Biology subjects

Pellegrini, M.

Publications and source records attributed to Pellegrini, M..

At least 73 records · Page 4Linked to original sources

bioRxiv2021

High-quality genome and methylomes illustrate features underlying evolutionary success of oaks

The genus Quercus, which emerged ~55 million years ago during globally warm temperatures, diversified into ~450 species. We present a high-quality de novo genome assembly of a California endemic oak, Quercus lobata, revealing features consistent with oak evolutionary success. Effective population size remained large throughout history despite declining since the early Miocene. Analysis of 39,373 mapped protein-coding genes outlined copious duplications consistent with genetic and phenotypic diversity, both by retention of genes created during the ancient{gamma} whole genome hexaploid duplication event and by tandem duplication within families, including the numerous resistance genes and also unexpected candidate genes for an incompatibility system involving multiple non-self-recognition genes. An additional surprising finding is that subcontext-specific patterns of DNA methylation associated with transposable elements reveal broadly-distributed heterochromatin in intergenic regions, similar to grasses (another highly successful taxon). Collectively, these features promote genetic and phenotypic variation that would facilitate adaptability to changing environments.

genomics↗

bioRxiv2021

PFKFB3 DEPLETION ACTIVATES β-CELL REPLICATION BY CELL COMPETITIVE CULLING OF COMPROMISED β-CELLS UNDER STRESS

Highly conserved hypoxia-inducible factor 1 alpha (HIF1) and its target 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) play a critical role in the survival of damaged {beta}-cells in type 2 diabetes (T2D) while rendering {beta}-cells non-responsive to glucose stimulation by mitochondrial suppression. HIF1-PFKFB3 is activated in 30-50% of all {beta}-cells in diabetic islets, leaving an open question of whether targeting this pathway may adjust {beta}-cell mass and function to the specific metabolic demands during diabetogenic stress. Our previous studies of {beta}-cells under amyloidogenic stress by human islet amyloid polypeptide (hIAPP) revealed that PFKFB3 is a metabolic execution arm of the HIF1 pathway with potent implications on Ca2+ homeostasis, metabolome, and mitochondrial form and function. To discriminate the role of PFKFB3 from HIF1 in vivo, we generated mice with conditional {beta}-cell specific disruption of the Pfkfb3 gene on a hIAPP+/- background and a high-fat diet (HFD) [PFKFB3{beta}KO + diabetogenic stress (DS)]. PFKFB3 disruption in {beta}-cells under diabetogenic stress led to selective purging of hIAPP-damaged {beta}-cells and the disappearance of bihormonal insulin- and glucagon-positive cells, thus compromised {beta}-cells. At the same time, PFKFB3 disruption led to a three-fold increase in {beta}-cell replication resembling control levels as measured with minichromosome maintenance 2 protein (MCM2). PFKFB3 disruption depleted bihormonal cells while increased {beta}-cell replication that was reflected in the increased {beta}-/-cell ratio and maintained {beta}-cell mass. Analysis of metabolic performance indicated comparable glucose intolerance and reduced plasma insulin levels in PFKFB3{beta}KO DS relative to PFKFB3WT DS mice. In the PFKFB3{beta}KO DS group, plasma glucagon levels were reduced compared to PFKFB3WT DS mice and were in line with increased insulin sensitivity. Glucose intolerance in PFKFB3{beta}KO DS mice could be explained by the compensatory expression of HIF1 after disruption of PFKFB3. Our data strongly suggest that the replication and functional recovery of {beta}-cells under diabetogenic stress depend on selective purification of HIF1 and PFKFB3-positive {beta}-cells. Thus, HIF1-PFKFB3-dependent activation of cell competition and purging of compromised {beta}-cells may yield functional competent {beta}-cell mass in diabetes.

cell biology↗

bioRxiv2021

Epigenetic models predict age and aging in plains zebras and other equids

Five of the seven extant wild species of the genus Equus are species of significant conservation concern. Effective conservation and management of such threatened wildlife populations depends on the ability to estimate demographic trends and population viability and therefore requires accurate assessment of age structure. However, reliably aging wildlife is challenging as many methods are highly invasive, inaccurate, or both. Epigenetic aging models, which estimate individual age with high accuracy based on genomic methylation patterns, are promising developments in this regard. Importantly, epigenetic aging models developed for one species can potentially predict age with high accuracy in sister taxa. Using blood and biopsy samples from known age plains zebras (Equus quagga), we developed epigenetic clocks (ECs) to predict chronological age, and epigenetic pacemaker (EPM) models to predict biological age. We tested the ability of our blood-based EC to predict ages of Grevys zebras, Somali asses and domestic horses, from blood samples. Because our samples came from a population with a complex pedigree, we also leveraged information from a previous sequencing effort to measure the association between levels of inbreeding (F and ROH) and the age acceleration as measured by DNA methylation. The resulting models describe the trajectory of epigenetic aging in plains zebras and accurately predict the ages of plains zebras and other equids. We found moderate support for a slight acceleration of aging with increased inbreeding.

