Biology subjects

Wagner, B.

Publications and source records attributed to Wagner, B..

At least 19 recordsLinked to original sources

bioRxiv2025

Dynamic connectivities of plant metacommunities at a millennial time-scale: the Beringia testbed

Ecological connectivity shapes ecosystem responses to climate change and is thought to underpin stability, yet its millennial-scale dynamics remain poorly resolved. We asked how spatial and temporal connectivity of plant metacommunities changed over the last 40 ka and which processes drove it. We analysed and compiled plant sedimentary DNA from 20 lake cores across Beringia (Siberia, Alaska) to investigate community dynamics and, for a high-resolution subset, applied beta- and zeta-diversity to track connectivity. Vegetation changed coherently across the glacial-Holocene transition, with trait shifts mirroring functional composition. Connectivity peaked during the late MIS3 and Last Glacial Maximum--likely aided by the Bering Land Bridge, mass effects and facilitation--collapsed during the Deglacial with rapid turnover, and rebounded in the Holocene as shrub and boreal communities expanded. Temporal zeta within sites exceeded spatial zeta, indicating strong local persistence and resilience. Tundra sites uninvaded by forest maintained continuous species pools. Overall, these patterns underscore the value of a metacommunity perspective for assessing millennial-scale connectivity changes.

ecology↗

bioRxiv2025

Inducible re-epithelialization of cancer cells increases autophagy and DNA damage: implications for breast cancer dormancy

Epithelial lineage differentiation is pivotal to mammary gland development and it can pause metastasis of breast cancer (BC) by inducing tumor dormancy. To simulate this, we expressed epithelial genes in mesenchymal BC cells. Inducible expression of the epithelial OVOL genes in metastatic BC cells suppressed proliferation and migration. We found that C1ORF116, an OVOLs target, is susceptible to genetic and epigenetic aberrations in BC. It is regulated by steroids and functions as a putative autophagy receptor that inhibits antioxidants like thioredoxin. Accordingly, boosting epithelialization lowered glutathione, elevated reactive oxygen species and increased both DNA oxidation and double strand breaks. Epithelialization also associated with redistribution of NRF2 and an altered interplay among p38, ATM, and the other kinases regulating the DNA damage response. Hence, hormonal regulation of OVOLs and chronic stress might permit epithelial differentiation and retard exit from dormancy, while altering redox homeostasis and permitting DNA damage accumulation, which may awaken dormant tumors.

cancer biology↗

bioRxiv2024

SARS-CoV-2 serosurvey of healthy, privately owned cats presenting to a New York City animal hospital in the early phase of the COVID-19 pandemic (2020-2021)

SARS-CoV-2, the cause of the ongoing COVID-19 pandemic, not only infects humans but is also known to infect various species, including domestic and wild animals. While many species have been identified as susceptible to SARS-CoV-2, there are limited studies on the prevalence of SARS-CoV-2 in animals. Both domestic and non-domestic cats are now established to be susceptible to infection by SARS-CoV-2. While serious disease in cats may occur in some instances, the majority of infections appear to be subclinical. Differing prevalence data for SARS-CoV-2 infection of cats have been reported, and are highly context-dependent. Here, we report a retrospective serological survey of cats presented to an animal practice in New York City, located in close proximity to a large medical center that treated the first wave of COVID-19 patients in the U.S. in the Spring of 2020. We sampled 79, mostly indoor, cats between June 2020 to May 2021, the early part of which time the community was under a strict public health "lock-down". Using a highly sensitive and specific fluorescent bead-based multiplex assay, we found an overall prevalence of 13/79 (16%) serologically-positive animals for the study period; however, cats sampled in the Fall of 2020 had a confirmed positive prevalence of 44%. For SARS-CoV-2 seropositive cats, we performed viral neutralization test with live SARS-CoV-2 to additionally confirm presence of SARS-CoV-2 specific antibodies. Of the thirteen seropositive cats, 7/13 (54%) were also positive by virus neutralization, and two of seropositive cats had previously documented respiratory signs, with high neutralization titers of 1/1024 and 1/4096; overall however, there was no statistically significant association of SARS-CoV-2 seropositivity with respiratory signs, or with breed, sex or age of the animals. Follow up sampling of cats showed that positive serological titers were maintained over time. In comparison, we found an overall confirmed positive prevalence of 51% for feline coronavirus (FCoV), an endemic virus of cats, with 30% confirmed negative for FCoV. We demonstrate the impact of SARS-CoV-2 in a defined feline population during the first wave of SARS-CoV-2 infection of humans, and suggest that human-cat transmission was substantial in our study group. Our study provide a new context for SARS-CoV-2 transmission events across species. SignificanceSARS-CoV-2 has a broad animal tropism and can infect a wide range of animal species, leading to an expansion of the viral reservoir. Expansion of this viral reservoir may result in the accumulation of mutations within these species, potentially giving rise to new viral variants and facilitating reverse zoonotic transmission. Domestic cats are particularly noteworthy in this regard due to their close contact with humans. Currently, there are very limited studies on the prevalence of SARS-CoV-2 infection in domestic cats during the early stages of the pandemic, especially in the United States. This retrospective study addresses the gap by investigating seroprevalence of SARS-CoV-2 in cats in New York City, the epicenter of the COVID-19 pandemic in the United States during the early pandemic. Our work underscores the importance of adopting a One Health approach to pandemic prevention and conducting routine surveillance across different animal species

