The current state of the quality of homeopathic clinical research.

Homeopathy is a system of therapeutics that treats disease with highly diluted substances based on the Law of Similars, which holds that "like cures like." Despite widespread use, homeopathy lacks a comprehensive and robust evidence base. We examined the state of homeopathic clinical research by critically assessing the overall quality of peer-reviewed, recently published, English-language, homeopathic clinical research in terms of internal, external, and model validity using standard and homeopathic-specific instruments.

Omega-7 Mixed Fatty Acid Supplementation Fails to Reduce Serum Inflammatory Biomarkers: A Placebo-Controlled, Double-Blind Randomized Crossover Trial.

Unlabelled: We report the effects of mixed omega-7 fatty acid supplementation on changes in serum hsCRP, TNFα, and IL-6 levels and self-reported outcomes in people with non-specific chronic musculoskeletal discomfort.

Design: A double-blind, placebo-controlled, 1:1 randomized single crossover trial composed of 688 mg/day palmiteolate for the verum and an equivalent amount of medium-chain triglycerides for the placebo.

Method: Data were analyzed in two independent groups and as a crossover group.

Dispositional Humility Of Clinicians In An Interprofessional Primary Care Environment: A Mixed Methods Study.

Objectives: Dispositional humility in professionals is a character trait that allows one to monitor self-centered occupational drive and to pay attention to the needs of other professionals. The aim of this study is to test whether or not clinicians working in interprofessional team care environments identify the character trait of humility as an important factor for successful collaborative relationships. This study aimed to revise a concept map of dispositional humility created through literature review.

Concept map of dispositional humility among professionals in an interdisciplinary healthcare environment: qualitative synthesis.

Background: US healthcare consumers increasingly demand more integrative medical care. Collaboration among clinicians trained in different professional disciplines and specialties may require particular character traits and/or training that focus on factors that facilitate effective collaborative work. Dispositional humility may be a factor that balances self-focused desire for recognition with other-focused professional collaboration to serve patients.

Translatome Regulation in Neuronal Injury and Axon Regrowth.

Transcriptional events leading to outgrowth of neuronal axons have been intensively studied, but the role of translational regulation in this process is not well understood. Here, we use translatome analyses by ribosome pull-down and protein synthesis characterization by metabolic isotopic labeling to study nerve injury and axon outgrowth proteomes in rodent dorsal root ganglia (DRGs) and sensory neurons. We identify over 1600 gene products that are primarily translationally regulated in DRG neurons after nerve injury, many of which contain a 5'UTR cytosine-enriched regulator of translation (CERT) motif, implicating the translation initiation factor Eif4e in the injury response.

Ribosomal Proteins Rpl22 and Rpl22l1 Control Morphogenesis by Regulating Pre-mRNA Splicing.

Most ribosomal proteins (RP) are regarded as essential, static components that contribute only to ribosome biogenesis and protein synthesis. However, emerging evidence suggests that RNA-binding RP are dynamic and can influence cellular processes by performing "extraribosomal," regulatory functions involving binding to select critical target mRNAs. We report here that the RP, Rpl22, and its highly homologous paralog Rpl22-Like1 (Rpl22l1 or Like1) play critical, extraribosomal roles in embryogenesis.

Dynamic Axonal Translation in Developing and Mature Visual Circuits.

Local mRNA translation mediates the adaptive responses of axons to extrinsic signals, but direct evidence that it occurs in mammalian CNS axons in vivo is scant. We developed an axon-TRAP-RiboTag approach in mouse that allows deep-sequencing analysis of ribosome-bound mRNAs in the retinal ganglion cell axons of the developing and adult retinotectal projection in vivo. The embryonic-to-postnatal axonal translatome comprises an evolving subset of enriched genes with axon-specific roles, suggesting distinct steps in axon wiring, such as elongation, pruning, and synaptogenesis.

Genome-wide identification of AR-regulated genes translated in Sertoli cells in vivo using the RiboTag approach.