developmental biology↗

bioRxiv2021

Systematic evaluation of transcriptomics-based deconvolution methods and references using thousands of clinical samples

Estimating cell type composition of blood and tissue samples is a biological challenge relevant in both laboratory studies and clinical care. In recent years, a number of computational tools have been developed to estimate cell type abundance using gene expression data. While these tools use a variety of approaches, they all leverage expression profiles from purified cell types to evaluate the cell type composition within samples. In this study, we compare ten deconvolution tools and evaluate their performance while using each of eleven separate reference profiles. Specifically, we have run deconvolution tools on over 4,000 samples with known cell type proportions, spanning both immune and stromal cell types. Twelve of these represent in vitro synthetic mixtures and 300 represent in silico synthetic mixtures prepared using single cell data. A final 3,728 clinical samples have been collected from the Framingham Cohort, for which cell populations have been quantified using electrical impedance cell counting. When tools are applied to the Framingham dataset, the tool EPIC produces the highest correlation while GEDIT produces the lowest error. The best tool for other datasets is varied, but CIBERSORT and GEDIT most consistently produce accurate results. In terms of reference choice, we find that the Human Primary Cell Atlas (HPCA) and references published by the EPIC authors produce accurate results for the largest number of tools and datasets. When applying deconvolution to blood samples, the leukocyte reference matrix LM22 is also a suitable choice, usually (but not always) outperforming HPCA and EPIC. Running time varies substantially across tools. For as many as 5052 samples, SaVanT and dtangle reliably finish in under one minute, while slower tools may require up to two hours. However, when using custom references, CIBERSORT can run very slowly, taking over 24 hours to complete for large datasets. We conclude that combining the best tools with optimal reference datasets can provide significant gains in accuracy when carrying out deconvolution tasks.

bioinformatics↗

bioRxiv2021

Hibernation slows epigenetic aging in yellow-bellied marmots

Species that hibernate live longer than would be expected based solely on their body size. Hibernation is characterized by long periods of metabolic suppression (torpor) interspersed by short periods of increased metabolism (arousal). The torpor-arousal cycles occur multiple times during hibernation, and it has been suggested that processes controlling the transition between torpor and arousal states cause aging suppression. Metabolic rate is also a known correlate of longevity, we thus proposed the hibernation-aging hypothesis whereby aging is suspended during hibernation. We tested this hypothesis in a well-studied population of yellow-bellied marmots (Marmota flaviventer), which spend 7-8 months per year hibernating. We used two approaches to estimate epigenetic age: the epigenetic clock and the epigenetic pacemaker. Variation in epigenetic age of 149 samples collected throughout the life of 73 females were modeled using generalized additive mixed models (GAMM), where season (cyclic cubic spline) and chronological age (cubic spline) were fixed effects. As expected, the GAMM using epigenetic ages calculated from the epigenetic pacemaker was better able to detect nonlinear patterns in epigenetic age change over time. We observed a logarithmic curve of epigenetic age with time, where the epigenetic age increased at a higher rate until females reached sexual maturity (2-years old). With respect to circannual patterns, the epigenetic age increased during the summer and essentially stalled during the winter. Our enrichment analysis of age-related CpG sites revealed pathways related to development and cell differentiation, while the season-related CpGs enriched pathways related to central carbon metabolism, immune system, and circadian clock. Taken together, our results are consistent with the hibernation-aging hypothesis and may explain the enhanced longevity in hibernators.

evolutionary biology↗

bioRxiv2021

A mammalian methylation array for profiling methylation levels at conserved sequences