microbiology↗

bioRxiv2023

Modeling cellular self-organization in strain-stiffening hydrogels

We develop a three-dimensional mathematical model framework for the collective evolution of cell populations by an agent-based model (ABM) that mechanically interacts with the surrounding extra-cellular matrix (ECM) modeled as a hydrogel. We derive effective two-dimensional models for the geometrical set-up of a thin hydrogel sheet to study cell-cell and cell-hydrogel mechanical interactions for a range of external conditions and intrinsic material properties. We show that without any stretching of the hydrogel sheets, cells show the well-known tendency to form long chains with varying orientations. Our results further show that external stretching of the sheet produces the expected nonlinear strain-softening or stiffening response, with, however, little qualitative variation of the over-all cell dynamics for all the materials considered. The behavior is remarkably different when solvent is entering or leaving from strain softening or stiffening hydrogels, respectively.

bioengineering↗

bioRxiv2023

Top dressed biochar increases tree seedling growth and decreases sodium leaching

De-icing salts on roadways are nearly ubiquitous in northern cities during winter months, leading to contamination of soils adjacent to roadways. Sodium chloride salts often have detrimental impacts on water and trees, though some species are more sensitive than others. Biochar has the potential to mitigate sodiums harmful effects due to its large surface area:volume ratio and subsequent ability to sorb ions from solution. We conducted a four-month greenhouse experiment to test if biochar applied as either a top dressing or incorporated into the growing medium reduced sodium leaching and buffered tree responses to sodium stress. We also evaluated the effects of salt addition and biochar on four tree species that vary in salt tolerance: Catalpa speciosa (tolerant), Gleditsia triacanthos (tolerant), Acer saccharum (intolerant), and Quercus rubra (intolerant). We found no interactive effects of sodium addition and biochar on sodium leaching or tree growth and physiology. However, we did find that top dressed biochar broadly decreased sodium leaching, likely via positive effects of top dressed biochar on tree seedling growth, Catalpa speciosa in particular. Incorporated biochar, on the other hand, had positive or neutral effects on sodium leaching and negative effects on the production of new shoots and fine roots. Given that biochar is a relatively expensive amendment, it should be used sparingly to improve urban tree growth and health. Overall, this study shows that biochar application decisions have implications for tree growth and soil management.

plant biology↗

bioRxiv2023

FALCON systematically interrogates free fatty acid biology and identifies a novel mediator of lipotoxicity

Cellular exposure to free fatty acids (FFA) is implicated in the pathogenesis of obesity-associated diseases. However, studies to date have assumed that a few select FFAs are representative of broad structural categories, and there are no scalable approaches to comprehensively assess the biological processes induced by exposure to diverse FFAs circulating in human plasma. Furthermore, assessing how these FFA- mediated processes interact with genetic risk for disease remains elusive. Here we report the design and implementation of FALCON (Fatty Acid Library for Comprehensive ONtologies) as an unbiased, scalable and multimodal interrogation of 61 structurally diverse FFAs. We identified a subset of lipotoxic monounsaturated fatty acids (MUFAs) with a distinct lipidomic profile associated with decreased membrane fluidity. Furthermore, we developed a new approach to prioritize genes that reflect the combined effects of exposure to harmful FFAs and genetic risk for type 2 diabetes (T2D). Importantly, we found that c-MAF inducing protein (CMIP) protects cells from exposure to FFAs by modulating Akt signaling and we validated the role of CMIP in human pancreatic beta cells. In sum, FALCON empowers the study of fundamental FFA biology and offers an integrative approach to identify much needed targets for diverse diseases associated with disordered FFA metabolism. HighlightsO_LIFALCON (Fatty Acid Library for Comprehensive ONtologies) enables multimodal profiling of 61 free fatty acids (FFAs) to reveal 5 FFA clusters with distinct biological effects C_LIO_LIFALCON is applicable to many and diverse cell types C_LIO_LIA subset of monounsaturated FAs (MUFAs) equally or more toxic than canonical lipotoxic saturated FAs (SFAs) leads to decreased membrane fluidity C_LIO_LINew approach prioritizes genes that represent the combined effects of environmental (FFA) exposure and genetic risk for disease C_LIO_LIC-Maf inducing protein (CMIP) is identified as a suppressor of FFA-induced lipotoxicity via Akt-mediated signaling C_LI

