An immune-adrenergic pathway induces lethal levels of platelet-activating factor in mice

Acute immune responses with excess production of cytokines, lipid/chemical mediators, or coagulation factors, often result in lethal damage. In addition, the innate immune system utilizes multiple types of receptors that recognize neurotransmitters as well as pathogen-associated molecular patterns, making immune responses complex and clinically unpredictable. We here report an innate immune and adrenergic link inducing lethal levels of platelet-activating factor. Injecting mice with toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS), cell wall N-glycans of Candida albicans, and the α₂-adrenergic receptor (α₂-AR) agonist medetomidine induces lethal damage. Knocking out the C-type lectin Dectin-2 prevents the lethal damage. In spleen, large amounts of platelet-activating factor (PAF) are detected, and knocking out lysophospholipid acyltransferase 9 (LPLAT9/LPCAT2), which encodes an enzyme that converts inactive lyso-PAF to active PAF, protects mice from the lethal damage. These results reveal a linkage/crosstalk between the nervous and the immune system, possibly inducing lethal levels of PAF

First Detection of Tetrodotoxins in the Cotylean Flatworm Prosthiostomum trilineatum

Several polyclad flatworm species are known to contain high levels of tetrodotoxin (TTX), but currently TTX-bearing flatworms seem to be restricted to specific Planocera lineages belonging to the suborder Acotylea. During our ongoing study of flatworm toxins, high concentrations of TTXs were detected for the first time in the flatworm Prosthiostomum trilineatum, suborder Cotylea, from the coastal area of Hayama, Kanagawa, Japan. Toxin levels were investigated by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), revealing that this species contains comparable concentrations of toxins as seen in planocerid flatworms such as Planocera multitentaculata. This finding indicated that there may be other species with significant levels of TTXs. The distribution of TTXs among other flatworm species is thus of great interest

Dominant parameters for maximum velocity induced by body-force models for plasma actuators

This study investigates the relationship between body-force fields and maximum velocity induced in quiescent air for development of a simple body-force model of a plasma actuator. Numerical simulations are conducted with the body force near a wall. The spatial distribution and temporal variation of the body force are a Gaussian distribution and steady actuation, respectively. The dimensional analysis is performed to derive a reference velocity and Reynolds number based on the body-force distribution. It is found that the derived Reynolds number correlates well with the nondimensional maximum velocity induced in quiescent conditions when the center of the Gaussian distribution is fixed at the wall. Additionally, two flow regimes are identified in terms of the Reynolds number. Considering the variation of the center of gravity of force fields, another Reynolds number is defined by introducing a new reference length. The nondimensional maximum velocity is found to be scaled with the latter Reynolds number, i.e., the maximum induced velocity in quiescent conditions is determined from three key parameters of the force field: the total induced momentum per unit time, the height of the center of gravity, and the standard deviation from it. This scaling turns out to be applicable to existing body-force models of the plasma actuator, despite the force distributions different from the Gaussian distribution. Comparisons of velocity profiles with experimental data validate the results and show that the flow induced by a plasma actuator can be simulated with simple force distributions by adjustment of the key body-force parameters

Characterization and phylogenetic position of two sympatric sister species of toxic flatworms Planocera multitentaculata and Planocera reticulata (Platyhelminthes: Acotylea)

The complete mitochondrial genomes of two toxic flatworm species of the genus Planocera were determined. The total length of mitochondrial DNA (mtDNA) was 15,657 bp in Planocera multitentaculata and 15,486 bp in Planocera reticulata and included 12 protein-coding genes, 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 4 non-coding regions. The mitochondrial gene arrangement of these planocerid species was identical to that of previously described acotylean species, Hoploplana elisabelloi, and also to those of other polyclads. Maximum likelihood analysis against 14 Platyhelminthes showed that a tree was robustly constructed using 12 protein-coding genes than COI gene

Effusion detected by ultrasonography and overweight may predict the risk of knee osteoarthritis in females with early knee osteoarthritis: a retrospective analysis of Iwaki cohort data

