Bis(2-acetylpyridine-κ2 N,O)silver(I) tetra­fluoridoborate: a complex with silver in a seesaw coordination geometry

The reaction of 2-acetylpyridine with silver(I) tetra­fluorido­borate leads to the discrete title complex, [Ag(C7H7NO)2]BF4, in the cation of which the Ag atom is coordinated by two 2-acetylpyridine ligands, each of which is N,O-bidentate, albeit with stronger bonding to the N atoms [Ag—N = 2.2018 (15) and 2.2088 (14) Å; Ag—O = 2.5380 (13) and 2.5454 (13) Å]. The four-coordinate Ag atom has a seesaw coordination geometry with a τ4 index of 0.51. The tetra­fluoridoborate anion is disordered over two orientations with 0.568 (10):0.432 (10) occupancies

Platinum trimethyl bipyridyl thiolates – new, tunable, red- to near IR emitting luminophores for bioimaging applications

Synthetic, spectroscopic, computational and biological imaging studies of platinum trimethyl bipyridyl thiolate complexes of the general formula [PtMe3(bpy)SR] reveal these to be easily accessed, tunable bioimaging agents which feature an unusual σ–π* Inter-Ligand Charge Transfer (ILCT) transition, and in some cases emit into the Near infra-red (NIR)

Hybrid photonic circuit for multiplexed heralded single photons

A key resource for quantum optics experiments is an on-demand source of single and multiple photon states at telecommunication wavelengths. This letter presents a heralded single photon source based on a hybrid technology approach, combining high efficiency periodically poled lithium niobate waveguides, low-loss laser inscribed circuits, and fast (>1 MHz) fibre coupled electro-optic switches. Hybrid interfacing different platforms is a promising route to exploiting the advantages of existing technology and has permitted the demonstration of the multiplexing of four identical sources of single photons to one output. Since this is an integrated technology, it provides scalability and can immediately leverage any improvements in transmission, detection and photon production efficiencies.Comment: 5 pages, double column, 3 figure

HOPS-associated neurological disorders (HOPSANDs): linking endolysosomal dysfunction to the pathogenesis of dystonia

The homotypic fusion and protein sorting (HOPS) complex is the structural bridge necessary for the fusion of late endosomes and autophagosomes with lysosomes. Recent publications linked mutations in genes encoding HOPS complex proteins with the aetiopathogenesis of inherited dystonias (i.e. VPS16, VPS41, and VPS11). Functional and microstructural studies conducted on patient-derived fibroblasts carrying mutations of HOPS complex subunits displayed clear abnormalities of the lysosomal and autophagic compartments. We propose to name this group of diseases HOPS-associated neurological disorders (HOPSANDs), which are mainly characterized by dystonic presentations. The delineation of HOPSANDs further confirms the connection of lysosomal and autophagic dysfunction with the pathogenesis of dystonia, prompting researchers to find innovative therapies targeting this pathway

Search for Magnetic Monopoles Trapped in Matter

There have been many searches for magnetic monopoles in flight, but few for monopoles in matter. We have searched for magnetic monopoles in meteorites, schists, ferromanganese nodules, iron ores and other materials. The detector was a superconducting induction coil connected to a SQUID (Superconducting Quantum Interference Device) with a room temperature bore 15 cm in diameter. We tested a total of more than 331 kg of material including 112 kg of meteorites. We found no monopole and conclude the overall monopole/nucleon ratio in the samples is $<1.2 \times 10^{-29}$ with a 90\% confidence level.Comment: 6 pages, rev tex, no figure

Single-Molecule Imaging Reveals Aβ42:Aβ40 Ratio-Dependent Oligomer Growth on Neuronal Processes

