Heat Resistance Correlated with DNA Content in Bacillus megaterium Spores

Two subpopulations of Bacillus megaterium spores (1.360 and 1.355 g/ml) were obtained by density gradient centrifugation. The heavier spores had a higher thermoresistance (e.g., D₈₀ = 186 versus 81 min) and a higher DNA content (1.25 × 10⁻¹⁴ versus 0.65 × 10⁻¹⁴ g per spore, apparently corresponding to digenomic versus monogenomic spores). No appreciable differences were found in the mineral and dipicolinic acid contents or in the inactivation kinetics of the two subpopulations. The implications of the findings are discussed with regard to mechanisms of heat resistance and of inactivation.     

Patterns of ribosomal RNA evolution in salamanders

Sequence comparisons are presented for four segments of the large subunit of ribosomal RNA, including divergent domains D7a and D7b, portions of the large divergent domains D2, D3, and D8, and evolutionarily conservative sequences flanking divergent domains. These results resolve phylogenetic relationships among exemplars of seven families of salamanders and the three amphibian orders. Phylogenetic analysis confirms the prediction that divergent domains feature the highest relative rates of base substitution and length variation within the ribosome, but the divergent domains evolve more slowly than nuclear noncoding DNA and the silent sites of structural genes. Base substitutions demonstrate approximately twice as many transitions as transversions and an uneven distribution among sites within the divergent domains but no apparent bias in base composition. Length mutations are primarily small insertions and deletions, with deletions predominating. The divergent domains appear to be a good source of phylogenetic information for evolutionary events occurring approximately 100-200 million years ago.      

Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease

Background  

Huntington's disease is a progressive autosomal dominant neurodegenerative disorder that is caused by a CAG repeat expansion in the HD or Huntington's disease gene. Although micro array studies on patient and animal tissue provide valuable information, the primary effect of mutant huntingtin will inevitably be masked by secondary processes in advanced stages of the disease. Thus, cell models are instrumental to study early, direct effects of mutant huntingtin. mRNA changes were studied in an inducible PC12 model of Huntington's disease, before and after aggregates became visible, to identify groups of genes that could play a role in the early pathology of Huntington's disease.     

Association of a gliotoxic activity with active multiple sclerosis in US patients.

We recently found that cerebrospinal fluid (CSF) from multiple sclerosis (MS) patients contains a gliotoxic activity which induces programmed cell death of astrocytes and oligodendrocytes and could be the main contributing factor to the massive glial cell death seen in MS active lesions. A previous clinical study aimed at evaluating the gliotoxicity of CSF from a cohort of MS patients from France indicated that MS patients with the active form of the disease do indeed present significant CSF gliotoxicity. To extend this observation, the effect of 141 CSFs from United States patients with different neurological diseases (including 71 MS) was tested on immortalized astrocytes. A cell death assay showed that a gliotoxic activity is significantly present in the CSF from MS patients with the active forms. Thus, this gliotoxic activity may represent a critical pathogenic factor in the neuropathology of active MS by playing a role both in demyelinisation and alteration of the blood-brain barrier.     

A significant reduction of the diaphragm in mdx:MyoD-/-(9th) embryos suggests a role for MyoD in the diaphragm development

To further investigate the role of MyoD during skeletal myogenesis, we backcrossed mdx mutant mice (lacking dystrophin) with MyoD knock-out mice to obtain viable mice with MyoD allele on a pure mdx background. However, after nine generations of backcrossing, it was not possible to obtain a viable mdx:MyoD-/- phenotype (designated as: mdx:MyoD-/-(9th)). The compound-mutant embryos were examined just before birth. Essentially normal Myf5-dependent and most of the MyoD-dependent musculature was observed. By contrast, the skeletal muscle compartment of the diaphragm was significantly reduced. The mesenchymal compartment of the diaphragm was intact and no herniations were observed. Other examined organs (e.g., liver, kidney, brain, etc.) showed no histological abnormalities. Pulmonary hypoplasia was determined as the cause of neonatal death. Therefore, using a different approach, our new data supplement our previous findings and suggest an essential role for MyoD in development of skeletal muscle of the diaphragm. The failure of mdx:MyoD-/-(9th) diaphragm to develop normally is not caused by a reduced number of satellite cells, but from the inability of stem cells to progress through the myogenic program. Our data also suggest that functions of MyoD and Myf5 (and the respective muscle precursor cell sub-populations) are not entirely redundant by term, as previously suggested, since Myf5 is not capable of fully substituting for MyoD in the diaphragm development.     

