Kentaro Sakamoto - Academia.edu (original) (raw)
Papers by Kentaro Sakamoto
Japanese Journal of Veterinary Research, May 31, 2002
Chemical senses, 2015
Inbreeding avoidance is essential to providing offspring with genetic diversity. Females' mat... more Inbreeding avoidance is essential to providing offspring with genetic diversity. Females' mate choice is more crucial than males' for successful reproduction because of the high cost of producing gametes and limited chances to mate. However, the mechanism of female inbreeding avoidance is still unclear. To elucidate the mechanism underlying inbreeding avoidance by females, we conducted Y-maze behavioral assays using BALB/c and C57BL/6 female mice. In both strains, the avoidance of male urine from the same strain was lower in the low estrogen phase than in the high estrogen phase. The estrous cycle-dependent avoidance was completely prevented by vomeronasal organ (VNO) removal. To assess the regulation of the vomeronasal system by estrogen, the neural excitability was evaluated by immunohistochemistry of the immediate early gene products. Although estrogen did not affect neural excitability in the VNO, estrogen enhanced the neural excitability of the mitral cell layer in the ...
Journal of Veterinary Medical Science, Oct 1, 2009
Novel cytochrome P450 1A (CYP1A) cDNA fragments were isolated from the liver of nine Japanese amp... more Novel cytochrome P450 1A (CYP1A) cDNA fragments were isolated from the liver of nine Japanese amphibian species using reverse transcription polymerase chain reaction (RT-PCR). Degenerate PCR primers were used to amplify 122-bp fragments of CYP1A cDNAs. Construction of a phylogenetic tree revealed that urodele and anuran amphibians formed two branches. Within the anuran species, three branches were formed: 1) Ranidae and Rhacophoridae, 2) Bufo japonicus formosus and Hyla japonica, and 3) Xenopus laevis. The cDNA nucleotide sequence of these CYP1A fragments showed identities ranging 72-98% (all), 72-78% (Anura vs. Urodela), 75 to 98% (Anura), 81% (Urodela), 74-80% (Xenopus laevis vs. nine Japanese amphibians).
The Japanese Journal of Veterinary Research, Aug 1, 2008
The wide use of organophosphorus (OP) pesti-cides in agriculture has several interesting implicat... more The wide use of organophosphorus (OP) pesti-cides in agriculture has several interesting implications for environmental safety, such as their persistence and selective toxicity for insects rather
Japanese Journal of Veterinary Research, Aug 1, 2014
Contamination levels of coplanar polychlorinated biphenyls (Co-PCBs), polycyclic aromatic hydroca... more Contamination levels of coplanar polychlorinated biphenyls (Co-PCBs), polycyclic aromatic hydrocarbons (PAHs), and dichlorodiphenyltrichloroethane (DDTs) were measured in the entire body of the large Japanese field mouse (Apodemus speciosus) collected from Hokkaido (Ishikari and Rankoshi) and Aomori prefecture (Takko) in Japan. Higher concentrations of PCBs including Co-PCBs, were observed in the mice collected from Ishikari than those from Rankoshi. The concentration of PAHs in the soil from Ishikari was also higher than that in the other sampling sites. The findings suggest that Ishikari is the most polluted area, probably because of human activities, depending on the population distribution. However, the observed contaminant levels were extremely lower compared to those in previous studies. The ratio of testis weight to body weight (TW/BW) was the lowest in the mice collected from Ishikari, which is the area contaminated with PAHs and p,p'-dichlorodiphenyldichloroethylene (DDE). However, the serum testosterone levels of mice from the Ishikari area were higher than those from the non-contaminated other areas although no significant differences. Previous studies have shown that a low-level exposure to dioxin related compounds (DRCs) disturbances in sexual function, resulting in the production of testosterone. This study showed that POPs exposure is one of the possibility of the high testosterone concentration in the mice of the Ishikari area in addition to a cause of biological and environmental factors such as habitat density, age, temperatures and/or food riches.
