Advances in geroscience: impact on healthspan and chronic disease.

Population aging is unprecedented, without parallel in human history, and the 21st century will witness even more rapid aging than did the century just past. Improvements in public health and medicine are having a profound effect on population demographics worldwide. By 2017, there will be more people over the age of 65 than under age 5, and by 2050, two billion of the estimated nine billion people on Earth will be older than 60 (http://unfpa.

Epicardially derived fibroblasts preferentially contribute to the parietal leaflets of the atrioventricular valves in the murine heart.

The importance of the epicardium for myocardial and valvuloseptal development has been well established; perturbation of epicardial development results in cardiac abnormalities, including thinning of the ventricular myocardial wall and malformations of the atrioventricular valvuloseptal complex. To determine the spatiotemporal contribution of epicardially derived cells to the developing fibroblast population in the heart, we have used a mWt1/IRES/GFP-Cre mouse to trace the fate of EPDCs from embryonic day (ED)10 until birth. EPDCs begin to populate the compact ventricular myocardium around ED12.

Differential Notch signaling in the epicardium is required for cardiac inflow development and coronary vessel morphogenesis.

Rationale: The proepicardium is a transient structure comprising epicardial progenitor cells located at the posterior limit of the embryonic cardiac inflow. A network of signals regulates proepicardial cell fate and defines myocardial and nonmyocardial domains at the venous pole of the heart. During cardiac development, epicardial-derived cells also contribute to coronary vessel morphogenesis.

The sinus venosus progenitors separate and diversify from the first and second heart fields early in development.

Aims: During development, the heart tube grows by differentiation of Isl1(+)/Nkx2-5(+) progenitors to the arterial and venous pole and dorsal mesocardium. However, after the establishment of the heart tube, Tbx18(+) progenitors were proposed to form the Tbx18(+)/Nkx2-5(-) sinus venosus and proepicardium. To elucidate the relationship between these contributions, we investigated the origin of the Tbx18(+) sinus venosus progenitor population in the cardiogenic mesoderm and its spatial and temporal relation to the second heart field during murine heart development.

Moorean tree snail survival revisited: a multi-island genealogical perspective.

Background: The mass extirpation of the island of Moorea's endemic partulid tree snail fauna, following the deliberate introduction of the alien predator Euglandina rosea, represents one of the highest profile conservation crises of the past thirty years. All of the island's partulids were thought to be extirpated by 1987, with five species persisting in zoos, but intensive field surveys have recently detected a number of surviving wild populations. We report here a mitochondrial (mt) phylogenetic estimate of Moorean partulid wild and captive lineage survival calibrated with a reference museum collection that pre-dates the predator's introduction and that also includes a parallel dataset from the neighboring island of Tahiti.

Defective ciliogenesis, embryonic lethality and severe impairment of the Sonic Hedgehog pathway caused by inactivation of the mouse complex A intraflagellar transport gene Ift122/Wdr10, partially overlapping with the DNA repair gene Med1/Mbd4.

Primary cilia are assembled and maintained by evolutionarily conserved intraflagellar transport (IFT) proteins that are involved in the coordinated movement of macromolecular cargo from the basal body to the cilium tip and back. The IFT machinery is organized in two structural complexes named complex A and complex B. Recently, inactivation in the mouse germline of Ift genes belonging to complex B revealed a requirement of ciliogenesis, or proteins involved in ciliogenesis, for Sonic Hedgehog (Shh) signaling in mammals.

High-content imaging characterization of cell cycle therapeutics through in vitro and in vivo subpopulation analysis.

Although the cycling of eukaryotic cells has long been a primary focus for cancer therapeutics, recent advances in imaging and data analysis allow even further definition of cellular events as they occur in individual cells and cellular subpopulations in response to treatment. High-content imaging (HCI) has been an effective tool to elucidate cellular responses to a variety of agents; however, these data were most frequently observed as averages of the entire captured population, unnecessarily decreasing the resolution of each assay. Here, we dissect the eukaryotic cell cycle into individual cellular subpopulations using HCI in conjunction with unsupervised K-means clustering.

