MEK/ERK Signaling Regulates Reconstitution of the Dopaminergic Nerve Circuit in the Planarian Dugesia japonica.

Planarian Dugesia japonica is a flatworm that can autonomously regenerate its own body after an artificial amputation. A recent report showed the role of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK) pathway in the head morphogenesis during the planarian regeneration process after amputation; however, neuron-specific regeneration mechanisms have not yet been reported. Here, whether MEK/ERK pathway was involved in the dopaminergic neuronal regeneration in planarians was investigated. Planarians regenerated their body within 14 days after amputation; however, the head region morphogenesis was inhibited by MEK inhibitor U0126 (3 or 10 µM). Furthermore, the number of planarian tyrosine hydroxylase (DjTH)-positive dopaminergic neurons in the regenerated head region was also decreased by U0126. The 6-hydroxydopamine (6-OHDA), a dopaminergic neurotoxin, can decrease the number of dopaminergic neurons; however, planarians can regenerate dopaminergic neurons after injecting 6-OHDA into the intestinal tract. MEK inhibitor PD98059 (30 µM) or U0126 (10 µM) significantly decreased dopaminergic neurons 5 days after the 6-OHDA injection. During the regeneration process of dopaminergic neurons, phosphorylated histone H3 (H3P)-positive stem cells known as "neoblasts" were increased in the head region; however, MEK inhibitors significantly decreased the number of H3P-positive neoblasts. These results suggested that dopaminergic neuronal regeneration in planarian was regulated by the MEK/ERK pathway.

Development of a human-tissue-like phantom for 3.0-T MRI.

PURPOSE: A 3.0-T MRI phantom having human-tissue-equivalent relaxation times was developed. METHODS: The ingredients of the phantom are carrageenan (for gelatinization), GdCl(3) (as a T(1)-relaxation modifier), agarose (as a T(2)-relaxation modifier), and NaN(3) (as an antiseptic agent). Numerous samples with varying concentrations of GdCl(3) and agarose were prepared, and T(1) and T(2) were measured using 3.0-T MRI. RESULTS: Relaxation times of the phantom samples ranged from 395 to 2601 ms for T(1) values and 29 to 334 ms for T(2) values. Based on the measured results, empirical formulae were devised to express the relationships between the concentrations of relaxation modifiers and relaxation times. CONCLUSIONS: Adjustment of GdCl(3) and agarose concentrations allows arbitrary setting of relaxation times, and the creation of a phantom that can mimic relaxation times of human-tissue. Carrageenan is considered the most suitable as a gelling agent for an MRI phantom, as it permits the relatively easy and inexpensive production of a large phantom such as for the human torso, and which can be easily shaped with a knife.

Cartilage structure increases swimming efficiency of underwater robots.

Underwater robots are useful for exploring valuable resources and marine life. Traditional underwater robots use screw propellers, which may be harmful to marine life. In contrast, robots that incorporate the swimming principles, morphologies, and softness of aquatic animals are expected to be more adaptable to the surrounding environment. Rajiform is one of the swimming forms observed in nature, which swims by generating the traveling waves on flat large pectoral fins. From an anatomical point of view, Rajiform fins consist of cartilage structures encapsulated in soft tissue, thereby realizing anisotropic stiffness. We hypothesized that such anisotropy is responsible for the generation of traveling waves that enable a highly efficient swimming. We validate our hypothesis through the development of a stingray robot made of silicone-based cartilages and soft tissue. For comparison, we fabricate a robot without cartilages, as well as the one combining soft tissue and cartilage materials. The fabricated robots are tested to clarify their stiffness and swimming performance. The results show that inclusion of cartilage structure in the robot fins increases the swimming efficiency. It is suggested that arrangement and distribution of soft and hard areas inside the body structure is a key factor to realize high-performance soft underwater robots.

Production of a human-tissue-equivalent MRI phantom: optimization of material heating.

