Digital Commons Network^™

Pediatric Reporting Of Genomic Results Study (Progress): A Mixed-Methods, Longitudinal, Observational Cohort Study Protocol To Explore Disclosure Of Actionable Adult- And Pediatric-Onset Genomic Variants To Minors And Their Parents, Juliann M Savatt, Jessica Mozersky, Et Al

Open Access Publications

BACKGROUND: Exome and genome sequencing are routinely used in clinical care and research. These technologies allow for the detection of pathogenic/likely pathogenic variants in clinically actionable genes. However, fueled in part by a lack of empirical evidence, controversy surrounds the provision of genetic results for adult-onset conditions to minors and their parents. We have designed a mixed-methods, longitudinal cohort study to collect empirical evidence to advance this debate.

METHODS: Pediatric participants in the Geisinger MyCode® Community Health Initiative with available exome sequence data will have their variant files assessed for pathogenic/likely pathogenic variants in 60 genes designated as actionable by …

Coronary Heart Disease And Mortality Following A Breast Cancer Diagnosis, Aixia Guo, Kathleen W Zhang, Kristi Reynolds, Randi E Foraker

Open Access Publications

BACKGROUND: Coronary heart disease (CHD) is a leading cause of morbidity and mortality for breast cancer survivors, yet the joint effect of adverse cardiovascular health (CVH) and cardiotoxic cancer treatments on post-treatment CHD and death has not been quantified.

METHODS: We conducted statistical and machine learning approaches to evaluate 10-year risk of these outcomes among 1934 women diagnosed with breast cancer during 2006 and 2007. Overall CVH scores were classified as poor, intermediate, or ideal for 5 factors, smoking, body mass index, blood pressure, glucose/hemoglobin A1c, and cholesterol from clinical data within 5 years prior to the breast cancer diagnosis. …

Transcriptional Analyses Of Adult And Pediatric Adamantinomatous Craniopharyngioma Reveals Similar Expression Signatures Regarding Potential Therapeutic Targets, Eric Prince, Chibueze Agwu, David D Limbrick, Et Al

Open Access Publications

Adamantinomatous craniopharyngioma (ACP) is a biologically benign but clinically aggressive lesion that has a significant impact on quality of life. The incidence of the disease has a bimodal distribution, with peaks occurring in children and older adults. Our group previously published the results of a transcriptome analysis of pediatric ACPs that identified several genes that were consistently overexpressed relative to other pediatric brain tumors and normal tissue. We now present the results of a transcriptome analysis comparing pediatric to adult ACP to identify biological differences between these groups that may provide novel therapeutic insights or support the assertion that potential …

Radiation Induces Iatrogenic Immunosuppression By Indirectly Affecting Hematopoiesis In Bone Marrow, Vaishali Kapoor, Andrea Collins, Kaylan Griffith, Subhajit Ghosh, Nathan Wong, Xiaowei Wang, Grant A. Challen, Joseph Krambs, Dan Link, Dennis E. Hallahan, Dinesh Thotala

Open Access Publications

The immune system plays a vital role in cancer therapy, especially with the advent of immunotherapy. Radiation therapy induces iatrogenic immunosuppression referred to as radiation-induced lymphopenia (RIL). RIL correlates with significant decreases in the overall survival of cancer patients. Although the etiology and severity of lymphopenia are known, the mechanism(s) of RIL are largely unknown. We found that irradiation not only had direct effects on circulating lymphocytes but also had indirect effects on the spleen, thymus, and bone marrow. We found that irradiated cells traffic to the bone marrow and bring about the reduction of hematopoietic stem cells (HSC) and …

Contribution Of Ctcf Binding To Transcriptional Activity At The Hoxa Locus In Npm1-Mutant Aml Cells, Reza Ghasemi, Heidi Struthers, Elisabeth R Wilson, David H Spencer

Open Access Publications

Transcriptional regulation of the HOXA genes is thought to involve CTCF-mediated chromatin loops and the opposing actions of the COMPASS and Polycomb epigenetic complexes. We investigated the role of these mechanisms at the HOXA cluster in AML cells with the common NPM1c mutation, which express both HOXA and HOXB genes. CTCF binding at the HOXA locus is conserved across primary AML samples, regardless of HOXA gene expression, and defines a continuous chromatin domain marked by COMPASS-associated histone H3 trimethylation in NPM1-mutant primary AML samples. Profiling of the three-dimensional chromatin architecture in primary AML samples with the NPM1c mutation identified chromatin …

