Biology subjects

White, P.

Publications and source records attributed to White, P..

At least 19 recordsLinked to original sources

bioRxiv2026

BioDCASE: Using data challenges to make community advances in computational bioacoustics

Computational bioacoustics has seen significant advances in recent decades. However, the rate of insights from automated analysis of bioacoustic audio lags behind our rate of collecting the data - due to key capacity constraints in data annotation and bioacoustic algorithm development. Gaps in analysis methodology persist: not because they are intractable, but because of resource limitations in the bioacoustics community. To bridge these gaps, we advocate the open science method of data challenges, structured as public contests. We conducted a bioacoustics data challenge named BioDCASE, within the format of an existing event (DCASE). In this work we report on the procedures needed to select and then conduct useful bioacoustics data challenges. We consider aspects of task design such as dataset curation, annotation, and evaluation metrics. We report the three tasks included in BioDCASE 2025 and the resulting progress made. Based on this we make recommendations for open community initiatives in computational bioacoustics.

animal behavior and cognition↗

bioRxiv2026

SEZ6L2 Loss Disrupts Motor Coordination, Cognitive Function, and Synaptic Connectivity

The SEZ6 family, composed of SEZ6, SEZ6L, and SEZ6L2, plays essential roles in neurodevelopment, synaptic organization, and complement regulation. However, the specific contribution of SEZ6L2 to brain function remains largely unexplored. In this study, we provide the first comprehensive behavioral and neurobiological characterization of Sez6l2 knockout (KO) mice and directly compare their phenotype with Sez6 triple knockout (TKO) mice, which lack all three Sez6 family genes. Sez6l2 KO mice exhibit impairments across multiple behavioral domains, including motor coordination, gait, sociability, sensory processing, and goal-directed repetitive behaviors. Several phenotypes, particularly motor deficits, worsen with age. Male Sez6l2 KO mice also demonstrate enhanced fear learning and increased prepulse inhibition, revealing sex-specific alterations in sensorimotor gating. At the synaptic level, Sez6l2 KO mice show reduced dendritic spine length and decreased expression of key postsynaptic proteins suggesting impaired excitatory synaptic connectivity. These structural and molecular abnormalities likely contribute to the observed behavioral deficits. In comparison, Sez6 TKO mice display more severe impairments across most measures. Together, these findings establish SEZ6L2 as a critical and non-redundant regulator of motor, cognitive, and synaptic function and provide mechanistic insight into how dysfunction within the SEZ6 family may contribute to neurodevelopmental and neurodegenerative disorders.

neuroscience↗

bioRxiv2025

Computational Stabilization of the Human VH Germline Repertoire to Enable Conditional Multi-Specific Therapeutic Development

Protein-based biologic therapies, particularly antibody-like therapeutics, have emerged as a major modality to treat nearly all chronic and infectious diseases. Antagonists have dominated the first wave of antibody and antibody-like biologics, whereas agonism has generally been challenging due to systemic activation leading to issues with therapeutic index and problems with pleiotropic activity. Additionally, agonists that use native proteins such as cytokines can be challenging to produce at scale given these proteins evolved to act locally and are not designed for large scale manufacturing. To address these challenges, we generated a biologics platform comprised of stabilized human VH domains (VH-Select) which encompass the entire human germline repertoire with the goal of building multispecific biologics denoted Tentacles that use avidity-based binding to achieve conditional activity directed to specific cell types or tissues. Stabilizing disulfides and point mutations were identified computationally with Rosetta, evaluated in vitro, and combined into designs with 3-5 amino acid substitutions for each of the seven germline families (VH1-VH7). Computational design was also employed to reduce dimerization from both VL and homotypic VH-VH interactions. Optimization of specific sequences improved expression by greater than 600-fold and thermostability by more than 20{degrees}C. Each of the germline variants were screened for low HLA class II binding and incorporated into a library which demonstrated significant improvements in cellular protein production, thereby increasing sequence diversity for screening campaigns. These VH-Select scaffolds are useful for the discovery of novel binders used to build multispecific Tentacles designed for cis-interactions that achieve cell- and tissue-specific activation. As an example of the utility of the platform, we generated a set of Tentacles that use VH-Select binders to conditionally agonize IL2R{gamma}{beta} and 41BB on PD1+, LAG3+, or CD8+ T cells. These Tentacles demonstrate promising manufacturability, antibody-like exposure in vivo, and strong anti-tumor activity in a humanized tumor model. Overall, we believe the incorporation of VH-Select binders into multispecific Tentacles has the potential to create a host of conditionally active biologics to treat various chronic and acute diseases.

