Macamides and their synthetic analogs: Evaluation of in vitro FAAH inhibition

Maca (Lepidium meyenii), a traditional food crop of the Peruvian Andes is now widely touted as a dietary supplement. Among the various chemical constituents isolated from the plant are a unique series of non-polar, long-chain fatty acid N-benzylamides known as macamides. We have synthesized 11 of the 19 reported macamides and have tested each as potential inhibitors of the human enzyme, fatty acid amide hydrolase (FAAH). The five most potent macamides were FAAH inhibitors (IC₅₀ = 10–17 μM). These amides were derivatives of oleic, linoleic and linolenic acids and benzylamine or 3-methoxybenzylamine. Of the three compounds evaluated in a pre-incubation time study, two macamides were not irreversible inhibitors of FAAH. The third, a carbamate structurally related to macamides, was shown to be an irreversible inhibitor of FAAH (IC₅₀ = 0.153 μM).     

Structure of the Essential Diversity-Generating Retroelement Protein bAvd and Its Functionally Important Interaction with Reverse Transcriptase

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Highlights? bAvd forms a highly positively charged pentameric barrel ? bAvd binds both DNA and RNA, but without sequence preference ? The coding sequence for bAvd serves dual purposes ? The interaction of bAvd with bRT is likely to be important for retrohoming     

Development of a core outcome set for clinical trials in rosacea: study protocol for a systematic review of the literature and identification of a core outcome set using a Delphi survey

BackgroundRosacea is a chronic inflammatory disorder affecting millions of individuals worldwide. Diagnosis is based on signs and symptoms with management and treatment aimed to suppress inflammatory lesions, erythema, and telangiectasia. While many clinical trials of rosacea exist, the lack of consensus in outcome reporting across all trials poses a concern. Proper evaluation and comparison of treatment modalities is challenging. In order to address the inconsistencies present, this project aims to determine a core set of outcomes which should be evaluated in all clinical trials of rosacea.Methods/designThis project will utilize a methodology similar to previous core outcome set research. A long list of outcomes will be extracted over four phases: (1) systematic literature review, (2) patient interviews, (3) other published sources, and (4) stakeholder involvement. Potential outcomes will be examined by the Steering Committee to provide further insight. The Delphi process will then be performed to prioritize and condense the list of outcomes generated. Two homogenous groups of physicians and patients will participate in two consecutive rounds of Delphi surveys. A consensus meeting, composed of physicians, patients, and stakeholders, will be conducted after the Delphi exercise to further select outcomes, taking into account participant scores. By the end of the meeting, members will vote and decide on a final recommended set of core outcomes. For the duration of the study, we will be in collaboration with both the Core Outcome Measures in Effectiveness Trials (COMET) and Cochrane Skin Group - Core Outcome Set Initiative (CSG-COUSIN).DiscussionThis study aims to develop a core outcome set to guide assessment in clinical trials of rosacea. The end-goal is to improve the reliability and consistency of outcome reporting, thereby allowing sufficient evaluation of treatment effectiveness and patient satisfaction.

Electronic supplementary material

The online version of this article (doi:10.1186/s13063-016-1554-3) contains supplementary material, which is available to authorized users.     

Dispersal patterns in a medium‐density Irish badger population: Implications for understanding the dynamics of tuberculosis transmission

European badgers (Meles meles) are group‐living mustelids implicated in the spread of bovine tuberculosis (TB) to cattle and act as a wildlife reservoir for the disease. In badgers, only a minority of individuals disperse from their natal social group. However, dispersal may be extremely important for the spread of TB, as dispersers could act as hubs for disease transmission. We monitored a population of 139 wild badgers over 7 years in a medium‐density population (1.8 individuals/km²). GPS tracking collars were applied to 80 different individuals. Of these, we identified 25 dispersers, 14 of which were wearing collars as they dispersed. This allowed us to record the process of dispersal in much greater detail than ever before. We show that dispersal is an extremely complex process, and measurements of straight‐line distance between old and new social groups can severely underestimate how far dispersers travel. Assumptions of straight‐line travel can also underestimate direct and indirect interactions and the potential for disease transmission. For example, one female disperser which eventually settled 1.5 km from her natal territory traveled 308 km and passed through 22 different territories during dispersal. Knowledge of badgers' ranging behavior during dispersal is crucial to understanding the dynamics of TB transmission, and for designing appropriate interventions, such as vaccination.     

Assessment of the genetic diversity of Frankia microsymbionts of Elaeagnus angustifolia L. plants growing in a Tunisian date-palm oasis by analysis of PCR amplified nifD-K intergenic spacer

Diversity of Frankia microsymbionts of non-native Elaeagnus angustifolia L. plants spontaneously growing in a Tunisian desertic retreat area, the date-palm oasis of Tozeur, was investigated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and PCR-sequencing techniques targeting the nifD-K intergenic spacer. Three PCR-RFLP haplotypes (I, II, and III) were detected among collected nodules. Haplotype I was detected at all five sampling sites and dominated the other haplotypes present at these sites. This haplotype was also exhibited by strain BMG5.10, which was isolated by a plant-capturing assay in 1998 from soil collected in the same locality, qualifying it to be the most competitive haplotype in the edapho-climatic condition of the studied desertic date-palm oasis. nifD-K sequences of the three haplotypes formed a closely related phylogenetic subgroup. These results suggest that Frankia variability is constrained by severe edapho-climatic conditions of retreated desert in Tunisian area.     

Alterations in immunological and neurological gene expression patterns in Alzheimer's disease tissues

Microarray technology was utilized to isolate disease-specific changes in gene expression by sampling across inferior parietal lobes of patients suffering from late onset AD or non-AD-associated dementia and non-demented controls. Primary focus was placed on understanding how inflammation plays a role in AD pathogenesis. Gene ontology analysis revealed that the most differentially expressed genes related to nervous system development and function and neurological disease followed by genes involved in inflammation and immunological signaling. Pathway analysis also implicated a role for chemokines and their receptors, specifically CXCR4 and CCR3, in AD. Immunohistological analysis revealed that these chemokine receptors are upregulated in AD patients. Western analysis demonstrated an increased activation of PKC, a downstream mediator of chemokine receptor signaling, in the majority of AD patients. A very specific cohort of genes related to amyloid beta accumulation and clearance were found to be significantly altered in AD. The most significantly downregulated gene in this data set was the endothelin converting enzyme 2 (ECE2), implicated in amyloid beta clearance. These data were subsequently confirmed by real-time PCR and Western blot analysis. Together, these findings open up new avenues of investigation and possible therapeutic strategies targeting inflammation and amyloid clearance in AD patients.