Photoprocesses in Derivatives of 1,4- and 1,3-Diazadistyryldibenzenes

Photoprocesses in 1,4-diazadistyrylbenzene (1) and 1,3-diazadistyrylbenzene derivative (2) diperchlorates in MeCN were studied by absorption, luminescence, and kinetic laser spectroscopies. For compound 1, trans-cis-photoisomerization and intersystem crossing to a triplet state are observed. For compound 2, photoelectrocyclization is suggested. Quantum chemical calculations of diazadistyrylbenzene structures in the ground and excited states were carried out. The schemes for photoreactions were proposed.     

Addition of Synthetic Biomaterials to Deproteinized Bovine Bone Mineral (DBBM) for Bone Augmentation—A Preclinical In Vivo Study

(1) Aim: To investigate the effect of synthetic bone substitutes, α-tricalcium phosphate (α-TCP) or bi-layered biphasic calcium-phosphate (BBCP) combined with deproteinized bovine bone mineral (DBBM), on bone formation. (2) Methods: Thirty critical size defects were randomly treated with the following five different treatment modalities: (1) negative control (NC, empty), (2) DBBM, (3) α-TCP + DBBM (1:1), (4) BBCP 3%HA/97%α-TCP + DBBM (1:1), and (5) BBCP 6%HA/94%α-TCP + DBBM (1:1). The samples, at four weeks post-surgery, were investigated by micro-CT and histological analysis. (3) Results: A similar level of new bone formation was demonstrated in the DBBM with α-TCP bone substitute groups when compared to the negative control by histomorphometry. DBBM alone showed significantly lower new bone area than the negative control (p = 0.0252). In contrast to DBBM, the micro-CT analysis revealed resorption of the α-TCP + DBBM, BBCP 3%HA/97%α-TCP + DBBM and BBCP 6%HA/94%α-TCP + DBBM, as evidenced by a decrease of material density (p = 0.0083, p = 0.0050 and p = 0.0191, respectively), without changing their volume. (4) Conclusions: New bone formation was evident in all defects augmented with biomaterials, proving the osteoconductive properties of the tested material combinations. There was little impact of the HA coating degree on α-TCP in bone augmentation potential and material resorption for four weeks when mixed with DBBM.     

The Flavonol Quercitrin Hinders GSK3 Activity and Potentiates the Wnt/β-Catenin Signaling Pathway

The Wnt/β-catenin signaling pathway dictates cell proliferation and differentiation during embryonic development and tissue homeostasis. Its deregulation is associated with many pathological conditions, including neurodegenerative disease, frequently downregulated. The lack of efficient treatment for these diseases, including Alzheimer’s disease (AD), makes Wnt signaling an attractive target for therapies. Interestingly, novel Wnt signaling activating compounds are less frequently described than inhibitors, turning the quest for novel positive modulators even more appealing. In that sense, natural compounds are an outstanding source of potential drug leads. Here, we combine different experimental models, cell-based approaches, neuronal culture assays, and rodent behavior tests with Xenopus laevis phenotypic analysis to characterize quercitrin, a natural compound, as a novel Wnt signaling potentiator. We find that quercitrin potentiates the signaling in a concentration-dependent manner and increases the occurrence of the Xenopus secondary axis phenotype mediated by Xwnt8 injection. Using a GSK3 biosensor, we describe that quercitrin impairs GSK3 activity and increases phosphorylated GSK3β S9 levels. Treatment with XAV939, an inhibitor downstream of GSK3, impairs the quercitrin-mediated effect. Next, we show that quercitrin potentiates the Wnt3a-synaptogenic effect in hippocampal neurons in culture, which is blocked by XAV939. Quercitrin treatment also rescues the hippocampal synapse loss induced by intracerebroventricular injection of amyloid-β oligomers (AβO) in mice. Finally, quercitrin rescues AβO-mediated memory impairment, which is prevented by XAV939. Thus, our study uncovers a novel function for quercitrin as a Wnt/β-catenin signaling potentiator, describes its mechanism of action, and opens new avenues for AD treatments.     

Kozak Similarity Score Algorithm Identifies Alternative Translation Initiation Codons Implicated in Cancers

Ribosome profiling and mass spectroscopy have identified canonical and noncanonical translation initiation codons (TICs) that are upstream of the main translation initiation site and used to translate oncogenic proteins. There have previously been conflicting reports about the patterns of nucleotides that surround noncanonical TICs. Here, we use a Kozak Similarity Score algorithm to find that nearly all of these TICs have flanking nucleotides closely matching the Kozak sequence. Remarkably, the nucleotides flanking alternative noncanonical TICs are frequently closer to the Kozak sequence than the nucleotides flanking TICs used to translate the gene’s main protein. Of note, the 5′ untranslated region (5‘UTR) of cancer-associated genes with an upstream TIC tend to be significantly longer than the same region in genes not associated with cancer. The presence of a longer-than-typical 5′UTR increases the likelihood of ribosome binding to upstream noncanonical TICs, and may be a distinguishing feature of a number of genes overexpressed in cancer. Noncanonical TICs that are located in the 5′UTR, although thought by some to be disadvantageous and suppressed by evolution, may translate oncogenic proteins because of their flanking nucleotides.     

