Time-related changes of motor unit properties in the rat medial gastrocnemius muscle after spinal cord injury. I. Effects of total spinal cord transection

The contractile properties of motor units (MUs) were electrophysiologically investigated in the medial gastrocnemius (MG) muscle in 17 Wistar three-month-old female rats: 14, 30, 90 and 180 days after the total transection of the thoracic spinal cord and compared to those in intact (control) rats. A sag phenomenon, regularly observed in unfused tetani of fast units in intact animals at 40 Hz stimulation, almost completely disappeared in spinal rats. Therefore, the MUs of intact and spinal rats were classified as fast or slow types basing on 20 Hz tetanus index, the value of which was lower or equal 2.0 for fast and higher than 2.0 for slow MUs. The MUs composition of MG muscle changed with time after the spinal cord transection: an increasing proportion of fast fatigable (FF) units starting one month after injury and a disappearance of slow (S) units within the three months were observed. In all MUs investigated the twitch contraction and half-relaxation time were significantly prolonged after injury (p < 0.01, Mann–Whitney U-test). Moreover, a decrease of the fatigue index for fast resistant (FR) and slow MUs was observed in subsequent groups of spinal rats. No significant changes were found between twitch forces in all MU types of spinal animals (p > 0.05). However, due to a decrease of the maximal tetanic force, a significant rise of the twitch-to-tetanus ratio of all MUs in spinal rats was detected (p < 0.01). The considerable reduction of ability to potentiate the force was noticed for fast, especially FF type MUs. In conclusion, the spinal cord transection leads to changes in the proportion of the three MU types in rat MG muscle. The majority of changes in MUs’ contractile properties were developed progressively with time after the spinal cord injury. However, the most intensive alterations of twitch-time parameters were observed in rats one month after the transection.     

Clinical features,treatment and genetic background of Treacher Collins syndrome

Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development. The major features of the disease include midface hypoplasia, micrognathia, microtia, conductive hearing loss and cleft palate. Current procedures of surgical treatment of TCS are discussed and novel findings concerning the genetic background of TCS are described. The TCS locus has been mapped to chromosome 5q31.3-32. The TCOF1 gene contains 26 exons and encodes a 1411 amino acid protein named treacle. In the TCOF1 gene 51 mutations have been identified. Most of these mutations are insertions or deletions, which result in an introduction of a premature termination codon into the reading frame. Mutational spectra support the hypothesis that TCS results from haploinsufficiency of treacle.     

The influences of somatic and dendritic inhibition on bursting patterns in a neuronal circuit model

The balance between inhibition and excitation plays a crucial role in the generation of synchronous bursting activity in neuronal circuits. In human and animal models of epilepsy, changes in both excitatory and inhibitory synaptic inputs are known to occur. Locations and distribution of these excitatory and inhibitory synaptic inputs on pyramidal cells play a role in the integrative properties of neuronal activity, e.g., epileptiform activity. Thus the location and distribution of the inputs onto pyramidal cells are important parameters that influence neuronal activity in epilepsy. However, the location and distribution of inhibitory synapses converging onto pyramidal cells have not been fully studied. The objectives of this study are to investigate the roles of the relative location of inhibitory synapses on the dendritic tree and soma in the generation of bursting activity. We investigate influences of somatic and dendritic inhibition on bursting activity patterns in several paradigms of potential connections using a simplified multicompartmental model. We also investigate the effects of distribution of fast and slow components of GABAergic inhibition in pyramidal cells. Interspike interval (ISI) analysis is used for examination of bursting patterns. Simulations show that the inhibitory interneuron regulates neuronal bursting activity. Bursting behavior patterns depend on the synaptic weight and delay of the inhibitory connection as well as the location of the synapse. When the inhibitory interneuron synapses on the pyramidal neuron, inhibitory action is stronger if the inhibitory synapse is close to the soma. Alterations of synaptic weight of the interneuron can be compensatory for changes in the location of synaptic input. The relative changes in these parameters exert a considerable influence on whether synchronous bursting activity is facilitated or reduced. Additional simulations show that the slow GABAergic inhibitory component is more effective than the fast component in distal dendrites. Taken together, these findings illustrate the potential for GABAergic inhibition in the soma and dendritic tree to play an important modulatory role in bursting activity patterns.     

