schistosoma mansoni in gabon: emerging or ignored?schistosomiasis affects millions of people across africa. we detected eggs of schistosoma mansoni in western lowland gorilla and central chimpanzee fecal samples in loango national park, gabon. we analyzed nuclear and mitochondrial dna, namely internal transcribed spacer and cytochrome c oxidase subunit 1 fragments, and the resulting maximum likelihood phylogenetic analyses and haplotype network of the its and coi, respectively, showed that the samples from gorillas and chimpanzees clustered cle ...201627503513
socioecological correlates of clinical signs in two communities of wild chimpanzees (pan troglodytes) at gombe national park, tanzania.disease and other health hazards pose serious threats to the persistence of wild ape populations. the total chimpanzee population at gombe national park, tanzania, has declined from an estimated 120 to 150 individuals in the 1960's to around 100 individuals by the end of 2013, with death associated with observable signs of disease as the leading cause of mortality. in 2004, we began a non-invasive health-monitoring program in the two habituated communities in the park (kasekela and mitumba) with ...201627182786
safety, immunogenicity and efficacy of prime-boost vaccination with chad63 and mva encoding me-trap against plasmodium falciparum infection in adults in senegal.malaria transmission is in decline in some parts of africa, partly due to the scaling up of control measures. if the goal of elimination is to be achieved, additional control measures including an effective and durable vaccine will be required. studies utilising the prime-boost approach to deliver viral vectors encoding the pre-erythrocytic antigen me-trap (multiple epitope thrombospondin-related adhesion protein) have shown promising safety, immunogenicity and efficacy in sporozoite challenge s ...201627978537
baculovirus-expressed plasmodium reichenowi eba-140 merozoite ligand is host specific.plasmodium reichenowi, an ape malaria parasite is morphologically identical and genetically similar to plasmodium falciparum, infects chimpanzees but not humans. genomic studies revealed that all primate malaria parasites belong to laverania subgenus. laverania parasites exhibit strict host specificity, but the molecular mechanisms underlying these host restrictions remain unexplained. plasmodium merozoites express multiple binding ligands that recognize specific receptors on erythrocytes, inclu ...201627443851
why are nigeria-cameroon chimpanzees (pan troglodytes ellioti) free of sivcpz infection?simian immunodeficiency virus (siv) naturally infects two subspecies of chimpanzee: pan troglodytes troglodytes from central africa (sivcpzptt) and p. t. schweinfurtii from east africa (sivcpzpts), but is absent in p. t. verus from west africa and appears to be absent in p. t. ellioti inhabiting nigeria and western cameroon. one explanation for this pattern is that p. t. troglodytes and p. t schweinfurthii may have acquired sivcpz after their divergence from p. t. verus and p. t. ellioti. howeve ...201627505066
a new sensitive indicator cell line reveals cross-transactivation of the viral ltr by gorilla and chimpanzee simian foamy viruses.the majority of currently identified simian foamy virus (sfv)-infected cameroonian and gabonese individuals harbor sfv from the gorilla lineage. we constructed an indicator cell line for the quantification of gorilla sfvs, in which the u3 sequence of a gorilla sfv directs the expression of the β-galactosidase protein. the gorilla foamy virus activated β-galactosidase (gfab) cells efficiently quantified two zoonotic primary gorilla isolates and sfvs from three chimpanzee subspecies. primary goril ...201627348053
potency of a thermostabilised chimpanzee adenovirus rift valley fever vaccine in cattle.development of safe and efficacious vaccines whose potency is unaffected by long-term storage at ambient temperature would obviate major vaccine deployment hurdles and limit wastage associated with breaks in the vaccine cold chain. here, we evaluated the immunogenicity of a novel chimpanzee adenovirus vectored rift valley fever vaccine (chadox1-gngc) in cattle, following its thermostabilisation by slow desiccation on glass fiber membranes in the non-reducing sugars trehalose and sucrose. thermos ...201627020712
chimpanzee adenovirus vaccine provides multispecies protection against rift valley fever.rift valley fever virus (rvfv) causes recurrent outbreaks of acute life-threatening human and livestock illness in africa and the arabian peninsula. no licensed vaccines are currently available for humans and those widely used in livestock have major safety concerns. a 'one health' vaccine development approach, in which the same vaccine is co-developed for multiple susceptible species, is an attractive strategy for rvfv. here, we utilized a replication-deficient chimpanzee adenovirus vaccine pla ...201626847478
multigenomic delineation of plasmodium species of the laverania subgenus infecting wild-living chimpanzees and gorillas.plasmodium falciparum, the major cause of malaria morbidity and mortality worldwide, is only distantly related to other human malaria parasites and has thus been placed in a separate subgenus, termed laverania parasites morphologically similar to p. falciparum have been identified in african apes, but only one other laverania species, plasmodium reichenowi from chimpanzees, has been formally described. although recent studies have pointed to the existence of additional laverania species, their p ...201627289102
