A glycine receptor is involved in the organization of swimming movements in an invertebrate chordate

Background  

Rhythmic motor patterns for locomotion in vertebrates are generated in spinal cord neural networks known as spinal Central Pattern Generators (CPGs). A key element in pattern generation is the role of glycinergic synaptic transmission by interneurons that cross the cord midline and inhibit contralaterally-located excitatory neurons. The glycinergic inhibitory drive permits alternating and precisely timed motor output during locomotion such as walking or swimming. To understand better the evolution of this system we examined the physiology of the neural network controlling swimming in an invertebrate chordate relative of vertebrates, the ascidian larva Ciona intestinalis.     

Discovery of temperature-dependent phenomena of muon-catalyzed fusion in solid deuterium and tritium mixtures

A systematic experimental study on muon-catalyzed fusion was conducted using a series of solid deuterium and tritium mixtures. A variety of conditions were investigated, i.e., tritium concentrations from 20% to 70%, and temperatures from 5 to 16 K. With decreasing temperature, we observed an unexpected decrease in the muon cycling rate (lambda(c)) and an increase in the muon loss probability (W). The origins of these observed changes were interpreted by the temperature-dependence in the dt mu formation process for lambda(c) and that in the muon reactivation process after muon-to-alpha sticking for W.     

Experimental evidence of guided-resonances in photonic crystals with aperiodically ordered supercells

We report on the first experimental evidence of guided resonances (GRs) in photonic crystal slabs based on aperiodically ordered supercells. Using Ammann-Beenker (quasiperiodic, eightfold symmetric) tiling geometry, we present our study on the fabrication, experimental characterization, and full-wave numerical simulation of two representative structures (with different filling parameters) operating at near-IR wavelengths (1300-1600 nm). Our results show a fairly good agreement between measurements and numerical predictions and pave the way for the development of new strategies (based on, e.g., the lattice symmetry breaking) for GR engineering.     

Enhanced Thermal Oxidation Stability of Reduced Graphene Oxide by Nitrogen Doping

Nitrogen‐doped reduced graphene oxide (N‐doped RGO) samples with a high level of doping, up to 13 wt. %, have been prepared by annealing graphene oxide under a flow of pure ammonia. The presence of nitrogen within the structure of RGO induces a remarkable increase in the thermal stability against oxidation by air. The thermal stability is closely related with the temperature of synthesis and the nitrogen content. The combustion reaction of nitrogen in different coordination environments (pyridinic, pyrrolic, and graphitic) is analyzed against a graphene fragment (undoped) from a thermodynamic point of view. In agreement with the experimental observations, the combustion of undoped graphene turns out to be more spontaneous than when nitrogen atoms are present.     

Pharmacokinetic Characterization of the DDAH1 Inhibitors ZST316 and ZST152 in Mice Using a HPLC-MS/MS Method

The pharmacokinetic profile of ZST316 and ZST152, arginine analogues with inhibitory activity towards human dimethylarginine dimethylaminohydrolase-1 (DDAH1), was investigated in mice using a newly developed HPLC-MS/MS method. The method proved to be reproducible, precise, and accurate for the measurement of the compounds in plasma and urine. Four-week-old female FVB mice received a single dose of ZST316 and ZST152 by intravenous bolus (30 mg/Kg) and oral gavage (60 mg/Kg). ZST316 Cmax was 67.4 µg/mL (intravenous) and 1.02 µg/mL (oral), with a half-life of 6 h and bioavailability of 4.7%. ZST152 Cmax was 24.9 µg/mL (intravenous) and 1.65 µg/mL (oral), with a half-life of 1.2 h and bioavailability of 33.3%. Urinary excretion of ZST152 and ZST316 was 12.5%–22.2% and 2.3%–7.5%, respectively. At least eight urinary metabolites were identified. After chronic intraperitoneal treatment with the more potent DDAH1 inhibitor, ZST316 (30 mg/Kg/day for three weeks), the bioavailability was 59% and no accumulation was observed. Treatment was well tolerated with no changes in body weight vs. untreated animals and no clinical signs of toxicity or distress. The results of this study show that ZST316 has a favorable pharmacokinetic profile, following intraperitoneal administration, to investigate the effects of DDAH1 inhibition in mice.     

Characterization and Valorization of the Agricultural Waste Obtained from Lavandula Steam Distillation for Its Reuse in the Food and Pharmaceutical Fields

The main focus of the current research was the characterization of the by-products from the steam distillation of Lavandula angustifolia Mill. (LA) and Lavandula x intermedia Emeric ex Loisel (LI) aerial parts, as they are important sources of bioactive compounds suitable for several applications in the food, cosmetic, and pharmaceutical industries. The oil-exhausted biomasses were extracted and the total polyphenol and flavonoid contents were, respectively, 19.22 ± 4.16 and 1.56 ± 0.21 mg/g for LA extract and 17.06 ± 3.31 and 1.41 ± 0.10 mg/g for LI extract. The qualitative analysis by liquid chromatography-electrospray tandem mass spectrometry (HPLC-ESI-MS) revealed that both the extracts were rich in phenolic acids and glycosylated flavonoids. The extracts exhibited radical scavenging, chelating, reducing activities, and inhibitory capacities on acetylcholinesterase and tyrosinase. The IC50 values against acetylcholinesterase and tyrosinase were, respectively, 5.35 ± 0.47 and 5.26 ± 0.02 mg/mL for LA, and 6.67 ± 0.12 and 6.56 ± 0.16 mg/mL for LI extracts. In conclusion, the oil-exhausted biomasses demonstrated to represent important sources of bioactive compounds, suitable for several applications in the food, cosmetic, and pharmaceutical industries.     

