Role of satellite cell-derived l-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy

Paclitaxel is one of the most commonly used antineoplastic drugs for the treatment of solid tumors. Unfortunately, its use is often associated with dose-limiting painful peripheral neuropathy and subsequent neuropathic pain that is resistant to standard analgesics. However, there are few clinically available drugs or drug classes for the treatment of paclitaxel-induced neuropathy due to a lack of information regarding the mechanisms responsible for it. In this study, we examined the involvement of L-serine in paclitaxel-induced hyperalgesia/allodynia and decrease in sensory nerve conduction velocity (SNCV). We used a preclinical rat model of paclitaxel-induced painful peripheral neuropathy. Response to von Frey filaments, SNCV, 3-phosphoglycerate dehydrogenase (3PGDH) expression, and L-serine concentration were examined. Effects of L-serine administration were also investigated. Paclitaxel treatment induced mechanical allodynia/hyperalgesia and reduction of SNCV. Paclitaxel also decreased the L-serine concentration in the dorsal root ganglion (DRG) but not in the sciatic nerve or spinal cord. In addition, paclitaxel decreased expression of 3PGDH, a biosynthetic enzyme of L-serine, in the DRG. Immunohistochemistry showed that 3PGDH was localized in satellite cells but not in neurons in the DRG. Intraperitoneal administration of L-serine improved both paclitaxel-induced mechanical allodynia/hyperalgesia and the reduction of SNCV. These results suggest that satellite cell-derived L-serine in the DRG plays an important role in paclitaxel-induced painful peripheral neuropathy. These findings may lead to novel strategies for the treatment of paclitaxel-induced painful peripheral neuropathy.ArticleNEUROSCIENCE. 174(0):190-199 (2011)journal articl

Dance Type and Flight Parameters Are Associated with Different Mushroom Body Neural Activities in Worker Honeybee Brains

Background: Honeybee foragers can transmit the information concerning the location of food sources to their nestmates using dance communication. We previously used a novel immediate early gene, termed kakusei, to demonstrate that the neural activity of a specific mushroom body (MB) neuron subtype is preferentially enhanced in the forager brain. The sensory information related to this MB neuron activity, however, remained unclear. Methodology/Principal Findings: Here, we used kakusei to analyze the relationship between MB neuron activity and types of foraging behavior. The number of kakusei-positive MB neurons was higher in the round dancers that had flown a short distance than in the waggle dancers that had flown a long distance. Furthermore, the amount of kakusei transcript in the MBs inversely related to the waggle-phase duration of the waggle dance, which correlates with the flight distance. Using a narrow tunnel whose inside was vertically or axially lined, we manipulated the pattern of visual input, which is received by the foragers during flight, and analysed kakusei expression. The amount of kakusei transcript in the MBs was related to the foraging frequency but not to the tunnel pattern. In contrast, the number of kakusei-positive MB neurons was affected by the tunnel patterns, but not related to foraging frequency. Conclusions/Significance: These results suggest that the MB neuron activity depends on the foraging frequency, whereas the number of active MB neurons is related to the pattern of visual input received during foraging flight. Our results sugges

Ice-Shelf Tidal Flexure and Subglacial Pressure Variations

We develop a model of an ice shelf-ice stream system as a viscoelastic beam partially supported by an elastic foundation. When bed rock near the grounding line acts as a fulcrum, leverage from the ice shelf dropping at low tide can cause significant (approx 1 cm) uplift in the first few kilometers of grounded ice.This uplift and the corresponding depression at high tide lead to basal pressure variations of sufficient magnitude to influence subglacial hydrology.Tidal flexure may thus affect basal lubrication, sediment flow, and till strength, all of which are significant factors in ice-stream dynamics and grounding-line stability. Under certain circumstances, our results suggest the possibility of seawater being drawn into the subglacial water system. The presence of sea water beneath grounded ice would significantly change the radar reflectivity of the grounding zone and complicate the interpretation of grounded versus floating ice based on ice-penetrating radar observations