The Gossypium Longicalyx Genome As A Resource For Cotton Breeding And Evolution, Corrinne E Grover, Mengqiao Pan, Daojun Yuan, Mark A Arick, Guanjing Hu, Logan Brase, David M Stelly, Zefu Lu, Robert J Schmitz, Daniel G Peterson, Jonathan F Wendel, Joshua A Udall

2020-Current year OA Pubs

Cotton is an important crop that has made significant gains in production over the last century. Emerging pests such as the reniform nematode have threatened cotton production. The rare African diploid species

A New Gorilla Adenoviral Vector With Natural Lung Tropism Avoids Liver Toxicity And Is Amenable To Capsid Engineering And Vector Retargeting, Zhi Hong Lu, Igor P. Dmitriev, Douglas E. Brough, Elena A. Kashentseva, Jie Li, David T. Curiel

Open Access Publications

Human adenoviruses have many attractive features for gene therapy applications. However, the high prevalence of preexisting immunity against these viruses in general populations worldwide has greatly limited their clinical utility. In addition, the most commonly used human adenovirus, human adenovirus subgroup C serotype 5 (HAd5), when systemically administered, triggers systemic inflammation and toxicity, with the liver being the most severely affected organ. Here, we evaluated the utility and safety of a new low-seroprevalence gorilla adenovirus (GAd; GC46) as a gene transfer vector in mice. Biodistribution studies revealed that systemically administered GAd had a selective and robust lung endothelial cell (EC) …

De Novo Identification Of Toxicants That Cause Irreparable Damage To Parasitic Nematode Intestinal Cells, Douglas P. Jasmer, Bruce A. Rosa, Rahul Tyagi, Christina A. Bulman, Brenda Beerntsen, Joseph F. Urban Jr, Judy Sakanari, Makedonka Mitreva

Open Access Publications

Efforts to identify new drugs for therapeutic and preventive treatments against parasitic nematodes have gained increasing interest with expanding pathogen omics databases and drug databases from which new anthelmintic compounds might be identified. Here, a novel approach focused on integrating a pan-Nematoda multi-omics data targeted to a specific nematode organ system (the intestinal tract) with evidence-based filtering and chemogenomic screening was undertaken. Based on de novo computational target prioritization of the 3,564 conserved intestine genes in A. suum, exocytosis was identified as a high priority pathway, and predicted inhibitors of exocytosis were tested using the large roundworm (Ascaris suum larval …

Wnt Regulation: Exploring Axin-Disheveled Interactions And Defining Mechanisms By Which The Scf E3 Ubiquitin Ligase Is Recruited To The Destruction Complex, Kristina N. Schaefer, Mira I. Pronobis, Clara E. Williams, Shiping Zhang, Lauren Bauer, Dennis Goldfarb, Feng Yan, M. Ben Major, Mark Peifer

Open Access Publications

Wnt signaling plays key roles in embryonic development and adult stem cell homeostasis and is altered in human cancer. Signaling is turned on and off by regulating stability of the effector β-catenin (β-cat). The multiprotein destruction complex binds and phosphorylates β-cat and transfers it to the SCF-TrCP E3-ubiquitin ligase for ubiquitination and destruction. Wnt signals act though Dishevelled to turn down the destruction complex, stabilizing β-cat. Recent work clarified underlying mechanisms, but important questions remain. We explore β-cat transfer from the destruction complex to the E3 ligase, and test models suggesting Dishevelled and APC2 compete for association with Axin. We …

Targeting Usp1-Dependent Kdm4a Protein Stability As A Potential Prostate Cancer Therapy, Shu-Zhong Cui, Zi-Ying Lei, Tian-Pei Guan, Ling-Ling Fan, You-Qiang Li, Xin-Yan Geng, De-Xue Fu, Hao-Wu Jiang, Song-Hui Xu

Open Access Publications

The histone demethylase lysine-specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream …

Nodal And Planar Cell Polarity Signaling Cooperate To Regulate Zebrafish Convergence And Extension Gastrulation Movements, Margot L.K. Williams, Lilianna Solnica-Krezel

