Desensitization of the δ-Opioid Receptor Correlates with Its Phosphorylation in SK-N-BE Cells: Involvement of a G Protein-Coupled Receptor Kinase

Abstract: Phosphorylation of G protein-coupled receptors is considered an important step during their desensitization. In SK-N-BE cells, recently presented as a pertinent model for the studies of the human δ-opioid receptor, pretreatment with the opioid agonist etorphine increased time-dependently the rate of phosphorylation of a 51-kDa membrane protein. Immunological characterization of this protein with an antibody, raised against the amino-terminal region of the cloned human δ-opioid receptor, revealed that it corresponded to the δ-opioid receptor. During prolonged treatment with etorphine, phosphorylation increased as early as 15 min to reach a maximum within 1 h. Phosphorylation and desensitization of adenylyl cyclase inhibition paralleled closely and okadaic acid inhibited the resensitization, a result strongly suggesting that phosphorylation of the δ-opioid receptor plays a prominent role in its rapid desensitization. The increase in phosphorylation of the δ-opioid receptor, as well as its desensitization, was not affected by H7, an inhibitor of protein kinase A and protein kinase C, but was drastically reduced by heparin or Zn²⁺, known to act as G protein-coupled receptor kinase (GRK) inhibitors. These results are the first to show, on endogenously expressed human δ-opioid receptor, that a close link exists between receptor phosphorylation and agonist-promoted desensitization and that desensitization involves a GRK.     

Synthesis of 6(α,β)-aminocholestanols as ergosterol biosynthesis inhibitors

Δ⁷-5-Desaturase catalyses one of the last steps in ergosterol biosynthesis in fungi. Moreover Δ⁵-unsaturation is necessary for the sparking function. Synthesis of three pairs of C-6 epimeric cholestanol derivatives are described as potential growth inhibitors. Preliminary results suggest that 6β-aminocholestanol is a potent antifungal agent.     

On Branching Processes and the Early Stages of the Spread of an Epidemic

Branchingprocess(BP)isusedtomodeltheearlystagesofthespreadofasexuallytransmitteddisease.TheearlystagesofAIDSspreadwhichistransmittedbothhomosexuallyandheterosexuallyarestudiedasaBP.     

The emerging role of miR-200 family in metastasis: focus on EMT,CSCs, angiogenesis,and anoikis

Introduction

Cancer is the second major threat to human society and one of the main challenges facing healthcare systems. One of the main problems of cancer care is the metastases of cancer cells that cause 90% of deaths due to cancer. Multiple molecular mechanisms are involved in cancer cell metastasis. Therefore, a better understanding of these molecular mechanisms is necessary for designing restrictive strategies against cancer cell metastasis. Accumulating data suggests that MicroRNAs (miRNAs) are involved in metastasis and invasion of human tumors through regulating multiple genes expression levels that are involved in molecular mechanisms of metastasis. The goal of this review is to present the molecular pathways by which the miR 200 family manifests its effects on EMT, cancer stem cells, angiogenesis, anoikis, and the effects of tumor cell metastases.

Methods

A detailed literature search was conducted to find information about the role of the miR-200 family in the processes involved in metastasis in various databases.

Results

Numerous lines of evidence revealed an association between the mir-200 family and metastasis of human tumors by impressing processes such as cancer stem cells, EMT, angiogenesis, and anoikis.

Conclusions

Understanding the molecular mechanisms associated with metastasis in which the miR-200 family is involved can be effective in treating metastatic cancers.

Graphic abstract

     

Crystal structure of human PACRG in complex with MEIG1 reveals roles in axoneme formation and tubulin binding

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Trapping Elusive Cats: Using Intensive Camera Trapping to Estimate the Density of a Rare African Felid

Camera trapping studies have become increasingly popular to produce population estimates of individually recognisable mammals. Yet, monitoring techniques for rare species which occur at extremely low densities are lacking. Additionally, species which have unpredictable movements may make obtaining reliable population estimates challenging due to low detectability. Our study explores the effectiveness of intensive camera trapping for estimating cheetah (Acinonyx jubatus) numbers. Using both a more traditional, systematic grid approach and pre-determined, targeted sites for camera placement, the cheetah population of the Northern Tuli Game Reserve, Botswana was sampled between December 2012 and October 2013. Placement of cameras in a regular grid pattern yielded very few (n = 9) cheetah images and these were insufficient to estimate cheetah density. However, pre-selected cheetah scent-marking posts provided 53 images of seven adult cheetahs (0.61 ± 0.18 cheetahs/100km²). While increasing the length of the camera trapping survey from 90 to 130 days increased the total number of cheetah images obtained (from 53 to 200), no new individuals were recorded and the estimated population density remained stable. Thus, our study demonstrates that targeted camera placement (irrespective of survey duration) is necessary for reliably assessing cheetah densities where populations are naturally very low or dominated by transient individuals. Significantly our approach can easily be applied to other rare predator species.