oesophagostomiasis in non-human primates of gombe national park, tanzania.oesophagostomum sp. is a parasitic nematode that frequently infects wild chimpanzees. although nodular lesions are commonly associated with infection, some wild chimpanzee populations seem to tolerate oesophagostomum nodular lesions while those at gombe and other sites suffer from associated morbidity and mortality. from august 2004 to december 2013, we examined demographic (i.e., age, sex) and individual correlates (i.e., fecal consistency, oesophagostomum egg production) to oesophagostomum-ass ...201627309976
a comparative molecular survey of malaria prevalence among eastern chimpanzee populations in issa valley (tanzania) and kalinzu (uganda).habitat types can affect vector and pathogen distribution and transmission dynamics. the prevalence and genetic diversity of plasmodium spp. in two eastern chimpanzee populations-kalinzu forest reserve, uganda and issa valley, tanzania-inhabiting different habitat types was investigated. as a follow up study the effect of host sex and age on infections patterns in kalinzu forest reserve chimpanzees was determined.201627543045
the host specificity of ape malaria parasites can be broken in confined environments.recent studies have revealed a large diversity of plasmodium spp. among african great apes. some of these species are related to plasmodium falciparum, the most virulent agent of human malaria (subgenus laverania), and others to plasmodium ovale, plasmodium malariae and plasmodium vivax (subgenus plasmodium), three other human malaria agents. laverania parasites exhibit strict host specificity in their natural environment. plasmodium reichenowi, plasmodium billcollinsi, plasmodium billbrayi and ...201627486075
noninvasive tuberculosis screening in free-living primate populations in gombe national park, tanzania.recent advances in noninvasive detection methods for mycobacterial infection in primates create new opportunities for exploring the epidemiology of tuberculosis in free-living species. chimpanzees (pan troglodytes schweinfurthii) and baboons (papio anubis) in gombe national park, tanzania, were screened for infection with pathogens of the mycobacterium tuberculosis complex using fecal is6110 pcr; none was positive. this study demonstrates the feasibility of large-scale mycobacterial screening in ...201626419483
use of chad3-ebo-z ebola virus vaccine in malian and us adults, and boosting of malian adults with mva-bn-filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial.the 2014 west african zaire ebola virus epidemic prompted worldwide partners to accelerate clinical development of replication-defective chimpanzee adenovirus 3 vector vaccine expressing zaire ebola virus glycoprotein (chad3-ebo-z). we aimed to investigate the safety, tolerability, and immunogenicity of chad3-ebo-z in malian and us adults, and assess the effect of boosting of malians with modified vaccinia ankara expressing zaire ebola virus glycoprotein and other filovirus antigens (mva-bn-filo ...201626546548
t cell interleukin-15 surface expression in chimpanzees infected with human immunodeficiency virus.interleukin-15 (il-15) contributes to natural killer cell development and immune regulation. however, il-15 and interferon-gamma (ifn-γ) production are significantly reduced during progression to aids. we have previously reported that hiv infected chimpanzees (pan troglodytes) express cd3-cd8+ ifn-γ+ natural killer (nk) cells with an inverse correlation to plasma hiv viral load. to expand on our initial study, we examined a larger population of hiv infected chimpanzees (n=10). whole blood flow c ...201624565973
beyond the cut hunter: a historical epidemiology of hiv beginnings in central africa.in the absence of direct evidence, an imagined "cut hunter" stands in for the index patient of pandemic hiv/aids. during the early years of colonial rule, this explanation goes, a hunter was cut or injured from hunting or butchering a chimpanzee infected with simian immunodeficiency virus, resulting in the first sustained human infection with the virus that would emerge as hiv-1m. we argue here that the "cut hunter" relies on a historical misunderstanding and ecological oversimplification of hum ...201627718030
effect of hiv-1 envelope cytoplasmic tail on adenovirus primed virus encoded virus-like particle immunizations.the low number of envelope (env) spikes presented on native hiv-1 particles is a major impediment for hiv-1 prophylactic vaccine development. we designed virus-like particle encoding adenoviral vectors utilizing sivmac239 gag as an anchor for full length and truncated hiv-1 m consensus env. truncated env overexpressed vrc01 and 17b binding antigen on the surface of transduced cells while the full length env vaccine presented more and similar amounts of antigen binding to the trimer conformation ...201627633665
