Molecular bridge-mediated ultralow-power gas sensing

We report the electrical detection of captured gases through measurement of the quantum tunneling characteristics of gas-mediated molecular junctions formed across nanogaps. The gas-sensing nanogap device consists of a pair of vertically stacked gold electrodes separated by an insulating 6 nm spacer (~1.5 nm of sputtered α-Si and ~4.5 nm ALD SiO2), which is notched ~10 nm into the stack between the gold electrodes. The exposed gold surface is functionalized with a self-assembled monolayer (SAM) of conjugated thiol linker molecules. When the device is exposed to a target gas (1,5-diaminopentane), the SAM layer electrostatically captures the target gas molecules, forming a molecular bridge across the nanogap. The gas capture lowers the barrier potential for electron tunneling across the notched edge region, from ~5 eV to ~0.9 eV and establishes additional conducting paths for charge transport between the gold electrodes, leading to a substantial decrease in junction resistance. We demonstrated an output resistance change of >108 times upon exposure to 80 ppm diamine target gas as well as ultralow standby power consumption of <15 pW, confirming electron tunneling through molecular bridges for ultralow-power gas sensing.

TNFAIP8 is a novel phosphoinositide-binding inhibitory regulator of Rho GTPases that promotes cancer cell migration

More than half of human tumors exhibit aberrantly dysregulated phosphoinositide signaling, yet how this is controlled remains not fully understood. While somatic mutations of PI3K, PTEN and Ras account for many cases of the hyperactivated lipid signals, other mechanisms for these dysfunctions in cancer are also being discovered. We report here that TNFAIP8 interacts with PtdIns(4,5)P2 and PtdIns(3,4,5)P3 and is likely to be hijacked by cancer cells to facilitate directional migration during malignant transformation. TNFAIP8 maintains the quiescent cellular state by sequestering inactive Rho GTPases in the cytosolic pool, which can be set free upon chemoattractant activation at the leading edge. Consequently, loss of TNFAIP8 results in severe defects of chemotaxis and adhesion. Thus, TNFAIP8, whose expression can be induced by inflammatory cytokines such as TNFα from tumor microenvironment, represents a molecular bridge from inflammation to cancer by linking NF-κB pathway to phosphoinositide signaling. Our study on the conserved hydrophobic cavity structure will also advise in silico drug screening and development of new TNFAIP8-based strategies to combat malignant human diseases.

Endocrine-Disrupting Chemicals’ (EDCs) Effects on Tumour Microenvironment and Cancer Progression: Emerging Contribution of RACK1

Endocrine disruptors (EDCs) can display estrogenic and androgenic effects, and their exposure has been linked to increased cancer risk. EDCs have been shown to directly affect cancer cell regulation and progression, but their influence on tumour microenvironment is still not completely elucidated. In this context, the signalling hub protein RACK1 (Receptor for Activated C Kinase 1) could represent a nexus between cancer and the immune system due to its roles in cancer progression and innate immune activation. Since RACK1 is a relevant EDCs target that responds to steroid-active compounds, it could be considered a molecular bridge between the endocrine-regulated tumour microenvironment and the innate immune system. We provide an analysis of immunomodulatory and cancer-promoting effects of different EDCs in shaping tumour microenvironment, with a final focus on the scaffold protein RACK1 as a pivotal molecular player due to its dual role in immune and cancer contexts.

The silencing factor Sir3 is a molecular bridge that sticks together distant loci

ABSTRACTPhysical contacts between distant loci contribute to regulate genome function. However, the molecular mechanisms responsible for settling and maintaining such interactions remain poorly understood. Here we investigate the well conserved interactions between heterochromatin loci. In budding yeast, the 32 telomeres cluster in 3-5 foci in exponentially growing cells. This clustering is functionally linked to the formation of heterochromatin in subtelomeric regions through the recruitment of the silencing complex SIR composed of Sir2/3/4. Combining microscopy and Hi-C on strains expressing different alleles of SIR3, we show that the binding of Sir3 directly promotes long range contacts between distant regions, including the rDNA, telomeres, and internal Sir3 bound sites. Furthermore, we unveil a new property of Sir3 in promoting rDNA compaction. Finally, using a synthetic approach we demonstrate that Sir3 can bond loci belonging to different chromosomes together, when targeted to these loci, independently of its interaction with its known partners (Rap1, and Sir4), Sir2 activity or chromosome context. Altogether these data suggest that Sir3 represents an uncommon example of protein able to bridge directly distant loci.