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Objectives Pembrolizumab is a standard treatment for non-small cell lung cancer (NSCLC) with high-PD-L1 expression; however, its effect is dismal in patients with poor physical condition. Additionally, the effect of immunotherapy is generally limited in NSCLC harboring driver mutations such asEGFR, ALK, or RET gene aberrations. Results We report the beneficial effect of pembrolizumab in a patient with poor performance status and PD-L1+ lung adenocarcinoma with theCCDC6–RET fusion gene and co-occurring NF1/TP53 mutations, complicated by multiple cancer-associated thrombi and respiratory failure. Conclusions Further studies are warranted to establish the role of co-occurring NF1/TP53 mutations as a positive predictive biomarker for pembrolizumab in NSCLC harboring RET fusion genes.

Due to increasing anthropogenic impacts on deep-sea hydrothermal vent ecosystems, it is essential to understand population structure and maintenance through larval recruitment and recovery of vent faunas after disturbances. In this study, we quantified vent animal recruitment in the Okinawa Trough, in the western Pacific Ocean. This is the first study to investigate recruitment patterns at a man-made hydrothermal vent. Colonization plates were deployed at three sites. Site 1 manifested new hydrothermal shimmering with small chimneys, white bacterial mats, and some alvinocaridid shrimp that arrived after drilling. Site 2 showed no evidence of newly arrived foundation species after drilling, and Site 3 had pre-existing animal communities in the vicinity of the new vent. Twenty-two months after deployment, colonization plates were retrieved and recruited animals were inventoried. Species composition and abundance differed among sites, but relatively high similarity in species composition was observed at Sites 1 and 3, though not at Site 2. Newly established communities on the plates at Sites 1 and 2 (no pre-existing fauna) showed lower species richness and abundance than at Site 3. Differences in abundance and size-frequency distributions of major recruits on the plates (i.e. Lepetodrilus nux , Bathymodiolus spp.) suggest the importance of reproductive and early life-history characteristics in spatial variability of recruitment. Lepetodrilus nux populations established on the plates at Site 1 showed high genetic connectivity. These results illustrate the importance of localized recruitment, which may have a significant impact on sustainability of vent faunal populations, despite the existence of regional metapopulations.

The one-pot reaction between bis(hydroxymethyl)phenol derivatives and diamines or triamines afforded novel azacalixarenes with bridged structures. Basket-type macrocycles of cone conformations, molecules that contained two aza[3.1.1.1]calixarene skeletons connected by a chain, or novel saucer-type azacalixarenes were obtained from the reaction. Structures of some of them were determined by crystallographic analyses.

The present study aimed to generate genome-wide single nucleotide polymorphisms (SNPs) for the deep-sea mussel Bathymodiolus platifrons via a combination of genome survey sequencing and the type IIB endonuclease restriction-site associated DNA (2b-RAD) sequencing, assess the potential use of SNPs in detecting fine-sale population genetic structure and signatures of divergent selection, as well as their cross-species application in other bathymodioline mussels. Genome survey sequencing was conducted for one individual of B. platifrons. De novo assembly resulted in 781,720 sequences with a scaffold N50 of 2.9 kb. Using these sequences as a reference, 9307 genome-wide SNPs were identified by 2b-RAD for 28 B. platifrons individuals collected from a seep and a vent population. Among these SNPs, nine outliers showed significant evidence for divergent selection, and their positions in the genes or scaffolds were identified. The F ST estimated based on the putative neutral SNPs was low (0.0126) indicating the two B. platifrons populations having a high genetic connectivity. However, the permutation test detected significant differences ( P Bathymodiolus japonicus , Bathymodiolus aduloides and Idas sp. with different phylogenetic distances from B. platifrons. Overall, our study has demonstrated the feasibility and effectiveness of combining genome survey sequencing and 2b-RAD to rapidly generate genomic resources for use in fine-scale population genetic studies, and various cross-species applications.

