Non-primate Animals Research Articles

Engineered materials for organoid systems.

Organoids are 3D cell culture systems that mimic some of the structural and functional characteristics of an organ. Organoid cultures provide the opportunity to study organ-level biology in models that mimic human physiology more closely than 2D cell culture systems or non-primate animal models. Many organoid cultures rely on decellularized extracellular matrices as scaffolds, which are often poorly chemically defined and allow only limited tunability and reproducibility. By contrast, the biochemical and biophysical properties of engineered matrices can be tuned and optimized to support the development and maturation of organoid cultures. In this Review, we highlight how key cell-matrix interactions guiding stem-cell decisions can inform the design of biomaterials for the reproducible generation and control of organoid cultures. We survey natural, synthetic and protein-engineered hydrogels for their applicability to different organoid systems and discuss biochemical and mechanical material properties relevant for organoid formation. Finally, dynamic and cell-responsive material systems are investigated for their future use in organoid research.

A review of novel trends in management of canine spinal cord injury

Severe spinal cord injury (SCI) causing significant morbidity and mortality remains one of the most challenging problems in both human and veterinary medicine. Due to the restricted regeneration potential of the central nervous system (CNS) in mammals, the neurological deficit caused by spinal cord (SC) injury is permanent, and no therapeutic measures are able to completely restore neurological functions either in primates or in non-primate animals with traumatic tetraparesis/tetraplegia or paraparesis/paraplegia. The constant progress in the understanding of pathophysiologic events developing after spinal cord trauma constitute an unremitting inspiration for neuroscientists and health care professionals to test novel medicaments and treatment strategies to cope with this situation. Recent experimental studies and preclinical trials have delivered promising results. The aim of this review is a presentation of generally accepted methods of management of dogs with SCI as well as a report on new therapeutic modalities, and comment on their potential for clinical translation. The research strategy involved a search of PubMed, Medline, and ISI Web of Science from January 2010 to December 2018 using the terms “spinal cord injuryˮ and “management of spinal traumaˮ in the English language literature. References from selected papers were also scanned and evaluated for relevance.

Effects of primatological training on anthropomorphic valuations of emotions

Anthropomorphism implies the attribution of human like emotions and cognition to non-human animals. This tendency may be conditioned by similar morphologies between mammals and is particularly important in primatology. Some neurocognitive findings suggest that prefrontal brain activity associated to conceptual learning influences anthropomorphic judgments, nevertheless, individual differences are also presented indicating that training on primate behavior may influence anthropomorphism. We identified and interpreted brain activity registered by functional magnetic resonance imaging while seven trained primatologists (39.42 ± 10.86 yr.) inferred emotions in human primates, non-human primates and non-primate animals; comparisons were made with seven matched scholars with no primatological training (38.71 ± 9.34 yr.). Primatologists manifested cerebellar, occipital and frontal activity related to sensory and motor processes when valuating humans and non-human primates, but not for other animals. So, primatological training and experience may elicit brain plasticity processes allowing inner motor and sensory models through frontal and cerebellar interactions.

The porcine corticospinal decussation: A combined neuronal tracing and tractography study

BackgroundPigs and minipigs are increasingly used as non-primate large animal models for preclinical research on nervous system disorders resulting in motor dysfunction. Knowledge of the minipig pyramidal tract is therefore essential to support such models. Aim and methodsThis study used 5 female Göttingen minipigs aging 11–15 months. The Göttingen minipig corticospinal tract was investigated, in the same animals, with in vivo neuronal tracing and with postmortem diffusion weighted MRI tractography to provide a thorough insight in the encephalic distribution of this primary motor pathway and its decussation at the craniocervical junction. ResultsThe two methods similarly outlined the course of the pyramidal tract from its origin in the motor cortex down through the internal capsule to the craniocervical junction, where both methods displayed an axonal crossover at the pyramid decussation. The degree of crossover was quantified with unbiased stereology, where 81–93% of the traced corticospinal fibers crossed to the contralateral spinal cord. Accordingly, in the upper cervical spinal cord the corticospinal tract is primarily distributed in the contralateral lateral funiculus and in close relation to the gray matter, wherein some direct terminations on large ventral column gray matter neurons could be identified. DiscussionThe combination of neuronal tracing and tractography exploited the strengths of the respective methods to gain a better understanding of the encephalic distribution and craniocervical decussation of the Göttingen minipig corticospinal tract. Moreover, a quantification of the crossing fibers was obtained from the tracing data, which was not possible with tractography. Our data indicate that the porcine corticospinal system is quite lateralized down to the investigated upper cervical levels. However, further elucidation of this point will require a full examination of the corticospinal tracing pattern into the caudal spinal cord combined with an analysis of the direct versus indirect termination pattern on the lower motor neurons.

