Molecular sensing of mechano- and ligand-dependent adhesion GPCR dissociation.

Adhesion G-protein-coupled receptors (aGPCRs) bear notable similarity to Notch proteins1, a class of surface receptors poised for mechano-proteolytic activation2-4, including an evolutionarily conserved mechanism of cleavage5-8. However, so far there is no unifying explanation for why aGPCRs are autoproteolytically processed. Here we introduce a genetically encoded sensor system to detect the dissociation events of aGPCR heterodimers into their constituent N-terminal and C-terminal fragments (NTFs and CTFs, respectively). An NTF release sensor (NRS) of the neural latrophilin-type aGPCR Cirl (ADGRL)9-11, from Drosophila melanogaster, is stimulated by mechanical force. Cirl-NRS activation indicates that receptor dissociation occurs in neurons and cortex glial cells. The release of NTFs from cortex glial cells requires trans-interaction between Cirl and its ligand, the Toll-like receptor Tollo (Toll-8)12, on neural progenitor cells, whereas expressing Cirl and Tollo in cis suppresses dissociation of the aGPCR. This interaction is necessary to control the size of the neuroblast pool in the central nervous system. We conclude that receptor autoproteolysis enables non-cell-autonomous activities of aGPCRs, and that the dissociation of aGPCRs is controlled by their ligand expression profile and by mechanical force. The NRS system will be helpful in elucidating the physiological roles and signal modulators of aGPCRs, which constitute a large untapped reservoir of drug targets for cardiovascular, immune, neuropsychiatric and neoplastic diseases13.

Coherent photo-thermal noise cancellation in a dual-wavelength optical cavity for narrow-linewidth laser frequency stabilisation.

Optical resonators are used for the realisation of ultra-stable frequency lasers. The use of high reflectivity multi-band coatings allows the frequency locking of several lasers of different wavelengths to a single cavity. While the noise processes for single wavelength cavities are well known, the correlation caused by multi-stack coatings has as yet not been analysed experimentally. In our work, we stabilise the frequency of a 729 nm and a 1069 nm laser to one mirror pair and determine the residual-amplitude modulation (RAM) and photo-thermal noise (PTN). We find correlations in PTN between the two lasers and observe coherent cancellation of PTN for the 1069 nm coating. We show that the fractional frequency instability of the 729 nm laser is limited by RAM at 1 × 10-14. The instability of the 1069 nm laser is at 3 × 10-15 close to the thermal noise limit of 1.5 × 10-15.

A Modular and Catalytic Methodology To Access 2,5-Furan-Based Phenylene/Thiophene Oligomers through a One-Pot Decarboxylative Cross-Coupling from 5-Bromofurfural.

A library of 2,5-furan-based phenylene/thiophene oligomers were synthesized starting from 5-bromofurfural, a derivative of biomass-derived furfural. Varied electronic groups are coupled onto the furan motif, followed by the installation of a phenylene or thiophene central linker through a one-pot Pd-catalyzed decarboxylative cross-coupling reaction. Resulting oligomers containing the furan-phenylene-furan core possess high photoluminescent quantum yields in solution (83-98%), which are crucial for optoelectronic devices. Absorbance and photoluminescence maxima are tuned by changing peripheral functional groups and the center linker coupled onto the furan backbone.

Strategic Priorities for Implementation of Father-Inclusive Practice in Mental Health Services for Children and Families: A Delphi Expert Consensus Study.

The aim of this study was to investigate expert consensus on barriers and facilitators to the organizational implementation of Father-Inclusive Practice (FIP) in child and family services to establish strategic priorities for implementation. An international panel of 56 experts in child and family service provision and father inclusion were surveyed using the Delphi technique. Three online questionnaires were used to gather opinions and measure experts' levels of agreement in regard to factors that enable or hinder the organizational implementation of FIP. Survey design, analysis and interpretation was guided by the Consolidated Framework for Implementation Research (CFIR). Consensus was achieved for 46.4% (n = 13) statements. Eight barriers and five facilitators were identified as strategic priorities to organizational implementation of FIP. The key factors were related to the following CFIR themes: leadership engagement, access to information and knowledge, implementation climate, structural characteristics, networks and communication, client needs and resources, external policies and incentives, and reflecting and evaluating. The study findings suggest that issues related to central prioritization, top-down organizational processes and external policy context should represent priority areas for implementation. Our results prioritise methods for improving FIP by highlighting the key areas of organizational practice to be addressed by tailored implementation strategies.