cell biology↗

bioRxiv2022

Predicting disordered regions driving phase separationof proteins under variable salt concentration

We investigate intrinsically disordered regions (IDRs) of phase separating proteins regarding their impact on liquid-liquid phase separation (LLPS) of the full protein. Our theoretical approach uses a mean-field theory that accounts for sequence-dependent electrostatic interactions via a random-phase approximation (RPA) and in addition allows for variable salt concentration for the condensed and dilute protein phases. The numerical solution of the complete phase diagrams together with the tie lines that we derive for this model system leaves two parameters to be determined by fitting experimental data on concentrations of all species involved in the system. For our comparisons, we focus on two proteins, PGL-3 and FUS, known to undergo LLPS. For PGL-3 we predict that its long IDR near the C-terminus promotes LLPS, which we validate through direct comparison with in vitro experimental results under the same physiological conditions. For the structurally more complex protein FUS the role of the low complexity (LC) domain in LLPS has been intensively studied. Apart from the LC domain we here investigate theoretically two IDRs, one near the N-terminus and another near the C-terminus. Our theoretical analysis of these domains predict that the IDR at the N-terminus (aa 1-285) is the main driver of LLPS of FUS by comparison to in vitro experiments of the full length protein under the same physiological temperature and salt conditions. SIGNIFICANCEIntrinsically disordered proteins are drivers of cellular liquid-liquid phase separation. However, it remains a challenge to directly predict the phase behaviour of a protein based on its primary sequence, and under physiological conditions. We present a random-phase approximation that allows for variable salt concentration and thus accounts for salt partitioning. We use this to link the sequence of the disordered regions with the behaviour of the complete protein through direct comparisons to in vitro phase-separation assays. In particular, for FUS we determine the exact region responsible for LLPS, weighting in a long-standing debate.

biophysics↗

bioRxiv2022

Fluorescein-based sensors to purify human α-cells for functional and transcriptomic analyses

Pancreatic -cells secrete glucagon, an insulin counter-regulatory peptide hormone critical for the maintenance of glucose homeostasis. Investigation of the function of human -cells remains a challenge due to the lack of cost-effective purification methods to isolate high-quality -cells from islets. Here, we use the reaction-based probe diacetylated Zinpyr1 (DA-ZP1) to introduce a novel and simple method for enriching live -cells from dissociated human islet cells with > 97% purity. The -cells, confirmed by sorting and immunostaining for glucagon, were cultured up to 10 days to form -pseudoislets. The -pseudoislets could be maintained in culture without significant loss of viability, and responded to glucose challenge by secreting appropriate levels of glucagon. RNA-sequencing analyses (RNA-seq) revealed that expression levels of key -cell identity genes were sustained in culture while some of the genes such as DLK1, GSN, SMIM24 were altered in -pseudoislets in a time-dependent manner. In conclusion, we report a method to sort human primary -cells with high purity that can be used for downstream analyses such as functional and transcriptional studies.

cell biology↗

bioRxiv2022

Dopamine regulates decision thresholds in human reinforcement learning.

