26 research outputs found
A Forward Genetic Screen for Molecules Involved in Pheromone-Induced Dauer Formation in Caenorhabditis elegans
Animals must constantly assess their surroundings and integrate sensory cues to make appropriate behavioral and developmental decisions. Pheromones produced by conspecific individuals provide critical information regarding environmental conditions. Ascaroside pheromone concentration and composition are instructive in the decision of Caenorhabditis elegans to either develop into a reproductive adult or enter into the stress-resistant alternate dauer developmental stage. Pheromones are sensed by a small set of sensory neurons, and integrated with additional environmental cues, to regulate neuroendocrine signaling and dauer formation. To identify molecules required for pheromone-induced dauer formation, we performed an unbiased forward genetic screen and identified phd (pheromone response-defective dauer) mutants. Here, we describe new roles in dauer formation for previously identified neuronal molecules such as the WD40 domain protein QUI-1 and MACO-1 Macoilin, report new roles for nociceptive neurons in modulating pheromone-induced dauer formation, and identify tau tubulin kinases as new genes involved in dauer formation. Thus, phd mutants define loci required for the detection, transmission, or integration of pheromone signals in the regulation of dauer formation. ยฉ 2016 Neal et al.1
Impact of Left Atrial Appendage Morphology on Recurrence in Embolic Stroke of Undetermined Source and Atrial Cardiopathy
Background: The left atrial appendage (LAA) is a major source of thrombus and non-chicken wing (CW). LAA morphology is a risk factor for embolic events in atrial fibrillation. However, the association of non-CW morphology with embolic stroke recurrence is unknown in patients with embolic stroke of undetermined source (ESUS) and atrial cardiopathy.Methods: We conducted retrospective analyses using a prospective institutional stroke registry (2013โ2017). Patients with ESUS and atrial cardiopathy were enrolled. Atrial cardiopathy was diagnosed if an increased left atrial diameter (>40 mm, men; >38 mm, women), supraventricular tachycardia, or LAA filling defect on computed tomography (CT) were present. Patients admitted >24 h after onset were excluded. LAA morphology was evaluated using CT and categorized into CW vs. non-CW types. The primary outcome was embolic stroke recurrence. Multivariable Cox proportional hazards models were used to examine the independent association between LAA morphology and outcome.Results: Of 157 patients, 81 (51.6%) had CW LAA morphology. The median follow-up was 41.5 (interquartile range 12.3โ58.5) months corresponding to 509.8 patient years. In total, 18 participants experienced embolic stroke recurrences (3.80 per 100 patient-years). Non-CW morphology was more associated with embolic stroke recurrence than CW morphology (hazard ratio (HR), 3.17; 95% confidence interval (CI), 1.13โ8.91; p = 0.029). After adjusting for CHA2DS2-VASc score and number of potential embolic sources, non-CW morphology showed an independent association with outcome (adjusted HR, 2.90; 95% CI, 1.02โ8.23; p = 0.045).Conclusions: The LAA morphology types may help identify high risk of embolic stroke recurrence in ESUS with atrial cardiopathy. LAA morphology in atrial cardiopathy may provide clues for developing therapies tailored to specific mechanisms
Predictive biomarkers for 5-fluorouracil and oxaliplatin-based chemotherapy in gastric cancers via profiling of patient-derived xenografts.
