Exploring the Impact of BDNF Val66Met Genotype on Serotonin Transporter and Serotonin-1A Receptor Binding

Much of the impact of genes on mood disorders likely depends on interactions between genes and the environment. Recent studies demonstrating an interaction between specific genes and life stressful events (early and/or adult) in the modulation of several mood disorders (e.g., serotonin transporter and brain-derived neurotrophic factor genes) have compelled researchers to incorporate information about adverse environmental experiences into the study of genetic risk factors; these same gene-by-environment (G×E) interactions have been identified in mouse models. Notably, G×E not yet described in humans (e.g., serotonin 1A receptor gene) have been uncovered, providing helpful indications to discover similar interactions in humans. Accurate knowledge of the modality of expression of gene-by-stress interaction may help design prevention protocols aimed at identifying susceptibility to mood disorders on the basis of genetic predisposition and exposure to environmental stressful conditions, thus providing patients with appropriate pharmacological and psychological support.

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Design of a companion bioinformatic tool to detect the emergence and geographical distribution of SARS-CoV-2 Spike protein genetic variants

Journal of Translational Medicine ◽

10.1186/s12967-020-02675-4 ◽

2020 ◽

Vol 18 (1) ◽

Author(s):

Alice Massacci ◽

Eleonora Sperandio ◽

Lorenzo D’Ambrosio ◽

Mariano Maffei ◽

Fabio Palombo ◽

...

Keyword(s):

Receptor Binding ◽

Consensus Sequence ◽

Cell Epitope ◽

Vaccine Design ◽

Binding Domain ◽

Spike Protein ◽

Antibody Activity ◽

Binding Motif ◽

Receptor Binding Domain ◽

The Impact

Abstract Background Tracking the genetic variability of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) is a crucial challenge. Mainly to identify target sequences in order to generate robust vaccines and neutralizing monoclonal antibodies, but also to track viral genetic temporal and geographic evolution and to mine for variants associated with reduced or increased disease severity. Several online tools and bioinformatic phylogenetic analyses have been released, but the main interest lies in the Spike protein, which is the pivotal element of current vaccine design, and in the Receptor Binding Domain, that accounts for most of the neutralizing the antibody activity. Methods Here, we present an open-source bioinformatic protocol, and a web portal focused on SARS-CoV-2 single mutations and minimal consensus sequence building as a companion vaccine design tool. Furthermore, we provide immunogenomic analyses to understand the impact of the most frequent RBD variations. Results Results on the whole GISAID sequence dataset at the time of the writing (October 2020) reveals an emerging mutation, S477N, located on the central part of the Spike protein Receptor Binding Domain, the Receptor Binding Motif. Immunogenomic analyses revealed some variation in mutated epitope MHC compatibility, T-cell recognition, and B-cell epitope probability for most frequent human HLAs. Conclusions This work provides a framework able to track down SARS-CoV-2 genomic variability.

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The Impact on Infectivity and Neutralization Efficiency of SARS-CoV-2 Lineage B.1.351 Pseudovirus

Viruses ◽

10.3390/v13040633 ◽

2021 ◽

Vol 13 (4) ◽

pp. 633

Author(s):

Yeong Jun Kim ◽

Ui Soon Jang ◽

Sandrine M. Soh ◽

Joo-Youn Lee ◽

Hye-Ra Lee

Keyword(s):

