Non-primate Mammals Research Articles

Accelerated healing of skin burns by anti-Gal/α-gal liposomes interaction

Topical application of α-gal liposomes on burns results in rapid local recruitment of neutrophils and macrophages. Recruited macrophages are pivotal for healing of burns because they secrete cytokines/growth factors that induce epidermis regeneration and tissue repair. α-Gal liposomes have glycolipids with α-gal epitopes (Galα1-3Galβ1-4GlcNAc-R) which bind anti-Gal, the most abundant natural antibody in humans constituting ∼1% of immunoglobulins. Interaction of α-gal liposomes with anti-Gal within the fluid film formed on burns, activates complement and generates chemotactic complement cleavage peptides which effectively recruit neutrophils and macrophages. Anti-Gal IgG coating α-gal liposomes further binds to Fcγ receptors on macrophages and activates them to secrete cytokines/growth factors. Efficacy of α-gal liposomes treatment in accelerating burn healing is demonstrated in the experimental model of α1,3galactosyltransferase knockout mice. These mice are the only available nonprimate mammals that can produce anti-Gal in titers similar to those in humans. Pairs of burns in mice were covered either with a spot bandage coated with 10 mg α-gal liposomes, or with a control spot bandage coated with saline. On Day 3 post-treatment, the α-gal liposomes treated burns contained ∼5-fold as many neutrophils as control burns, whereas macrophages were found only in α-gal liposomes treated burns. On Day 6, 50–100% of the surface area of α-gal liposomes treated burns were covered with regenerating epidermis (re-epithelialization), whereas almost no epidermis was found in control burns. The extensive recruitment of macrophages by anti-Gal/α-gal liposomes interaction was further demonstrated in vivo with polyvinyl alcohol (PVA) sponge discs containing α-gal liposomes, implanted subcutaneously. Since anti-Gal is abundant in all humans, it is suggested that treatment with α-gal liposomes will be effective also in patients with burns and other skin wounds.

Horse (Equus caballus) whinnies: a source of social information

Many animal species that rely mainly on calls to communicate produce individual acoustic structures, but we wondered whether individuals of species better known as visual communicants, with small vocal repertoires, would also exhibit individual distinctiveness in calls. Moreover, theoretical advances concerning the evolution of social intelligence are usually based on primate species data, but relatively little is known about the social cognitive capacities of non-primate mammals. However, some non-primate species demonstrate auditory recognition of social categories and possess mental representation of their social network. Horses (Equus caballus) form stable social networks and although they display a large range of visual signals, they also use long-distance whinny calls to maintain contact. Here, we investigated the potential existence of individual acoustic signatures in whinny calls and the ability of horses to discriminate by ear individuals varying in their degree of familiarity. Our analysis of the acoustic structure of whinnies of 30 adult domestic horses (ten stallions, ten geldings, ten mares) revealed that some of the frequency and temporal parameters carried reliable information about the caller's sex, body size and identity. However, no correlations with age were found. Playback experiments evaluated the behavioural significance of this variability. Twelve horses heard either control white noise or whinnies emitted by group members, familiar neighbours or unfamiliar horses. While control sounds did not induce any particular response, horses discriminated the social category of the callers and reacted with a sound-specific behaviour (vigilance and attraction varied with familiarity). Our results support the existence of social knowledge in horses and suggest a process of vocal coding/decoding of information.

Repair-Mediated Duplication by Capture of Proximal Chromosomal DNA Has Shaped Vertebrate Genome Evolution

DNA double-strand breaks (DSBs) are a common form of cellular damage that can lead to cell death if not repaired promptly. Experimental systems have shown that DSB repair in eukaryotic cells is often imperfect and may result in the insertion of extra chromosomal DNA or the duplication of existing DNA at the breakpoint. These events are thought to be a source of genomic instability and human diseases, but it is unclear whether they have contributed significantly to genome evolution. Here we developed an innovative computational pipeline that takes advantage of the repetitive structure of genomes to detect repair-mediated duplication events (RDs) that occurred in the germline and created insertions of at least 50 bp of genomic DNA. Using this pipeline we identified over 1,000 probable RDs in the human genome. Of these, 824 were intra-chromosomal, closely linked duplications of up to 619 bp bearing the hallmarks of the synthesis-dependent strand-annealing repair pathway. This mechanism has duplicated hundreds of sequences predicted to be functional in the human genome, including exons, UTRs, intron splice sites and transcription factor binding sites. Dating of the duplication events using comparative genomics and experimental validation revealed that the mechanism has operated continuously but with decreasing intensity throughout primate evolution. The mechanism has produced species-specific duplications in all primate species surveyed and is contributing to genomic variation among humans. Finally, we show that RDs have also occurred, albeit at a lower frequency, in non-primate mammals and other vertebrates, indicating that this mechanism has been an important force shaping vertebrate genome evolution.