a truncated nef peptide from sivcpz inhibits the production of hiv-1 infectious progeny.nef proteins from all primate lentiviruses, including the simian immunodeficiency virus of chimpanzees (sivcpz), increase viral progeny infectivity. however, the function of nef involved with the increase in viral infectivity is still not completely understood. nonetheless, until now, studies investigating the functions of nef from sivcpz have been conducted in the context of the hiv-1 proviruses. in an attempt to investigate the role played by nef during the replication cycle of an sivcpz, a ne ...201627399760
novel conserved-region t-cell mosaic vaccine with high global hiv-1 coverage is recognized by protective responses in untreated infection.an effective human immunodeficiency virus type 1 (hiv-1) vaccine is the best solution for halting the acquired immune deficiency syndrome epidemic. here, we describe the design and preclinical immunogenicity of t-cell vaccine expressing novel immunogens thivconsvx, vectored by dna, simian (chimpanzee) adenovirus, and poxvirus modified vaccinia virus ankara (mva), a combination highly immunogenic in humans. the thivconsvx immunogens combine the three leading strategies for elicitation of effectiv ...201626743582
non-human primate schlafen11 inhibits production of both host and viral proteins.schlafen11 (encoded by the slfn11 gene) has been shown to inhibit the accumulation of hiv-1 proteins. we show that the slfn11 gene is under positive selection in simian primates and is species-specific in its activity against hiv-1. the activity of human schlafen11 is relatively weak compared to that of some other primate versions of this protein, with the versions encoded by chimpanzee, orangutan, gibbon, and marmoset being particularly potent inhibitors of hiv-1 protein production. interesting ...201628027315
ion channel activity of vpu proteins is conserved throughout evolution of hiv-1 and siv.the human immunodeficiency virus type 1 (hiv-1) protein vpu is encoded exclusively by hiv-1 and related simian immunodeficiency viruses (sivs). the transmembrane domain of the protein has dual functions: it counteracts the human restriction factor tetherin and forms a cation channel. since these two functions are causally unrelated it remains unclear whether the channel activity has any relevance for viral release and replication. here we examine structure and function correlates of different vp ...201627916968
viral metagenomics of fecal samples from non-human primates revealed human astrovirus in a chimpanzee, china.human astroviruses (hastvs) are commonly identified worldwide as important aetiological agents of acute gastroenteritis in all age groups. more and more evidences challenged the paradigm that astv infections are species-specific. yet to date, astvs associated with human infections have not been detected in any animal hosts.201627826361
recapitulating cross-species transmission of simian immunodeficiency virus sivcpz to humans by using humanized blt mice.the origins of human immunodeficiency virus type 1 (hiv-1) have been widely accepted to be the consequences of simian immunodeficiency viruses from wild chimpanzees (sivcpz) crossing over to humans. however, there has not been any in vivo study of sivcpz infection of humans. also, it remains largely unknown why only specific sivcpz strains have achieved cross-species transmission and what transmission risk might exist for those sivcpz strains that have not been found to infect humans. closing th ...201627307566
hepatitis c virus infection treatment: an era of game changer direct acting antivirals and novel treatment strategies.chronic hepatitis c virus infection and associated liver diseases represent a major health care burden all over the world. the current standard of care, i.e. peginterferon-alfa (peg-ifnα) plus ribavirin (rbv) are associated with frequent and sometimes serious adverse effects and contraindications, which further limit their therapeutic efficacy. the approval of first and second generation hcv protease inhibitors represents a major breakthrough in the development of novel direct acting antivirals ...201625373616
virus-specific cellular response in hepatitis c virus infection.studies performed on chimpanzees and humans have revealed that strong, multispecific and sustained cd4(+) and cd8(+) t cell immune responses is a major determinant of hepatitis c virus (hcv) clearance. however, spontaneous elimination of the virus occurs in minority of infected individuals and cellular response directed against hcv antigens is not persistent in individuals with chronic infection. this review presents characteristics of the hcv-specific t cell response in patients with different ...201626429740
highly-immunogenic virally-vectored t-cell vaccines cannot overcome subversion of the t-cell response by hcv during chronic infection.an effective therapeutic vaccine for the treatment of chronic hepatitis c virus (hcv) infection, as an adjunct to newly developed directly-acting antivirals (daa), or for the prevention of reinfection, would significantly reduce the global burden of disease associated with chronic hcv infection. a recombinant chimpanzee adenoviral (chad3) vector and a modified vaccinia ankara (mva), encoding the non-structural proteins of hcv (nsmut), used in a heterologous prime/boost regimen induced multi-spec ...201627490575
