Calcium dynamics regulating the timing of decision-making in <i>C. elegans</i>

Brains regulate behavioral responses with distinct timings. Here we investigate the cellular and molecular mechanisms underlying the timing of decision-making during olfactory navigation in Caenorhabditis elegans. We find that, based on subtle changes in odor concentrations, the animals appear to choose the appropriate migratory direction from multiple trials as a form of behavioral decision-making. Through optophysiological, mathematical and genetic analyses of neural activity under virtual odor gradients, we further find that odor concentration information is temporally integrated for a decision by a gradual increase in intracellular calcium concentration ([Ca2+]i), which occurs via L-type voltage-gated calcium channels in a pair of olfactory neurons. In contrast, for a reflex-like behavioral response, [Ca2+]i rapidly increases via multiple types of calcium channels in a pair of nociceptive neurons. Thus, the timing of neuronal responses is determined by cell type-dependent involvement of calcium channels, which may serve as a cellular basis for decision-making

Data from: Calcium dynamics regulating the timing of decision-making in C. elegans

Brains regulate behavioral responses with distinct timings. Here we investigate the cellular and molecular mechanisms underlying the timing of decision-making during olfactory navigation in Caenorhabditis elegans. We find that, based on subtle changes in odor concentrations, the animals appear to choose the appropriate migratory direction from multiple trials as a form of behavioral decision-making. Through optophysiological, mathematical and genetic analyses of neural activity under virtual odor gradients, we further find that odor concentration information is temporally integrated for a decision by a gradual increase in intracellular calcium concentration ([Ca2+]i), which occurs via L-type voltage-gated calcium channels in a pair of olfactory neurons. In contrast, for a reflex-like behavioral response, [Ca2+]i rapidly increases via multiple types of calcium channels in a pair of nociceptive neurons. Thus, the timing of neuronal responses is determined by cell type-dependent involvement of calcium channels, which may serve as a cellular basis for decision-making

Paliperidone palmitate: Japanese postmarketing mortality results in patients with schizophrenia

<p><b>Objective:</b> Paliperidone palmitate once-monthly injectable (PP1M) is approved in Japan and other countries for the treatment of schizophrenia. During the 6 month Japanese early postmarketing phase vigilance (EPPV) period, 32 deaths were reported. This report reviews potential contributing factors to the fatal outcomes in the PP1M-treated population.</p> <p><b>Research design and methods:</b> All spontaneously reported adverse events following PP1M use received during EPPV from 19 November 2013 to 18 May 2014 were entered into the global safety database and these events were analyzed.</p> <p><b>Results:</b> During the EPPV period, 10,962 patients were estimated to have been treated with PP1M in Japan. The mortality reporting rate during this EPPV period was higher than that observed in the US or globally after PP1M launch (5.84, 0.43, and 0.38 per 1000 patient-years, respectively), but was consistent with the mortality incidence rates (10.2 per 1000 person-years) observed during interventional clinical studies in Japan and in observational patient cohorts. Of the 32 deaths reported during the Japanese PP1M EPPV period, 19/32 (59.4%) were in patients over 50 years of age, 23/32 (71.9%) reported cardiovascular risk factors and 25/32 (78.1%) received antipsychotic polypharmacy.</p> <p><b>Conclusions:</b> Based on this review of the 32 fatal cases in the PP1M EPPV period, the observed death rate does not necessarily result from a risk with PP1M treatment in Japanese patients. The higher mortality reporting rates in Japan may be attributed to a variety of factors: the effectiveness of mortality reporting in the unique Japanese EPPV program, the advanced age of the fatal cases, high cardiovascular risk factors, multiple underlying diseases and high antipsychotic polypharmacy among the cases with fatal outcomes.</p

The data of 100 worms during odor avoidance behavior.

The Excel sheets contains x and y positions (mm), the odor concentration at the position (micro-M) and the behavioral states (Run or Pirouette) of 100 animals during 121-720 s of the odor avoidance assay. This dataset was used in Figures 1 and 2

Constitutional SAMD9L mutations cause familial myelodysplastic syndrome and transient monosomy 7

Familial myelodysplastic syndromes arise from haploinsufficiency of genes involved in hematopoiesis and are primarily associated with early-onset disease. Here we describe a familial syndrome in seven patients from four unrelated pedigrees presenting with myelodysplastic syndrome and loss of chromosome 7/7q. Their median age at diagnosis was 2.1 years (range, 1–42). All patients presented with thrombocytopenia with or without additional cytopenias and a hypocellular marrow without an increase of blasts. Genomic studies identified constitutional mutations (p.H880Q, p.R986H, p.R986C and p.V1512M) in the SAMD9L gene on 7q21, with decreased allele frequency in hematopoiesis. The non-random loss of mutated SAMD9L alleles was attained via monosomy 7, deletion 7q, UPD7q, or acquired truncating SAMD9L variants p.R1188X and p.S1317RfsX21. Incomplete penetrance was noted in 30% (3/10) of mutation carriers. Long-term observation revealed divergent outcomes with either progression to leukemia and/or accumulation of driver mutations (n=2), persistent monosomy 7 (n=4), and transient monosomy 7 followed by spontaneous recovery with SAMD9L-wildtype UPD7q (n=2). Dysmorphic features or neurological symptoms were absent in our patients, pointing to the notion that myelodysplasia with monosomy 7 can be a sole manifestation of SAMD9L disease. Collectively, our results define a new subtype of familial myelodysplastic syndrome and provide an explanation for the phenomenon of transient monosomy 7. Registered at: www.clinicaltrials.gov; #NCT00047268