Synthesis,molecular docking,and biological activity of 2-vinyl chromones: Toward selective butyrylcholinesterase inhibitors for potential Alzheimer's disease therapeutics

We investigated the biological activity of a series of substituted chromeno[3,2-c]pyridines, including compounds previously synthesized by our group and novel compounds whose syntheses are reported here. Tandem transformation of their tetrahydropyridine ring under the action of activated alkynes yielding 2-vinylsubstituted chromones was used to prepare nitrogen-containing derivatives of a biologically active chromone system. The inhibitory activity of these chromone derivatives against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE) was investigated using the methods of enzyme kinetics and molecular docking. Antioxidant (antiradical) activity of the compounds was assessed in the ABTS assay. The results demonstrated that a subset of the studied chromone derivatives selectively inhibit BChE but do not exhibit antiradical activity. In addition, the results of molecular docking effectively explained the observed features in the efficacy, selectivity, and mechanism of BChE inhibition by the chromone derivatives.     

Advertising individual identity by mother and adolescent contact calls in Siberian wapiti Cervus elaphus sibiricus

Individualistic contact calls facilitate mother‐offspring reunion after separation. However, in many mammals, both the acoustic structure and individuality of contact calls differ between mother and young. In contrast, in Siberian wapiti Cervus elaphus sibiricus, contact calls are similar in the acoustics between mother and young, whereas effects of this similarity on vocal individuality were not investigated. In this study, we analyzed acoustic differences between closed‐mouth (nasal) and open‐mouth (oral) contact calls and examined individuality of the most usual oral calls of 19 Siberian wapiti (9 hinds and 10 5–6‐month adolescents) emitted in response to mother‐offspring separation. In the oral calls, the values of frequency and power variables were higher than in the nasal calls. Calls of hinds and adolescents did not differ by the maximum fundamental frequency and duration, whereas the peak frequency was higher in the young. Discriminant function analysis (DFA) based on 11 acoustic variables of oral calls accurately classified to individual 92.5% of hind calls and 96.9% of adolescent calls (chi‐square test for differences between hinds and adolescents, p = 0.19). Variables mainly contributing to vocal identity (duration, start, and maximum fundamental frequency) were the same in calls of mothers and adolescents. We conclude that similarities in the acoustics calls of mothers and adolescents mean that they do not differ in their potential for encoding individual identity, suggesting a mutual process of mother‐offspring vocal recognition in Siberian wapiti.     

Fractura de cadera en el paciente anciano: factores pronóstico de mortalidad y recuperación funcional al año

Objective

The aim of this study is to identify the risks factors for mortality and functional recovery in elderly patients admitted to hospital with a hip fracture.

Effect of Soil Type on Carrot Weevil Movement Behavior

To examine the effect of soil type on carrot weevil, Listronotus oregonensis, (Coleoptera: Curculionidae), movement behavior we conducted a series of laboratory arena experiments with the use of three soil types: mineral soil, organic soil and pure sand. We found that soil type influences carrot weevil burrowing activity and movement and showed that carrot weevil is more inclined to burrow into mineral and organic soils than pure sand and displays avoidance of the latter. While barriers constructed out of pure sand induced burrowing activity only in 3% of tested weevils, mineral and organic soil barriers initiated burrowing in 67% and 38% of tested weevils respectively. All weevils crossed pure sand barriers, whereas 18% (mineral soil) and 6% (organic soil) were arrested and engaged in burrowing activities. In addition, carrot weevil movement behavior at the border of two substrates, revealed high edge permeability of mineral and organic soils and reduced permeability of pure sand edges. Over 70% of weevils released on organic soil ended up not crossing the border with another substrate. All tested weevils released on pure sand crossed the border within less than 1 min. Replication of the experiments with autoclaved soil suggested that the observed differences in carrot weevil movement behavior were largely due to soil texture and not strongly influenced by micro-organisms or odor.     

Synthesis,spectroscopic studies and biological evaluation of acridine derivatives: The role of aggregation on the photodynamic efficiency

Two new photoactive compounds (1 and 2) derived from the 9-amidoacridine chromophore have been synthesized and fully characterized. Their abilities to produce singlet oxygen upon irradiation have been compared. The synthesized compounds show very different self-aggregating properties since only 1 present a strong tendency to aggregate in water. Biological assays were conducted with two cell types: hepatoma cells (Hep3B) and human umbilical vein endothelial cells (HUVEC). Photodynamic therapy (PDT) studies carried out with Hep3B cells showed that non-aggregating compound 2 showed photoxicity, ascribed to the production of singlet oxygen, being aggregating compound 1 photochemically inactive. On the other hand suspensions of 1, characterized as nano-sized aggregates, have notable antiproliferative activity towards this cell line in the dark.     

