Dsg2 via Src-mediated transactivation shapes EGFR signaling towards cell adhesion

Rapidly renewing epithelial tissues such as the intestinal epithelium require precise tuning of intercellular adhesion and proliferation to preserve barrier integrity. Here, we provide evidence that desmoglein 2 (Dsg2), an adhesion molecule of desmosomes, controls cell adhesion and proliferation via epidermal growth factor receptor (EGFR) signaling. Dsg2 is required for EGFR localization at intercellular junctions as well as for Src-mediated EGFR activation. Src binds to EGFR and is required for localization of EGFR and Dsg2 to cell–cell contacts. EGFR is critical for cell adhesion and barrier recovery. In line with this, Dsg2-deficient enterocytes display impaired barrier properties and increased cell proliferation. Mechanistically, Dsg2 directly interacts with EGFR and undergoes heterotypic-binding events on the surface of living enterocytes via its extracellular domain as revealed by atomic force microscopy. Thus, our study reveals a new mechanism by which Dsg2 via Src shapes EGFR function towards cell adhesion.     

CAS directly interacts with vinculin to control mechanosensing and focal adhesion dynamics

Focal adhesions are cellular structures through which both mechanical forces and regulatory signals are transmitted. Two focal adhesion-associated proteins, Crk-associated substrate (CAS) and vinculin, were both independently shown to be crucial for the ability of cells to transmit mechanical forces and to regulate cytoskeletal tension. Here, we identify a novel, direct binding interaction between CAS and vinculin. This interaction is mediated by the CAS SRC homology 3 domain and a proline-rich sequence in the hinge region of vinculin. We show that CAS localization in focal adhesions is partially dependent on vinculin, and that CAS–vinculin coupling is required for stretch-induced activation of CAS at the Y410 phosphorylation site. Moreover, CAS–vinculin binding significantly affects the dynamics of CAS and vinculin within focal adhesions as well as the size of focal adhesions. Finally, disruption of CAS binding to vinculin reduces cell stiffness and traction force generation. Taken together, these findings strongly implicate a crucial role of CAS–vinculin interaction in mechanosensing and focal adhesion dynamics.     

Rab5 is necessary for the biogenesis of the endolysosomal system in vivo

An outstanding question is how cells control the number and size of membrane organelles. The small GTPase Rab5 has been proposed to be a master regulator of endosome biogenesis. Here, to test this hypothesis, we developed a mathematical model of endosome dependency on Rab5 and validated it by titrating down all three Rab5 isoforms in adult mouse liver using state-of-the-art RNA interference technology. Unexpectedly, the endocytic system was resilient to depletion of Rab5 and collapsed only when Rab5 decreased to a critical level. Loss of Rab5 below this threshold caused a marked reduction in the number of early endosomes, late endosomes and lysosomes, associated with a block of low-density lipoprotein endocytosis. Loss of endosomes caused failure to deliver apical proteins to the bile canaliculi, suggesting a requirement for polarized cargo sorting. Our results demonstrate for the first time, to our knowledge, the role of Rab5 as an endosome organizer in vivo and reveal the resilience mechanisms of the endocytic system.     

Early maize agriculture and interzonal interaction in southern Peru

Over the past decade, increasing attention to the recovery and identification of plant microfossil remains from archaeological sites located in lowland South America has significantly increased knowledge of pre-Columbian plant domestication and crop plant dispersals in tropical forests and other regions. Along the Andean mountain chain, however, the chronology and trajectory of plant domestication are still poorly understood for both important indigenous staple crops such as the potato (Solanum sp.) and others exogenous to the region, for example, maize (Zea mays). Here we report the analyses of plant microremains from a late preceramic house (3,431 +/- 45 to 3,745 +/- 65 14C bp or approximately 3,600 to 4,000 calibrated years bp) in the highland southern Peruvian site of Waynuna. Our results extend the record of maize by at least a millennium in the southern Andes, show on-site processing of maize into flour, provide direct evidence for the deliberate movement of plant foods by humans from the tropical forest to the highlands, and confirm the potential of plant microfossil analysis in understanding ancient plant use and migration in this region.     

A Permutation-Translation Simulated Annealing Algorithm for L1 and L2 Unidimensional Scaling

Given a set of objects and a symmetric matrix of dissimilarities between them, Unidimensional Scaling is the problem of finding a representation by locating points on a continuum. Approximating dissimilarities by the absolute value of the difference between coordinates on a line constitutes a serious computational problem. This paper presents an algorithm that implements Simulated Annealing in a new way, via a strategy based on a weighted alternating process that uses permutations and point-wise translations to locate the optimal configuration. Explicit implementation details are given for least squares loss functions and for least absolute deviations. The weighted, alternating process is shown to outperform earlier implementations of Simulated Annealing and other optimization strategies for Unidimensional Scaling in run time efficiency, in solution quality, or in both.     

Thyroid hormone synthesis during hypothermia in rats

Zusammenfassung Tiefe und oberflächliche Hypothermie an Ratten reduziert die Radiojodfixation der Schilddrüse. Markierte Jodtyrosine werden dedektiert, während Jodtyronine fehlen.