Dopamine fundamentally contributes to reinforcement learning by encoding prediction errors, deviations of an outcome from expectation. Prediction error coding in dopaminergic regions in human functional neuroimaging studies is well replicated. In contrast, replications of behavioral and neural effects of pharmacological modulations of the dopamine system in human reinforcement learning are scarce. Additionally, dopamine contributes to action selection, but direct evidence and process-specific accounts in human reinforcement learning are lacking. Here we examined dopaminergic mechanisms underlying human reinforcement learning in a within-subjects pharmacological approach in male human volunteers (n=31, within-subjects design; Placebo, 150mg L-dopa, 2mg Haloperidol) in combination with functional magnetic resonance imaging and a stationary reinforcement learning task. We had two aims. First, we aimed to replicate previously reported beneficial effects of L-dopa vs. Haloperidol on reinforcement learning from gains. This replication was not successful. We observed no performance benefit of L-Dopa vs. Haloperidol, and no evidence for alterations in neural prediction error signaling. In contrast, Bayesian analyses provided moderate evidence in favor of the null hypothesis. This unsuccessful replication is likely at least partly due to a number of differences in experimental design. Second, using combined reinforcement learning drift diffusion models, we tested the recent proposal that dopamine contributes to action selection by regulating decision thresholds. Model comparison revealed that the data were best accounted for by a reinforcement learning drift diffusion model with separate learning rates for positive and negative prediction errors. The model accounted for both reductions in RTs and increases in accuracy over the course of learning. The only parameter showing robust drug effects was the boundary separation parameter, which revealed reduced decision thresholds under both L-Dopa and Haloperidol, compared to Placebo, and the degree of threshold reduction accounted for individual differences in RTs between conditions. Results are in line with the idea that striatal dopamine regulates decision thresholds during action selection, and that lower dosages of D2 receptor antagonists increase striatal DA release via an inhibition of autoreceptor-mediated feedback mechanisms.

neuroscience↗

bioRxiv2022

A linear SARS-CoV-2 DNA vaccine candidate reduces virus shedding in ferrets

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused more than 600 million cases and over 6 million deaths worldwide. Vaccination has been the main strategy used to contain the spread of the virus, and to avoid hospitalizations and deaths. Currently, there are two mRNA-based and one adenovirus vectored vaccines approved and available for use in the U.S. population. The versatility, low cost and rapid-to-manufacture attributes of DNA vaccines are important advantages over other platforms. However, DNA vaccination must meet higher efficiency levels for use in humans. Importantly, in vivo DNA delivery combined with electroporation (EP) has been successfully used in the veterinary field. Here we evaluated the safety, immunogenicity and protective efficacy of a novel linear SARS-CoV-2 DNA vaccine candidate for delivered by intramuscular injection followed by electroporation (Vet-ePorator) in ferrets. The results demonstrated that the linear SARS-CoV-2 DNA vaccine candidate did not cause unexpected side effects, and was able to elicit neutralizing antibodies and T cell responses using a low dose of the linear DNA construct in prime-boost regimen, and significantly reduced shedding of infectious SARS-CoV-2 through oral and nasal secretions in a ferret model.

immunology↗

bioRxiv2021

Conjunctival epithelial cells resist productive SARS-CoV-2 infection

Although tropism of SARS-CoV-2 for respiratory tract epithelial cells is well established, an open question is whether the conjunctival epithelium is also a target for SARS-CoV-2. Conjunctival epithelial cells, which express viral entry receptors ACE2 and TMPRSS2, constitute the largest exposed epithelium of the ocular surface tissue, and may represent a relevant viral entry route. To address this question, we generated an organotypic air-liquid-interface model of conjunctival epithelium, composed of progenitor, basal and superficial epithelial cells and fibroblasts, which could be maintained successfully up to day 75 of differentiation. Using single-cell RNA Seq, with complementary imaging and virological assays, we observed that while all conjunctival cell types were permissive to SARS-CoV-2 genome expression, a productive infection did not ensue. The early innate immune response to SARS-CoV-2 infection in conjunctival cells was characterised by a robust autocrine and paracrine NF-K{beta} activity, without activation of antiviral interferon signalling. Collectively, these data enrich our understanding of SARS-CoV-2 infection at the human ocular surface, with potential implications for the design of preventive strategies and conjunctival transplants.

cell biology↗

bioRxiv2021

Synthetic periphyton as a model community to examine species dynamics in complex microbial consortia

Phototrophic biofilms, also known as periphyton, are microbial freshwater communities that drive crucial ecological processes in streams and lakes. Gaining a deep mechanistic understanding of the biological processes occurring in natural periphyton remains challenging due to the high complexity and variability of such communities. To address this challenge, we rationally developed a workflow to construct a synthetic community by co-culturing 26 phototrophic species (i.e., diatoms, green algae and cyanobacteria) that were inoculated in a successional sequence to create a periphytic biofilm on glass slides. We show that this community is diverse, stable and highly reproducible in terms of microbial composition, function and 3D spatial structure of the biofilm. We also demonstrate the ability to monitor microbial dynamics at the single species level during periphyton development and how their abundances are impacted by stressors such as increased temperature and a herbicide, singly and in combination. Overall, such a synthetic periphyton, grown under controlled conditions, can be used as a model system for theory testing through targeted manipulation.

synthetic biology↗

bioRxiv2021

Increased temporal discounting and reduced model-based control in problem gambling are not substantially modulated by exposure to virtual gambling environments.

