Resistance to radial expansion limits muscle strain and work

The collagenous extracellular matrix (ECM) of skeletal muscle functions to transmit force, protect sensitive structures, and generate passive tension to resist stretch. The mechanical properties of the ECM change with age, atrophy, and neuromuscular pathologies, resulting in an increase in the relative amount of collagen and an increase in stiffness. Although numerous studies have focused on the effect of muscle fibrosis on passive muscle stiffness, few have examined how these structural changes may compromise contractile performance. Here we combine a mathematical model and experimental manipulations to examine how changes in the mechanical properties of the ECM constrain the ability of muscle fibers and fascicles to radially expand and how such a constraint may limit active muscle shortening. We model the mechanical interaction between a contracting muscle and the ECM using a constant volume, pressurized, fiber-wound cylinder. Our model shows that as the proportion of a muscle cross section made up of ECM increases, the muscle’s ability to expand radially is compromised, which in turn restricts muscle shortening. In our experiments, we use a physical constraint placed around the muscle to restrict radial expansion during a contraction. Our experimental results are consistent with model predictions and show that muscles restricted from radial expansion undergo less shortening and generate less mechanical work under identical loads and stimulation conditions. This work highlights the intimate mechanical interaction between contractile and connective tissue structures within skeletal muscle and shows how a deviation from a healthy, well-tuned relationship can compromise performance.     

Immunogold localisation of endogenous immunoglobulin-G in ultrathin frozen sections of the human placenta

Summary Endogenous immunoglobulin-G was localised in ultrathin frozen sections of human term placenta by use of an indirect immuno electron-histochemical methodology. Immunoreactivity of endogenous IgG to rabbit anti-human immunoglobulin-G antibody was visualised by use of protein-A — colloidal gold complex. Gold marked the syncytiotrophoblast in both coated and uncoated regions of the apical plasmalemma, in vesicles and multivesicular bodies, and in vesicles near the basal plasmalemma. Immunoreactivity was also seen in the interstitial space between the trophoblast and the fetal endothelial layer as well as in various types of vesicles within the endothelial cells. No immunoreactivity was seen in the intercellular clefts of the endothelium. The pattern of localisation observed is consistent with receptor-mediated uptake of immunoglobulin-G into the syncytiotrophoblast of the human placenta followed by release into the interstitial space and then vesciular transport through the endothelium.     

Effects of trichomes on the behavior and distribution of Platyprepia virginalis caterpillars

Trichomes are an important physical resistance mechanism of plants, as they reduce insect herbivore movement, feeding, and digestion. However, we know little about how trichomes influence herbivore distributions and populations. We conducted laboratory and field experiments to evaluate the preferences of Platyprepia virginalis (Boisduval) (Lepidoptera: Arctiidae) caterpillars to natural and manipulated densities of trichomes on their primary food, Lupinus arboreus Sims (Fabaceae). We then conducted field surveys to determine whether variation in trichome density among lupine bushes affected caterpillar spatial distribution on the landscape. Platyprepia virginalis caterpillars preferred lupine leaves with fewer trichomes in choice and no‐choice experiments. In the field, caterpillar feeding damage was found more often on leaves with fewer trichomes. These preferences scaled up to the level of bushes in the landscape such that more caterpillars were found on bushes with lower trichome densities than on bushes with higher trichome densities. This is one of few studies to show the potential for trichome density to influence herbivore population size and distribution in a natural system at a landscape level. The results are consistent with trichomes functioning as a resistance mechanism with consequences for herbivore choice, performance, and distribution.     

Respiratory function impairment and cardiopulmonary consequences in long-time residents of the Canadian Arctic.

Spirometry, roentgenography and electrocardiography were performed during community health surveys in 1976-78 in 176 Inuit and other long-time residents of the northeastern (Arctic Bay) and western (Inuvik) Canadian Arctic, and the results were related to age, ethnic origin, occupation and history of climatic exposure, smoking and hospitalization for tuberculosis. In Arctic Bay the young men showed excellent respiratory function, normal-sized pulmonary arteries and normal electrocardiograms, but abnormalities of all three types were increasingly frequent and severe after age 25. The forced mid-expiratory flow (FMF) fell to less than 50% of the norm by age 40, and dilatation of the pulmonary artery, hypertrophy of the right ventricle, right bundle branch block and a pseudoinfarction pattern on the ECG were frequently associated. In contrast, the men in Inuvik, an urbanized centre, maintained above normal respiratory function until age 40, and the FMF and pulmonary artery diameter remained normal in the older men except for Inuit and white trappers over 60 years old who had run fox trap lines along the Arctic coast in the 1920s and 30s. These data suggest that inhalation of extremely cold air at maximum ventilation may be a prime factor in the chronic obstructive lung disease of Inuit hunters, whereas smoking has only a minor role and hospitalization for tuberculosis appears to protect from rather than contribute to this disorder.     

Assessing the contribution of tumor mutational phenotypes to cancer progression risk

Cancer occurs via an accumulation of somatic genomic alterations in a process of clonal evolution. There has been intensive study of potential causal mutations driving cancer development and progression. However, much recent evidence suggests that tumor evolution is normally driven by a variety of mechanisms of somatic hypermutability, which act in different combinations or degrees in different cancers. These variations in mutability phenotypes are predictive of progression outcomes independent of the specific mutations they have produced to date. Here we explore the question of how and to what degree these differences in mutational phenotypes act in a cancer to predict its future progression. We develop a computational paradigm using evolutionary tree inference (tumor phylogeny) algorithms to derive features quantifying single-tumor mutational phenotypes, followed by a machine learning framework to identify key features predictive of progression. Analyses of breast invasive carcinoma and lung carcinoma demonstrate that a large fraction of the risk of future clinical outcomes of cancer progression—overall survival and disease-free survival—can be explained solely from mutational phenotype features derived from the phylogenetic analysis. We further show that mutational phenotypes have additional predictive power even after accounting for traditional clinical and driver gene-centric genomic predictors of progression. These results confirm the importance of mutational phenotypes in contributing to cancer progression risk and suggest strategies for enhancing the predictive power of conventional clinical data or driver-centric biomarkers.     

Functional development in the mauthner cell system of embryos and larvae of the zebra fish

In the embryonic zebra fish as early as 40 hr after fertilization, the Mauthner cells (M-cells) initiate an escape response, elicited by tactile-vibrational stimulation. The initial part of this behavior is similar to the acoustic startle reflex seen during the larval stage which begins at 96 hr. The embryonic response is directional and is followed by a series of strong tail flexures which are more pronounced than those during swimming. In the embryo the M-cell fired at the beginning of the response and rarely fired again during subsequent contractions; in our experiments the M-cell did not mediate iterative movements of the tail. The M-cell system is probably involved in evoked hatching behavior, as the tactile response is sufficient to rupture the egg membrane and allow the animal to escape. The M-cell sometimes fired spontaneously, which suggests that it might function also in spontaneous hatching behavior which occurs in the absence of phasic stimulation. At 48 hr the M-cell has morphologically mature synapses on its soma and dendrites, but its cytoplasm is relatively undifferentiated; it has few oriented neurofilaments and no distinct axon hillock. During these stages the extracellular M-spike is longer in duration and smaller in amplitude than at later times when the cell is more mature morphologically. Our data suggest that long-term inhibitory control of the M-cell system begins to function at about the time of hatching. At this time the cell is morphologically mature and is richly supplied with synaptic endings over its soma and dendrites.