scholarly journals Serotonin Receptor 1A Variation Is Associated with Anxiety and Agonistic Behavior in Chimpanzees

2019 ◽  
Vol 36 (7) ◽  
pp. 1418-1429 ◽  
Author(s):  
Nicky Staes ◽  
Chet C Sherwood ◽  
Hani Freeman ◽  
Sarah F Brosnan ◽  
Steven J Schapiro ◽  
...  
Keyword(s):  
Amino Acid ◽  
Agonistic Behavior ◽  
Serotonin Receptor ◽  
Systematic Investigation ◽  
Monoamine Oxidase A ◽  
Receptor Subtype ◽  
Polymorphic Variation ◽  
Coding Region ◽  
Intracellular Loop ◽  
And Behavior

Abstract Serotonin is a neurotransmitter that plays an important role in regulating behavior and personality in humans and other mammals. Polymorphisms in genes coding for the serotonin receptor subtype 1A (HTR1A), the serotonin transporter (SLC6A4), and the serotonin degrading enzyme monoamine oxidase A (MAOA) are associated with anxiety, impulsivity, and neurotic personality in humans. In primates, previous research has largely focused on SLC6A4 and MAOA, with few studies investigating the role of HTR1A polymorphic variation on behavior. Here, we examined variation in the coding region of HTR1A across apes, and genotyped polymorphic coding variation in a sample of 214 chimpanzees with matched measures of personality and behavior. We found evidence for positive selection at three amino acid substitution sites, one in chimpanzees-bonobos (Thr26Ser), one in humans (Phe33Val), and one in orangutans (Ala274Gly). Investigation of the HTR1A coding region in chimpanzees revealed a polymorphic site, where a C/A single nucleotide polymorphism changes a proline to a glutamine in the amino acid sequence (Pro248Gln). The substitution is located in the third intracellular loop of the receptor, a region important for serotonin signal transduction. The derived variant is the major allele in this population (frequency 0.67), and is associated with a reduction in anxiety, decreased rates of male agonistic behavior, and an increase in socio-positive behavior. These results are the first evidence that the HTR1A gene may be involved in regulating social behavior in chimpanzees and encourage further systematic investigation of polymorphic variation in other primate populations with corresponding data on behavior.

Assessment for the Role of Serotonin Receptor Subtype 3 for the Analgesic Action of Morphine at the Spinal Level

2005 ◽  
Vol 18 (2) ◽  
pp. 113
Author(s):  
Myung Ha Yoon ◽  
Hong Buem Bae ◽  
Jeong Il Choi ◽  
Seok Jae Kim ◽  
Chang Mo Kim ◽  
...  
Keyword(s):  
Serotonin Receptor ◽  
Receptor Subtype ◽  
Analgesic Action ◽  
Spinal Level ◽  
Subtype 3

scholarly journals Living-Cell Diffracted X-ray Tracking Analysis Confirmed Internal Salt Bridge Is Critical for Ligand-Induced Twisting Motion of Serotonin Receptors

2021 ◽  
Vol 22 (10) ◽  
pp. 5285
Author(s):  
Kazuhiro Mio ◽  
Shoko Fujimura ◽  
Masaki Ishihara ◽  
Masahiro Kuramochi ◽  
Hiroshi Sekiguchi ◽  
...  
Keyword(s):  
Serotonin Receptors ◽  
Serotonin Receptor ◽  
Frame Rate ◽  
Receptor Subtype ◽  
Transmembrane Segment ◽  
Hek 293 ◽  
Gold Nanocrystals ◽  
X Ray ◽  
Time Dynamics ◽  
Analytical Technique