A historical perspective on porphyrin-based metal-organic frameworks and their applications.

Porphyrins are important molecules widely found in nature in the form of enzyme active sites and visible light absorption units. Recent interest in using these functional molecules as building blocks for the construction of metal-organic frameworks (MOFs) have rapidly increased due to the ease in which the locations of, and the distances between, the porphyrin units can be controlled in these porous crystalline materials. Porphyrin-based MOFs with atomically precise structures provide an ideal platform for the investigation of their structure-function relationships in the solid state without compromising accessibility to the inherent properties of the porphyrin building blocks. This review will provide a historical overview of the development and applications of porphyrin-based MOFs from early studies focused on design and structures, to recent efforts on their utilization in biomimetic catalysis, photocatalysis, electrocatalysis, sensing, and biomedical applications.

Molecular Copper(I)-Copper(II) Photosensitizer-Catalyst Photoelectrode for Water Oxidation.

Copper(II)-based electrocatalysts for water oxidation in aqueous solution have been studied previously, but photodriving these systems still remains a challenge. In this work, a bis(diimine)copper(I)-based donor-chromophore-acceptor system is synthesized and applied as the light-harvesting component of a photoanode. This molecular assembly was integrated onto a zinc oxide nanowire surface, and upon photoexcitation, chronoamperometric studies reveal that the integrated triad can inject electrons directly into the conduction band of zinc oxide, generating oxidizing equivalents that are then transferred to a copper(II) water oxidation catalyst in aqueous solution, yielding O2 from water with a Faradaic efficiency of 76%.

Morphological Engineering of Winged Au@MoS2 Heterostructures for Electrocatalytic Hydrogen Evolution.

Molybdenum disulfide (MoS2) has been recognized as a promising cost-effective catalyst for water-splitting hydrogen production. However, the desired performance of MoS2 is often limited by insufficient edge-terminated active sites, poor electrical conductivity, and inefficient contact to the supporting substrate. To address these limitations, we developed a unique nanoarchitecture (namely, winged Au@MoS2 heterostructures enabled by our discovery of the "seeding effect" of Au nanoparticles for the chemical vapor deposition synthesis of vertically aligned few-layer MoS2 wings). The winged Au@MoS2 heterostructures provide an abundance of edge-terminated active sites and are found to exhibit dramatically improved electrocatalytic activity for the hydrogen evolution reaction. Theoretical simulations conducted for this unique heterostructure reveal that the hydrogen evolution is dominated by the proton adsorption step, which can be significantly promoted by introducing sufficient edge active sites. Our study introduces a new morphological engineering strategy to make the pristine MoS2 layered structures highly competitive earth-abundant catalysts for efficient hydrogen production.

From Transition Metals to Lanthanides to Actinides: Metal-Mediated Tuning of Electronic Properties of Isostructural Metal-Organic Frameworks.

Isostructural metal-organic frameworks (MOFs) have been prepared from a variety of metal-oxide clusters, including transition metals, lanthanides, and actinides. Experimental and calculated shifts in O-H stretching frequencies for hydroxyl groups associated with the metal-oxide nodes reveal varying electronic properties for these units, thereby offering opportunities to tune support effects for other materials deposited onto these nodes.

Excimer Formation and Symmetry-Breaking Charge Transfer in Cofacial Perylene Dimers.

The use of multiple chromophores as photosensitizers for catalysts involved in energy-demanding redox reactions is often complicated by electronic interactions between the chromophores. These interchromophore interactions can lead to processes, such as excimer formation and symmetry-breaking charge separation (SB-CS), that compete with efficient electron transfer to or from the catalyst. Here, two dimers of perylene bound either directly or through a xylyl spacer to a xanthene backbone were synthesized to probe the effects of interchromophore electronic coupling on excimer formation and SB-CS using ultrafast transient absorption spectroscopy. Two time constants for excimer formation in the 1-25 ps range were observed in each dimer due to the presence of rotational isomers having different degrees of interchromophore coupling. In highly polar acetonitrile, SB-CS competes with excimer formation in the more weakly coupled isomers followed by charge recombination with τCR = 72-85 ps to yield the excimer. The results of this study of perylene molecular dimers can inform the design of chromophore-catalyst systems for solar fuel production that utilize multiple perylene chromophores.

Effect of Perylene Photosensitizer Attachment to [Pd(triphosphine)L]2+ on CO2 Electrocatalysis.

