Chemoenzymatic Asymmetric Synthesis of Pyridine-Based α-Fluorinated Secondary Alcohols

Fluoro-substituted and heteroaromatic compounds are valuable intermediates for a variety of applications in pharma- and agrochemistry and synthetic chemistry. This study investigates the chemoenzymatic preparation of chiral alcohols bearing a heteroaromatic ring with an increasing degree of fluorination in α-position. Starting from readily available picoline derivatives prochiral α-halogenated acyl moieties were introduced with excellent selectivity and 64–95 % yield. The formed carbonyl group was subsequently reduced to the corresponding alcohols using the alcohol dehydrogenase from Lactobacillus kefir, yielding an enantiomeric excess of 95–>99 % and up to 98 % yield.     

What Can We Learn from FGF-2 Isoform-Specific Mouse Mutants? Differential Insights into FGF-2 Physiology In Vivo

Fibroblast growth factor 2 (FGF-2), ubiquitously expressed in humans and mice, is functionally involved in cell growth, migration and maturation in vitro and in vivo. Based on the same mRNA, an 18-kilo Dalton (kDa) FGF-2 isoform named FGF-2 low molecular weight (FGF-2LMW) isoform is translated in humans and rodents. Additionally, two larger isoforms weighing 21 and 22 kDa also exist, summarized as the FGF-2 high molecular weight (FGF-2HMW) isoform. Meanwhile, the human FGF-2HMW comprises a 22, 23, 24 and 34 kDa protein. Independent studies verified a specific intracellular localization, mode of action and tissue-specific spatiotemporal expression of the FGF-2 isoforms, increasing the complexity of their physiological and pathophysiological roles. In order to analyze their spectrum of effects, FGF-2LMW knock out (ko) and FGF-2HMWko mice have been generated, as well as mice specifically overexpressing either FGF-2LMW or FGF-2HMW. So far, the development and functionality of the cardiovascular system, bone formation and regeneration as well as their impact on the central nervous system including disease models of neurodegeneration, have been examined. This review provides a summary of the studies characterizing the in vivo effects modulated by the FGF-2 isoforms and, thus, offers a comprehensive overview of its actions in the aforementioned organ systems.     

Sperm metabolism is altered during storage by female insects: evidence from two-photon autofluorescence lifetime measurements in bedbugs

We explore the possibility of characterizing sperm cells without the need to stain them using spectral and fluorescence lifetime analyses after multi-photon excitation in an insect model. The autofluorescence emission spectrum of sperm of the common bedbug, Cimex lectularius, was consistent with the presence of flavins and NAD(P)H. The mean fluorescence lifetimes showed smaller variation in sperm extracted from the male (tau m, τ_m = 1.54–1.84 ns) than in that extracted from the female sperm storage organ (tau m, τ_m = 1.26–2.00 ns). The fluorescence lifetime histograms revealed four peaks. These peaks (0.18, 0.92, 2.50 and 3.80 ns) suggest the presence of NAD(P)H and flavins and show that sperm metabolism can be characterized using fluorescence lifetime imaging. The difference in fluorescence lifetime variation between the sexes is consistent with the notion that female animals alter the metabolism of sperm cells during storage. It is not consistent, however, with the idea that sperm metabolism represents a sexually selected character that provides females with information about the male genotype.     

Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

Fair‐Weather Friends: Evidence of Lipoxin Dysregulation in Neurodegeneration

Lipoxins (LXs) are autacoids, specialized proresolving lipid mediators (SPMs) acting locally in a paracrine or autocrine fashion. They belong to a complex superfamily of dietary small polyunsaturated fatty acid (PUFA)–metabolites, which direct potent cellular responses to resolve inflammation and restore tissue homeostasis. Together, these SPM activities have been intensely studied in systemic inflammation and acute injury or infection, but less is known about LX signaling and activities in the central nervous system. LXs are derived from arachidonic acid, an omega‐6 PUFA. In addition to well‐established roles in systemic inflammation resolution, they have increasingly become implicated in regulating neuroinflammatory and neurodegenerative processes. In particular, chronic inflammation plays a central role in Alzheimer's disease (AD) etiology, and dysregulated LX production and activities have been reported in a variety of AD rodent models and clinical tissue samples, yet with complex and sometimes conflicting results. In addition, reduced LX production following retinal injury has been reported recently by the authors, and an intriguing direct neuronal activity promoting survival and homeostasis in retinal and cortical neurons is demonstrated. Here, the authors review and clarify this growing literature and suggest new research directions to further elaborate the role of lipoxins in neurodegeneration.     

Test Case Generation as an AI Planning Problem

While Artificial Intelligence techniques have been applied to a variety of software engineering applications, the area of automated software testing remains largely unexplored. Yet, test cases for certain types of systems (e.g., those with command language interfaces and transaction based systems) are similar to plans. We have exploited this similarity by constructing an automated test case generator with an AI planning system at its core. We compared the functionality and output of two systems, one based on Software Engineering techniques and the other on planning, for a real application: the StorageTek robot tape library command language. From this, we showed that AI planning is a viable technique for test case generation and that the two approaches are complementary in their capabilities.     

Comment and discussion on digital processing of PD pulses

Some of the more salient aspects of the digital processing technology of PD signals are examined. Most of the efforts in this field are concentrated on the application of digital analyzers for pulse height analysis, pattern recognition and identification of the physical phenomena. It is demonstrated that errors in the signal processing unit can lead to dominant mistakes in the interpretation of the test results