Role of N-terminus of tyrosine hydroxylase in the biosynthesis of catecholamines

Tyrosine hydroxylase (TH) catalyzes the conversion of L: -tyrosine to L: -dopa, which is the initial and rate-limiting step in the biosynthesis of catecholamines [CA; dopamine (DA), noradrenaline, and adrenaline], and plays a central role in the neurotransmission and hormonal actions of CA. Thus, TH is related to various neuro-psychiatric diseases such as TH deficiency, Parkinson's disease (PD), and schizophrenia. Four isoforms of human TH (hTH1-hTH4) are produced from a single gene by alternative mRNA splicing in the N-terminal region, whereas two isoforms exist in monkeys and only a single protein exist in all non-primate mammals. A catalytic domain is located within the C-terminal two-thirds of molecule, whereas the part of the enzyme controlling enzyme activity is assigned to the N-terminal end as the regulatory domain. The catalytic activity of TH is end product inhibited by CA, and the phosphorylation of Ser residues (Ser(19), Ser(31), and especially Ser(40) of hTH1) in the N-terminus relieves the CA-mediated inhibition. Ota and Nakashima et al. have investigated the role of the N-terminus of TH enzyme in the regulation of both the catalytic activity and the intracellular stability by producing various mutants of the N-terminus of hTH1. The expression of the following three enzymes, TH, GTP cyclohydrolase I, which synthesizes the tetrahydrobiopterin cofactor of TH, and aromatic-L: -amino acid decarboxylase, which produces DA from L: -dopa, were induced in the monkey striatum using harmless adeno-associated virus vectors, resulting in a remarkable improvement in the symptoms affecting PD model monkeys Muramatsu (Hum Gene Ther 13:345-354, 2002). Increased knowledge concerning the amino acid sequences of the N-terminus of TH that control enzyme activity and stability will extend the spectrum of the gene-therapy approach for PD.

The Evolution of Primate Color Vision

The article discusses the evolution of color vision in primates including human beings. The differences between the color vision of primates between the vision of nonprimate mammals are discussed, noting the presence of trichromacy, which depends of three varieties of light-activated pigments located in the retina. INSETS: Two Kinds of Mammalian Color Vision;EVOLUTIONARY ADVANTAGE?;Two Designs for Primate Vision;Untitled.

First description of the surgical anatomy of the cynomolgus monkey liver

No detailed description of nonhuman primate liver anatomy has been reported and little is known about the similarity between such livers and human liver. The cynomolgus monkey (Macaca fascicularis) was used to establish a preclinical model of genetically modified hepatocytes auto transplantation. Here, we report information gleaned from careful observation and notes obtained from 59 female cynomolgus monkeys undergoing 44 anatomical hepatic resections, 12 main portal vein division dissections and selective branch ligations, and 46 portographies. Additionally, three anatomical liver dissections after total resection at autopsy were performed and served to confirm peroperative observations and for photography to provide illustrations. Our results indicate that the cynomolgus monkey liver has four lobes: the median (the largest), the right and left lateral, and the caudate lobes. In 60% (N=20) of individuals the portal bifurcates into right and left portal veins, in the remaining 40% (N=14) the portal vein trifurcates into right anterior, right posterior, and left portal veins. The anatomy and branching pattern of the hepatic artery and bile ducts closely follow those of the portal branches. Functionally, the cynomolgus monkey liver can be divided into eight independent segments. Thus, we report the first detailed description of the hepatic and portal surgical anatomy of the cynomolgus monkey. The cynomolgus monkey liver is more similar to the human liver than are livers of any small or large nonprimate mammals that have been described.

