Recent Advances in the Synthesis of Isocoumarins and Polyaromatic Hydrocarbons for Photoactive Materials

The discovery of transition metal-catalyzed selective activation of aromatic carbon–hydrogen bonds in 1993 has opened a new era in the synthesis of carbo- and heterocyclic compounds. This review covers the applications of oxidative annulations of aromatic compounds with alkynes involving CH activation for the synthesis of isocoumarins and polyaromatic hydrocarbons (PAHs). The limitations, advantages, and mechanical aspects of this approach as well as the current tendencies in the application of the reaction products for photoactive materials are discussed.

Activation of PKCε-ALDH2 Axis Prevents 4-HNE-Induced Pain in Mice

Protein kinase Cε (PKCε) is highly expressed in nociceptor neurons and its activation has been reported as pro-nociceptive. Intriguingly, we previously demonstrated that activation of the mitochondrial PKCε substrate aldehyde dehydrogenase-2 (ALDH2) results in anti-nociceptive effects. ALDH2 is a major enzyme responsible for the clearance of 4-hydroxy-2-nonenal (4-HNE), an oxidative stress byproduct accumulated in inflammatory conditions and sufficient to induce pain hypersensitivity in rodents. Here we determined the contribution of the PKCε-ALDH2 axis during 4-HNE-induced mechanical hypersensitivity. Using knockout mice, we demonstrated that PKCε is essential for the nociception recovery during 4-HNE-induced hypersensitivity. We also found that ALDH2 deficient knockin mice display increased 4-HNE-induced nociceptive behavior. As proof of concept, the use of a selective peptide activator of PKCε (ΨεHSP90), which favors PKCε translocation to mitochondria and activation of PKCε-ALDH2 axis, was sufficient to block 4-HNE-induced hypersensitivity in WT, but not in ALDH2-deficient mice. Similarly, ΨεHSP90 administration prevented mechanical hypersensitivity induced by endogenous production of 4-HNE after carrageenan injection. These findings provide evidence that selective activation of mitochondrial PKCε-ALDH2 axis is important to mitigate aldehyde-mediated pain in rodents, suggesting that ΨεHSP90 and small molecules that mimic it may be a potential treatment for patients with pain.

Selective activation of central thalamic fiber pathway facilitates behavioral performance in healthy non-human primates

Central thalamic deep brain stimulation (CT-DBS) is an investigational therapy to treat enduring cognitive dysfunctions in structurally brain injured (SBI) patients. However, the mechanisms of CT-DBS that promote restoration of cognitive functions are unknown, and the heterogeneous etiology and recovery profiles of SBI patients contribute to variable outcomes when using conventional DBS strategies,which may result in off-target effects due to activation of multiple pathways. To disambiguate the effects of stimulation of two adjacent thalamic pathways, we modeled and experimentally compared conventional and novel ‘field-shaping’ methods of CT-DBS within the central thalamus of healthy non-human primates (NHP) as they performed visuomotor tasks. We show that selective activation of the medial dorsal thalamic tegmental tract (DTTm), but not of the adjacent centromedian-parafascicularis (CM-Pf) pathway, results in robust behavioral facilitation. Our predictive modeling approach in healthy NHPs directly informs ongoing and future clinical investigations of conventional and novel methods of CT-DBS for treating cognitive dysfunctions in SBI patients, for whom no therapy currently exists.

Anchoring does not activate examples associated with the anchor value

In the standard anchoring paradigm, people first compare a selected attribute of a target to a numeric value—an anchor. A subsequent absolute judgment of the target's attribute value is biased in the direction of the anchor. A prominent theory of the anchoring effect, the selective accessibility model, argues that people make the initial comparison by focusing on similarities between the target and the anchor, which activates information compatible with the anchor value being the target value. This activated information biases the subsequent estimate of the target value. To test the selective activation of information, the present study asked people to provide an example of the target's category following its comparison with an anchor. The attribute values of the provided examples were not biased in the direction of the anchor. However, they were positively associated with estimates of the target value. The study thus provides evidence for the use of activated information in the absolute judgment in the standard anchoring paradigm, but it does not show the selective activation of information compatible with the anchor value predicted by the selective accessibility model.

Maternally-inherited anti-sense piRNAs antagonize transposon expression in teleost embryos

Transposable elements threaten genome stability, and the Piwi-piRNA system has evolved to silence transposons in the germline. However, it remains largely unknown what mechanisms are utilized in early vertebrate embryos prior to germline establishment and ping-pong piRNA production. To address this, we first characterized small RNAs in early zebrafish embryos and detected abundant maternally-deposited, Ziwi-associated, antisense piRNAs that map largely to evolutionarily young long terminal repeat (LTR) retrotransposons. Notably, the focal establishment of the repressive modification H3K9me2/3 coincides with these young LTR elements, is deposited independent of transcription, and is required for LTR silencing. We find piRNAs highly enriched and maintained in primordial germ cells (PGCs), which display lower LTR expression than somatic cells. To examine the consequences of piRNA loss, we used reciprocal zebrafish-medaka hybrids, which display selective activation of LTRs that lack maternally-contributed targeting piRNAs. Thus, the Piwi-piRNA system actively antagonizes transposons in the soma and PGCs during early vertebrate embryogenesis.

The methodology of using bluetooth technology to solve the problems of identifying and determining the position of objects.

The article analyzes the possibility of using Bluetooth Low Energy technology to solve the problem of identifying and positioning objects. The analysis and comparison of methods for solving the problem of navigation in the room and the problems of identification and positioning of objects is carried out. The features in the methodology, the positioning algorithm and the architecture of the information system are revealed. An adaptive logic for the operation of labels is proposed. The methods of intelligent processing of signals from labels are considered. The method of selective activation of labels and methods of limiting the activation and signal reception zones are described.