Takako Miyabe-Nishiwaki

Differential Prefrontal White Matter Development in Chimpanzees and Humans

A comparison of developmental patterns of white matter (WM) within the prefrontal region between humans and nonhuman primates is key to understanding human brain evolution. WM mediates complex cognitive processes and has reciprocal connections with posterior processing regions [1, 2]. Although the developmental pattern of prefrontal WM in macaques differs markedly from that in humans [3], this has not been explored in our closest evolutionary relative, the chimpanzee. The present longitudinal study of magnetic resonance imaging scans demonstrated that the prefrontal WM volume in chimpanzees was immature and had not reached the adult value during prepuberty, as observed in humans but not in macaques. However, the rate of prefrontal WM volume increase during infancy was slower in chimpanzees than in humans. These results suggest that a less mature and more protracted elaboration of neuronal connections in the prefrontal portion of the developing brain existed in the last common ancestor of chimpanzees and humans, and that this served to enhance the impact of postnatal experiences on neuronal connectivity. Furthermore, the rapid development of the human prefrontal WM during infancy may help the development of complex social interactions, as well as the acquisition of experience-dependent knowledge and skills to shape neuronal connectivity.

Developmental patterns of chimpanzee cerebral tissues provide important clues for understanding the remarkable enlargement of the human brain.

Developmental prolongation is thought to contribute to the remarkable brain enlargement observed in modern humans (Homo sapiens). However, the developmental trajectories of cerebral tissues have not been explored in chimpanzees (Pan troglodytes), even though they are our closest living relatives. To address this lack of information, the development of cerebral tissues was tracked in growing chimpanzees during infancy and the juvenile stage, using three-dimensional magnetic resonance imaging and compared with that of humans and rhesus macaques (Macaca mulatta). Overall, cerebral development in chimpanzees demonstrated less maturity and a more protracted course during prepuberty, as observed in humans but not in macaques. However, the rapid increase in cerebral total volume and proportional dynamic change in the cerebral tissue in humans during early infancy, when white matter volume increases dramatically, did not occur in chimpanzees. A dynamic reorganization of cerebral tissues of the brain during early infancy, driven mainly by enhancement of neuronal connectivity, is likely to have emerged in the human lineage after the split between humans and chimpanzees and to have promoted the increase in brain volume in humans. Our findings may lead to powerful insights into the ontogenetic mechanism underlying human brain enlargement.

Aqueous chromatographic system for the quantification of propofol in biological fluids using a temperature-responsive polymer modified stationary phase

A new method for the quantitative analysis of monkey serum propofol, which is widely used as an anaesthetic agent, was developed by utilizing a temperature-responsive polymer of N-isopropylacrylamide (NIPAAm) and butyl methacrylate (BMA) as the stationary phase of HPLC-fluorescence detection. This poly(NIPAAm-co-BMA) copolymer undergoes a reversible phase transition from a hydrophilic to a hydrophobic microstructure when triggered by change in the temperature. Also this chromatographic system is possible to separate the analytes by using only water as a mobile phase. A pretreatment of the serum (80 microL) was only solid-phase extraction, and the recovery rate of propofol and internal standard was more than 77%, respectively. This method covered the calibration range from 0.5 microg/mL to 10 microg/mL and allowed a reproducible quantification of the serum propofol in administrated monkey serum. The intra- and inter-assay relative standard deviations were less than 14.1%. In addition, there was good relationship of the quantification values between the developed method and the widely used reversed-phase HPLC method. Our developed method has proven to be useful for a simple analysis of propofol in clinical practice, because the avoidance of complicated mobile phase preparation was possible, and only temperature changing could regulate the retention time of the analyte. In addition, by using water instead of fossil fuel, it is the ideal analytical method according to green chemistry.

Streptococcus troglodytae sp. nov., from the chimpanzee oral cavity.

