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Reactive mesothelial hyperplasia mimicking mesothelioma in an African green monkey (Chlorocebus aethiops). 非洲绿猴(Chlorocebus aethiops)的反应性间皮瘤增生模拟间皮瘤。
Q2 Agricultural and Biological Sciences Pub Date : 2020-06-15 eCollection Date: 2020-01-01 DOI: 10.5194/pb-7-5-2020
Roland Plesker, Kernt Köhler, Susanne von Gerlach, Klaus Boller, Markus Vogt, Inke S Feder

A spontaneous reactive mesothelial hyperplasia occurred in a female, 15.7-year-old African green monkey (grivet; Chlorocebus aethiops). At necropsy, massive effusions were found in the abdomen, the thorax, and the pericardium. Additionally, multiple small, beige-gray nodules were detected on the serosal surfaces of the abdominal organs. Histopathologically, the mesothelial cells resembled the epithelioid subtype of a mesothelioma, but no infiltrative or invasive growth could be demonstrated. The mesothelial cells on the thoracis, liver, and intestinal serosa were accompanied by chronic serositis. Mesothelial cells expressed cytokeratin, vimentin, calretinin, desmin, Wilms Tumor 1 (WT-1) protein, and epithelial membrane antigen (EMA). Cells were negative for carcinoembryonic antigen (CEA), cluster of differentiation 15 (CD15), and podoplanin. Ultrastructurally, cells revealed a moderate amount of microvilli of medium length, perinuclear tonofilament bundles, and long desmosomes. In fluorescence in situ hybridization (FISH) for the detection of characteristic gene loss (p16; CDKN2A), NF2, and MTAP, no deletions were detected. No asbestos fibers and no presence of Simian virus 40 antigen (SV40) could be demonstrated.

一例自发性反应性间皮增生发生于一只15.7岁的雌性非洲绿猴(grivet;Chlorocebus aethiops)。尸检发现腹部、胸腔和心包膜有大量积液。此外,在腹部脏器的浆膜表面检测到多个小的,浅灰色的结节。组织病理学上,间皮瘤细胞类似于间皮瘤的上皮样亚型,但未见浸润性或侵袭性生长。胸、肝、肠浆膜间皮细胞伴慢性浆膜炎。间皮细胞表达细胞角蛋白、波形蛋白、calretinin、desmin、Wilms Tumor 1 (WT-1)蛋白和上皮膜抗原(EMA)。细胞癌胚抗原(CEA)、分化簇15 (CD15)和podoplanin均阴性。细胞超微结构上可见中等长度的微绒毛、核周张力丝束和较长的桥粒。荧光原位杂交(FISH)检测特征基因丢失(p16;CDKN2A), NF2和MTAP,未检测到缺失。未发现石棉纤维,未发现猿猴病毒40抗原(SV40)。
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引用次数: 1
Group size experiences with enhanced pre- and postnatal development studies in the long-tailed macaque (Macaca fascicularis). 在长尾猕猴(Macaca fascicularis)出生前后发育研究中加强群体大小的经验。
Q2 Agricultural and Biological Sciences Pub Date : 2020-03-11 eCollection Date: 2020-01-01 DOI: 10.5194/pb-7-1-2020
C Marc Luetjens, Antje Fuchs, Ann Baker, Gerhard F Weinbauer

Enhanced pre- and postnatal development (ePPND) studies have become the default developmental toxicity test for biopharmaceuticals if nonhuman primates represent the relevant species. Spontaneous pregnancy losses and infant deaths can be significant in macaques such as long-tailed macaques. The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guideline S6(R1) states that pregnancy outcome can be judged also by the normogram-based variability of reference data according to a publication by Jarvis et al. (2010) defining a study as valid with six to eight live infants in the control group on postnatal day 7 (PND7). Since the release of ICH S6(R1) (2011), ePPND studies for biologics have replaced the former separate embryo-fetal and PPND study types. This work provides a retrospective analysis of pregnancy outcomes from 21 ePPND studies and group sizes of 14-24 animals per group. All studies reached the goal of at least six to eight infants on PND7, with overall losses ranging between 5 % and 45 %. Consistently, a group size of 14-24 maternal animals yielded more than six to eight infants on PND7. Therefore, it is suggested to reduce ePPND study group sizes from 20 to 14, yielding an animal number reduction of approx. 30 %.

