Increased expression of GDF-15 may mediate ICU-acquired weakness by down-regulating muscle microRNAs

RATIONALE: The molecular mechanisms underlying the muscle atrophy of intensive care unit-acquired weakness (ICUAW) are poorly understood. We hypothesised that increased circulating and muscle growth and differentiation factor-15 (GDF-15) causes atrophy in ICUAW by changing expression of key microRNAs. OBJECTIVES: To investigate GDF-15 and microRNA expression in patients with ICUAW and to elucidate possible mechanisms by which they cause muscle atrophy in vivo and in vitro. METHODS: In an observational study, 20 patients with ICUAW and seven elective surgical patients (controls) underwent rectus femoris muscle biopsy and blood sampling. mRNA and microRNA expression of target genes were examined in muscle specimens and GDF-15 protein concentration quantified in plasma. The effects of GDF-15 on C2C12 myotubes in vitro were examined. MEASUREMENTS AND MAIN RESULTS: Compared with controls, GDF-15 protein was elevated in plasma (median 7239 vs 2454 pg/mL, p=0.001) and GDF-15 mRNA in the muscle (median twofold increase p=0.006) of patients with ICUAW. The expression of microRNAs involved in muscle homeostasis was significantly lower in the muscle of patients with ICUAW. GDF-15 treatment of C2C12 myotubes significantly elevated expression of muscle atrophy-related genes and down-regulated the expression of muscle microRNAs. miR-181a suppressed transforming growth factor-β (TGF-β) responses in C2C12 cells, suggesting increased sensitivity to TGF-β in ICUAW muscle. Consistent with this suggestion, nuclear phospho-small mothers against decapentaplegic (SMAD) 2/3 was increased in ICUAW muscle. CONCLUSIONS: GDF-15 may increase sensitivity to TGF-β signalling by suppressing the expression of muscle microRNAs, thereby promoting muscle atrophy in ICUAW. This study identifies both GDF-15 and associated microRNA as potential therapeutic targets

Dependence on Dectin-1 Varies With Multiple Candida Species

This is the final version. Available from Frontiers Media via the DOI in this recordFour Candida spp. (albicans, glabrata, tropicalis, parapsilosis) cause >95% of invasive Candida infections. C. albicans elicits immune responses via pathogen recognition receptors including C-type lectin-like receptors (CLRs). The CLR, Dectin-1 is important for host immunity to C. albicans and C. glabrata, however, whether Dectin-1 is important for host defense against C. tropicalis or C. parapsilosis is unknown. Therefore, we compared the involvement of Dectin-1 in response to these four diverse Candida spp. We found that Dectin-1 mediates innate cytokine responses to these Candida spp. in a species- and cell-dependent manner. Dectin-1 KO mice succumbed to infection with highly virulent C. albicans while they mostly survived infection with less virulent Candida spp. However, Dectin-1 KO mice displayed increased fungal burden following infection with each Candida spp. Additionally, T cells from Dectin-1 KO mice displayed enhanced effector functions likely due to the inability of Dectin-1 KO mice to clear the infections. Together, these data indicate that Dectin-1 is important for host defense to multiple Candida spp., although the specific roles for Dectin-1 varies with different Candida spp.Wellcome TrustRoyal SocietyUK Dementia Research InstituteMRC Centre for Medical Mycolog

Analysis of defect-related inhomogeneous electroluminescence in InGaN/GaN QW LEDs

The inhomogeneous electroluminescence (EL) of InGaN/GaN quantum well light emitting diode structures was investigated in this study. Electroluminescence hyperspectral images showed that inhomogeneities in the form of bright spots exhibited spectrally blue-shifted and broadened emission. Scanning electron microscopy combined with cathodoluminescence (SEM-CL) was used to identify hexagonal pits at the centre of approximately 20% of these features. Scanning transmission electron microscopy imaging with energy dispersive X-ray spectroscopy (STEM-EDX) indicated there may be p-doped AlGaN within the active region caused by the presence of the pit. Weak beam dark-field TEM (WBDF-TEM) revealed the presence of bundles of dislocations associated with the pit, suggesting the surface features which cause the inhomogeneous EL may occur at coalescence boundaries, supported by trends in the number of features observed across the wafer.The European Research Council has provided financial support under the European Community’s Seventh Framework Programme/ ERC grant agreement no. 279361 (MACONS).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.spmi.2016.03.03