Abstract Background Knee osteoarthritis (OA) has enormous medical and socioeconomic burdens, which early diagnosis and intervention can reduce. We investigated the influence of knee effusion on the progression of knee OA in patients with early knee OA. Methods A total of 404 participants without radiographic knee OA were assessed from a 3-year longitudinal analysis. Participants were classified into non-OA and early knee OA groups. The effusion area (mm2) was quantified using ultrasonography. Receiver operating characteristic and logistic regression analyses were performed. Results At the 3-year follow-up, 114 of 349 knees (32%) had progressed from non-OA and 32 of 55 knees (58%) had progressed from early knee OA to radiographic knee OA. Logistic regression analysis showed that female sex (odds ratio [OR] 3.36, 95% confidence interval [CIs] 2.98–5.42), early knee OA (OR 2.02, 95% CI 1.08–3.75), body mass index (OR 1.11, 95% CI 1.02–1.19), and effusion area (OR 1.01, 95% CI 1.01–1.02) were significantly correlated with knee OA progression. Women who were overweight (body mass index ≥ 25 kg/m2) with more severe effusion had a higher risk of OA progression (area under the curve = 0.691, OR = 6.00) compared to those not overweight (area under the curve = 0.568, OR = 1.91). Conclusion Knee effusion may be an indicator of the progression of early-stage knee OA

Phylogenetic position of the Atlantic Gnomefish, Scombrops oculatus (Teleostei: Scombropidae), within the genus Scombrops, inferred from the sequences of complete mitochondrial genome and cytochrome c oxidase subunit I genes

We determined the complete mitochondrial genome of the Atlantic Gnomefish, Scombrops oculatus (Scombropidae). The total length of mitochondrial DNA (mtDNA) was 16,515 bp and included 13 protein-coding genes, two ribosomal RNA genes, 22 transfer RNA genes, and one control region. The gene arrangement of S. oculatus was identical to those of three Japanese scombropid species and those of other teleosts. The phylogenetic analysis using the whole mtDNA, excluding the control region, indicates the Atlantic species is distinct from the Japanese clade, whereas that using cytochrome c oxidase subunit I gene showed the Atlantic species is most closely related to the African species

Local Differences in the Toxin Amount and Composition of Tetrodotoxin and Related Compounds in Pufferfish (Chelonodon patoca) and Toxic Goby (Yongeichthys criniger) Juveniles

Tetrodotoxin (TTX)-bearing fish ingest TTX from their preys through the food chain and accumulate TTX in their bodies. Although a wide variety of TTX-bearing organisms have been reported, the missing link in the TTX supply chain has not been elucidated completely. Here, we investigated the composition of TTX and 5,6,11-trideoxyTTX in juveniles of the pufferfish, Chelonodon patoca, and toxic goby, Yongeichthys criniger, using LC–MS/MS, to resolve the missing link in the TTX supply chain. The TTX concentration varied among samples from different localities, sampling periods and fish species. In the samples from the same locality, the TTX concentration was significantly higher in the toxic goby juveniles than in the pufferfish juveniles. The concentration of TTX in all the pufferfish juveniles was significantly higher than that of 5,6,11-trideoxyTTX, whereas the compositional ratio of TTX and 5,6,11-trideoxyTTX in the goby was different among sampling localities. However, the TTX/5,6,11-trideoxyTTX ratio in the goby was not different among samples collected from the same locality at different periods. Based on a species-specific PCR, the detection rate of the toxic flatworm (Planocera multitentaculata)-specific sequence (cytochrome c oxidase subunit I) also varied between the intestinal contents of the pufferfish and toxic goby collected at different localities and periods. These results suggest that although the larvae of the toxic flatworm are likely to be responsible for the toxification of the pufferfish and toxic goby juveniles by TTX, these fish juveniles are also likely to feed on other TTX-bearing organisms depending on their habitat, and they also possess different accumulation mechanisms of TTX and 5,6,11-trideoxyTTX

Levels of Tetrodotoxins in Spawning Pufferfish, <i>Takifugu alboplumbeus</i>

Tetrodotoxin (TTX), also known as pufferfish toxin, is an extremely potent neurotoxin thought to be used as a biological defense compound in organisms bearing it. Although TTX was thought to function as a chemical agent for defense and anti-predation and an attractant for TTX-bearing animals including pufferfish, it has recently been demonstrated that pufferfish were also attracted to 5,6,11-trideoxyTTX, a related compound, rather than TTX alone. In this study, we attempted to estimate the roles of TTXs (TTX and 5,6,11-trideoxyTTX) in the pufferfish, Takifugu alboplumbeus, through examining the location of TTXs in various tissues of spawning pufferfish from Enoshima and Kamogawa, Japan. TTXs levels in the Kamogawa population were higher than those in the Enoshima population, and there was no significant difference in the amount of TTXs between the sexes in either population. Individual differences were greater in females than in males. However, the location of both substances in tissues differed significantly between sexes: male pufferfish accumulated most of their TTX in the skin and liver and most of their 5,6,11-trideoxyTTX in the skin, whereas females accumulated most of their TTX and 5,6,11-trideoxyTTX in the ovaries and skin