如果相关物种为非人灵长类动物,则增强产前和产后发育(ePPND)研究已成为生物制药的默认发育毒性测试方法。猕猴(如长尾猕猴)的自发妊娠损失和婴儿死亡可能很严重。国际人用药品技术要求协调理事会(ICH)准则 S6(R1)规定,根据 Jarvis 等人(2010 年)发表的一篇文章,妊娠结局也可通过参考数据的常模变异性来判断,该文章将一项研究定义为在产后第 7 天(PND7)对照组中有 6 到 8 个活产婴儿为有效。自 ICH S6(R1)(2011 年)发布以来,生物制剂的 ePPND 研究已取代了以前独立的胚胎-胎儿和 PPND 研究类型。本研究对 21 项 ePPND 研究的妊娠结局进行了回顾性分析,每组 14-24 只动物。所有研究都达到了在 PND7 至少产下 6 到 8 个婴儿的目标,总体损失率在 5% 到 45% 之间。一致的是,14-24 头母畜一组在 PND7 出生的婴儿超过了 6 到 8 个。因此,建议将 ePPND 研究组的规模从 20 人减少到 14 人,从而减少约 30% 的动物数量。
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引用次数: 0
Baboon induced pluripotent stem cell generation by piggyBac transposition of reprogramming factors. 通过piggyBac转位重编程因子生成狒狒诱导多能干细胞。
Q2 Agricultural and Biological Sciences Pub Date : 2019-07-29 eCollection Date: 2019-01-01 DOI: 10.5194/pb-6-75-2019
Ignacio Rodriguez-Polo, Michael Stauske, Alexander Becker, Iris Bartels, Ralf Dressel, Rüdiger Behr

Clinical application of regenerative therapies using embryonic or induced pluripotent stem cells is within reach. Progress made during recent years has encouraged researchers to address remaining open questions in order to finally translate experimental cell replacement therapies into application in patients. To achieve this, studies in translationally relevant animal models are required to make the final step to the clinic. In this context, the baboon (Papio anubis) may represent a valuable nonhuman primate (NHP) model to test cell replacement therapies because of its close evolutionary relationship to humans and its large body size. In this study, we describe the reprogramming of adult baboon skin fibroblasts using the piggyBac transposon system. Via transposon-mediated overexpression of six reprogramming factors, we generated five baboon induced pluripotent stem cell (iPSC) lines. The iPSC lines were characterized with respect to alkaline phosphatase activity, pluripotency factor expression analysis, teratoma formation potential, and karyotype. Furthermore, after initial cocultivation with mouse embryonic fibroblasts, we were able to adapt iPSC lines to feeder-free conditions. In conclusion, we established a robust and efficient protocol for iPSC generation from adult baboon fibroblasts.

利用胚胎干细胞或诱导多能干细胞进行再生治疗的临床应用指日可待。近年来取得的进展鼓励研究人员解决尚未解决的问题,以便最终将实验性细胞替代疗法应用于患者。为实现这一目标,需要对转化相关的动物模型进行研究,以迈出临床的最后一步。在这种情况下,狒狒(Papio anubis)可能是测试细胞替代疗法的一种有价值的非人灵长类动物(NHP)模型,因为它与人类的进化关系密切,而且体型庞大。在这项研究中,我们描述了利用piggyBac转座子系统对成年狒狒皮肤成纤维细胞进行重编程的过程。通过转座子介导的六种重编程因子的过表达,我们产生了五个狒狒诱导多能干细胞(iPSC)系。我们从碱性磷酸酶活性、多能因子表达分析、畸胎瘤形成潜能和核型等方面对这些 iPSC 株进行了鉴定。此外,在与小鼠胚胎成纤维细胞进行初始共培养后,我们能够使 iPSC 株系适应无饲养者条件。总之,我们建立了从成年狒狒成纤维细胞生成 iPSC 的稳健而高效的方案。
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引用次数: 0
Effect of ovariectomy on proximal tibia metaphysis and lumbar vertebral body in common marmoset monkeys. 卵巢切除对普通狨猴胫骨近端干骺端和腰椎椎体的影响。
Q2 Agricultural and Biological Sciences Pub Date : 2019-07-12 eCollection Date: 2019-01-01 DOI: 10.5194/pb-6-65-2019
Christina Schlumbohm, Dana Seidlová-Wuttke, Eberhard Fuchs

