Explore the vast range of titles available.

Trapping and transport in an optical nanochannel One of the obstacles to the development of active nanosystems is the ability to controllably deliver nanoscopic matter to and within nanostructures. This paper describes the combination of near-field optical forces (such as those used in optical traps) to confine nanoscopic matter inside a liquid core-slot waveguide and photon scattering forces to transport them. The waveguide overcomes the diffraction limits of conventional optical trapping systems to manipulate objects down to tens of nanometres in scale. As the waveguide is linear, it can also manipulate extended biomolecules demonstrated by trapping and transporting DNA molecules. This paper describes the combination of near-field optical forces (such as those used in optical traps) to confine nanoscopic matter inside a liquid core-slot waveguide and photon scattering forces to transport them. The waveguide overcomes the diffraction limits of conventional optical trapping systems to manipulate objects down to tens of nanometres in scale. As the waveguide is linear, it can also manipulate extended biomolecules demonstrated by trapping and transporting DNA molecules. The ability to manipulate nanoscopic matter precisely is critical for the development of active nanosystems. Optical tweezers 1 , 2 , 3 , 4 are excellent tools for transporting particles ranging in size from several micrometres to a few hundred nanometres. Manipulation of dielectric objects with much smaller diameters, however, requires stronger optical confinement and higher intensities than can be provided by these diffraction-limited 5 systems. Here we present an approach to optofluidic transport that overcomes these limitations, using sub-wavelength liquid-core slot waveguides 6 . The technique simultaneously makes use of near-field optical forces to confine matter inside the waveguide and scattering/adsorption forces to transport it. The ability of the slot waveguide to condense the accessible electromagnetic energy to scales as small as 60 nm allows us also to overcome the fundamental diffraction problem. We apply the approach here to the trapping and transport of 75-nm dielectric nanoparticles and λ-DNA molecules. Because trapping occurs along a line, rather than at a point as with traditional point traps 7 , 8 , the method provides the ability to handle extended biomolecules directly. We also carry out a detailed numerical analysis that relates the near-field optical forces to release kinetics. We believe that the architecture demonstrated here will help to bridge the gap between optical manipulation and nanofluidics.

Next generation biosensor platforms will require significant improvements in sensitivity, specificity and parallelity in order to meet the future needs of a variety of fields ranging from in vitro medical diagnostics, pharmaceutical discovery and pathogen detection. Nanobiosensors, which exploit some fundamental nanoscopic effect in order to detect a specific biomolecular interaction, have now been developed to a point where it is possible to determine in what cases their inherent advantages over traditional techniques (such as nucleic acid microarrays) more than offset the added complexity and cost involved constructing and assembling the devices. In this paper we will review the state of the art in nanoscale biosensor technologies, focusing primarily on optofluidic type devices but also covering those which exploit fundamental mechanical and electrical transduction mechanisms. A detailed overview of next generation requirements is presented yielding a series of metrics (namely limit of detection, multiplexibility, measurement limitations, and ease of fabrication/assembly) against which the various technologies are evaluated. Concluding remarks regarding the likely technological impact of some of the promising technologies are also provided.

Squamous cell carcinomas (SCCs) comprise one of the most common histologic types of human cancer. Transcriptional dysregulation of SCC cells is orchestrated by tumor protein p63 (TP63) , a master transcription factor (TF) and a well-researched SCC-specific oncogene. In the present study, both Gene Set Enrichment Analysis (GSEA) of SCC patient samples and in vitro loss-of-function assays establish fatty-acid metabolism as a key pathway downstream of TP63. Further studies identify sterol regulatory element binding transcription factor 1 (SREBF1) as a central mediator linking TP63 with fatty-acid metabolism, which regulates the biosynthesis of fatty-acids, sphingolipids (SL), and glycerophospholipids (GPL), as revealed by liquid chromatography tandem mass spectrometry (LC-MS/MS)-based lipidomics. Moreover, a feedback co-regulatory loop consisting of SREBF1/TP63/ Kruppel like factor 5 (KLF5) is identified, which promotes overexpression of all three TFs in SCCs. Downstream of SREBF1, a non-canonical, SCC-specific function is elucidated: SREBF1 cooperates with TP63/KLF5 to regulate hundreds of cis-regulatory elements across the SCC epigenome, which converge on activating cancer-promoting pathways. Indeed, SREBF1 is essential for SCC viability and migration, and its overexpression is associated with poor survival in SCC patients. Taken together, these data shed light on mechanisms of transcriptional dysregulation in cancer, identify specific epigenetic regulators of lipid metabolism, and uncover SREBF1 as a potential therapeutic target and prognostic marker in SCC. The relevance and underlying molecular mechanisms of epigenetic regulation in squamous cell carcinomas (SCC) await further characterization. Here, the authors show a transcriptional regulatory loop involving SREBF1, TP63 and KLF5 driving tumourigenesis in SCC through fatty acid, ERBB and mTOR pathway regulation.