The Triadic Roots of Human Cognition: "Mind" Is the Ability to go Beyond Dyadic Associations.

Empirical evidence is reviewed indicating that the extraordinary aspects of the human mind are due to our species’ ability to go beyond simple “dyadic associations” and to process the relations among three items of information simultaneously. Classic explanations of the “triadic” nature of human skills have been advocated by various scholars in the context of the evolution of human cognition. Here I summarize the core processes as found in (i) the syntax of language, (ii) tool-usage, and (iii) joint attention. I then review the triadic foundations of two perceptual phenomena of great importance in human aesthetics: (iv) harmony perception and (v) pictorial depth perception. In all five subfields of human psychology, most previous work has emphasized the recursive, hierarchical complexity of such “higher cognition,” but a strongly reductionist approach indicates that the core mechanisms are triadic. It is concluded that the cognitive skills traditionally considered to be “uniquely” human require three-way associational processing that most non-Primate animal species find difficult or impossible, but all members of Homo sapiens – regardless of small cultural differences – find easy and inherently intriguing.

Non-motor Characterization of the Basal Ganglia: Evidence From Human and Non-human Primate Electrophysiology.

Although the basal ganglia have been implicated in a growing list of human behaviors, they include some of the least understood nuclei in the brain. For several decades studies have employed numerous methodologies to uncover evidence pointing to the basal ganglia as a hub of both motor and non-motor function. Recently, new electrophysiological characterization of the basal ganglia in humans has become possible through direct access to these deep structures as part of routine neurosurgery. Electrophysiological approaches for identifying non-motor function have the potential to unlock a deeper understanding of pathways that may inform clinical interventions and particularly neuromodulation. Various electrophysiological modalities can also be combined to reveal functional connections between the basal ganglia and traditional structures throughout the neocortex that have been linked to non-motor behavior. Several reviews have previously summarized evidence for non-motor function in the basal ganglia stemming from behavioral, clinical, computational, imaging, and non-primate animal studies; in this review, instead we turn to electrophysiological studies of non-human primates and humans. We begin by introducing common electrophysiological methodologies for basal ganglia investigation, and then we discuss studies across numerous non-motor domains–emotion, response inhibition, conflict, decision-making, error-detection and surprise, reward processing, language, and time processing. We discuss the limitations of current approaches and highlight the current state of the information.