Abnormal conduction and morphology in the atrioventricular node of mice with atrioventricular canal targeted deletion of Alk3/Bmpr1a receptor.

Background: The atrioventricular (AV) node is essential for the sequential excitation and optimized contraction of the adult multichambered heart; however, relatively little is known about its formation from the embryonic AV canal. A recent study demonstrated that signaling by Alk3, the type 1a receptor for bone morphogenetic proteins, in the myocardium of the AV canal was required for the development of both the AV valves and annulus fibrosus. To test the hypothesis that bone morphogenetic protein signaling also plays a role in AV node formation, we investigated conduction system function and AV node morphology in adult mice with conditional deletion of Alk3 in the AV canal.

Prehistoric inter-archipelago trading of Polynesian tree snails leaves a conservation legacy.

Inter-archipelago exchange networks were an important aspect of prehistoric Polynesian societies. We report here a novel genetic characterization of a prehistoric exchange network involving an endemic Pacific island tree snail, Partula hyalina. It occurs in the Society (Tahiti only), Austral and Southern Cook Islands.

Tahitian tree snail mitochondrial clades survived recent mass extirpation.

Oceanic islands frequently support endemic faunal radiations that are highly vulnerable to introduced predators [1]. This vulnerability is epitomized by the rapid extinction in the wild of all but five of 61 described Society Islands partulid tree snails [2], following the deliberate introduction of an alien biological control agent: the carnivorous snail Euglandina rosea[3]. Tahiti's tree snail populations have been almost completely extirpated and three of the island's eight endemic Partula species are officially extinct, a fourth persisting only in captivity [2].

Identification and characterization of a novel Schwann and outflow tract endocardial cushion lineage-restricted periostin enhancer.

Periostin is a fasciclin-containing adhesive glycoprotein that facilitates the migration and differentiation of cells that have undergone epithelial-mesenchymal transformation during embryogenesis and in pathological conditions. Despite the importance of post-transformational differentiation as a general developmental mechanism, little is known how periostin's embryonic expression is regulated. To help resolve this deficiency, a 3.

Apoptosis in the developing mouse heart.

Apoptosis occurs at high frequency in the myocardium of the developing avian cardiac outflow tract (OFT). Up- or down-regulating apoptosis results in defects resembling human conotruncal heart anomalies. This finding suggested that regulated levels of apoptosis are critical for normal morphogenesis of the four-chambered heart.

E pluribus unum: A phylogenetic and phylogeographic reassessment of Laevapex (Pulmonata: Ancylidae), a North American genus of freshwater limpets.

The North American freshwater limpet genus Laevapex (Walker, 1903) is a ubiquitous inhabitant of lentic and slow-moving lotic habitats east of the Rocky Mountains, but uncertainty clouds its systematic affinities, the phylogenetic validity of its constituent nominal species, and its degree of genetic connectivity among drainages. We addressed these issues by sampling the genus throughout much of its collective range and constructing representative nuclear and mitochondrial (mt) gene trees, in addition to performing morphometric analyses of shell shape variation. Our results identify neotropical Gundlachia and South American Uncancylus as sister lineages for Laevapex and reveal a pronounced sub-familial dichotomy within the Ancylidae, separating these three New World genera from a Holarctic (Ferrissia (Ancylus, Rhodacmea)) sister clade.

Bone marrow cells transdifferentiate to cardiomyocytes when introduced into the embryonic heart.

Since rates of cardiomyocyte generation in the embryo are much higher than within the adult, we explored whether the embryonic heart would serve as useful experimental system for examining the myocardial potential of adult stem cells. Previously, we reported that the long-term culturing of adult mouse bone marrow produced a cell population that was both highly enriched for macrophages and cardiac competent. In this study, the myocardial potential of this cell population was analyzed in greater detail using the embryonic chick heart as recipient tissue.

Epicardial retinoid X receptor alpha is required for myocardial growth and coronary artery formation.