Infinium methylation arrays are not available for the vast majority of non-human mammals. Moreover, even if species-specific arrays were available, probe differences between them would confound cross-species comparisons. To address these challenges, we developed the mammalian methylation array, a single custom array that measures 36k CpGs that are well conserved across mammalian species. We designed a set of probes on the array that can tolerate specific cross-species mutations. We annotate the array in over 200 species and report CpG island status and chromatin states in select species. Calibration experiments demonstrate the high fidelity in humans, rats, and mice. The mammalian methylation array has several strengths: it applies to all mammalian species even those that have not yet been sequenced, it provides deep coverage of conserved cytosines facilitating the development epigenetic biomarkers, and it increases the probability that biological insights gained in one species will translate to others.

bioinformatics↗

bioRxiv2021

The intensity of the immune response to LPS and E. coli regulates the induction of preterm labor in Rhesus Macaques

Intrauterine infection/inflammation (IUI) is a major contributor to preterm labor (PTL). However, IUI does not invariably cause PTL. We hypothesized that quantitative and qualitative differences in immune response exist in subjects with or without PTL. To define the triggers for PTL, we developed Rhesus macaque models of IUI driven by lipopolysaccharyde (LPS) or live E. coli. PTL did not occur in LPS challenged Rhesus macaque while E. coli infected animals frequently delivered preterm. Although LPS and live E. coli both caused immune cell infiltration, E. coli infected animals showed higher levels of inflammatory mediators, particularly IL6 and prostaglandins, in the chorioamnion decidua and amniotic fluid. Neutrophil infiltration in the chorion was a common feature to both LPS and E. coli. However, neutrophilic infiltration and IL6 and PTGS2 expression in the amnion was specifically induced by live E. coli. RNASeq analysis of fetal membranes revealed that specific pathways involved in augmentation of inflammation including type I interferon response, chemotaxis, sumoylation and iron homeostasis were upregulated in the E. coli group compared to the LPS group. Our data suggest that intensity of the host immune response to IUI may determine susceptibility to PTL.

immunology↗

bioRxiv2020

Single Cell and Spatial Transcriptomics Defines the Cellular Architecture of the Antimicrobial Response Network in Human Leprosy Granulomas

Granulomas are complex cellular structures comprised predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated single cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RR), a dynamic process in which some patients with disseminated lepromatous leprosy (L-lep) transition towards self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions, and regulated by IFN-{gamma} and IL-1{beta}. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts contribute to the antimicrobial response.

immunology↗

bioRxiv2020

Comparative Analysis of Embryo Proper and Suspensor Transcriptomes in Plant Embryos With Different Morphologies

An important question is what genes govern the differentiation of plant embryos into suspensor and embryo-proper regions following fertilization and division of the zygote. We compared embryo proper and suspensor transcriptomes of four plants that vary in embryo morphology within the suspensor region. We determined that genes encoding enzymes in several metabolic pathways leading to the formation of hormones, such as gibberellic acid, and other metabolites are up-regulated in giant Scarlet Runner Bean and Common Bean suspensors. Genes involved in transport and Golgi body organization are up-regulated within the suspensors of these plants as well - strengthening the view that giant specialized suspensors serve as a hormone factory and a conduit for transferring substances to the developing embryo proper. By contrast, genes controlling transcriptional regulation, development, and cell division are up-regulated primarily within the embryo proper. Transcriptomes from less specialized soybean and Arabidopsis suspensors demonstrated that fewer genes encoding metabolic enzymes and hormones are up-regulated. Genes active in the embryo proper, however, are functionally similar to those active in Scarlet Runner Bean and Common Bean embryo proper regions. We uncovered a set of suspensor- and embryo-proper-specific transcription factors (TFs) that are shared by all embryos irrespective of morphology, suggesting that they are involved in early differentiation processes common to all plants. ChIP-Seq experiments with Scarlet Runner Bean and soybean WOX9, an up-regulated suspensor TF, gained entry into a regulatory network important for suspensor development irrespective of morphology. SignificanceHow plant embryos are differentiated into embryo proper and suspensor regions following fertilization is a major unanswered question. The suspensor is unique because it can vary in morphology in different plant species. We hypothesized that regulatory genes controlling the specification of embryo proper and suspensor regions should be shared by all plants irrespective of embryo morphology. We compared embryo proper and suspensor transcriptomes of plants with distinct suspensor morphologies. Scarlet Runner Bean and Common Bean have highly specialized giant suspensor regions, whereas soybean and Arabidopsis suspensors are smaller and less specialized. We uncovered a small set of embryo-proper- and suspensor-specific transcription factors shared by all embryos irrespective of morphology, suggesting that they play an important role in early embryo differentiation.

