Digital Commons Network^™

Exploratory Bioinformatics Study Of Lncrnas In Alzheimer's Disease Mrna Sequences With Application To Drug Development, T. Holden, A. Nguyen, E. Lin, E. Cheung, S. Dehipawala, J. Ye, G. Tremberger, D. Lieberman, T. Cheung

Publications and Research

Long noncoding RNA (lncRNA) within mRNA sequences of Alzheimer's disease genes, namely, APP, APOE, PSEN1, and PSEN2, has been analyzed using fractal dimension (FD) computation and correlation analysis. We examined lncRNA by comparing mRNA FD to corresponding coding DNA sequences (CDSs) FD. APP, APOE, and PSEN1 CDSs select slightly higher FDs compared to the mRNA, while PSEN2 CDSs FDs are lower. The correlation coefficient for these sequences is 0.969. A comparative study of differentially expressed MAPK signaling pathway lncRNAs in pancreatic cancer cells shows a correlation of 0.771. Selection of higher FD CDSs could indicate interaction of Alzheimer's gene products …

Sex-Specific Brain Deficits In Auditory Processing In An Animal Model Of Cocaine-Related Schizophrenic Disorders, Patricia A. Broderick, Taylor Rosenbaum

Publications and Research

Cocaine is a psychostimulant in the pharmacological class of drugs called Local Anesthetics. Interestingly, cocaine is the only drug in this class that has a chemical formula comprised of a tropane ring and is, moreover, addictive. The correlation between tropane and addiction is well-studied. Another well-studied correlation is that between psychosis induced by cocaine and that psychosis endogenously present in the schizophrenic patient. Indeed, both of these psychoses exhibit much the same behavioral as well as neurochemical properties across species. Therefore, in order to study the link between schizophrenia and cocaine addiction, we used a behavioral paradigm called Acoustic Startle. …

Conservation Genetics Of Extremely Isolated Urban Populations Of The Northern Dusky Salamander (Desmognathus Fuscus) In New York City, Jason Munshi-South, Yana Zak, Ellen Pehek

Publications and Research

Urbanization is a major cause of amphibian decline. Stream-dwelling plethodontid salamanders are particularly susceptible to urbanization due to declining water quality and hydrological changes, but few studies have examined these taxa in cities. The northern dusky salamander (Desmognathus fuscus) was once common in the New York City metropolitan area, but has substantially declined throughout the region in recent decades. We used five tetranucleotide microsatellite loci to examine population differentiation, genetic variation, and bottlenecks among five remnant urban populations of dusky salamanders in NYC. These genetic measures provide information on isolation, prevalence of inbreeding, long-term prospects for population persistence, and potential …

Neural Processing Of Facial Identity And Emotion In Infants At High-Risk For Autism Spectrum Disorders, Sharon E. Fox, Jennifer B. Wagner, Christine L. Shrock, Helen Tager-Flusberg, Charles A. Nelson

Publications and Research

Deficits in face processing and social impairment are core characteristics of autism spectrum disorder. The present work examined 7-month-old infants at high-risk for developing autism and typically developing controls at low-risk, using a face perception task designed to differentiate between the effects of face identity and facial emotions on neural response using functional Near-Infrared Spectroscopy. In addition, we employed independent component analysis, as well as a novel method of condition-related component selection and classification to identify group differences in hemodynamic wave forms and response distributions associated with face and emotion processing.The results indicate similarities of waveforms, but differences in the …

Overexpression Of Full-Length Centrobin Rescues Limb Malformation But Not Male Fertility Of The Hypodactylous (Hd) Rats, František Liška, Claudia Gosele, Elena Popova, Blanka Chylíková, Drahomíra Křenová, Vladimír Křen, Michael Bader, Laura L. Tres, Norbert Hubner, Abraham L. Kierszenbaum

Publications and Research

Rat hypodactyly (hd) mutation is characterized by abnormal spermatogenesis and sperm decapitation, limb malformation (missing digits II and III) and growth retardation. We have previously reported centrobin (centrosome BRCA2-interacting protein) truncation at the C-terminus in the hd mutant. Here, we report data from a transgenic rescue experiment carried out to determine a role of centrobin in pathogenesis of hd. The transgenic construct, consisting of full-length-coding cDNA linked to a ubiquitous strong promoter/enhancer combination, was inserted to chromosome 16 into a LINE repeat. No known gene is present in the vicinity of the insertion site. Transgenic centrobin was expressed in all …