In an attempt to explore the functioning of nitric oxide (NO) in pancreatic exocrine cells, we ha... more In an attempt to explore the functioning of nitric oxide (NO) in pancreatic exocrine cells, we have recently obtained several lines of circumstantial evidence indicating that one of molecular targets of NO is phospholipase C (PLC), the activation of which leads to an increase in the cytosolic Ca2+ concentration ([Ca2+]i) via inositol 1, 4, 5-trisphosphate, IP3. However, whether IP3 is actually produced by NO has not yet been substantiated. The present study was therefore designed to directly measure the intracellular IP3, concentration ([IP3]i) for better understanding of the underlying mechanisms with the help of pharmacological tools. [IP3]i was measured using a fluorescence polarization technique (HitHunter). We obtained the following results: 1) varying concentrations of an NO donor, sodium nitroprusside (SNP), elevated [IP3]i, 2) this elevation was completely inhibited in the presence of the soluble guanylyl cyclase (sGC) inhibitor, 1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one (ODQ), 3) varying concentrations of the cGMP analogue, 8-Br-cGMP, also increased [IP3]i, 4) the cGMP analogue-induced IP3 production was abolished by pretreatment with either a PLC inhibitor, U73122, or a G-protein inhibitor, GP2A, and 5) KT5823, a potent and highly selective inhibitor of cGMP-dependent protein kinase G (PKG), also abolished the IP3 production induced by 8-Br-cGMP. These results suggest that the NO-induced [Ca2+]i increase is triggered by an increase in [IP3]i located downstream from intracellular cGMP elevation. In this intracellular pathway, each sGC, cGMP-dependent PKG, G-protein and PLC were suggested to be involved. The present work provides new insights into the intracellular signaling accelerated by NO. NO triggers a [Ca2+]I increase via cGMP and IP3 in pancreatic acinar cells.
The flight ability of animals is restricted by the scaling effects imposed by physical and physio... more The flight ability of animals is restricted by the scaling effects imposed by physical and physiological factors. In comparisons of the power available from muscle and the mechanical power required to fly, theoretical studies have predicted that the margin between the powers should decrease with body size and that flying animals have a maximum body size 1-7 . However, predicting an absolute value of this upper limit has been difficult because wing morphology and flight styles vary among species. Albatrosses and petrels have long, narrow, aerodynamically efficient wings and are considered to be soaring birds. Here, using animal-borne accelerometers, we show that scaling analyses of wing-flapping frequencies in these seabirds indicate that the maximum size limit for soaring animals is a body mass of 41 kg and a wingspan of 5.1 m. Soaring seabirds were observed to have two modes of flapping frequencies: vigorous flapping during takeoff and sporadic flapping during cruising flight. In these species, high and low flapping frequencies were found to scale with body mass (mass -0.30 and mass -0.18 ) in a manner similar to the predictions from biomechanical flight models (mass -1/3 and mass -1/6 ) 2, 4, 6, 8-10 . The
Journal of the Yamashina Institute for Ornithology, 2008
Journal of Antimicrobial Chemotherapy, 2008
Drug Metabolism and Disposition, 2009
Diazepam (7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one) is widely used as a ... more Diazepam (7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one) is widely used as a sedative, hypnotic, and anti-anxiety drug. At low diazepam concentrations, p-hydroxylation is the major metabolic pathway in rat liver microsomes. However, there are marked ( approximately 300-fold) inter- and intrastrain differences in the activity among Sprague-Dawley, Brown Norway, Dark Agouti, and Wistar rats. In our previous study, we determined that a deficiency of CYP2D3 protein, not CYP2D2, was responsible for the inter- and intrastrain differences in diazepam p-hydroxylation (Drug Metab Dispos 33:1657-1660, 2005). Quantitative real-time polymerase chain reaction (PCR) did not provide enough evidence to explain the inter- and intrastrain differences in the expression of CYP2D3 protein. Nucleotide sequence analysis revealed the insertion of a thymine in exon 8 of the CYP2D3 gene in the poor diazepam metabolizers. This single nucleotide mutation caused a shift in the reading frame and introduced a premature termination signal. It is noteworthy that the heme binding region, which is essential to maintain proper heme binding and active cytochrome P450 enzymes, was consequently deleted by the premature termination signal. In contrast, no mutation was detected in the CYP2D3 gene of extensive metabolizers. Thus, the truncated CYP2D3 must be a nonfunctional enzyme in poor metabolizers. In addition, we developed a convenient and specific genotyping assay using PCR-restriction, fragment-length polymorphism to distinguish homozygotes from heterozygotes. The genotyping gave results fully consistent with those of the inter- and intrastrain differences in diazepam p-hydroxylation.
