The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling

The mammalian target of rapamycin (mTOR) protein kinase is a master growth promoter that nucleates two complexes, mTORC1 and mTORC2. Despite the diverse processes controlled by mTOR, few substrates are known. We defined the mTOR-regulated phosphoproteome by quantitative mass spectrometry and characterized the primary sequence motif specificity of mTOR using positional scanning peptide libraries. We found that the phosphorylation response to insulin is largely mTOR dependent and that mTOR exhibits a unique preference for proline, hydrophobic, and aromatic residues at the +1 position. The adaptor protein Grb10 was identified as an mTORC1 substrate that mediates the inhibition of phosphoinositide 3-kinase typical of cells lacking tuberous sclerosis complex 2 (TSC2), a tumor suppressor and negative regulator of mTORC1. Our work clarifies how mTORC1 inhibits growth factor signaling and opens new areas of investigation in mTOR biology.     

Leptin regulates striatal regions and human eating behavior

Studies of the fat-derived hormone leptin have provided key insights into the molecular and neural components of feeding behavior and body weight regulation. An important challenge lies in understanding how the rewarding properties of food interact with, and can override, physiological satiety signals and promote overeating. We used functional magnetic resonance imaging to measure brain responses in two human patients with congenital leptin deficiency who were shown images of food before and after 7 days of leptin replacement therapy. Leptin was found to modulate neural activation in key striatal regions, suggesting that the hormone acts on neural circuits governing food intake to diminish the perception of food reward while enhancing the response to satiety signals generated during food consumption.     

Chiral fiber gratings

Chiral gratings with double helix symmetry were produced by twisting glass optical fiber with a noncircular core cross section as it passed through a miniature oven. We observed polarization-selective transmission in chiral fibers with pitches of tens of micrometers. Two modes of optical interaction were differentiated. In chirallong-period gratings, dips in transmission were observed at wavelengths associated with scattering into distinct cladding modes mediated by the chiral grating. In chiral intermediateperiod gratings, a broad scattering band was observed. These gratings can be used to produce sharp or broad polarization-selective filters.     

Hemoxygenase-2 is an oxygen sensor for a calcium-sensitive potassium channel

Modulation of calcium-sensitive potassium (BK) channels by oxygen is important in several mammalian tissues, and in the carotid body it is crucial to respiratory control. However, the identity of the oxygen sensor remains unknown. We demonstrate that hemoxygenase-2 (HO-2) is part of the BK channel complex and enhances channel activity in normoxia. Knockdown of HO-2 expression reduced channel activity, and carbon monoxide, a product of HO-2 activity, rescued this loss of function. Inhibition of BK channels by hypoxia was dependent on HO-2 expression and was augmented by HO-2 stimulation. Furthermore, carotid body cells demonstrated HO-2-dependent hypoxic BK channel inhibition, which indicates that HO-2 is an oxygen sensor that controls channel activity during oxygen deprivation.     

Traces of human migrations in Helicobacter pylori populations

Helicobacter pylori, a chronic gastric pathogen of human beings, can be divided into seven populations and subpopulations with distinct geographical distributions. These modern populations derive their gene pools from ancestral populations that arose in Africa, Central Asia, and East Asia. Subsequent spread can be attributed to human migratory fluxes such as the prehistoric colonization of Polynesia and the Americas, the neolithic introduction of farming to Europe, the Bantu expansion within Africa, and the slave trade.     

Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton

Cell contact is required for efficient transmission of human T cell leukemia virus- type 1 (HTLV-I) between cells and between individuals, because naturally infected lymphocytes produce virtually no cell-free infectious HTLV-I particles. However, the mechanism of cell-to-cell spread of HTLV-I is not understood. We show here that cell contact rapidly induces polarization of the cytoskeleton of the infected cell to the cell-cell junction. HTLV-I core (Gag protein) complexes and the HTLV-I genome accumulate at the cell-cell junction and are then transferred to the uninfected cell. Other lymphotropic viruses, such as HIV-1, may similarly subvert normal T cell physiology to allow efficient propagation between cells.     

Two-dimensional nanosheets produced by liquid exfoliation of layered materials

If they could be easily exfoliated, layered materials would become a diverse source of two-dimensional crystals whose properties would be useful in applications ranging from electronics to energy storage. We show that layered compounds such as MoS(2), WS(2), MoSe(2), MoTe(2), TaSe(2), NbSe(2), NiTe(2), BN, and Bi(2)Te(3) can be efficiently dispersed in common solvents and can be deposited as individual flakes or formed into films. Electron microscopy strongly suggests that the material is exfoliated into individual layers. By blending this material with suspensions of other nanomaterials or polymer solutions, we can prepare hybrid dispersions or composites, which can be cast into films. We show that WS(2) and MoS(2) effectively reinforce polymers, whereas WS(2)/carbon nanotube hybrid films have high conductivity, leading to promising thermoelectric properties.     

Wireless solar water splitting using silicon-based semiconductors and earth-abundant catalysts

We describe the development of solar water-splitting cells comprising earth-abundant elements that operate in near-neutral pH conditions, both with and without connecting wires. The cells consist of a triple junction, amorphous silicon photovoltaic interfaced to hydrogen- and oxygen-evolving catalysts made from an alloy of earth-abundant metals and a cobalt|borate catalyst, respectively. The devices described here carry out the solar-driven water-splitting reaction at efficiencies of 4.7% for a wired configuration and 2.5% for a wireless configuration when illuminated with 1 sun (100 milliwatts per square centimeter) of air mass 1.5 simulated sunlight. Fuel-forming catalysts interfaced with light-harvesting semiconductors afford a pathway to direct solar-to-fuels conversion that captures many of the basic functional elements of a leaf.     

The coming paradigm shift in forensic identification science

Converging legal and scientific forces are pushing the traditional forensic identification sciences toward fundamental change. The assumption of discernible uniqueness that resides at the core of these fields is weakened by evidence of errors in proficiency testing and in actual cases. Changes in the law pertaining to the admissibility of expert evidence in court, together with the emergence of DNA typing as a model for a scientifically defensible approach to questions of shared identity, are driving the older forensic sciences toward a new scientific paradigm.