South Africa ◽

Monoclonal Antibodies ◽

Cell Fusion ◽

Receptor Binding ◽

Neutralizing Antibodies ◽

Receptor Binding Domain ◽

Viral Spread ◽

New Variant ◽

Global Concern ◽

The Impact

A new variant of SARS-CoV-2 B.1.351 lineage (first found in South Africa) has been raising global concern due to its harboring of multiple mutations in the spike that potentially increase transmissibility and yield resistance to neutralizing antibodies. We here tested infectivity and neutralization efficiency of SARS-CoV-2 spike pseudoviruses bearing particular mutations of the receptor-binding domain (RBD) derived either from the Wuhan strains (referred to as D614G or with other sites) or the B.1.351 lineage (referred to as N501Y, K417N, and E484K). The three different pseudoviruses B.1.351 lineage related significantly increased infectivity compared with other mutants that indicated Wuhan strains. Interestingly, K417N and E484K mutations dramatically enhanced cell–cell fusion than N501Y even though their infectivity were similar, suggesting that K417N and E484K mutations harboring SARS-CoV-2 variant might be more transmissible than N501Y mutation containing SARS-CoV-2 variant. We also investigated the efficacy of two different monoclonal antibodies, Casirivimab and Imdevimab that neutralized SARS-CoV-2, against several kinds of pseudoviruses which indicated Wuhan or B.1.351 lineage. Remarkably, Imdevimab effectively neutralized B.1.351 lineage pseudoviruses containing N501Y, K417N, and E484K mutations, while Casirivimab partially affected them. Overall, our results underscore the importance of B.1.351 lineage SARS-CoV-2 in the viral spread and its implication for antibody efficacy.

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PW01-155 - Seasonal alterations of serotonin-1A receptor binding in the healthy human brain

European Psychiatry ◽

10.1016/s0924-9338(10)71554-6 ◽

2010 ◽

Vol 25 ◽

pp. 1571

Author(s):

C. Spindelegger ◽

P. Stein ◽

W. Wadsak ◽

M. Fink ◽

M. Mitterhauser ◽

...

Keyword(s):

Human Brain ◽

Receptor Binding ◽

Serotonin 1A Receptor ◽

Healthy Human

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S.04.08 Serotonin-1A receptor binding potential in dorsal raphe nuclei predicts orbitofrontal reactivity in healthy subjects

European Neuropsychopharmacology ◽

10.1016/s0924-977x(09)70211-1 ◽

2009 ◽

Vol 19 ◽

pp. S182-S183

Author(s):

A. Hahn ◽

M. Savli ◽

P. Stein ◽

L.K. Mien ◽

A. Holik ◽

...

Keyword(s):

Receptor Binding ◽

Healthy Subjects ◽

Dorsal Raphe ◽

Raphe Nuclei ◽

Binding Potential ◽

Serotonin 1A Receptor ◽

Raphé Nuclei ◽

Dorsal Raphé

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The interaction between serotonin transporter allelic variation and maternal care modulates sociability on Instagram

10.31234/osf.io/dkvnf ◽

2020 ◽

Cited By ~ 2

Author(s):

Andrea Bonassi ◽

Ilaria Cataldo ◽

Giulio Gabrieli ◽

Moses Tandiono ◽

Jia Nee Foo ◽

...

Keyword(s):

Serotonin Transporter ◽

Social Desirability ◽

Parental Bonding ◽

Serotonin Transporter Gene ◽

Individual Development ◽

Environment Interaction ◽

Transporter Gene ◽

Gene Environment ◽

The Impact ◽

Desirability Index

Human social interactions ensure recognition and approval from others, both in offline and online environments. This study applies a model from behavioural genetics on Instagram sociability to explore the impact of individual development on the behaviour on social networks.We hypothesize that sociable attitudes on Instagram resulted from an interaction between serotonin transporter gene alleles and the individual’s social relationship with caregivers. We assess environmental and genetic components of 57 Instagram users. The self-report questionnaire Parental Bonding Instrument is adopted to determine the quality of parental bonding. The number of posts, followed users (“followings”), and followers are collected from Instagram as measures of online social activity. Additionally, the ratio between the number of followers and followings (“Social Desirability Index”) was calculated to estimate the asymmetry of each user’s social network. Finally, buccal mucosa cell samples were acquired, and the polymorphism rs25531 (T/T homozygotes vs C-carriers) within the serotonin transporter gene was examined.In the preliminary analysis, we identified a gender effect on the number of followings. In line with our predictions, we specifically found a gene- environment interaction on the standardized Instagram “Social Desirability Index”: users with the genotype more sensitive to environmental influences (T/T homozygotes) showed a higher Instagram “Social Desirability Index” than non-sensitive ones (C-carriers) when they experienced positive maternal care.This result may contribute to the understanding of online social behaviour from a gene*environment perspective.