Two new covalently linked chromophore-CO2 reduction catalyst systems were prepared using a perylene chromophore and a bis[(dicyclohexylphosphino)ethyl]phenylphosphinopalladium(II) catalyst. The primary goal of this study is to probe the influence of photosensitizer attachment on the electrocatalytic performance. The position either para or meta to the phosphorus on the phenyl group of the palladium complex was linked via a 2,5-xylyl group to the 3 position of perylene. The electrocatalytic CO2 reduction activity of the palladium complex is maintained in the meta-linked system, but is lost in the para-linked system, possibly because of unfavorable interactions of the perylene chromophore with the glassy carbon electrode used. Following selective photoexcitation of the perylene, an enhanced perylene excited-state decay rate was observed in the palladium complexes compared to perylene attached to the free ligands. This decrease is accompanied by formation of the perylene cation radical, showing that electron transfer from perylene to the palladium catalyst occurs. Electron transfer and charge recombination were both found to be faster in the para-linked system than in the meta-linked one, which is attributed to stronger electronic coupling in the former. These results illustrate the need to carefully tune the electronic coupling between a photosensitizer chromophore and the catalyst to promote photodriven electron transfer yet inhibit adverse electronic effects of the chromophore on electrocatalysis.

Serum concentrations of HGF and IL-8 in patients with active Graves' orbitopathy before and after methylprednisolone therapy.

INTRODUCTION: Graves' disease is the most common cause of hyperthyroidism, and orbitopathy is the most frequent extrathyroidal manifestation of Graves' disease. The aims of this study were as follows: (1) to evaluate the serum concentration of HGF and IL-8 in the blood of newly diagnosed Graves' disease patients with the first episode of active GO and healthy controls; (2) to estimate the influence of the thyroid function (euthyreosis vs. hyperthyreosis) on HGF and IL-8 blood levels in patients with active GO; (3) to evaluate the influence of intravenous (i.v.) methylprednisolone (MP) pulse therapy and additional oral MP treatment on HGF and IL-8 blood levels in patients with active GO. PATIENTS AND METHODS: Thirty-nine Graves' disease patients with the first episode of clinically active GO (Group A) were enrolled in the study. To estimate the influence of the thyroid function on serum concentrations of the studied proangiogenic factors, Group A was divided into Group A I (n = 18) in euthyroid and Group A II (n = 21) in hyperthyroid stage of Graves' disease in moderate-to-severe stage of GO. The control group consisted of 20 healthy volunteers age- and sex-matched to the GO group. Concentrations of the studied proangiogenic factors in serum samples were measured by an enzyme-linked immunosorbent assay before (Group A) and after (Group A1) intensive pulse i.v.MP treatment and 1 month after the end of additional oral MP treatment (Group A2). RESULTS: We found a significant increase in serum concentrations of studied factors in the GO group before immunosuppressive therapy when compared with the control group and decrease after i.v.MP treatment. One month after the end of additional oral MP treatment (Group A2), serum concentrations of HGF and IL-8 still decreased and no significant difference was observed in HGF and IL-8 concentrations when compared with the control group. We did not find the difference in serum concentration of the studied proangiogenic factors between patients in euthyroid and hyperthyroid stage of Graves' disease before MP therapy. CONCLUSIONS: Serum HGF and IL-8 concentrations are elevated in Graves' disease patients with active Graves' orbitopathy as compared to the healthy control group. Successful management of active Graves' orbitopathy with glucocorticoids is associated with a decrease in HGF and IL-8 serum concentrations.

Direct C-F bond formation using photoredox catalysis.

We have developed the first example of a photoredox catalytic method for the formation of carbon-fluorine (C-F) bonds. The mechanism has been studied using transient absorption spectroscopy and involves a key single-electron transfer from the (3)MLCT (triplet metal-to-ligand charge transfer) state of Ru(bpy)3(2+) to Selectfluor. Not only does this represent a new reaction for photoredox catalysis, but the mild reaction conditions and use of visible light also make it a practical improvement over previously developed UV-mediated decarboxylative fluorinations.

Effects of increasing ligand conjugation in Cu(I) photosensitizers on NiO semiconductor surfaces.

