Preclinical comparison study between [18F]fluoromethyl-PBR28 and its deuterated analog in a rat model of neuroinflammation

We designed and synthesized deuterium-substituted [¹⁸F]fluoromethyl-PBR28 ([¹⁸F]1-d₂) as a novel translocator protein 18?kDa (TSPO)-targeted radioligand with enhanced in vivo stability. The comparison studies between [¹⁸F]fluoromethyl-PBR28 ([¹⁸F]1) and its deuterate analog ([¹⁸F]1-d₂) were investigated in terms of in vitro binding affinity, lipophilicity and in vivo stability. In addition, the accuracies of both radioligands were determined by comparing the PET imaging data in the same LPS-induced neuroinflammation rat model. Both aryloxyanilide analogs showed similar lipophilicity and in vitro affinity for TSPO. However, [¹⁸F]1-d₂ provided significantly lower femur uptake than [¹⁸F]1 (1.5?±?1.2 vs. 4.1?±?1.7%ID/g at 2?h post-injection) in an ex vivo biodistribution study. [¹⁸F]1-d₂ was also selectively accumulated in the inflammatory lesion with the binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BP_ND?=?3.17?±?0.48), in a LPS-induced acute neuroinflammation rat model, comparable to that of [¹⁸F]1 (BP_ND?=?2.13?±?0.51). These results indicate that [¹⁸F]1-d₂ had higher in vivo stability, which resulted in an enhanced target-to-background ratio compared to that induced by [¹⁸F]1.     

Production of high-fructose syrup from date by-products in a packed bed bioreactor using a novel thermostable invertase from Aspergillus awamori

Abstract

Dates by-products (discarded dates) from the sucrose-rich variety of ‘Deglet Nour’ were used as starting biomass to produce high-fructose syrup (HFS) based on an immobilized invertase process. A novel extracellular thermostable invertase obtained from Aspergillus awamori cultivated in submerged medium was induced with sucrose at 1% and used for this purpose. A zymogram of the crude extract showed the presence of a unique enzyme form that was optimally produced on the 5^th day. This enzyme preparation was biochemically characterized and immobilized on acetic acid-solubilized chitosan by covalent binding using glutaraldehyde (Yi = 88%, Ya = 54% and 15.53 U/g). When deployed in a packed bed reactor (PBR), HFS was efficiently and continuously produced from sucrose derived from aqueous date extracts. Feeding with an extract initially containing 139.2 g/L total sugar with 78.6 g/L sucrose at a flow rate of 17 ml/h, 50°C and pH 6 resulted in a conversion factor of 0.95 and a final fructose content in the syrup of 69 g/L.     

Long‐term abundance trends of the northern form of the short‐finned pilot whale (Globicephala macrorhynchus) along the Pacific coast of Japan

The abundance of the northern form of the short‐finned pilot whale, Globicephala macrorhynchus, in the Pacific waters of northern Japan was estimated from a line transect survey conducted in 2006 and data from seven previous surveys collected between 1985 and 1997. To overcome the difficulty of small sample size and inconsistency in survey design, we used an adjustment method using multiple covariates and sensitivity analysis by considering several scenarios. Abundance estimates showed similar long‐term trends among scenarios. The northern form of G. macrorhynchus was more abundant in 1985 than in 1991–2006. The annual catch of the northern form of G. macrorhynchus exceeded the potential biological removal (PBR), especially in the 1980s. Thus, the commercial take in the early 1980s was suspected as a partial cause of a serious abundance decrease. These results provide valuable information for interpreting the impacts of coastal whaling, and to develop future management plans.