Biopsies from the vastus lateralis muscle were obtained from three astronauts before and after two 5-day flights and from five astronauts before and after one 11-day flight (space shuttle flights: STS-32, -33, and -34). Muscle fibers from two separate samples from each biopsy were classified as type I and II or as type I, IIA, and IIB by using qualitative myofibrillar adenosinetriphosphatase (ATPase) staining. Cross-sectional area (CSA), number of capillaries per fiber, and the activities of succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase (GPD), and myofibrillar ATPase were determined from one sample of fibers of each myofibrillar ATPase type. Postflight biopsies had 6-8% fewer type I fibers than preflight. Mean fiber CSAs were 16-36% smaller after the 11-day flight with the relative effect being type IIB > IIA > I. Mean fiber CSAs were 11 and 24% smaller in type I and II fibers after 5 days of flight. Myofibrillar ATPase activities increased in type II but not in type I fibers after flight, whereas SDH activity was unaffected in either fast or slow fibers. GPD activity in type I fibers was approximately 80% higher (P > 0.05) postflight compared with preflight. Myofibrillar ATPase/SDH ratios in type II fibers were higher after than before flight, suggesting that some fast fibers were more susceptible to fatigue after flight. The GPD/SDH ratios were elevated in some type I fibers after spaceflight. The number of capillaries per fiber was 24% lower after than before flight, whereas the number of capillaries per unit CSA of muscle tissue was unchanged. These data suggest that adaptations in the size, metabolic properties, and vascularity of muscle fibers can occur rapidly in the space environment. These adaptations were qualitatively similar to those observed in animals after actual or simulated spaceflight conditions for short periods.

The myosin heavy chain composition of single fibres (n = 1088) was analysed with an electrophoretic technique in biopsy material from m. vastus lateralis (n = 5) and m. biceps brachii (n = 4) of young (23-31 years old) and elderly men (68-70 years old). In m. vastus lateralis, elderly subjects had a higher proportion of fibres showing a coexistence of myosin heavy chain types I and IIa (20 +/- 3% vs 8 +/- 1%, P less than 0.05) and of myosin heavy chain types IIa and IIb (33 +/- 2% vs 12 +/- 4%, P less than 0.05). In contrast, the young subjects had a higher proportion of fibres containing only myosin heavy chain type I (50 +/- 5% vs 33 +/- %, P less than 0.05) and type IIa (26 +/- 3% vs 12 +/- 2%, P less than 0.05). A similar pattern of myosin heavy chain expression was found in single fibres from m. biceps brachii, with the exception that the elderly subjects had a lower proportion of fibres with coexistence of types IIa and IIb (23 +/- 1% vs 34 +/- 2%, P less than 0.05) and a higher proportion of fibres containing only myosin heavy chain type IIa (25 +/- 5% vs 12 +/- 2%, P less than 0.05). Three fibres from m. biceps brachii contained all three isoforms. These results indicate that coexistence of myosin heavy chain isoforms in single fibres is present in skeletal muscles of young adults, and that there is an increased occurrence of this phenomenon with ageing.(ABSTRACT TRUNCATED AT 250 WORDS)

Highlights d High rate of NF1 loss in the R0 compared to neoadjuvant chemotherapy (NACT) group d Lower chromothripsis-like pattern and higher neoantigens in the R0 versus NACT group d Increased number of infiltrated T cells and decreased macrophages in the R0 group d Significant transcriptomic and proteomic variations between HGSC subgroups

Abstract. Expression of a control protein, chloramphenicol acetyltransferase (CAT), by the same strategy, had no effect on these responses. In vitro studies showed that NIF prevented mouse PMN adhesion consistent with the inhibition of lung uptake after LPS challenge in NIF transgene-expressing mice. We conclude that pulmonary vascular expression of NIF, a specific ␤ 2 integrinbinding protein, is a potentially useful gene transfer strategy in modulating the infiltration of PMN across the alveolarcapillary epithelial barrier and in preventing lung vascular endothelial injury. (