bioengineering↗

bioRxiv2025

Amino acids bind to phase-separating proteins and modulate biomolecular condensate stability and dynamics

AbstractBiomolecular condensates (BCs) are versatile intracellular compartments that help organize intracellular space and perform diverse biological functions. In living cells, BCs are surrounded by a complex environment, of which amino acids (AAs) are prominent components. However, it is unclear how AAs interact with condensate components and influence the formation and material properties of condensates. Here, we show that phase separation is suppressed with increasing glycine concentration by using model heterotypic condensates made of nucleophosmin 1 (NPM1) and ribosomal ribonucleic acid (RNA): the condensate density is decreased and the dynamics inside the condensate are increased. We find that glycine weakly binds to amide groups in the protein backbone and aromatic groups in the side chains with a 1[~]2 M affinity, weakening the backbone-backbone interactions between neutral and charged disordered proteins while strengthening the interactions between aromatic stickers. This leads to different modulations of the phase behaviour in condensates formed by cation/{pi}-{pi} interactions and condensates formed by charge complexation. We further show that a similar modulation effect on BCs is observed for other proteinogenic AAs and can be transferred to short peptides. These insights offer a better understanding of BC stability, with implications for new strategies to modulate the dynamic properties of BCs in vivo.

biophysics↗

bioRxiv2024

Identification of Long Non-coding RNA Candidate Disease Genes Associated with Clinically Reported CNVs in Congenital Heart Disease

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSCopy Number Variants (CNVs) contribute to 3-10% of isolated Congenital Heart Disease (CHD) cases, but their roles in disease pathogenesis are often unclear. Traditionally, diagnostics have focused on protein-coding genes, overlooking the pathogenic potential of non-coding regions constituting 99% of the genome. Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in development and disease. MethodsIn this study, we systematically analyzed candidate lncRNAs overlapping with clinically validated CNVs in 1,363 CHD patients from the Cytogenomics of Cardiovascular Malformations (CCVM) Consortium. We identified heart-expressed lncRNAs, constructed a gene regulatory network using Weighted Gene Co-expression Network Analysis (WGCNA), and identified gene modules significantly associated with heart development. Functional enrichment analyses and network visualizations were conducted to elucidate the roles of these lncRNAs in cardiac development and disease. The code is stably archived at https://doi.org/10.5281/zenodo.13799847. ResultsWe identified 18 lncRNA candidate genes within modules significantly correlated with heart tissue, highlighting their potential involvement in CHD pathogenesis. Notably, lncRNAs such as lnc-STK32C-3, lnc-TBX20-1, and CRMA demonstrated strong associations with known CHD genes. Strikingly, while only 7.6% of known CHD genes were impacted by a CNV, 68.8% of the CNVs contained a lncRNA expressed in the heart. ConclusionsOur findings highlight the critical yet underexplored role of lncRNAs in the genomics of CHD. By investigating CNV-associated lncRNAs, this study paves the way for deeper insights into the genetic basis of CHD by incorporating non-coding genomic regions. The research underscores the need for advanced annotation techniques and broader genetic database inclusion to fully capture the potential of lncRNAs in disease mechanisms. Overall, this work emphasizes the importance of the non-coding genome as a pivotal factor in CHD pathogenesis, potentially uncovering novel contributors to disease risk.

genomics↗

bioRxiv2023

SNVstory: A dockerized algorithm for rapid and accurate inference of sub-continental ancestry

Knowing a patients genetic ancestry is crucial in clinical settings, providing benefits such as tailored genetic testing, targeted health screening based on ancestral disease-predisposition rates, and personalized medication dosages. However, self-reported ancestry can be subjective, making it difficult to apply consistently. Moreover, existing approaches utilize genome sequencing data to infer ancestry at the continental level, creating the need for methods optimized for individual ancestry assignment. We present SNVstory, a method built upon three independent machine learning models for accurately inferring the sub-continental ancestry of individuals. SNVstory includes a feature-importance scheme, unique among open-source ancestral tools, which allows the user to track the ancestral signal broadcast by a given gene or locus. We apply SNVstory to a clinical dataset, comparing self-reported ethnicity and race to our inferred genetic ancestry. SNVstory represents a significant advance in methods to assign genetic ancestry, predicting ancestry across 36 different populations with high accuracy.

