Orexinergic Neurotransmission in Temperature Responses to Methamphetamine and Stress: Mathematical Modeling as a Data Assimilation Approach

Experimental Data

Orexinergic neurotransmission is involved in mediating temperature responses to methamphetamine (Meth). In experiments in rats, SB-334867 (SB), an antagonist of orexin receptors (OX1R), at a dose of 10 mg/kg decreases late temperature responses (t>60 min) to an intermediate dose of Meth (5 mg/kg). A higher dose of SB (30 mg/kg) attenuates temperature responses to low dose (1 mg/kg) of Meth and to stress. In contrast, it significantly exaggerates early responses (t<60 min) to intermediate and high doses (5 and 10 mg/kg) of Meth. As pretreatment with SB also inhibits temperature response to the stress of injection, traditional statistical analysis of temperature responses is difficult.

Mathematical Modeling

We have developed a mathematical model that explains the complexity of temperature responses to Meth as the interplay between excitatory and inhibitory nodes. We have extended the developed model to include the stress of manipulations and the effects of SB. Stress is synergistic with Meth on the action on excitatory node. Orexin receptors mediate an activation of on both excitatory and inhibitory nodes by low doses of Meth, but not on the node activated by high doses (HD). Exaggeration of early responses to high doses of Meth involves disinhibition: low dose of SB decreases tonic inhibition of HD and lowers the activation threshold, while the higher dose suppresses the inhibitory component. Using a modeling approach to data assimilation appears efficient in separating individual components of complex response with statistical analysis unachievable by traditional data processing methods.     

Pulmonary Toxocariasis Mimicking Invasive Aspergillosis in a Patient with Ulcerative Colitis

A 45-year-old-male who had underlying ulcerative colitis and presented with fever and dry cough. Initially, the patient was considered to have invasive aspergillosis due to a positive galactomannan assay. He was treated with amphotericin B followed by voriconazole. Nevertheless, the patient deteriorated clinically and radiographically. The lung biopsy revealed eosinophilic pneumonia, and ELISA for Toxocara antigen was positive, leading to a diagnosis of pulmonary toxocariasis. After a 10-day treatment course with albendazole and adjunctive steroids, the patient recovered completely without any sequelae. Pulmonary toxocariasis may be considered in patients with subacute or chronic pneumonia unresponsive to antibiotic agents, particularly in cases with eosinophilia.     

Nonthermal Plasma‐Induced Degradation of Morin and Enhancement of Biological Activities

In the present study, non‐thermal dielectric barrier discharge (DBD) plasma of induced structural changes of morin resulted in the isolation of one previously undescribed benzofuranone derivative, along with two known compounds. The chemical structures of these degradation products were elucidated by UV, NMR and FAB‐MS spectroscopic analyses. The isolated three compounds showed potent antioxidative activities in two different tests, with IC₅₀ values in the range of 12.9–41.8 μm in the 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS⁺) radical scavenging activity, 19.0–71.9 μm for hydroxyl radical scavenging activity test. Furthermore, the new methoxylated benzofuranone exhibited enhancement of inhibitory effects against pancreatic lipase with an IC₅₀ value of 90.7±1.6 μm , when compared to the parent morin. These results suggested that the degradation products isolated from plasma exposed morin might be beneficial for prevention of obesity and related diseases.     

Simple atomistic modeling of dominant B m I n clusters in boron diffusion

In this paper, we present a simple atomistic model for describing the evolution of interstitial clusters during boron diffusion in kinetic Monte-Carlo (KMC) calculation. It has been known that clusters generated after ion implantation play a decisive role in the enhanced boron diffusion at the tail region while being immobile at the peak region. Our model, which is based on the simple continuum model, takes the intermediate clusters into account as well as dominant clusters for describing the evolutionary behavior of interstitial clusters during boron diffusion. We found that the intermediate clusters such as B₃I₃ and B₂I₃ play a significant role during the evolution of clusters despite the fact that the lifetimes of the corresponding intermediate clusters are relatively short due to low binding energies. Further, our investigation revealed that B₃I is the most dominant cluster after annealing. We applied our simple atomistic model to the study of boron retardation in arsenic pre-doped substrate. KMC simulation results were compared with experimental SIMS data, which supports our theoretical model.     

The subunit composition of Portunus trituberculatus hemocyanin polymers

The subunit composition of isolated polymeric forms of Portunus trituberculatus hemocyanin were analysed by immunological techniques. The dodecamers contain four monomeric subunits corresponding to subunits I, II, III and IV, whereas the hexamers are devoid of subunit IV. These results suggest that subunit IV is required as a joining piece for the assembly of dodecamers.     

