SUMMARY Cancer-secreted miRNAs are emerging mediators of cancer–host crosstalk. Here we show that miR-105, which is characteristically expressed and secreted by metastatic breast cancer cells, is a potent regulator of migration through targeting the tight junction protein ZO-1. In endothelial monolayers, exosome-mediated transfer of cancer-secreted miR-105 efficiently destroys tight junctions and the integrity of these natural barriers against metastasis. Overexpression of miR-105 in non-metastatic cancer cells induces metastasis and vascular permeability in distant organs, whereas inhibition of miR-105 in highly metastatic tumors alleviates these effects. MiR-105 can be detected in the circulation at the pre-metastatic stage, and its levels in the blood and tumor are associated with ZO-1 expression and metastatic progression in early-stage breast cancer.

Magnetosomes are membranous bacterial organelles sharing many features of eukaryotic organelles. Using electron cryotomography, we found that magnetosomes are invaginations of the cell membrane flanked by a network of cytoskeletal filaments. The filaments appeared to be composed of MamK, a homolog of the bacterial actin-like protein MreB, which formed filaments in vivo. In a mamK deletion strain, the magnetosome-associated cytoskeleton was absent and individual magnetosomes were no longer organized into chains. Thus, it seems that prokaryotes can use cytoskeletal filaments to position organelles within the cell.

In prokaryotes, FtsZ (the filamentous temperature sensitive protein Z) is a nearly ubiquitous GTPase that localizes in a ring at the leading edge of constricting plasma membranes during cell division. Here we report electron cryotomographic reconstructions of dividing Caulobacter crescentus cells wherein individual arc-like filaments were resolved just underneath the inner membrane at constriction sites. The filaments' position, orientation, time of appearance, and resistance to A22 all suggested that they were FtsZ. Predictable changes in the number, length, and distribution of filaments in cells where the expression levels and stability of FtsZ were altered supported that conclusion. In contrast to the thick, closed-ring-like structure suggested by fluorescence light microscopy, throughout the constriction process the Z-ring was seen here to consist of just a few short (B100 nm) filaments spaced erratically near the division site. Additional densities connecting filaments to the cell wall, occasional straight segments, and abrupt kinks were also seen. An 'iterative pinching' model is proposed wherein FtsZ itself generates the force that constricts the membrane in a GTP-hydrolysis-driven cycle of polymerization, membrane attachment, conformational change, depolymerization, and nucleotide exchange.

Chemoreceptors are key components of the high-performance signal transduction system that controls bacterial chemotaxis. Chemoreceptors are typically localized in a cluster at the cell pole, where interactions among the receptors in the cluster are thought to contribute to the high sensitivity, wide dynamic range, and precise adaptation of the signaling system. Previous structural and genomic studies have produced conflicting models, however, for the arrangement of the chemoreceptors in the clusters. Using whole-cell electron cryo-tomography, here we show that chemoreceptors of different classes and in many different species representing several major bacterial phyla are all arranged into a highly conserved, 12-nm hexagonal array consistent with the proposed ''trimer of dimers'' organization. The various observed lengths of the receptors confirm current models for the methylation, flexible bundle, signaling, and linker sub-domains in vivo. Our results suggest that the basic mechanism and function of receptor clustering is universal among bacterial species and was thus conserved during evolution.bacterial ultrastructure ͉ chemotaxis ͉ electron cryo-tomography

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The bacterial flagellum is one of nature's most amazing and well-studied nanomachines. Its cell-wall-anchored motor uses chemical energy to rotate a microns-long filament and propel the bacterium towards nutrients and away from toxins. While much is known about flagellar motors from certain model organisms, their diversity across the bacterial kingdom is less well characterized, allowing the occasional misrepresentation of the motor as an invariant, ideal machine. Here, we present an electron cryotomographical survey of flagellar motor architectures throughout the Bacteria. While a conserved structural core was observed in all 11 bacteria imaged, surprisingly novel and divergent structures as well as different symmetries were observed surrounding the core. Correlating the motor structures with the presence and absence of particular motor genes in each organism suggested the locations of five proteins involved in the export apparatus including FliI, whose position below the C-ring was confirmed by imaging a deletion strain. The combination of conserved and specially-adapted structures seen here sheds light on how this complex protein nanomachine has evolved to meet the needs of different species.

Several types of extra-galactic high-energy transients have been discovered, which include high-luminosity and low-luminosity long-duration gamma-ray bursts (GRBs), short-duration GRBs, supernova shock breakouts (SBOs), and tidal disruption events (TDEs) without or with an associated relativistic jet. In this paper, we apply a unified method to systematically study the redshift-dependent event rate densities and the global luminosity functions (ignoring redshift evolution) of these transients. We introduce some empirical formulae for the redshift-dependent event rate densities for different types of transients, and derive the local specific event rate density, which also represents its global luminosity function. Long GRBs have a large enough sample to reveal features in the global luminosity function, which is best characterized as a triple power law. All the other transients are consistent with having a single power law luminosity function. The total event rate density depends on the minimum luminosity, and we obtain the following values in units of Gpc −3 yr −1 : 0.8 +0.1 −0.1 for high-luminosity long GRBs above 10 50 erg s −1 ; 164 +98 −65 for low-luminosity long GRBs above 5 × 10 46 erg s −1 ; 1.3 +0.4 −0.3 , 1.2 +0.4 −0.3 , and 3.3 +1.0 −0.8 above 10 50 erg s −1 for short GRBs with three different merger delay models (Gaussian, log-normal, and power law); 1.9 +2.4 −1.2 × 10 4 above 10 44 erg s −1 for SBOs, 4.8 +3.2 −2.1 × 10 2 for normal TDEs above 10 44 erg s −1 ; and 0.03 +0.04 −0.02 above 10 48 erg s −1 for TDE jets as discovered by Swift. Intriguingly, the global luminosity functions of different kinds of transients, which cover over 12 orders of magnitude, are consistent with a single power law with an index of -1.6.

Two-dimensional (2D) nanomaterials such as graphene, boron nitride (BN), and molybdenum disulfide (MoS 2 ) have been attracting increasing research interest in the past few years due to their unique material properties. However, the lack of a reliable large-scale production method is an inhibiting issue for their practical applications. Here we report a facile, efficient, and scalable method for the fabrication of monolayer and few-layer BN, MoS 2 , and graphene using combined low-energy ball milling and sonication. Ball milling generates two forces on layered materials, shear force and compression force, which can cleave layered materials into 2D nanosheets from the top/bottom surfaces, and the edge of layered materials. Subsequent sonication would further break larger crystallites into smaller crystallites. These fabricated 2D nanosheets can be well dispersed in aqueous solutions at high concentrations, 1.2 mg mL À1 for BN, 0.8 mg mL À1 for MoS 2 , and 0.9 mg mL À1 for graphene, which are highly advantageous over other methods. These advantages render great potential in the construction of high-performance 2D material-based devices at low cost. For example, a prototype gas sensor is demonstrated in our study using graphene and MoS 2 , respectively, which can detect several ppm of ammonia gas.