Gastric cancer (GC) is commonly treated by chemotherapy using 5-fluorouracil (5-FU) derivatives and platinum combination, but predictive biomarker remains lacking. We develop patient-derived xenografts (PDXs) from 31 GC patients and treat with a combination of 5-FU and oxaliplatin, to determine biomarkers associated with responsiveness. When the PDXs are defined as either responders or non-responders according to tumor volume change after treatment, the responsiveness of PDXs is significantly consistent with the respective clinical outcomes of the patients. An integrative genomic and transcriptomic analysis of PDXs reveals that pathways associated with cell-to-cell and cell-to-extracellular matrix interactions enriched among the non-responders in both cancer cells and the tumor microenvironment (TME). We develop a 30-gene prediction model to determine the responsiveness to 5-FU and oxaliplatin-based chemotherapy and confirm the significant poor survival outcomes among cases classified as non-responder-like in three independent GC cohorts. Our study may inform clinical decision-making when designing treatment strategies
์์๊ผฌ๋ง์ ์ถฉ์ G ๋จ๋ฐฑ์ง ์ฐ๊ฒฐ ์์ฉ๊ธฐ๋ฅผ ํตํ ๋๋ ์์กด์ ํ๊ฐ ํ๋์ ์ ํ์ ๊ดํ ๊ธฐ์ ์ฐ๊ตฌ
G-๋จ๋ฐฑ์ง ์ฐ๊ฒฐ ์์ฉ๊ธฐ, Chemotaxis, ํํผํ๋, Dimethyl trisulfide, ์์๊ผฌ๋ง์ ์ถฉAnimals detect and discriminate countless environmental chemicals for their wellbeing and survival. Although a single chemical can trigger opposing behavioral responses depending on its concentration, the mechanisms underlying such a concentration-dependent switching remain poorly understood. Here, we show that C. elegans exhibits either attraction or avoidance of the bacteria-derived volatile chemical dimethyl trisulfide (DMTS), depending on its concentration. This behavioral switching is mediated by two different types of chemosensory neurons, both of which express the DMTS-sensitive seven-transmembrane G protein-coupled receptor (GPCR) SRI-14. These two sensory neurons share downstream interneurons that process and translate DMTS signals via distinct glutamate receptors to generate the appropriate behavioral outcome. Thus, our results present one mechanism by which an animal connects two distinct types of chemosensory neurons detecting a common ligand to alternate downstream circuitry, thus efficiently switching between specific behavioral programs based on ligand concentration.|๋๋ฌผ๋ค์ ๊ทธ๋ค์ ์์กด๊ณผ ๋ฒ์ ๋ณด์กด์ ์ํด์ ์ฃผ๋ณํ๊ฒฝ์์ ๋ฐ์ํ๋ ์๋ง์ ํํ๋ฌผ์ง๋ค์ ๊ฐ์งํ๊ณ ๊ตฌ๋ณํด๋ธ๋ค. ๊ทธ ์ค์์ ์ฌ๋ฏธ์๋ ํ์ ์ค ํ๋๋, ์ฌ๋ฌ ์ข
์ ๋๋ฌผ๋ค์ด ๋์ผํ ํ๊ฐ๋ฌผ์ง์ ๋ํด ๋๋๋ฅผ ๋ค๋ฅด๊ฒ ๊ฐ์งํด ๋ด๊ณ ๊ทธ ๋๋์ ๋ฐ๋ผ ์ ๋ฐ๋์ ํ๋์ ๋ณด์ธ๋ค๋ ์ ์ด๋ค. ํ์ง๋ง ์ด๋ฌํ ๋๋ ์์กด์ ํ๊ฐ ํ๋ ์ ํ์ ๋ถ์์ ๊ธฐ์์ ๋ํด์๋ ์์ง ์ ์๋ ค์ง์ง ์์์๋ค. ์ด ์ฐ๊ตฌ๋ฅผ ํตํ์ฌ ๋ณธ ์ฐ๊ตฌ์๋ ์์๊ผฌ๋ง์ ์ถฉ์ด ๊ทธ๋ค์ ๋จน์ด์ ๊ฐ์ผ์์ ์ธ๊ท ์ข