Neurons in the white matter of the adult human neocortex

The white matter (WM) of the adult human neocortex contains the so-called “interstitial neurons”. They are most numerous in the superficial WM underlying the cortical gyri, and decrease in density toward the deep WM. They are morphologically heterogeneous. A subgroup of interstitial neurons display pyramidal-cell like morphologies, characterized by a polarized dendritic tree with a dominant apical dendrite, and covered with a variable number of dendritic spines. In addition, a large contingent of interstitial neurons can be classified as interneurons based on their neurochemical profile as well as on morphological criteria. WM- interneurons have multipolar or bipolar shapes and express GABA and a variety of other neuronal markers, such as calbindin and calretinin, the extracellular matrix protein reelin, or neuropeptide Y, somatostatin, and nitric oxide synthase. The heterogeneity of interstitial neurons may be relevant for the pathogenesis of Alzheimer disease and schizophrenia. Interstitial neurons are most prominent in human brain, and only rudimentary in the brain of non-primate mammals. These evolutionary differences have precluded adequate experimental work on this cell population, which is usually considered as a relict of the subplate, a transient compartment proper of development and without a known function in the adult brain. The primate-specific prominence of the subplate in late fetal stages points to an important role in the establishment of interstitial neurons. Neurons in the adult WM may be actively involved in coordinating inter-areal connectivity and regulation of blood flow. Further studies in primates will be needed to elucidate the developmental history, adult components and activities of this large neuronal system.

Exaptation of an ancient Alu short interspersed element provides a highly conserved vitamin D-mediated innate immune response in humans and primates.

BackgroundAbout 45% of the human genome is comprised of mobile transposable elements or "junk DNA". The exaptation or co-option of these elements to provide important cellular functions is hypothesized to have played a powerful force in evolution; however, proven examples are rare. An ancient primate-specific Alu short interspersed element (SINE) put the human CAMP gene under the regulation of the vitamin D pathway by providing a perfect vitamin D receptor binding element (VDRE) in its promoter. Subsequent studies demonstrated that the vitamin D-cathelicidin pathway may be a key component of a novel innate immune response of human to infection. The lack of evolutionary conservation in non-primate mammals suggested that this is a primate-specific adaptation. Evidence for evolutionary conservation of this regulation in additional primate lineages would provide strong evidence that the TLR2/1-vitamin D-cathelicidin pathway evolved as a biologically important immune response mechanism protecting human and non-human primates against infection.ResultsPCR-based amplification of the Alu SINE from human and non-human primate genomic DNA and subsequent sequence analysis, revealed perfect structural conservation of the VDRE in all primates examined. Reporter gene studies and induction of the endogenous CAMP gene in Rhesus macaque peripheral blood mononuclear cells demonstrated that the VDREs were conserved functionally. In addition, New World monkeys (NWMs) have maintained additional, functional steroid-hormone receptor binding sites in the AluSx SINE that confer retinoic acid responsiveness and provide potential thyroid hormone receptor binding sites. These sites were less well-conserved during human, ape and Old World monkey (OWM) evolution and the human CAMP gene does not respond to either retinoic acid or thyroid hormone.ConclusionWe demonstrated that the VDRE in the CAMP gene originated from the exaptation of an AluSx SINE in the lineage leading to humans, apes, OWMs and NWMs and remained under purifying selection for the last 55–60 million years. We present convincing evidence of an evolutionarily fixed, Alu-mediated divergence in steroid hormone nuclear receptor gene regulation between humans/primates and other mammals. Evolutionary selection to place the primate CAMP gene under regulation of the vitamin D pathway potentiates the innate immune response and may counter the anti-inflammatory properties of vitamin D.

Impact of Rhythmic Oral Activity on the Timing of Muscle Activation in the Swallow of the Decerebrate Pig

The pharyngeal swallow can be elicited as an isolated event but, in normal animals, it occurs within the context of rhythmic tongue and jaw movement (RTJM). The response includes activation of the multifunctional geniohyoid muscle, which can either protract the hyoid or assist jaw opening; in conscious nonprimate mammals, two bursts of geniohyoid EMG activity (GHemg) occur in swallow cycles at times consistent with these two actions. However, during experimentally elicited pharyngeal swallows, GHemg classically occurs at the same time as hyoglossus and mylohyoid activity (short latency response) but, when the swallow is elicited in the decerebrate in the absence of RTJM, GHemg occurs later in the swallow (long latency response). We tested the hypothesis that it was not influences from higher centers but a brain stem mechanism, associated with RTJM, which caused GHemg to occur earlier in the swallow. In 38 decerebrate piglets, RTJM occurred sporadically in seven animals. Before RTJM, GHemg had a long latency, but, during RTJM, swallow related GHemg occurred synchronously with activity in hyoglossus and mylohyoid, early in the swallow. Both early and late responses were present during the changeover period. During this changeover period, duplicate electrodes in the geniohyoid could individually detect either the early or the late burst in the same swallow. This suggested that two sets of geniohyoid task units existed that were potentially active in the swallow and that they were differentially facilitated or inhibited depending on the presence or absence of rhythmic activity originating in the brain stem.

