The effect of temperature on conduction velocity in human muscle fibers

The effects of variation of intramuscular temperature (T) on conduction velocity (CV) of the action potential along single human muscle fibers of the biceps brachii was studied in situ in 15 normal volunteers (mean age 39 years, range 21–62 years). Cooling was obtained by direct application of ice over a rectangular skin region including the stimulating and recording area. The intramuscular T was monitored by a needle thermocouple (copperconstantane). In all the 24 muscle fibers studied, a linear relationship was observed between CV and T. The slopes of the regression lines, ranging between 0.190 and 0.079 m/s, were positively correlated with the starting CV at 36°C ranging between 2.2 and 5.2 m/s. If conduction changes are expressed as a percentage of the basal CV at 36°C, the CV/T coefficient is the same for all the fibers and independent of the individual CV: 3.4% of CV/°C.     

Plant functional types and climatic change: Introduction

Abstract. Plant functional types are a necessary device for reducing the complex and often uncharted characteristics of species diversity in function and structure when attempting to project the nature and function of species assemblages into future environments. A workshop was held to review the current methods commonly used for defining plant functional types, either globally or for particular biomes, and to compare them with the field experiences of specialists for specific biomes of the world. The methods fall into either an objective and inductive approach or a subjective and deductive approach. When the different methods were tested, it was generally found that the classification for one site or environment was not wholly applicable to a different site or environment. However, the degree of change which is necessary for adjustment between environments may not prove to be a major limitation in the use of functional types.     

A novel Golgi mannosidase inhibitor: Molecular design,synthesis, enzyme inhibition,and inhibition of spheroid formation

Effective chemotherapy for solid cancers is challenging due to a limitation in permeation that prevents anticancer drugs from reaching the center of the tumor, therefore unable to limit cancer cell growth. To circumvent this issue, we planned to apply the drugs directly at the center by first collapsing the outer structure. For this, we focused on cell–cell communication (CCC) between N-glycans and proteins at the tumor cell surface. Mature N-glycans establish CCC; however, CCC is hindered when numerous immature N-glycans are present at the cell surface. Inhibition of Golgi mannosidases (GMs) results in the transport of immature N-glycans to the cell surface. This can be employed to disrupt CCC. Here, we describe the molecular design and synthesis of an improved GM inhibitor with a non-sugar mimic scaffold that was screened from a compound library. The synthesized compounds were tested for enzyme inhibition ability and inhibition of spheroid formation using cell-based methods. Most of the compounds designed and synthesized exhibited GM inhibition at the cellular level. Of those, AR524 had higher inhibitory activity than a known GM inhibitor, kifunensine. Moreover, AR524 inhibited spheroid formation of human malignant cells at low concentration (10 µM), based on the disruption of CCC by GM inhibition.     

Changes in lower limb muscle activity after walking on a split-belt treadmill in individuals post-stroke

Background: There is growing evidence that stroke survivors can adapt and improve step length symmetry in the context of split-belt treadmill (SBT) walking. However, less knowledge exists about the strategies involved for such adaptations. This study analyzed lower limb muscle activity in individuals post-stroke related to SBT-induced changes in step length. Methods: Step length and surface EMG activity of six lower limb muscles were evaluated in individuals post-stroke (n = 16) during (adaptation) and after (after-effects) walking at unequal belt speeds. Results: During adaptation, significant increases in EMG activity were mainly found in proximal muscles (p ⩽ 0.023), whereas after-effects were observed particularly in the distal muscles. The plantarflexor EMG increased after walking on the slow belt (p ⩽ 0.023) and the dorsiflexors predominantly after walking on the fast belt (p ⩽ 0.017) for both, non-paretic and paretic-fast conditions. Correlation analysis revealed that after-effects in step length were mainly associated with changes in distal paretic muscle activity (0.522 ⩽ r ⩽ 0.663) but not with functional deficits. Based on our results, SBT walking could be relevant for training individuals post-stroke who present shorter paretic step length combined with dorsiflexor weakness, or individuals with shorter nonparetic step length and plantarflexor weakness.     

Electromyographic analysis of upper limb muscles during standardized isotonic and isokinetic robotic exercise of spastic elbow in patients with stroke

Although it has been reported that strengthening exercise in stroke patients is beneficial for their motor recovery, there is little evidence about which exercise method is the better option. The purpose of this study was to compare isotonic and isokinetic exercise by surface electromyography (EMG) analysis using standardized methods.Nine stroke patients performed three sets of isotonic elbow extensions at 30% of their maximal voluntary isometric torque followed by three sets of maximal isokinetic elbow extensions with standardization of mean angular velocity and the total amount of work for each matched set in two strengthening modes. All exercises were done by using 1-DoF planner robot to regulate exact resistive torque and speed. Surface electromyographic activity of eight muscles in the hemiplegic shoulder and elbow was recorded. Normalized root mean square (RMS) values and co-contraction index (CCI) were used for the analysis.The isokinetic mode was shown to activate the agonists of elbow extension more efficiently than the isotonic mode (normalized RMS for pooled triceps: 96.0 ± 17.0 (2nd), 87.8 ± 14.4 (3rd) in isokinetic, 80.9 ± 11.0 (2nd), 81.6 ± 12.4 (3rd) in isotonic contraction, F[1, 8] = 11.168; P = 0.010) without increasing the co-contraction of muscle pairs, implicating spasticity or synergy.     