Mechanistic determinants of MBNL activity

Muscleblind-like (MBNL) proteins are critical RNA processing factors in development. MBNL activity is disrupted in the neuromuscular disease myotonic dystrophy type 1 (DM1), due to the instability of a non-coding microsatellite in the DMPK gene and the expression of CUG expansion (CUG^exp) RNAs. Pathogenic interactions between MBNL and CUG^exp RNA lead to the formation of nuclear complexes termed foci and prevent MBNL function in pre-mRNA processing. The existence of multiple MBNL genes, as well as multiple protein isoforms, raises the question of whether different MBNL proteins possess unique or redundant functions. To address this question, we coexpressed three MBNL paralogs in cells at equivalent levels and characterized both specific and redundant roles of these proteins in alternative splicing and RNA foci dynamics. When coexpressed in the same cells, MBNL1, MBNL2 and MBNL3 bind the same RNA motifs with different affinities. While MBNL1 demonstrated the highest splicing activity, MBNL3 showed the lowest. When forming RNA foci, MBNL1 is the most mobile paralog, while MBNL3 is rather static and the most densely packed on CUG^exp RNA. Therefore, our results demonstrate that MBNL paralogs and gene-specific isoforms possess inherent functional differences, an outcome that could be enlisted to improve therapeutic strategies for DM1.     

Arteriovenous oscillations of the redox potential: Is the redox state influencing blood flow?

Objective: Studies on the regulation of human blood flow revealed several modes of oscillations with frequencies ranging from 0.005 to 1 Hz. Several mechanisms were proposed that might influence these oscillations, such as the activity of vascular endothelium, the neurogenic activity of vessel wall, the intrinsic activity of vascular smooth muscle, respiration, and heartbeat. These studies relied typically on non-invasive techniques, for example, laser Doppler flowmetry. Oscillations of biochemical markers were rarely coupled to blood flow.

Methods: The redox potential difference between the artery and the vein was measured by platinum electrodes placed in the parallel homonymous femoral artery and the femoral vein of ventilated anesthetized pigs.

Results: Continuous measurement at 5 Hz sampling rate using a digital nanovoltmeter revealed fluctuating signals with three basic modes of oscillations: ～ 1, ～ 0.1 and ～ 0.01 Hz. These signals clearly overlap with reported modes of oscillations in blood flow, suggesting coupling of the redox potential and blood flow.

Discussion: The amplitude of the oscillations associated with heart action was significantly smaller than for the other two modes, despite the fact that heart action has the greatest influence on blood flow. This finding suggests that redox potential in blood might be not a derivative but either a mediator or an effector of the blood flow control system.     

mPSQed: a software for the design of multiplex pyrosequencing assays

Molecular-based diagnostic assays are the gold standard for infectious diseases today, since they allow a rapid and sensitive identification and typing of various pathogens. While PCR can be designed to be specific for a certain pathogen, a subsequent sequence analysis is frequently required for confirmation or typing. The design of appropriate PCR-based assays is a complex task, especially when conserved discriminating polymorphisms are rare or if the number of types which need to be differentiated is high. One extremely useful but underused method for this purpose is the multiplex pyrosequencing technique. Unfortunately there is no software available to aid researchers in designing multiplex pyrosequencing assays. Here, we present mPSQed (Multiplex PyroSeQuencing EDitor), a program targeted at closing this gap. We also present the design of an exemplarily theoretical assay for the differentiation of human adenovirus types A-F using two pyrosequencing primers on two distinct PCR products, designed quickly and easily using our software.     

Overrepresentation of interactions between homologous proteins in interactomes

It is well proved that the probability that a protein interacts with itself is higher than that it interacts with another protein. It has been recently shown that the probability of interaction is also higher for proteins with significant sequence similarity. In this paper we show that proteins sharing identical PFAM domains interact more often than expected by chance in Saccharomyces cerevisiae and Escherichia coli. We also analyze the variety of domain interfaces used by homologous proteins to interact and show that the overrepresentation of interactions between homological proteins is not caused by small number of pairs of identical "sticky domains" shared between interacting proteins.