Dye-sensitized photoelectrodes may be used as heterogeneous components for fuel-forming reactions in photoelectrochemical cells. There has been increasing interest in developing Earth-abundant cheaper photosensitizers based on first-row transition metals. We describe here the synthesis, characterization, and study of the ground and excited state properties of three Cu(I) complexes bearing ligands with varying electron-accepting capacities and conjugation that may act as photosensitizers for wide bandgap semiconductors. Femtosecond transient absorption studies indicate that the nature of the final excited state is dictated by the extent of conjugation in the electron-accepting ligand, where shorter conjugation leads to the formation of a singly reduced ligand and longer conjugation leads to the formation of a ligand-centered final excited state. These complexes were surface anchored onto nanostructured NiO on conductive fluorine-doped tin oxide glass to fabricate photocathodes. It was found that even though the ligands with increasing conjugation have an effect on the formation of the final excited state in solution, all complexes exhibit similar photocurrents upon white light illumination, suggesting that charge transfer to NiO happens in advance of the formation of the final excited state.

Long live(d) CsPbBr3 superlattices: colloidal atomic layer deposition for structural stability.

Superlattice formation afforded by metal halide perovskite nanocrystals has been a phenomenon of interest due to the high structural order induced in these self-assemblies, an order that is influenced by the surface chemistry and particle morphology of the starting building block material. In this work, we report on the formation of superlattices from aluminum oxide shelled CsPbBr3 perovskite nanocrystals where the oxide shell is grown by colloidal atomic layer deposition. We demonstrate that the structural stability of these superlattices is preserved over 25 days in an inert atmosphere and that colloidal atomic layer deposition on colloidal perovskite nanocrystals yields structural protection and an enhancement in photoluminescence quantum yields and radiative lifetimes as opposed to gas phase atomic layer deposition on pre-assembled superlattices or excess capping group addition. Structural analyses found that shelling resulted in smaller nanocrystals that form uniform supercrystals. These effects are in addition to the increasingly static capping group chemistry initiated where oleic acid is installed as a capping ligand directly on aluminum oxide. Together, these factors lead to fundamental observations that may influence future superlattice assembly design.

Cleavage of DNA by proton-coupled electron transfer to a photoexcited, hydrated Ru(II) 1,10-phenanthroline-5,6-dione complex.

Visible light irradiation of a ruthenium(II) quinone-containing complex, [(phen)(2)Ru(phendione)](2+) (1(2+)), where phendione = 1,10-phenanthroline-5,6-dione, leads to DNA cleavage in an oxygen independent manner. A combination of NMR analyses, transient absorption spectroscopy, and fluorescence measurements in water and acetonitrile reveal that complex 1(2+) must be hydrated at the quinone functionality, giving [(phen)(2)Ru(phenH(2)O)](2+) (1H(2)O(2+), where phenH(2)O = 1,10-phenanthroline-6-one-5-diol), in order to access a long-lived (3)MLCT(hydrate) state (τ ∼ 360 ns in H(2)O) which is responsible for DNA cleavage. In effect, hydration at one of the carbonyl functions effectively eliminates the low-energy (3)MLCT(SQ) state (Ru(III) phen-semiquinone radical anion) as the predominant nonradiative decay pathway. This (3)MLCT(SQ) state is very short-lived (<1 ns) as expected from the energy gap law for nonradiative decay, (1) and too short-lived to be the photoactive species. The resulting excited state in 1H(2)O(2+)* has photophysical properties similar to the (3)MLCT state in [Ru(phen)(3)](2+)* with the added functionality of basic sites at the ligand periphery. Whereas [Ru(phen)(3)](2+)* does not show direct DNA cleavage, the deprotonated form of 1H(2)O(2+)* does via a proton-coupled electron transfer (PCET) mechanism where the peripheral basic oxygen sites act as the proton acceptor. Analysis of the small molecule byproducts of DNA scission supports the conclusion that cleavage occurs via H-atom abstraction from the sugar moieties, consistent with a PCET mechanism. Complex 1(2+) is a rare example of a ruthenium complex which 'turns on' both reactivity and luminescence upon switching to a hydrated state.

Long-lived, directional photoinduced charge separation in RuII complexes bearing laminate polypyridyl ligands.