Modulation of DNA synthesis in aortic smooth muscle cells by dinitrotoluenes

Studies were conducted to determine if in vivo exposure to dinitrotoluenes (DNT), which is associated with circulatory disorders of atherosclerotic etiology in humans, is associated with alterations of vascular smooth muscle cells (SMC) consistent with the atherogenic process. Sprague-Dawley rats (150-180 g) were injected IP for 5 days/week for 8 weeks with 2,4- or 2,6-DNT (0.5, 5, or 10 mg/kg) or medium chain triglyceride (MCT) oil. Histopathologic evaluation of aortae from animals exposed to either isomer showed dysplasia and rearrangement of SMC at all doses tested. Reduced ³H-thymidine incorporation was observed in primary cultures of aortic SMC from DNT-exposed animals relative to vehicle controls. This inhibitory response was maintained for up to two passages in culture after which a significant increase in thymidine incorporation was observed. Exposure of SMC from naive animals to DNT in vitro (1–100 µM) did not alter the extent of thymidine incorporation in cycling or growth-arrested cultures. In contrast, exposure to 2,4- or 2,6-diaminotoluene (DAT) (1–100 µM), carcinogens which share toxic metabolic intermediates in common with DNT, inhibited replicative DNA synthesis and stimulated unscheduled DNA synthesis in cycling and growth-arrested cultures of SMC, respectively. Our results suggest that modulation of DNA synthesis in aortic SMC by DNT metabolites generated in vivo contribute to the development of vascular lesions.Abbreviation DAT diaminotuluene - tDNT technical grade dinitrotoluene - DNT dinitrotoluenes - HU hydroxyurea - IP intraperitoneal - LDH lactate dehydrogenase - MCT oil medium chain triglyceride - NPTC non-protein thiol content - RDS replicative DNA synthesis - SEM standard error of the mean - SMC smooth muscle cells - UDS unscheduled DNA synthesis     

Developmental pattern of the bony tentorium of spider monkeys (Ateles)

Based on their developmental patterns, the bony tentorium (BT) and bony falx (BF) of mammals can be classified into two types, the carnivoran type and the dolphin type. The former develops as part of the skull bones during the fetal period and is already completed at birth, while the latter is gradually formed by ossification in the tentorium cerebelli (TC) and falx cerebri (FC) during the course of aging. The BT of spider monkeys is assigned to the dolphin type.     

Site-Specific Structural Variations Accompanying Tubular Assembly of the HIV-1 Capsid Protein

The 231-residue capsid (CA) protein of human immunodeficiency virus type 1 (HIV-1) spontaneously self-assembles into tubes with a hexagonal lattice that is believed to mimic the surface lattice of conical capsid cores within intact virions. We report the results of solid-state nuclear magnetic resonance (NMR) measurements on HIV-1 CA tubes that provide new information regarding changes in molecular structure that accompany CA self-assembly, local dynamics within CA tubes, and possible mechanisms for the generation of lattice curvature. This information is contained in site-specific assignments of signals in two- and three-dimensional solid-state NMR spectra, conformation-dependent ¹⁵N and ¹³C NMR chemical shifts, detection of highly dynamic residues under solution NMR conditions, measurements of local variations in transverse spin relaxation rates of amide ¹H nuclei, and quantitative measurements of site-specific ¹⁵N–¹⁵N dipole–dipole couplings. Our data show that most of the CA sequence is conformationally ordered and relatively rigid in tubular assemblies and that structures of the N-terminal domain (NTD) and the C-terminal domain (CTD) observed in solution are largely retained. However, specific segments, including the N-terminal β-hairpin, the cyclophilin A binding loop, the inter-domain linker, segments involved in intermolecular NTD–CTD interactions, and the C-terminal tail, have substantial static or dynamical disorder in tubular assemblies. Other segments, including the 3₁₀-helical segment in CTD, undergo clear conformational changes. Structural variations associated with curvature of the CA lattice appear to be localized in the inter-domain linker and intermolecular NTD–CTD interface, while structural variations within NTD hexamers, around local 3-fold symmetry axes, and in CTD–CTD dimerization interfaces are less significant.