Synthesis, Biological Activity And Molecular Modelling Studies Of Tricyclic Alkylimidazo-, Pyrimido- And Diazepinopurinediones, Anna Drabczyńska, Tadeusz Karcz, Ewa Szymańska, Meryem Köse, Christa E. Müller, Minka Paskaleva, Janina Karolak-Wojciechowska, Jadwiga Handzlik, Olga Yuzlenko, Katarzyna Kieć-Kononowicz

Publications and Research

Syntheses and biological activities of imidazo-, pyrimido- and diazepino[2,1-f]purinediones containing N-alkyl substituents (with straight, branched or unsaturated chains) are described. Tricyclic derivatives were synthesized by the cyclization of 8-bromo-substituted 7-(2-bromoethyl)-, 7-(3-chloropropyl)- or 7-(4-bromobutyl)-theophylline with primary amines under various conditions. Compound 22 with an ethenyl substituent was synthesized by dehydrohalogenation of 9-(2-bromoethyl)-1,3-dimethyltetrahydropyrimido[2,1-f]purinedione. The obtained derivatives (5–35) were initially evaluated for their affinity at rat A1 and A2A adenosine receptors (AR), showing moderate affinity for both adenosine receptor subtypes. The best ligands were diazepinopurinedione 28 (Ki = 0.28 μM) with fivefold A2A selectivity and the non-selective A1/A2A AR ligand pyrimidopurinedione 35 (Ki …

Create Cornerstone: Introduction To Scientific Thinking, A New Course For Stem-Interested Freshmen, Demystifies Scientific Thinking Through Analysis Of Scientific Literature, Alan J. Gottesman, Sally G. Hoskins

Publications and Research

The Consider, Read, Elucidate hypotheses, Analyze and interpret data, Think of the next Experiment (CREATE) strategy for teaching and learning uses intensive analysis of primary literature to improve students’ critical-thinking and content integration abilities, as well as their self-rated science attitudes, understanding, and confidence. CREATE also supports maturation of undergraduates’ epistemological beliefs about science. This approach, originally tested with upper-level students, has been adapted in Introduction to Scientific Thinking, a new course for freshmen. Results fromthis course’s initial semesters indicate that freshmen in a one-semester introductory course that uses a narrowly focused set of readings to promote development of analytical …

The Use Of Statistics In Experimental Physics, Thomas J. Pfaff, Maksim Sipos, M. C. Sullivan, B. G. Thompson, Max Tran

Publications and Research

Most mathematicians are aware of the importance of statistics in biological sciences, business, and economics, but are less aware that statistics is used every day in experimental physics. This paper gives three interesting examples of how statistics plays a vital role in physics. These examples use the basic statistical tools of residuals analysis and goodness of fit.

Age-Period-Cohort Projections Of Ischaemic Heart Disease Mortality By Socio-Economic Position In A Rapidly Transitioning Chinese Population, Irene O.L. Won, Benjamin J. Cowling, Gabriel M. Leung, Mary Schooling

Publications and Research

Background
With economic development and population aging, ischaemic heart disease (IHD) is becoming a leading cause of mortality with widening inequalities in China. To forewarn the trends in China we projected IHD trends in the most economically developed part of China, i.e., Hong Kong.

Methods
Based on sex-specific IHD mortality rates from 1976 to 2005, we projected mortality rates by neighborhood-level socio-economic position (i.e., low- or high-income groups) to 2020 in Hong Kong using Poisson age-period-cohort models with autoregressive priors.

Results
In the low-income group, age-standardized IHD mortality rates among women declined from 33.3 deaths in 1976–1980 to 19.7 per …

End-Point Variability Is Not Noise In Saccade Adaptation, James P. Herman, C. Phillip Cloud, Josh Wallman

Publications and Research

When each of many saccades is made to overshoot its target, amplitude gradually decreases in a form of motor learning called saccade adaptation. Overshoot is induced experimentally by a secondary, backwards intrasaccadic target step (ISS) triggered by the primary saccade. Surprisingly, however, no study has compared the effectiveness of different sizes of ISS in driving adaptation by systematically varying ISS amplitude across different sessions. Additionally, very few studies have examined the feasibility of adaptation with relatively small ISSs. In order to best understand saccade adaptation at a fundamental level, we addressed these two points in an experiment using a range …