genomics↗

bioRxiv2023

Norovirus NS3 protein induces apoptosis through translation repression and dysregulation of BCL-2 pro-survival proteins

Norovirus infection is characterised by a rapid onset of disease and the development of debilitating symptoms including projectile vomiting and diffuse diarrhoea. Vaccines and antivirals are sorely lacking and developments in these areas are hampered by the lack of an adequate cell culture system to investigate human norovirus replication and pathogenesis. Herein, we describe how the model norovirus, Mouse norovirus (MNV), produces a viral protein, NS3, with the functional capacity to attenuate host protein translation which invokes the activation cell death via apoptosis. We show that this function of NS3 is conserved between human and mouse viruses and map the protein domain attributable to this function. Our study highlights a critical viral protein that mediates crucial activities during replication, potentially identifying NS3 as a worthy target for antiviral drug development.

microbiology↗

bioRxiv2022

Development of SARS-CoV-2 mRNA vaccines encoding spike N-terminal and receptor binding domains

With the success of mRNA vaccines against coronavirus disease 2019 (COVID-19), strategies can now focus on improving vaccine potency, breadth, and stability. We present the design and preclinical evaluation of domain-based mRNA vaccines encoding the wild-type spike-protein receptor-binding (RBD) and/or N-terminal domains (NTD). An NTD-RBD linked candidate vaccine, mRNA-1283, showed improved antigen expression, antibody responses, and stability at refrigerated temperatures (2-8{degrees}C) compared with the clinically available mRNA-1273, which encodes the full-length spike protein. In mice administered mRNA-1283 as a primary series, booster, or variant-specific booster, similar or greater immune responses and protection from viral challenge were observed against wild-type, beta, delta, or omicron (BA. 1) compared with mRNA-1273 immunized mice, especially at lower vaccine dosages. These results support clinical assessment of mRNA-1283 (NCT05137236). One Sentence SummaryA domain-based mRNA vaccine, mRNA-1283, is immunogenic and protective against SARS-CoV-2 and emerging variants in mice.

immunology↗

bioRxiv2022

Single cell RNA sequencing analysis of mouse cochlear supporting cell transcriptomes with activated ERBB2 receptor, a candidate mediator of hearing restoration mechanisms.

Hearing loss caused by the death of cochlear hair cells might be restored through regeneration from supporting cells via dedifferentiation and proliferation, as observed in birds. We recently found that in mice, activation of ERBB2 in supporting cells promoted the differentiation of hair cell-like cells. Here we analyze transcriptomes of neonatal mouse cochlear supporting cells with activated ERBB2 using single-cell RNA sequencing. ERBB2 induction in vivo generated a new population of cells expressing de novo SIBLING (small integrin-binding ligand n-linked glycoproteins) proteins and their regulators, particularly Secreted Phosphoprotein 1 (SPP1). In other systems, SIBLINGs promote cell survival, proliferation, and differentiation. ERBB2 signaling induced after noise exposure in young adult mice also up-regulated both SPP1 protein and the SPP1 receptor CD44, and drove formation of proliferating stem-like cell aggregates in the organ of Corti. Our results suggest that ectopic activation of ERBB2 signaling in cochlear supporting cells alters the microenvironment, promoting proliferation and cell rearrangements. Together these results suggest a novel mechanism for inducing stem cell-like activity in the adult mammalian cochlea.

