Cardiac stem cell therapy among Clinics of Uncertain Regulatory Status (COURS): under-regulated, under-observed, incompletely understood.

BACKGROUND: Although a large body of information exists relating to cellular therapies, much of this information is either anecdotal or has been obtained from relatively small clinical trials, so that the level of evidence available to direct adoption of therapeutic approaches is quite limited. Despite this, a large number of clinics offer various cellular treatments without having gone through the processes of FDA approval. Florida is considered a "hotspot" of such sites, with a large number of clinics relative to the population. METHODS: To better understand the magnitude and scope of this issue with a specific focus on cardiovascular disease, we surveyed clinics in Florida advertising "cell therapy for heart failure". We identified only 8 clinics that "treat cardiac conditions, including heart failure." Data on administration route, cell type used, dose, success rate, cost, and training of persons performing procedures were collected when available, via email, telephone, or website information. RESULTS: A total of 20,135 patients were identified as treated: 2157 for cardiac conditions. All clinics reported administering cells intravenously, using either adipose- or umbilical-derived sources. Doses ranged from 30 to 150 million cells per treatment. The "success rate" ranged from 65 to 85%, with costs from $6000 to $20,700. Procedures were performed by PAs, MDs, and DOs. CONCLUSION: Large numbers of patients (> 10% of all 20,135 patients) have been and presumably are still are being treated for "cardiac conditions." We conclude that implementation of uniform data collection with an outcome registry, as well as creation of a public database listing FDA-approved cell-based clinical trials, would be useful to patients and the cardiovascular field at large.

Bark beetles use a spring-loaded mechanism to produce variable song patterns.

Many insects vary their song patterns to communicate different messages, but the underlying biomechanisms are often poorly understood. Here, we report on the mechanics of sound production and variation in an elytro-tergal stridulator, male Dendroctonus valens bark beetles. Using ablation experiments coupled with high-speed video and audio recordings, we show that: (1) chirps are produced using a stridulatory file on the left elytron (forewing) and a protrusion (plectrum) on the seventh abdominal segment; (2) chirps are produced by 'spring stridulation', a catch-and-release mechanism whereby the plectrum catches on a file tooth and, upon release, springs forward along the file; and (3) variability in chirp types is caused by introducing multiple catch-and-release events along the file to create regular interruptions. These results provide experimental evidence for the mechanics of elytro-tergal stridulation, and provide insight into how an insect can incorporate variability into its acoustic repertoire using a spring-loaded mechanism.

What is the password? Female bark beetles (Scolytinae) grant males access to their galleries based on courtship song.

Acoustic signals are commonly used by insects in the context of mating, and signals can vary depending on the stage of interaction between a male and female. While calling songs have been studied extensively, particularly in the Orthoptera, much less is known about courtship songs. One outstanding question is how potential mates are differentiated by their courtship signal characteristics. We examined acoustic courtship signals in a new system, bark beetles (Scolytinae). In the red turpentine beetle (Dendroctonus valens) males produce chirp trains upon approaching the entrance of a female's gallery. We tested the hypotheses that acoustic signals are honest indicators of male condition and that females choose males based on signal characteristics. Males generated two distinct chirp types (simple and interrupted), and variability in their prevalence correlated with an indicator of male quality, body size, with larger males producing significantly more interrupted chirps. Females showed a significant preference for males who produced interrupted chirps, suggesting that females distinguish between males on the basis of their chirp performances. We suggest that interrupted chirps during courtship advertise a male's size and/or motor skills, and function as the proverbial 'passwords' that allow him entry to a female's gallery.

Autophosphorylation of the C2 domain inhibits translocation of the novel protein kinase C (nPKC) Apl II.

Protein kinase Cs (PKCs) are critical signaling molecules controlled by complex regulatory pathways. Herein, we describe an important regulatory role for C2 domain phosphorylation. Novel PKCs (nPKCs) contain an N-terminal C2 domain that cannot bind to calcium. Previously, we described an autophosphorylation site in the Aplysia novel PKC Apl II that increased the binding of the C2 domain to lipids. In this study, we show that the function of this phosphorylation is to inhibit PKC translocation. Indeed, a phosphomimetic serine-glutamic acid mutation reduced translocation of PKC Apl II while blocking phosphorylation with a serine-alanine mutation enhanced translocation and led to the persistence of the kinase at the membrane longer after the end of the stimulation. Consistent with a role for autophosphorylation in regulating kinase translocation, inhibiting PKC activity using bisindolymaleimide 1 increased physiological translocation of PKC Apl II, whereas inhibiting phosphatase activity using calyculin A inhibited physiological translocation of PKC Apl II in neurons. Our results suggest a major role for autophosphorylation-dependent regulation of translocation.