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Koga, K.,Descalzi, G.,Chen, T.,Ko, H.G.,Lu, J.,Li, S.,Son, J.,Kim, T.,Kwak, C.,Huganir, Richard L.,Zhao, M.g.,Kaang, B.K.,Collingridge, Graham L.,Zhuo, M. Cell Press 2015 Neuron Vol.85 No.2
Chronic pain can lead to anxiety and anxiety can enhance the sensation of pain.@?Unfortunately, little is known about the synaptic mechanisms that mediate these re-enforcing interactions. Here we characterized two forms of long-term potentiation (LTP) in the anterior cingulate cortex (ACC); a presynaptic form (pre-LTP) that requires kainate receptors and a postsynaptic form (post-LTP) that requires N-methyl-D-aspartate receptors. Pre-LTP also involves adenylyl cyclase and protein kinase A and is expressed via a mechanism involving hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Interestingly, chronic pain and anxiety both result in selective occlusion of pre-LTP. Significantly, microinjection of the HCN blocker ZD7288 into the ACC in vivo produces both anxiolytic and analgesic effects. Our results provide a mechanism by which two forms of LTP in the ACC may converge to mediate the interaction between anxiety and chronic pain.
Tmem64 Modulates Calcium Signaling during RANKL-Mediated Osteoclast Differentiation
Kim, H.,Kim, T.,Jeong, B.C.,Cho, I.T.,Han, D.,Takegahara, N.,Negishi-Koga, T.,Takayanagi, H.,Lee, J.,Sul, J.Y.,Prasad, V.,Lee, S.,Choi, Y. Cell Press 2013 Cell metabolism Vol.17 No.2
Osteoclast maturation and function primarily depend on receptor activator of NF-κB ligand (RANKL)-mediated induction of nuclear factor of activated T cells c1 (NFATc1), which is further activated via increased intracellular calcium ([Ca<SUP>2+</SUP>]<SUB>i</SUB>) oscillation. However, the coordination mechanism that mediates Ca<SUP>2+</SUP> oscillation during osteoclastogenesis remains ill defined. Here, we identified transmembrane protein 64 (Tmem64) as a regulator of Ca<SUP>2+</SUP> oscillation during osteoclastogenesis. We found that Tmem64-deficient mice exhibit increased bone mass due in part to impaired osteoclast formation. Using in vitro osteoclast culture systems, we show here that Tmem64 interacts with sarcoplasmic endoplasmic reticulum Ca<SUP>2+</SUP> ATPase 2 (SERCA2) and modulates its activity. Consequently, Tmem64 deficiency significantly diminishes RANKL-induced [Ca<SUP>2+</SUP>]<SUB>i</SUB> oscillation, which results in reduced Ca<SUP>2+</SUP>/calmodulin-dependent protein kinases (CaMK) IV and mitochondrial ROS, both of which contribute to achieving the CREB activity necessary for osteoclast formation. These data demonstrate that Tmem64 is a positive modulator of osteoclast differentiation via SERCA2-dependent Ca<SUP>2+</SUP> signaling.
OSCAR is a collagen receptor that costimulates osteoclastogenesis in DAP12-deficient humans and mice
Barrow, A.D.,Raynal, N.,Andersen, T.L.,Slatter, D.A.,Bihan, D.,Pugh, N.,Cella, M.,Kim, T.,Rho, J.,Negishi-Koga, T. American Society for Clinical Investigation 2011 The Journal of clinical investigation Vol.121 No.9
Koga, A.,Kurata, K.,Ohata, K.,Nakajima, M.,Hirose, H.,Furukawa, R.,Kanai, Y.,Chikamune, T. Asian Australasian Association of Animal Productio 1999 Animal Bioscience Vol.12 No.6
From previous studies, there is a strong possibility in buffaloes that the marked increase in blood volume (BV) under hot conditions contributes to heat transportation from the rectum to the skin. The present study was done to clarify changes with environmental temperature on water-shift between blood and extracellular fluid (ECF), heat distribution between the rectum and the skin, and blood flow rates (BFR) at the hind legs (reflecting the skin surface). Four buffaloes and four Friesian cows were successively exposed to three different temperatures of $20^{\circ}C$, $30^{\circ}C$ and $35^{\circ}C$. BV and ECF volume were measured with Evans' blue and sodium-thiocyanate dilution methods, respectively. Rectal and subcutaneous (as the skin) temperatures were measured by copper-constantan thermocouples. BFR were measured by a supersonic blood flow meter. With an increase in environmental temperature, skin temperature in buffaloes increased significantly than cows, but rectal temperature was not significantly different between two species. BV, especially plasma compartment, increased significantly in only buffaloes, while ECF volume did not change in both species. BFR increased significantly in buffaloes, but not in cows. From these results, the increased of BV may be caused by water flowing from ECF compartment. The water-shift may induce the increase of BFR and skin temperature. It is suggested in the present study that internal changes of blood compartment in buffaloes contribute to transfer of heat to the skin surface.
Thermoregulatory Responses of Swamp Buffaloes and Friesian Cows to Diurnal Changes in Temperature
Koga, A.,Kurata, K.,Furukawa, R.,Nakajima, M.,Kanai, Y.,Chikamune, T. Asian Australasian Association of Animal Productio 1999 Animal Bioscience Vol.12 No.8
Several reports have indicated that a rectal temperature of buffaloes is easily influenced by their surroundings. To clarify an effect of changing environmental temperature on thermoregulatory responses of buffaloes, an environment with diurnal temperature changes of $25^{\circ}C$ to $35^{\circ}C$ was created using an artificial climate laboratory. Three swamp buffaloes and three Friesian cows were exposed to three different experimental periods as follows: Period 1 (constant temperature of $30^{\circ}C$, Period 2 (diurnally changing temperature) and Period 3 (diurnally changing temperature and fasting). Heat production, rectal temperature, respiration rate, heart rate and respiration volume were measured during each period. Rectal temperature of the buffaloes fluctuated diurnally with the changing temperature (Periods 2 and 3), but remained constant in cows. Mean heat production was significantly lower in buffaloes than in cows in Period 2 and 3. However, the maximum rectal temperature and the increment of heat production were not always lower in buffaloes than in cows during Period 2. These results show that a rectal temperature and heat production in buffaloes are markedly influenced by the diurnal changes in temperature. Compared with Bos Taurus cows, the differences may be attributed to the physiological features of buffaloes including a high heat conductivity of their bodies and an lower heat production.
Crystal structure of metagenome-derived LC9-RNase H1 with atypical DEDN active site motif
Nguyen, T.N.,You, D.J.,Kanaya, E.,Koga, Y.,Kanaya, S. North-Holland Pub ; Elsevier Science Ltd 2013 FEBS letters Vol.587 No.9
The crystal structure of metagenome-derived LC9-RNase H1 was determined. The structure-based mutational analyses indicated that the active site motif of LC9-RNase H1 is altered from DEDD to DEDN. In this motif, the location of the second glutamate residue is moved from αA-helix to β1-strand immediately next to the first aspartate residue, as in the active site of RNase H2. However, the structure and enzymatic properties of LC9-RNase H1 highly resemble those of RNase H1, instead of RNase H2. We propose that LC9-RNase H1 represents bacterial RNases H1 with an atypical DEDN active site motif, which are evolutionarily distinct from those with a typical DEDD active site motif.