Two-piconewton slip bond between fibronectin and the cytoskeleton depends on talin

Mechanical forces on matrix-integrin-cytoskeleton linkages are crucial for cell viability, morphology and organ function. The production of force depends on the molecular connections from extracellular-matrix-integrin complexes to the cytoskeleton. The minimal matrix complex causing integrin-cytoskeleton connections is a trimer of fibronectin's integrin-binding domain FNIII7-10 (ref. 4). Here we report a specific, molecular slip bond that was broken repeatedly by a force of 2 pN at the cellular loading rate of 60 nm x s(-1); this occurred with single trimer beads but not with monomer. Talin1, which binds to both integrins and actin filaments in vitro, is required for the 2-pN slip bond and rapid cytoskeleton binding. Further, inhibition of fibronectin binding to alpha(v)beta3 and deletion of beta3 markedly decreases the 2-pN force peak. We suggest that talin1 initially forms a molecular slip bond between closely packed fibronectin-integrin complexes and the actin cytoskeleton, which can apply a low level of force to fibronectin until many bonds form or a signal is received to activate a force response.     

Molecular gas in the host galaxy of a quasar at redshift z = 6.42

Observations of molecular hydrogen in quasar host galaxies at high redshifts provide fundamental constraints on galaxy evolution, because it is out of this molecular gas that stars form. Molecular hydrogen is traced by emission from the carbon monoxide molecule, CO; cold H2 itself is generally not observable. Carbon monoxide has been detected in about ten quasar host galaxies with redshifts z > 2; the record-holder is at z = 4.69 (refs 1-3). Here we report CO emission from the quasar SDSS J114816.64 + 525150.3 (refs 5, 6) at z = 6.42. At that redshift, the Universe was only 1/16 of its present age, and the era of cosmic reionization was just ending. The presence of about 2 x 1010 M\circ of H2 in an object at this time demonstrates that molecular gas enriched with heavy elements can be generated rapidly in the youngest galaxies.     

Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination

Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination.     

Compartments revealed in food-web structure

Compartments in food webs are subgroups of taxa in which many strong interactions occur within the subgroups and few weak interactions occur between the subgroups. Theoretically, compartments increase the stability in networks, such as food webs. Compartments have been difficult to detect in empirical food webs because of incompatible approaches or insufficient methodological rigour. Here we show that a method for detecting compartments from the social networking science identified significant compartments in three of five complex, empirical food webs. Detection of compartments was influenced by food web resolution, such as interactions with weights. Because the method identifies compartmental boundaries in which interactions are concentrated, it is compatible with the definition of compartments. The method is rigorous because it maximizes an explicit function, identifies the number of non-overlapping compartments, assigns membership to compartments, and tests the statistical significance of the results. A graphical presentation reveals systemic relationships and taxa-specific positions as structured by compartments. From this graphic, we explore two scenarios of disturbance to develop a hypothesis for testing how compartmentalized interactions increase stability in food webs.     

Asymmetric pores in a silicon membrane acting as massively parallel brownian ratchets

The brownian motion of mesoscopic particles is ubiquitous and usually random. But in systems with periodic asymmetric barriers to movement, directed or 'rectified' motion can arise and may even modulate some biological processes. In man-made devices, brownian ratchets and variants based on optical or quantum effects have been exploited to induce directed motion, and the dependence of the amplitude of motion on particle size has led to the size-dependent separation of biomolecules. Here we demonstrate that the one-dimensional pores of a macroporous silicon membrane, etched to exhibit a periodic asymmetric variation in pore diameter, can act as massively parallel and multiply stacked brownian ratchets that are potentially suitable for large-scale particle separations. We show that applying a periodic pressure profile with a mean value of zero to a basin separated by such a membrane induces a periodic flow of water and suspended particles through the pores, resulting in a net motion of the particles from one side of the membrane to the other without moving the liquid itself. We find that the experimentally observed pressure dependence of the particle transport, including an inversion of the transport direction, agrees with calculations of the transport properties in the type of ratchet devices used here.