Although many deep-sea species are considered to have transoceanic distribution, this assumption has rarely been critically tested. Using Hesiolyra (Hesionidae) as a case study, we showed that careful molecular and morphological analyses are required for refuting/accepting claims about such wide distribution. Hesiolyra is a genus of polychaetes commonly found in hydrothermal vents of the Eastern Pacific, Atlantic and Indian Ocean. Nevertheless, H. bergi Blake, 1985, a species originally described from the Eastern Pacific Rise (EPR), is the only recognized species in this genus. Phylogenetic analyses based on the COI and 16 S rRNA genes revealed two monophyletic clades that were distinct from a clade consisting of H. bergi sequences. With the average K2P distances from 7.69% to 14.17% for the COI gene, we erected two new species of Hesiolyra, herein named as H. longqiensis n. Sp. from the Southwest Indian Ridge (SWIR) and H. heteropoda n. Sp. from the Central Indian Ridge (CIR) and the Carlsberg Ridge (CR). Among them, H. longqiensis n. Sp. from SWIR is more closely related to H. bergi from EPR than to H. heteropoda n. Sp. from CIR and CR, which called for alternative hypotheses on how historical oceanographic conditions might have driven the dispersal and speciation of this genus along the global mid-ocean ridges. Morphologically, the two newly described species can be easily distinguished from H. bergi. The notopodia and neuropodia of H. bergi and H. longqiensis n. Sp., are of similar sizes, but the morphology of their lyrate chaetae and their dorsal cirri alternation patterns are different. In H. heteropoda n. Sp., the notopodia are remarkably slimmer than the neuropodia, and it does not possess lyrate chaetae. Overall, in this study we have described two new species of Hesiolyra from the Indian Ocean ridges and show that the distribution of H. bergi is restricted to the Eastern Pacific Rise. Future exploration of other mid-ocean ridges is required to discover the true diversity of this genus of polychaetes inhabiting hydrothermal vent fields.

After the adoption of the Aichi Target, data accumulation and evaluation regarding biodiversity have progressed rapidly. The use of ecologically and biologically significant areas (EBSAs) criteria to evaluate important areas enables the identification of effective and prioritized areas for ecosystem management. This includes strategic environmental assessment and discussions aimed at establishing protected marine areas based on scientific data. This paper reviews previous and current ideas as well as the methods used, for the identification of EBSAs. In particular, the following issues are addressed: problems associated with different types of marine ecosystems in the Japanese Archipelago, such as seagrass and seaweed beds, coral reefs, offshore pelagic plankton, and deep-sea benthic ecosystems; and problems associated with the integration of multiple criteria that are not totally exclusive. Several candidate variables accounting for each of the 7 criteria used to identify ecologically important areas are presented. Data availability is the most important criterion that allowed for the comprehensive evaluation of different types of ecosystems in the same localities. In particular, for coastal ecosystems such as seagrass, seaweed beds, and coral reefs, it is possible to carry out broad spatial comparisons using variables representing most of these 7 criteria. Regarding methods for the quantitative evaluation of each criterion and their integration, application of these methods to kelp forest ecosystems in Hokkaido, Northern Japan is presented as a case study.

Growing evidence suggests that a broad range of behavioral anomalies in people with autism spectrum disorder (ASD) can be linked with morphological and functional alterations in the brain. However, the neuroanatomical underpinnings of ASD have been investigated using either structural magnetic resonance imaging (MRI) or diffusion tensor imaging (DTI), and the relationships between abnormalities revealed by these two modalities remain unclear. This study applied a multimodal data-fusion method, known as linked independent component analysis (ICA), to a set of structural MRI and DTI data acquired from 46 adult males with ASD and 46 matched controls in order to elucidate associations between different aspects of atypical neuroanatomy of ASD. Linked ICA identified two composite components that showed significant between-group differences, one of which was significantly correlated with age. In the other component, participants with ASD showed decreased gray matter (GM) volumes in multiple regions, including the bilateral fusiform gyri, bilateral orbitofrontal cortices, and bilateral pre- and post-central gyri. These GM changes were linked with a pattern of decreased fractional anisotropy (FA) in several white matter tracts, such as the bilateral inferior longitudinal fasciculi, bilateral inferior fronto-occipital fasciculi, and bilateral corticospinal tracts. Furthermore, unimodal analysis for DTI data revealed significant reductions of FA along with increased mean diffusivity in those tracts for ASD, providing further evidence of disrupted anatomical connectivity. Taken together, our findings suggest that, in ASD, alterations in different aspects of brain morphology may co-occur in specific brain networks, providing a comprehensive view for understanding the neuroanatomy of this disorder., Highlights • Structural alterations of gray (GM) and white matter (WM) in ASD were investigated. • Linked independent component analysis was used for multimodal data analysis. • Alterations of GM and WM in ASD co-occurred in cognitive and affective networks. • Results reveal an integrative view of multiple aspects of structural changes in ASD.