The aim of the present study was to investigate the possible interaction between intracellular Ca... more The aim of the present study was to investigate the possible interaction between intracellular Ca(2+) and nitric oxide (NO) in rat pancreatic acinar cells, especially intracellular signaling events. (1) Nitric oxide donors SNP (0.1-100 μM) and NOR-3 (50-400 μM) induced Ca(2+) oscillations in fluo-4-loaded acini, that appeared to be analogous to what we usually observe in acini stimulated with physiological secretagogues such as CCK-8 and this oscillations were abolished in the presence of carboxy-PTIO. (2) The NO donors-evoked Ca(2+) oscillations were not abolished even in the absence of extracellular Ca(2+) but totally disappeared when cells were pretreated with thapsigargin, a sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase (SERCA) inhibitor. (3) Inhibition of guanylate cyclase with 1 H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) attenuated Ca(2+) oscillations evoked by SNP in the absence of extracellular Ca(2+). (4) Inhibitors of phospholipase C activity, U73122 and the IP(3)R blocker xestospongin C, both abolished the SNP-induced Ca(2+) response. (5) Furthermore, we found that both CCK-8 and carbachol (CCh) induced NO production in DAF-2-loaded acinar cells and that an inhibitor of NO synthase, N(G)-monomethyl-l-arginine (L-NMMA), significantly reduced CCK-8-induced Ca(2+) oscillation. These results indicate that NO mobilizes Ca(2+) from internal stores through activation of guanylate cyclase and resultant cGMP production. In addition, PLC activation of IP(3) production is also suggested to be involved in Ca(2+) mobilization via IP(3) receptors. This suggests the presence of cross-talk between Ca(2+) and NO in pancreatic acini and this cascade may, at least partially, participate in physiological secretagogue-evoked Ca(2+) dynamics in pancreatic acinar cells.
The Japanese journal of veterinary research, 2004
In order to examine whether iodine supplements may have caused a global decline in sperm concentr... more In order to examine whether iodine supplements may have caused a global decline in sperm concentrations during the past several decades, the synchronicity of the decline in mean sperm counts and the introduction of iodine supplements was analyzed statistically. A positive correlation between the incidence of thyroid disease and sperm counts has been detected in Europe. In addition, it has been shown that sperm counts began falling around 1965 in the United States, 40 years after iodine supplements were introduced. Mean sperm counts before and after 1965 were 111 x 10(6)/ml and 70 x 10(6)/ml, respectively, in calculations weighted by the number of subjects included in each individual publication. The timing of the declines coincided with the introduction of iodine supplements in the United States, France, and the United Kingdom. The implications are that the global decline in sperm concentrations may be caused by iodine intake. Geographical variation in the types of sperm count decli...
Journal of Toxicological Sciences, 2008
Warfarin is commonly used worldwide as a rodenticide. It inhibits coagulation of blood by inhibit... more Warfarin is commonly used worldwide as a rodenticide. It inhibits coagulation of blood by inhibiting vitamin K 2,3-epoxide reductase (VKOR) activity. An inadequate supply of vitamin K blocks the production of prothrombin and causes hemorrhage. It has been reported that repeated or long-term treatments with this drug cause resistance in wild rodents. However, the mechanism of warfarin resistance in rodents is still not known precisely. Recent studies reported and identified the function of the molecule, vitamin K epoxide reductase complex subunit 1 (VKORC1), which is the main unit of VKOR. An amino acid substitution in VKORC1 is one of the supposed mechanisms of warfarin resistance. An accelerated detoxification system involving cytochrome P450 (CYP) could also cause the rodenticide resistance. Administration of SKF-525A, a potent inhibitor for P450, increased the mortality due to reduction of warfarin metabolism in warfarin-resistant rats. Meanwhile, the appearance of warfarin-resistant rodents has led to the development of the more effective and toxic rodenticide superwarfarin, which is widely used in Europe and the USA. However, animals resistant to this second-generation rodenticide have already been reported in Europe. In this review, we focus on the mechanism and the pleiotropic effects of pesticide resistance in wild rodents.
An ethogram is a catalogue of discrete behaviors typically employed by a species. Traditionally a... more An ethogram is a catalogue of discrete behaviors typically employed by a species. Traditionally animal behavior has been recorded by observing study individuals directly. However, this approach is difficult, often impossible, in the case of behaviors which occur in remote areas and/or at great depth or altitude. The recent development of increasingly sophisticated, animal-borne data loggers, has started to overcome this problem. Accelerometers are particularly useful in this respect because they can record the dynamic motion of a body in e.g. flight, walking, or swimming. However, classifying behavior using body acceleration characteristics typically requires prior knowledge of the behavior of free-ranging animals. Here, we demonstrate an automated procedure to categorize behavior from body acceleration, together with the release of a user-friendly computer application, ''Ethographer''. We evaluated its performance using longitudinal acceleration data collected from a foot-propelled diving seabird, the European shag, Phalacrocorax aristotelis. The time series data were converted into a spectrum by continuous wavelet transformation. Then, each second of the spectrum was categorized into one of 20 behavior groups by unsupervised cluster analysis, using k-means methods. The typical behaviors extracted were characterized by the periodicities of body acceleration. Each categorized behavior was assumed to correspond to when the bird was on land, in flight, on the sea surface, diving and so on. The behaviors classified by the procedures accorded well with those independently defined from depth profiles. Because our approach is performed by unsupervised computation of the data, it has the potential to detect previously unknown types of behavior and unknown sequences of some behaviors.