Vitamin A signals play critical roles during embryonic development. In particular, heart morphogenesis depends on vitamin A signals mediated by the retinoid X receptor alpha (RXRalpha), as the systemic mutation of this receptor results in thinning of the myocardium and embryonic lethality. However, the molecular and cellular mechanisms controlled by RXRalpha signaling in this process are unclear, because a myocardium-restricted RXRalpha mutation does not perturb heart morphogenesis.

The serosal mesothelium is a major source of smooth muscle cells of the gut vasculature.

Most internal organs are situated in a coelomic cavity and are covered by a mesothelium. During heart development, epicardial cells (a mesothelium) move to and over the heart, undergo epithelial-mesenchymal transition (EMT), and subsequently differentiate into endothelial and vascular smooth muscle cells. This is thought to be a unique process in blood vessel formation.

The risk of posterior subcapsular cataracts in granulocyte donors.

Background: Therapeutic use of adrenal corticosteroids is a risk factor for the development of posterior subcapsular cataract (PSC). Because corticosteroids are given to donors of apheresis granulocytes (PMNs) to improve yield, this study was performed to determine the prevalence of PSCs in PMN donors relative to a matched control group of apheresis platelet (PLT) donors.

Study Design And Methods: This study was a cross-sectional study stratified by age, sex, and lifetime apheresis experience at three sites.

Alk3/Bmpr1a receptor is required for development of the atrioventricular canal into valves and annulus fibrosus.

Endocardial cushions are precursors of mature atrioventricular (AV) valves. Their formation is induced by signaling molecules originating from the AV myocardium, including bone morphogenetic proteins (BMPs). Here, we hypothesized that BMP signaling plays an important role in the AV myocardium during the maturation of AV valves from the cushions.

Regulation of GATA gene expression during vertebrate development.

GATA factors regulate critical events in hematopoietic lineages (GATA-1/2/3), the heart and gut (GATA-4/5/6) and various other tissues. Transgenic approaches have revealed that GATA genes are regulated in a modular fashion by sets of enhancers that govern distinct temporal and/or spatial facets of the overall expression patterns. Efforts are underway to resolve how these GATA gene enhancers are themselves regulated in order to elucidate the genetic and molecular hierarchies that govern GATA expression in particular developmental contexts.

Architectural plan for the heart: early patterning and delineation of the chambers and the nodes.

During folding of the embryo, lateroanterior visceral mesoderm forms the embryonic tubular heart at the midline, just ventral to the foregut. In mice, this nascent tube contains the future left ventricle and atrioventricular canal. Mesenchymal cells subsequently recruited to the cardiac lineage at the intake and the outflow of the tube will form the atria and the right ventricle and outflow tract, respectively.

GATA-6 gene enhancer contains nested regulatory modules for primary myocardium and the embedded nascent atrioventricular conduction system.

The cGATA-6 gene is flanked by an enhancer that selectively marks the atrioventricular conduction system (AVCS) in transgenic mice. This enhancer reads anterior/posterior and medial/lateral positional information very early in the cardiogenic program and remains active in progressively more restricted regions of primary myocardium leading up to the emergence of a histologically distinct AVCS. We undertook to parse this enhancer to resolve how the respective AVCS-specific transcription program is regulated at the molecular level.

A cohort study of thyroid cancer and other thyroid diseases after the Chornobyl accident: objectives, design and methods.

The thyroid gland in children is one of the organs that is most sensitive to external exposure to X and gamma rays. However, data on the risk of thyroid cancer in children after exposure to radioactive iodines are sparse. The Chornobyl accident in Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly (131)I.

Transcriptional regulation in the mouse atrioventricular conduction system.

We identified a GATA6 gene enhancer that selectively marks the developing atrioventricular conduction system (AVCS) in transgenic mice. This enhancer reads anterior/posterior and medial/lateral positional information early in the cardiogenic programme and remains active in progressively more restricted subsets of heart cells leading up to AVCS formation. Additional experiments will be required to determine if the potential to be recruited into the AVCS is similarly restricted to a subset of myocardial cells early in the cardiogenic programme or if this enhancer can also be activated de novo in cells that initially reside outside this field.