This study aimed to investigate the effect of estrogen withdrawal on bone tissue in adult female marmoset monkeys. In a 1-year follow-up study we used quantitative computer tomography to measure total bone mineral density (BMD) of the proximal tibia and the second-last lumbar vertebral body (L5/L6) before and 1, 3, 6, and 12 months after ovariectomy. Body mass did not significantly change during the 1-year observation period. However, a significant decline of total BMD after ovariectomy was observed in the proximal tibia but not in L5/L6. In addition, regression analysis showed a significant positive relationship between BMD and body mass in both tibia and L5/L6. The results of our study support the idea that ovariectomized marmoset monkeys may serve as a model to investigate bone loss related to decline of estrogen production.

本研究旨在探讨雌激素停药对成年雌性绒猴骨组织的影响。在一项为期1年的随访研究中,我们使用定量计算机断层扫描测量了卵巢切除术前和卵巢切除术后1、3、6和12个月的胫骨近端和倒数第二腰椎椎体(L5/L6)的总骨密度(BMD)。在1年的观察期内,体重无明显变化。然而,卵巢切除术后,在胫骨近端观察到总骨密度的显著下降,而在L5/L6没有。此外,回归分析显示,骨密度与胫骨和L5/L6的体重均呈显著正相关。我们的研究结果支持这样一种观点,即卵巢切除的狨猴可以作为研究骨质流失与雌激素分泌下降相关的模型。
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引用次数: 0
Active anti-predator behaviour of red titi monkeys (Plecturocebus cupreus). 红山猴(Plecturocebus cupreus)的主动反捕食行为。
Q2 Agricultural and Biological Sciences Pub Date : 2019-06-05 eCollection Date: 2019-01-01 DOI: 10.5194/pb-6-59-2019
Sofya Dolotovskaya, Camilo Flores Amasifuen, Caroline Elisabeth Haas, Fabian Nummert, Eckhard W Heymann

Due to their inconspicuous behaviour and colouration, it has been assumed that titi monkeys' main anti-predator behaviour is passive crypsis and hiding. So far, active predator mobbing has been documented only for black-fronted titi monkeys, Callicebus nigrifrons. Here we report for the first time mobbing behaviour of red titi monkeys, Plecturocebus cupreus (previously Callicebus cupreus), as reaction to an ocelot (Leopardus pardalis) and a Boa constrictor. We also report other active anti-predator behaviours, such as alarm calling and approaching, as reactions to tayras (Eira barbara) and raptors. Our observations provide additional evidence for sex differences in anti-predator behaviour, possibly related to the evolution and maintenance of social monogamy.

由于它们不显眼的行为和颜色,人们一直认为titi猴的主要反捕食行为是被动隐蔽和躲藏。到目前为止,只有黑额山雀(Callicebus nigrifrons)有记录的捕食者的活动。本文首次报道了红山猴Plecturocebus cupreus(以前的calicebus cupreus)对豹猫(豹猫)和蟒蛇的攻击行为。我们还报告了其他主动的反捕食者行为,如报警和接近,作为对泰拉(Eira barbara)和迅猛龙的反应。我们的观察为反捕食者行为的性别差异提供了额外的证据,这可能与社会一夫一妻制的进化和维持有关。
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引用次数: 13
Experimental autoimmune encephalomyelitis in the common marmoset: a translationally relevant model for the cause and course of multiple sclerosis. 普通狨猴的实验性自身免疫性脑脊髓炎:多发性硬化症病因和病程的翻译相关模型
Q2 Agricultural and Biological Sciences Pub Date : 2019-05-10 eCollection Date: 2019-01-01 DOI: 10.5194/pb-6-17-2019
Bert A 't Hart

Aging Western societies are facing an increasing prevalence of chronic autoimmune-mediated inflammatory disorders (AIMIDs) for which treatments that are safe and effective are scarce. One of the main reasons for this situation is the lack of animal models, which accurately replicate clinical and pathological aspects of the human diseases. One important AIMID is the neuroinflammatory disease multiple sclerosis (MS), for which the mouse experimental autoimmune encephalomyelitis (EAE) model has been frequently used in preclinical research. Despite some successes, there is a long list of experimental treatments that have failed to reproduce promising effects observed in murine EAE models when they were tested in the clinic. This frustrating situation indicates a wide validity gap between mouse EAE and MS. This monography describes the development of an EAE model in nonhuman primates, which may help to bridge the gap.