AbstractSoluble oligomers of the amyloid-β peptide have been implicated as proximal neurotoxins in Alzheimer’s disease. However, the identity of the neurotoxic aggregate(s) and the mechanisms by which these species induce neuronal dysfunction remain uncertain. Physiologically relevant experimentation is hindered by the low endogenous concentrations of the peptide, the metastability of Aβ oligomers, and the wide range of observed interactions between Aβ and biological membranes. Single-molecule microscopy represents one avenue for overcoming these challenges. Using this technique, we find that Aβ binds to primary rat hippocampal neurons at physiological concentrations. Although amyloid-β(1–40) as well as amyloid-β(1–42) initially form larger oligomers on neurites than on glass slides, a 1:1 mix of the two peptides result in smaller neurite-bound oligomers than those detected on-slide or for either peptide alone. With 1 nM peptide in solution, Aβ40 oligomers do not grow over the course of 48 h, Aβ42 oligomers grow slightly, and oligomers of a 1:1 mix grow substantially. Evidently, small Aβ oligomers are capable of binding to neurons at physiological concentrations and grow at rates dependent on local Aβ42:Aβ40 ratios. These results are intriguing in light of the increased Aβ42:Aβ40 ratios shown to correlate with familial Alzheimer’s disease mutations

Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration-probing the role of PPARα.

Dietary inorganic nitrate prevents aspects of cardiac mitochondrial dysfunction induced by hypoxia, although the mechanism is not completely understood. In both heart and skeletal muscle, nitrate increases fatty acid oxidation capacity, and in the latter case, this involves up-regulation of peroxisome proliferator-activated receptor (PPAR)α expression. Here, we investigated whether dietary nitrate modifies mitochondrial function in the hypoxic heart in a PPARα-dependent manner. Wild-type (WT) mice and mice without PPARα (Ppara-/-) were given water containing 0.7 mM NaCl (control) or 0.7 mM NaNO3 for 35 d. After 7 d, mice were exposed to normoxia or hypoxia (10% O2) for the remainder of the study. Mitochondrial respiratory function and metabolism were assessed in saponin-permeabilized cardiac muscle fibers. Environmental hypoxia suppressed mass-specific mitochondrial respiration and additionally lowered the proportion of respiration supported by fatty acid oxidation by 18% (P < 0.001). This switch away from fatty acid oxidation was reversed by nitrate treatment in hypoxic WT but not Ppara-/- mice, indicating a PPARα-dependent effect. Hypoxia increased hexokinase activity by 33% in all mice, whereas lactate dehydrogenase activity increased by 71% in hypoxic WT but not Ppara-/- mice. Our findings indicate that PPARα plays a key role in mediating cardiac metabolic remodeling in response to both hypoxia and dietary nitrate supplementation.-Horscroft, J. A., O'Brien, K. A., Clark, A. D., Lindsay, R. T., Steel, A. S., Procter, N. E. K., Devaux, J., Frenneaux, M., Harridge, S. D. R., Murray, A. J. Inorganic nitrate, hypoxia, and the regulation of cardiac mitochondrial respiration-probing the role of PPARα

Intertemporal Choice Behavior in Emerging Adults and Adults: Effects of Age Interact with Alcohol Use and Family History Status

Adults with alcohol use disorders (AUDs) show marked immediate reward selection (or “Now”) bias in intertemporal choice tasks. This Now bias persists long into abstinence, suggesting an irreversible consequence of chronic alcohol abuse or a pre-existing AUD intermediate phenotype. However, some data show substantial Now bias among emerging adults (18–25), regardless of drinking behavior, suggesting age-dependent effects on Now bias. The objectives of the present study were to determine (1) whether Now bias is greater among emerging adults relative to adults, (2) whether any such age effect on Now bias is diminished in sub-clinical heavy alcohol users, and (3) whether having a problem drinking first degree relative is independently associated with elevated Now bias. To achieve these objectives, we used an intertemporal choice task to quantify Now bias in n = 237 healthy participants (ages 18–40; 50% female), and a wide range of non-zero alcohol use, based on the Alcohol Use Disorders Identification Test (AUDIT). We found that among non-heavy drinkers, Now bias inversely correlated with age; this relationship was not present among heavy drinkers. We found no significant relationship between AUDIT score and Now bias among emerging adults, but AUDIT scores and Now bias were positively correlated among 26–40 year olds. Additionally, non-heavy drinking adults who reported a problem drinking first degree relative showed greater Now bias compared to those not reporting familial problem drinking. While not definitive, these findings lend support for elevated Now bias in adulthood as an intermediate phenotype for AUDs. Moreover, non-additive effects of age and heavy drinking on Now bias suggest perturbations in largely common neural circuits in both groups