PLoS ONE, 2009
The flight ability of animals is restricted by the scaling effects imposed by physical and physio... more The flight ability of animals is restricted by the scaling effects imposed by physical and physiological factors. In comparisons of the power available from muscle and the mechanical power required to fly, it is predicted that the margin between the powers should decrease with body size and that flying animals have a maximum body size. However, predicting the absolute value of this upper limit has proven difficult because wing morphology and flight styles varies among species. Albatrosses and petrels have long, narrow, aerodynamically efficient wings and are considered soaring birds. Here, using animal-borne accelerometers, we show that soaring seabirds have two modes of flapping frequencies under natural conditions: vigorous flapping during takeoff and sporadic flapping during cruising flight. In these species, high and low flapping frequencies were found to scale with body mass (mass 20.30 and mass 20.18 ) in a manner similar to the predictions from biomechanical flight models (mass 21/3 and mass 21/6 ). These scaling relationships predicted that the maximum limits on the body size of soaring animals are a body mass of 41 kg and a wingspan of 5.1 m. Albatross-like animals larger than the limit will not be able to flap fast enough to stay aloft under unfavourable wind conditions. Our result therefore casts doubt on the flying ability of large, extinct pterosaurs. The largest extant soarer, the wandering albatross, weighs about 12 kg, which might be a pragmatic limit to maintain a safety margin for sustainable flight and to survive in a variable environment.
Testosterone affects male sexual-, aggressive-, and parental-behaviors in bird species. To unders... more Testosterone affects male sexual-, aggressive-, and parental-behaviors in bird species. To understand the breadth of the proximate contribution of testosterone to breeding behaviors in male Black-tailed Gulls Larus crassirostris, sexual behaviors, aggressive behaviors against egg-predators and conspecifics, and chick-provisioning behavior of five testosterone-implanted males (T-males) were observed and compared with those of three control males (placebo-implanted; C-males). T-males showed significantly higher levels of courtship and copulation behaviors than C-males. The levels of aggressiveness against egg-predators and against conspecifics, and the rate of feeding of chicks did not differ between T-and C-males. These results suggest that sexual and mating behaviors in male Black-tailed Gulls may be affected by testosterone, while aggressive-and feeding-behaviors are affected by certain ecological factors, such as individual age, or a necessity for high levels of feeding by males, rather than by testosterone.
Polar Biology, 2012
Seals are known to be periodic breathers with eupneic and apneic phases at rest. We video-recorde... more Seals are known to be periodic breathers with eupneic and apneic phases at rest. We video-recorded a resting Weddell seal (Leptonychotes weddellii) that appeared head up from an ice hole in McMurdo Sound, Antarctica. From the video recorded, the duration of each eupneic and apneic phase was extracted, and heart rate in apneic phase was obtained by counting ripples of the sea surface around the neck of a seal. The results indicated that the distribution of instantaneous heart rate was bimodal. In addition, the higher the apneic heart rate, the shorter the apneic duration as well as the combination of apneic duration and successive eupneic duration (A-E duration). From these analyses, we characterized the periodic breathing of a resting Weddell seal.
Journal of Experimental Biology, 2013
Albatrosses are known to expend only a small amount of energy during flight. The low energy cost ... more Albatrosses are known to expend only a small amount of energy during flight. The low energy cost of albatross flight has been attributed to energy-efficient gliding (soaring) with sporadic flapping, although little is known about how much time and energy albatrosses expend in flapping versus gliding during cruising flight. Here, we examined the heart rates (used as an instantaneous index of energy expenditure) and flapping activities of free-ranging black-browed albatrosses (Thalassarche melanophrys) to estimate the energy cost of flapping as well as time spent in flapping activities. The heart rate of albatrosses during flight (144beatsmin -1 ) was similar to that while sitting on the water (150beatsmin -1 ). In contrast, heart rate was much higher during takeoff and landing (ca. 200beatsmin -1 ). Heart rate during cruising flight was linearly correlated with the number of wing flaps per minute, suggesting an extra energy burden of flapping. Albatrosses spend only 4.6±1.4% of their time flapping during cruising flight, which was significantly lower than during and shortly after takeoff (9.8±3.5%). Flapping activity, which amounted to just 4.6% of the time in flight, accounted for 13.3% of the total energy expenditure during cruising flight. These results support the idea that albatrosses achieve energy-efficient flight by reducing the time spent in flapping activity, which is associated with high energy expenditure.
