Plasmonic response of metallic nanojunctions driven by single atom motion: Quantum transport revealed in optics

The correlation between transport properties across subnanometric metallic gaps and the optical response of the system is a complex effect that is determined by the fine atomic-scale details of the junction structure. As experimental advances are progressively accessing transport and optical characterization of smaller nanojunctions, a clear connection between the structural, electronic, and optical properties in these nanocavities is needed. Using ab initio calculations, we present here a study of the simultaneous evolution of the structure and the optical response of a plasmonic junction as the particles forming the cavity, two Na380 clusters, approach and retract. Atomic reorganizations are responsible for a large hysteresis of the plasmonic response of the system, which shows a jump-to-contact instability during the approach process and the formation of an atom-sized neck across the junction during retraction. Our calculations demonstrate that, due to the quantization of the conductance in metal nanocontacts, atomic-scale reconfigurations play a crucial role in determining the optical response of the whole system. We observe abrupt changes in the intensities and spectral positions of the dominating plasmon resonances and find a one-to-one correspondence between these jumps and those of the quantized transport as the neck cross-section diminishes. These results reveal an important connection between transport and optics at the atomic scale, which is at the frontier of current optoelectronics and can drive new options in optical engineering of signals driven by the motion and manipulation of single atoms.We acknowledge financial support from Projects FIS2013-41184-P and MAT2013-46593-C6-2-P from MINECO. M.B., P.K., F.M., and D.S.P. also acknowledge support from the ANR-ORGAVOLT project and the Euroregion Aquitaine-Euskadi program. M.B. acknowledges support from the Departamento de Educacion of the Basque Government through a Ph.D. grant. P.K. acknowledges financial support from the Fellows Gipuzkoa program of the Gipuzkoako Foru Aldundia through the FEDER funding scheme of the European Union. J.A. also acknowledges support from Grant 70NANB15H321, “PLASMOQUANTUM”, from the US Department of Commerce (NIST).Peer Reviewe

Novel Role for CFTR in Fluid Absorption from the Distal Airspaces of the Lung

The active absorption of fluid from the airspaces of the lung is important for the resolution of clinical pulmonary edema. Although ENaC channels provide a major route for Na+ absorption, the route of Cl− transport has been unclear. We applied a series of complementary approaches to define the role of Cl− transport in fluid clearance in the distal airspaces of the intact mouse lung, using wild-type and cystic fibrosis ΔF508 mice. Initial studies in wild-type mice showed marked inhibition of fluid clearance by Cl− channel inhibitors and Cl− ion substitution, providing evidence for a transcellular route for Cl− transport. In response to cAMP stimulation by isoproterenol, clearance was inhibited by the CFTR inhibitor glibenclamide in both wild-type mice and the normal human lung. Although isoproterenol markedly increased fluid absorption in wild-type mice, there was no effect in ΔF508 mice. Radioisotopic clearance studies done at 23°C (to block active fluid absorption) showed ∼20% clearance of 22Na in 30 min both without and with isoproterenol. However, the clearance of 36Cl was increased by 47% by isoproterenol in wild-type mice but was not changed in ΔF508 mice, providing independent evidence for involvement of CFTR in cAMP-stimulated Cl− transport. Further, CFTR played a major role in fluid clearance in a mouse model of acute volume-overload pulmonary edema. After infusion of saline (40% body weight), the lung wet-to-dry weight ratio increased by 28% in wild-type versus 64% in ΔF508 mice. These results provide direct evidence for a functionally important role for CFTR in the distal airspaces of the lung

Atomistic near-field nanoplasmonics: Reaching atomic-scale resolution in nanooptics

Electromagnetic field localization in nanoantennas is one of the leitmotivs that drives the development of plasmonics. The near-fields in these plasmonic nanoantennas are commonly addressed theoretically within classical frameworks that neglect atomic-scale features. This approach is often appropriate since the irregularities produced at the atomic scale are typically hidden in far-field optical spectroscopies. However, a variety of physical and chemical processes rely on the fine distribution of the local fields at this ultraconfined scale. We use time-dependent density functional theory and perform atomistic quantum mechanical calculations of the optical response of plasmonic nanoparticles, and their dimers, characterized by the presence of crystallographic planes, facets, vertices, and steps. Using sodium clusters as an example, we show that the atomistic details of the nanoparticles morphologies determine the presence of subnanometric near-field hot spots that are further enhanced by the action of the underlying nanometric plasmonic fields. This situation is analogue to a self-similar nanoantenna cascade effect, scaled down to atomic dimensions, and it provides new insights into the limits of field enhancement and confinement, with important implications in the optical resolution of field-enhanced spectroscopies and microscopies.We acknowledge financial support from projects FIS2013-14481-P and MAT2013-46593-C6-2-P from MINECO. M.B., P.K., F.M., and D.S.P. also acknowledge support from the ANR-ORGAVOLT project and the Euroregion Aquitaine-Euskadi program. M.B. acknowledges support from the Departamento de Educacion of the Basque Government through a PhD grant, as well as from Euskampus and the DIPC at the initial stages of this work. R.E. and P.K. acknowledge financial support from the Fellows Gipuzkoa program of the Gipuzkoako Foru Aldundia through the FEDER funding scheme of the European Union, “Una manera de hacer Europa”.Peer Reviewe