Individuals with autism spectrum disorders (ASD) often have sensory processing abnormalities. However, limited measures that assess these problems in adults with ASD have been developed till date, particularly in Japan. Robertson and Simmons (2012) developed a self-rating scale to investigate sensory sensitivity: the Glasgow Sensory Questionnaire (GSQ). In the present study, we developed a Japanese version of GSQ and investigated sensory abnormalities in adults with ASD. We compared results of the Japanese version of GSQ in adults between an ASD group ( n = 64) and a control group ( n = 70). In addition, we also administered these individuals with the autism spectrum quotient (AQ), which is a questionnaire for assessing autistic traits. The Japanese version of GSQ scores was significantly higher in the ASD group than that in the control group. The total GSQ score and each sensory subscale showed a positive correlation with AQ in the total study sample. These results indicate that individuals with pronounced autistic traits have more frequent and extreme sensory processing problems compared with that in individuals with less pronounced autistic traits. We also assessed validity of the new test. Cronbach's α of the questionnaire was calculated, and its high value indicates that the Japanese version of GSQ has high reliability.

Deep-sea polychaetes in the genus Amphisamytha are well known from numerous hydrothermal vents and hydrocarbon seeps in the Pacific and Atlantic oceans. Records from the Indian Ocean, however, have not been characterized morphologically or genetically. Here, we examined specimens taken from deep-sea vents on three mid-ocean ridges in the Indian Ocean, including Southwest Indian Ridge (SWIR), Central Indian Ridge (CIR), and Carlsberg Ridge (CR), and re-assessed phylogenetic relationships within the genus including the Indian Ocean records. Multi-gene phylogenetic analyses using a concatenated alignment of 16S rRNA, 18S rRNA, 28S rRNA, and COI genes recovered four distinct, hitherto unreported, lineages in the Indian Ocean interpreted to represent four undescribed species. One of these, formally described as Amphisamytha marisindica n. sp. herein, is characterized by relatively large body size, conspicuous nuchal organs, smooth abdominal glandular pads, and 17–19 abdominal chaetigers. It was found to span all three ridges, representing one of the most widespread species in the genus. Two further sympatric species, Amphisamytha collaris n. sp. and Amphisamytha sp. Longqi, appeared to prefer relict/inactive chimneys in the Longqi field, SWIR. Amphisamytha collaris n. sp. is unique for its V-shaped collar on the posterior lobe of prostomium. Due to the scarcity and condition of the samples available, Amphisamytha sp. Longqi was not formally described. Lastly, Amphisamytha wocanensis n. sp. was only recorded from the Wocan field, CR, and no reliable morphological characteristics could separate it from A. carldarei and A. fauchaldi, indicative of cryptic speciation. Monophyly of the genus Amphisamytha was not supported in the current phylogeny, warranting further revisions at the genus level. The four Indian Ocean species were placed into two well-supported clades: Amphisamytha sp. Longqi and A. collaris n. sp. formed sister-relationship with the Southwest Pacific A. julianeae, while A. marisindica n. sp. and A. wocanensis were recovered as crown taxa in a clade composed of their East Pacific and Atlantic congeners, indicating two separate evolutionary lineages of Amphisamytha meeting in the Indian Ocean. The sister-relationship of species from the Carlsberg Ridge and East Pacific suggests extreme long-distance dispersal of their ancestor, or points towards numerous undescribed or extinct species belonging to this clade.

Hydrothermal vent fields in the deep-sea are highly productive and host highly specific animals adapted to chemosynthesis-based ecosystems. Knowledge on the distribution range of dominant fauna in these ecosystems help elucidate their biogeography, as well as contribute key baseline data for managing conservation strategies. Here, we report faunal compositions for two hydrothermal vent fields, Myojin-sho Caldera and the Bayonnaise Knoll, on the Izu–Bonin–Mariana (IBM) Arc, a submarine volcanic arc system in the western Pacific, and examined biogeographical subdivisions within. Similarity indices and subsequent analyses based on species presence/absence data revealed three groups, namely those in the Izu area, shallower vents in the Bonin–Mariana area, and deeper vents in the Bonin–Mariana area. This pattern of subdivision indicates that water depth and tectonic discontinuity, in this case the Sofugan Tectonic Line, contribute to the distribution ranges of vent specific animals on the IBM Arc, but the conjunction of Mariana and West Mariana ridges have little contribution. This is the first data for faunal subdivision of vents on the 9000 km-long submarine volcanic chain of the western Pacific extending further south of the IBM Arc, and further analyses on faunal distribution of other vents in this area and larval ecology of vent animals are required to understand subdivisions across the entire chain.