A Myosin-Va Tail Fragment Sequesters Dynein Light Chains Leading To Apoptosis In Melanoma Cells, Tc Izidoro-Toledo, Ac Borges, Dd Araujo, Dps Leitao Mazzi, Fo Nascimento Junior, Jf Sousa, Cp Alves, Apb Paiva, Dm Trindade, Ev Patussi, Pablo M. Peixoto, Kw Kinnally, Em Espreafico

Publications and Research

Previous studies proposed that myosin-Va regulates apoptosis by sequestering pro-apoptotic Bmf to the actin cytoskeleton through dynein light chain-2 (DLC2). Adhesion loss or other cytoskeletal perturbations would unleash Bmf, allowing it to bind and inhibit pro-survival Bcl2 proteins. Here, we demonstrated that over expression of a myosin-Va medial tail fragment (MVaf) harboring the binding site for DLC2 dramatically decreased melanoma cell viability. Morphological and molecular changes, including surface blebbing, mitochondrial outer membrane permeabilization, cytochrome-c and Smac release, as well as caspase-9/-3 activation and DNA fragmentation indicated that melanoma cells died of apoptosis. Immobilized MVaf interacted directly with DLCs, but complexed …

The Evolutionary Dynamics Of Protein-Protein Interaction Networks Inferred From The Reconstruction Of Ancient Networks, Yuliang Jin, Dmitrij Turaev, Thomas Weinmaier, Thomas Rattei, Hernán A. Makse

Publications and Research

Cellular functions are based on the complex interplay of proteins, therefore the structure and dynamics of these protein-protein interaction (PPI) networks are the key to the functional understanding of cells. In the last years, large-scale PPI networks of several model organisms were investigated. A number of theoretical models have been developed to explain both the network formation and the current structure. Favored are models based on duplication and divergence of genes, as they most closely represent the biological foundation of network evolution. However, studies are often based on simulated instead of empirical data or they cover only single organisms. Methodological …

Dissociated Grey Matter Changes With Prolonged Addiction And Extended Abstinence In Cocaine Users, Colm G. Connolly, Ryan P. Bell, John J. Foxe, Hugh Garavan

Publications and Research

Extensive evidence indicates that current and recently abstinent cocaine abusers compared to drug-naïve controls have decreased grey matter in regions such as the anterior cingulate, lateral prefrontal and insular cortex. Relatively little is known, however, about the persistence of these deficits in long-term abstinence despite the implications this has for recovery and relapse. Optimized voxel based morphometry was used to assess how local grey matter volume varies with years of drug use and length of abstinence in a cross-sectional study of cocaine users with various durations of abstinence (1–102 weeks) and years of use (0.3–24 years). Lower grey matter volume …

Rage Deficiency Improves Postinjury Sciatic Nerve Regeneration In Type 1 Diabetic Mice, Judyta K. Juranek, Matthew S. Geddis, Fei Song, Jinghua Zhang, Jose Garcia, Rosa Rosario, Shi Fang Yan, Thomas H. Brannagan, Ann Marie Schmidt

Publications and Research

Peripheral neuropathy and insensate limbs and digits cause significant morbidity in diabetic individuals. Previous studies showed that deletion of the receptor for advanced end-glycation products (RAGE) in mice was protective in long-term diabetic neuropathy. Here, we tested the hypothesis that RAGE suppresses effective axonal regeneration in superimposed acute peripheral nerve injury attributable to tissue-damaging inflammatory responses. We report that deletion of RAGE, particularly in diabetic mice, resulted in significantly higher myelinated fiber densities and conduction velocities consequent to acute sciatic nerve crush compared with wild-type control animals. Consistent with key roles for RAGE-dependent inflammation, reconstitution of diabetic wild-type mice with …

A Novel Cell-Based Hybrid Acoustic Wave Biosensor With Impedimetric Sensing Capabilities, Fei Liu, Fang Li, Anis Nurashikin Nordin, Ioana Voiculescu