neuroscience↗

bioRxiv2022

Siglec-5 is an inhibitory immune checkpoint molecule for human T cells

Sialic acid-binding immunoglobulin-type lectins (Siglecs) are a family of immunoglobulin-type lectins that mediate protein-carbohydrate interactions via sialic acids attached to glycoproteins or glycolipids. Most of the CD33-related Siglecs (CD33rSiglecs), a major subfamily of rapidly evolving Siglecs, contain a cytoplasmic signaling domain consisting of the immunoreceptor tyrosine-based inhibitory motif (ITIM) and immunoreceptor tyrosine-based switch motif (ITSM) and mediate suppressive signals for lymphoid and myeloid cells. While most CD33rSiglecs are expressed by innate immune cells, such as monocytes and neutrophils, to date, the expression of Siglecs in human T cells has not been well appreciated. In this study, we found that Siglec-5, a member of the CD33rSiglecs, is expressed by most activated T cells upon antigen receptor stimulation. Functionally, Siglec-5 suppresses T cell activation. In support of these findings, we found that Siglec-5 overexpression abrogates antigen receptor induced activation of Nuclear factor of activated T cells (NFAT) and Activator protein 1 (AP-1). Furthermore, we show that GBS {beta}-protein, a known bacterial ligand of Siglec-5, reduces the production of cytokines and cytolytic molecules by activated primary T cells in a Siglec-5 dependent manner. Our data also show that some cancer cell lines express a putative Siglec-5 ligand(s), and that the presence of soluble Siglec-5 enhances tumor-cell specific T cell activation, suggesting that some tumor cells inhibit T cell activation via Siglec-5. Together, our data demonstrate that Siglec-5 is a previously unrecognized inhibitory T cell immune checkpoint molecule and suggests that blockade of Siglec-5 could serve as a new strategy to enhance anti-tumor T cell functions. One Sentence SummarySiglec-5 is a novel checkpoint receptor expressed by activated human T cells that antagonizes TCR mediated activation and suppresses T cell effector functions such as cytokine production.

immunology↗

bioRxiv2021

Extrinsic motivators drive children's cooperation to conserve forests

Forests are essential common-pool resources. It is increasingly critical to nurture a lifelong concern for forest health both locally and globally. Here, in two experiments, we demonstrate that school age children (6-18 yrs. old; N>1000;) of three nationalities (China, D. R. Congo and U.S.) do not have levels of intrinsic motivation to allow for successful cooperation in common-pool goods games requiring them to maintain a forest. We instead find that the size, timing, and certainty of receiving individual payoffs from cooperation significantly boost the odds of successful conservation efforts. We also provide evidence that the experience of playing this game increases longer term motivation to conserve forests. Results have implications for designing policy and curriculum to encourage collective action for forest conservation. One Sentence SummaryExtrinsic motivation boosts concern for forests among children and adolescents in the United States, China, and the Democratic Republic of the Congo.

scientific communication and education↗

bioRxiv2021

Psychological stress disrupts intestinal epithelial cell function and mucosal integrity through microbe and host-directed processes

Psychological stress alters the gut microbiota and predisposes individuals to increased risk for enteric infections and chronic bowel conditions. Intestinal epithelial cells (IECs) are responsible for maintaining homeostatic interactions between the gut microbiota and its host. In this study, we hypothesized that disruption to colonic IECs is a key factor underlying stress-induced disturbances to intestinal homeostasis. Conventionally raised (CONV-R) and germ-free (GF) mice were exposed to a social disruption stressor (Str) to ascertain how stress modifies colonic IECs, the mucosal layer, and the gut microbiota. RNA sequencing of IECs isolated from CONV-R mice revealed a robust pro-inflammatory (Saa1, Il18), pro-oxidative (Duox2, Nos2), and antimicrobial (Reg3b/g) transcriptional profile as a result of Str. This response occurred concomitant to mucus layer thinning and signs of microbial translocation. In contrast to their CONV-R counterparts, IECs from GF mice or mice treated with broad spectrum antibiotics exhibited no detectable transcriptional changes in response to Str. Nevertheless, IECs from Str-exposed GF mice exhibited an altered response to ex vivo bacterial challenge (increased dual Oxidase-2 [Duox2] and nitric oxide synthase-2 (Nos2)), indicating that STR primes host IEC pro-oxidative responses. In CONV-R mice stress-induced increases in colonic Duox2 and Nos2 (ROS generating enzymes) strongly paralleled changes to microbiome composition and function, evidencing Str-mediated ROS production as a primary factor mediating gut-microbiota dysbiosis. In conclusion, a mouse model of social stress disrupts colonic epithelial and mucosal integrity, a response dependent on an intact microbiota and host stress signals. Together these preclinical findings may provide new insight into mechanisms of stress-associated bowel pathologies in humans.

immunology↗

bioRxiv2021

A novel mechanism for the loss of mRNA activity in lipid nanoparticle delivery systems.