Japanese Journal of Veterinary Research, May 31, 2002
Chemical senses, 2015
Inbreeding avoidance is essential to providing offspring with genetic diversity. Females' mat... more Inbreeding avoidance is essential to providing offspring with genetic diversity. Females' mate choice is more crucial than males' for successful reproduction because of the high cost of producing gametes and limited chances to mate. However, the mechanism of female inbreeding avoidance is still unclear. To elucidate the mechanism underlying inbreeding avoidance by females, we conducted Y-maze behavioral assays using BALB/c and C57BL/6 female mice. In both strains, the avoidance of male urine from the same strain was lower in the low estrogen phase than in the high estrogen phase. The estrous cycle-dependent avoidance was completely prevented by vomeronasal organ (VNO) removal. To assess the regulation of the vomeronasal system by estrogen, the neural excitability was evaluated by immunohistochemistry of the immediate early gene products. Although estrogen did not affect neural excitability in the VNO, estrogen enhanced the neural excitability of the mitral cell layer in the ...
Journal of Veterinary Medical Science, Oct 1, 2009
Novel cytochrome P450 1A (CYP1A) cDNA fragments were isolated from the liver of nine Japanese amp... more Novel cytochrome P450 1A (CYP1A) cDNA fragments were isolated from the liver of nine Japanese amphibian species using reverse transcription polymerase chain reaction (RT-PCR). Degenerate PCR primers were used to amplify 122-bp fragments of CYP1A cDNAs. Construction of a phylogenetic tree revealed that urodele and anuran amphibians formed two branches. Within the anuran species, three branches were formed: 1) Ranidae and Rhacophoridae, 2) Bufo japonicus formosus and Hyla japonica, and 3) Xenopus laevis. The cDNA nucleotide sequence of these CYP1A fragments showed identities ranging 72-98% (all), 72-78% (Anura vs. Urodela), 75 to 98% (Anura), 81% (Urodela), 74-80% (Xenopus laevis vs. nine Japanese amphibians).
The Japanese Journal of Veterinary Research, Aug 1, 2008
The wide use of organophosphorus (OP) pesti-cides in agriculture has several interesting implicat... more The wide use of organophosphorus (OP) pesti-cides in agriculture has several interesting implications for environmental safety, such as their persistence and selective toxicity for insects rather
Japanese Journal of Veterinary Research, Aug 1, 2014
Contamination levels of coplanar polychlorinated biphenyls (Co-PCBs), polycyclic aromatic hydroca... more Contamination levels of coplanar polychlorinated biphenyls (Co-PCBs), polycyclic aromatic hydrocarbons (PAHs), and dichlorodiphenyltrichloroethane (DDTs) were measured in the entire body of the large Japanese field mouse (Apodemus speciosus) collected from Hokkaido (Ishikari and Rankoshi) and Aomori prefecture (Takko) in Japan. Higher concentrations of PCBs including Co-PCBs, were observed in the mice collected from Ishikari than those from Rankoshi. The concentration of PAHs in the soil from Ishikari was also higher than that in the other sampling sites. The findings suggest that Ishikari is the most polluted area, probably because of human activities, depending on the population distribution. However, the observed contaminant levels were extremely lower compared to those in previous studies. The ratio of testis weight to body weight (TW/BW) was the lowest in the mice collected from Ishikari, which is the area contaminated with PAHs and p,p'-dichlorodiphenyldichloroethylene (DDE). However, the serum testosterone levels of mice from the Ishikari area were higher than those from the non-contaminated other areas although no significant differences. Previous studies have shown that a low-level exposure to dioxin related compounds (DRCs) disturbances in sexual function, resulting in the production of testosterone. This study showed that POPs exposure is one of the possibility of the high testosterone concentration in the mice of the Ishikari area in addition to a cause of biological and environmental factors such as habitat density, age, temperatures and/or food riches.