Serotonin receptors play important roles in neuronal excitation, emotion, platelet aggregation, and vasoconstriction. The serotonin receptor subtype 2A (5-HT2AR) is a Gq-coupled GPCR, which activate phospholipase C. Although the structures and functions of 5-HT2ARs have been well studied, little has been known about their real-time dynamics. In this study, we analyzed the intramolecular motion of the 5-HT2AR in living cells using the diffracted X-ray tracking (DXT) technique. The DXT is a very precise single-molecular analytical technique, which tracks diffraction spots from the gold nanocrystals labeled on the protein surface. Trajectory analysis provides insight into protein dynamics. The 5-HT2ARs were transiently expressed in HEK 293 cells, and the gold nanocrystals were attached to the N-terminal introduced FLAG-tag via anti-FLAG antibodies. The motions were recorded with a frame rate of 100 μs per frame. A lifetime filtering technique demonstrated that the unliganded receptors contain high mobility population with clockwise twisting. This rotation was, however, abolished by either a full agonist α-methylserotonin or an inverse agonist ketanserin. Mutation analysis revealed that the “ionic lock” between the DRY motif in the third transmembrane segment and a negatively charged residue of the sixth transmembrane segment is essential for the torsional motion at the N-terminus of the receptor.

Identification of a new 2‐amino acid insertion in the integrase coding region of HIV‐1 subtype G isolates

2021 ◽  
Author(s):  
João Pereira‐Vaz ◽  
Pedro Crespo ◽  
Luísa Mocho ◽  
Patrícia Martinho ◽  
Teresa Fidalgo ◽  
...  
Keyword(s):  
Amino Acid ◽  
Coding Region ◽  
Amino Acid Insertion ◽  
Hiv 1

scholarly journals Murine erythropoietin gene: cloning, expression, and human gene homology.

1986 ◽  
Vol 6 (3) ◽  
pp. 849-858 ◽  
Author(s):  
C B Shoemaker ◽  
L D Mitsock
Keyword(s):  
Amino Acid ◽  
Genomic Library ◽  
Cdna Probe ◽  
Amino Acid Sequences ◽  
Nucleotide Sequence Analysis ◽  
Coding Region ◽  
Transcription Control ◽  
Erythroid Progenitor ◽  
Human Genes ◽  
Cell Expression

The gene for murine erythropoietin (EPO) was isolated from a mouse genomic library with a human EPO cDNA probe. Nucleotide sequence analysis permitted the identification of the murine EPO coding sequence and the prediction of the encoded amino acid sequence based on sequence conservation between the mouse and human EPO genes. Both the coding DNA and the amino acid sequences were 80% conserved between the two species. Transformation of COS-1 cells with a mammalian cell expression vector containing the murine EPO coding region resulted in secretion of murine EPO with biological activity on both murine and human erythroid progenitor cells. The transcription start site for the murine EPO gene in kidneys was determined. This permitted tentative identification of the transcription control region. The region included 140 base pairs upstream of the cap site which was over 90% conserved between the murine and human genes. Surprisingly, the first intron and much of the 5'- and 3'-untranslated sequences were also substantially conserved between the genes of the two species.

Advancing RNA Virus Discovery and Biology with Whole Genome Sequencing

2021 ◽  
Author(s):  
◽  
Mariah Taylor ◽  
Keyword(s):  
Genetic Variation ◽  
Amino Acid ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Rna Virus ◽  
Animal Health ◽  
Functional Domains ◽  
Whole Genome ◽  
Coding Region