MiRonTop: mining microRNAs targets across large scale gene expression studies

Summary: Current challenges in microRNA (miRNA) research are to improve the identification of in vivo mRNA targets and clarify the complex interplay existing between a specific miRNA and multiple biological networks. MiRonTop is an online java web tool that integrates DNA microarrays or high-throughput sequencing data to identify the potential implication of miRNAs on a specific biological system. It allows a rapid characterization of the most pertinent mRNA targets according to several existing miRNA target prediction approaches. It also provides useful representations of the enrichment scores according to the position of the target site along the 3′-UTR, where the contribution of the sites located in the vicinity of the stop codon and of the polyA tail can be clearly highlighted. It provides different graphs of miRNA enrichment associated with up- or down-regulated transcripts and different summary tables about selections of mRNA targets and their functional annotations by Gene Ontology

MiR-200 family controls late steps of postnatal forebrain neurogenesis via Zeb2 inhibition

During neurogenesis, generation, migration and integration of the correct numbers of each neuron sub-Type depends on complex molecular interactions in space and time. MicroRNAs represent a key control level allowing the flexibility and stability needed f

A roadmap for the Human Developmental Cell Atlas

The Human Developmental Cell Atlas (HDCA) initiative, which is part of the Human Cell Atlas, aims to create a comprehensive reference map of cells during development. This will be critical to understanding normal organogenesis, the effect of mutations, environmental factors and infectious agents on human development, congenital and childhood disorders, and the cellular basis of ageing, cancer and regenerative medicine. Here we outline the HDCA initiative and the challenges of mapping and modelling human development using state-of-the-art technologies to create a reference atlas across gestation. Similar to the Human Genome Project, the HDCA will integrate the output from a growing community of scientists who are mapping human development into a unified atlas. We describe the early milestones that have been achieved and the use of human stem-cell-derived cultures, organoids and animal models to inform the HDCA, especially for prenatal tissues that are hard to acquire. Finally, we provide a roadmap towards a complete atlas of human development

Chronic lung diseases are associated with gene expression programs favoring SARS-CoV-2 entry and severity

Patients with chronic lung disease (CLD) have an increased risk for severe coronavirus disease-19 (COVID-19) and poor outcomes. Here, we analyze the transcriptomes of 611,398 single cells isolated from healthy and CLD lungs to identify molecular characteristics of lung cells that may account for worse COVID-19 outcomes in patients with chronic lung diseases. We observe a similar cellular distribution and relative expression of SARS-CoV-2 entry factors in control and CLD lungs. CLD AT2 cells express higher levels of genes linked directly to the efficiency of viral replication and the innate immune response. Additionally, we identify basal differences in inflammatory gene expression programs that highlight how CLD alters the inflammatory microenvironment encountered upon viral exposure to the peripheral lung. Our study indicates that CLD is accompanied by changes in cell-type-specific gene expression programs that prime the lung epithelium for and influence the innate and adaptive immune responses to SARS-CoV-2 infection

miR-199a-5p Is Upregulated during Fibrogenic Response to Tissue Injury and Mediates TGFbeta-Induced Lung Fibroblast Activation by Targeting Caveolin-1

As miRNAs are associated with normal cellular processes, deregulation of miRNAs is thought to play a causative role in many complex diseases. Nevertheless, the precise contribution of miRNAs in fibrotic lung diseases, especially the idiopathic form (IPF), remains poorly understood. Given the poor response rate of IPF patients to current therapy, new insights into the pathogenic mechanisms controlling lung fibroblasts activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies for this devastating disease. To identify miRNAs with potential roles in lung fibrogenesis, we performed a genome-wide assessment of miRNA expression in lungs from two different mouse strains known for their distinct susceptibility to develop lung fibrosis after bleomycin exposure. This led to the identification of miR-199a-5p as the best miRNA candidate associated with bleomycin response. Importantly, miR-199a-5p pulmonary expression was also significantly increased in IPF patients (94 IPF versus 83 controls). In particular, levels of miR-199a-5p were selectively increased in myofibroblasts from injured mouse lungs and fibroblastic foci, a histologic feature associated with IPF. Therefore, miR-199a-5p profibrotic effects were further investigated in cultured lung fibroblasts: miR-199a-5p expression was induced upon TGFβ exposure, and ectopic expression of miR-199a-5p was sufficient to promote the pathogenic activation of pulmonary fibroblasts including proliferation, migration, invasion, and differentiation into myofibroblasts. In addition, we demonstrated that miR-199a-5p is a key effector of TGFβ signaling in lung fibroblasts by regulating CAV1, a critical mediator of pulmonary fibrosis. Remarkably, aberrant expression of miR-199a-5p was also found in unilateral ureteral obstruction mouse model of kidney fibrosis, as well as in both bile duct ligation and CCl4-induced mouse models of liver fibrosis, suggesting that dysregulation of miR-199a-5p represents a general mechanism contributing to the fibrotic process. MiR-199a-5p thus behaves as a major regulator of tissue fibrosis with therapeutic potency to treat fibroproliferative diseases. © 2013 Lino Cardenas et al