In an attempt to explore the functioning of nitric oxide (NO) in pancreatic exocrine cells, we ha... more In an attempt to explore the functioning of nitric oxide (NO) in pancreatic exocrine cells, we have recently obtained several lines of circumstantial evidence indicating that one of molecular targets of NO is phospholipase C (PLC), the activation of which leads to an increase in the cytosolic Ca2+ concentration ([Ca2+]i) via inositol 1, 4, 5-trisphosphate, IP3. However, whether IP3 is actually produced by NO has not yet been substantiated. The present study was therefore designed to directly measure the intracellular IP3, concentration ([IP3]i) for better understanding of the underlying mechanisms with the help of pharmacological tools. [IP3]i was measured using a fluorescence polarization technique (HitHunter). We obtained the following results: 1) varying concentrations of an NO donor, sodium nitroprusside (SNP), elevated [IP3]i, 2) this elevation was completely inhibited in the presence of the soluble guanylyl cyclase (sGC) inhibitor, 1H-[1, 2, 4] oxadiazolo [4, 3-a] quinoxalin-1-one (ODQ), 3) varying concentrations of the cGMP analogue, 8-Br-cGMP, also increased [IP3]i, 4) the cGMP analogue-induced IP3 production was abolished by pretreatment with either a PLC inhibitor, U73122, or a G-protein inhibitor, GP2A, and 5) KT5823, a potent and highly selective inhibitor of cGMP-dependent protein kinase G (PKG), also abolished the IP3 production induced by 8-Br-cGMP. These results suggest that the NO-induced [Ca2+]i increase is triggered by an increase in [IP3]i located downstream from intracellular cGMP elevation. In this intracellular pathway, each sGC, cGMP-dependent PKG, G-protein and PLC were suggested to be involved. The present work provides new insights into the intracellular signaling accelerated by NO. NO triggers a [Ca2+]I increase via cGMP and IP3 in pancreatic acinar cells.
The flight ability of animals is restricted by the scaling effects imposed by physical and physio... more The flight ability of animals is restricted by the scaling effects imposed by physical and physiological factors. In comparisons of the power available from muscle and the mechanical power required to fly, theoretical studies have predicted that the margin between the powers should decrease with body size and that flying animals have a maximum body size 1-7 . However, predicting an absolute value of this upper limit has been difficult because wing morphology and flight styles vary among species. Albatrosses and petrels have long, narrow, aerodynamically efficient wings and are considered to be soaring birds. Here, using animal-borne accelerometers, we show that scaling analyses of wing-flapping frequencies in these seabirds indicate that the maximum size limit for soaring animals is a body mass of 41 kg and a wingspan of 5.1 m. Soaring seabirds were observed to have two modes of flapping frequencies: vigorous flapping during takeoff and sporadic flapping during cruising flight. In these species, high and low flapping frequencies were found to scale with body mass (mass -0.30 and mass -0.18 ) in a manner similar to the predictions from biomechanical flight models (mass -1/3 and mass -1/6 ) 2, 4, 6, 8-10 . The
Journal of the Yamashina Institute for Ornithology, 2008
Journal of Antimicrobial Chemotherapy, 2008
Drug Metabolism and Disposition, 2009
Diazepam (7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one) is widely used as a ... more Diazepam (7-chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one) is widely used as a sedative, hypnotic, and anti-anxiety drug. At low diazepam concentrations, p-hydroxylation is the major metabolic pathway in rat liver microsomes. However, there are marked ( approximately 300-fold) inter- and intrastrain differences in the activity among Sprague-Dawley, Brown Norway, Dark Agouti, and Wistar rats. In our previous study, we determined that a deficiency of CYP2D3 protein, not CYP2D2, was responsible for the inter- and intrastrain differences in diazepam p-hydroxylation (Drug Metab Dispos 33:1657-1660, 2005). Quantitative real-time polymerase chain reaction (PCR) did not provide enough evidence to explain the inter- and intrastrain differences in the expression of CYP2D3 protein. Nucleotide sequence analysis revealed the insertion of a thymine in exon 8 of the CYP2D3 gene in the poor diazepam metabolizers. This single nucleotide mutation caused a shift in the reading frame and introduced a premature termination signal. It is noteworthy that the heme binding region, which is essential to maintain proper heme binding and active cytochrome P450 enzymes, was consequently deleted by the premature termination signal. In contrast, no mutation was detected in the CYP2D3 gene of extensive metabolizers. Thus, the truncated CYP2D3 must be a nonfunctional enzyme in poor metabolizers. In addition, we developed a convenient and specific genotyping assay using PCR-restriction, fragment-length polymorphism to distinguish homozygotes from heterozygotes. The genotyping gave results fully consistent with those of the inter- and intrastrain differences in diazepam p-hydroxylation.
