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Discusses the effects of environmental parameters, salinity, temperature and chloroquine on plasmid topology in the halophilic archaeon Haloferax volcanii. Comparison with effects produced in Escherichia coli; Reagents and enzymes; Strain and culture conditions; Plasmid purification; Determination of superhelical density values in vitro.

Abstract: Objectives. – We developed a non-invasive method allowing for an accurate analysis of the locomotion pattern in mouse. Synthesis of facts. – This method is based on cineradiography which associates high speed cinematography (250 pictures/s) and X-ray photography. It has been applied to the study of swimming exercise in a constant flow swimming pool. Our results provide the first evidence that swimming is characterized by micro intermittence which is defined as cyclic sequence of a power stroke time which is followed by a latency time. The duration of these two steps is within the range of m second. The functional relevance of each segment and the change of its time duration during training constitute a key of performance improvement. [Copyright &y& Elsevier]

We describe a new design for a mirage cell which is much more compact than the previously described setup and whose sensitivity has been improved by an order of magnitude. This cell has been successfully coupled to Fourier transform infrared spectrometers, visible spectrometers, and a thermal wave imaging setup. [ABSTRACT FROM AUTHOR]

Presents a study which conducted a thermal-wave nondestructive evaluation of a carbon epoxy composite with the use of mirage effect. Principle of the method; Description of the samples; Experimental results and discussion.

A letter to the editor is presented on the somatic KRAS mutation as highly predictive of resistance to anti-EGFR antibodies in metastatic colorectal cancer (MCRC) patients.

The predictive value of KRAS mutation in metastatic colorectal cancer (MCRC) patients treated with cetuximab plus chemotherapy has recently been suggested. In our study, 59 patients with a chemotherapy-refractory MCRC treated with cetuximab plus chemotherapy were included and clinical response was evaluated according to response evaluation criteria in solid tumours (RECIST). Tumours were screened for KRAS mutations using first direct sequencing, then two sensitive methods based on SNaPshot and PCR-ligase chain reaction (LCR) assays. Clinical response was evaluated according to gene mutations using the Fisher exact test. Times to progression (TTP) were calculated using the Kaplan–Meier method and compared with log-rank test. A KRAS mutation was detected in 22 out of 59 tumours and, in six cases, was missed by sequencing analysis but detected using the SNaPshot and PCR-LCR assays. Remarkably, no KRAS mutation was found in the 12 patients with clinical response. KRAS mutation was associated with disease progression (P=0.0005) and TTP was significantly decreased in mutated KRAS patients (3 vs 5.5 months, P=0.015). Our study confirms that KRAS mutation is highly predictive of a non-response to cetuximab plus chemotherapy in MCRC and highlights the need to use sensitive molecular methods, such as SNaPshot or PCR-LCR assays, to ensure an efficient mutation detection.British Journal of Cancer (2007) 96, 1166–1169. doi:10.1038/sj.bjc.6603685 www.bjcancer.com Published online 20 March 2007 [ABSTRACT FROM AUTHOR]

Spinal Muscular Atrophy (SMA) is a neurodegenerative disease characterized by the loss of spinal motor neurons and progressive muscular atrophy, due to insufficient level of survival of motor neuron protein (SMN). SMA is defined as a non-cell autonomous disease, involving numerous tissues and cell-types, including skeletal muscles. In this context, strategies to overexpress SMN protein and approaches to maintain neuromuscular functions are currently developed and appear as promising long-term prospect for therapy in SMA. We evaluated the efficacy of Sarconeos (API BIO101), a Mas receptor activator, as monotherapy and in combination with ASO therapy in severe SMA-like mice (SmnΔ7/Δ7; 2 copies SMN2+/−). We showed beneficial effects of BIO101 as monotherapy on the entire motor unit with a complete protection of lumbar motor neurons, a limited muscular atrophy (-17% in the tibialis, -40% in the plantaris, and -12% in the soleus), an increased vascularization (+10% in the tibialis and the plantaris, +3% in the soleus), and an accelerated maturation of both muscular fibers and neuromuscular junctions. Interestingly, these benefits were independent of SMN expression. In combination with ASO therapy, BIO101 demonstrated synergistic effects on body weight (+1% with BIO101, +11% with ASO, +32% with ASO + BIO101 at 10 days after birth compared to vehicle) and increased survival (+5 days of median survival). Most importantly, the co-treated SMA-like mice improved their moving capacity (+40%) and their fatigue resistance (4,2-fold) compared to SMA-like mice treated only with ASO. These results provide strong evidence that BIO101, with beneficial effects on the entire motor unit, constitutes an efficient SMN-expression-independent therapy for improving muscle function and should be considered as a potential combinatorial option for a new therapeutic strategy in SMA patient. [ABSTRACT FROM AUTHOR]