Ectopic Pregnancy in Two Cats

Background: Ectopic pregnancy mainly refers to tubal pregnancy and abdominal pregnancy. Tubal pregnancy presents as an implanted embryo that develops in the fallopian tubes, and is relatively common in humans. In animals, tubal pregnancy occurs primarily in primates, for example monkeys. The probability of a tubal pregnancy in non-primate animals is extremely low. Abdominal pregnancy is a type of ectopic pregnancy that occurs outside of the uterus, fallopian tube, ovary, and ligament(broad ligament, ovarian ligament, suspensory ligament).This paper describes two cases of ectopic pregnancy in cats.Cases: Cat 1. The presenting sign was a significant increase in abdominal circumference. The age and immune and sterilization status of the cat were unknown. On palpation, a 4 cm, rough, oval-shaped, hard mass was found in the posterior abdomen. Radiographic examination showed three high-density images in the posterior abdomen. The fetus was significantlycalcified and some feces was evident in the colon. The condition was preliminarily diagnosed as ectopic pregnancy. Cat 2. The owner of a 2-year-old British shorthair cat visited us because of a hard lump in the cat’s abdomen. The cat had a normal diet and was drinking normally. Routine immunization and insect repulsion had been implemented. The cat had naturally delivered five healthy kittens two months previous. Radiographs showed an oval-shaped mass with a clear edge in the middle abdominal cavity. Other examinations were normal. The case was preliminarily diagnosed as ectopic pregnancy, and the pregnancy was surgically terminated. The ectopic pregnancies were surgically terminated. During surgery, the structures of the uterus and ovary of cat 1 were found to be intact and the organs were in a normal physiological position.Cat 1 was diagnosed with primary abdominal pregnancy. In cat 2, the uterus left side was small and the fallopian tube on the same side was both enlarged and longer than normal. Immature fetuses were found in the gestational sac. Thus, cat 2 was diagnosed with tubal ectopic pregnancy based on the presenting pathology.Discussion: Cats with ectopic pregnancies generally show no obvious clinical symptoms. The ectopic fetus can remain within the body for several months or even years. Occasionally, necrotic ectopic tissues or mechanical stimulation of the ectopic fetus can lead to a systemic inflammatory response, loss of appetite, and apathy. The two cats in our reportshowed no significant clinical symptoms. To our knowledge, there have been no previous reports of the development of an ectopic fetus to maturity, within the abdominal cavity of felines, because the placenta of cats cannot support the growth and development of the fetus outside of the uterus. Secondary abdominal ectopic pregnancy, lacking any signs of uterine rupture is likely associated with the strong regenerative ability of uterine muscles. A damaged uterus or fallopian tube can quickly recover and rarely leaves scar tissue. In the present report, cat 1 showed no apparent scar tissue, nor signs of a ruptured ovary or fallopian tubes. It was diagnosed with primary ectopic abdominal pregnancy, which could arise from the descent of the fertilized egg from the fallopian tube into the abdominal cavity. There was an abnormal protrusion in left of the fallopian tubes in cat 2, to which the gestational sac was directly connected. Based on pathological examination of the uterus, fallopian tubes, and gestational sac, the cat was diagnosed with a tubal pregnancy. Placental tissues and signs of fetal calcification were observed in both the fallopian tube and gestational sac.Keywords: tubal pregnancy, abdominal pregnancy, feline, ectopic fetus, fallopian tube, gestational sac.

Pirouetting pigs: A large non-primate animal model based on unilateral 6-hydroxydopamine lesioning of the nigrostriatal pathway

IntroductionThe rotating 6-hydroxydopamine (6-OHDA) rat model has long been important when developing new treatment strategies for Parkinson’s disease (PD). Similar non-human primate models have been developed for translational research purposes as large animal models are required by regulatory bodies as an intermediate “phase 0” trial step. However, experimental research in non-human primates encounters several economical and regulatory issues, which may be avoided by the alternative use of pigs as a large animal model for experimental brain research. ObjectiveThe primary aim of this study was to examine if unilateral injections of 6-OHDA into the Göttingen minipig nigrostriatal pathway would lead to dopaminergic imbalance and rotational behavior similar to the 6-OHDA unilateral symptomatic model of PD created in other species. The secondary aim was to attempt to verify the rotational behavior as a parkinsonian symptom using subthalamic deep brain stimulation (STN-DBS) to minimize the elicited rotational pattern. Materials and methodsUsing an MRI-based stereotactic procedure, ten female Göttingen minipigs were injected unilaterally with 6-OHDA in the nigrostriatal pathway. Postoperatively, an MRI was performed, and the animals were injected with amphetamine and apomorphine and observed for rotational behavior. After a survival period of three months the brains were removed and immunohistochemically stained for tyrosine hydroxylase (TH). One week before sacrifice two animals had DBS electrodes unilaterally implanted in the subthalamic nucleus and various stimulation protocols were conducted during amphetamine challenge. ResultsAs expected most animals rotated towards the side of the lesion when given amphetamine (3.5–4.0 mg/kg), whereas the predicted opposite response to apomorphine were much harder to reproduce. T1- and T2-weighted postoperative MRI could demonstrate the size and the location of the 6-OHDA injection. Postmortem TH-staining of the final two animals receiving a medial and a lateral injection of 25 μL of 6-OHDA (8 μg/μL, injection rate 5 μL/min) into the diencephalic nigrostriatal pathway showed a prominent unilateral decrease in TH-staining of the substantia nigra pars compacta, the ventral tegmental area and the nigrostriatal pathway on the lesioned side. These two animals displayed spontaneous rotational behavior toward the lesioned side for the first 2–3 days postoperatively, and this behavior could later on be reelicited by amphetamine and attenuated by ipsilateral STN-DBS. ConclusionFemale Göttingen minipigs are susceptible to unilateral dopaminergic degeneration when properly injected unilaterally with sufficient amounts of 6-OHDA in the nigrostriatal pathway. The location of the 6-OHDA injections and thus the accuracy of the employed stereotaxy can be verified in vivo using MRI postoperatively. The injected minipigs display unilateral parkinsonism with a well-defined rotational response to amphetamine that may be ameliated by STN-DBS performed on the lesioned side. The response to apomorphine was, however, not consistent, illustrating that further work on this promising non-primate large animal model is needed, before it is fully similar to the established 6-OHDA models in other species.