plant biology↗

bioRxiv2020

DNA methylation study of age and sex in baboons and four other primates

DNA methylation data have been successfully used to develop highly accurate estimators of age ("epigenetic clocks") in many mammalian species. With a view of extending such epigenetic clocks to all primate species, we analyzed DNA methylation profiles of 2400 tissues derived from 37 primate species including 11 haplorhine species (baboons, marmosets, vervets, rhesus macaque, chimpanzees, gorillas, orangutan, humans) and 26 strepsirrhine species (suborders Lemuriformes and Lorisiformes). From these we present here, pan-primate epigenetic clocks which are highly accurate for all primates including humans (age correlation R=0.98). We also carried out in-depth analysis of baboon DNA methylation profiles and generated five epigenetic clocks for baboons (Olive-yellow baboon hybrid), one of which, the pan-tissue epigenetic clock, was trained on seven tissue types (fetal cerebral cortex, adult cerebral cortex, cerebellum, adipose, heart, liver, and skeletal muscle) with ages ranging from late fetal life to 22.8 years of age. To facilitate translation of findings in baboons to humans, we further constructed two dual-species, human-baboon clocks. We also identified and present here, epigenetic predictors of sex that apply to all primate species. Low overlap can be observed between age- and sex-related CpGs. Overall, this study advances our understanding of conserved age- and sex-related epigenetic changes in primates, and provides biomarkers to study the aging of all primate species with the facility to readily translate any findings between primate species.

developmental biology↗

bioRxiv2020

Single cell transcriptomic analysis reveals the impact of elevating neurogenic factor expression on human retinal organoid development

The developing retina expresses multiple bHLH transcription factors. Their precise functions and interactions in uncommitted retinal progenitors remain to be fully elucidated. Here, we investigate the roles of bHLH factors ATOH7 and Neurog2 in developing human ES cell-derived 3D retinal organoids. Single cell transcriptome analyses identify three states of proliferating retinal progenitors: pre-neurogenic, neurogenic, and cell cycle-exiting progenitors. Each shows different expression profile of bHLH factors. The distinct cell cycle-exiting progenitors feed into a postmitotic heterozygous neuroblast pool that gives rise to early born neuronal lineages. Elevating ATOH7 or Neurog2 expression accelerates the transition from the pre-neurogenic to the neurogenic state, and expands the exiting progenitor and neuroblast populations. In addition, ATOH7 and Neurog2 significantly, yet differentially, enhance retinal ganglion cell and cone photoreceptor production. Moreover, single cell transcriptome analyses reveal that ATOH7 and Neurog2 assert positive autoregulation, suppress key bHLH factors associated with the neurogenic progenitors, and elevate bHLH factors expressed by exiting progenitors and differentiating neuroblasts. This study thus provides novel insight regarding how ATOH7 and Neurog2 impact human retinal progenitor behaviors and neuroblast fate choices.

developmental biology↗

bioRxiv2020

BiSulfite Bolt: A BiSulfite Sequencing Analysis Platform

BackgroundBisulfite sequencing is commonly employed to measure DNA methylation. Processing bisulfite sequencing data is often challenging due to the computational demands of mapping a low complexity, asymmetrical library and the lack of a unified processing toolset to produce an analysis ready methylation matrix from read alignments. To address these shortcomings, we have developed BiSulfite Bolt (BSBolt); a fast and scalable bisulfite sequencing analysis platform. BSBolt performs a pre-alignment sequencing read assessment step to improve efficiency when handling asymmetrical bisulfite sequencing libraries. FindingsWe evaluated BSBolt against simulated and real bisulfite sequencing libraries. We found that BSBolt provides accurate and fast bisulfite sequencing alignments and methylation calls. We also compared BSBolt to several existing bisulfite alignment tools and found BSBolt outperforms Bismark, BSSeeker2, BISCUIT, and BWA-Meth based on alignment accuracy and methylation calling accuracy. ConclusionBSBolt offers streamlined processing of bisulfite sequencing data through an integrated toolset that offers support for simulation, alignment, methylation calling, and data aggregation. BSBolt is implemented as a python package and command line utility for flexibility when building informatics pipelines. BSBolt is available at https://github.com/NuttyLogic/BSBolt under an MIT license.

bioinformatics↗

bioRxiv2020

Single-Cell RNA Sequencing of Batch Chlamydomonas Cultures Reveals Heterogeneity in their Diurnal Cycle Phase