Two RNA virus families that pose a threat to human and animal health are Hantaviridae and Coronaviridae. These RNA viruses which originate in wildlife continue and will continue to cause disease, and hence, it is critical that scientific research define the mechanisms as to how these viruses spillover and adapt to new hosts to become endemic. One gap in our ability to define these mechanisms is the lack of whole genome sequences for many of these viruses. To address this specific gap, I developed a versatile amplicon-based whole-genome sequencing (WGS) approach to identify viral genomes of hantaviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within reservoir and spillover hosts. In my research studies, I used the amplicon-based WGS approach to define the genetic plasticity of viral RNA within pathogenic and nonpathogenic hantavirus species. The standing genetic variation of Andes orthohantavirus and Prospect Hill orthohantavirus was mapped out and amino acid changes occurring outside of functional domains were identified within the nucleocapsid and glycoprotein. I observed several amino acid changes in functional domains of the RNA-dependent RNA polymerase, as well as single nucleotide polymorphisms (SNPs) within the 3’ non-coding region (NCR) of the S-segment. To identify whether virus adaptation would occur within the S- and L-segments we attempted to adapt hantaviruses in vitro in a spillover host model through passaging experiments. In early passages we identified few mutations in the M-segment with the majority being identified in the S-segment 3’ NCR and the L-segment. This work suggests that hantavirus adaptation occurs in the S- and L-segments although the effect of these mutants on pathology is yet to be determined. While sequencing laboratory isolates is easily accomplished, sequencing low concentrations of virus within the reservoir is a formidable task. I further translated our amplicon-based WGS approach into a pan-oligonucleotide amplicon-based WGS approach to sequence hantavirus vRNA and mRNA from reservoir and spillover hosts in Ukraine. This approach successfully identified a novel Puumala orthohantavirus (PUUV) strain in Ukraine and using Bayesian phylogenetics we found this strain to be associated with the PUUV Latvian lineage. Early during the SARS-CoV-2 pandemic, I applied the knowledge gained in the hantavirus WGS efforts to sequencing of SARS-CoV-2 from nasopharyngeal swabs collected in April 2020. The genetic diversity of 45 SARS-CoV-2 isolates was evaluated with the methods I developed. We identified D614G, a notable mutation known for increasing transmission, in over 90% of our isolates. Two major lineages distinguish SARS-CoV-2 variants worldwide, lineages A and B. While most of our isolates were found within B lineage, we also identified one isolate within lineage A. We performed in vitro work which confirmed A lineage isolates as having poor replication in the trachea as compared to the nasal cavity. Five of these isolates presented a unique array of mutations which were assessed in the keratin 18 human angiotensin-converting enzyme 2 (K18-hACE2) mouse model for its response immunologically and pathogenically. We identified a distinction of pathogenesis between the A and B lineages with emphysema being common amongst A lineage isolates. Additionally, we discovered a small cohort of likely SNPs that defined the late induction of eosinophils during infection. In summary, this work will further define the dynamics of genetic variation and plasticity within virus populations that cause disease outbreaks and will allow a deeper understanding of the virus-host relationship.

Changes in serotonin levels and 5-HT receptor activity in duodenum of streptozotocin-diabetic rats

2001 ◽  
Vol 281 (3) ◽  
pp. G798-G808 ◽  
Author(s):  
H. Takahara ◽  
M. Fujimura ◽  
S. Taniguchi ◽  
N. Hayashi ◽  
T. Nakamura ◽  
...  
Keyword(s):  
Small Intestine ◽  
Motor Activity ◽  
Serotonin Receptor ◽  
Ex Vivo ◽  
Diabetic Rats ◽  
Receptor Activity ◽  
Diabetic Rat ◽  
Receptor Subtype ◽  
Serotonin Content ◽  
Rat Duodenum

Few previous studies have discussed the changes in serotonin receptor activity in the small intestine of diabetic animals. Therefore, we examined serotonin content in duodenal tissue and dose-dependent effects of serotonin agonists and antagonists on the motor activity of ex vivo vascularly perfused duodenum of streptozotocin (STZ)-diabetic rats. Serotonin content was significantly increased in enterochromaffin cells but not altered in serotonin-containing neurons in STZ-diabetic rats. Motor activity assessed by frequency, amplitude, and percent motility index per 10 min of pressure waves was reduced in the duodenum of diabetic rats, and this reduction was reversed by insulin treatment. Serotonin dose dependently increased the motor activity in control rat duodenum but only a higher concentration of serotonin increased the motor activity in diabetic rats. The 5-hydroxytryptamine (5-HT) receptor subtype 4 (5-HT4) antagonist SB-204070 dose dependently reduced motor activity in both control and diabetic rats, whereas the 5-HT3receptor antagonist azasetron, even at a higher concentration, failed to affect motor activity in diabetic rat duodenum but dose dependently reduced motor activity in control rat duodenum. These results suggest that 5-HT3receptor activity was impaired but 5-HT4receptor activity was intact in STZ-diabetic rat duodenum. Such an impairment of 5-HT3receptor activity may induce the motility disturbance in the small intestine of diabetes mellitus.