Detection of Neural Activity in the Brains of Japanese Honeybee Workers during the Formation of a “Hot Defensive Bee Ball”

Anti-predator behaviors are essential to survival for most animals. The neural bases of such behaviors, however, remain largely unknown. Although honeybees commonly use their stingers to counterattack predators, the Japanese honeybee (Apis cerana japonica) uses a different strategy to fight against the giant hornet (Vespa mandarinia japonica). Instead of stinging the hornet, Japanese honeybees form a “hot defensive bee ball” by surrounding the hornet en masse, killing it with heat. The European honeybee (A. mellifera ligustica), on the other hand, does not exhibit this behavior, and their colonies are often destroyed by a hornet attack. In the present study, we attempted to analyze the neural basis of this behavior by mapping the active brain regions of Japanese honeybee workers during the formation of a hot defensive bee ball. First, we identified an A. cerana homolog (Acks = Apis cerana kakusei) of kakusei, an immediate early gene that we previously identified from A. mellifera, and showed that Acks has characteristics similar to kakusei and can be used to visualize active brain regions in A. cerana. Using Acks as a neural activity marker, we demonstrated that neural activity in the mushroom bodies, especially in Class II Kenyon cells, one subtype of mushroom body intrinsic neurons, and a restricted area between the dorsal lobes and the optic lobes was increased in the brains of Japanese honeybee workers involved in the formation of a hot defensive bee ball. In addition, workers exposed to 46°C heat also exhibited Acks expression patterns similar to those observed in the brains of workers involved in the formation of a hot defensive bee ball, suggesting that the neural activity observed in the brains of workers involved in the hot defensive bee ball mainly reflects thermal stimuli processing

M\=aori algorithmic sovereignty: idea, principles, and use

Due to the emergence of data-driven technologies in Aotearoa New Zealand that use M\=aori data, there is a need for values-based frameworks to guide thinking around balancing the tension between the opportunities these create, and the inherent risks that these technologies can impose. Algorithms can be framed as a particular use of data, therefore data frameworks that currently exist can be extended to include algorithms. M\=aori data sovereignty principles are well-known and are used by researchers and government agencies to guide the culturally appropriate use of M\=aori data. Extending these principles to fit the context of algorithms, and re-working the underlying sub-principles to address issues related to responsible algorithms from a M\=aori perspective leads to the M\=aori algorithmic sovereignty principles. We define this idea, present the updated principles and subprinciples, and highlight how these can be used to decolonise algorithms currently in use, and argue that these ideas could potentially be used to developed Indigenised algorithms

Motion of a vortex sheet on a sphere with pole vortices

We cons i der the motion of a vortex sheet on the surface of a unit sphere in the presence of point vortices xed on north and south poles.Analytic and numerical research revealed that a vortex sheet in two-dimensional space has the following three properties.First,the vortex sheet is linearly unstable due to Kelvin-Helmholtz instability.Second,the curvature of the vortex sheet diverges in nite time.Last,the vortex sheet evolves into a rolling-up doubly branched spiral,when the equation of motion is regularized by the vortex method.The purpose of this article is to investigate how the curvature of the sphere and the presence of the pole vortices

Measurement and comparison of individual external doses of high-school students living in Japan, France, Poland and Belarus -- the "D-shuttle" project --

Twelve high schools in Japan (of which six are in Fukushima Prefecture), four in France, eight in Poland and two in Belarus cooperated in the measurement and comparison of individual external doses in 2014. In total 216 high-school students and teachers participated in the study. Each participant wore an electronic personal dosimeter "D-shuttle" for two weeks, and kept a journal of his/her whereabouts and activities. The distributions of annual external doses estimated for each region overlap with each other, demonstrating that the personal external individual doses in locations where residence is currently allowed in Fukushima Prefecture and in Belarus are well within the range of estimated annual doses due to the background radiation level of other regions/countries

Role of satellite cell-derived l-serine in the dorsal root ganglion in paclitaxel-induced painful peripheral neuropathy