High-performance virtual reality (VR) technology has opened new possibilities for the examination of the reactivity towards addiction-related cues (cue-reactivity) in addiction. In this preregistered study (https://osf.io/4mrta), we investigated the subjective, physiological, and behavioral effects of gambling-related VR environment exposure in participants reporting frequent or pathological gambling (n=31) as well as non-gambling controls (n=29). On two separate days, participants explored two rich and navigable VR-environments (neutral: cafe vs. gambling-related: casino/sports-betting facility), while electrodermal activity and heart rate were continuously measured using remote sensors. Within VR, participants performed a temporal discounting task and a sequential decision-making task designed to assess model-based and model-free contributions to behavior. Replicating previous findings, we found strong evidence for increased temporal discounting and reduced model-based control in participants reporting frequent or pathological gambling. Although VR gambling environment exposure increased subjective craving, there was if anything inconclusive evidence for further behavioral or physiological effects. Instead, VR exposure substantially increased physiological arousal (electrodermal activity), across groups and conditions. VR is a promising tool for the investigation of context effects in addiction, but some caution is warranted since effects of real gambling environments might not generally replicate in VR. Future studies should delineate how factors such as cognitive load and ecological validity could be balanced to create a more naturalistic VR experience.

neuroscience↗

bioRxiv2021

A single-cell atlas of lymphocyte adaptive immune repertoires and transcriptomes reveals age-related differences in convalescent COVID-19 patients

COVID-19 disease outcome is highly dependent on adaptive immunity from T and B lymphocytes, which play a critical role in the control, clearance and long-term protection against SARS-CoV-2. To date, there is limited knowledge on the composition of the T and B cell immune receptor repertoires [T cell receptors (TCRs) and B cell receptors (BCRs)] and transcriptomes in convalescent COVID-19 patients of different age groups. Here, we utilize single-cell sequencing (scSeq) of lymphocyte immune repertoires and transcriptomes to quantitatively profile the adaptive immune response in COVID-19 patients of varying age. We discovered highly expanded T and B cells in multiple patients, with the most expanded clonotypes coming from the effector CD8+ T cell population. Highly expanded CD8+ and CD4+ T cell clones show elevated markers of cytotoxicity (CD8: PRF1, GZMH, GNLY; CD4: GZMA), whereas clonally expanded B cells show markers of transition into the plasma cell state and activation across patients. By comparing young and old convalescent COVID-19 patients (mean ages = 31 and 66.8 years, respectively), we found that clonally expanded B cells in young patients were predominantly of the IgA isotype and their BCRs had incurred higher levels of somatic hypermutation than elderly patients. In conclusion, our scSeq analysis defines the adaptive immune repertoire and transcriptome in convalescent COVID-19 patients and shows important age-related differences implicated in immunity against SARS-CoV-2.

immunology↗

bioRxiv2021

Single-cell sequencing of plasma cells from COVID-19 patients reveals highly expanded clonal lineages produce specific and neutralizing antibodies to SARS-CoV-2

Isolation and characterization of antibodies in COVID-19 patients has largely focused on memory B cells, however it is the antibody-secreting plasma cells that are directly responsible for the production of serum antibodies, which play a critical role in controlling and resolving SARS-CoV-2 infection. To date there is little known about the specificity of plasma cells in COVID-19 patients. This is largely because plasma cells lack surface antibody expression, which complicates their screening. Here, we describe a technology pipeline that integrates single-cell antibody repertoire sequencing and high-throughput mammalian display screening to interrogate the specificity of plasma cells from 16 convalescent COVID-19 patients. Single-cell sequencing allows us to profile antibody repertoire features in these patients and identify highly expanded clonal lineages. Mammalian display screening is employed to reveal that 37 antibodies (out of 132 candidates) derived from expanded plasma cell clonal lineages are specific for SARS-CoV-2 antigens, including antibodies that target the receptor binding domain (RBD) with high affinity and exhibit potent neutralization of SARS-CoV-2. One Sentence SummarySingle-cell antibody repertoire sequencing and high-throughput screening identifies highly expanded plasma cells from convalescent COVID-19 patients that produce SARS-CoV-2-specific antibodies capable of potent neutralization.