Open Access Publications

During vertebrate gastrulation, convergence and extension (C and E) of the primary anteroposterior (AP) embryonic axis is driven by polarized mediolateral (ML) cell intercalations and is influenced by AP axial patterning. Nodal signaling is essential for patterning of the AP axis while planar cell polarity (PCP) signaling polarizes cells with respect to this axis, but how these two signaling systems interact during C and E is unclear. We find that the neuroectoderm of Nodal-deficient zebrafish gastrulae exhibits reduced C and E cell behaviors, which require Nodal signaling in both cell- and non-autonomous fashions. PCP signaling is partially active in Nodal-deficient …

Neural Circuit Dynamics For Sensory Detection, Sruti Mallik, Srinath Nizampatnam, Anirban Nandi, Debajit Saha, Baranidharan Raman, Shinung Ching

2020-Current year OA Pubs

We consider the question of how sensory networks enable the detection of sensory stimuli in a combinatorial coding space. We are specifically interested in the olfactory system, wherein recent experimental studies have reported the existence of rich, enigmatic response patterns associated with stimulus onset and offset. This study aims to identify the functional relevance of such response patterns (i.e., what benefits does such neural activity provide in the context of detecting stimuli in a natural environment). We study this problem through the lens of normative, optimization-based modeling. Here, we define the notion of a low-dimensional latent representation of stimulus identity, …

Cd4+ T Cell Expression Of The Il-10 Receptor Is Necessary For Facial Motoneuron Survival After Axotomy, Elizabeth M Runge, Abhirami K Iyer, Deborah O Setter, Felicia M Kennedy, Virginia M Sanders, Kathryn J Jones

Open Access Publications

BACKGROUND: After peripheral nerve transection, facial motoneuron (FMN) survival depends on an intact CD4+ T cell population and a central source of interleukin-10 (IL-10). However, it has not been determined previously whether CD4+ T cells participate in the central neuroprotective IL-10 cascade after facial nerve axotomy (FNA).

METHODS: Immunohistochemical labeling of CD4+ T cells, pontine vasculature, and central microglia was used to determine whether CD4+ T cells cross the blood-brain barrier and enter the facial motor nucleus (FMNuc) after FNA. The importance of IL-10 signaling in CD4+ T cells was assessed by performing adoptive transfer of IL-10 receptor beta (IL-10RB)-deficient …

Covid-19 Clinical Trials: A Primer For The Cardiovascular And Cardio-Oncology Communities, Bonnie Ky, Douglas L Mann

Open Access Publications

The COVID-19 pandemic has resulted in a proliferation of clinical trials that are designed to slow the spread of SARS-CoV-2, the virus that causes COVID-19. The overwhelming majority of cardiovascular and cancer patients are at increased risk for SARS-CoV-2 infection; accordingly, the cardiovascular and cardio-oncology communities are playing a major role in caring for COVID-19 patients. Many of the therapeutic agents that are being used to treat patients with COVID-19 are repurposed treatments for influenza, drugs that were not effective in Ebola patients, or treatments for malaria that were developed decades ago, and are unlikely to be familiar to the …

The Histone Deacetylase Complex Midac Regulates A Neurodevelopmental Gene Expression Program To Control Neurite Outgrowth, Baisakhi Mondal, Hongjian Jin, Satish Kallappagoudar, Yurii Sedkov, Tanner Martinez, Monica F. Sentmanat, Greg J. Poet, Chunliang Li, Yiping Fan, Shondra M. Pruett-Miller, Hans-Martin Herz

Open Access Publications

The mitotic deacetylase complex (MiDAC) is a recently identified histone deacetylase (HDAC) complex. While other HDAC complexes have been implicated in neurogenesis, the physiological role of MiDAC remains unknown. Here, we show that MiDAC constitutes an important regulator of neural differentiation. We demonstrate that MiDAC functions as a modulator of a neurodevelopmental gene expression program and binds to important regulators of neurite outgrowth. MiDAC upregulates gene expression of pro-neural genes such as those encoding the secreted ligands SLIT3 and NETRIN1 (NTN1) by a mechanism suggestive of H4K20ac removal on promoters and enhancers. Conversely, MiDAC inhibits gene expression by reducing H3K27ac …