Six strains, TKU 25, TKU 28, TKU 30, TKU 31(T), TKU 33 and TKU 34, were isolated from the oral cavity of a chimpanzee (Pan troglodytes). Colonies of strains grown on Mitis-Salivarius agar were similar in morphology to that of Streptococcus mutans. The novel strains were Gram-stain-positive, facultatively anaerobic cocci that lacked catalase activity. Analysis of the partial 16S rRNA gene sequences of these isolates showed that the most closely related strain was the type strain of S. mutans (96.4 %). The next closely related strains to the isolates were the type strains of Streptococcus devriesei (94.5 %) and Streptococcus downei (93.9 %). These isolates could be distinguished from S. mutans by inulin fermentation and alkaline phosphatase activity (API ZYM system). The peptidoglycan type of the novel isolates was Glu-Lys-Ala(3). Strains were not susceptible to bacitracin. On the basis of phenotypic characterization, partial 16S rRNA gene and two housekeeping gene (groEL and sodA) sequence data, we propose a novel taxon, Streptococcus troglodytae sp. nov.; the type strain is TKU 31(T) ( = JCM 18038(T) = DSM 25324(T)).

Early changes in Homer1 proteins in the spinal dorsal horn are associated with loose ligation of the rat sciatic nerve.

BACKGROUND: Plasticity in the spinal dorsal horn is thought to underlie, at least in part, pain behavior after peripheral nerve injury. Homer1 proteins play an important role in synaptic plasticity through an activity-dependent remodeling of the postsynaptic density (PSD). In this study, we examined the early consequences of the loose ligation of the sciatic nerve on the levels of Homer1a and Homer1b/c proteins in the PSD of spinal dorsal horn neurons. METHODS: Male rats were randomly assigned to control, sham-operated, or ligated groups. Four hours after sciatic exposure or ligation, the animals were anesthetized and killed. Dorsal horn ipsilateral and contralateral quadrants were homogenized and centrifuged to obtain a PSD-containing LP1 fraction. Homer1 isoforms were identified in Western immunoblots. In some animals, Homer1 small interfering RNA (siRNA), nontarget siRNA, MK-801, or U01026 was injected intrathecally before surgery to assess the effects of this treatment on the levels of Homer1 isoforms and on 2 signs of injury-associated pain behavior, a shift in weight-bearing distribution and thermal hyperalgesia. RESULTS: In ligated animals, the protein levels of Homer1a increased and those of Homer1b/c decreased in the ipsilateral LP1 fraction of the spinal dorsal horn. In contrast, no changes were detected in the contralateral LP1 fraction of ligated animals or the ipsilateral or contralateral LP1 fraction of sham-operated animals. Intrathecal injections of Homer1 siRNA, but not nontarget siRNA, 2 h before the ligation prevented the accumulation of Homer1a and loss of Homer1b/c in the ipsilateral LP1 fraction. The same pretreatment with Homer1 siRNA also alleviated both a shift in weight-bearing behavior and thermal hyperalgesia in the ligated animals. Intrathecal injections of MK-801 or U0126 15 min before the ligation similarly prevented the injury-associated changes in Homer1 protein levels and the behavioral signs of pain. CONCLUSION: The ligation-associated changes in the protein levels of Homer1a and Homer1b/c in the ipsilateral PSD of spinal dorsal horn neurons may be an important early reflection of the injury-associated plasticity that in time leads to the development of persistent pain.

Tetraparesis resembling acute transverse myelitis in a captive chimpanzee (Pan troglodytes): long-term care and recovery.

Background  A 24‐year‐old, male chimpanzee (Pan troglodytes) developed acute tetraparesis. Magnetic resonance imaging showed a diffuse T2‐weighted hyperintensive lesion, indicating inflammation at the C1–2 level. All infective, autoimmune, and vascular investigations were unremarkable.

Evaluation of the predictive performance of a pharmacokinetic model for propofol in Japanese macaques (Macaca fuscata fuscata)

Propofol is a short-acting intravenous anesthetic used for induction/maintenance anesthesia. The objective of this study was to assess a population pharmacokinetic (PPK) model for Japanese macaques during a step-down infusion of propofol. Five male Japanese macaques were immobilized with ketamine (10 mg/kg) and atropine (0.02 mg/kg). A bolus dose of propofol (5 mg/kg) was administrated intravenously (360 mg/kg/h) followed by step-down infusion at 40 mg/kg/h for 10 min, 20 mg/kg/h for 10 min, and then 15 mg/kg/h for 100 min. Venous blood samples were repeatedly collected following the administration. The plasma concentration of propofol (Cp) was measured by high-speed LC-FL. PPK analyses were performed using NONMEM VII. Median absolute prediction error and median prediction error (MDPE), the indices of prediction inaccuracy and bias, respectively, were calculated, and PE - individual MDPE vs. time was depicted to show the variability of prediction errors. In addition, we developed another population pharmacokinetic model using previous and current datasets. The previous PK model achieved stable prediction of propofol Cp throughout the study period, although it underestimates Cp. The step-down infusion regimen described in this study would be feasible in macaques during noninvasive procedures.

