In a 4-cell stage C. elegans embryo, signaling by the P2 blastomere induces anterior-posterior polarity in the adjacent EMS blastomere, leading to endoderm formation. We have taken genetic and reverse genetic approaches toward understanding the molecular basis for this induction. These studies have identified a set of genes with sequence similarity to genes that have been shown to be, or are implicated in, Wnt/Wingless signaling pathways in other systems. The C. elegans genes described here are related to wnt/wingless, porcupine, frizzled, beta-catenin/armadillo, and the human adenomatous polyposis coli gene, APC. We present evidence that there may be partially redundant inputs into endoderm specification and that a subset of these genes appear also to function in determining cytoskeletal polarity in certain early blastomeres.

There is growing interest in non-invasive brain stimulation (NIBS) as a novel treatment option for substance-use disorders (SUDs). Recent momentum stems from a foundation of preclinical neuroscience demonstrating links between neural circuits and drug consuming behavior, as well as recent FDA-approval of NIBS treatments for mental health disorders that share overlapping pathology with SUDs. As with any emerging field, enthusiasm must be tempered by reason; lessons learned from the past should be prudently applied to future therapies. Here, an international ensemble of experts provides an overview of the state of transcranial-electrical (tES) and transcranial-magnetic (TMS) stimulation applied in SUDs. This consensus paper provides a systematic literature review on published data-emphasizing the heterogeneity of methods and outcome measures while suggesting strategies to help bridge knowledge gaps. The goal of this effort is to provide the community with guidelines for best practices in tES/TMS SUD research. We hope this will accelerate the speed at which the community translates basic neuroscience into advanced neuromodulation tools for clinical practice in addiction medicine.

Objective-To investigate the clinical features and natural history of mal de debarquement (MdD).Design-Retrospective case review with follow-up questionnaire and telephone interviews. Setting-University Neurotology Clinic.Patients-Patients seen between 1980 and 2006 who developed a persistent sensation of rocking or swaying for at least 3 days after exposure to passive motion.Main outcome measure-Clinical features, diagnostic testing, and questionnaire responses.Results-Of 64 patients (75 % women) identified with MdD, 34 completed follow-up questionnaires and interviews in 2006. Most patients had normal neurological exams, ENGs and brain MRIs. The average age of the first MdD episode was 39 ± 13 years. A total of 206 episodes were experienced by 64 patients. Of these, 104 episodes (51 %) lasted > 1 month; 18 %, > 1 year; 15 %, > 2 years; 12 %, > 4 years, and 11 %, > 5 years. Eighteen patients (28 %) subsequently developed spontaneous episodes of MdD-like symptoms after the initial MdD episode. There was a much higher rate of migraine in patients who went on to develop spontaneous episodes (73 %) than in those who did not (22 %). Subsequent episodes were longer than earlier ones in most patients who had multiple episodes. Re-exposure to passive motion temporarily decreased symptoms in most patients (66 %). Subjective intolerance to visual motion increased (10 % to 66 %) but self-motion sensitivity did not (37 % to 50 %) with onset of MdD.Conclusion-The majority of MdD episodes lasting longer than 3 days resolve in less than one year but the probability of resolution declines each year. Many patients experience multiple MdD episodes. Some patients develop spontaneous episodes after the initial motion-triggered episode with migraine being a risk factor.