๋ค์์ ๊ณตํต์ผ๋ก ๋ถ๋น๋๋ DMTS๋ผ๋ ํฉํํฉ๋ฌผ์ ๋ํด ๊ทธ ๋๋์ ๋ฐ๋ผ ์ข์ํ๊ธฐ๋ ํ๊ณ ์ซ์ดํ๊ธฐ๋ ํ๋ ๋๋ ์์กด์ ํ๊ฐ ํ๋์ ๋ณด์์ ํ์ธํ์๋ค. ๋ํ ์ด๋ฌํ ํ๋์ ์ ํ์ SRI-14 G ๋จ๋ฐฑ์ง ์ฐ๊ฒฐ ์์ฉ๊ธฐ๋ฅผ ๋ฐํํ๊ณ ์๋ ๋ค๋ฅธ ๋์ข
๋ฅ์ AWC ์ ASH ๊ฐ๊ฐ๋ด๋ฐ๋ค์ ์ํด์ ๋งค๊ฒ ๋๋ค๋ ๊ฒ์ ํ์ธํ์๋ค. ๋ณธ ์ฐ๊ตฌ์์ ๋์ฐ๋ณ์ด ์คํ์ ์ํ๋ฉด ๋ ๊ฐ๊ฐ๋ด๋ฐ ์ค AWC ํ๊ฐ ๋ด๋ฐ์ด ์๋ ์ ์ถฉ์ ๊ฒฝ์ฐ ๋ฎ์ ๋๋์ DMTS์ ๋ํ ์ ํธ๋ฐ์์ด ์ฌ๋ผ์ก์ผ๋ฉฐ, ASH ํต๊ฐ ๋ด๋ฐ์ด ์๋ ์ ์ถฉ์ ๊ฒฝ์ฐ ๋์ ๋๋์ DMTS์ ๋ํ ํํผ๋ฐ์์ ๋ณด์ด์ง ์๋ ๊ฒ์ ํ์ธํ์๋ค. AWC์ ASH๋ด๋ฐ์ ๊ณตํต์ ์ผ๋ก SRI-14 G ๋จ๋ฐฑ์ง ์ฐ๊ฒฐ ์์ฉ๊ธฐ๋ฅผ ๋ฐํํ๊ณ ์๊ธฐ ๋๋ฌธ์ ์ด SRI-14 ๋จ๋ฐฑ์ง์ด DMTS๋ฅผ ๊ฐ์งํ๋ค๋ ๊ฐ์ค์ ์ธ์ฐ๊ฒ ๋์๊ณ
SRI-14์ ๋์ฐ๋ณ์ด์์ DMTS์ ๋ํ ์ ํธ๋ฐ์๊ณผ ํํผ๋ฐ์์ด ๋ชจ๋ ์ฌ๋ผ์ง๋ ๊ฒ์ ํ์ธํ์๋ค. SRI-14 ๋์ฐ๋ณ์ด๋ค์๊ฒ SRI-14์ ์ ์๋ฅผ AWC๋ด๋ฐ์ ํน์ ํ๊ฒ ์ฌ ๋ฐํ์์ผ ์ฃผ์์ ๊ฒฝ์ฐ ์ ๋๋์ DMTS์ ๋ํ ์ ํธ๋ฐ์์ด ํ๋ณต๋์์ผ๋ ๊ณ ๋๋์ ๋ํ ํํผ๋ฐ์์ ํ๋ณต๋์ง ์์๋ค. ๋ฐ๋๋ก ASH ํต๊ฐ ๋ด๋ฐ์ SRI-14 ์ ์ ์๋ฅผ ์ฌ ๋ฐํ์์ผ ์ฃผ์์ ๊ฒฝ์ฐ ๊ณ ๋๋ DMTS์ ๋ํ ํํผ๋ฐ์์ ๋์์์ผ๋ ์ ๋๋์ ๋ํ ์ ํธ๋ฐ์์ ๋์์ค์ง ์์๋ค. ๋ฐ๋ผ์ ๋ณธ ์ฐ๊ตฌ์๋ AWC ํ๊ฐ ๋ด๋ฐ์ ๋ฐํํ๋ SRI-14 ์์ฉ๊ธฐ๊ฐ ๋ฎ์ ๋๋์ ๋ํ DMTS ์ ํธ๋ฐ์์ ๋งค๊ฐํ๊ณ ASH ํต๊ฐ ๋ด๋ฐ์ ๋ฐํํ๋ SRI-14 ์์ฉ๊ธฐ๋ DMTS์ ๋ํ ํํผ๋ฐ์์ ๋งค๊ฐํ๋ค๋ ๊ฒ์ ํ์ธํ์๋ค. ๋ค์์ผ๋ก 1) SRI-14๊ฐ ๋ณธ๋๋ ๋ฐํํ์ง ์๋ ADL ๊ฐ๊ฐ๋ด๋ฐ์ SRI-14๋ฅผ ๋ฐํ์ํจ ํ์ง์ ํ ๋๋ฌผ๋ค์ ADL ๋ด๋ฐ์ ์นผ์์ด๋ฏธ์ง์์ DMTS์ ๋ํ ๋น์ ์์ ์ธ Ca2+ ๋ฐ์์ด ์์ฑ๋๋ค๋ ์ ์์, 2) ๋ํ ์ธ๊ฐ์ธํฌ์ SRI-14 ์์ฉ๊ธฐ๋ฅผ ๋ฐํ์์ผฐ์ ๋ ์ด ์ธํฌ๋ DMTS ๋
ธ์ถ์ ๋ฐ๋ผ ๋ฐ์์ ๋ํ๋์ ํ์ธํจ์ผ๋ก์จ, SRI-14๊ฐ ์ค์ ๋ก DMTS์ ๊ฒฐํฉํ๋ ์์ฉ๊ธฐ์์ ์ฆ๋ช
ํ๋ค. ๋ค์์ผ๋ก, ๋ณธ ์ฐ๊ตฌ์๋ ์ ์ถฉ์ด ์ด๋ฌํ ๋๋ ์์กด์ ํ๋ ์ ํ์ ๋ณด์ด๊ธฐ ์ํด ASH ์ AWC ํ์์ ์ธํฐ๋ด๋ฐ์ด DMTS ์ ํธ๋ฅผ ์ด๋ป๊ฒ ๋ฒ์ญํ๊ณ ์ฒ๋ฆฌํ๋์ง๋ฅผ ์กฐ์ฌํ๋ค. ๋ณธ ์ฐ๊ตฌ์๋ AWC์ ASH ๋ด๋ฐ์์ ์ ํธ๋ฅผ ์์ ํ๋ AIB interneuron์ด DMTS์ ๋๋์ ๋ฐ๋ผ ๋๋ ทํ Ca2+ ๋ฐ์์ ๋ณด์ธ๋ค๋ ๊ฒ์ ๋ฐ๊ฒฌํ๋ค. ๋ํ, AIB interneuron์ ์์ด์ ๊ฒฝ์ฐ DMTS์ ๋ํ ์ ํธ์ ํํผ๋ฐ์์ด ์ฝํด์ง์ ํ์ธํ์๋ค. ์ ํ ์ฐ๊ตฌ์ ์ํ์ฌ AWC์ ASH๋ด๋ฐ์ ๊ธ๋ฃจํ๋ฉ์ดํธ๋ฅผ ํตํ์ฌ ํ์ ๋ด๋ฐ์ ์ ํธ๋ฅผ ๋ณด๋ธ๋ค๋ ๊ฒ์ด ์๋ ค์ ธ ์์๋ค. ๋ฐ๋ผ์ DMTS์ ๋ํ ์ ํธ๋ค๋ ๊ธ๋ฃจํ๋ฉ์ดํธ๋ฅผ ํตํด ์ ๋ฌ๋ ๊ฒ์ด๋ผ ๊ฐ์ค์ ์ธ์ ๊ณ ๊ธ๋ฃจํ๋ฉ์ดํธ์ ์์ก ๋จ๋ฐฑ์ง์ ๋์ฐ๋ณ์ด ๋๋ฌผ๋ค์ ๊ฒฝ์ฐ DMTS์ ๋ํ ์ ํธ๋ฐ์๊ณผ ํํผ๋ฐ์์ด ์ฝํด์ง๋ ๊ฒ์ ํ์ธํ์๋ค. ๋ค์์ผ๋ก AIB ์ธํฐ๋ด๋ฐ์ด ์ด๋ ํ ์์ฉ๊ธฐ๋ฅผ ํตํด์ AWC์ ASH๋ก๋ถํฐ ์ค๋ DMTS ์ ๋ณด๋ฅผ ๋ฐ์๋ค์ด๋์ง ์์๋ณด์๋ค.YI. INTRODUCTION 1
1.1 Chemosensory systems in C. elegans 1
1.2 AWC olfactory neurons 2
1.3 ASH nociceptive neurons 3
1.4 Concentration dependent odor preferences in animals 4
1.5 Concentration dependent odor preferences in C. elegans 4
1.6 The across-fiber pattern Theories 5
1.7 The labeled-line theory 6
1.8 Overall introduction 14
II. MATERIALS AND METHODS 17
III. RESULTS 27
3.1 C. elegans is attracted to bacteria-derived sulfur odors 27
3.2 C. elegans avoids high concentration DMTS 34