老龄化的西方社会正面临着越来越普遍的慢性自身免疫介导的炎症性疾病(aimid),而安全有效的治疗方法却很少。造成这种情况的主要原因之一是缺乏能够准确复制人类疾病临床和病理方面的动物模型。一个重要的目标是神经炎性疾病多发性硬化(MS),小鼠实验性自身免疫性脑脊髓炎(EAE)模型已被频繁用于临床前研究。尽管取得了一些成功,但有一长串的实验性治疗方法在临床测试时未能重现在小鼠EAE模型中观察到的有希望的效果。这种令人沮丧的情况表明,在小鼠EAE和ms之间存在巨大的有效性差距。本专著描述了非人灵长类动物EAE模型的发展,这可能有助于弥合这一差距。
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引用次数: 10
Is Colobus guereza gallarum a valid endemic Ethiopian taxon? 斑点疣是埃塞俄比亚一个有效的地方性分类群吗?
Q2 Agricultural and Biological Sciences Pub Date : 2019-04-18 eCollection Date: 2019-01-01 DOI: 10.5194/pb-6-7-2019
Dietmar Zinner, Dereje Tesfaye, Nils C Stenseth, Afework Bekele, Aemro Mekonnen, Steve Doeschner, Anagaw Atickem, Christian Roos

Black-and-white colobus (Colobus guereza Rüppell, 1835) are arboreal Old World monkeys inhabiting large parts of the deciduous and evergreen forests of sub-Saharan Africa. Two of the eight subspecies of Colobus guereza are endemic to Ethiopia: C. g. gallarum and C. g. guereza. However, the validity of the Ethiopian taxa is debated and observed morphological differences were attributed to clinal variation within C. g. guereza. To date, no molecular phylogeny of the Ethiopian guerezas is available to facilitate their taxonomic classification. We used mitochondrial DNA markers from 94 samples collected across Ethiopia to reconstruct a phylogeny of respective mitochondrial lineages. In our phylogenetic reconstruction, augmented by orthologous sequence information of non-Ethiopian black-and-white colobus from GenBank, we found two major Ethiopian mitochondrial clades, with one being largely congruent with the distribution of C. g. guereza. The second clade was found only at two locations in the eastern part of the putative range of C. g. gallarum. This second lineage clustered with the lowland form, C. g. occidentalis, from central Africa, whereas the C. g. guereza lineages clustered with C. g. caudatus and C. g. kikuyuensis from Kenya and northern Tanzania. These two guereza lineages diverged around 0.7 million years ago. In addition, mitochondrial sequence information does not support unequivocally a distinction of C. g. caudatus and C. g. kikuyuensis. Our findings indicate a previous biogeographic connection between the ranges of C. g. occidentalis and C. g. gallarum and a possible secondary invasion of Ethiopia by members of the C. g. guereza-C. g. caudatus-C. g. kikuyuensis clade. Given these phylogenetic relationships, our study supports the two-taxa hypothesis, making C. g. gallarum an Ethiopian endemic, and, in combination with the taxon's very restricted range, makes it one of the most endangered subspecies of black-and-white colobus.

