In 14 patients with Parkinson's disease on long-term therapy the erythrocyte catechol-O-methyltransferase activity was found to correlate average plasma concentration ratio of 3-O-methyldopa levodopa and fasting 3-O methyldopa levodopa. Patients higher activities were those less favorable clinical responses Since may reflect that enzyme in major metabolizing tissues, would seem be a significant determinant response

Significance Roundworms carry out crucial sensory behaviors with a relatively small number of neurons. We find that male roundworms have strong preferences for particular concentrations sex-specific molecule cues secreted by their potential mates. These emerge from the dynamics population four apparently identical male-specific The response these neurons is not uniform, some being excitatory and others inhibitory, timing varies concentration. features allow this single neuronal class to...

Animals respond to changes in their environment and internal states via neuromodulation. Neuropeptides modulate neural circuits with flexibility because one gene can produce either multiple copies of the same neuropeptide or different neuropeptides. However, this architectural complexity, function discrete active neuropeptides is muddled. Here, we design a genetic tool that facilitates functional analysis individual peptides. We engineered Escherichia coli bacteria express peptides, fed...

The same bimodal distribution of erythrocyte catechol-O-methyltransferase (RBC-COMT) was found in normal Caucasians and Orientals, but the frequency high RBC-COMT activity Orientals significantly greater than that Caucasians. There no difference between Oriental ethnic groups studied (i.e., Chinese Filipinos). Since with Parkinson's disease who had appeared to have more adverse effects from levodopa (L-dopa) those low activity, L-dopa doses responses Filipinos parkinsonism were compared...

Biogenic amine neurotransmitters play a central role in metazoan biology, and both their chemical structures cognate receptors are evolutionarily conserved. Their primary roles cell-to-cell signaling, as biogenic amines not normally recruited for communication between separate individuals. Here, we show that the nematode C. elegans, neurotransmitter-sensing G protein-coupled receptor, TYRA-2, is required avoidance responses to osas#9, an ascaroside pheromone incorporates neurotransmitter,...

The nematode Caenorhabditis elegans utilizes chemosensation to navigate an ever-changing environment for its survival. A class of secreted small-molecule pheromones, termed ascarosides, play important role in olfactory perception by affecting biological functions ranging from development behavior. ascaroside #8 (ascr#8) mediates sex-specific behaviors, driving avoidance hermaphrodites and attraction males. Males sense ascr#8 via the ciliated male-specific cephalic sensory (CEM) neurons,...

Chemical communication in nematodes such as the model organism Caenorhabditis elegans is modulated by a variety of glycosides based on dideoxysugar l-ascarylose. Comparative ascaroside profiling nematode exometabolome extracts using GC-EIMS screen reveals that several basic components including ascr#1 (asc-C7), ascr#2 (asc-C6-MK), ascr#3 (asc-ΔC9), ascr#5 (asc-ωC3), and ascr#10 (asc-C9) are highly conserved among Caenorhabditis. Three novel side chain hydroxylated derivatives were...

Abstract Dioecious species are a hallmark of the animal kingdom, with opposing sexes responding differently to identical sensory cues. Here, we study response C. elegans small-molecule pheromone, ascr#8, which elicits behavioral valences in each sex. We identify novel neuropeptide-neuropeptide receptor (NP/NPR) module that is active males, but not hermaphrodites. Using paradigm neuropeptide rescue established, leverage bacterial expression individual peptides sex-specific ascr#8. Concurrent...

The use of calcium indicators has greatly enhanced our understanding neural dynamics and regulation. nematode Caenorhabditis elegans, with its completely mapped nervous system transparent anatomy, presents an ideal model for real-time using indicators. In combination microfluidic technologies experimental designs, calcium-imaging studies these are performed in both free-moving trapped animals. However, most previous utilizing trapping devices, such as the olfactory chip described Chronis et...

Identification of pheromone receptors plays a central role for uncovering signaling pathways that underlie chemical communication in animals. Here, we describe the synthesis and bioactivity photoaffinity probes ascaroside ascr#8, sex-pheromone model nematode, Caenorhabditis elegans. Structure-activity studies guided incorporation alkyne- diazirine-moieties revealed addition functionality sidechain ascr#8 was well tolerated, whereas modifications to ascarylose moiety resulted loss biological...

Abstract Dioecious species are a hallmark of the animal kingdom, with opposing sexes responding differently to identical sensory cues. Here, we study response C. elegans’ small-molecule pheromone, ascr#8, which elicits behavioral valences in each sex. We identify novel neuropeptide-neuropeptide receptor (NP/NPR) module that is active males, but not hermaphrodites. Using paradigm neuropeptide rescue established, leverage bacterial expression individual peptides sex-specific ascr#8. Concurrent...

Abstract Animals constantly respond to changes in their environment and internal states via neuromodulation. Neuropeptide genes modulate neural circuits by encoding either multiple copies of the same neuropeptide or different neuropeptides. This architectural complexity makes it difficult determine function discrete active Here, we present a novel genetic tool that facilitates functional analysis individual peptides. We engineered Escherichia coli bacteria express peptides fed...

Abstract Animals constantly respond to changes in their environment and internal states via neuromodulation. Neuropeptide genes modulate neural circuits by encoding either multiple copies of the same neuropeptide or different neuropeptides. This architectural complexity makes it difficult determine function discrete active Here, we present a novel genetic tool that facilitates functional analysis individual peptides. We engineered Escherichia coli bacteria express peptides fed...

Summary The nematode Caenorhabditis elegans utilizes chemosensation to navigate an ever-changing environment for its survival. A class of secreted small-molecule pheromones, termed ascarosides, play important role in olfactory perception by affecting biological functions ranging from development behavior. ascaroside ascr#8 mediates sex-specific behaviors, driving avoidance hermaphrodites and attraction males. Males sense via the ciliated male-specific cephalic sensory (CEM) neurons, which...