Responses of medullary and spinal cord neurons to simulataneous stimulation of two locomotor points

Responses of neurons in the medulla and cervical segments of the spinal cord to simultaneous repetitive stimulation (50 pps) of two locomotor points (LP) that exceed the threshold for evoking walking by one to two times were investigated in mesencephalic cats. In most cases a neuron responsed to stimulation of only one LP. Stimulation of a second LP usually enhanced the firing index of that response, if it was low. Or it decreased the firing index if it was high, and it had no effect if the firing index was about 0.1. Some of the neurons responded to stimulation of one LP by increasing the baseline activity, though the pulses were not locked to individual stimuli. The effect of stimulation of the second LP on this increase in activity depended on the size of the increase. Data were also obtained on the convergence of effects on single neurons from the ipsi- and contralateral LPs of the midbrain and medulla. Possible mechanisms of the summation of subthreshold excitation of a pair of LPs during the initiation of locomotion are discussed.Institute of Information Transmission Problems, Russian Academy of Sciences, Moscow. Translated from Neirofiziologiya, Vol. 24, No. 4, pp. 471–481, July–August, 1992.     

Anisotropic connections in the cat midbrain tegmentum

Single unit responses of the cat midbrain tectum to stimuli applied through a microelectrode 500µ rostrally to the recording electrode were recorded extracellularly. The mean latency of both direct and monosynaptic responses was 0.3 msec greater than that for local microstimulation. The responses were identified from their latent and refractory periods, the presence of summation, and the dependence of the firing index on sodium glutamate application to the recorded neuron. Thresholds of synaptic responses were measured during vertical displacement of the stimulating electrode. The experimental relationships can be approximated by parabolic functions. The results indicate that rostrocaudal projections in the midbrain tegmentum are arranged horizontally.     

Peroxiredoxin 2 deficiency reduces white adipogenesis due to the excessive ROS generation

Reactive oxygen species (ROS) act as signaling molecules to regulate various cell functions. Numerous studies have demonstrated ROS to be essential for the differentiation of adipocytes. Peroxiredoxins (Prxs) are a ubiquitous family of antioxidant enzymes in mammalian cells. Prx2 is present in the cytoplasm and cell membranes and demonstrates ROS scavenging activity. We focused on Prx2 involvement in regulating adipogenesis and lipid accumulation and demonstrated that Prx2 expression was upregulated during adipocyte differentiation. In addition, the silencing of Prx2 (shPrx2) inhibited adipogenesis by modulating adipogenic gene expression, and cell death was enhanced via increased ROS production in shPrx2‐3T3‐L1 cells. These results demonstrate that shPrx2 triggers adipocyte cell death and weakens adipocyte function via ROS production. Taken together, our data suggest the participation of Prx2 in adipocyte function and differentiation. Our results also imply that the downregulation of Prx2 activity could help prevent obesity. Overall, findings support the development of ROS‐based therapeutic solutions for the treatment of obesity and obesity‐related metabolic disorders.     

Molecular Dynamics Study on Protein and it's Water Structure at High Pressure

Abstract

We have performed NPT molecular dynamics simulations (Langevin Piston Method) on two types of solvated proteins-‘denaturation-unfavorable’ protein (insulin) and ‘denaturation-favorable protein’ (ribonuclease A) at high pressure (from 1 bar up to 20 kbar). The method is based on the extended system formalism introduced by Andersen, where the deterministic equations of motion for the piston degree of freedom are replaced by Langevin equation. We report the structural changes of proteins (ribonuclease A and insulin) and water molecules through radius of gyration, solvent accessible surface area, hydrogen bond pattern, and the topology of water clusters connected by the hydrogen bonded circular network. The solvent accessibility of ribonuclease A is mainly decreased by hydrophilic residues rather than hydrophobic residues under high pressure. From the results of hydrogen bond analysis, we have found that α-helix is more stable than β-sheet under high pressure. In addition, from the analysis of the water cluster, we have observed that for ribonuclease A, 5-membered ring structure is more favorable than 6-membered ring at higher pressure. However, for insulin, the ratio of 5 to 6-ring is constant over the pressure ranges for which we have performed MD simulation. This indicates that the water structure around insulin does not change under high pressure.     

A Modified Valley Restrained Monte Carlo Method to Efficiently Search the Low Energy Structures of Peptides

Abstract

A new Monte Carlo sampling scheme, namely the Modified Valley Restrained Monte Carlo procedure, is used to obtain the global energy minimum conformations for polypeptides, such as Met-enkephalin and Melittin. For each peptide, we found close agreement with previous results from both theoretical and experimental studies. The simple idea for controlling the step size according to the Valley Function, provides useful suggestions in searching the global energy minimum structures, and furthermore helps solve the multiple minima problem.