Intranasal oxytocin modulates neural functional connectivity during human social interaction.

Oxytocin (OT) modulates social behavior in primates and many other vertebrate species. Studies in non-primate animals have demonstrated that, in addition to influencing activity within individual brain areas, OT influences functional connectivity across networks of areas involved in social behavior. Previously, we used fMRI to image brain function in human subjects during a dyadic social interaction task following administration of either intranasal oxytocin (INOT) or placebo, and analyzed the data with a standard general linear model. Here, we conduct an extensive re-analysis of these data to explore how OT modulates functional connectivity across a neural network that animal studies implicate in social behavior. OT induced widespread increases in functional connectivity in response to positive social interactions among men and widespread decreases in functional connectivity in response to negative social interactions among women. Nucleus basalis of Meynert, an important regulator of selective attention and motivation with a particularly high density of OT receptors, had the largest number of OT-modulated connections. Regions known to receive mesolimbic dopamine projections such as the nucleus accumbens and lateral septum were also hubs for OT effects on functional connectivity. Our results suggest that the neural mechanism by which OT influences primate social cognition may include changes in patterns of activity across neural networks that regulate social behavior in other animals.

Genetic diversity of Blastocystis in non-primate animals.

Blastocystis is an anaerobic protist, commonly inhabiting the intestinal tract of both humans and other animals. Blastocystis is extremely diverse comprising 17 genetically distinct subtypes in mammals and birds. Pathogenicity of this enteric microbe is currently disputed and knowledge regarding its distribution, diversity and zoonotic potential is fragmentary. Most research has focused on Blastocystis from primates, while sampling from other animals remains limited. Herein, we investigated the prevalence and distribution of Blastocystis in animals held within a conservation park in South East England. A total of 118 samples were collected from 27 vertebrate species. The barcoding region of the small-subunit ribosomal RNA was used for molecular identification and subtyping. Forty one per cent of the species were sequence positive for Blastocystis indicating a high prevalence and wide distribution among the animals in the park. Six subtypes were identified, one of which is potentially novel. Moreover, the majority of animals were asymptomatic carriers, suggesting that Blastocystis is not pathogenic in animals. This study provides a thorough investigation of Blastocystis prevalence within a wildlife park in the UK and can be used as a platform for further investigations on the distribution of other eukaryotic gut microbes.

The Value of Duane Rumbaugh’s Comparative Perspective—in Neurobiology

One commonality across the wide-ranging influences Duane Rumbaugh had on late-20th century science was his commitment to the comparative perspective in psychology. I argue here that a commitment similar in force to Rumbaugh’s also infuses mainstream experimental neurobiology. This connection is ironic because Rumbaugh eschewed brain intervention experimentation in vivo throughout his scientific career. Still, the influence and value of a perspective similar to Rumbaugh’s can be found in neurobiology in at least three places. First, recent neurobiology has made good on one of Rumbaugh’s predictions, that rearing and early environment will be shown to influence behavior and cognition in nonprimate animals. Second, the epistemologically justified use of animal models in experimental neurobiology to investigate human brain mechanism presupposes a strong commitment to the comparative perspective. Third, commitment to the comparative perspective raises the most pressing ethical concern in neurobiology, namely, how is it ethical to perform brain intervention experiments on animal models if their brain mechanisms and behaviors compare closely enough with ours to justifiably generalize these experiments’ results?

Pig models on intestinal development and therapeutics.