Barnacles of the superfamily Coronuloidea are obligate epibionts of various marine mammals, marine reptiles and large crustaceans. We used five molecular markers: 12S rDNA, 16S rDNA, 18S rDNA, 28S rDNA and Histone 3 to infer phylogenetic relationships among sixteen coronuloids, representing most of the recent genera of barnacles of this superfamily. Our analyses confirm the monophyly of Coronuloidea and that this superfamily and Tetraclitoidea are sister groups. The six-plated Austrobalanus clusters with these two superfamilies. Based on BEAST and ML trees, Austrobalanus is basal and sister to the Coronuloidea, but the NJ tree places Austrobalanus within the Tetraclitoidae, and in the MP tree it is sister to both Coronuloidea and Tetraclitoidae. Hence the position of Austrobalanus remains unresolved. Within the Coronuloidea we identified four clades. Chelonibia occupies a basal position within the Coronuloidea which is in agreement with previous studies. The grouping of the other clades does not conform to previous studies. Divergence time analyses show that some of the time estimates are congruent with the fossil record while some others are older, suggesting the possibility of gaps in the fossil record.

Deep-sea hydrothermal vents and cold seeps are scattered and limited habitats, and species that are confined to these benthic habitats often have a planktonic larval stage in their life history to maintain dispersal and gene flow among discrete populations. We have reared the larvae of Ashinkailepas seepiophila , inhabiting inactive vents and active cold seeps, through their entire larval development under atmospheric pressure. Using two temperatures (4 °C, 10 °C) we examined whether larval development resembles other vent species in being affected by thermal stimulation. Under laboratory conditions, A. seepiophila completed larval development in 65 days at 4 °C. This is considerably shorter than the 100 days previously reported to be required at the same temperature by Neoverruca sp., a species confined to inhabiting active vents. Also in contrast to Neoverruca sp., A. seepiophila did not drastically shorten the developmental period from nauplius VI to cyprid when exposed to temperature of 10 °C. We conclude that there is no need for late naupliar stages of A. seepiophila to develop into cyprids more quickly at elevated temperatures because this species does not inhabit active vents. The difference in response to water temperature during larval development may contribute to the separated distribution of the two species at active vents ( Neoverruca sp.) and inactive vents and cold seep ( A. seepiophila ) environments.

People with Asperger's syndrome (AS) experience mental comorbidities, and behavioral symptoms that can deepen social isolation and handicaps. We compared the frequency of mental and behavioral symptoms, motor abnormality, and life history between adults with AS and those with no mental disorders but with disturbance of social functions and communication skills (ND) from our outpatient clinic. Participants with AS (n = 99) as compared with ND subjects (n = 63) showed significant higher rate of depressive mood, anxiety, unstable emotion, mood swings, oversensitivity to normal situation obsessive compulsive symptoms, persecutory idea, loss of energy, insomnia carelessness, restlessness, confusion in new environments, episodic agitation, inflexible adherence, egocentric behavior, self harm, circumscribed interest, poor lifestyle habits, non-athleticism, clumsiness, bulling at school, school non-attendance, social withdrawal, and lack of friendships. In AS, emotional instability and confusion in new environments might lead to social isolation. The findings demonstrated that individuals with AS experience greater social isolation and distress, as well as a wider range of mental and behavioral symptoms and disturbances of motor skills as compared to healthy subjects with disturbances of social functions and communication skills. These factors are interrelated and may be used as supplementary methods for differential diagnosis of AS from other conditions.