Publications and Research

A novel multiparametric biosensor system based on living cells will be presented. The biosensor system includes two biosensing techniques on a single device: resonant frequency measurements and electric cell-substrate impedance sensing (ECIS). The multiparametric sensor system is based on the innovative use of the upper electrode of a quartz crystal microbalance (QCM) resonator as working electrode for the ECIS technique. The QCM acoustic wave sensor consists of a thin AT-cut quartz substrate with two gold electrodes on opposite sides. For integration of the QCM with the ECIS technique a semicircular counter electrode was fabricated near the upper electrode on the …

Unconscious Processing Of Unattended Features In Human Visual Cortex, Tatiana Aloi Emmanouil, Philip Burton, Tony Ro

Publications and Research

Unconscious processing has been convincingly demonstrated for task-relevant feature dimensions. However, it is possible that the visual system is capable of more complex unconscious operations, extracting visual features even when they are unattended and task irrelevant. In the current study, we addressed this question by measuring unconscious priming using a task in which human participants attended to a target object's shape while ignoring its color. We measured both behavioral priming effects and priming-related fMRI activations from primes that were unconsciously presented using metacontrast masking. The results showed faster RTs and decreases in fMRI activation only when the primes were identical …

Molecular Immunologic Correlates Of Spontaneous Latency In A Rabbit Model Of Pulmonary Tuberculosis, Selvakumar Subbian, Paul O'Brien, Nicole L. Kushner, Guibin Yang, Liana Tsenova, Blas Peixoto, Nirmalya Bandyopadhyay, Joel S. Bader, Petros C. Karakousis, Dorothy Fallows, Gilla Kaplan

Publications and Research

Background: Infection of humans with Mycobacterium tuberculosis (Mtb) results in latent tuberculosis infection (LTBI) in 90-95% of immune competent individuals, with no symptoms of active disease. The World Health Organization estimates that 1.5 billion people have LTBI, which can reactivate in the setting of waning host immunity, posing a threat to global TB control. Various animal models have been used to study the pathogenesis of TB. However, besides nonhuman primates, rabbits are the only animal model that fully recapitulates the pathological features of human TB, including progressive disease with necrosis and cavitation or establishment of spontaneous latency.

Results: We …

Landscape Genetics Of Leaf-Toed Geckos In The Tropical Dry Forest Of Northern Mexico, Christopher Blair, Victor H. Jimenez-Arcos, Fausto R. Mendez De La Cruz, Robert W. Murphy

Publications and Research

Habitat fragmentation due to both natural and anthropogenic forces continues to threaten the evolution and maintenance of biological diversity. This is of particular concern in tropical regions that are experiencing elevated rates of habitat loss. Although less well-studied than tropical rain forests, tropical dry forests (TDF) contain an enormous diversity of species and continue to be threatened by anthropogenic activities including grazing and agriculture. However, little is known about the processes that shape genetic connectivity in species inhabiting TDF ecosystems. We adopt a landscape genetic approach to understanding functional connectivity for leaf-toed geckos (Phyllodactylus tuberculosus) at multiple sites …

Extinction Hazards In Experimental Daphnia Magna Populations: Effects Of Genotype Diversity And Environmental Variation, John D. Robinson, John P. Wares, John M. Drake

Publications and Research

Extinction is ubiquitous in natural systems and the ultimate fate of all biological populations. However, the factors that contribute to population extinction are still poorly understood, particularly genetic diversity and composition. A laboratory experiment was conducted to examine the influences of environmental variation and genotype diversity on persistence in experimental Daphnia magna populations. Populations were initiated in two blocks with one, two, three, or six randomly selected and equally represented genotypes, fed and checked for extinction daily, and censused twice weekly over a period of 170 days. Our results show no evidence for an effect of the number of genotypes …

Curatedovariandata: Clinically Annotated Data For The Ovarian Cancer Transcriptome, Benjamin Frederick Ganzfried, Markus Riester, Benjamin Haibe-Kains, Thomas Risch, Svitlana Tyekucheva, Ina Jazic, Xin Victoria Wang, Mahnaz Ahmadifar, Michael J. Birrer, Giovanni Parmigiani, Curtis Huttenhower, Levi Waldron

Publications and Research

This article introduces a manually curated data collection for gene expression meta-analysis of patients with ovarian cancer and software for reproducible preparation of similar databases. This resource provides uniformly prepared microarray data for 2970 patients from 23 studies with curated and documented clinical metadata. It allows users to efficiently identify studies and patient subgroups of interest for analysis and to perform meta-analysis immediately without the challenges posed by harmonizing heterogeneous microarray technologies, study designs, expression data processing methods and clinical data formats. We confirm that the recently proposed biomarker CXCL12 is associated with patient survival, independently of stage and optimal …