Unfolding the codes of short-term feed appetence in farm and companion animals. A comparative oronasal nutrient sensing biology review

The evolution of the chemical senses has resulted in a sensory apparatus for high taste and smell acuity in mammals and birds to ensure self-nourishment. Such peripheral chemosensory systems function as a code to unfold the nutritional value of feedstuffs. Food ingestion simultaneously evokes odor, taste and thermo-mechanical (somatosensing) sensations. Olfaction represents the capacity to identify feed volatiles that are predominantly derived from essential nutrients in plants. Comparative biology of olfaction shows that primates and chickens have a smaller olfactory epithelium and fewer olfactory receptor (OR) genes than non-primate mammals studied to date including farm and companion animals, such as the pig, the cow, the dog, the cat and the horse. A significant proportion of the total OR genes in mammals and birds have lost their functionality (pseudogenes) in a process that seems to reflect a decrease in the animal’s reliance on the sense of smell, particularly in humans and cows. The taste system allows animals to recognize a diverse repertoire of nutrient (sugars, amino acids, salts, acids and fats) or toxic related chemical entities that provide valuable information about the quality of food. Taste senses non-volatile molecules in the oral cavity through taste receptors (TR). The TR are expressed in the sensory cells forming the taste buds of the tongue’s papillae. Taste cells are linked to a network of solitary chemosensory cells diffused through many non-taste tissues involved in metabolic homeostasis. The number of functional taste receptor genes (TASR) in humans is equivalent to that in other mammals and superior to that in chickens. The TASR family 1 (TAS1R coding for umami and sweet TR) is conserved, in number and type, across the species evaluated, with the exception of the sweet receptor in chicken and feline species. The TASR family 2 (TAS2R coding for bitter TR) shows a strong adaptive capacity to dietary sources and digestive physiology across vertebrates. Pseudogenization (loss of gene functionality) in the TAS2R family seems to be a frequent strategy. The implications of oronasal nutrient sensing related to comparative animal feeding strategies and behaviors such as neophobia, feed refusal and hedonic preferences are discussed. Feed palatability and appetence might be one of the main driving forces in short-term feed consumption. Finally, practical applications relevant to animal production are outlined. Key words: Nutrient sensing, taste, olfaction, somatosensing, feed intake, farm, companion animals

Scaling of chew cycle duration in primates

The biomechanical determinants of the scaling of chew cycle duration are important components of models of primate feeding systems at all levels, from the neuromechanical to the ecological. Chew cycle durations were estimated in 35 species of primates and analyzed in conjunction with data on morphological variables of the feeding system estimating moment of inertia of the mandible and force production capacity of the chewing muscles. Data on scaling of primate chew cycle duration were compared with the predictions of simple pendulum and forced mass-spring system models of the feeding system. The gravity-driven pendulum model best predicts the observed cycle duration scaling but is rejected as biomechanically unrealistic. The forced mass-spring model predicts larger increases in chew cycle duration with size than observed, but provides reasonable predictions of cycle duration scaling. We hypothesize that intrinsic properties of the muscles predict spring-like behavior of the jaw elevator muscles during opening and fast close phases of the jaw cycle and that modulation of stiffness by the central nervous system leads to spring-like properties during the slow close/power stroke phase. Strepsirrhines show no predictable relationship between chew cycle duration and jaw length. Anthropoids have longer chew cycle durations than nonprimate mammals with similar mandible lengths, possibly due to their enlarged symphyses, which increase the moment of inertia of the mandible. Deviations from general scaling trends suggest that both scaling of the jaw muscles and the inertial properties of the mandible are important in determining the scaling of chew cycle duration in primates.