infection of common marmosets with gb virus b chimeric virus encoding the major nonstructural proteins ns2 to ns4a of hepatitis c virus.a lack of immunocompetent-small-primate models has been an obstacle for developing hepatitis c virus (hcv) vaccines and affordable antiviral drugs. in this study, hcv/gb virus b (gbv-b) chimeric virus carrying the major nonstructural proteins ns2 to ns4a (hcv ns2 to -4a chimera) was produced and used to infect common marmosets, since hcv ns2 to ns4a proteins are critical proteases and major antigens. seven marmosets were inoculated intrahepatically with hcv ns2 to -4a chimera rna for primary inf ...201627384651
mouse systems to model hepatitis c virus treatment and associated resistance.while addition of the first-approved protease inhibitors (pis), telaprevir and boceprevir, to pegylated interferon (peg-ifn) and ribavirin (rbv) combination therapy significantly increased sustained virologic response (svr) rates, pi-based triple therapy for the treatment of chronic hepatitis c virus (hcv) infection was prone to the emergence of resistant viral variants. meanwhile, multiple direct acting antiviral agents (daas) targeting either the hcv ns3/4a protease, ns5a or ns5b polymerase ha ...201627338446
cellular immune response to hepatitis-c-virus in subjects without viremia or seroconversion: is it important?hepatitis c virus (hcv) causes chronic infection and represents a global health burden. to date, there is no licensed vaccine for hcv. the high viral replication rate and the existence of several hcv genotypes and quasispecies hamper the development of an effective universal vaccine. in this regard, the current hcv vaccine candidates show genotype-specific protection or narrow cross reactivity against other genotypes. importantly, hcv spontaneous clearance occurs in 15-50 % of infected subjects, ...201627186234
spontaneous and natural cytotoxicity receptor-mediated cytotoxicity are effector functions of distinct natural killer subsets in hepatitis c virus-infected chimpanzees.in humans, cd16 and cd56 are used to identify functionally distinct natural killer (nk) subsets. due to ubiquitous cd56 expression, this marker cannot be used to distinguish between nk cell subsets in chimpanzees. therefore, functional analysis of distinct nk subsets during hepatitis c virus (hcv) infection has never been performed in these animals. in the present study an alternative strategy was used to identify four distinct nk subsets on the basis of the expression of cd16 and cd94. the expr ...201626850369
persistent hepatitis c viral replication despite priming of functional cd8+ t cells by combined therapy with a vaccine and a direct-acting antiviral.exhaustion of antiviral cd8(+) t cells contributes to persistence of hepatitis c viral (hcv) infection. this immune response has proved difficult to restore by therapeutic vaccination, even when hcv replication is suppressed using antiviral regimens containing type i interferon. because immunomodulatory effects of type i interferon may be a factor in poor t-cell priming, we undertook therapeutic vaccination in two chronically infected chimpanzees during treatment with a direct-acting antiviral ( ...201626513111
role of microbial translocation in soluble cd14 up-regulation in hiv-, but not in hcv-, infected chimpanzees.during human immunodeficiency virus (hiv) infection, soluble cd14 (scd14) is up-regulated as a consequence of pathological disruption of the gut epithelial barrier, and subsequent increased microbial translocation. also in hepatitis c virus (hcv)-infected patients with advanced liver fibrosis, increased levels of scd14 have been reported. since the liver plays an important role in clearance of translocated bacterial products, hepatic fibrosis may negatively affect clearance and thus contribute t ...201627534537
pauci-immune glomerulonephritis in a captive chimpanzee (pan troglodytes), and a review of spontaneous cases in animals.crescentic glomeruli are the hallmark finding in rapidly progressive glomerulonephritis (rpgn) and are characterized by disruption and proliferation of the glomerular capsule and an influx of cells into bowman's space. pauci-immune-type rpgn is identified by a lack of immunoglobulins and immune complexes in the glomerular basement membrane.201627506330
expanding the host range of hepatitis c virus through viral adaptation.hepatitis c virus (hcv) species tropism is incompletely understood. we have previously shown that at the level of entry, human cd81 and occludin (ocln) comprise the minimal set of human factors needed for viral uptake into murine cells. as an alternative approach to genetic humanization, species barriers can be overcome by adapting hcv to use the murine orthologues of these entry factors. we previously generated a murine tropic hcv (mthcv or jc1/mcd81) strain harboring three mutations within the ...201627834208
chimpanzee adenovirus vector-based avian influenza vaccine completely protects mice against lethal challenge of h5n1.highly pathogenic avian h5n1 viruses may give rise to the next influenza pandemic due to their reassortment and mutation of the genome. vaccine against this virus is important for coping with its potential threat. chimpanzee adenovirus (ad) vectors are a novel type of vaccine vectors that share the advantages of human serotype ad vectors but without being affected by pre-existing human neutralizing antibody to the vaccine vector. based on a replication-deficient chimpanzee ad vector, adc7, we ge ...201627576071