The photosynthetic unicellular alga Chlamydomonas (Chlamydomonas reinhardtii) is a versatile reference for algal biology because of the facility with which it can be cultured in the laboratory. Genomic and systems biology approaches have previously been used to describe how the transcriptome responds to environmental changes, but this analysis has been limited to bulk data, representing the average behavior from pools of cells. Here, we apply single-cell RNA sequencing (scRNA-seq) to probe the heterogeneity of Chlamydomonas cell populations under three environments and in two genotypes differing in the presence of a cell wall. First, we determined that RNA can be extracted from single algal cells with or without a cell wall, offering the possibility to sample algae communities in the wild. Second, scRNA-seq successfully separated single cells into non-overlapping cell clusters according to their growth conditions. Cells exposed to iron or nitrogen deficiency were easily distinguished despite a shared tendency to arrest cell division to economize resources. Notably, these groups of cells recapitulated known patterns observed with bulk RNA-seq, but also revealed their inherent heterogeneity. A substantial source of variation between cells originated from their endogenous diurnal phase, although cultures were grown in constant light. We exploited this result to show that circadian iron responses may be conserved from algae to land plants. We propose that bulk RNA-seq data represent an average of varied cell states that hides underappreciated heterogeneity. One-sentence summaryWe show that single-cell RNA-seq (scRNA-seq) can be applied to Chlamydomonas cultures to reveal the that heterogenity in bulk cultures is largely driven by diurnal cycle phases The author responsible for distribution of materials integral to the findings presented in this article in accordance with the policy described in the Instructions for Authors (www.plantcell.org) is: Matteo Pellegrini (matteop@mcdb.ucla.edu)

genomics↗

bioRxiv2020

A DNAmRep epigenetic fingerprint for determining cellular replication age

ii.Aging is known to elicit dramatic changes to DNA methylation (DNAm), although the causes and consequences of such alterations are not clear and require further exploration. Our ability to experimentally uncover mechanisms of epigenetic aging will be greatly enhanced by our ability to study and manipulate these changes using in vitro models. However, it remains unclear whether the changes elicited by cells in culture can serve as a model of what is observed in aging tissues in vivo. To test this, we serially passaged mouse embryonic fibroblasts (MEFs) and assessed changes in DNAm at each time-point via RRBS. By developing a measure that tracked cellular aging in vitro, we tested whether it tracked physiological aging in various mouse tissues and whether anti-aging interventions modulate this measure. Our measure, termed DNAmCULTURE, was shown to strongly increase with age when examined in multiple tissues (liver, lung, kidney, blood, and adipose). As a control, we confirmed that the measure was not a marker of cellular senescence, suggesting that it reflects a distinct yet progressive cellular aging phenomena that can be induced in vitro. Furthermore, we demonstrated slower epigenetic aging in animals undergoing caloric restriction and a resetting of our measure in lung and kidney fibroblasts when re-programmed to iPSCs. Enrichment and clustering analysis implicated SUZ12, EED and Polycomb group (PcG) factors as potentially important chromatin regulators in translational culture aging phenotypes. Overall, this study supports the concept that physiologically relevant aging changes can be induced in vitro and moving forward, used to uncover mechanistic insights into epigenetic aging.

pathology↗

bioRxiv2020

Mechanism and inhibition of SARS-CoV-2 PLpro

Coronaviruses, including SARS-CoV-2, encode multifunctional proteases that are essential for viral replication and evasion of host innate immune mechanisms. The papain-like protease PLpro cleaves the viral polyprotein, and reverses inflammatory ubiquitin and anti-viral ubiquitin-like ISG15 protein modifications1,2. Drugs that target SARS-CoV-2 PLpro (hereafter, SARS2 PLpro) may hence be effective as treatments or prophylaxis for COVID-19, reducing viral load and reinstating innate immune responses3. We here characterise SARS2 PLpro in molecular and biochemical detail. SARS2 PLpro cleaves Lys48-linked polyubiquitin and ISG15 modifications with high activity. Structures of PLpro bound to ubiquitin and ISG15 reveal that the S1 ubiquitin binding site is responsible for high ISG15 activity, while the S2 binding site provides Lys48 chain specificity and cleavage efficiency. We further exploit two strategies to target PLpro. A repurposing approach, screening 3727 unique approved drugs and clinical compounds against SARS2 PLpro, identified no compounds that inhibited PLpro consistently or that could be validated in counterscreens. More promisingly, non-covalent small molecule SARS PLpro inhibitors were able to inhibit SARS2 PLpro with high potency and excellent antiviral activity in SARS-CoV-2 infection models.

