Splicing factors control C. elegans behavioural learning in a single neuron by producing DAF-2c receptor

Alternative splicing generates protein diversity essential for neuronal properties. However, the precise mechanisms underlying this process and its relevance to physiological and behavioural functions are poorly understood. To address these issues, we focused on a cassette exon of the Caenorhabditis elegans insulin receptor gene daf-2, whose proper variant expression in the taste receptor neuron ASER is critical for taste-avoidance learning. We show that inclusion of daf-2 exon 11.5 is restricted to specific neuron types, including ASER, and is controlled by a combinatorial action of evolutionarily conserved alternative splicing factors, RBFOX, CELF and PTB families of proteins. Mutations of these factors cause a learning defect, and this defect is relieved by DAF-2c (exon 11.5þ) isoform expression only in a single neuron ASER. Our results provide evidence that alternative splicing regulation of a single critical gene in a single critical neuron is essential for learning ability in an organism.UTokyo Research掲載「飢餓の記憶の形成に必要な分子が作られるしくみ」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/production-of-a-molecule-for-memory-of-salt-concentration.htmlUTokyo Research "Production of a molecule for memory of salt concentration" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/production-of-a-molecule-for-memory-of-salt-concentration.htm

RS3PE syndrome with subsequent PMR caused by long-term DPP-4 inhibitor use

Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome has been reported in patients treated with dipeptidyl peptidase-4 inhibitors (DPP-4i). We experienced a case of RS3PE syndrome in a 73-year-old man with a history of type 2 diabetes, who developed RS3PE as a side effect of vildagliptin. Further to this, the patient developed polymyalgia rheumatica (PMR), the first such case associated with long-term DPP-4i use

Vaporized Hydrogen Peroxide and Ozone Gas Synergistically Reduce Prion Infectivity on Stainless Steel Wire

Prions are infectious agents causing prion diseases, which include Creutzfeldt–Jakob disease (CJD) in humans. Several cases have been reported to be transmitted through medical instruments that were used for preclinical CJD patients, raising public health concerns on iatrogenic transmissions of the disease. Since preclinical CJD patients are currently difficult to identify, medical instruments need to be adequately sterilized so as not to transmit the disease. In this study, we investigated the sterilizing activity of two oxidizing agents, ozone gas and vaporized hydrogen peroxide, against prions fixed on stainless steel wires using a mouse bioassay. Mice intracerebrally implanted with prion-contaminated stainless steel wires treated with ozone gas or vaporized hydrogen peroxide developed prion disease later than those implanted with control prion-contaminated stainless steel wires, indicating that ozone gas and vaporized hydrogen peroxide could reduce prion infectivity on wires. Incubation times were further elongated in mice implanted with prion-contaminated stainless steel wires treated with ozone gas-mixed vaporized hydrogen peroxide, indicating that ozone gas mixed with vaporized hydrogen peroxide reduces prions on these wires more potently than ozone gas or vaporized hydrogen peroxide. These results suggest that ozone gas mixed with vaporized hydrogen peroxide might be more useful for prion sterilization than ozone gas or vaporized hydrogen peroxide alone

Evidence for Marine Consumption During the Upper Palaeolithic at “El Pirulejo” Inland Rock- Shelter (Southern Iberia Peninsula, Spain)

During the Last Glacial Maximum and deglaciation, the Iberian Peninsula served as a faunal and human population refugium. Human foodways have always played a pivotal role in understanding social and cultural practices in prehistory. Nonetheless, the limited number of archaeological sites and human remains in this region hinders the complete understanding of these critical communities’ diet. To increase our knowledge about human consumption patterns, we selected three Magdalenian levels from the site of El Pirulejo (Southern Iberia Peninsula, Spain). These levels are characterized by a high abundance of rabbit (Oryctolagus cuniculus) remains (76–97% MNI), initially suggesting that rabbits were the primary source of protein for site inhabitants. Stable isotope analysis was conducted on two human teeth in tandem with stable isotope analysis of the rabbit teeth. Contrary to the expectations derived from the zooarchaeological analysis, rabbits were not a significant source of dietary protein. Carbon and nitrogen bulk isotopic values are the most enriched found in sampled human remains for this area and context. Our data supports aquatic food resource inclusion and increased resource diversity among Iberian hunter-gatherers during the Magdalenian. This study is consistent with previous studies that suggested a socio-economic network among human groups between inland and coastal regions in the terminal Pleistocene Southern Iberia

Specific degradation of CRABP-II via cIAP1-mediated ubiquitylation induced by hybrid molecules that crosslink cIAP1 and the target protein

