Dotsondurham5625

The appropriate arrangement of myonuclei within skeletal muscle myofibers is of critical importance for normal muscle function, and improper myonuclear localization has been linked to a variety of skeletal muscle diseases, such as centronuclear myopathy and muscular dystrophies. However, the molecules that govern myonuclear positioning remain elusive. Here, we report that skeletal muscle-specific CIP (sk-CIP) is a regulator of nuclear positioning. Genetic deletion of sk-CIP in mice results in misalignment of myonuclei along the myofibers and at specialized structures such as neuromuscular junctions (NMJs) and myotendinous junctions (MTJs) in vivo, impairing myonuclear positioning after muscle regeneration, leading to severe muscle dystrophy in mdx mice, a mouse model of Duchenne muscular dystrophy. sk-CIP is localized to the centrosome in myoblasts and relocates to the outer nuclear envelope in myotubes upon differentiation. Mechanistically, we found that sk-CIP interacts with the Linker of Nucleoskeleton and Cytoskeleton (LINC) complex and the centriole Microtubule Organizing Center (MTOC) proteins to coordinately modulate myonuclear positioning and alignment. These findings indicate that sk-CIP may function as a muscle-specific anchoring protein to regulate nuclear position in multinucleated muscle cells.The international scope of the Mediterranean wine trade in Late Antiquity raises important questions concerning sustainability in an ancient international economy and offers a valuable historical precedent to modern globalization. Such questions involve the role of intercontinental commerce in maintaining sustainable production within important supply regions and the vulnerability of peripheral regions believed to have been especially sensitive to environmental and political disturbances. https://www.selleckchem.com/products/fm19g11.html We provide archaeobotanical evidence from trash mounds at three sites in the central Negev Desert, Israel, unraveling the rise and fall of viticulture over the second to eighth centuries of the common era (CE). Using quantitative ceramic data obtained in the same archaeological contexts, we further investigate connections between Negev viticulture and circum-Mediterranean trade. Our findings demonstrate interrelated growth in viticulture and involvement in Mediterranean trade reaching what appears to be a commercial scale in the fourth to mid-sixth centuries. Following a mid-sixth century peak, decline of this system is evident in the mid- to late sixth century, nearly a century before the Islamic conquest. These findings closely correspond with other archaeological evidence for social, economic, and urban growth in the fourth century and decline centered on the mid-sixth century. Contracting markets were a likely proximate cause for the decline; possible triggers include climate change, plague, and wider sociopolitical developments. In long-term historical perspective, the unprecedented commercial florescence of the Late Antique Negev appears to have been unsustainable, reverting to an age-old pattern of smaller-scale settlement and survival-subsistence strategies within a time frame of about two centuries.Blood platelets are formed by fragmentation of long membrane extensions from bone marrow megakaryocytes in the blood flow. Using lattice-Boltzmann/immersed boundary simulations we propose a biological Rayleigh-Plateau instability as the biophysical mechanism behind this fragmentation process. This instability is akin to the surface tension-induced breakup of a liquid jet but is driven by active cortical processes including actomyosin contractility and microtubule sliding. Our fully three-dimensional simulations highlight the crucial role of actomyosin contractility, which is required to trigger the instability, and illustrate how the wavelength of the instability determines the size of the final platelets. The elasto-hydrodynamic origin of the fragmentation explains the strong acceleration of platelet biogenesis in the presence of an external flow, which we observe in agreement with experiments. Our simulations then allow us to disentangle the influence of specific flow conditions While a homogeneous flow with uniform velocity leads to the strongest acceleration, a shear flow with a linear velocity gradient can cause fusion events of two developing platelet-sized swellings during fragmentation. A fusion event may lead to the release of larger structures which are observable as preplatelets in experiments. Together, our findings strongly indicate a mainly physical origin of fragmentation and regulation of platelet size in flow-accelerated platelet biogenesis.The "income inequality hypothesis" holds that rising income inequality affects the distribution of a wide range of social and economic outcomes. Although it is often alleged that rising income inequality will increase the advantages of the well-off in the competition for college, some researchers have provided descriptive evidence at odds with the income inequality hypothesis. In this paper, we track long-term trends in family income inequalities in college enrollment and completion ("collegiate inequalities") using all available nationally representative datasets for cohorts born between 1908 and 1995. We show that the trends in collegiate inequalities moved in lockstep with the trend in income inequality over the past century. There is one exception to this general finding For cohorts at risk for serving in the Vietnam War, collegiate inequalities were high, while income inequality was low. During this period, inequality in college enrollment and completion was significantly higher for men than for women, suggesting a bona fide "Vietnam War" effect. Aside from this singular confounding event, a century of evidence establishes a strong association between income and collegiate inequality, providing support for the view that rising income inequality is fundamentally changing the distribution of life chances.While tree rings have enabled interannual examination of the influence of climate on trees, this is not possible for most shrubs. Here, we leverage a multidecadal record of annual foliar carbon isotope ratio collections coupled with 39 y of survey data from two populations of the drought-deciduous desert shrub Encelia farinosa to provide insight into water-use dynamics and climate. This carbon isotope record provides a unique opportunity to examine the response of desert shrubs to increasing temperature and water stress in a region where climate is changing rapidly. Population mean carbon isotope ratios fluctuated predictably in response to interannual variations in temperature, vapor pressure deficit, and precipitation, and responses were similar among individuals. We leveraged the well-established relationships between leaf carbon isotope ratios and the ratio of intracellular to ambient CO2 concentrations to calculate intrinsic water-use efficiency (iWUE) of the plants and to quantify plant responses to long-term environmental change.