Isosteric ribavirin analogues: Synthesis and antiviral activities

The novel isosteric ribavirin analogues were synthesized by two different ways. Some of them showed significant antiviral action against hepatitis C virus (HCV), herpes simplex (HCV-1) and influenza A virus comparable to that of ribavirin itself. The data obtained confirm the proposed theory of the ribavirin possible antiviral activity mechanism related with bioisosterism.     

Synthesis and biological evaluation of novel mono- and bivalent ASGP-R-targeted drug-conjugates

Asialoglycoprotein receptor (ASGP-R) is a promising biological target for drug delivery into hepatoma cells. Nevertheless, there are only few examples of small-molecule conjugates of ASGP-R selective ligand equipped by a therapeutic agent for the treatment of hepatocellular carcinoma (HCC). In the present work, we describe a convenient and versatile synthetic approach to novel mono- and multivalent drug-conjugates containing N-acetyl-2-deoxy-2-aminogalactopyranose and anticancer drug – paclitaxel (PTX). Several molecules have demonstrated high affinity towards ASGP-R and good stability under physiological conditions, significant in vitro anticancer activity comparable to PTX, as well as good internalization via ASGP-R-mediated endocytosis. Therefore, the conjugates with the highest potency can be regarded as a promising therapeutic option against HCC.     

Sustainability governance service providers: the role of third-party product certification in facilitating corporate life cycle management

Purpose

This article aims to analyze the role that third-party product sustainability certifications play in supply chain sustainability governance and hence the impact that they may have on facilitating corporate life cycle management (LCM). Particular emphasis is given to exploring the extent to which such schemes allow firms to outsource the work of communication, motivation, enablement, and control of sustainability-related information and performance upstream in the supply chain.

Methods

The research design is based on a comparative case study methodology. The corporate practices of sourcing the sustainability certified products in the food retailing and textile sectors are compared, to explain when third-party product sustainability certification reduces the corporate need to engage in collaborative relationships with suppliers, thereby reducing efforts associated with implementation of corporate life cycle management.

Results and discussion

In our study, we found evidence that affirms the role of third-party product sustainability certification in reducing corporate necessity to actively engage with coordination of sustainability issues upstream in the supply chain. However, we also identified a range of factors—the intention of the buying company, the supply chain context, and the design of the certification scheme—that influence the extent, to which third-party product sustainability certification replaces the corporate need for additional work to facilitate supplier compliance. Some of these factors, e.g., the design of the certification scheme, are new and have been underexplored in the supply chain management and value chain governance literature yet.

Conclusions

Our findings suggest that corporate LCM practitioners should consider third-party sustainability certification as an instrument for the transfer of significant life cycle information along the supply chain and as a tool to facilitate corporate life cycle management. The extent to which third-party product sustainability certification would be able to facilitate corporate life cycle management depends not only on whether certification requirements are based on the LCA studies but also on the market scope of the certification schemes, the scope of the certification requirements, and the architecture of the certification management services. If these parameters are aligned with corporate ambitions and allow buyers to fully outsource the work associated with communication, motivation, enablement, and control of sustainability-related information and supplier performance, the life cycle management can be exercised by companies by simply choosing to procure sustainability certified products.

     

Biodegradation of sulfamethoxazole by a bacterial consortium of Achromobacter denitrificans PR1 and Leucobacter sp. GP

In the last decade, biological degradation and mineralization of antibiotics have been increasingly reported feats of environmental bacteria. The most extensively described example is that of sulfonamides that can be degraded by several members of Actinobacteria and Proteobacteria. Previously, we reported sulfamethoxazole (SMX) degradation and partial mineralization by Achromobacter denitrificans strain PR1, isolated from activated sludge. However, further studies revealed an apparent instability of this metabolic trait in this strain. Here, we investigated this instability and describe the finding of a low-abundance and slow-growing actinobacterium, thriving only in co-culture with strain PR1. This organism, named GP, shared highest 16S rRNA gene sequence similarity (94.6–96.9%) with the type strains of validly described species of the genus Leucobacter. This microbial consortium was found to harbor a homolog to the sulfonamide monooxygenase gene (sadA) also found in other sulfonamide-degrading bacteria. This gene is overexpressed in the presence of the antibiotic, and evidence suggests that it codes for a group D flavin monooxygenase responsible for the ipso-hydroxylation of SMX. Additional side reactions were also detected comprising an NIH shift and a Baeyer–Villiger rearrangement, which indicate an inefficient biological transformation of these antibiotics in the environment. This work contributes to further our knowledge in the degradation of this ubiquitous micropollutant by environmental bacteria.