Design,synthesis and biological evaluation of new carbazole derivatives as anti-cancer and anti-migratory agents

Based on the efficacy of EHop-016 as an inhibitor of migration and Rac1 activation, a new series of carbazole derivatives has been synthesized. Cytotoxic and anti-migratory effects of these compounds were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. Preliminary investigations of their anticancer activity demonstrated that several compounds have moderate antiproliferative effects on cancer cell lines with GI₅₀ values in the range of 13–50?µM. Furthermore, compounds 3b and 11b inhibit migration activity of metastatic cell line MDA-MB-231 by 32% and 34%, respectively. Compound 11b was shown to inhibit activation of the Rho GTPase Rac1 by 55% at 250?nM in both MDA-MB-231 and MDA-MB-435 cell lines. Compared with the IC₅₀ of Rac1 inhibition by lead compound EHop-016 of 1.1?µM, compound 11b demonstrates 4X improved in vitro efficacy.     

Look in the trees: Hylobatids as evolutionary models for extinct hominins

Studying extant apes is of central importance to paleoanthropology. This approach is informative in inferring how hominin skeletal morphology reflects phylogeny, behavior, development, and ecological context. Traditionally, great apes have dominated the paleoanthropological literature as extant analogs for extinct hominins, to the exclusion of their phylogenetic sister group, the hylobatids. Phylogenetic proximity, large body size, and high encephalization quotients may have contributed to decisions to use great apes as models for hominins. However, if we reexamine hylobatids as extant models for extinct hominins—using modern phylogenetic, behavioral, and ecological data—this clade is uniquely poised to inform future frameworks in paleoanthropology. The following features make hylobatids strong analogs for extinct hominins: taxonomic diversity, the timing of diversification, hybridization between species, small body size, and reduced sexual dimorphism. Based on these shared features, hylobatids offer future opportunities to paleoanthropology, and provide a much richer extant analog than is currently recognized.     

Use of RNA Immunoprecipitation Method for Determining <Emphasis Type="Italic">Sinorhizobium meliloti</Emphasis> RNA<Emphasis Type="Italic">-</Emphasis>Hfq Protein Associations In Vivo

Background

Soil bacterium Sinorhizobium meliloti (S. meliloti) forms an endosymbiotic partnership with Medicago truncatula (M. truncatula) roots which results in root nodules. The bacteria live within root nodules where they function to fix atmospheric N₂ and supply the host plant with reduced nitrogen. The bacterial RNA-binding protein Hfq (Hfq) is an important regulator for the effectiveness of the nitrogen fixation. RNA immunoprecipitation (RIP) method is a powerful method for detecting the association of Hfq protein with specific RNA in cultured bacteria, yet a RIP method for bacteria living in root nodules remains to be described.

Results

A modified S. meliloti gene encoding a His-tagged Hfq protein (Hfq^His) was placed under the regulation of the native Hfq gene promoter (P_hfqsm). The trans produced Hfq^His protein was accumulated at its nature levels during all stages of the symbiosis, allowing RNAs that associated with the given protein to be immunoprecipitated with the anti-His antibody against the protein from root nodule lysates. RNAs that associated with the protein were selectively enriched in the immunoprecipitated sample. The RNAs were recovered by a simple method using heat and subsequently analyzed by RT-PCR. The nature of PCR products was determined by DNA sequencing. Hfq association with specific RNAs can be analyzed at different conditions (e. g. young or older root nodules) and/or in wild-type versus mutant strains.

Conclusions

This article describes the RIP method for determining Sinorhizobium meliloti RNA-Hfq associations in vivo. It is also applicable to other rhizobia living in planta, although some tissue-specific modification related to sample disruption and homogenization may be needed.

     

Detection of immune complexes and evaluation of alcoholic individuals' serological profile in the diagnosis of strongyloidiasis

Strongyloidiasis is a human parasitosis that is considered a public health problem. Early diagnosis of this infection is extremely important in immunocompromised patients (i.e. subjects with alcoholism). This study aimed to evaluate anti-Strongyloides immunoglobulin G (IgG) and immunoglobulin A (IgA), assess levels of circulating immune complexes (IC) and determine IgG avidity in serum samples from alcoholic and nonalcoholic individuals. A total of 140 blood samples were collected from male individuals (70 alcoholic and 70 nonalcoholic subjects). Serum was obtained and analysed by enzyme-linked immunosorbent assay for IgG, IgA, IC detection and avidity determination. Anti-Strongyloides IgG was detected in 55.7% of alcoholic subjects and 32.8% nonalcoholics, while IC levels showed frequencies of 38.6% and 17.1% in these groups, respectively. Anti-Strongyloides IgA was lower among alcoholics (4.3%) than nonalcoholics (34.3%). Spearman's correlation coefficient reported a positive correlation between IgG, IC and IgA in alcoholic individuals and no correlation in nonalcoholics. The median avidity index was higher in alcoholics (83.8%) than nonalcoholic subjects (73.2%). In conclusion, this study shows that alcoholic subjects produced specific antibodies against S. stercoralis regardless of the possible immunosuppression caused by chronic alcoholism. Considering that alcoholics are more susceptible to the severe forms of strongyloidiasis, the implementation of immunological methods as a complementary approach to parasitological diagnostics (i.e. detection of IgG, IC and antibody avidity) appears to be an alternative method for early diagnosis in these individuals.     

Launch of a new report: “Road testing organizational life cycle assessment around the world: applications,experiences and lessons learned”

Purpose

Organizational life cycle assessment (O-LCA) is still a rather young proposal, but moving towards becoming more broadly accepted as a scientifically mature and practical method. The UNEP/SETAC flagship project “LCA of organizations” concluded its “road-testing” phase and is glad to announce the publication of the final report “Road testing organizational life cycle assessment around the world: applications, experiences and lessons learned.” The full report can be accessed at http://www.lifecycleinitiative.org/download/6060. This article shortly summarizes the flagship project phases and main outcomes, particularly the report recently launched, and pinpoints future actions.

Methods

In 2015, the “Guidance on Organizational Life Cycle Assessment” was published. During the following 2 years, the flagship project accompanied 12 organizations in the road testing of that O-LCA Guidance. They represent four world regions, different sectors and sizes. The road testers’ case studies and their feedback are the basis of the Road-testing Report.

Results and discussion

The Road-testing Report aims to complement the O-LCA Guidance through the road testers’ experience, thus delivering advice for future practitioners and inspiration to method developers. It includes executive summaries of the O-LCA road testers’ case studies and the main results of a comprehensive survey through which the road testers share their experience, feedback, and lessons learned. The road testing confirmed the application potential of the O-LCA method and the positive outcomes of the road testing have shown that no immediate updates to the O-LCA Guidance are needed, but some priority actions were identified in order to further ease the application of O-LCA.

Conclusions

Three main tasks for the coming years are identified by the authors: firstly, the challenges highlighted during the road testing should be addressed in the future by the LCA community; specific methodological difficulties of certain kinds of organizations, like the service sector, should be targeted; and finally, the potential revealed by the organizational perspective can be deployed in adjacent LCA fields. The flagship project team hopes that this second publication, together with the great acceptance of the O-LCA Guidance and the contribution of third parties, will pave the way to make O-LCA a mainstream tool.