The gastrointestinal tract plays a vital role in nutrient supply, digestion, and absorption, and has a crucial impact on the entire organism. Much attention is being paid to utilize animal models to study the pathogenesis of gastrointestinal diseases in response to intestinal development and health. The piglet has a body size similar to that of the human and is an omnivorous animal with comparable anatomy, nutritional requirements, and digestive and associated inflammatory processes, and displays similarities to the human intestinal microbial ecosystem, which make piglets more appropriate as an animal model for human than other non-primate animals. Therefore, the objective of this review is to summarize key attributes of the piglet model with which to study human intestinal development and intestinal health through probing into the etiology of several gastrointestinal diseases, thus providing a theoretical and hopefully practical, basis for further studies on mammalian nutrition, health, and disease, and therapeutics. Given the comparable nutritional requirements and strikingly similar brain developmental patterns between young piglets and humans, the piglet has been used as an important translational model for studying neurodevelopmental outcomes influenced by pediatric nutrition. Because of similarities in anatomy and physiology between pigs and mankind, more emphasises are put on how to use the piglet model for human organ transplantation research.

Disruption of redox homeostasis in liver function and activation of apoptosis on consumption of aspartame in folate deficient rat model

This study assesses the effect of long-term intake of aspartame on liver function and apoptosis signaling pathway in the Wistar albino rats. Several reports have suggested that methanol is one of the major metabolites of Aspartame. Non-primate animals are usually resistant to methanol-induced metabolic acidosis due to high levels of hepatic folate content; hence a folate deficiency model was induced by treating animals with methotrexate (MTX) prior to aspartame exposure. The aspartame treated MTX animals exhibited a marked significant increase in hepatic alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactic acid dehydrogenase (LDH) activity compared to controls. Aspartame treated MTX animals additionally exhibited down-regulation of genes namely B-cell lymphoma 2 (Bcl2) expression and up-regulation of Bcl-2-associated X protein (Bax), Fas-associated protein with death domain (FADD) and Caspase 3, 9 genes and apoptotic protein expression, indicating the augmentation of hepatic apoptosis. Nuclear condensation, micro vacuole formation in the cytoplasm and necrosis were observed in the liver of the aspartame treated animals on histopathology evaluation. Additionally, Immunohistochemical analysis revealed a significant increase in positive cells expressing Fas, FADD, Bax and Caspase 9 protein, indicating an increase in apoptotic protein expression in the liver. Thus, Aspartame may act as a chemical stressor which alters the functional status of liver, leading to hepatotoxicity.

Molecular Cloning and Characterization of Marmoset Aldehyde Oxidase.

Common marmosets (Callithrix jacchus), New World monkeys, are a promising primate model for preclinical drug metabolism studies because of the similarities of cytochrome P450 (P450) enzyme function to those of humans. Despite an increasing number of drug candidates catalyzed by non-P450 enzymes, drug metabolizing enzymes other than P450s have been hardly identified or characterized in marmosets. In this study, we identified aldehyde oxidase (AOX) 1 gene by marmoset genome analysis. AOX1 cDNA was cloned from marmoset livers by reverse transcription-polymerase chain reaction. Deduced amino acid sequences of AOX1 cDNA showed high sequence identities (92-93%) with primate AOX1s. Phylogenetic analysis showed that marmoset AOX1 was closely clustered with primate AOX1s, unlike nonprimate animal model AOX1s of pig, rabbit, rat, and mouse used in drug metabolism. The tissue expression analyses by real-time reverse-transcription polymerase chain reaction and immunoblotting showed that marmoset AOX1 mRNA and protein were abundantly expressed in livers, similar to cynomolgus monkeys and humans. Marmoset AOX1 heterologously expressed in Escherichia coli catalyzed the oxidation of carbazeran and phthalazine, typical AOX1 substrates, similar to cynomolgus monkey and human AOX1s. Human and marmoset AOX1 effectively catalyzed phthalazine oxidation when assessed with Michaelis-Menten kinetics, but cynomolgus monkey AOX1 catalyzed this reaction with cooperative kinetics with high capacity. These results indicated that tissue distribution and enzymatic function of AOX1 enzyme is similar between marmosets and humans, suggesting that marmosets are a suitable primate model for AOX-dependent drug metabolism in preclinical studies.