PURPOSE: We conceived a 2-stage heating method to dissolve the ingredients of magnetic resonance (MR) imaging phantoms to overcome issues of uneven quality in conventional MR imaging phantoms, and we evaluated uniformity and the reproducibility of our method. METHODS: We used a 3-liter capacity, column-shaped, enamel-coated porcelain container to produce a muscle-equivalent phantom (diameter, 160 mm; height, 100 mm; volume, 2 liters). The phantom contained: 1) carrageenan as a gelling agent; 2) agarose as a T2 modifier; 3) GdCl3 as a T1 modifier; 4) NaN3 as an antiseptic; and 5) distilled water. We applied both direct heating and 2-stage heating of pre-soaked materials. We placed powdered materials directly into hot water for direct heating but soaked them in water one day before use (post-swelling) in 2-stage heating. The materials in the container were melted in a silicone oil bath of 120 or 140 degrees C under various conditions, then allowed to gel by natural cooling. We observed the resulting gel phantoms macroscopically using a CCD camera and evaluated their uniformity by microscopy and MR imaging. RESULTS: We found it necessary to raise the temperature inside the phantom to 100.0 degrees C, to produce a uniform gel with stable homogeneity and few bubbles. Use of an enamel-coated porcelain container required setting the temperature of the oil bath at 140 degrees C. CONCLUSION: A uniform and reproducible human tissue-equivalent phantom with few bubbles can be manufactured using our 2-stage heating method, which employs pre-soaking in a silicone oil bath at 140 degrees C for 30 min. We then added the swollen carrageenan to the agarose solution, which heating the temperature to 140 degrees C for 30 min while continuously stirring at 120 rpm, following with natural cooling.

Thermodynamic implications of high Q 10 of thermo-TRP channels in living cells.

The activity of thermo-transient receptor potential (TRP) channels is highly dependent on temperature, and thus thermo-TRP reactions have a high temperature coefficient Q 10. In thermodynamics, a high value of Q 10 indicates the existence of a large activation energy (i.e., a large enthalpy) over a short period during the transition process between the closed and open states of the channels. The Gibbs free energy equation shows that a large entropy is required to compensate for this large enthalpy and permit activation of the channels, suggesting a large conformational change of the channels. These large values of enthalpy and entropy seem to be a match for the values of the unfolding process of globular proteins. We outline these thermodynamic issues in thermo-TRPs.

Modular network evolution under selection for robustness to noise.

Real networks often exhibit modularity, which is defined as the degree to which a network can be decomposed into several subnetworks. The question of how a modular network arises is still open to discussion. The leading hypothesis is that high modularity evolves under multiple goals, which are decomposable to subproblems, as well as under the evolutionary constraint that selection prefers sparse links in a network. In the present study, we investigate an alternative evolutionary constraint entailing increased robustness to noise. To examine this, we present noise-interfused network models involving an analytically solvable linear system and biologically inspired nonlinear systems. The models demonstrate that it is possible to evolve a modular network under both modularly changing goal orientations and enhancing robustness to noise, thereby reducing sensitivity to noise. By performing theoretical analyses of linear systems, it is shown that the evolutionary constraint enforces the establishment of well-balanced noise sensitivities of multiple noise sources and leads to a modular network underlying a modular structure in goals. Moreover, computer simulations confirm that the presented mechanisms of modular network evolution are robust to variations of nonlinearity in network functions. Our findings suggest a positive role for the presence of noise in network evolution.

Development of MRI phantom equivalent to human tissues for 3.0-T MRI.

PURPOSE: A 3.0-T MRI phantom (called the CAGN-3.0T phantom) having human-equivalent relaxation times and human-equivalent conductivity was developed. METHODS: The ingredients of the phantom are carrageenan (as a gelatinizer), agarose (as a T2-relaxation modifier), GdCl3 (as a T1-relaxation modifier), NaCl (as a conductivity modifier), and NaN3 (as an antiseptic). Numerous samples with varying concentrations of agarose, GdCl3, and NaCl were prepared, and T1 and T2 values were measured using 3.0-T MRI. RESULTS: The T1 values of the CAGN-3.0T phantom were unaffected by NaCl, while the T2 values were only slightly affected. Based on the measured data, empirical formulae were devised to express the relationships between the concentrations of agarose, GdCl3, and NaCl and the relaxation times. The formula for expressing the conductivity of the CAGN-3.0T phantom was obtained. CONCLUSIONS: By adjustments to the concentrations of agarose, GdCl3, and NaCl, the relaxation times and conductivity of almost all types of human tissues can be simulated by CAGN-3.0T phantoms. The phantoms have T1 values of 395-2601 ms, T2 values of 29-334 ms, and conductivity of 0.27-1.26 S/m when concentrations of agarose, GdCl3, and NaCl are varied from 0 to 2.0 w/w%, 0 to 180 µmol/kg, and 0 to 0.7 w/w%, respectively. The CAGN-3.0T phantom has sufficient strength to replicate the torso without using reinforcing agents, and can be cut with a knife into any shape.