Little is known about the cognitive profiles of high-functioning Pervasive Developmental Disorders (PDD) in adults based on the Wechsler Intelligence Scale III (WAIS-III). We examined cognitive profiles of adults with no intellectual disability (IQ > 70), and in adults with Asperger's disorder (AS; n = 47), high-functioning autism (HFA; n = 24), and pervasive developmental disorder not otherwise specified (PDDNOS; n = 51) using the WAIS-III. Verbal Intelligence (VIQ)–Performance Intelligence (PIQ) differences were detected between the three groups. Full Intelligence (FIQ) and VIQ scores were significantly higher in AS than in HFA and PDDNOS. Vocabulary, Information, and Comprehension subtest scores in the Verbal Comprehension index were significantly higher in AS than in the other subgroups, while Digit-Symbol Coding and Symbol Search subtest scores in the Processing Speed index were significantly lower in HFA. The findings demonstrated cognitive profiles characteristic of adults with high-functioning PDD.

Dysfunction of the prefrontal cortex has been previously reported in individuals with Asperger's disorder. In the present study, we used multi-channel near-infrared spectroscopy (NIRS) to detect changes in the oxygenated hemoglobin concentration ([oxy-Hb]) during two verbal fluency tasks. The subjects were 20 individuals with Asperger's disorder and 18 age- and IQ-matched healthy controls. The relative [oxy-Hb] in the prefrontal cortex was measured during the category and letter fluency tasks. The mean total [oxy-Hb] during the category fluency task did not differ significantly between the groups; however, during the letter fluency task, the mean [oxy-Hb] in persons with Asperger's disorder was significantly lower than that in controls. These results suggested task-relevant or task-specific prefrontal dysfunction in persons with Asperger's disorder.

Hyperventilation (HV) is widely used to induce EEG abnormalities and epileptic seizures. However, it is still controversial how long it should be done in routine EEG. We analyzed 1,184 routine EEG data recorded in our institution between October, 2016 and September, 2017. Among them, 970 patients tried to perform HV lasting 4 min, and 949 patients completed it age mean, range. During HV, interictal epileptiform discharges (IED) were induced in 82 patients (9%). Generalized IED were seen in 70 patients, focal IED in eight, bi-temporal slow wave in three, and rhythmic theta activity (focal) in one. IED appeared only after 3-min HV in 11 patients (13%) out of 82. Epileptic seizures were induced by HV in 25 patients (3%). Absence seizures occurred in 23 patients, and focal seizures in two. Two patients (12%) had seizures after 3-min HV. No adverse event occurred during 4-min HV, not only during this study period, but also more than 40 years of our practice. We concluded that 4-min HV is effective and safe for epilepsy patients.

application/pdf, The elongation of poly(A) tails in cytoplasm is essential for oogenesis and early embryogenesis in Xenopus laevis. mGLD-2 is a mouse homologue of Xenopus cytoplasmic poly(A) polymerase xGLD-2. We found an association of mGLD-2 with cytoplasmic polyadenylation components, CPEB and CPSF described in Xenopus oocytes. To clarify the role of mGLD-2 in mouse, we produced an mGLD-2 disrupted mouse line by homologous recombination. In spite of the ubiquitous expression of mGLD-2, the disrupted mice were apparently normal and healthy. Moreover, it was demonstrated that mGLD-2 disruption did not affect the poly(A) tail elongation in oocytes using reporter RNAs. Coincide with these observations, the maturation of the oocytes was normal and the mice were fertile. Thus mGLD-2 is dispensable for full-term development and oogenesis. Our results also indicate that there is another source of cytoplasmic poly(A) polymerase in mouse.

Cytoplasmic polyadenylation of mRNAs is involved in post-transcriptional regulation of genes, including translational activation. In addition to yeast Cid1 and Cid13 and mouse TPAP, GLD-2 has been recently identified as a cytoplasmic poly(A) polymerase in Caenorhabditis elegans and Xenopus oocytes. In this study, we have characterized mouse GLD-2, mGLD-2, in adult tissues, meiotically maturing oocytes, and NIH3T3 cultured cells. mGLD-2 was ubiquitously present in all tissues and cells tested. mGLD-2 was localized in the nucleus as well as in the cytoplasm of somatic, testicular, and cultured cells. Transfection of expression plasmids encoding mGLD-2 and the mutant proteins into NIH3T3 cells revealed that a 17-residue sequence in the N-terminal region of mGLD-2 probably acts as a localization signal required for the transport into the nucleus. Analysis of reverse transcriptase-polymerase chain reaction indicated the presence of mGLD-2 mRNA in the oocytes throughout meiotic maturation. However, 54-kDa mGLD-2 was found in the oocytes only at the metaphases I and II after germinal vesicle breakdown, presumably due to translational control. When mGLD-2 synthesis was artificially inhibited and enhanced by injection of double-stranded and polyadenylated RNAs into the germinal vesicle-stage oocytes, respectively, oocyte maturation was significantly arrested at the metaphase-I stage. These results suggest that mGLD-2 may act in the ooplasm on the progression of metaphase I to metaphase II during oocyte maturation.