hemagglutinin-targeting artificial micrornas expressed by adenovirus protect mice from different clades of h5n1 infection.influenza virus (iv) is a continuously evolving virus that widely spreads in humans and contributes to substantial morbidity and mortality. re-emergence of human infection with avian influenza virus h5n1 poses extra challenge to iv control. artificial microrna (amirna)-mediated rna interference has become a powerful antiviral approach due to its high specificity and rapid effect. here, we designed several amirnas targeting the hemagglutinin gene of h5n1, a major determinant of pathogenicity. exp ...201627093169
t- and b-cell responses to multivalent prime-boost dna and viral vectored vaccine combinations against hepatitis c virus in non-human primates.immune responses against multiple epitopes are required for the prevention of hepatitis c virus (hcv) infection, and the progression to phase i trials of candidates may be guided by comparative immunogenicity studies in non-human primates. four vectors, dna, sfv, human serotype 5 adenovirus (huad5) and modified vaccinia ankara (mva) poxvirus, all expressing hepatitis c virus core, e1, e2 and ns3, were combined in three prime-boost regimen, and their ability to elicit immune responses against hcv ...201627416077
transmission of ebola virus disease: an overview.ebola is a viral illness of which the initial symptoms can include a sudden fever, intense weakness, muscle pain and a sore throat, according to the world health organization (who). airborne transmission of ebola virus has been hypothesized but not demonstrated in humans. ebola is not spread through the air or by water, or in general, by food. however, in africa, ebola may be spread as a result of handling bushmeat (wild animals hunted for food) and contact with infected bats. the disease infect ...201625960093
a monovalent chimpanzee adenovirus ebola vaccine boosted with mva.the west african outbreak of ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. the development of an effective ebola vaccine is a priority for control of a future outbreak.201625629663
molecular identification of entamoeba species in savanna woodland chimpanzees (pan troglodytes schweinfurthii).to address the molecular diversity and occurrence of pathogenic species of the genus entamoeba spp. in wild non-human primates (nhp) we conducted molecular-phylogenetic analyses on entamoeba from wild chimpanzees living in the issa valley, tanzania. we compared the sensitivity of molecular [using a genus-specific polymerase chain reaction (pcr)] and coproscopic detection (merthiolate-iodine-formaldehyde concentration) of entamoeba spp. we identified entamoeba spp. in 72 chimpanzee fecal samples ...201626935395
prospective population management for hepatitis b in the chimpanzee (pan troglodytes) ssp® population.hepatitis b virus causes horizontally transmitted infectious hepatopathy of primates and may progress to hepatocellular carcinoma. historically, a small number of chimpanzees ( pan troglodytes ) living in accredited north american zoos have been confirmed with positive hepatitis b serology consistent with exposure. however, the overall status for this population and the interpretation of these individual test results have not been established previously. the current u.s. zoo-housed population (n ...201627691953
activating the innate immune response to counter chronic hepatitis b virus infection.chronic infection with hepatitis b virus (hbv) is endemic to several populous parts of the world, where resulting complicating cirrhosis and hepatocellular carcinoma occur commonly. licensed drugs to treat the infection have limited curative efficacy, and development of therapies that eliminate all replication intermediates of hbv is a priority. areas covered: the recent demonstration that the activation of the innate immune response may eradicate hbv from infected hepatocytes has a promising th ...201627603796
experimental in vitro and in vivo models for the study of human hepatitis b virus infection.chronic infection with the hepatitis b virus (hbv) affects an estimate of 240 million people worldwide despite the availability of a preventive vaccine. medication to repress viral replication is available but a cure is rarely achieved. the narrow species and tissue tropism of the virus and the lack of reliable in vitro models and laboratory animals susceptible to hbv infection, have limited research progress in the past. as a result, several aspects of the hbv life cycle as well as the network ...201627084033
in vivo models of hepatitis b and c virus infection.globally, more than 500 million individuals are chronically infected with hepatitis b (hbv), delta (hdv), and/or c (hcv) viruses, which can result in severe liver disease. mechanistic studies of viral persistence and pathogenesis have been hampered by the scarcity of animal models. the limited species and cellular host range of hbv, hdv, and hcv, which robustly infect only humans and chimpanzees, have posed challenges for creating such animal models. in this review, we will discuss the barriers ...201627009462