The objective of this report was to analyse a potential role for FGF6 in muscle resistance to mechanical stress. Normal or regenerating muscles of FGF6 (-/-) mice versus wild-type mice were submitted to different protocols of damaging eccentric contractions (eccentric electrostimulation and intermittent downhill exercise). Then muscular structural properties were analysed by histological and immunochemistry techniques to evaluate the post-injury muscle recovery; their muscle contractile parameters (maximal tetanic force, kinetics properties and fatigue resistance) were assessed. The absence of FGF6 causes (1) a fast-to-slow myofibre type switch in adult control and regenerating Tibialis anterior (TA) muscle; (2) muscle weakness in regenerating muscles in animals submitted to eccentric exercise protocols due to aberrant extensive necrotic zones. These observations point out a crucial and unexpected role for FGF6 in muscle integrity and muscle protection against mechanical stress. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that activation of the EGFR pathway leads to malignant transformation only if the p53 protein is inactivated. Therefore, we evaluated the impact of TP53 mutations on cetuximab-based chemotherapy (CT) sensitivity in combination with KRAS mutations that have been associated with cetuximab resistance. KRAS and TP53 status were assessed in tumours from 64 metastatic colorectal cancer patients treated with cetuximab-based CT and correlated to clinical response using the Fisher's exact test. Times to progression (TTPs) according to gene status were calculated using the Kaplan-Meier method and compared with log-rank test. TP53 mutations were found in 41 patients and were significantly associated with controlled disease (CD), as defined as complete response, partial response or stable disease (P=0.037) and higher TTP (20 vs 12 weeks, P=0.004). Remarkably, in the subgroup of 46 patients without KRAS mutation, but not in patients with KRAS mutation, TP53 mutations were also associated with CD (P=0.008) and higher TTP (24 vs 12 weeks, P=0.0007). This study suggests that TP53 mutations are predictive of cetuximab sensitivity, particularly in patients without KRAS mutation, and that TP53 genotyping could have a clinical interest to select patients who should benefit from cetuximab-based CT. [ABSTRACT FROM AUTHOR]

Abstract Aim: The aim of this report is to show that eccentric exercise under well-controlled conditions is an alternative model, to chemical and mechanical analyses, and analyse the process of degeneration/regeneration in mouse soleus. Methods: For this, mice were submitted to a single bout of eccentric exercise on a treadmill down a 14° decline for 150 min and the soleus muscle was analysed at different times following exercise by histology and in situ hybridization in comparison with cardiotoxin-injured muscles. Results: We analyse the regenerative process by detection of the accumulation of transcripts coding for the two myogenic regulatory factors, Myf-5 and MyoD, which are good markers of the activated satellite cells. From 24 h post-exercise (P-E), clusters of mononucleated Myf-5/MyoD-positive cells were detected. Their number increased up to 96 h P-E when young MyoD-positive myotubes with central nuclei began to appear. From 96 to 168 h P-E the number of myotubes increased, about 10-fold, the new myotubes representing 58% of the muscle cells (168 h P-E). Conclusion: These results show that this protocol of eccentric exercise is able to induce a drastic degeneration/regeneration process in the soleus muscle. This offers the opportunity to perform biochemical and molecular analyses of a process of regeneration without muscle environment defects. The advantages of this model are discussed in the context of fundamental and therapeutical perspectives. [ABSTRACT FROM AUTHOR]