immunology↗

bioRxiv2021

Susceptibility of white-tailed deer (Odocoileus virginianus) to SARS-CoV-2

The origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing the global coronavirus disease 19 (COVID-19) pandemic, remains a mystery. Current evidence suggests a likely spillover into humans from an animal reservoir. Understanding the host range and identifying animal species that are susceptible to SARS-CoV-2 infection may help to elucidate the origin of the virus and the mechanisms underlying cross-species transmission to humans. Here we demonstrated that white-tailed deer (Odocoileus virginianus), an animal species in which the angiotensin converting enzyme 2 (ACE2) - the SARS-CoV-2 receptor - shares a high degree of similarity to humans, are highly susceptible to infection. Intranasal inoculation of deer fawns with SARS-CoV-2 resulted in established subclinical viral infection and shedding of infectious virus in nasal secretions. Notably, infected animals transmitted the virus to non-inoculated contact deer. Viral RNA was detected in multiple tissues 21 days post-inoculation (pi). All inoculated and indirect contact animals seroconverted and developed neutralizing antibodies as early as day 7 pi. The work provides important insights into the animal host range of SARS-CoV-2 and identifies white-tailed deer as a susceptible wild animal species to the virus. IMPORTANCEGiven the presumed zoonotic origin of SARS-CoV-2, the human-animal-environment interface of COVID-19 pandemic is an area of great scientific and public- and animal-health interest. Identification of animal species that are susceptible to infection by SARS-CoV-2 may help to elucidate the potential origin of the virus, identify potential reservoirs or intermediate hosts, and define the mechanisms underlying cross-species transmission to humans. Additionally, it may also provide information and help to prevent potential reverse zoonosis that could lead to the establishment of a new wildlife hosts. Our data show that upon intranasal inoculation, white-tailed deer became subclinically infected and shed infectious SARS-CoV-2 in nasal secretions and feces. Importantly, indirect contact animals were infected and shed infectious virus, indicating efficient SARS-CoV-2 transmission from inoculated animals. These findings support the inclusion of wild cervid species in investigations conducted to assess potential reservoirs or sources of SARS-CoV-2 of infection.

microbiology↗

bioRxiv2020

Myosin 10 and a Cytoneme-Localized Ligand Complex Promote Morphogen Transport

Morphogens function in concentration-dependent manners to instruct cell fate during tissue patterning. Molecular mechanisms by which these signaling gradients are established and reinforced remain enigmatic. The cytoneme transport model posits that specialized filopodia extend between morphogen-sending and responding cells to ensure that appropriate signal activation thresholds are achieved across developing tissues. How morphogens are transported along and deployed from cytonemes is not known. Herein we show that the actin motor Myosin 10 promotes cytoneme-based transport of Sonic Hedgehog (SHH) morphogen to filopodial tips, and that SHH movement within cytonemes occurs by vesicular transport. We demonstrate that cytoneme-mediated deposition of SHH onto receiving cells induces a rapid signal response, and that SHH cytonemes are promoted by a complex containing a ligand-specific deployment protein and associated co-receptor. One-Sentence summaryCytoneme-based delivery of the Sonic Hedgehog activation signal is promoted by Myosin 10 and BOC/CDON co-receptor function.

cell biology↗

bioRxiv2020

A causal role for estradiol in human reinforcement learning

The sex hormone estrogen is hypothesized to play a key role in human cognition via its interactions with the dopaminergic system. Work in rodents has shown that estrogens most potent form, estradiol, impacts striatal dopamine functioning predominately via increased D1-receptor signalling, while human work has suggested that high estradiol levels are associated with altered reward sensitivity. Here, we addressed two fundamental questions: 1) whether estradiol causally alters reward sensitivity in men, and 2) whether this effect of estradiol is moderated by individual variation in polymorphisms of dopaminergic genes. To test this, we performed a double-blind placebo-controlled administration study in which hundred men received either a single dose of estradiol (2 mg) or placebo. We found that estradiol administration increased reward sensitivity, which was moderated by baseline dopamine. This was observed in choice behaviour and increased learning rates. These results confirm a causal role of estradiol in reinforcement learning in men that is moderated by the striatal dopaminergic pathway.

neuroscience↗