Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

Tumours and tremors: how PTEN regulation underlies both

Mutations of the tumour suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) are seen in many human cancers. However, dysregulation of PTEN may be involved in other disease states such as Parkinson's disease. This minireview describes recent work examining PTEN regulation and its implications for the development of both cancer and neurodegenerative disease

Hypermethylation of CpG islands in the mouse asparagine synthetase gene: relationship to asparaginase sensitivity in lymphoma cells. Partial methylation in normal cells

We have sequenced the promoter region of the murine asparagine synthetase gene and examined its methylation profile in the CpG islands of L-asparaginase-sensitive 6C3HED cells (asparagine auxotrophs) and resistant variants (prototrophs). In the former, complete methylation of the CpG island is correlated with failure of expression of mRNA: cells of the latter possess both methylated and unmethylated alleles, as do cells of the intrinsically asparagine-independent lines L1210 and EL4. A similar phenomenon was seen in normal splenic cells of adult mice. This was age related: no methylation was found in weanlings, but up to 45% of gene copies in animals 18 weeks or older were methylated. It was also tissue related, with methylation occurring rarely in liver cells. The relationship of these changes to oncogenesis is considered. http://www.bjcancer.com © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Unusual finding of endocervical-like mucinous epithelium in continuity with urothelium in endocervicosis of the urinary bladder

Endocervicosis in the urinary bladder is a rare benign condition. We present a case in a 37-year-old woman with classical clinical and pathological features of endocervicosis. The unusual observation of endocervical-like mucinous epithelium in continuity with the urothelium in addition to fully developed endocervicosis prompted immunohistochemical profiling of the case using antibodies to cytokeratins (AE1/AE3, CK19, CK7, CK5/6, CK20), HBME-1, estrogen receptor (ER) and progesterone receptor (PR) to assess the relationship of the surface mucinous and endocervicosis glandular epithelia. The surface mucinous epithelium, urothelium and endocervicosis glands were immunopositive for AE1/AE3, CK7 and CK19 while CK20 was only expressed by few urothelial umbrella cells. The surface mucinous epithelium was CK5/6 and HBME-1 immunonegative but showed presence of ER and PR. This was in contrast to the urothelium's expression of CK5/6 but not ER and PR. In comparison, endocervicosis glands expressed HBME-1, unlike the surface mucinous epithelium. The endocervicosis epithelium also demonstrated the expected presence of ER and PR and CK5/6 immunonegativity. The slightly differing immunohistochemical phenotypes of the surface mucinous and morphologically similar endocervicosis glandular epithelium is interesting and requires further clarification to its actual nature. The patient has remained well and without evidence of disease 18-months following transurethral resection of the lesion

Neural hypernetwork approach for pulmonary embolism diagnosis

Background Hypernetworks are based on topological simplicial complexes and generalize the concept of two-body relation to many-body relation. Furthermore, Hypernetworks provide a significant generalization of network theory, enabling the integration of relational structure, logic and analytic dynamics. A pulmonary embolism is a blockage of the main artery of the lung or one of its branches, frequently fatal. Results Our study uses data on 28 diagnostic features of 1427 people considered to be at risk of pulmonary embolism enrolled in the Department of Internal and Subintensive Medicine of an Italian National Hospital “Ospedali Riuniti di Ancona”. Patients arrived in the department after a first screening executed by the emergency room. The resulting neural hypernetwork correctly recognized 94 % of those developing pulmonary embolism. This is better than previous results obtained with other methods (statistical selection of features, partial least squares regression, topological data analysis in a metric space). Conclusion In this work we successfully derived a new integrative approach for the analysis of partial and incomplete datasets that is based on Q-analysis with machine learning. The new approach, called Neural Hypernetwork, has been applied to a case study of pulmonary embolism diagnosis. The novelty of this method is that it does not use clinical parameters extracted by imaging analysis

Mutation and deletion analysis of GFRα-1, encoding the co-receptor for the GDNF/RET complex, in human brain tumours

Glial cell line-derived neurotrophic factor (GDNF) plays a key role in the control of vertebrate neuron survival and differentiation in both the central and peripheral nervous systems. GDNF preferentially binds to GFRα-1 which then interacts with the receptor tyrosine kinase RET. We investigated a panel of 36 independent cases of mainly advanced sporadic brain tumours for the presence of mutations in GDNF and GFRα-1. No mutations were found in the coding region of GDNF. We identified six previously described GFRα-1 polymorphisms, two of which lead to an amino acid change. In 15 of 36 brain tumours, all polymorphic variants appeared to be homozygous. Of these 15 tumours, one also had a rare, apparently homozygous, sequence variant at codon 361. Because of the rarity of the combination of homozygous sequence variants, analysis for hemizygous deletion was pursued in the 15 samples and loss of heterozygosity was found in 11 tumours. Our data suggest that intragenic point mutations of GDNF or GFRα-1 are not a common aetiologic event in brain tumours. However, either deletion of GFRα-1 and/or nearby genes may contribute to the pathogenesis of these tumours

In Vitro Contraction of Cytokinetic Ring Depends on Myosin II but not on Actin Dynamics

10.1038/ncb2781Nature Cell Biology157853-859NCBI