3.3 The chemosensory GPCR SRI-14 is required for concentration-dependent DMTS response 40
3.4 The AWC and ASH neurons respond differently to DMTS via SRI-14 50
3.5 The AIB interneurons process DMTS signals from AWC and ASH 60
3.6 Distinct glutamate receptors mediate concentration-dependent behavioral switching upon DMTS exposure 67
3.7 SRI-14 GPCR is a chemosensory receptor for DMTS 71
IV. DISCUSSIONS 79
V. REFERENCES 84
VI. SUMMARY IN Koreans 97DoctordCollectio
The chemosensory GPCR SRI-14 are required for concentration-dependent odor preference in C. elegans
The complete chloroplast genome of Scapania ampliata Steph., 1897 (Scapaniaceae, Jungermanniales)
We completed chloroplast genome of Scapania ampliata Steph., presenting distinct morphological features including yellowish brown, one-celled gemmae, and decurrent dorsal lobe. It is 118,026โbp long and has four subregions: 80,850โbp of large single copy (LSC) and 19,436โbp of small single copy (SSC) regions are separated by 8,870โbp of inverted repeat (IR) regions including 130 genes (86 protein-coding genes, 8 ribosomal RNAs, and 36 transfer RNAs). The overall guanine cytosine (GC) content is 34.0% and those in the LSC, SSC, and IR regions are 31.9%, 31.0%, and 46.3%, respectively. Phylogenetic trees show S. ampliata is clustered with Scapania ciliata
The complete chloroplast genome of Wiesnerella denudata (Mitt.) Steph. (Wiesnerellaceae, Marchantiophyta)
We completed chloroplast genome of Wiesnerella denudata (Mitt.) Steph, only one species of the monotypic Wiesnerella genus and family Wiesnerellaceae Inoue. It is 122,500โbp and has four subregions: 82,143โbp of large single copy (LSC) and 20,009โbp of small single copy (SSC) regions are separated by 10,174โbp of inverted repeat (IR) regions including 132 genes (88 protein-coding genes, eight rRNAs, and 36 tRNAs). The overall GC content is 28.8% and those in the LSC, SSC, and IR regions are 26.4, 24.6, and 42.8%, respectively. Phylogenetic trees show incongruencies of phylogenetic relationship of W. denudata, requiring additional research
Long-Term Outcomes of Local Tirofiban Infusion for Intracranial Atherosclerosis-Related Occlusion
Local tirofiban infusion has been reported as a rescue strategy for intracranial atherosclerotic stenosis (ICAS)-related stroke. However, the long-term outcomes of local tirofiban infusion during endovascular reperfusion therapy (ERT) for ICAS-related stroke are still uncertain. This study aimed to investigate the long-term outcomes of local tirofiban infusion during ERT. We retrospectively analyzed acute patients with ICAS-related stroke who were treated with local tirofiban as a rescue strategy during ERT. The