Experiment K-6-09. Morphological and biochemical investigation of microgravity-induced nerve and muscle breakdown. Part 1: Investigation of nerve and muscle breakdown during spaceflight; Part 2: Biochemical analysis of EDL and PLT muscles

The present findings on rat hindlimb muscles suggest that skeletal muscle weakness induced by prolonged spaceflight can result from a combination of muscle fiber atrophy, muscle fiber segmental necrosis, degeneration of motor nerve terminals and destruction of microcirculatory vessels. Damage was confined to the red adductor longus (AL) and soleus muscles. The midbelly region of the AL muscle had more segmental necrosis and edema than the ends. Macrophages and neutrophils were the major mononucleated cells infiltrating and phagocytosing the cellular debris. Toluidine blue-positive mast cells were significantly decreased in Flight AL muscles compared to controls; this indicated that degranulation of mast cells contributed to tissue edema. Increased ubiquitination of disrupted myofibrils may have promoted myofilament degradation. Overall, mitochondria content and SDH activity were normal, except for a decrease in the subsarcolemmal region. The myofibrillar ATPase activity shifted toward the fast type in the Flight AL muscles. Some of the pathological changes may have occurred or been exacerbated during the 2 day postflight period of readaptation to terrestrial gravity. While simple atrophy should be reversible by exercise, restoration of pathological changes depends upon complex processes of regeneration by stem cells. Initial signs of muscle and nerve fiber regeneration were detected. Even though regeneration proceeds on Earth, the space environment may inhibit repair and cause progressive irreversible deterioration during long term missions. Muscles obtained from Flight rats sacrificed immediately (within a few hours) after landing are needed to distinguish inflight changes from postflight readaptation

hSSB1 interacts directly with the MRN complex stimulating its recruitment to DNA double-strand breaks and its endo-nuclease activity

hSSB1 is a recently discovered single-stranded DNA binding protein that is essential for efficient repair of DNA double-strand breaks (DSBs) by the homologous recombination pathway. hSSB1 is required for the efficient recruitment of the MRN complex to sites of DSBs and for the efficient initiation of ATM dependent signalling. Here we explore the interplay between hSSB1 and MRN. We demonstrate that hSSB1 binds directly to NBS1, a component of the MRN complex, in a DNA damage independent manner. Consistent with the direct interaction, we observe that hSSB1 greatly stimulates the endo-nuclease activity of the MRN complex, a process that requires the C-terminal tail of hSSB1. Interestingly, analysis of two point mutations in NBS1, associated with Nijmegen breakage syndrome, revealed weaker binding to hSSB1, suggesting a possible disease mechanism.Publisher PDFPeer reviewe

The structure of causal sets

More often than not, recently popular structuralist interpretations of physical theories leave the central concept of a structure insufficiently precisified. The incipient causal sets approach to quantum gravity offers a paradigmatic case of a physical theory predestined to be interpreted in structuralist terms. It is shown how employing structuralism lends itself to a natural interpretation of the physical meaning of causal sets theory. Conversely, the conceptually exceptionally clear case of causal sets is used as a foil to illustrate how a mathematically informed rigorous conceptualization of structure serves to identify structures in physical theories. Furthermore, a number of technical issues infesting structuralist interpretations of physical theories such as difficulties with grounding the identity of the places of highly symmetrical physical structures in their relational profile and what may resolve these difficulties can be vividly illustrated with causal sets.Comment: 19 pages, 4 figure

Density-dependent processes in the transmission of human onchocerciasis: relationship between the numbers of microfilariae ingested and successful larval development in the simuliid vector

A previous paper reported that the intake of Onchocerca volvulus microfilariae (mff) by different species of Simulium is essentially proportional to the parasite load in the skin of infected carriers. This paper examines the fate of the ingested mff in susceptible vectors to assess the relationship between parasite intake and infective larval output in blackfly species with and without well-developed cibarial armatures. Analysis is based on data from 3 onchocerciasis endemic areas: Guatemala (S. ochraceum s.l.), West Africa (S. damnosum s.l./S. sirbanum) and the Amazonian focus between South Venezuela and Northern Brazil (S. guianense and S. oyapockense s.l.). The data, which include published and unedited information collected in the field, record experimental studies of parasite uptake by wild flies maintained in captivity until the completion of the extrinsic incubation period. The relationship between L3 output (measured as the mean number of successful larvae/fly or, as the proportion of flies with infective larvae) and average microfilarial intake, was strongly non-linear. This non-linearity was best represented by a sigmoid function in case of armed simuliids (S. ochraceum s.l., S. oyapockense s.l.), or by a hyperbolic expression in that of unarmed flies (S. damnosum s.l., S. guianense). These results are compatible, respectively, with the patterns of ‘initial facilitation' and ‘limitation' described in culicid vectors of lymphatic filariases. A maximum mean number of 1-3 L3/fly was observed in all 4 vectors. It is concluded that O. volvulus larval development to the infective stage is regulated by density-dependent mechanisms acting at the early phase of microfilarial migration out of the blackfly's bloodmeal. Damage by the bucco-pharyngeal armature may also be density dependent. A hypothesis, based on this density dependence is forwarded to explain initial facilitation, so far only recorded in vectors with well-developed cibarial teeth. Our results provide quantitative support for the conjecture that chemotherapy alone is likely to have a greater impact on reducing onchocerciasis transmission in endemic areas where the main vector has a toothed fore-gut than in foci where the vectors have unarmed cibari