interferon-γ and tumor necrosis factor-α produced by t cells reduce the hbv persistence form, cccdna, without cytolysis.viral clearance involves immune cell cytolysis of infected cells. however, studies of hepatitis b virus (hbv) infection in chimpanzees have indicated that cytokines released by t cells also can promote viral clearance via noncytolytic processes. we investigated the noncytolytic mechanisms by which t cells eliminate hbv from infected hepatocytes.201626416327
cd4+ t cells are not required for suppression of hepatitis b virus replication in the liver of vaccinated chimpanzees.humans vaccinated with hepatitis b virus (hbv) surface antigen (hbsag) sometimes develop humoral and cellular immunity to hbv proteins such as core and polymerase that are not vaccine components, providing indirect evidence that vaccine-induced immunity is not sterilizing. we previously described cd4(+) t-cell immunity against hbsag and polymerase in chimpanzees after vaccination and hbv challenge. here, vaccinated chimpanzees with protective levels of anti-hbsag antibodies were rechallenged wit ...201626324781
ebola virus vaccines: where do we stand?the recent outbreak of ebola virus disease in west africa has led to more than 11,000 deaths, with a peak in mortality from august through december of 2014. a meeting convened by the world health organization (who) in september 2014, concluded that an urgent unmet need exists for efficacy and safety testing of the ebola virus vaccine candidates and that clinical trials should be expedited. these vaccines could be used both in an outbreak setting and to provide long-term protection in populations ...201627910805
a little cooperation helps murine cytomegalovirus (mcmv) go a long way: mcmv co-infection rescues a chemokine salivary gland defect.cytomegaloviruses (cmvs) produce chemokines (vcxcls) that have both sequence and functional homology to host chemokines. assessment of vcxcl-1's role in cmv infection is limited to in vitro and in silico analysis due to cmvs species specificity. in this study, we used the murine cmv (mcmv) mouse model to evaluate the function of vcxcl-1 in vivo. recombinant mcmvs expressing chimpanzee cmv vcxcl-1 (vcxcl-1ccmv) or host chemokine, mcxcl1, underwent primary dissemination to the popliteal lymph node ...201627638684
complete genome sequence of a novel chimpanzee polyomavirus from a western common chimpanzee.we report here the full-length genome sequence of a novel chimpanzee polyomavirus. viral sequences were recovered from colon, bladder, and ureter tissue from a western common chimpanzee. the virus is genetically closely related to the human bk polyomavirus.201626798086
safety and immunogenicity of chad63 and mva me-trap in west african children and infants.malaria remains a significant global health burden and a vaccine would make a substantial contribution to malaria control. chimpanzee adenovirus 63 modified vaccinia ankara multiple epitope thrombospondin adhesion protein (me-trap) and vaccination has shown significant efficacy against malaria sporozoite challenge in malaria-naive european volunteers and against malaria infection in kenyan adults. infants are the target age group for malaria vaccination; however, no studies have yet assessed t-c ...201627109630
safety and high level efficacy of the combination malaria vaccine regimen of rts,s/as01b with chimpanzee adenovirus 63 and modified vaccinia ankara vectored vaccines expressing me-trap.the need for a highly efficacious vaccine against plasmodium falciparum remains pressing. in this controlled human malaria infection (chmi) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (rts,s/as01b) and the other inducing potent t-cell responses to thrombospondin-related adhesion protein (trap) by using a viral vector.201627307573
genomes of cryptic chimpanzee plasmodium species reveal key evolutionary events leading to human malaria.african apes harbour at least six plasmodium species of the subgenus laverania, one of which gave rise to human plasmodium falciparum. here we use a selective amplification strategy to sequence the genome of chimpanzee parasites classified as plasmodium reichenowi and plasmodium gaboni based on the subgenomic fragments. genome-wide analyses show that these parasites indeed represent distinct species, with no evidence of cross-species mating. both p. reichenowi and p. gaboni are 10-fold more dive ...201627002652
l1base 2: more retrotransposition-active line-1s, more mammalian genomes.line-1 (l1) insertions comprise as much as 17% of the human genome sequence, and similar proportions have been recorded for other mammalian species. given the established role of l1 retrotransposons in shaping mammalian genomes, it becomes an important task to track and annotate the sources of this activity: full length elements, able to encode the cis and trans acting components of the retrotransposition machinery. the l1base database (http://l1base.charite.de) contains annotated full-length se ...201627924012