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Inhibition of SARS-CoV-2 viral entry upon blocking N- and O-glycan elaboration

eLife ◽

10.7554/elife.61552 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Qi Yang ◽

Thomas A Hughes ◽

Anju Kelkar ◽

Xinheng Yu ◽

Kai Cheng ◽

...

Keyword(s):

Receptor Binding ◽

Viral Entry ◽

Multiple Roles ◽

Spike Protein ◽

Receptor Binding Domain ◽

Mechanistic Studies ◽

Post Translational Modification ◽

Minor Contribution ◽

Chemical Inhibitors ◽

The Impact

The Spike protein of SARS-CoV-2, its receptor-binding domain (RBD), and its primary receptor ACE2 are extensively glycosylated. The impact of this post-translational modification on viral entry is yet unestablished. We expressed different glycoforms of the Spike-protein and ACE2 in CRISPR-Cas9 glycoengineered cells, and developed corresponding SARS-CoV-2 pseudovirus. We observed that N- and O-glycans had only minor contribution to Spike-ACE2 binding. However, these carbohydrates played a major role in regulating viral entry. Blocking N-glycan biosynthesis at the oligomannose stage using both genetic approaches and the small molecule kifunensine dramatically reduced viral entry into ACE2 expressing HEK293T cells. Blocking O-glycan elaboration also partially blocked viral entry. Mechanistic studies suggest multiple roles for glycans during viral entry. Among them, inhibition of N-glycan biosynthesis enhanced Spike-protein proteolysis. This could reduce RBD presentation on virus, lowering binding to host ACE2 and decreasing viral entry. Overall, chemical inhibitors of glycosylation may be evaluated for COVID-19.

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Cortisol plasma levels are associated with serotonin - 1A receptor binding in postmenopausal women

European Psychiatry ◽

10.1016/s0924-9338(11)72638-4 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 933-933

Author(s):

G. Kranz ◽

A. Hahn ◽

J. Ungersböck ◽

U. Kaufmann ◽

P. Stein ◽

...

Keyword(s):

Postmenopausal Women ◽

Receptor Binding ◽

Plasma Levels ◽

Hormone Replacement ◽

Binding Potential ◽

Serotonin 1A Receptor ◽

Strong Negative Correlation ◽

Logan Plot ◽

Increased Risk ◽

Relationship Of

IntroductionAlterations of the serotonin-1A receptor (5-HT1A) and the hypothalamic-pituitary-adrenal (HPA) axis have been reported in depression and anxiety disorders. We previously showed a strong negative correlation between cortisol plasma levels and 5-HT1A receptor binding potential (BP) in patients with social anxiety disorder but not in healthy controls using PET [1].ObjectivesTo investigate the relationship of cortisol and the 5-HT1A BP in postmenopausal women, a population that is at increased risk of suffering from depressive symptoms.MethodsSubjects: 19 postmenopausal women, aged 55.26 ± 4.98, medication free, no current substance abuse or hormone replacement therapy.PETDynamic measurements (50 frames, 90 min) were performed using the radioligand [carbonyl-11C]WAY100635 and a GE-Advance scanner. PET data were normalized to a ligand-specific template [2]. Regions-of-interest (ROI) were defined as given in [3]. TACs within ROIs were averaged and the 5-HT1A receptor BP was quantified using Logan-plot and PMOD 3.1. Measurement of total cortisol plasma levels was done using electrochemoluminescence.ResultsWe found negative correlations between cortisol and 5-HT1A BP in the midbrain (Spearman's rs = −0.54, p = 0.02), the median raphe nucleus (rs = −0.47, p = 0.04) and the nucleus accumbens (rs = −0.505, p = 0.03).ConclusionsIn line with our previous findings [1], the observed negative association between cortisol plasma levels and 5-HT1A BP might reflect an increased vulnerability for mood disorders in postmenopausal women.

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