biochemistry↗

bioRxiv2020

The IMEx Coronavirus interactome: an evolving map of Coronaviridae-Host molecular interactions

The current Coronavirus Disease 2019 (COVID-19) pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has spurred a wave of research of nearly unprecedented scale. Among the different strategies that are being used to understand the disease and develop effective treatments, the study of physical molecular interactions enables studying fine-grained resolution of the mechanisms behind the virus biology and the human organism response. Here we present a curated dataset of physical molecular interactions, manually extracted by IMEx Consortium curators focused on proteins from SARS-CoV-2, SARS-CoV-1 and other members of the Coronaviridae family. Currently, the dataset comprises over 2,200 binarized interactions extracted from 86 publications. The dataset can be accessed in the standard formats recommended by the Proteomics Standards Initiative (HUPO-PSI) at the IntAct database website (www.ebi.ac.uk/intact), and will be continuously updated as research on COVID-19 progresses.

bioinformatics↗

bioRxiv2020

Genetic polymorphisms do not predict inter-individual variability to cathodal transcranial direct current stimulation of the primary motor cortex

High variability between individuals (i.e. inter-individual variability) in response to transcranial direct current stimulation (tDCS) has become a commonly reported issue in the tDCS literature in recent years. Inherent genetic differences between individuals has been proposed as a contributing factor to observed response variability. This study investigated whether tDCS inter-individual variability was genetically mediated. A large sample-size of sixty-one healthy males received cathodal-tDCS (c-tDCS) and sham-tDCS, of the primary motor cortex at 1mA and 10-minutes via 6x4cm active and 7x5cm return electrodes. Corticospinal excitability (CSE) was assessed via twenty-five single-pulse transcranial magnetic stimulation motor evoked potentials (MEP). Intracortical inhibition (ICI) was assessed via twenty-five 3ms inter-stimulus interval (ISI) paired-pulse MEPs, known as short-interval intracortical inhibition (SICI). Intracortical facilitation (ICF) was assessed via twenty-five 10ms ISI paired-pulse MEPs. Gene variants encoding for excitatory and inhibitory neuroreceptors were determined via saliva samples. Pre-determined thresholds and statistical cluster analyses were used to subgroup individuals. Two distinct subgroups were identified, responders reducing CSE following c-tDCS and non-responders showing no reduction or even increase in CSE. Differences in CSE between responders and non-responders following c-tDCS were not explained by changes in SICI or ICF. No significant relationships were reported between gene variants and inter-individual variability to c-tDCS suggesting the chosen gene variants did not influence the activity of the neuroreceptors involved in eliciting changes in CSE in responders following c-tDCS. In this largest c-tDCS study of its kind, novel insights were reported into the contribution genetic factors may play in observed inter-individual variability to c-tDCS.

neuroscience↗

bioRxiv2020

How prior pair-bonding experience affects future bonding behavior in monogamous prairie voles

Monogamous prairie voles (Microtus ochrogaster) form mating-based pair bonds. Although wild prairie voles rarely re-pair following loss of a partner, laboratory studies have shown that previous pairing and mating does not negate the ability to form a new partner preference. However, little is known about how prior bond experience may alter the trajectory and display of a new pair bond. In the present study, we disrupted an initial pair bond by separating partners and then varied the amount of time before a new partner was introduced. We assessed how separation time affected the stability of partner preference over time and influenced decision-making in male voles performing a head-to-head partner preference test in which they chose between the first and second partner. We found that the ability to consistently display a preference for the second partner, supplanting the initial pair bond, depended on how long the test animal was separated from their first partner. Prior bonding experience also shaped the subsequent effects of mating on partner preference. Partner preference strength was sensitive to latency to mate with the second partner but not the first partner, irrespective of separation time. These results suggest that the ability to form a consistent, strong preference for a new partner after an initial pair bond depends upon the amount of time that has passed since separation from the first partner. These results provide valuable insight into how social bonds are dynamically shaped by prior social experience and identify variables that contribute to recovery from partner loss and the ability to form a new pair bond.Competing Interest StatementThe authors have declared no competing interest.View Full Text

animal behavior and cognition↗