黑白疣猴(疣猴guereza r ppell, 1835)是旧大陆的树栖猴,栖息在撒哈拉以南非洲的大部分落叶和常绿森林中。格莱萨疣虫的八个亚种中有两个是埃塞俄比亚特有的:C. g. gallarum和C. g.格莱萨。然而,埃塞俄比亚分类群的有效性存在争议,观察到的形态差异归因于C. g. guereza的临床变异。到目前为止,还没有埃塞俄比亚格莱萨的分子系统发育来促进它们的分类分类。我们使用来自埃塞俄比亚收集的94个样本的线粒体DNA标记来重建各自线粒体谱系的系统发育。在我们的系统发育重建中,利用来自GenBank的非埃塞俄比亚黑白疣体的同源序列信息,我们发现了两个主要的埃塞俄比亚线粒体分支,其中一个与C. g. guereza的分布基本一致。第二个分支只在假定的C. g. gallarum范围东部的两个地方被发现。第二种谱系与来自中非的低地物种C. g. occidentalis聚集在一起,而C. g. guereza谱系与来自肯尼亚和坦桑尼亚北部的C. g. caudatus和C. g. kikuyuensis聚集在一起。这两种格莱萨血统大约在70万年前分化。此外,线粒体序列信息并不能明确地支持C. g. caudatus和C. g. kikuyuensis的区别。我们的研究结果表明,C. g. occidentalis和C. g. gallarum的分布范围与C. g. guereza-C的成员可能二次入侵埃塞俄比亚之间存在先前的生物地理联系。g . caudatus-C。基库尤氏支。考虑到这些系统发育关系,我们的研究支持了两个分类群的假设,使C. g. gallarum成为埃塞俄比亚特有的,并且,结合分类群非常有限的范围,使其成为黑白疣子中最濒危的亚种之一。
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引用次数: 15
Seroprevalence of viral infections in captive rhesus and cynomolgus macaques. 圈养恒河猴和猕猴的病毒感染血清流行率。
Q2 Agricultural and Biological Sciences Pub Date : 2019-03-26 eCollection Date: 2019-01-01 DOI: 10.5194/pb-6-1-2019
Artur Kaul, Uwe Schönmann, Stefan Pöhlmann

Macaques serve as important animal models for biomedical research. Viral infection of macaques can compromise animal health as well as the results of biomedical research, and infected animals constitute an occupational health risk. Therefore, monitoring macaque colonies for viral infection is an important task. We used a commercial chip-based assay to analyze sera of 231 macaques for the presence of antibody responses against nine animal and human viruses. We report high seroprevalence of cytomegalovirus (CMV), lymphocryptovirus (LCV), rhesus rhadinovirus (RRV) and simian foamy virus (SFV) antibodies in all age groups. In contrast, antibodies against simian retrovirus type D (SRV/D) and simian T cell leukemia virus (STLV) were detected only in 5 % and 10 % of animals, respectively, and were only found in adult or aged animals. Moreover, none of the animals had antibodies against herpes B virus (BV), in keeping with the results of in-house tests previously used for screening. Finally, an increased seroprevalence of measles virus antibodies in animals with extensive exposure to multiple humans for extended periods of time was observed. However, most of these animals were obtained from external sources, and a lack of information on the measles antibody status of the animals at the time of arrival precluded drawing reliable conclusions from the data. In sum, we show, that in the colony studied, CMV, LCV, RRV and SFV infection was ubiquitous and likely acquired early in life while SRV/D and STLV infection was rare and likely acquired during adulthood.

猕猴是生物医学研究的重要动物模型。猕猴感染病毒会损害动物健康和生物医学研究成果,受感染的动物会构成职业健康风险。因此,监测猕猴群的病毒感染是一项重要任务。我们使用一种基于商用芯片的检测方法,分析了 231 只猕猴血清中是否存在针对九种动物和人类病毒的抗体反应。我们报告了巨细胞病毒(CMV)、淋巴细胞病毒(LCV)、恒河猴疱疹病毒(RRV)和猿猴泡沫病毒(SFV)抗体在所有年龄组中的高血清流行率。相比之下,只有5%和10%的动物分别检测到了猿逆转录病毒D型(SRV/D)和猿T细胞白血病病毒(STLV)抗体,而且只在成年或老年动物中发现。此外,没有一只动物体内有 B 型疱疹病毒(BV)抗体,这与之前用于筛查的内部测试结果一致。最后,在长期与多人广泛接触的动物中,发现麻疹病毒抗体的血清流行率有所上升。然而,这些动物大多是从外部获得的,而且缺乏动物到达时麻疹抗体状况的信息,因此无法从数据中得出可靠的结论。总之,我们的研究表明,在所研究的群体中,CMV、LCV、RRV 和 SFV 感染无处不在,很可能是在生命早期获得的,而 SRV/D 和 STLV 感染很少见,很可能是在成年期获得的。
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引用次数: 0
Spontaneous meningioma in a pig-tailed macaque (Macaca nemestrina). 猪尾猕猴(Macaca nemestrina)自发性脑膜瘤。
Q2 Agricultural and Biological Sciences Pub Date : 2018-04-05 eCollection Date: 2018-01-01 DOI: 10.5194/pb-5-7-2018
Roland Plesker, Martina Bleyer, Kerstin Mätz-Rensing