zinc finger domain of the prdm9 gene on chromosome 1 exhibits high diversity in ruminants but its paralog prdm7 contains multiple disruptive mutations.prdm9 is the sole hybrid sterility gene identified so far in vertebrates. prdm9 gene encodes a protein with an immensely variable zinc-finger (zf) domain that determines the site of meiotic recombination hotspots genome-wide. in this study, the terminal zf domain of prdm9 on bovine chromosome 1 and its paralog on chromosome 22 were characterized in 225 samples from five ruminant species (cattle, yak, mithun, sheep and goat). we found extraordinary variation in the number of prdm9 zinc fingers (6 ...201627203728
the occurrence of postconflict skills in captive immature chimpanzees (pan troglodytes).conflict management strategies can reduce costs of aggressive competition in group-living animals. postconflict behaviors such as reconciliation and third-party postconflict affiliation are widely accepted as social skills in primates and have been demonstrated in many species. although immature primates possess a repertoire of species-specific behaviors, it is thought that they gradually develop appropriate social skills throughout prolonged juvenility to establish and maintain complex social r ...201627257315
origins and evolution of hepatitis b virus and hepatitis d virus.members of the family hepadnaviridae fall into two subgroups: mammalian and avian. the detection of endogenous avian hepadnavirus dna integrated into the genomes of zebra finches has revealed a deep evolutionary origin of hepadnaviruses that was not previously recognized, dating back at least 40 million and possibly >80 million years ago. the nonprimate mammalian members of the hepadnaviridae include the woodchuck hepatitis virus (whv), the ground squirrel hepatitis virus, and arctic squirrel he ...201626729756
bacillus cereus biovar anthracis causing anthrax in sub-saharan africa-chromosomal monophyly and broad geographic distribution.through full genome analyses of four atypical bacillus cereus isolates, designated b. cereus biovar anthracis, we describe a distinct clade within the b. cereus group that presents with anthrax-like disease, carrying virulence plasmids similar to those of classic bacillus anthracis. we have isolated members of this clade from different mammals (wild chimpanzees, gorillas, an elephant and goats) in west and central africa (côte d'ivoire, cameroon, central african republic and democratic republic ...201627607836
schistosomiasis mansoni in the chimpanzee. the natural history of chronic infections after single and multiple exposures. 20164910119
protocultural aspects of chimpanzees' responsiveness to novel objects. 20165031297
peripheral nerve injuries: a comparative study of the anatomical and functional results following primary nerve repair in chimpanzees. 20164967468
modification of the effects of chlorpromazine on behavior in the chimpanzee. 20164823295
ape malaria transmission and potential for ape-to-human transfers in africa.recent studies have highlighted the large diversity of malaria parasites infecting african great apes (subgenus laverania) and their strong host specificity. although the existence of genetic incompatibilities preventing the cross-species transfer may explain host specificity, the existence of vectors with a high preference for a determined host represents another possibility. to test this hypothesis, we undertook a 15-mo-long longitudinal entomological survey in two forest regions of gabon, whe ...201627071123
erythrocytes from ggta1/cmah knockout pigs: implications for xenotransfusion and testing in non-human primates.pig erythrocytes are potentially useful to solve the worldwide shortage of human blood for transfusion. domestic pig erythrocytes, however, express antigens that are bound by human preformed antibodies. advances in genetic engineering have made it possible to rapidly knock out the genes of multiple xenoantigens, namely galactose α1,3 galactose (agal) and n-glycolylneuraminic acid (neu5gc). we have recently targeted the ggta1 and cmah genes with zinc finger endonucleases resulting in double knock ...201624986655
blood cell telomere lengths and shortening rates of chimpanzee and human females.slower rates of aging distinguish humans from our nearest living cousins. chimpanzees rarely survive their forties while large fractions of women are postmenopausal even in high-mortality hunter-gatherer populations. cellular and molecular mechanisms for these somatic aging differences remain to be identified, though telomeres might play a role. to find out, we compared telomere lengths across age-matched samples of female chimpanzees and women.201624633909
hippocampal pruning as a new theory of schizophrenia etiopathogenesis.pruning in neurons has been suggested to be strongly involved in schizophrenia's (skz) etiopathogenesis in recent biological, imaging, and genetic studies. we investigated the impact of protein-coding genes known to be involved in pruning, collected by a systematic literature research, in shaping the risk for skz in a case-control sample of 9,490 subjects (psychiatric genomics consortium). moreover, their modifications through evolution (humans, chimpanzees, and rats) and subcellular localizatio ...201625902861