An understanding of the molecular mechanisms by which androgens drive spermatogenesis has been thwarted by the fact that few consistent androgen receptor (AR) target genes have been identified. Here, we addressed this issue using next-generation sequencing coupled with the RiboTag approach, which purifies translated mRNAs expressed in cells that express cyclic recombinase (CRE). Using RiboTag mice expressing CRE in Sertoli cells (SCs), we identified genes expressed specifically in SCs in both prepubertal and adult mice.

RiboTag analysis of actively translated mRNAs in Sertoli and Leydig cells in vivo.

Male spermatogenesis is a complex biological process that is regulated by hormonal signals from the hypothalamus (GnRH), the pituitary gonadotropins (LH and FSH) and the testis (androgens, inhibin). The two key somatic cell types of the testis, Leydig and Sertoli cells, respond to gonadotropins and androgens and regulate the development and maturation of fertilization competent spermatozoa. Although progress has been made in the identification of specific transcripts that are translated in Sertoli and Leydig cells and their response to hormones, efforts to expand these studies have been restricted by technical hurdles.

FMR1 transcript isoforms: association with polyribosomes; regional and developmental expression in mouse brain.

The primary transcript of the mammalian Fragile X Mental Retardation-1 gene (Fmr1), like many transcripts in the central nervous system, is alternatively spliced to yield mRNAs encoding multiple proteins, which can possess quite different biochemical properties. Despite the fact that the relative levels of the 12 Fmr1 transcript isoforms examined here vary by as much as two orders of magnitude amongst themselves in both adult and embryonic mouse brain, all are associated with polyribosomes, consistent with translation into the corresponding isoforms of the protein product, FMRP (Fragile X Mental Retardation Protein). Employing the RiboTag methodology developed in our laboratory, the relative proportions of the 7 most abundant transcript isoforms were measured specifically in neurons and found to be similar to those identified in whole brain.

Lack of GPR88 enhances medium spiny neuron activity and alters motor- and cue-dependent behaviors.

The striatum regulates motor control, reward and learning. Abnormal function of striatal GABAergic medium spiny neurons (MSNs) is believed to contribute to the deficits in these processes that are observed in many neuropsychiatric diseases. The orphan G protein-coupled receptor GPR88 is robustly expressed in MSNs and is regulated by neuropharmacological drugs, but its contribution to MSN physiology and behavior is unclear.

Cell-type specific expression of a dominant negative PKA mutation in mice.

We employed the Cre recombinase/loxP system to create a mouse line in which PKA activity can be inhibited in any cell-type that expresses Cre recombinase. The mouse line carries a mutant Prkar1a allele encoding a glycine to aspartate substitution at position 324 in the carboxy-terminal cAMP-binding domain (site B). This mutation produces a dominant negative RIα regulatory subunit (RIαB) and leads to inhibition of PKA activity.

Cyclic nucleotides converge on brown adipose tissue differentiation.

Brown adipose tissue (BAT) is rich in mitochondria and can uncouple oxidative phosphorylation to produce heat as a by-product of fatty acid metabolism. This thermogenic effect helps to maintain body temperature and also plays a critical role in energy homeostasis and the regulation of body weight. Both cyclic adenosine monophosphate and cyclic guanosine monophosphate (cGMP) contribute to the intracellular regulation of mitochondrial biogenesis and the differentiation of BAT.

Elevated cyclic AMP and PDE4 inhibition induce chemokine expression in human monocyte-derived macrophages.

Macrophages are central mediators of the innate immune system that can be differentiated from monocytes upon exposure to cytokines. While increased cyclic adenosine monophosphate (cAMP) levels are known to inhibit many lipopolysaccharide-elicited macrophage inflammatory responses, the effects of elevated cAMP on monocyte/macrophage differentiation are not as well understood. We show here that during differentiation, cAMP agonists can cause a large increase in the mRNA and protein levels of several of the pro-inflammatory CXCL and CCL chemokines.