Methyl hydroperoxide (MHP) is produced by the CH3O2 + HO2 reaction in the oxidation cascade of volatile organic compounds (VOCs). During KORUS‐AQ (May–June 2016), aircraft observations over Seoul using chemical ionization mass spectrometry reported MHP concentrations exceeding 1 ppb in the planetary boundary layer, four times higher than simulated by the GEOS‐Chem atmospheric chemistry model. We show that this discrepancy can be explained in part by the instrument's positive interference from methanediol (MD) under high‐humidity conditions, where MD is produced in clouds by formaldehyde hydration. Including MD chemistry in GEOS‐Chem increases the global formic acid source by 11% but has otherwise minimal impact on the model chemistry. Observed MHP concentrations in the dry free troposphere are much less sensitive to MD interference and vary with the branching ratio of the CH3O2 reaction with HO2 versus NO, supporting current understanding of low‐NO and high‐NO chemical regimes for VOC oxidation.

Most mental disorders have a typical onset between 12 and 25 years of age, highlighting the importance of this period for the pathogenesis, diagnosis, and treatment of mental ill-health. This perspective addresses interactions between risk and protective factors and brain development as key pillars accounting for the emergence of psychopathology in youth. Moreover, we propose that novel approaches towards early diagnosis and interventions are required that reflect the evolution of emerging psychopathology, the importance of novel service models, and knowledge exchange between science and practitioners. Taken together, we propose a transformative early intervention paradigm for research and clinical care that could significantly enhance mental health in young people and initiate a shift towards the prevention of severe mental disorders.

Antarctic sea ice plays a critical role in the Earth system, influencing energy, heat and freshwater fluxes, air–sea gas exchange, ice shelf dynamics, ocean circulation, nutrient cycling, marine productivity and global carbon cycling. However, accurate simulation of recent sea-ice changes remains challenging and, therefore, projecting future sea-ice changes and their influence on the global climate system is uncertain. Reconstructing past changes in sea-ice cover can provide additional insights into climate feedbacks within the Earth system at different timescales. This paper is the first of two review papers from the Cycles of Sea Ice Dynamics in the Earth system (C-SIDE) working group. In this first paper, we review marine- and ice core-based sea-ice proxies and reconstructions of sea-ice changes throughout the last glacial–interglacial cycle. Antarctic sea-ice reconstructions rely mainly on diatom fossil assemblages and highly branched isoprenoid (HBI) alkenes in marine sediments, supported by chemical proxies in Antarctic ice cores. Most reconstructions for the Last Glacial Maximum (LGM) suggest that winter sea ice expanded all around Antarctica and covered almost twice its modern surface extent. In contrast, LGM summer sea ice expanded mainly in the regions off the Weddell and Ross seas. The difference between winter and summer sea ice during the LGM led to a larger seasonal cycle than today. More recent efforts have focused on reconstructing Antarctic sea ice during warm periods, such as the Holocene and the Last Interglacial (LIG), which may serve as an analogue for the future. Notwithstanding regional heterogeneities, existing reconstructions suggest that sea-ice cover increased from the warm mid-Holocene to the colder Late Holocene with pervasive decadal- to millennial-scale variability throughout the Holocene. Studies, supported by proxy modelling experiments, suggest that sea-ice cover was halved during the warmer LIG when global average temperatures were ∼2 ∘C above the pre-industrial (PI). There are limited marine (14) and ice core (4) sea-ice proxy records covering the complete 130 000 year (130 ka) last glacial cycle. The glacial–interglacial pattern of sea-ice advance and retreat appears relatively similar in each basin of the Southern Ocean. Rapid retreat of sea ice occurred during Terminations II and I while the expansion of sea ice during the last glaciation appears more gradual especially in ice core data sets. Marine records suggest that the first prominent expansion occurred during Marine Isotope Stage (MIS) 4 and that sea ice reached maximum extent during MIS 2. We, however, note that additional sea-ice records and transient model simulations are required to better identify the underlying drivers and feedbacks of Antarctic sea-ice changes over the last 130 ka. This understanding is critical to improve future predictions.