Multiplexed therapeutic drug monitoring of antipsychotics in dried plasma spots by LC‐MS/MS

In this work, a convenient method for the therapeutic monitoring of seven common antipsychotic drugs in “dried plasma spot” samples has been developed. It is based on the liquid chromatography tandem mass spectrometry technique, operating in multiple reaction monitoring mode, and a straightforward procedure for the simultaneous extraction of all antipsychotics in a single step, with high extraction yield. The method was fully validated with proper accuracy, precision, selectivity and sensitivity, for all the drugs. Limits of quantification were 0.12, 1.09, 1.46, 1.47, 5.70, 1.32, 1.33 µg/L for haloperidol, aripiprazole, olanzapine, quetiapine, clozapine, risperidone, and paliperidone, respectively. Accuracy, intra‐ and interday precision values were <10% for all drugs at all concentration levels examined. The method was tested in the analysis of 30 plasma samples from real patients for each drug. The proposed analytical approach, by combining practical and logistical advantages of microsampling with liquid chromatography tandem mass spectrometry analytical performance, could offer an ideal strategy for accurate and timely therapeutic drug monitoring of antipsychotic drugs in most clinical settings, even in remote centers and/or in out‐patient settings, bringing so many potential improvements in psychiatric patient care.     

Advances in Hybrid Composites for Photocatalytic Applications: A Review

Heterogeneous photocatalysts have garnered extensive attention as a sustainable way for environmental remediation and energy storage process. Water splitting, solar energy conversion, and pollutant degradation are examples of nowadays applications where semiconductor-based photocatalysts represent a potentially disruptive technology. The exploitation of solar radiation for photocatalysis could generate a strong impact by decreasing the energy demand and simultaneously mitigating the impact of anthropogenic pollutants. However, most of the actual photocatalysts work only on energy radiation in the Near-UV region (<400 nm), and the studies and development of new photocatalysts with high efficiency in the visible range of the spectrum are required. In this regard, hybrid organic/inorganic photocatalysts have emerged as highly potential materials to drastically improve visible photocatalytic efficiency. In this review, we will analyze the state-of-art and the developments of hybrid photocatalysts for energy storage and energy conversion process as well as their application in pollutant degradation and water treatments.     

Photoinduced enhancement in the luminescence of hydrophilic quantum dots coated with photocleavable ligands

In search of strategies to photoactivate the luminescence of semiconductor quantum dots, we devised a synthetic approach to attach photocleavable 2-nitrobenzyl groups to CdSe-ZnS core-shell quantum dots coated with hydrophilic polymeric ligands. The emission intensity of the resulting nanostructured constructs increases by more than 60% with the photolysis of the 2-nitrobenzyl appendages. Indeed, the photoinduced separation of the organic chromophores from the inorganic nanoparticles suppresses an electron-transfer pathway from the latter to the former and is mostly responsible for the luminescence enhancement. However, the thiol groups anchoring the polymeric envelope to the ZnS shell also contribute to the photoinduced emission increase. Presumably, their photooxidation eliminates defects on the nanoparticle surface and promotes the radiative deactivation of the excited quantum dots. This effect is fully reversible but its magnitude is only a fraction of the change caused by the photocleavage of the 2-nitrobenzyl groups. In addition, these particular quantum dots can cross the membrane of model cells and their luminescence increases by ~80% after the intracellular photocleavage of the 2-nitrobenzyl quenchers. Thus, photoswitchable luminescent constructs with biocompatible character can be assembled combining the established photochemistry of the 2-nitrobenzyl photocage with the outstanding photophysical properties of semiconductor quantum dots and the hydrophilic character of appropriate polymeric ligands.     

A Jocic-type approach for a practical and scalable synthesis of pyrrolonaphthoxazepine (PNOX)-based potent proapoptotic agents

We developed a Jocic-type protocol for the construction of the pyrrolonaphthoxazepine (PNOX) core. After an initial investigation based on the isolation of a trichloromethyl carbinol derivative, we shifted our attention towards a multicomponent single-step protocol. Screening of a variety of bases and solvents led to the identification of the optimum conditions for the preparation of the key α-aryloxy carboxylic acids to undergo intramolecular cyclization. The novel chemical route significantly improved overall yields for the preparation of PNOX-based compounds and was successfully extended to the preparation of 1,4-benzoxazinone-based templates.