The aim of the present study was to investigate the possible interaction between intracellular Ca... more The aim of the present study was to investigate the possible interaction between intracellular Ca(2+) and nitric oxide (NO) in rat pancreatic acinar cells, especially intracellular signaling events. (1) Nitric oxide donors SNP (0.1-100 μM) and NOR-3 (50-400 μM) induced Ca(2+) oscillations in fluo-4-loaded acini, that appeared to be analogous to what we usually observe in acini stimulated with physiological secretagogues such as CCK-8 and this oscillations were abolished in the presence of carboxy-PTIO. (2) The NO donors-evoked Ca(2+) oscillations were not abolished even in the absence of extracellular Ca(2+) but totally disappeared when cells were pretreated with thapsigargin, a sarcoplasmic-endoplasmic reticulum Ca(2+) ATPase (SERCA) inhibitor. (3) Inhibition of guanylate cyclase with 1 H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) attenuated Ca(2+) oscillations evoked by SNP in the absence of extracellular Ca(2+). (4) Inhibitors of phospholipase C activity, U73122 and the IP(3)R blocker xestospongin C, both abolished the SNP-induced Ca(2+) response. (5) Furthermore, we found that both CCK-8 and carbachol (CCh) induced NO production in DAF-2-loaded acinar cells and that an inhibitor of NO synthase, N(G)-monomethyl-l-arginine (L-NMMA), significantly reduced CCK-8-induced Ca(2+) oscillation. These results indicate that NO mobilizes Ca(2+) from internal stores through activation of guanylate cyclase and resultant cGMP production. In addition, PLC activation of IP(3) production is also suggested to be involved in Ca(2+) mobilization via IP(3) receptors. This suggests the presence of cross-talk between Ca(2+) and NO in pancreatic acini and this cascade may, at least partially, participate in physiological secretagogue-evoked Ca(2+) dynamics in pancreatic acinar cells.
The Japanese journal of veterinary research, 2004
In order to examine whether iodine supplements may have caused a global decline in sperm concentr... more In order to examine whether iodine supplements may have caused a global decline in sperm concentrations during the past several decades, the synchronicity of the decline in mean sperm counts and the introduction of iodine supplements was analyzed statistically. A positive correlation between the incidence of thyroid disease and sperm counts has been detected in Europe. In addition, it has been shown that sperm counts began falling around 1965 in the United States, 40 years after iodine supplements were introduced. Mean sperm counts before and after 1965 were 111 x 10(6)/ml and 70 x 10(6)/ml, respectively, in calculations weighted by the number of subjects included in each individual publication. The timing of the declines coincided with the introduction of iodine supplements in the United States, France, and the United Kingdom. The implications are that the global decline in sperm concentrations may be caused by iodine intake. Geographical variation in the types of sperm count decli...
Journal of Toxicological Sciences, 2008
Warfarin is commonly used worldwide as a rodenticide. It inhibits coagulation of blood by inhibit... more Warfarin is commonly used worldwide as a rodenticide. It inhibits coagulation of blood by inhibiting vitamin K 2,3-epoxide reductase (VKOR) activity. An inadequate supply of vitamin K blocks the production of prothrombin and causes hemorrhage. It has been reported that repeated or long-term treatments with this drug cause resistance in wild rodents. However, the mechanism of warfarin resistance in rodents is still not known precisely. Recent studies reported and identified the function of the molecule, vitamin K epoxide reductase complex subunit 1 (VKORC1), which is the main unit of VKOR. An amino acid substitution in VKORC1 is one of the supposed mechanisms of warfarin resistance. An accelerated detoxification system involving cytochrome P450 (CYP) could also cause the rodenticide resistance. Administration of SKF-525A, a potent inhibitor for P450, increased the mortality due to reduction of warfarin metabolism in warfarin-resistant rats. Meanwhile, the appearance of warfarin-resistant rodents has led to the development of the more effective and toxic rodenticide superwarfarin, which is widely used in Europe and the USA. However, animals resistant to this second-generation rodenticide have already been reported in Europe. In this review, we focus on the mechanism and the pleiotropic effects of pesticide resistance in wild rodents.
An ethogram is a catalogue of discrete behaviors typically employed by a species. Traditionally a... more An ethogram is a catalogue of discrete behaviors typically employed by a species. Traditionally animal behavior has been recorded by observing study individuals directly. However, this approach is difficult, often impossible, in the case of behaviors which occur in remote areas and/or at great depth or altitude. The recent development of increasingly sophisticated, animal-borne data loggers, has started to overcome this problem. Accelerometers are particularly useful in this respect because they can record the dynamic motion of a body in e.g. flight, walking, or swimming. However, classifying behavior using body acceleration characteristics typically requires prior knowledge of the behavior of free-ranging animals. Here, we demonstrate an automated procedure to categorize behavior from body acceleration, together with the release of a user-friendly computer application, ''Ethographer''. We evaluated its performance using longitudinal acceleration data collected from a foot-propelled diving seabird, the European shag, Phalacrocorax aristotelis. The time series data were converted into a spectrum by continuous wavelet transformation. Then, each second of the spectrum was categorized into one of 20 behavior groups by unsupervised cluster analysis, using k-means methods. The typical behaviors extracted were characterized by the periodicities of body acceleration. Each categorized behavior was assumed to correspond to when the bird was on land, in flight, on the sea surface, diving and so on. The behaviors classified by the procedures accorded well with those independently defined from depth profiles. Because our approach is performed by unsupervised computation of the data, it has the potential to detect previously unknown types of behavior and unknown sequences of some behaviors.