Lipid nanoparticle (LNP)-formulated mRNA vaccines were rapidly developed and deployed in response to the SARS-CoV-2 pandemic. Due to the labile nature of mRNA, identifying impurities that could affect product stability and efficacy is crucial to the long-term use of nucleic-acid based medicines. Herein reversed phase ion pair high performance liquid chromatography (RP-IP HPLC) was used to identify a class of impurity formed through lipid:mRNA reactions; such reactions are typically undetectable by traditional mRNA purity analytical techniques. The identified modifications render the mRNA untranslatable, leading to loss of protein expression. Specifically, an electrophilic impurity derived from the ionizable cationic lipid component is shown to be responsible. Mechanisms implicated in the formation of reactive species include oxidation and subsequent hydrolysis of the tertiary amine. It thus remains critical to ensure robust analytical methods and stringent manufacturing control to ensure mRNA stability and high activity in LNP delivery systems.

biochemistry↗

bioRxiv2021

Liver enhancer signature and regulatory network of non-alcoholic steatohepatitis resistance in humans with obesity

The molecular underpinnings of non-alcoholic steatohepatitis (NASH) development in patients are poorly understood. Active enhancer landscapes are known to determine cell states and behaviors. Super-enhancers, in particular, have helped reveal key disease drivers in several cancer types; however, they remain unexplored in human NASH. To define the enhancer signature of NASH-prone (NP) and NASH-resistant (NR) phenotypes in humans with obesity, we performed chromatin run-on sequencing (ChRO-seq) analysis on liver biopsies of individuals with obesity who were stratified into either NP or NR. We first demonstrated that NP and NR groups exhibit distinct active enhancer signatures. The subsequent identification of NP- and NR-specific super-enhancers revealed the specific genes that are likely the most critical for each of the phenotypes, including HES1 for NP and GATM for NR. Integrative analysis with results from genome-wide association studies of NAFLD and related traits identified disease/trait-loci specific to NP or NR enhancers. Further analysis of the ChRO-seq data pointed to critical roles for serine/glycine metabolism in NASH resistance, which was corroborate by profiling of circulating amino acids in the same patients. Overall, the distinct enhancer signatures of human NP and NR phenotypes revealed key genes, pathways, and transcription factor networks that promote NASH development.

genomics↗

bioRxiv2021

Discovery of Clinically Relevant Fusions in Pediatric Cancer

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSBackgroundC_ST_ABSPediatric cancers typically have a distinct genomic landscape when compared to adult cancers and frequently carry somatic gene fusion events that alter gene expression and drive tumorigenesis. Sensitive and specific detection of gene fusions through the analysis of next-generation-based RNA sequencing (RNA-Seq) data is computationally challenging and may be confounded by low tumor cellularity or underlying genomic complexity. Furthermore, numerous computational tools are available to identify fusions from supporting RNA-Seq reads, yet each algorithm demonstrates unique variability in sensitivity and precision, and no clearly superior approach currently exists. To overcome these challenges, we have developed an ensemble fusion calling approach to increase the accuracy of identifying fusions. ResultsOur ensemble fusion detection approach utilizes seven fusion calling algorithms: Arriba, CICERO, FusionMap, FusionCatcher, JAFFA, MapSplice, and STAR-Fusion, which are packaged as a fully automated pipeline using Docker and AWS serverless technology. This method uses paired end RNA-Seq sequence reads as input, and the output from each algorithm is examined to identify fusions detected by a consensus of at least three algorithms. These consensus fusion results are filtered by comparison to an internal database to remove likely artifactual fusions occurring at high frequencies in our internal cohort, while a "known fusion list" prevents failure to report known pathogenic events. We have employed the ensemble fusion-calling pipeline on RNA-Seq data from 229 patients with pediatric cancer or blood disorders studied under an IRB-approved protocol. The samples consist of 138 central nervous system tumors, 73 solid tumors, and 18 hematologic malignancies or disorders. The combination of an ensemble fusion-calling pipeline and a knowledge-based filtering strategy identified 67 clinically relevant fusions among our cohort (diagnostic yield of 29.3%), including RBPMS-MET, BCAN-NTRK1, and TRIM22-BRAF fusions. Following clinical confirmation and reporting in the patients medical record, both known and novel fusions provided medically meaningful information. ConclusionsOur ensemble fusion detection pipeline offers a streamlined approach to discover fusions in cancer, at higher levels of sensitivity and accuracy than single algorithm methods. Furthermore, this method accurately identifies driver fusions in pediatric cancer, providing clinical impact by contributing evidence to diagnosis and, when appropriate, indicating targeted therapies.