primary outcomes were ischemic stroke, transient ischemic stroke (TIA), and stroke-related death within 30 days. Secondary outcomes included ischemic stroke and TIA beyond 30 days and up to 2 years after ERT in the corresponding treated vessel, symptomatic brain hemorrhage, any stroke, and non-stroke-related death. During a median follow-up of 24.0 months, 12 patients developed an ischemic stroke and TIA (4 within 30 days and 8 afterward). The 1-year risk of stroke and TIA was 9.2% (95% confidence interval, 8.0โ18.6%). This study demonstrates that 1-year outcomes of local tirofiban infusion were comparable to the results of intracranial stenting in patients with symptomatic ICAS. Local tirofiban infusion for ICAS-related stroke may be a feasible rescue strategy that can have a bridging role until the maximum effect of antiplatelet agents is achieved
The complete mitochondrial genome of Wiesnerella denudata (Mitt.) Steph. (Wiesnerellaceae, Marchantiophyta): large number of intraspecific variations on mitochondrial genomes of W. denudata
Wiesnerella denudata (Mitt.) Steph. is a thallose liverwort distributed in Asian subtropical to tropical regions. It is the only one species in genus Wiesnerella and family Wiesnerellaceae. To investigate intraspecific variations on mitochondrial genomes of W. denudata, we completed mitochondrial genome of W. denudata. Its length is 185,640โbp, longer than that of the previously sequenced mitochondrial genome by 71โbp and contains 73 genes (41 protein-coding genes, 3 rRNAs, 28 tRNAs, and 1 pseudogene). A total of 149 single nucleotide polymorphisms (SNPs) and 3,033 insertions and deletions are identified, much higher than those of Marchantia polymorpha subsp. ruderalis and Riccia fluitans. Phylogenetic trees show that W. denudata is clustered with Monosolenium tenerum belonging to Monosoleniaceae
The complete mitochondrial genome of Scapania ampliata Steph., 1897 (Scapaniaceae, Jungermanniales)
Scapania ampliata Steph. is the endemic species in East Asia. To investigate intraspecific variations on mitochondrial genomes of S. ampliata, we completed mitochondrial genome of S. ampliata isolated in Korea. It is 143,664โbp long and contains 73 genes (41 protein-coding genes, three rRNAs, 28 tRNAs, and one pseudogene). 823 single nucleotide polymorphisms (SNPs; 0.057%) and 2,242 insertions and deletions were identified between two S. ampliata mitochondrial genomes, which is large number of intraspecific variations in comparison to the other cases of Bryophyte mitochondrial genomes. Phylogenetic trees show that S. ampliata is clustered with those of two Scapania species with high supportive values