The Clinical and Translational Science Award (CTSA) Consortium and the Translational Research Model

The shift from isolated researchers working in their individual laboratories to diverse research teams working in collaboration towards a common goal is a fundamental element of the Clinical and Translational Science Award (CTSA) (http://www.ctsaweb.org/). What is often misunderstood, however, is the depth and breadth of the translational paradigm. The NIH Roadmap discusses two basic steps of translation. First, basic science research must be translated to humans (the so-called T1 translation), and then secondarily translated into clinical practice (T2 translation) (http://nihroadmap.nih.gov/). Further work has demonstrated that in fact this second phase of translation includes two separate steps, first knowledge from T1 translational studies must be translated to patients (T2), and then we must translate our knowledge into actual clinical practice (T3 translation) (Westfall et al. 2007). Closer scrutiny, however, reveals more complexity and the need for many levels of translation. In this essay, I will briefly outline some of the myriad levels of translation necessary, and provide some examples to illustrate why further work is needed at these levels. Further, I will briefly describe the CTSA Consortium and discuss how this new model of research is attempting to address some of these needs. Translation takes many forms. If we start with a finding in a basic science laboratory that might have applications to the care of humans, such knowledge must go through many steps before it can have clinical applications. Basic scientific data must be translated into animal models, often this translation may start with non-primate mammals with subsequent translation into non-human primates. These pre-human experiments represent many layers of translation and require the collaboration of many scientists working in different research laboratories. Next, under the T1 translation, clinical researchers must assess the clinical applications in limited clinical conditions through controlled early-phase clinical trials. Next, knowledge from these early clinical experiments must be applied more broadly through phase 3 trials. Once clinical applications have been demonstrated through this T2 translation, clinicians must find ways to move these findings into the daily care of patient (T3). Merely translating findings to the actual bedside, however, is not enough. Moving scientific knowledge into the public sector and thereby changing people’s everyday lives represents a major challenge (T4). While many focus heavily on T1 and T2 translation, without T3 translation we cannot bring the benefits of medical research to individual patients. There exist many examples where despite excellent clinical research demonstrating clear benefit, individual physicians are slow to adopt best practices. One such example is the evidence that despite the clear benefits of statins in patients with elevated cholesterol, many patients for whom statins are indicated are not placed on appropriate therapy (Pasternak et al. 2002). Further, we must also translate scientific knowledge into people’s everyday lives. Merely knowing that an intervention can

The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates

The CD209 gene family that encodes C-type lectins in primates includes CD209 (DC-SIGN), CD209L (L-SIGN) and CD209L2. Understanding the evolution of these genes can help understand the duplication events generating this family, the process leading to the repeated neck region and identify protein domains under selective pressure. We compiled sequences from 14 primates representing 40 million years of evolution and from three non-primate mammal species. Phylogenetic analyses used Bayesian inference, and nucleotide substitutional patterns were assessed by codon-based maximum likelihood. Analyses suggest that CD209 genes emerged from a first duplication event in the common ancestor of anthropoids, yielding CD209L2 and an ancestral CD209 gene, which, in turn, duplicated in the common Old World primate ancestor, giving rise to CD209L and CD209. K(A)/K(S) values averaged over the entire tree were 0.43 (CD209), 0.52 (CD209L) and 0.35 (CD209L2), consistent with overall signatures of purifying selection. We also assessed the Toll-like receptor (TLR) gene family, which shares with CD209 genes a common profile of evolutionary constraint. The general feature of purifying selection of CD209 genes, despite an apparent redundancy (gene absence and gene loss), may reflect the need to faithfully recognize a multiplicity of pathogen motifs, commensals and a number of self-antigens.

Cone visual pigments in two marsupial species: the fat-tailed dunnart (Sminthopsis crassicaudata) and the honey possum (Tarsipes rostratus)

Uniquely for non-primate mammals, three classes of cone photoreceptors have been previously identified by microspectrophotometry in two marsupial species: the polyprotodont fat-tailed dunnart (Sminthopsis crassicaudata) and the diprotodont honey possum (Tarsipes rostratus). This report focuses on the genetic basis for these three pigments. Two cone pigments were amplified from retinal cDNA of both species and identified by phylogenetics as members of the short wavelength-sensitive 1 (SWS1) and long wavelength-sensitive (LWS) opsin classes. In vitro expression of the two sequences from the fat-tailed dunnart confirmed the peak absorbances at 363 nm in the UV for the SWS1 pigment and 533 nm for the LWS pigment. No additional expressed cone opsin sequences that could account for the middle wavelength cones could be amplified. However, amplification from the fat-tailed dunnart genomic DNA with RH1 (rod) opsin primer pairs identified two genes with identical coding regions but sequence differences in introns 2 and 3. Uniquely therefore for a mammal, the fat-tailed dunnart has two copies of an RH1 opsin gene. This raises the possibility that the middle wavelength cones express a rod rather than a cone pigment.