PLoS ONE, 2009
The flight ability of animals is restricted by the scaling effects imposed by physical and physio... more The flight ability of animals is restricted by the scaling effects imposed by physical and physiological factors. In comparisons of the power available from muscle and the mechanical power required to fly, it is predicted that the margin between the powers should decrease with body size and that flying animals have a maximum body size. However, predicting the absolute value of this upper limit has proven difficult because wing morphology and flight styles varies among species. Albatrosses and petrels have long, narrow, aerodynamically efficient wings and are considered soaring birds. Here, using animal-borne accelerometers, we show that soaring seabirds have two modes of flapping frequencies under natural conditions: vigorous flapping during takeoff and sporadic flapping during cruising flight. In these species, high and low flapping frequencies were found to scale with body mass (mass 20.30 and mass 20.18 ) in a manner similar to the predictions from biomechanical flight models (mass 21/3 and mass 21/6 ). These scaling relationships predicted that the maximum limits on the body size of soaring animals are a body mass of 41 kg and a wingspan of 5.1 m. Albatross-like animals larger than the limit will not be able to flap fast enough to stay aloft under unfavourable wind conditions. Our result therefore casts doubt on the flying ability of large, extinct pterosaurs. The largest extant soarer, the wandering albatross, weighs about 12 kg, which might be a pragmatic limit to maintain a safety margin for sustainable flight and to survive in a variable environment.
Testosterone affects male sexual-, aggressive-, and parental-behaviors in bird species. To unders... more Testosterone affects male sexual-, aggressive-, and parental-behaviors in bird species. To understand the breadth of the proximate contribution of testosterone to breeding behaviors in male Black-tailed Gulls Larus crassirostris, sexual behaviors, aggressive behaviors against egg-predators and conspecifics, and chick-provisioning behavior of five testosterone-implanted males (T-males) were observed and compared with those of three control males (placebo-implanted; C-males). T-males showed significantly higher levels of courtship and copulation behaviors than C-males. The levels of aggressiveness against egg-predators and against conspecifics, and the rate of feeding of chicks did not differ between T-and C-males. These results suggest that sexual and mating behaviors in male Black-tailed Gulls may be affected by testosterone, while aggressive-and feeding-behaviors are affected by certain ecological factors, such as individual age, or a necessity for high levels of feeding by males, rather than by testosterone.
Polar Biology, 2012
Seals are known to be periodic breathers with eupneic and apneic phases at rest. We video-recorde... more Seals are known to be periodic breathers with eupneic and apneic phases at rest. We video-recorded a resting Weddell seal (Leptonychotes weddellii) that appeared head up from an ice hole in McMurdo Sound, Antarctica. From the video recorded, the duration of each eupneic and apneic phase was extracted, and heart rate in apneic phase was obtained by counting ripples of the sea surface around the neck of a seal. The results indicated that the distribution of instantaneous heart rate was bimodal. In addition, the higher the apneic heart rate, the shorter the apneic duration as well as the combination of apneic duration and successive eupneic duration (A-E duration). From these analyses, we characterized the periodic breathing of a resting Weddell seal.
Journal of Experimental Biology, 2013
Albatrosses are known to expend only a small amount of energy during flight. The low energy cost ... more Albatrosses are known to expend only a small amount of energy during flight. The low energy cost of albatross flight has been attributed to energy-efficient gliding (soaring) with sporadic flapping, although little is known about how much time and energy albatrosses expend in flapping versus gliding during cruising flight. Here, we examined the heart rates (used as an instantaneous index of energy expenditure) and flapping activities of free-ranging black-browed albatrosses (Thalassarche melanophrys) to estimate the energy cost of flapping as well as time spent in flapping activities. The heart rate of albatrosses during flight (144beatsmin -1 ) was similar to that while sitting on the water (150beatsmin -1 ). In contrast, heart rate was much higher during takeoff and landing (ca. 200beatsmin -1 ). Heart rate during cruising flight was linearly correlated with the number of wing flaps per minute, suggesting an extra energy burden of flapping. Albatrosses spend only 4.6±1.4% of their time flapping during cruising flight, which was significantly lower than during and shortly after takeoff (9.8±3.5%). Flapping activity, which amounted to just 4.6% of the time in flight, accounted for 13.3% of the total energy expenditure during cruising flight. These results support the idea that albatrosses achieve energy-efficient flight by reducing the time spent in flapping activity, which is associated with high energy expenditure.