scholarly journals Impact of evolutionary selection on dynamic behavior of MCAK protein

2020 ◽  
Author(s):  
Shiwani Limbu
Keyword(s):  
Amino Acid ◽  
Amino Acid Position ◽  
Coding Region ◽  
Microtubule Depolymerization ◽  
Protein Coding ◽  
Microtubule Binding ◽  
Evolutionary Selection ◽  
Family Protein ◽  
Α Helix

AbstractKinesins of class 13 (kinesin-13s), also known as KinI family proteins, are non-motile microtubule binding kinesin proteins. Mitotic centromere-associated kinesin (MCAK), a member of KinI family protein, diffuses along the microtubule and plays a key role in microtubule depolymerization. Here we have demonstrated the role of evolutionary selection in MCAK protein coding region in regulating its dynamics associated with microtubule binding and stability. Our results indicate that evolutionary selection within MCAK motor domain at amino acid position 440 in carnivora and artiodactyla order results in significant change in the dynamics of α – helix and loop 11, indicating its likely impact on changing the microtubule binding and depolymerization process. Furthermore, evolutionary selections at amino acid position 600, 617 and 698 are likely to affect MCAK stability. A deeper understanding of evolutionary selections in MCAK can reveal the mechanism associated with change in microtubule dynamics within eutherian mammals.

scholarly journals Molecular Characterization of Mycoplasma arthritidis Variable Surface Protein MAA2

1998 ◽  
Vol 66 (6) ◽  
pp. 2576-2586 ◽  
Author(s):  
Leigh Rice Washburn ◽  
Keith E. Weaver ◽  
Elizabeth J. Weaver ◽  
Wendy Donelan ◽  
Suhaila Al-Sheboul
Keyword(s):  
Amino Acid ◽  
Signal Peptide ◽  
Dna Sequences ◽  
Surface Protein ◽  
Carboxypeptidase Y ◽  
Coding Region ◽  
Intact Cells ◽  
Mycoplasma Arthritidis ◽  
E Coli ◽  
Variable Surface

Earlier studies implied a role for Mycoplasma arthritidis surface protein MAA2 in cytadherence and virulence and showed that it exhibited both size and phase variability. Here we report the further analysis of MAA2 and the cloning and sequencing of the maa2 gene from two M. arthritidis strains, 158p10p9 and H606, expressing two size variants of MAA2. Triton X-114 partitioning and metabolic labeling with [3H]palmitic acid suggested lipid modification of MAA2. Surface exposure of the C terminus was indicated by cleavage of monoclonal antibody-specific epitopes from intact cells by carboxypeptidase Y. The maa2genes from both strains were highly conserved, consisting largely of six (for 158p10p9) or five (for H606) nearly identical, 264-bp tandem direct repeats. The deduced amino acid sequence predicted a largely hydrophilic, highly basic protein with a 29-amino-acid lipoprotein signal peptide. The maa2 gene was expressed inEscherichia coli from the lacZ promoter of vector pGEM-T. The recombinant product was approximately 3 kDa larger than the native protein, suggesting that the signal peptide was not processed in E. coli. The maa2 gene and upstream DNA sequences were cloned from M. arthritidisclonal variants differing in MAA2 expression state. Expression state correlated with the length of a poly(T) tract just upstream of a putative −10 box. Full-sized recombinant MAA2 was expressed inE. coli from genes derived from both ON and OFF expression variants, indicating that control of expression did not include alterations within the coding region.

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