Mucopolysaccharidosis II (Hunter syndrome), a lysosomal storage disorder caused by a deficiency of iduronate-2-sulfatase (IDS), has variable clinical phenotypes. Total by nearly 400 different mutations have been identified in IDS gene from patients with Hunter syndrome. Herein, we reported a patient who has a novel mutation in IDS gene with a severe clinical phenotype. Genetic analysis of the IDS gene revealed a novel 1-bp deletion in position c.1053T in exon 8 and resulting in a frameshift with a premature stop codon. Enzyme replacement therapy (ERT) using idursulfase (Elaprase®) was conducted to the patient and it improved hepatosplenomegaly, white blood cells and platelets number, and decreased the level of urinary glycosaminoglycan. ERT was proved to be effective at least in part in even an adult patient with severe type of Hunter syndrome.

As candidates for insulin mimetics, we prepared five vanadyl—dithiocarbamate complexes with VO(S 4 ) coordination mode, and determined their structures by elemental analysis, visible absorption, IR and electron spin resonance spectra; the five complexes were bis( N,N -dimethyldithiocarbamate)oxovanadium(IV) (VO-DMD), bis( N,N -diethyldithiocarbamate)oxovanadium(IV) (VO-DED), bis(pyrrolidine- N -dithiocarbamate)oxovanadium(IV) (VO-PYD), bis( N -methyl, N ′- d -glucamine-dithiocarbamate)oxovanadium(IV) (VO-MGD) and bis(sarcosine- N -dithiocarbamate)oxovanadium(IV) (VO-SAD). The insulin-mimetic activities were evaluated by in vitro and in vivo experiments. These complexes inhibited the release of free fatty acid (FFA) from isolated rat adipocytes, similar to the action of insulin. Among them, VO-PYD and VO-SAD complexes were found to be the most effective. In addition, the VO-PYD complex promoted the incorporation of glucose in rat L6 muscle cells. Based on these in vitro observations, both VO-PYD and VO-SAD complexes were given to streptozotocin-induced diabetic rats (STZ-rats) intraperitoneally or orally. Serum glucose levels of STZ-rats dropped from hyperglycemic levels to the normal range within 1 or 2 days after both intraperitoneal and oral administrations of the complexes. To understand the insulin-mimetic action of the VO-PYD complex, the organ distribution of vanadium was investigated. In normal rats treated with VO-PYD complex, vanadium was distributed in almost all tissues, indicating that the action of vanadium is not peripheral. In addition, vanadium was found in bone and kidney when VO-PYD was given. On the basis of these results, the VO-PYD complex is indicated to be a good agent to treat insulin-dependent diabetes in experimental animals.

The antinociceptive effects produced by the intracerebroventricular (i.c.v.) injection of dermorphin and [D-Arg 2 ] dermorphin were compared in conscious mice, using the combined administration of peptidase inhibitors. Nociception was assessed using a tail pressure assay. Dermorphin-induced antinociception was not potentiated by simultaneous administration of amastatin or captopril as judged from the ED 50 values. Co-administration of dermorphin and amastatin gave a longer duration than with dermorphin alone, whereas there was no significant effect on duration with captopril. The antinociceptive activity of dermorphin was significantly enhanced when the heptapeptide was injected simultaneously with both peptidase inhibitors. This result indicates that the heptapeptide sequence is required for the full expression of intrinsic opioid activity of dermorphin. In contrast, co-administration of amastanin brought about a significant enhancement of the antinociceptive activity induced by i.c.v. administration of [D-Arg 2 ]dermorphin, whereas the effect of [D-Arg 2 ]dermorphin was markedly decreased by the concurrent administration of captopril or thiorphan. The potency of captopril was much greater than that of thiorphan. The present results suggest that [D-Arg 2 ]dermorphin may be transformed metabolically to a peptide which has potent antinociceptive activity.