AbstractManipulation of protein stability with small molecules is a challenge in the field of drug discovery. Here we show that cellular retinoic acid binding protein-II (CRABP-II) can be specifically degraded by a novel compound, SNIPER-4, consisting of (−)-N-[(2S,3R)-3-amino-2-hydroxy-4-phenyl-butyryl]-l-leucine methyl ester and all-trans retinoic acid that are ligands for cellular inhibitor of apoptosis protein 1 (cIAP1) and CRABP-II, respectively. Mechanistic analysis revealed that SNIPER-4 induces cIAP1-mediated ubiquitylation of CRABP-II, resulting in the proteasomal degradation. The protein knockdown strategy employing the structure of SNIPER-4 could be applicable to other target proteins

Spectroscopic Observations of the WZ Sge-Type Dwarf Nova GW Librae during the 2007 Superoutburst

We carried out an international spectroscopic observation campaign of the dwarf nova GW Librae (GW Lib) during the 2007 superoutburst. Our observation period covered the rising phase of the superoutburst, maximum, slowly decaying phase (plateau), and long fading tail after the rapid decline from the plateau. The spectral features dramatically changed during the observations. In the rising phase, only absorption lines of H$\alpha$, H$\beta$, and H$\gamma$ were present. Around the maximum, the spectrum showed singly-peaked emission lines of H$\alpha$, He I 5876, He I 6678, He II 4686, and C III/N III as well as absorption lines of Balmer components and He I. These emission lines significantly weakened in the latter part of the plateau phase. In the fading tail, all the Balmer lines and He I 6678 were in emission, as observed in quiescence. We find that the center of the H$\alpha$ emission component was mostly stable over the whole orbital phase, being consistent with the low inclination of the system. Comparing with the observational results of WZ Sge during the 2001 superoutburst, the same type of stars as GW Lib seen with a high inclination angle, we interpret that the change of the H$\alpha$ profile before the fading tail phase is attributed to a photoionized region formed at the outer edge of the accretion disk, irradiated from the white dwarf and inner disk.Comment: 10 pages, 9 figures, accepted for publication in PAS

Rice Annotation Database (RAD): a contig-oriented database for map-based rice genomics

A contig-oriented database for annotation of the rice genome has been constructed to facilitate map-based rice genomics. The Rice Annotation Database has the following functional features: (i) extensive effort of manual annotations of P1-derived artificial chromosome/bacterial artificial chromosome clones can be merged at chromosome and contig-level; (ii) concise visualization of the annotation information such as the predicted genes, results of various prediction programs (RiceHMM, Genscan, Genscan+, Fgenesh, GeneMark, etc.), homology to expressed sequence tag, full-length cDNA and protein; (iii) user-friendly clone / gene query system; (iv) download functions for nucleotide, amino acid and coding sequences; (v) analysis of various features of the genome (GC-content, average value, etc.); and (vi) genome-wide homology search (BLAST) of contig- and chromosome-level genome sequence to allow comparative analysis with the genome sequence of other organisms. As of October 2004, the database contains a total of 215 Mb sequence with relevant annotation results including 30 000 manually curated genes. The database can provide the latest information on manual annotation as well as a comprehensive structural analysis of various features of the rice genome. The database can be accessed at http://rad.dna.affrc.go.jp/

Evaluation of acquired color vision deficiency in glaucoma using the Rabin cone contrast test.

To evaluate acquired color vision deficiency in glaucoma by using the Rabin cone contrast test (RCCT).Twenty-seven eyes of 27 patients with glaucoma (glaucoma group) and 27 eyes of 27 normal subjects (control group) were included in this study. Long (L), medium (M), and short (S) CCT scores (L CCTs, M CCTs, and S CCTs, respectively) were measured using the RCCT in both groups. Visual field examinations were performed with Humphrey automated perimetry using the Swedish interactive thresholding algorithm 30-2, and the mean deviation (MD) was evaluated. The macular ganglion cell/inner plexiform layer (GCIPL) thickness was measured using high-definition optical coherence tomography in the glaucoma group.The mean M CCTs and S CCTs in the glaucoma group were significantly lower (P<0.05 for both comparisons) than in the control group (M CCTs, 80.7±16.8 vs. 91.9±8.22; S CCTs, 83.9±19.5 vs. 97.4±3.77, respectively); the L CCTs did not differ significantly (P=0.065) from those of the controls (91.8±12.8 vs. 97.4±3.50, respectively). The M CCTs and S CCTs were correlated significantly with those of MD (M CCTs, r=0.47; S CCTs, r=0.44; P<0.05 for both comparisons) and GCIPL thickness (M CCTs, r=0.70; P<0.0001; S CCTs, r=0.57; P<0.01).The chromatic discrimination thresholds measured by RCCT in the glaucoma group were significantly different from those measured in the control group and were correlated with the MD and GCIPL thickness. The RCCT may be useful for evaluating acquired color vision deficiency in glaucoma and may help advance current understanding of the pathophysiology of glaucomatous damage