Alterations in DNA methylation in cancer include global hypomethylation and gene-specific hypermethylation. It is not clear whether these two epigenetic errors are mechanistically linked or occur independently. This study was performed to determine the relationship between DNA hypomethylation, hypermethylation and microsatellite instability in cancer. We examined 61 cancer cell lines and 60 colorectal carcinomas and their adjacent tissues using LINE-1 bisulfite-PCR as a surrogate for global demethylation. Colorectal carcinomas with sporadic microsatellite instability (MSI), most of which are due to a CpG island methylation phenotype (CIMP) and associated MLH1 promoter methylation, showed in average no difference in LINE-1 methylation between normal adjacent and cancer tissues. Interestingly, some tumor samples in this group showed increase in LINE-1 methylation. In contrast, MSI-showed a significant decrease in LINE-1 methylation between normal adjacent and cancer tissues (P<0.001). Microarray analysis of repetitive element methylation confirmed this observation and showed a high degree of variability in hypomethylation between samples. Additionally, unsupervised hierarchical clustering identified a group of highly hypomethylated tumors, composed mostly of tumors without microsatellite instability. We extended LINE-1 analysis to cancer cell lines from different tissues and found that 50/61 were hypomethylated compared to peripheral blood lymphocytes and normal colon mucosa. Interestingly, these cancer cell lines also exhibited a large variation in demethylation, which was tissue-specific and thus unlikely to be resultant from a stochastic process. Global hypomethylation is partially reversed in cancers with microsatellite instability and also shows high variability in cancer, which may reflect alternative progression pathways in cancer.

Nuclear energy provides more than 10% of electrical power internationally and the increasing engagement of nuclear energy is essential to meet the rapid worldwide increase in energy demand. A paramount challenge in the development of advanced nuclear reactors is the discovery of advanced structural materials that can endure extreme environments, such as severe neutron irradiation damage at high temperatures. It has been known for decades that high dose radiation can introduce significant void swelling accompanied by precipitation in austenitic stainless steel (SS). Here we report, however, that through nanoengineering, ultra-fine grained (UFG) 304L SS with an average grain size of ~100 nm, can withstand Fe ion irradiation at 500°C to 80 displacements-per-atom (dpa) with moderate grain coarsening. Compared to coarse grained (CG) counterparts, swelling resistance of UFG SS is improved by nearly an order of magnitude and swelling rate is reduced by a factor of 5. M 23 C 6 precipitates, abundant in irradiated CG SS, are largely absent in UFG SS. This study provides a nanoengineering approach to design and discover radiation tolerant metallic materials for applications in extreme radiation environments.

There is a gap in understanding the effect of the essential ω-3 and ω-6 long-chain polyunsaturated fatty acids (LCPUFA) on Phase I retinopathy of prematurity (ROP), which precipitates proliferative ROP. Postnatal hyperglycemia contributes to Phase I ROP by delaying retinal vascularization. In mouse neonates with hyperglycemia-associated Phase I retinopathy, dietary ω-3 (vs. ω-6 LCPUFA) supplementation promoted retinal vessel development. However, ω-6 (vs. ω-3 LCPUFA) was also developmentally essential, promoting neuronal growth and metabolism as suggested by a strong metabolic shift in almost all types of retinal neuronal and glial cells identified with single-cell transcriptomics. Loss of adiponectin (APN) in mice (mimicking the low APN levels in Phase I ROP) decreased LCPUFA levels (including ω-3 and ω-6) in retinas under normoglycemic and hyperglycemic conditions. ω-3 (vs. ω-6) LCPUFA activated the APN pathway by increasing the circulating APN levels and inducing expression of the retinal APN receptor. Our findings suggested that both ω-3 and ω-6 LCPUFA are crucial in protecting against retinal neurovascular dysfunction in a Phase I ROP model; adequate ω-6 LCPUFA levels must be maintained in addition to ω-3 supplementation to prevent retinopathy. Activation of the APN pathway may further enhance the ω-3 and ω-6 LCPUFA's protection against ROP.

The “dark matter of life” describes microbes and even entire divisions of bacterial phyla that have evaded cultivation and have yet to be sequenced. We present a genome from the globally distributed but elusive candidate phylum TM6 and uncover its metabolic potential. TM6 was detected in a biofilm from a sink drain within a hospital restroom by analyzing cells using a highly automated single-cell genomics platform. We developed an approach for increasing throughput and effectively improving the likelihood of sampling rare events based on forming small random pools of single-flow–sorted cells, amplifying their DNA by multiple displacement amplification and sequencing all cells in the pool, creating a “mini-metagenome.” A recently developed single-cell assembler, SPAdes, in combination with contig binning methods, allowed the reconstruction of genomes from these mini-metagenomes. A total of 1.07 Mb was recovered in seven contigs for this member of TM6 (JCVI TM6SC1), estimated to represent 90% of its genome. High nucleotide identity between a total of three TM6 genome drafts generated from pools that were independently captured, amplified, and assembled provided strong confirmation of a correct genomic sequence. TM6 is likely a Gram-negative organism and possibly a symbiont of an unknown host (nonfree living) in part based on its small genome, low-GC content, and lack of biosynthesis pathways for most amino acids and vitamins. Phylogenomic analysis of conserved single-copy genes confirms that TM6SC1 is a deeply branching phylum.