development, diet and dynamism: longitudinal and cross-sectional predictors of gut microbial communities in wild baboons.gut bacterial communities play essential roles in host biology, but to date we lack information on the forces that shape gut microbiota between hosts and over time in natural populations. understanding these forces in wild primates provides a valuable comparative context that enriches scientific perspectives on human gut microbiota. to this end, we tested predictors of gut microbial composition in a well-studied population of wild baboons. using cross-sectional and longitudinal samples collected ...201625818066
an analysis of bimanual actions in natural feeding of semi-wild chimpanzees.the objective of the current study was to investigate the lateral dominance for a bimanually coordinated natural feeding behavior in semi-wild chimpanzees.201626345277
a neuronal aging pattern unique to humans and common chimpanzees.lipofuscin pigment accumulation is among the most prominent markers of cellular aging in postmitotic cells. the formation of lipofuscin is related to oxidative enzymatic activity and free radical-induced lipid peroxidation. in various mammals such as rat, dog, macaque as well as in cheirogaleid primates, most of the large neurons, such as cerebellar purkinje cells and neocortical pyramidal cells, show heavy lipofuscin accumulation in adulthood. in contrast, a well-known yet poorly studied featur ...201625381006
[the emergence of ebola virus in humans: a long process not yet fully understood].since 1976 ebola virus regularly has caused small deadly outbreaks in central africa, usually controlled in a few months. for the first time, an ebola epidemic of exceptional magnitude dramatically engulfed several countries in west africa since december 2013. major failures of implementing measures to prevent human-to-human transmissions are the main cause of this large-scale ebola outbreak. after about one-week incubation period, the ebola virus disease is characterized by a sudden onset of hi ...201627509685
complete mitochondrial genome of the nigeria-cameroon chimpanzee, pan troglodytes ellioti (primates: hominidae).chimpanzees are especially suited to teach us about ourselves, both in terms of their similarities and differences with human, and such important similarities and differences have also been noted for the incidence and severity of several major human diseases. in the present work, we report the entire mitochondrial genome of the nigeria-cameroon chimpanzee (pan troglodytes ellioti) for the first time. results shows that this mitogenome is 16,559 bp long and consists of 13 protein-coding genes, 22 ...201625350739
raising the bar: the implications of the iom report on the use of chimpanzees in research. 201623138427
[cloning and gene expression of alpha-3/4-fucosyltransferase lewis in the chimpanzee] . 201611000864
the default mode network in chimpanzees (pan troglodytes) is similar to that of humans.the human default mode network (dmn), comprising medial prefrontal cortex, precuneus, posterior cingulate cortex, lateral parietal cortex, and medial temporal cortex, is highly metabolically active at rest but deactivates during most focused cognitive tasks. the dmn and social cognitive networks overlap significantly in humans. we previously demonstrated that chimpanzees (pan troglodytes) show highest resting metabolic brain activity in the cortical midline areas of the human dmn. human dmn is d ...201524046078
factors that drive variation among gut microbial communities.surveys of humans from around the world have revealed differences in gut microbiota composition among geographically separated populations. but because humans from the same regions often share common ancestry as well as dietary and cultural habits, most studies have not been able to differentiate among the effects of heritable factors and external factors on the composition of the gut microbiota. here we discuss how the analysis of gut microbial communities of chimpanzees residing in gombe strea ...201523941900
mating behavior of adolescent male chimpanzees (pan troglodytes) at ngogo, kibale national park, uganda.male mating tactics vary extensively in many primates. some variation occurs because adolescent males often are sexually active but cannot invest heavily in mating effort because of their limited ability to compete directly with adults and because they are still investing in growth; consequently, most of their mating attempts may be surreptitious and/or with females whose fecundity is low. chimpanzees (pan troglodytes) have a complex mating system: most copulations occur between estrous females ...201525344150
the sampling scheme matters: pan troglodytes troglodytes and p. t. schweinfurthii are characterized by clinal genetic variation rather than a strong subspecies break.populations of an organism living in marked geographical or evolutionary isolation from other populations of the same species are often termed subspecies and expected to show some degree of genetic distinctiveness. the common chimpanzee (pan troglodytes) is currently described as four geographically delimited subspecies: the western (p. t. verus), the nigerian-cameroonian (p. t. ellioti), the central (p. t. troglodytes) and the eastern (p. t. schweinfurthii) chimpanzees. although these taxa woul ...201525330245
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