Isolation and identification of <i>Bifidobacterium</i> species from feces of captive chimpanzees

Recently, gut-dwelling bifidobacteria from chimpanzees, which are phylogenetically close to humans and have feeding habits similar to humans, have been frequently investigated. Given this, we speculated that like humans, chimpanzees would have a unique diversity of bifidobacteria. We herein describe a taxonomically novel member of bifidobacteria isolated from fecal samples of captive chimpanzees. Bifidobacteria were detected in all fecal samples by quantitative polymerase chain reaction. A Bifidobacterium pseudolongum-like species, which could not be detected using B. pseudolongum-specific primers targeting the groEL gene sequence, was dominant in the feces of five chimpanzees. Seven bifidobacterial strains were isolated from this group of five chimpanzees, and all isolates were identified as B. pseudolongum. B. pseudolongum has previously often been isolated from non-primate animals as well as humans; however, here we demonstrate its presence in a nonhuman primate species.

Identification of SP110 in horse (Equus caballus): Isolation of novel splice variants and evidence of activation effects on macrophages

SP110 has previously shown to be a genetic determinant of host resistance to the intracellular pathogen infection in mouse and human. However, its relevant biological information in large non-primate animals still remains unknown. Here we report the novel discovery and characterization of three transcript variants of horse SP110. The transcript variant 1 (Tv1) of horse SP110 with the longest open reading frame has four domains (Sp100, SAND, PHD and Bromo domain). Tv2 and Tv3 share the same N-terminal sequence as Tv1, which contains Sp100 and SAND. We show that Tv2 is generated from alternative splicing and deletion of Exon17-Exon18 segment, while Tv3 is generated by pre-mature transcriptional termination at Exon 16. Furthermore, we demonstrate that the heterologous expression of horse SP110 variants stimulate macrophages into an activation-like phenotype. The macrophages underwent a shift in enhancing the secretion of cytokines (interleukin-1 (IL-1) and TNF-α) and accelerating inducible nitric oxide synthase (iNOS) activity, and eventually went into apoptotic cell death. Intriguingly, horse SP110 Tv1 showed more capability to trigger the immune activities compared to Tv2 and Tv3. To our knowledge, the identification of SP110 transcript variants from horse is the first report on biological function of SP110 in perissodactyla animals.

Next generation sequencing of SNPs using the HID-Ion AmpliSeq™ Identity Panel on the Ion Torrent PGM™ platform

The HID-Ion AmpliSeq™ Identity Panel (the HID Identity Panel) is designed to detect 124-plex single nucleotide polymorphisms (SNPs) with next generation sequencing (NGS) technology on the Ion Torrent PGM™ platform, including 90 individual identification SNPs (IISNPs) on autosomal chromosomes and 34 lineage informative SNPs (LISNPs) on Y chromosome. In this study, we evaluated performance for the HID Identity Panel to provide a reference for NGS-SNP application, focusing on locus strand balance, locus coverage balance, heterozygote balance, and background signals. Besides, several experiments were carried out to find out improvements and limitations of this panel, including studies of species specificity, repeatability and concordance, sensitivity, mixtures, case-type samples and degraded samples, population genetics and pedigrees following the Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines. In addition, Southern and Northern Chinese Han were investigated to assess applicability of this panel. Results showed this panel led to cross-reactivity with primates to some extent but rarely with non-primate animals. Repeatable and concordant genotypes could be obtained in triplicate with one exception at rs7520386. Full profiles could be obtained from 100pg input DNA, but the optimal input DNA would be 1ng–200pg with 21 initial PCR cycles. A sample with ≥20% minor contributor could be considered as a mixture by the number of homozygotes, and full profiles belonging to minor contributors could be detected between 9:1 and 1:9 mixtures with known reference profiles. Also, this assay could be used for case-type samples and degraded samples. For autosomal SNPs (A-SNPs), FST across all 90loci was not significantly different between Southern and Northern Chinese Han or between male and female samples. All A-SNP loci were independent in Chinese Han population. Except for 18loci with He <0.4, most of the A-SNPs in the HID Identity Panel presented high polymorphisms. Forensic parameters were calculated as >99.999% for combined discrimination power (CDP), 0.999999724 for combined power of exclusion (CPE), 1.390×1011 for combined likelihood ratio (CLR) of trios, and 2.361×106 for CLR of motherless duos. For Y-SNPs, a total of 8 haplotypes were observed with the value of 0.684 for haplotype diversity. As a whole, the HID Identity Panel is a well-performed, robust, reliable and high informative NGS-SNP assay and it can fully meet requirements for individual identification and paternity testing in forensic science.