genomics↗

bioRxiv2021

Primed to Die: An Investigation of the Genetic Mechanisms Underlying Noise-Induced Hearing Loss and Cochlear Damage in Homozygous Foxo3-knockout Mice

The prevalence of noise-induced hearing loss (NIHL) continues to increase, with limited therapies available for individuals with cochlear damage. We have previously established that the transcription factor FOXO3 is necessary to preserve outer hair cells (OHCs) and hearing thresholds up to two weeks following a mild noise exposure in mice. The mechanisms by which FOXO3 preserves cochlear cells and function are unknown. In this study, we analyzed the immediate effects of mild noise exposure on wild-type, Foxo3 heterozygous (Foxo3+/KO), and Foxo3 knock-out (Foxo3KO/KO) mice to better understand FOXO3s role(s) in the mammalian cochlea. We used confocal and multiphoton microscopy to examine well-characterized components of noise-induced damage including calcium regulators, oxidative stress, necrosis, and caspase-dependent and -independent apoptosis. Lower immunoreactivity of the calcium buffer oncomodulin in Foxo3KO/KO OHCs correlated with cell loss beginning 4 hours post-noise exposure. Using immunohistochemistry, we identified parthanatos as the cell death pathway for OHCs. Oxidative stress response pathways were not significantly altered in FOXO3s absence. We used RNA sequencing to identify and RT-qPCR to confirm differentially expressed genes. We further investigated a gene downregulated in the unexposed Foxo3KO/KO mice that may contribute to OHC noise susceptibility. Glycerophosphodiester Phosphodiesterase Domain Containing 3 (GDPD3), a possible endogenous source of lysophosphatidic acid (LPA), has not previously been described in the cochlea. As LPA reduces OHC loss after severe noise exposure, we treated noise exposed Foxo3KO/KO mice with exogenous LPA. LPA treatment delayed immediate damage to OHCs but was insufficient to ultimately prevent their death or prevent hearing loss. These results suggest that FOXO3 acts prior to acoustic insult to maintain cochlear resilience, possibly through sustaining endogenous LPA levels.

neuroscience↗

bioRxiv2021

Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever

Importing necessary metabolites into the mitochondrial matrix is a crucial step of fuel choice during stress adaptation. Branched chain-amino acids (BCAA, Valine, Leucine, and Isoleucine) are essential for anabolic processes like protein synthesis, but they are also imported into the mitochondria for catabolic reactions. What controls the distinct subcellular BCAA utilization during stress adaptation is insufficiently understood. The present study reports the role of SLC25A44, a recently identified mitochondrial BCAA carrier (MBC), in the regulation of mitochondrial BCAA catabolism and adaptive response to fever. We found that mitochondrial BCAA oxidation in brown adipose tissue (BAT) is significantly enhanced during fever in response to the pyrogenic mediator prostaglandin E2 (PGE2) and psychological stress. Genetic deletion of MBC in a BAT-specific manner blunts mitochondrial BCAA oxidation and non-shivering thermogenesis following intracerebroventricular PGE2 administration. At a cellular level, MBC is required for mitochondrial BCAA deamination as well as the synthesis of mitochondrial amino acids and TCA intermediates. Together, these results illuminate the role of MBC as a determinant of metabolic flexibility to mitochondrial BCAA catabolism and optimal febrile responses. This study also offers an opportunity to control fever by rewiring the subcellular BCAA fate.

cell biology↗

bioRxiv2021

Cooperative Communication with Humans Evolved to Emerge Early in Dogs

While we know that dogs evolved from wolves through a process of domestication, it remains unclear how this process may have affected dog cognitive development. Here we tested dog (N=44) and wolf (N=37) puppies, 5-18 weeks old, on a battery of temperament and cognition tasks. Dog puppies were more attracted to humans, read human gestures more skillfully and made more eye contact with humans than wolf puppies. The two species were similarly attracted to objects and performed similarly on nonsocial measures of memory and inhibitory control. These results demonstrate the role of domestication in enhancing the cooperative communication skills of dogs through selection on attraction to humans, which altered developmental pathways. One Sentence Summary Domestication altered dogs developmental pathways to enhance their cooperative communication with humans.

animal behavior and cognition↗