Impaired Air Conditioning within the Nasal Cavity in Flat-Faced Homo.

We are flat-faced hominins with an external nose that protrudes from the face. This feature was derived in the genus Homo, along with facial flattening and reorientation to form a high nasal cavity. The nasal passage conditions the inhaled air in terms of temperature and humidity to match the conditions required in the lung, and its anatomical variation is believed to be evolutionarily sensitive to the ambient atmospheric conditions of a given habitat. In this study, we used computational fluid dynamics (CFD) with three-dimensional topology models of the nasal passage under the same simulation conditions, to investigate air-conditioning performance in humans, chimpanzees, and macaques. The CFD simulation showed a horizontal straight flow of inhaled air in chimpanzees and macaques, contrasting with the upward and curved flow in humans. The inhaled air is conditioned poorly in humans compared with nonhuman primates. Virtual modifications to the human external nose topology, in which the nasal vestibule and valve are modified to resemble those of chimpanzees, change the airflow to be horizontal, but have little influence on the air-conditioning performance in humans. These findings suggest that morphological variation of the nasal passage topology was only weakly sensitive to the ambient atmosphere conditions; rather, the high nasal cavity in humans was formed simply by evolutionary facial reorganization in the divergence of Homo from the other hominin lineages, impairing the air-conditioning performance. Even though the inhaled air is not adjusted well within the nasal cavity in humans, it can be fully conditioned subsequently in the pharyngeal cavity, which is lengthened in the flat-faced Homo. Thus, the air-conditioning faculty in the nasal passages was probably impaired in early Homo members, although they have survived successfully under the fluctuating climate of the Plio-Pleistocene, and then they moved “Out of Africa” to explore the more severe climates of Eurasia.

Streptococcus panodentis sp. nov. from the oral cavities of chimpanzees

Three strains TKU9, TKU49 and TKU50T, were isolated from the oral cavities of chimpanzees (Pan troglodytes). The isolates were all gram‐positive, facultative anaerobic cocci that lacked catalase activity. Analysis of partial 16S rRNA gene sequences showed that the most closely related species was Streptococcus infantis (96.7%). The next most closely related species to the isolates were S. rubneri, S. mitis, S. peroris and S. australis (96.6 to 96.4%). Based on the rpoB and gyrB gene sequences, TKU50T was clustered with other member of the mitis group. Enzyme activity and sugar fermentation patterns differentiated this novel bacterium from other members of the mitis group streptococci. The DNA G + C content of strain TKU50T was 46.7 mol%, which is the highest reported value for members of the mitis group (40–46 mol%). On the basis of the phenotypic characterization, partial 16S rRNA gene and sequences data for two housekeeping gene (gyrB and rpoB), we propose a novel taxa, S. panodentis for TKU 50T (type strain = CM 30579T = DSM 29921T), for these newly described isolates.

Urological Screening of a Wild Group of Japanese Macaques (Macaca fuscata yakui): Investigating Trends in Nutrition and Health

Primates are among the most threatened of animal taxa, and it is therefore increasingly important to examine ways to monitor their health in the wild. We here investigate trends in nutrition and health in Japanese macaques (Macaca fuscata yakui) under natural conditions using a common tool from human and veterinary health practices: urinalysis. Between October 2007 and August 2009, we collected 103 urine samples ad libitum from 29 identified individuals of a group of macaques on Yakushima Island. We used multireagent dipstick analysis to examine variation in 10 urine chemistry parameters across subjects in combination with systematic monitoring of clinical signs of disease (via focal sampling). Positive tests tended to be transient and weak, i.e., analytes detected in trace amounts, and were not associated with clinical signs of disease. In addition, most urine samples we collected were highly concentrated (urine specific gravity ≥1.030), which could have increased the likelihood of detecting clinically insignificant amounts of analytes that can occur in urine. However, we found that ketone bodies, which are not normally found in urine, were more prevalent during winter than summer, which may indicate that Japanese macaques inhabiting the richest habitat available to the species nonetheless experience an energy deficit during periods of low food quality and high thermoregulatory costs. We conclude that dipstick urinalysis can be used to examine general trends in nutrition and health, but that results must be interpreted with care because positive tests may not reflect clinically significant urological conditions in many cases.