Interleukin-1-β and Tumor Necrosis Factor-α Increase Peripheral-Type Benzodiazepine Binding Sites in Cultured Polygonal Astrocytes

Peripheral-type benzodiazepine binding sites (PTBBS) are markedly increased in the injured CNS. Astrocytes appear to be the primary cell type which express increased PTBBS. Because certain cytokines within the injured CNS are potent mitogens for astrocytes, we examined the effects of two such cytokines, interleukin (IL)-1 beta and tumor necrosis factor (TNF), on PTBBS in cultured astrocytes using [3H]Ro 5-4864 as the specific ligand. Purified cultures of either polygonal or process-bearing astrocytes were prepared from neonatal rat cerebral hemispheres. At a concentration of 1.8 nM, specific binding of the radioactive ligand to polygonal astrocytes reached equilibrium within 60 min and was half-maximal by 5-10 min. By contrast, specific binding to process-bearing astrocytes barely exceeded background levels. IL-1 and TNF increased PTBBS within polygonal astrocytes in both dose- and time-dependent manners. At 10-50 ng/ml, IL-1 beta and TNF-alpha elevated [3H]Ro 5-4864 binding in polygonal astrocyte cultures 65 and 87%, respectively, above the level in control cultures. However, no changes in PTBBS were seen within polygonal astrocytes after IL-2 treatment. Scatchard analysis of saturation binding experiments suggested that the increase in PTBBS promoted by TNF was due to an increased number of binding sites present in polygonal astrocytes and not due to an increase in receptor affinity. Binding data suggested that PTBBS within cultures of process-bearing astrocytes were virtually absent irrespective of the treatment. These in vitro data suggest that certain cytokines found in the injured brain may be involved in up-regulating PTBBS within a particular subtype of astrocyte.     

Cancer Cell Analyses at the Single Cell-Level Using Electroactive Microwell Array Device

Circulating tumor cells (CTCs), shed from primary tumors and disseminated into peripheral blood, are playing a major role in metastasis. Even after isolation of CTCs from blood, the target cells are mixed with a population of other cell types. Here, we propose a new method for analyses of cell mixture at the single-cell level using a microfluidic device that contains arrayed electroactive microwells. Dielectrophoretic (DEP) force, induced by the electrodes patterned on the bottom surface of the microwells, allows efficient trapping and stable positioning of single cells for high-throughput biochemical analyses. We demonstrated that various on-chip analyses including immunostaining, viability/apoptosis assay and fluorescent in situ hybridization (FISH) at the single-cell level could be conducted just by applying specific reagents for each assay. Our simple method should greatly help discrimination and analysis of rare cancer cells among a population of blood cells.     

Ruptured fission yeast walls

Distributions of rupture sites of fission yeast cells ruptured by glass beads have been related to a new morphometric analysis. As shown previously (Johnson et al.,Cell Biophysics, 1995), ruptures were not randomly distributed nor was their distribution dictated by geometry, rather, ruptures at the extensile end were related to cell length just as the rate of extension is related to cell length. The extension patterns of early log, mid-log, late log, and stationary phase cells from suspension cultures were found to approximate the linear growth patterns of Kubitschek and Clay (1986). The median length of cells was found to decline through the log phase in an unbalanced manner.     

Spatiotemporal Segregation of Neural Response to Auditory Stimulation: An fMRI Study Using Independent Component Analysis and Frequency-Domain Analysis

Although auditory processing has been widely studied with conventional parametric methods, there have been a limited number of independent component analysis (ICA) applications in this area. The purpose of this study was to examine spatiotemporal behavior of brain networks in response to passive auditory stimulation using ICA. Continuous broadband noise was presented binaurally to 19 subjects with normal hearing. ICA was performed to segregate spatial networks, which were subsequently classified according to their temporal relation to the stimulus using power spectrum analysis. Classification of separated networks resulted in 3 stimulus-activated, 9 stimulus-deactivated, 2 stimulus-neutral (stimulus-dependent but not correlated with the stimulation timing), and 2 stimulus-unrelated (fluctuations that did not follow the stimulus cycles) components. As a result of such classification, spatiotemporal subdivisions were observed in a number of cortical structures, namely auditory, cingulate, and sensorimotor cortices, where parts of the same cortical network responded to the stimulus with different temporal patterns. The majority of the classified networks seemed to comprise subparts of the known resting-state networks (RSNs); however, they displayed different temporal behavior in response to the auditory stimulus, indicating stimulus-dependent temporal segregation of RSNs. Only one of nine deactivated networks coincided with the “classic” default-mode network, suggesting the existence of a stimulus-dependent default-mode network, different from that commonly accepted.     

Molecular dynamics simulation study of probe diffusion in liquid n-alkanes

We performed molecular dynamics simulations for the probe diffusion and friction dynamics of Lennard-Jones (LJ) particles modelled for methyl yellow (MY) in liquid n-alkanes of C₁₂–C₂₀₀ at temperatures of 318, 418, 518 and 618 K. Two LJ particles are chosen: MY1 with a mass of 114 g/mol, LJ parameters of σ = 4.0 Å and ? = 0.4 kJ/mol, and MY2 with a mass of 225 g/mol, σ = 6.0 Å and ? = 0.6 kJ/mol. We observed a clear transition in the power law dependence of MY2 diffusion on the molecular weight of n-alkanes at lower temperatures of 318 and 418 K. The sharp transitions occur near n-dotriacontane (C₃₂). However, no such transition is found for MY1 at all the temperatures and for MY2 at higher temperatures of 518 and 618 K. We also calculated the friction constants of both MY probe molecules in liquid n-alkanes. For the larger probe molecule (MY2), at lower temperatures, a large deviation of slope from the linear dependence of the friction of MY2 on the chain length of n-alkane is observed, which indicates a large reduction of friction in longer chains when compared with the shorter chains, enhancing the diffusion of the probe molecules (MY2).