Cell-type-specific isolation of ribosome-associated mRNA from complex tissues.

Gene profiling techniques allow the assay of transcripts from organs, tissues, and cells with an unprecedented level of coverage. However, most of these approaches are still limited by the fact that organs and tissues are composed of multiple cell types that are each unique in their patterns of gene expression. To identify the transcriptome from a single cell type in a complex tissue, investigators have relied upon physical methods to separate cell types or in situ hybridization and immunohistochemistry.

MBNL3/CHCR prevents myogenic differentiation by inhibiting MyoD-dependent gene transcription.

Muscle differentiation is controlled by positive and negative signals. While much attention has been placed on proteins that promote muscle formation, the importance of negative regulators has been underemphasized. MBNL3/CHCR belongs to the muscleblind family of Cys3His zinc finger proteins implicated in myotonic dystrophy.

Alpha4 integrins are type I cAMP-dependent protein kinase-anchoring proteins.

A-kinase anchoring proteins (AKAPs) control the localization and substrate specificity of cAMP-dependent protein kinase (PKA), tetramers of regulatory (PKA-R) and catalytic (PKA-C) subunits, by binding to PKA-R subunits. Most mammalian AKAPs bind Type II PKA through PKA-RII (ref. 2), whereas dual specificity AKAPs bind both PKA-RI and PKA-RII (ref.

Identification, cloning and characterization of a novel 47 kDa murine PKA C subunit homologous to human and bovine Cbeta2.

Background: Two main genes encoding the catalytic subunits Calpha and Cbeta of cyclic AMP dependent protein kinase (PKA) have been identified in all vertebrates examined. The murine, bovine and human Cbeta genes encode several splice variants, including the splice variant Cbeta2. In mouse Cbeta2 has a relative molecular mass of 38 kDa and is only expressed in the brain.

Multiple promoter elements required for leukemia inhibitory factor-stimulated M2 muscarinic acetylcholine receptor promoter activity.

Treatment of neuronal cells with leukemia inhibitory factor (LIF) results in increased M(2) muscarinic acetylcholine receptor promoter activity. We demonstrate here that multiple promoter elements mediate LIF stimulation of M(2) gene transcription. We identify a LIF inducible element (LIE) in the M(2) promoter with high homology to a cytokine-inducible ACTG-containing sequence in the vasoactive intestinal peptide promoter.

Proteolytic processing of the p75 neurotrophin receptor and two homologs generates C-terminal fragments with signaling capability.

The 75 kDa neurotrophin receptor (p75NTR) and two neurotrophin receptor homologs (NRH1, NRH2) constitute a subfamily of the nerve growth factor/tumor necrosis factor receptor superfamily. NRH1 coexists with p75NTR in fish, amphibians, and birds but is absent in mammals, whereas NRH2 exists only in mammals. Unlike p75NTR and NRH1, NRH2 lacks a canonical extracellular ligand binding domain.

The essential role of RI alpha in the maintenance of regulated PKA activity.

Cloning of the individual regulatory (R) and catalytic (C) subunits of the cAMP-dependent protein kinase (PKA) and expression of these subunits in cell culture have provided mechanistic answers about the rules for PKA holoenzyme assembly. One of the central findings of these studies is the essential role of the RI alpha regulatory subunit in maintaining the catalytic subunit under cAMP control. The role of RI alpha as the key compensatory regulatory subunit in this enzyme family was confirmed by gene knockouts of the three other regulatory subunits in mice.

Increased basal cAMP-dependent protein kinase activity inhibits the formation of mesoderm-derived structures in the developing mouse embryo.

A targeted disruption of the RIalpha isoform of protein kinase A (PKA) was created by using homologous recombination in embryonic stem cells. Unlike the other regulatory and catalytic subunits of PKA, RIalpha is the only isoform that is essential for early embryonic development. RIalpha homozygous mutant embryos fail to develop a functional heart tube at E8.