Scaling of the retinogeniculostriate pathway in mammals

Studies of the relative sizes of brain components in mammals suggest that areas responsible for sensory processing, including visual processing, are correlated with aspects of ecology. Primate orbit convergence and binocular vision are correlated with overall size of the brain as well as components of the visual pathway, such as the lateral geniculate nucleus. The question remains whether components of the visual pathway (optic tract, lateral geniculate nucleus, and primary visual cortex) are similarly correlated in non‐primate mammals.This study examines the relationship between orbit convergence, binocular field overlap, overall brain size, and the volumes of components of the visual pathway. Data on orbit orientation are combined with those on overall brain size in primates, and non‐primate mammals. In addition, data on brain component volumes were collated for a subset of these taxa. Volumetric data on neural components of the visual pathway are correlated with convergence among the taxa included in this study. Binocular taxa have relatively larger optic tracts, lateral geniculate nuclei and primary visual cortices when brain volume is held constant. Primates are not unique in the relationship between binocularity and brain size; however, since primates are the most binocular of the mammals, they also have the relatively largest components of the visual pathway.

Food Habits of an Endangered Carnivore,Cryptoprocta Ferox, in the Dry Deciduous Forests of Western Madagascar

We describe the diet of fossas (Cryptoprocta ferox) in a dry deciduous forest of western Madagascar from 376 scats collected between June 1994 and September 1996, from which 554 prey items were identified. More than 90% of these were vertebrates, and more than 50% were lemurs. No other nonprimate mammal includes such a high proportion of primate items in its diet. The principal prey comprised approximately 6 lemur species and 2 or 3 spiny tenrec species, along with snakes and small mammals. Significant differences were apparent in the composition of the scats in wet and dry seasons, with a higher proportion of Tenrec in the former, and fewer lemurs. Within the confines of a diet of vertebrates, fossas appeared to be opportunistic predators. For those prey types for which data were available, a significant relationship was found between the estimated relative number of individuals taken of any one type of prey and its abundance. Fossas were estimated to remove up to 19% of their prey populations per year. This high impact suggests that they were living close to the maximum population density possible on the available prey. Species of a wide range of body masses were included in the diet. Verreaux's sifaka (Propithecus verreauxi), weighing more than one-half of the body mass of the fossa, constituted approximately 11% of the prey biomass.

霊長類と他の動物の混群現象についての研究の現状

I reviewed the studies on polyspecific associations between primates and non-primate animals to appreciate the present situation about this topic. I collected 104 case studies from 50 publications. The partner animals included 19 mammal species, 33-34 bird species, 1 reptile species, and 1-2 insect species, respectively. Among them, associations with non-primate mammals (n=43) and birds (n=59) occupied most of the reported cases. Many polyspecific associations between primates and other mammal species were reported from Asia and Africa, while those between primates and bird species were reported from Central and South America. 34 primate species worldwide formed associations with non-primate animals.Polyspecific associations between primates and other animals included 1) that primates (or other animals) provide food resources to their partner animals and 2) that primates (or other animals) provide anti-predator behavior (e.g., sentinel behavior, loud call, and alarm call). The former association increases foraging benefits to the partner animals, and the latter association decreases predation risk of the partner animals. Most studies, however, pointed out that benefit from given associations are commensalisic, (or even parasitism), i. e. biased to non-primate species.Most of these studies are anecdotal, and do not show quantitative data for the frequency of the association or the benefit of partner animals from participating in the associations. Thus, this interesting phenomenon has not been discussed from an ecological perspective. I recommend several approaches for how to overcome these present challenges.