Paclitaxel is one of the most commonly used antineoplastic drugs for the treatment of solid tumors. Unfortunately, its use is often associated with dose-limiting painful peripheral neuropathy and subsequent neuropathic pain that is resistant to standard analgesics. However, there are few clinically available drugs or drug classes for the treatment of paclitaxel-induced neuropathy due to a lack of information regarding the mechanisms responsible for it. In this study, we examined the involvement of L-serine in paclitaxel-induced hyperalgesia/allodynia and decrease in sensory nerve conduction velocity (SNCV). We used a preclinical rat model of paclitaxel-induced painful peripheral neuropathy. Response to von Frey filaments, SNCV, 3-phosphoglycerate dehydrogenase (3PGDH) expression, and L-serine concentration were examined. Effects of L-serine administration were also investigated. Paclitaxel treatment induced mechanical allodynia/hyperalgesia and reduction of SNCV. Paclitaxel also decreased the L-serine concentration in the dorsal root ganglion (DRG) but not in the sciatic nerve or spinal cord. In addition, paclitaxel decreased expression of 3PGDH, a biosynthetic enzyme of L-serine, in the DRG. Immunohistochemistry showed that 3PGDH was localized in satellite cells but not in neurons in the DRG. Intraperitoneal administration of L-serine improved both paclitaxel-induced mechanical allodynia/hyperalgesia and the reduction of SNCV. These results suggest that satellite cell-derived L-serine in the DRG plays an important role in paclitaxel-induced painful peripheral neuropathy. These findings may lead to novel strategies for the treatment of paclitaxel-induced painful peripheral neuropathy.ArticleNEUROSCIENCE. 174(0):190-199 (2011)journal articl

Small Molecules with Similar Structures Exhibit Agonist, Neutral Antagonist or Inverse Agonist Activity toward Angiotensin II Type 1 Receptor

Small differences in the chemical structures of ligands can be responsible for agonism, neutral antagonism or inverse agonism toward a G-protein-coupled receptor (GPCR). Although each ligand may stabilize the receptor conformation in a different way, little is known about the precise conformational differences. We synthesized the angiotensin II type 1 receptor blocker (ARB) olmesartan, R239470 and R794847, which induced inverse agonism, antagonism and agonism, respectively, and then investigated the ligand-specific changes in the receptor conformation with respect to stabilization around transmembrane (TM)3. The results of substituted cysteine accessibility mapping studies support the novel concept that ligand-induced changes in the conformation of TM3 play a role in stabilizing GPCR. Although the agonist-, neutral antagonist and inverse agonist-binding sites in the AT1 receptor are similar, each ligand induced specific conformational changes in TM3. In addition, all of the experimental data were obtained with functional receptors in a native membrane environment (in situ)

Investigation on the possibility of artificial propagation, cultivation and brood stock management of Vannamei shrimp

Project was carried out at the Gomishan Centre for training and education which is located 15 km far from Gomishan City in the Golestan Province. Prebroodstocks were chosen from ponds (stocking density: 3/m^2). 860 male and 890 female broodstocks were separated and transferred into greenhouse (400 m^2). The average growth rate per day was 0.3 g and survival rate was 90%. After reaching 42 g in males and 52 g in females they were ready for Eyes stalk Brood stocks were transferred into propagation hall in June and after a week females gone under Eyes stalk. 10,890,000 eggs were yielded from 50 females and consequently 7, 187, 0.50 nauplius were produced. Each broodstock spawned 1.34 Times. The maximum hatching was 75% that in was average 64.2%. Mass of Cetocerous Algae was mass produced to be fed for post larvae. Finally 35,000 PL15 were yielded. PL15 were transferred into two half hectare and one 1 ha ponds in July. The stocking density was 18 PL/m^2. Biometric parameters together with air and water temperatures, and pH were recorded daily. Results indicate that the maximum survival rate was 58% (pond No. 5) and minimum was 52% (pond No. 17). The average weight after 101 days cultivating was 23 g which is appropriate. Also the average daily growth rate was 0.2g and the FCR was 1