RuII complexes incorporating both amide-linked bithiophene donor ancillary ligands and laminate acceptor ligands; dipyrido[3,2-a:2',3'-c]phenazine (dppz), tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine (tpphz), and 9,11,20,22-tetraazatetrapyrido[3,2-a:2',3'-c:3'',2''-l:2''',3''']-pentacene (tatpp) exhibit long-lived charge separated (CS) states, which have been analyzed using time-resolved transient absorption (TA), fluorescence, and electronic absorption spectroscopy in addition to ground state electrochemical and spectroelectrochemical measurements. These complexes possess two electronically relevant ³MLCT states related to electron occupation of MOs localized predominantly on the proximal "bpy-like" portion and central (or distal) "phenazine-like" portion of the acceptor ligand as well as energetically similar ³LC and ³ILCT states. The unusually long excited state lifetimes (τ up to 7 µs) observed in these complexes reflect an equilibration of the ³MLCTprox or ³MLCTdist states with additional triplet states, including a ³LC state and a ³ILCT state that formally localizes a hole on the bithiophene moiety and an electron on the laminate acceptor ligand. Coordination of a ZnII ion to the open coordination site of the laminate acceptor ligand is observed to significantly lower the energy of the ³MLCTdist state by decreasing the magnitude of the excited state dipole and resulting in much shorter excited state lifetimes. The presence of the bithiophene donor group is reported to substantially extend the lifetime of these Zn adducts via formation of a ³ILCT state that can equilibrate with the ³MLCTdist state. In tpphz complexes, ZnII coordination can reorder the energy of the ³MLCTprox and ³MLCTdist states such that there is a distinct switch from one state to the other. The net result is a series of complexes that are capable of forming CS states with electron-hole spatial separation of up to 14 Å and possess exceptionally long lifetimes by equilibration with other triplet states.

Photonic enhancement in photoluminescent metal halide perovskite-photonic crystal bead hybrids.

We report two photonic crystal-perovskite nanocrystal microbead hybrids with photoluminescence matching that of the parent nanocrystals but with increased photoluminescence quantum yields. Time-resolved photoluminescence spectroscopy quantifies the radiative enhancement afforded by the photonic environment of the microbeads. The reported hybrids also demonstrate markedly better resistance to degradation in water over 30 days of immersion.

Altered gene expression profiles impair the nervous system development in individuals with 15q13.3 microdeletion.

The 15q13.3 microdeletion has pleiotropic effects ranging from apparently healthy to severely affected individuals. The underlying basis of the variable phenotype remains elusive. We analyzed gene expression using blood from three individuals with 15q13.3 microdeletion and brain cortex tissue from ten mice Df[h15q13]/+. We assessed differentially expressed genes (DEGs), protein-protein interaction (PPI) functional modules, and gene expression in brain developmental stages. The deleted genes' haploinsufficiency was not transcriptionally compensated, suggesting a dosage effect may contribute to the pathomechanism. DEGs shared between tested individuals and a corresponding mouse model show a significant overlap including genes involved in monogenic neurodevelopmental disorders. Yet, network-wide dysregulatory effects suggest the phenotype is not caused by a single critical gene. A significant proportion of blood DEGs, silenced in adult brain, have maximum expression during the prenatal brain development. Based on DEGs and their PPI partners we identified altered functional modules related to developmental processes, including nervous system development. We show that the 15q13.3 microdeletion has a ubiquitous impact on the transcriptome pattern, especially dysregulation of genes involved in brain development. The high phenotypic variability seen in 15q13.3 microdeletion could stem from an increased vulnerability during brain development, instead of a specific pathomechanism.

Ligand-triplet-fueled long-lived charge separation in ruthenium(II) complexes with bithienyl-functionalized ligands.

Ruthenium(II) polypyridyl complexes with pendant bithienyl ligands exhibiting unusually long-lived (τ ~ 3-7 µs) charge-separated excited states and a large amount of stored energy (ΔG° ~ 2.0 eV) are reported. A long-lived ligand-localized triplet acts as an energy reservoir to fuel population of an interligand charge-transfer state via an intermediate metal-to-ligand charge-transfer state in these complexes.

Charge transfer and intraligand excited state interactions in platinum-sensitized dithienylethenes.

The photophysical behavior for two photochromic Pt-terpyridine acetylide complexes containing pendant dithienylethenes (DTEs) bound to the metal through the alkynyl linkage is presented. Selective excitation of the Pt complex with visible light resulted in the metal-sensitized ring closing of the DTE unit. The central purpose of this study was to understand how excited state interactions govern the photophysics by correlating differences in the linkage of the two components with differences in the intramolecular energy transfer processes that occur between the Pt complex and the DTE. A series of model complexes without photochromic ligands were prepared and studied to elucidate the contributions of the triplet metal-to-ligand charge transfer and triplet intraligand states. It is demonstrated that reducing the orbital overlap of the metal-based and intraligand states by lengthening the linkage and eliminating a conjugated pathway is effective at dramatically decreasing the efficiency of intramolecular energy transfer. This is evidenced by the appearance of Pt-terpyridine based phosphorescence and a significant decrease in the observed rate of metal-sensitized ring closing of the DTE.