Sleep Modulates Alcohol Toxicity in Drosophila

Alcohol abuse is a significant public health problem. While considerable research has shown that alcohol use affects sleep, little is known about the role of sleep deprivation in alcohol toxicity. We investigated sleep as a factor modulating alcohol toxicity using Drosophila melanogaster, a model for studies of sleep, alcohol, and aging. Following 24 h of sleep deprivation using a paradigm that similarly affects males and females and induces rebound sleep, flies were given binge-like alcohol exposures. Sleep deprivation increased mortality, with no sex-dependent differences. Sleep deprivation also abolished functional tolerance measured at 24 h after the initial alcohol exposure, although there was no effect on alcohol absorbance or clearance. We investigated the effect of chronic sleep deprivation using mutants with decreased sleep, insomniac and insulin-like peptide 2, finding increased alcohol mortality. Furthermore, we investigated whether pharmacologically inducing sleep prior to alcohol exposure using the GABA_A-receptor agonist 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP) mitigated the effects of alcohol toxicity on middle-aged flies, flies with environmentally disrupted circadian clocks, and flies with short sleep. Pharmacologically increasing sleep prior to alcohol exposure decreased alcohol-induced mortality. Thus, sleep prior to binge-like alcohol exposure affects alcohol-induced mortality, even in vulnerable groups such as aging flies and those with circadian dysfunction.     

Microbial Precipitation of Pb(II) with Wild Strains of Paraclostridium bifermentans and Klebsiella pneumoniae Isolated from an Industrially Obtained Microbial Consortium

The study focused on determining the microbial precipitation abilities of bacterial strains that were isolated from an industrially obtained Pb(II)-resistant microbial consortium. Previous research has demonstrated the effectiveness of the consortium on the bioprecipitation and adsorption of Pb(II) from solution. The bioremediation of Pb(II) using microbial precipitation provides an alternative option for Pb(II) removal from wastewater. Both strains, Klebsiella pneumoniae and Paraclostridium bifermentans, were successfully isolated from the consortium obtained from a battery recycling plant in South Africa. The experiments were conducted over both 30 h and 5 d, providing insight into the short- and long-term precipitation abilities of the bacteria. Various initial concentrations of Pb(II) were investigated, and it was found that P. bifermentans was able to remove 83.8% of Pb(II) from solution with an initial Pb(II) concentration of 80 mg L−1, while K. pneumoniae was able to remove 100% of Pb(II) with the same initial Pb(II) concentration after approximately 5 d. With the same initial Pb(II) concentration, P. bifermentans was able to remove 86.1% of Pb(II) from solution, and K. pneumoniae was able to remove 91.1% of Pb(II) from solution after 30 h. The identities of the precipitates obtained for each strain vary, with PbS and Pb0 being the main species precipitated by P. bifermentans and PbO with either PbCl or Pb3(PO4)2 precipitated by K. pneumoniae. Various factors were investigated in each experiment, such as metabolic activity, nitrate concentration, residual Pb(II) concentration, extracellular and intracellular Pb(II) concentration and the precipitate identity. These factors provide a greater understanding of the mechanisms utilised by the bacteria in the bioprecipitation and adsorption of Pb(II). These results can be used as a step towards applying the process on an industrial scale.     

Physiological and Pathological Remodeling of Cerebral Microvessels

There is growing evidence that the remodeling of cerebral microvessels plays an important role in plastic changes in the brain associated with development, experience, learning, and memory consolidation. At the same time, abnormal neoangiogenesis, and deregulated regulation of microvascular regression, or pruning, could contribute to the pathogenesis of neurodevelopmental diseases, stroke, and neurodegeneration. Aberrant remodeling of microvesselsis associated with blood–brain barrier breakdown, development of neuroinflammation, inadequate microcirculation in active brain regions, and leads to the dysfunction of the neurovascular unit and progressive neurological deficits. In this review, we summarize current data on the mechanisms of blood vessel regression and pruning in brain plasticity and in Alzheimer’s-type neurodegeneration. We discuss some novel approaches to modulating cerebral remodeling and preventing degeneration-coupled aberrant microvascular activity in chronic neurodegeneration.     

Flow-Seq Evaluation of Translation Driven by a Set of Natural Escherichia coli 5′-UTR of Variable Length

Flow-seq is a method that combines fluorescently activated cell sorting and next-generation sequencing to deduce a large amount of data about translation efficiency from a single experiment. Here, we constructed a library of fluorescent protein-based reporters preceded by a set of 648 natural 5′-untranslated regions (5′-UTRs) of Escherichia coli genes. Usually, Flow-seq libraries are constructed using uniform-length sequence elements, in contrast to natural situations, where functional elements are of heterogenous lengths. Here, we demonstrated that a 5′-UTR library of variable length could be created and analyzed with Flow-seq. In line with previous Flow-seq experiments with randomized 5′-UTRs, we observed the influence of an RNA secondary structure and Shine–Dalgarno sequences on translation efficiency; however, the variability of these parameters for natural 5′-UTRs in our library was smaller in comparison with randomized libraries. In line with this, we only observed a 30-fold difference in translation efficiency between the best and worst bins sorted with this factor. The results correlated with those obtained with ribosome profiling.     

Reaction of Corroles with Sarcosine and Paraformaldehyde: A New Facet of Corrole Chemistry

Details on the unexpected formation of two new (dimethylamino)methyl corrole isomers from the reaction of 5,10,15-tris(pentafluorophenyl)corrolatogallium(III) with sarcosine and paraformaldehyde are presented. Semi-empirical calculations on possible mechanism pathways seem to indicate that the new compounds are probably formed through a Mannich-type reaction. The extension of the protocol to the free-base 5,10,15-tris(pentafluorophenyl)corrole afforded an unexpected new seven-membered ring corrole derivative, confirming the peculiar behavior of corroles towards known reactions when compared to the well-behaved porphyrin counterparts.