Sex Differences In Cancer Mechanisms, Joshua B Rubin, Joseph S Lagas, Lauren Broestl, Jasmin Sponagel, Nathan Rockwell, Gina Rhee, Sarah F Rosen, Si Chen, Robyn S Klein, Princess Imoukhuede, Jingqin Luo

Open Access Publications

We now know that cancer is many different diseases, with great variation even within a single histological subtype. With the current emphasis on developing personalized approaches to cancer treatment, it is astonishing that we have not yet systematically incorporated the biology of sex differences into our paradigms for laboratory and clinical cancer research. While some sex differences in cancer arise through the actions of circulating sex hormones, other sex differences are independent of estrogen, testosterone, or progesterone levels. Instead, these differences are the result of sexual differentiation, a process that involves genetic and epigenetic mechanisms, in addition to acute sex …

Reinforcement Biases Subsequent Perceptual Decisions When Confidence Is Low, A Widespread Behavioral Phenomenon, Armin Lak, Emily Hueske, Junya Hirokawa, Paul Masset, Torben Ott, Anne E. Urai, Tobias H. Donner, Matteo Carandini, Susumu Tonegawa, Naoshige Uchida, Adam Kepecs

Open Access Publications

Learning from successes and failures often improves the quality of subsequent decisions. Past outcomes, however, should not influence purely perceptual decisions after task acquisition is complete since these are designed so that only sensory evidence determines the correct choice. Yet, numerous studies report that outcomes can bias perceptual decisions, causing spurious changes in choice behavior without improving accuracy. Here we show that the effects of reward on perceptual decisions are principled: past rewards bias future choices specifically when previous choice was difficult and hence decision confidence was low. We identified this phenomenon in six datasets from four laboratories, across mice, …

Prevalence Of Clinically Actionable Disease Variants In Exceptionally Long-Lived Families, Paige Carlson, Mary K Wojczynski, Todd Druley, Joseph H Lee, Joseph M Zmuda, Bharat Thyagarajan

2020-Current year OA Pubs

BACKGROUND: Phenotypic expression of pathogenic variants in individuals with no family history of inherited disorders remains unclear.

METHODS: We evaluated the prevalence of pathogenic variants in 25 genes associated with Mendelian-inherited disorders in 3015 participants from 485 families in the Long Life Family Study (LLFS). Boot-strapping and Fisher's exact test were used to determine whether allele frequencies in LLFS were significantly different from the allele frequencies reported in publicly available genomic databases.

RESULTS: The proportions of pathogenic autosomal dominant mutation carriers in BRCA1 and SDHC in LLFS study participants were similar to those reported in publicly available genomic databases (0.03% …

Assessment Of Biological Role And Insight Into Druggability Of The Plasmodium Falciparum Protease Plasmepsin V, Alexander J Polino, Armiyaw S Nasamu, Jacquin C Niles, Daniel E Goldberg

Open Access Publications

Upon infecting a red blood cell (RBC), the malaria parasite

Cd300lf Is The Primary Physiologic Receptor Of Murine Norovirus But Not Human Norovirus, Vincent R. Graziano, Forrest C. Walker, Elizabeth A. Kennedy, Ebrahim Hassan, Arthur S. Kim, Megan T. Baldridge, Et Al.

Open Access Publications

Murine norovirus (MNoV) is an important model of human norovirus (HNoV) and mucosal virus infection more broadly. Viral receptor utilization is a major determinant of cell tropism, host range, and pathogenesis. The bona fide receptor for HNoV is unknown. Recently, we identified CD300lf as a proteinaceous receptor for MNoV. Interestingly, its paralogue CD300ld was also sufficient for MNoV infection in vitro. Here we explored whether CD300lf is the sole physiologic receptor in vivo and whether HNoV can use a CD300 ortholog as an entry receptor. We report that both CD300ld and CD300lf are sufficient for infection by diverse MNoV strains …

Association Between Immune-Related Adverse Events And Recurrence-Free Survival Among Patients With Stage Iii Melanoma Randomized To Receive Pembrolizumab Or Placebo: A Secondary Analysis Of A Randomized Clinical Trial, Alexander M M Eggermont, Leonel Hernandez-Aya, Et Al

Open Access Publications

Importance: Whether immune-related adverse events (irAEs) indicate drug activity in patients treated with immune checkpoint inhibitors remains unknown.