Transcranial Electrical Stimulation Accelerates Human Sleep Homeostasis, Davide Reato, Fernando Gasca, Abhishek Datta, Marom Bikson, Lisa Marshall, Lucas C. Parra

Publications and Research

The sleeping brain exhibits characteristic slow-wave activity which decays over the course of the night. This decay is thought to result from homeostatic synaptic downscaling. Transcranial electrical stimulation can entrain slow-wave oscillations (SWO) in the human electro-encephalogram (EEG). A computational model of the underlying mechanism predicts that firing rates are predominantly increased during stimulation. Assuming that synaptic homeostasis is driven by average firing rates, we expected an acceleration of synaptic downscaling during stimulation, which is compensated by a reduced drive after stimulation. We show that 25 minutes of transcranial electrical stimulation, as predicted, reduced the decay of SWO in the …

Association Of Neighborhood-Level Factors With Hospitalization For Community-Associated Methicillin-Resistant Staphylococcus Aureus, New York City, 2006: A Multilevel Observational Study, Amanda M. Farr, Melissa A. Marx, Don Weiss, Denis Nash

Publications and Research

Background Hospitalizations with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infection have increased in New York City, with substantial geographic variation across neighborhoods. While individual-level risk factors, such as age, sex, HIV infection, and diabetes have been described, the role of neighborhood-level factors (e.g., neighborhood HIV prevalence or income) has not been examined. Methods To explore plausible neighborhood-level factors associated with CA-MRSA-related hospitalizations, a retrospective analysis was conducted using New York City hospital discharges from 2006 and New York City-specific survey and health department surveillance data. CA-MRSA-related hospitalizations were identified using diagnosis codes and admission information. Associations were determined by using sex-specific …

Isoflurane Increases Neuronal Cell Death Vulnerability By Downregulating Mir-214, Hailiang Yan, Tao Xu, Hongfeng Zhao, Kuo-Chieh Lee, Hoau-Yan Wang, Yan Zhang

Publications and Research

Since accumulating evidence suggests the application of anesthetics may increase the risk of Alzheimer’s disease (AD), we investigated the cytotoxicity of inhaled general anesthesia in neurons and its underlying mechanism. Using primary cultured rat hippocampal neurons as the study model, here we show that isoflurane increases vulnerability to intracellular or extracellular amyloid b with or without serum deprivation. This isoflurane-induced effect is mediated by the downregulation of miR-214 level that lead to an elevated expression of Bax, a prominent target for miR-214. We conclude that isoflurane increases cell death in the presence of amyloid b by increasing Bax level through …

Assessing Regional And Interspecific Variation In Threshold Responses Of Forest Breeding Birds Through Broad Scale Analyses, Yntze Van Der Hoek, Rosalind Renfrew, Lisa L. Manne

Publications and Research

Background: Identifying persistence and extinction thresholds in species-habitat relationships is a major focal point of ecological research and conservation. However, one major concern regarding the incorporation of threshold analyses in conservation is the lack of knowledge on the generality and transferability of results across species and regions. We present a multi-region, multi-species approach of modeling threshold responses, which we use to investigate whether threshold effects are similar across species and regions.

Methodology/Principal Findings: We modeled local persistence and extinction dynamics of 25 forest-associated breeding birds based on detection/non-detection data, which were derived from repeated breeding bird atlases for the state …

Ecological Genetics Of Chinese Rhesus Macaque In Response To Mountain Building: All Things Are Not Equal, Shan-Jin Wu, Jing Luo, Qing-Qing Li, Yan-Qin Wang, Robert E. Murphy, Christopher Blair, Shi-Fang Wu, Bi-Song Yue, Ya-Ping Zhang

Publications and Research

Pliocene uplifting of the Qinghai-Tibetan Plateau (QTP) and Quaternary glaciation may have impacted the Asian biota more than any other events. Little is documented with respect to how the geological and climatological events influenced speciation as well as spatial and genetic structuring, especially in vertebrate endotherms. Macaca mulatta is the most widely distributed non-human primate. It may be the most suitable model to test hypotheses regarding the genetic consequences of orogenesis on an endotherm.