Disrupted Maturation of the Microbiota and Metabolome among Extremely Preterm Infants with Postnatal Growth Failure

Growth failure during infancy is a major global problem that has adverse effects on long-term health and neurodevelopment. Preterm infants are disproportionately affected by growth failure and its effects. Herein we found that extremely preterm infants with postnatal growth failure have disrupted maturation of the intestinal microbiota, characterized by persistently low diversity, dominance of pathogenic bacteria within the Enterobacteriaceae family, and a paucity of strictly anaerobic taxa including Veillonella relative to infants with appropriate postnatal growth. Metabolomic profiling of infants with growth failure demonstrated elevated serum acylcarnitines, fatty acids, and other byproducts of lipolysis and fatty acid oxidation. Machine learning algorithms for normal maturation of the microbiota and metabolome among infants with appropriate growth revealed a pattern of delayed maturation of the microbiota and metabolome among infants with growth failure. Collectively, we identified novel microbial and metabolic features of growth failure in preterm infants and potentially modifiable targets for intervention

Self Running Droplet: Emergence of Regular Motion from Nonequilibrium Noise

Spontaneous motion of an oil droplet driven by chemical nonequilibricity is reported. It is shown that the droplet undergoes regular rhythmic motion under appropriately designed boundary conditions, whereas it exhibits random motion in an isotropic environment. This study is a novel manifestation on the direct energy transformation of chemical energy into regular spatial-motion under isothermal conditions. A simple mathematical equation including noise reproduces the essential feature of the transition from irregularity into periodic regular motion. Our results will inspire the theoretical study on the mechanism of molecular motors in living matter, working under significant influence of thermal fluctuation.Comment: 4 pages, 4 figure

Strained tetragonal states and Bain paths in metals

Paths of tetragonal states between two phases of a material, such as bcc and fcc, are called Bain paths. Two simple Bain paths can be defined in terms of special imposed stresses, one of which applies directly to strained epitaxial films. Each path goes far into the range of nonlinear elasticity and reaches a range of structural parameters in which the structure is inherently unstable. In this paper we identify and analyze the general properties of these paths by density functional theory. Special examples include vanadium, cobalt and copper, and the epitaxial path is used to identify an epitaxial film as related uniquely to a bulk phase.Comment: RevTeX, 4 pages, 4 figures, submitted to Phys. Rev. Let

Sigma-phase in Fe-Cr and Fe-V alloy systems and its physical properties

A review is presented on physical properties of the sigma-phase in Fe-Cr and Fe-V alloy systems as revealed both with experimental -- mostly with the Mossbauer spectroscopy -- and theoretical methods. In particular, the following questions relevant to the issue have been addressed: identification of sigma and determination of its structural properties, kinetics of alpha-to-sigma and sigma-to-alpha phase transformations, Debye temperature and Fe-partial phonon density of states, Curie temperature and magnetization, hyperfine fields, isomer shifts and electric field gradients.Comment: 26 pages, 23 figures and 83 reference

Radiative association and inverse predissociation of oxygen atoms

The formation of \mbox{O}_2 by radiative association and by inverse predissociation of ground state oxygen atoms is studied using quantum-mechanical methods. Cross sections, emission spectra, and rate coefficients are presented and compared with prior experimental and theoretical results. At temperatures below 1000~K radiative association occurs by approach along the $1\,{}^3\Pi_u$ state of \mbox{O}_2 and above 1000~K inverse predissociation through the \mbox{B}\,{}^3\Sigma_u^- state is the dominant mechanism. This conclusion is supported by a quantitative comparison between the calculations and data obtained from hot oxygen plasma spectroscopy.Comment: submitted to Phys. Rev. A (Sept. 7., 1994), 19 pages, 4 figures, latex (revtex3.0 and epsf.sty

Leading together, learning together: music education and music therapy students' perceptions of a shared practicum

The health benefits of musical engagement extend across the lifespan, with research documenting developmental and quality of life outcomes in senior adulthood. Whilst the psychological functions of music include three broad domains: cognitive, emotional and social, the social factors of music consumption have been, for the most part, ignored. This project is predicated on the understanding that students "construct" their own knowledge through engagement with others. It also reflects the belief that it is possible to link the world of learning with a world of action through a reflective process with small cooperative learning groups.This article reports on a collaborative creativity leadership project implemented by music therapy and music education students. In particular, it explores the perceptions of the students as they employed a teaching/therapeutic intervention with ageing participants from a local private retirement village. The project involved lyric rewriting and singing performance. Drawing on the students' reflective journals and interview transcripts, four themes emerged relating to students' perceptions of the learning experience. These themes were: learning about facilitating, learning about self, learning about the musical process, and learning about the context/ageing. Each of these themes is explored before conclusions about the process of leading a creative collaboration are drawn. The implications of this analysis extend beyond the context of a retirement village, and into various educational and therapeutic contexts where creative collaboration is facilitated