Objective: To investigate the association between irAEs and recurrence-free survival (RFS) in the double-blind EORTC 1325/KEYNOTE-054 clinical trial comparing pembrolizumab therapy and placebo for the treatment of patients with high-risk stage III melanoma.

Design, Setting, and Participants: A total of 1019 adults with stage III melanoma were randomly assigned on a 1:1 ratio to receive treatment with pembrolizumab therapy or placebo. Eligible patients were adults 18 years and older with complete resection of cutaneous melanoma metastatic to lymph nodes, classified with stage …

Role Of Yttrium-90 Selective Internal Radiation Therapy In The Treatment Of Liver-Dominant Metastatic Colorectal Cancer: An Evidence-Based Expert Consensus Algorithm, D Rohan Jeyarajah, Maria B Majella Doyle, N Joseph Espat, Paul D Hansen, David A Iannitti, Joseph Kim, Thavam Thambi-Pillai, Brendan C. Visser

Open Access Publications

Surgical resection of colorectal liver metastases is associated with greater survival compared with non-surgical treatment, and a meaningful possibility of cure. However, the majority of patients are not eligible for resection and may require other non-surgical interventions, such as liver-directed therapies, to be converted to surgical eligibility. Given the number of available therapies, a general framework is needed that outlines the specific roles of chemotherapy, surgery, and locoregional treatments [including selective internal radiation therapy (SIRT) with Y-90 microspheres]. Using a data-driven, modified Delphi process, an expert panel of surgical oncologists, transplant surgeons, and hepatopancreatobiliary (HPB) surgeons convened to create a …

Assessment Of Benefit Of Advanced Inflammatory Bowel Disease Training: Challenges And Solutions, Kelly C Cushing, Tomer Adar, Matthew Ciorba, Ashwin N Ananthakrishnan

2020-Current year OA Pubs

BACKGROUND: Advanced inflammatory bowel disease (IBD) fellowships are available for gastroenterologists who wish to increase their expertise in complex IBD. However, little is known about the outcomes of such training. The aims of this study were to assess clinical and academic outcomes following advanced training in IBD.

METHODS: We surveyed gastroenterologists who completed advanced IBD fellowships and compared competency and outcomes to gastroenterologists focusing in IBD who completed gastroenterology training alone. Participants completed a survey via REDCap. Continuous variables were compared using the Wilcoxon rank-sum test. Categorical variables were compared using chi-square or Fisher's exact tests.

RESULTS: A total of …

Personal, Biomechanical, Psychosocial, And Organizational Risk Factors For Carpal Tunnel Syndrome: A Structural Equation Modeling Approach, Yves Roquelaure, Ronan Garlantézec, Bradley A. Evanoff, Alexis Descatha, Jean-Baptiste Fassier, Julie Bodin

2020-Current year OA Pubs

This longitudinal study aimed at exploring the direct and indirect relationships between organizational, psychosocial, biomechanical, and personal factors and carpal tunnel syndrome (CTS) in French workers. Between 2002 and 2005, 3710 workers were included in the Cosali cohort. Between 2007 and 2010, 1611 workers were re-examined using the same standardized clinical protocol. Subjects free from CTS at baseline were studied (804 men and 563 women). We used structural equation models to examine the relationships between incident CTS cases and organizational (machine-paced work or work pace dependent on customers' demand), psychosocial (job strain model), biomechanical (Borg's rating perceived exertion, wrist bending, …

Glanzmann Thrombasthenia: Genetic Basis And Clinical Correlates, Juliana Perez Botero, Kristy Lee, Brian R. Branchford, Paul F. Bray, Kathleen Freson, Michele P. Lambert, Minjie Luo, Shruthi Mohan, Justyne E Ross, Wolfgang Bergmeier, Jorge Di Paola, Clingen Platelet Disorder Variant Curation Expert Panel

Open Access Publications

Glanzmann thrombasthenia (GT) is an autosomal recessive disorder of platelet aggregation caused by quantitative or qualitative defects in integrins αIIb and β3. These integrins are encoded by the

Reduced Neurosteroid Potentiation Of Gabaa Receptors In Epilepsy And Depolarized Hippocampal Neurons, Suchitra Joshi, William H Roden, Jaideep Kapur, Laura A Jansen

Open Access Publications

OBJECTIVE: Neurosteroids regulate neuronal excitability by potentiating γ-aminobutyric acid type-A receptors (GABARs). In animal models of temporal lobe epilepsy, the neurosteroid sensitivity of GABARs is diminished and GABAR subunit composition is altered. We tested whether similar changes occur in patients with epilepsy and if depolarization-induced increases in neuronal activity can replicate this effect.

