Prediction of muscle performance during dynamic repetitive movement.

BACKGROUND: During long-duration spaceflight, astronauts experience progressive muscle atrophy and often perform strenuous extravehicular activities. Post-flight, there is a lengthy recovery period with an increased risk for injury. Currently, there is a critical need for an enabling tool to optimize muscle performance and to minimize the risk of injury to astronauts while on-orbit and during post-flight recovery. Consequently, these studies were performed to develop a method to address this need. METHODS: Eight test subjects performed a repetitive dynamic exercise to failure at 65% of their upper torso weight using a Lordex spinal machine. Surface electromyography (SEMG) data was collected from the erector spinae back muscle. The SEMG data was evaluated using a 5th order autoregressive (AR) model and linear regression analysis. RESULTS: The best predictor found was an AR parameter, the mean average magnitude of AR poles, with r = 0.75 and p = 0.03. This parameter can predict performance to failure as early as the second repetition of the exercise. CONCLUSION: A method for predicting human muscle performance early during dynamic repetitive exercise was developed. The capability to predict performance to failure has many potential applications to the space program including evaluating countermeasure effectiveness on-orbit, optimizing post-flight recovery, and potential future real-time monitoring capability during extravehicular activity.

Further delineation of renal-coloboma syndrome in patients with extreme variability of phenotype and identical PAX2 mutations.

Renal-coloboma syndrome is a recently described autosomal dominant syndrome of abnormal optic nerve and renal development. Two families have been reported with renal-coloboma syndrome and mutations of the PAX2 gene. The PAX2 gene, which encodes a DNA-binding protein, is expressed in the developing ear, CNS, eye, and urogenital tract. Ocular and/or renal abnormalities have been consistently noted in the five reports of patients with renal-coloboma syndrome, to date, but PAX2 expression patterns suggest that auditory and CNS abnormalities may be additional features of renal-coloboma syndrome. To determine whether additional clinical features are associated with PAX2 mutations, we have used PCR-SSCP to identify PAX2 gene mutations in patients. We report here four patients with mutations in exon 2, one of whom has severe ocular and renal disease, microcephaly, and retardation, and another who has ocular and renal disease with high-frequency hearing loss. Unexpectedly, extreme variability in clinical presentation was observed between a mother, her son, and an unrelated patient, all of whom had the same PAX2 mutation as previously described in two siblings with renal-coloboma syndrome. These results suggest that a sequence of seven Gs in PAX2 exon 2 may be particularly prone to mutation.

Cranial nerve abnormalities in CHARGE association.

Many children with the CHARGE association have facial paralysis and feeding and swallowing difficulties. Indeed, facial paralysis and pharyngeal incoordination may be important diagnostic indicators of CHARGE association [Davenport et al., 1986a; Mitchell et al., 1985]. We describe an individual with dysfunction of multiple cranial nerves (Möbius sequence) and CHARGE association, a previously unrecognized combination. Our review of 150 patients from the literature and 13 patients from this center with CHARGE association documented that dysfunction of cranial nerves is frequent in CHARGE association, and that often cranial nerve abnormalities are multiple. Such multiple cranial nerve abnormalities may be the primary underlying cause for the facial paralysis, feeding difficulties and sensorineural hearing loss seen in many individuals with CHARGE association.

The metR binding site in the Salmonella typhimurium metH gene: DNA sequence constraints on activation.

Transcription of the metH gene in Salmonella typhimurium and Escherichia coli is positively regulated by the metR gene product, a DNA binding protein. The interaction between the MetR activator protein and the S. typhimurium metH control region was investigated. In vitro gel mobility shift assays and DNase I protection assays established that the MetR protein binds to and protects a 24-bp sequence in the metH promoter region from DNase I attack. This region includes the proposed metR recognition sequence 5'-TGAANNNNNCTCA-3'. Single-base-pair changes were introduced into the proposed MetR recognition sequence within the promoter region of a metH-lacZ gene fusion by oligonucleotide-directed mutagenesis. Two classes of mutations were identified. In the first class, the mutations caused reduced activation of the metH-lacZ fusions that correlated with reduced MetR binding. In the second class, activation of the metH-lacZ fusion was reduced, yet there was no appreciable reduction in MetR binding, indicating that the presence of bound MetR is not sufficient for activation of metH-lacZ gene expression. These two classes of mutations in the DNA binding site are grouped spatially, suggesting that the proposed MetR recognition sequence can be divided into two functional domains, one for binding and the other for activation.

Escherichia coli metR mutants that produce a MetR activator protein with an altered homocysteine response.

Using an Escherichia coli lac deletion strain lysogenized with a lambda phage carrying a metH-lacZ gene fusion, we isolated trans-acting mutations that result in simultaneous 4- to 6-fold-elevated metH-lacZ expression, 5- to 22-fold-lowered metE-lacZ expression, and 9- to 20-fold-elevated metR-lacZ expression. The altered regulation of these genes occurs in the presence of high intracellular levels of homocysteine, a methionine pathway intermediate which normally inhibits metH and metR expression and stimulates metE expression. P1 transductions and complementation tests indicate that the mutations are in the metR gene. Our data suggest that the mutations result in an altered MetR activator protein that has lost the ability to use homocysteine as a modulator of gene expression.