In Vivo Evaluation of Blood Based and Reference Tissue Based PET Quantifications of [11C]DASB in the Canine Brain.

This first-in-dog study evaluates the use of the PET-radioligand [11C]DASB to image the density and availability of the serotonin transporter (SERT) in the canine brain. Imaging the serotonergic system could improve diagnosis and therapy of multiple canine behavioural disorders. Furthermore, as many similarities are reported between several human neuropsychiatric conditions and naturally occurring canine behavioural disorders, making this tracer available for use in dogs also provide researchers an interesting non-primate animal model to investigate human disorders. Five adult beagles underwent a 90 minutes dynamic PET scan and arterial whole blood was sampled throughout the scan. For each ROI, the distribution volume (VT), obtained via the one- and two- tissue compartment model (1-TC, 2-TC) and the Logan Plot, was calculated and the goodness-of-fit was evaluated by the Akaike Information Criterion (AIC). For the preferred compartmental model BPND values were estimated and compared with those derived by four reference tissue models: 4-parameter RTM, SRTM2, MRTM2 and the Logan reference tissue model. The 2-TC model indicated in 61% of the ROIs a better fit compared to the 1-TC model. The Logan plot produced almost identical VT values and can be used as an alternative. Compared with the 2-TC model, all investigated reference tissue models showed high correlations but small underestimations of the BPND-parameter. The highest correlation was achieved with the Logan reference tissue model (Y = 0.9266 x + 0.0257; R2 = 0.9722). Therefore, this model can be put forward as a non-invasive standard model for future PET-experiments with [11C]DASB in dogs.

Continuous MPTP intoxication in the Göttingen minipig results in chronic parkinsonian deficits.

Parkinson's disease (PD) is a common neurodegenerative disorder, resulting from progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNc). Neuroprotective therapies in PD are still not available, perhaps because animal models do not imitate the chronic and progressive nature of the clinical state of PD. To address this, we performed a feasibility study aimed at establishing a chronic non-primate large animal PD model in Göttingen minipigs based on continuous infusion of the neurotoxin 1-methyl-4-phenyl‑1,2,3,6-tetrahydropyridine (MPTP). Twelve female Göttingen minipigs were divided into groups of 2-4 animals and implanted with infusion pumps for continuous intramuscular MPTP delivery of 4-24 mg MPTP/day for 11 weeks. The animals showed parkinsonian symptoms with bradykinesia, rigidity, coordination and chewing difficulties. Symptoms were stable in the 12 and 18 mg MPTP/day groups, whereas the remaining groups showed partial or full behavioral recovery. Digital gait analysis, high performance liquid chromatography (HPLC) measurements and stereological counts of tyrosine hydroxylase-positive (TH+) neurons in the SNc revealed a dose-related decrease in gait velocity, striatal metabolite levels and neuron numbers with increasing doses of MPTP. No neuronal inclusions were observed, but alpha-synuclein staining intensified with increased cumulative MPTP dosages. We conclude that this large-animal model of chronic MPTP administration in Göttingen minipigs shows trends of stable parkinsonian deficits at 18 mg MPTP/day in all modalities examined. This PD model shares many of the characteristics seen in patients and, although preliminary, holds considerable promise for future pre-clinical trials of neuroprotective therapies.

Advances in Animal Models of Hepatitis B Virus Infection

Abstract Hepatitis B virus (HBV) infection seriously affects human health. Stable and reliable animal models of HBV infection bear significance in studying pathogenesis of this health condition and development of intervention measures. HBV exhibits high specificity for hosts, and chimpanzee is long used as sole animal model of HBV infection. However, use of chimpanzees is strictly constrained because of ethical reasons. Many methods were used to establish small-animal models of HBV infection. Tupaia is the only nonprimate animal that can be infected by HBV. Use of HBV-related duck hepatitis virus and marmot hepatitis virus infection model contributed to evaluation of mechanism of HBV replication and HBV treatment methods. In recent years, development of human–mouse chimeric model provided possibility of using common experimental animals to carry out HBV research. These models feature their own advantages and disadvantages and can be complementary in some ways. This study provides an overview of current and commonly used animal models of HBV infection.