METHODS: We determined GABAR α4 subunit expression in cortical tissue resected from pediatric epilepsy patients. Modulation of human GABARs by allopregnanolone and Ro15-4513 was measured in Xenopus oocytes using whole-cell patch clamp. To extend the findings obtained using tissue from epilepsy patients, we evaluated GABAR expression and …

Insights Into The Intracellular Localization, Protein Associations And Artemisinin Resistance Properties Of Plasmodium Falciparum K13, Nina F. Gnädig, Barbara H. Stokes, Rachel L. Edwards, Gavreel F. Kalantarov, Kim C. Heimsch, Michal Kuderjavy, Audrey Crane, Marcus C. S. Lee, Judith Straimer, Katja Becker, Ilya N. Trakht, Audrey R. Odom John, Sachel Mok, David A. Fidock

Open Access Publications

The emergence of artemisinin (ART) resistance in Plasmodium falciparum intra-erythrocytic parasites has led to increasing treatment failure rates with first-line ART-based combination therapies in Southeast Asia. Decreased parasite susceptibility is caused by K13 mutations, which are associated clinically with delayed parasite clearance in patients and in vitro with an enhanced ability of ring-stage parasites to survive brief exposure to the active ART metabolite dihydroartemisinin. Herein, we describe a panel of K13-specific monoclonal antibodies and gene-edited parasite lines co-expressing epitope-tagged versions of K13 in trans. By applying an analytical quantitative imaging pipeline, we localize K13 to the parasite endoplasmic reticulum, Rab-positive …

Differences In The Chitinolytic Activity Of Mammalian Chitinases On Soluble And Insoluble Substrates, Benjamin A Barad, Lin Liu, Roberto E Diaz, Ralp Basilio, Steven J Van Dyken, Richard M Locksley, James S Fraser

Open Access Publications

Chitin is an abundant polysaccharide used by many organisms for structural rigidity and water repulsion. As such, the insoluble crystalline structure of chitin poses significant challenges for enzymatic degradation. Acidic mammalian chitinase, a processive glycosyl hydrolase, is the primary enzyme involved in the degradation of environmental chitin in mammalian lungs. Mutations to acidic mammalian chitinase have been associated with asthma, and genetic deletion in mice increases morbidity and mortality with age. We initially set out to reverse this phenotype by engineering hyperactive acidic mammalian chitinase variants. Using a screening approach with commercial fluorogenic substrates, we identified mutations with consistent increases …

Incomplete Vesicular Docking Limits Synaptic Strength Under High Release Probability Conditions, Gerardo Malagon, Takafumi Miki, Van Tran, Laura C. Gomez, Alain Marty

Open Access Publications

Central mammalian synapses release synaptic vesicles in dedicated structures called docking/release sites. It has been assumed that when voltage-dependent calcium entry is sufficiently large, synaptic output attains a maximum value of one synaptic vesicle per action potential and per site. Here we use deconvolution to count synaptic vesicle output at single sites (mean site number per synapse: 3.6). When increasing calcium entry with tetraethylammonium in 1.5 mM external calcium concentration, we find that synaptic output saturates at 0.22 vesicle per site, not at 1 vesicle per site. Fitting the results with current models of calcium-dependent exocytosis indicates that the 0.22 …

The Sterlet Sturgeon Genome Sequence And The Mechanisms Of Segmental Rediploidization, Kang Du, Chad Tomlinson, Et Al

Open Access Publications

Sturgeons seem to be frozen in time. The archaic characteristics of this ancient fish lineage place it in a key phylogenetic position at the base of the ~30,000 modern teleost fish species. Moreover, sturgeons are notoriously polyploid, providing unique opportunities to investigate the evolution of polyploid genomes. We assembled a high-quality chromosome-level reference genome for the sterlet, Acipenser ruthenus. Our analysis revealed a very low protein evolution rate that is at least as slow as in other deep branches of the vertebrate tree, such as that of the coelacanth. We uncovered a whole-genome duplication that occurred in the Jurassic, early …