Attention on Weak Ties in Social and Communication Networks

Granovetter's weak tie theory of social networks is built around two central hypotheses. The first states that strong social ties carry the large majority of interaction events; the second maintains that weak social ties, although less active, are often relevant for the exchange of especially important information (e.g., about potential new jobs in Granovetter's work). While several empirical studies have provided support for the first hypothesis, the second has been the object of far less scrutiny. A possible reason is that it involves notions relative to the nature and importance of the information that are hard to quantify and measure, especially in large scale studies. Here, we search for empirical validation of both Granovetter's hypotheses. We find clear empirical support for the first. We also provide empirical evidence and a quantitative interpretation for the second. We show that attention, measured as the fraction of interactions devoted to a particular social connection, is high on weak ties --- possibly reflecting the postulated informational purposes of such ties --- but also on very strong ties. Data from online social media and mobile communication reveal network-dependent mixtures of these two effects on the basis of a platform's typical usage. Our results establish a clear relationships between attention, importance, and strength of social links, and could lead to improved algorithms to prioritize social media content

Osteocyte secreted factors inhibit skeletal muscle differentiation.

It is generally accepted that bone and muscle possess the capacity to act in an autocrine, paracrine, or endocrine manner, with a growing body of evidence that suggests muscle can secrete muscle specific cytokines or "myokines", which influence bone metabolism. However, there has been little investigation into the identity of bone specific cytokines that modulate skeletal muscle differentiation and function. This study aimed to elucidate the influence of osteocytes on muscle progenitor cells in vitro and to identify potential bone specific cytokines or "osteokines". We treated C2C12 myoblasts with media collected from differentiated osteocytes (Ocy454 cells) grown in 3D, either under static or fluid flow culture conditions (2 dynes/cm2). C2C12 differentiation was significantly inhibited with a 75% reduction in the number of myofibers formed. mRNA analysis revealed a significant reduction in the expression of myogenic regulatory genes. Cytokine array analysis on the conditioned media demonstrated that osteocytes produce a significant number of cytokines "osteokines" capable of inhibiting myogenesis. Furthermore, we demonstrated that when osteocytes are mechanically activated they induce a greater inhibitory effect on myogenesis compared to a static state. Lastly, we identified the downregulation of numerous cytokines, including Il-6, Il-13, Il-1β, MIP-1α, and Cxcl9, involved in myogenesis, which may lead to future investigation of the role "osteokines" play in musculoskeletal health and pathology

Large G protein α-subunit XLαs limits clathrin-mediated endocytosis and regulates tissue iron levels in vivo

Alterations in the activity/levels of the extralarge G protein α-subunit (XLαs) are implicated in various human disorders, such as perinatal growth retardation. Encoded by GNAS, XLαs is partly identical to the α-subunit of the stimulatory G protein (Gsα), but the cellular actions of XLαs remain poorly defined. Following an initial proteomic screen, we identified sorting nexin-9 (SNX9) and dynamins, key components of clathrin-mediated endocytosis, as binding partners of XLαs. Overexpression of XLαs in HEK293 cells inhibited internalization of transferrin, a process that depends on clathrin-mediated endocytosis, while its ablation by CRISPR/Cas9 in an osteocyte-like cell line (Ocy454) enhanced it. Similarly, primary cardiomyocytes derived from XLαs knockout (XLKO) pups showed enhanced transferrin internalization. Early postnatal XLKO mice showed a significantly higher degree of cardiac iron uptake than wild-type littermates following iron dextran injection. In XLKO neonates, iron and ferritin levels were elevated in heart and skeletal muscle, where XLαs is normally expressed abundantly. XLKO heart and skeletal muscle, as well as XLKO Ocy454 cells, showed elevated SNX9 protein levels, and siRNA-mediated knockdown of SNX9 in XLKO Ocy454 cells prevented enhanced transferrin internalization. In transfected cells, XLαs also inhibited internalization of the parathyroid hormone and type 2 vasopressin receptors. Internalization of transferrin and these G protein-coupled receptors was also inhibited in cells expressing an XLαs mutant missing the Gα portion, but not Gsα or an N-terminally truncated XLαs mutant unable to interact with SNX9 or dynamin. Thus, XLαs restricts clathrin-mediated endocytosis and plays a critical role in iron/transferrin uptake in vivo