Echocardiographic AV-interval optimization in patients with reduced left ventricular function

Background

Power Doppler (PD) has improved diagnostic capabilities of vascular sonography, mainly because it is independent from the angle of insonation. We evaluated this technique in a prospective comparison with conventional imaging, consisting in Duplex and Color Doppler, for the evaluation of Renal Artery (RA) stenosis.

Methods

Sensitivity, specificity and predictive values of PD and conventional imaging were assessed in a blinded fashion on eighteen patients, 9 with angiographic evidence of unilateral RA stenosis (hypertensive patients) and 9 with angiographically normal arteries (control group). PD images were interpreted with an angiography-like criteria.

Results

In the control group both techniques allowed correct visualization of 16 out of the 18 normal arteries (93% specificity). Only in five hypertensive patients RA stenosis was correctly identified with conventional technique (56% sensitivity and 86% negative predictive value); PD was successful in all hypertensive patients (100% sensitivity and negative predictive value), since the operators could obtain in each case of RA stenosis a sharp color signal of the whole vessel with a clear "minus" at the point of narrowing of the lumen. All results were statistically significant (p < 0.01).

Conclusions

This study demonstrates that PD is superior to conventional imaging, in terms of sensitivity and specificity, for the diagnosis of RA stenosis, because it allows a clear visualization of the whole stenotic vascular lumen. Especially if it is used in concert with the other sonographic techniques, PD can enable a more accurate imaging of renovascular disease with results that seem comparable to selective angiography.     

Moving instead of asking? Performance-based tests and BASFI-questionnaire measure different aspects of physical function in ankylosing spondylitis

Introduction

Ankylosing Spondylitis (AS) is characterised by limitations in physical function. The Bath Ankylosing Spondylitis Functional Index (BASFI) is considered to be the gold-standard to assess physical function in AS patients. However, the BASFI questionnaire is a self-reported outcome measure and susceptible to subjective interpretation (under- or over-estimation). More objective outcome measures, like performance-based tests, could provide an objective outcome measurement for the evaluation of limitations in physical function. Therefore, the primary aim of this study was to determine the association between performance-based measures and the BASFI questionnaire.

Methods

In this cross-sectional study 126 AS patients completed the BASFI questionnaire and eight performance-based tests based on BASFI-items. Each test received three scores: one for performance (time or points) and a score for exertion and pain experienced during performance (using modified Borg-scale and VAS 0-100 mm, respectively). Linear regression analyses were used to assess the associations between the BASFI questionnaire and performance-based tests.

Results

The univariable association between performance and BASFI-score was moderate with a R-square of 0.31 and Beta of 0.56 (p's < 0.05). In a multivariable analysis, the association between performance, exertion and pain on the one hand and BASFI-score on the other was assessed; R-square increased to 0.54: the Beta's for exertion and pain during performance were 0.38 and 0.26, respectively; the Beta for performance decreased to 0.19 (p's < 0.05).

Conclusions

This study demonstrates that alongside actual performance, patients seem to incorporate exertion and pain in their assessment of perceived physical function on the BASFI questionnaire. Performance-based tests could provide an objective outcome measurement for the evaluation of physical function and give relevant new information in addition to the BASFI questionnaire.     

Dissociable influences of auditory object vs. spatial attention on visual system oscillatory activity

Given that both auditory and visual systems have anatomically separate object identification ("what") and spatial ("where") pathways, it is of interest whether attention-driven cross-sensory modulations occur separately within these feature domains. Here, we investigated how auditory "what" vs. "where" attention tasks modulate activity in visual pathways using cortically constrained source estimates of magnetoencephalograpic (MEG) oscillatory activity. In the absence of visual stimuli or tasks, subjects were presented with a sequence of auditory-stimulus pairs and instructed to selectively attend to phonetic ("what") vs. spatial ("where") aspects of these sounds, or to listen passively. To investigate sustained modulatory effects, oscillatory power was estimated from time periods between sound-pair presentations. In comparison to attention to sound locations, phonetic auditory attention was associated with stronger alpha (7-13 Hz) power in several visual areas (primary visual cortex; lingual, fusiform, and inferior temporal gyri, lateral occipital cortex), as well as in higher-order visual/multisensory areas including lateral/medial parietal and retrosplenial cortices. Region-of-interest (ROI) analyses of dynamic changes, from which the sustained effects had been removed, suggested further power increases during Attend Phoneme vs. Location centered at the alpha range 400-600 ms after the onset of second sound of each stimulus pair. These results suggest distinct modulations of visual system oscillatory activity during auditory attention to sound object identity ("what") vs. sound location ("where"). The alpha modulations could be interpreted to reflect enhanced crossmodal inhibition of feature-specific visual pathways and adjacent audiovisual association areas during "what" vs. "where" auditory attention.