We present a case of spontaneous meningioma in a female pig-tailed macaque (Macaca nemestrina) more than 24 years old. Clinically, the monkey displayed slow, weak, and insecure movements and poor vision. A tumorous mass was present at the floor of the cranial vault extending from the optic chiasm towards the foramen magnum. It compressed adjacent parts of the brain, infiltrated the sphenoidal and occipital bone, and showed transcranial expansion into the pharyngeal area. Histologically, the tumor was consistent with a meningioma displaying mostly meningothelial and some microcystic components. Since only six cases of meningiomas in nonhuman primates have been reported so far and only two of these meningiomas have been described in detail, the findings of each case should be reported to expand the knowledge base of this type of tumor. In addition, this is the first description of a meningioma in pig-tailed macaques.

我们报告了一例年龄超过 24 岁的雌性猪尾猕猴(Macaca nemestrina)自发性脑膜瘤病例。从临床表现来看,这只猴子行动缓慢、虚弱、缺乏安全感,视力也很差。颅顶底部有一个肿瘤肿块,从视丘向枕骨大孔延伸。肿瘤压迫了大脑的邻近部位,浸润了蝶骨和枕骨,并出现了向咽部区域的颅内扩展。从组织学上看,肿瘤与脑膜瘤一致,主要表现为脑膜上皮细胞和一些微囊成分。迄今为止,关于非人灵长类脑膜瘤的报道只有六例,其中只有两例得到了详细描述,因此应报道每一例的研究结果,以扩大这类肿瘤的知识库。此外,这是首次描述猪尾猕猴脑膜瘤。
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引用次数: 0
Self-anointing behaviour in captive titi monkeys (Callicebus spp.). 圈养山地猴(Callicebus spp.)
Q2 Agricultural and Biological Sciences Pub Date : 2018-01-11 eCollection Date: 2018-01-01 DOI: 10.5194/pb-5-1-2018
João Pedro Souza-Alves, Natasha M Albuquerque, Luana Vinhas, Thayane S Cardoso, Raone Beltrão-Mendes, Leandro Jerusalinsky

Self-anointing behaviour using Bauhinia sp. was reported in two captive titi monkeys (Callicebus coimbrai and Callicebus barbarabrownae). The study was carried out from October 2013 to May 2014 during an experimental study investigating the gut passage time of these individuals at the Getúlio Vargas Zoobotanical Park, north-eastern Brazil. Although leaves, petioles and flowers of Bauhinia contain chemical substances that could affect the presence of ectoparasites, it is unclear if titi monkeys demonstrate self-anointing behaviour as a method of self-medication. However, due to the presence of large glands in C. coimbrai and C. barbarabrownae chests, and the high frequency of occurrence observed for the adult male, we cautiously suggest that the use of Bauhinia may be linked to olfactory communication.

据报道,两只人工饲养的缇猴(Callicebus coimbrai和Callicebus barbarabrownae)使用洋紫荆进行了自我指定行为。这项研究于 2013 年 10 月至 2014 年 5 月在巴西东北部的 Getúlio Vargas 动物园进行,期间对这些个体的肠道通过时间进行了实验研究。虽然洋紫荆的叶子、叶柄和花朵含有可能影响体外寄生虫存在的化学物质,但目前还不清楚缇猴是否会表现出自我膏药行为作为一种自我治疗方法。不过,由于科英布拉猴(C. coimbrai)和巴巴拉布朗猴(C. barbarabrownae)胸部有大腺体,而且观察到成年雄性出现的频率很高,我们谨慎地认为,紫荆花的使用可能与嗅觉交流有关。
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引用次数: 0
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Primate Biology
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