Evidence for surprise minimization over value maximization in choice behavior

Classical economic models are predicated on the idea that the ultimate aim of choice is to maximize utility or reward. In contrast, an alternative perspective highlights the fact that adaptive behavior requires agents' to model their environment and minimize surprise about the states they frequent. We propose that choice behavior can be more accurately accounted for by surprise minimization compared to reward or utility maximization alone. Minimizing surprise makes a prediction at variance with expected utility models; namely, that in addition to attaining valuable states, agents attempt to maximize the entropy over outcomes and thus 'keep their options open'. We tested this prediction using a simple binary choice paradigm and show that human decision-making is better explained by surprise minimization compared to utility maximization. Furthermore, we replicated this entropy-seeking behavior in a control task with no explicit utilities. These findings highlight a limitation of purely economic motivations in explaining choice behavior and instead emphasize the importance of belief-based motivations

High-yield parallel fabrication of quantum-dot monolayer single-electron devices displaying Coulomb staircase, contacted by graphene.

It is challenging for conventional top-down lithography to fabricate reproducible devices very close to atomic dimensions, whereas identical molecules and very similar nanoparticles can be made bottom-up in large quantities, and can be self-assembled on surfaces. The challenge is to fabricate electrical contacts to many such small objects at the same time, so that nanocrystals and molecules can be incorporated into conventional integrated circuits. Here, we report a scalable method for contacting a self-assembled monolayer of nanoparticles with a single layer of graphene. This produces single-electron effects, in the form of a Coulomb staircase, with a yield of 87 ± 13% in device areas ranging from 2 to 16 μm2, containing up to 650,000 nanoparticles. Our technique offers scalable assembly of ultra-high densities of functional particles or molecules that could be used in electronic integrated circuits, as memories, switches, sensors or thermoelectric generators

High-yield parallel fabrication of quantum-dot monolayer single-electron devices displaying Coulomb staircase, contacted by graphene

It is challenging for conventional top-down lithography to fabricate reproducible devices very close to atomic dimensions, whereas identical molecules and very similar nanoparticles can be made bottom-up in large quantities, and can be self-assembled on surfaces. The challenge is to fabricate electrical contacts to many such small objects at the same time, so that nanocrystals and molecules can be incorporated into conventional integrated circuits. Here, we report a scalable method for contacting a self-assembled monolayer of nanoparticles with a single layer of graphene. This produces single-electron effects, in the form of a Coulomb staircase, with a yield of 87 ± 13% in device areas ranging from < 800 nm^2 to 16 μm^2, containing up to 650,000 nanoparticles. Our technique offers scalable assembly of ultra-high densities of functional particles or molecules that could be used in electronic integrated circuits, as memories, switches, sensors or thermoelectric generators

Evidence for functional state transitions in intensively-managed soil ecosystems

Soils are fundamental to terrestrial ecosystem functioning and food security, thus their resilience to disturbances is critical. Furthermore, they provide effective models of complex natural systems to explore resilience concepts over experimentally-tractable short timescales. We studied soils derived from experimental plots with different land-use histories of long-term grass, arable and fallow to determine whether regimes of extreme drying and re-wetting would tip the systems into alternative stable states, contingent on their historical management. Prior to disturbance, grass and arable soils produced similar respiration responses when processing an introduced complex carbon substrate. A distinct respiration response from fallow soil here indicated a different prior functional state. Initial dry:wet disturbances reduced the respiration in all soils, suggesting that the microbial community was perturbed such that its function was impaired. After 12 drying and rewetting cycles, despite the extreme disturbance regime, soil from the grass plots, and those that had recently been grass, adapted and returned to their prior functional state. Arable soils were less resilient and shifted towards a functional state more similar to that of the fallow soil. Hence repeated stresses can apparently induce persistent shifts in functional states in soils, which are influenced by management history