Searching Mindfully: Are Libraries Up To The Challenge Of Competing With Google Books?, Amrita Dhawan

Publications and Research

Traditional research tools used by libraries, such as encyclopedias and catalogs (OPACs) were created in an age of print and information scarcity. They have not kept up with changes in the information world which assume an abundance of online information in different formats and interdisciplinary topics which attempt to solve ‘real world’ messy problems and not traditional theoretical questions. The traditional tools rest on an unwieldy and somewhat outdated collaboration between OCLC, LOC, private aggregators, librarians and faculty. The search results they deliver offer excessive information with very little guidance on how to systematically sift through them. This makes the …

The Impact Of Gut Passage By Binturongs (Arctictus Binturong) On Seed Germination, Christina P. Colon, Ahimsa Campos-Arceiz

Publications and Research

Binturongs (Arctictis binturong) are the largest of Asian civets and, due to their highly frugivorous diet, are expected to play an important role in seed dispersal processes. To study the effect of binturong gut passage on seed viability, we fed 10 captive binturongs with fruits of longan (Dimocarpus longan), papaya (Carica papaya) and chiku (Manilkara zapota), collected the seeds they defaecated, and planted these to determine seed germination rate and time. Of the defaecated seeds, 90.4% passed through binturong gut intact in under nine hours, and 99.4% passed in under 33 hours. Chiku seeds had the highest germination rate (35.7% …

The Passiflora Tripartita (Banana Passion) Fruit: A Source Of Bioactive Flavonoid C-Glycosides Isolated By Hsccc And Characterized By Hplc–Dad–Esi/Ms/Ms, Mario J. Simirgiotis, Guillermo Schmeda-Hirschmann, Jorge Bórquez, Edward J. Kennelly

Publications and Research

The banana passion fruit (Passiflora tripartita Breiter, Passifloraceae) known as “tumbo” is very appreciated in tropical and subtropical countries of South America. Methanolic extracts from peel and the fruit juice of P. tripartita growing in Chile were analyzed for antioxidant capacity as well as for flavonoid and phenolic content. A chromatographic method was developed for the rapid identification of the main phenolics in the samples by HPLC-DAD and HPLC-MS. The fast fingerprint analysis allowed the detection of eighteen flavonoid C-glycosides and four flavonoid O-glycoside derivatives which were characterized by UV spectra and ESI-MS-MS analysis. Several of the C-glycosides detected are …

Multiple Breast Cancer Cell-Lines Derived From A Single Tumor Differ In Their Molecular Characteristics And Tumorigenic Potential, Goar Mosoyan, Chandandeep Nagi, Svetlana Marukian, Avelino Teixeira, Anait Simonian, Lois Resnick-Silverman, Analisa Difeo, Dean Johnston, Sandra R. Reynolds, Daniel F. Roses, Arevik Mosoian

Publications and Research

Background Breast cancer cell lines are widely used tools to investigate breast cancer biology and to develop new therapies. Breast cancer tissue contains molecularly heterogeneous cell populations. Thus, it is important to understand which cell lines best represent the primary tumor and have similarly diverse phenotype. Here, we describe the development of five breast cancer cell lines from a single patient’s breast cancer tissue. We characterize the molecular profiles, tumorigenicity and metastatic ability in vivo of all five cell lines and compare their responsiveness to 4-hydroxytamoxifen (4-OHT) treatment. Methods Five breast cancer cell lines were derived from a single patient’s …

Integration Of Nodal And Bmp Signals In The Heart Requires Foxh1 To Create Left–Right Differences In Cell Migration Rates That Direct Cardiac Asymmetry, Kari F. Lenhart, Nathalia G. Holtzman, Jessica R. Williams, Rebecca D. Burdine

Publications and Research

Failure to properly establish the left–right (L/R) axis is a major cause of congenital heart defects in humans, but how L/R patterning of the embryo leads to asymmetric cardiac morphogenesis is still unclear. We find that asymmetric Nodal signaling on the left and Bmp signaling act in parallel to establish zebrafish cardiac laterality by modulating cell migration velocities across the L/R axis. Moreover, we demonstrate that Nodal plays the crucial role in generating asymmetry in the heart and that Bmp signaling via Bmp4 is dispensable in the presence of asymmetric Nodal signaling. In addition, we identify a previously unappreciated role …