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Beta-arrestins uncouple G protein-coupled receptors (GPCRs) from G proteins and promote their internalization, leading to desensitization and downregulation and serving as negative regulators of GPCR signaling. beta-Arrestins also function as scaffold proteins, interacting with several cytoplasmic proteins and linking GPCRs to intracellular signaling pathways such as the mitogen-activated protein kinase (MAPK) cascade. Recent work has also revealed that beta-arrestins translocate from the cytoplasm to the nucleus and associate with transcription factors such as histone acetyltransferase p300 and cyclic adenosine monophosphate (cAMP)-responsive element-binding protein. These substances also interact with regulators of transcription factors. We review findings on the effects of antidepressants on beta-arrestins and the plethora of antidepressant effects on signal transduction elements in which beta-arrestins serve as signaling scaffold proteins, focusing on the three major groups of MAPKs: extracellular signal-regulated kinases, c-Jun N-terminal kinases and p38 MAPKs, and on transcription factors and cofactors of which beta-arrestins mediate transcription regulation.

The focus of the seventh annual meeting of the International Society for Stem Cell Research was placed on several topics, such as cancer stem cells, stem cell transplantation, tissue regeneration, biology of embryonic and adult stem cells of various species and production of induced pluripotent stem cells via reprogramming of mammalian somatic cells. This report provides an overview of stem cell research, based on the proceedings of the meeting.

Receptorome screening is the process of characterizing one or more compounds for pharmacological activity (e.g., inhibition of radioligand binding, positive or negative efficacy) at a large panel of 'targets' (e.g., biologically relevant recombinant G protein-coupled receptors, ion channels and small-molecule transporters). Recently, receptorome profiles have led to mechanistic insights into the actions -both intentional and adverse- of several drugs. In the present review, I discuss in detail how receptorome screening increased our understanding of three drugs (salvinorin A, amisulpride and fenfluramine) and a class of medications (atypical antipsychotics). The cases presented suggest that receptorome screening of current medications, as well as investigational drugs and future compounds destined for use in humans, might enable us to predict salutary effects, as well as side effects, at the preclinical stage, which would have important economic and public health implications.

Ischemic stroke is associated with a high rate of disability and death. Establishing valid biomarkers could help accelerate the approval of promising new therapies for stroke. Whereas many serum biomarkers have been evaluated, possible imaging biomarkers of stroke lack validation. Magnetic resonance imaging (MRI) is a very sensitive technique to study acute stroke and MRI parameters have been established to assess the outcome of acute stroke. This review reassesses the criteria for the validation of MRI biomarkers of acute ischemic stroke (MRI-BAS). Seven criteria were used to review the validity of the main MRI-BAS: vascular status, lesion volume, reversibility on diffusion-weighted imaging, perfusion alteration, penumbra studied with diffusion-perfusion mismatch, clinical-diffusion mismatch, diffusion-angiography mismatch and hemorrhagic transformation. We analyzed the definitions of these biomarkers and the extent to which each fulfills the criteria for validation and found that few MRI-BAS have been fully validated. Further studies should help to improve the validation of current MRI-BAS and develop new biomarkers.

Although safer and more effective immunosuppressants as well as enhanced immunosuppressive protocols are continuously being developed in order to increase graft survival, they come at the steep price of drug-related complications and important side effects. In addition, the value of panel reactive antibodies determination, which at present is the single most used indicator of an increased risk of transplant rejection, is now being reevaluated. Therefore, effective tailoring of immunosuppressive therapy minimizing the above-mentioned pitfalls requires the existence of dependable biomarkers that adequately monitor rejection risk both before and after transplantation. Here we review the data yielded by studies assessing the usefulness of measuring soluble CD30 levels (sCD30) in kidney transplant rejection. These data collectively show that sCD30 serum content has a considerable predictive/diagnostic value for acute rejection of renal grafts, particularly when measured a few days after transplantation.