Revealing the molecular layer of the primate dorsal cochlear nucleus

In nonprimate mammals, the dorsal cochlear nucleus (DCN) is thought to play a role in the orientation of the head toward sounds of interest by integrating acoustic and somatosensory information. Humans and higher primates might not use this system because of reported phylogenetic changes in DCN cytoarchitecture [Moskowitz N (1969) Comparative aspects of some features of the central auditory system of primates. Ann N Y Acad Sci 167:357–369; Moore JK, Osen KK (1979) The cochlear nuclei in man. Am J Anat 154:393–418; Moore JK (1980) The primate cochlear nuclei: loss of lamination as a phylogenetic process. J Comp Neurol 193:609–629]. In this study, we re-evaluated this question from a comparative perspective and examined the rhesus monkey (cercopithecoid primate) using more sensitive probes and higher resolution imaging methods. We used electron microscopy to identify parallel fibers and their synapses, and molecular markers to determine that primates exhibit the main components of excitatory neurotransmission as other mammals. We observed that characteristics of the monkey molecular layer resembled what has been reported for nonprimates: (1) immunohistochemistry revealed many unmyelinated, thin axons and en passant glutamatergic synapses on dendritic spines; (2) immunohistochemistry for phosphodiesterase (PDE10A) showed the nuclei of granule cells distributed in the external molecular layer and the deep layers in the DCN; (3) antibodies for the inositol trisphosphate receptor (IP3r) and calbindin immunostained cartwheel cells; (4) postembedding immunogold labeling revealed synaptic expression of AMPA and delta glutamate receptor subunits on spines in parallel fiber endings; and (5) parallel fibers use vesicular glutamate transporter 1 (VGLUT1) to package glutamate into the synaptic vesicles and to mediate glutamate transport. These observations are consistent with the argument that the rhesus monkey DCN has neuronal features similar to those of other nonprimate mammals.

First order connections of the visual sector of the thalamic reticular nucleus in marmoset monkeys (Callithrix jacchus)

The thalamic reticular nucleus (TRN) supplies an important inhibitory input to the dorsal thalamus. Previous studies in non-primate mammals have suggested that the visual sector of the TRN has a lateral division, which has connections with first-order (primary) sensory thalamic and cortical areas, and a medial division, which has connections with higher-order (association) thalamic and cortical areas. However, the question whether the primate TRN is segregated in the same manner is controversial. Here, we investigated the connections of the TRN in a New World primate, the marmoset (Callithrix jacchus). The topography of labeled cells and terminals was analyzed following iontophoretic injections of tracers into the primary visual cortex (V1) or the dorsal lateral geniculate nucleus (LGNd). The results show that rostroventral TRN, adjacent to the LGNd, is primarily connected with primary visual areas, while the most caudal parts of the TRN are associated with higher order visual thalamic areas. A small region of the TRN near the caudal pole of the LGNd (foveal representation) contains connections where first (lateral TRN) and higher order visual areas (medial TRN) overlap. Reciprocal connections between LGNd and TRN are topographically organized, so that a series of rostrocaudal injections within the LGNd labeled cells and terminals in the TRN in a pattern shaped like rostrocaudal overlapping "fish scales." We propose that the dorsal areas of the TRN, adjacent to the top of the LGNd, represent the lower visual field (connected with medial LGNd), and the more ventral parts of the TRN contain a map representing the upper visual field (connected with lateral LGNd).

Normal human serum contains high levels of anti‐Galα1‐4GlcNAc antibodies

Natural xenoreactive antibodies (Abs) directed against the Bdi-epitope (Gal alpha 1-3Gal beta) on the cells of non-primate mammals take part in hyperacute rejection of xenotransplanted organs. We found that some Abs, which were one-step affinity purified on Bdi-Sepharose, cross-reacted with the disaccharide Gal alpha 1-4GlcNAc beta. The epitope Gal alpha 1-4GlcNAc has not been identified on mammals or bacterial polysaccharides yet. To isolate the antibodies of the corresponding specificity the disaccharide was immobilized on Sepharose and antibodies were affinity purified from pooled serum of blood group O individuals. These one-step purified Abs cross-reacted with Bdi, but after a prior absorption step on Bdi-Sepharose no cross-reactivity with Bdi was observed any longer. Surprisingly, the quantity of anti-Gal alpha 1-4GlcNAc isolated from the same serum pool, 4-7 microg/ml, was equal to that of anti-Bdi or more. Independently of ABO blood groups all the tested healthy donors had anti-Gal alpha 1-4GlcNAc Abs at a similar level. Monospecific anti-Gal alpha 1-4GlcNAc Abs were not cytotoxic towards porcine cells. 1. The actual concentration of monospecific, xenoreactive Gal alpha 1-3Gal beta Abs in blood may be considerably lower than the value referred to in the literature for 'anti-alpha Gal' or 'anti-Galili' antibodies. 2. Anti-Gal alpha 1-4GlcNAc Abs seem not to be important for xenotransplantation.